Actinic keratosis

Often precedes squamous cell carcinoma

Addison's disease
1 adrenocortical deficiency

Albright's syndrome
Polyostotic fibrous dysplasia, precocious puberty, caf-au-lait spots, short stature, young girls

Albuminocytologic dissociation
Guillain-Barr ( protein in CSF with only modest in cell count)

Alport's syndrome
Hereditary nephritis with nerve deafness

Anti-basement membrane antibodies

Goodpasture's syndrome

Anticentromere antibodies
Scleroderma (CREST)

Anti-double-stranded DNA antibodies (ANA antibodies)

SLE (type III hypersensitivity)

Anti-epithelial cell antibodies

Pemphigus vulgaris

Antigliadin antibodies
Celiac disease

Antihistone antibodies
Drug-induced SLE

Anti-IgG antibodies
Rheumatoid arthritis

Antimitochondrial antibodies
1 biliary cirrhosis

Antineutrophil antibodies
Vasculitis

Antiplatelet antibodies

Idiopathic thrombocytopenic purpura

Arachnodactyly
Marfan's syndrome

Argyll Robertson pupil

Neurosyphilis

Arnold-Chiari malformation
Cerebellar tonsillar herniation

Aschoff bodies
Rheumatic fever

Atrophy of the mammillary bodies

Wernicke's encephalopathy

Auer rods
Acute myelogenous leukemia (especially the promyelocytic type)

Autosplenectomy
Sickle cell anemia

Babinski's sign
UMN lesion

Baker's cyst in popliteal fossa

Rheumatoid arthritis

"Bamboo spine" on x-ray

Ankylosing spondylitis

Bartter's syndrome
Hyperreninemia

Basophilic stippling of RBCs

Lead poisoning

Becker's muscular dystrophy

Defective dystrophin; less severe than Duchenne's

Bell's palsy
LMN CN VII palsy

Bence Jones proteins

Multiple myeloma (kappa or lambda Ig light chains in urine), Waldenstrm's macroglobulinemia (IgM)

Berger's disease
IgA nephropathy

Bernard-Soulier disease
Defect in platelet adhesion

Bilateral hilar adenopathy, uveitis

Sarcoidosis

Birbeck granules on EM
Histiocytosis X (eosinophilic granuloma)

Bloody tap on LP
Subarachnoid hemorrhage

"Blue bloater"
Chronic bronchitis

Blue-domed cysts
Fibrocystic change of the breast

Blue sclera
Osteogenesis imperfecta

Boot-shaped heart on x-ray

Tetralogy of Fallot; RVH

Bouchard's nodes
Osteoarthritis (PIP swelling 2 to osteophytes)

Boutonnire deformity
Rheumatoid arthritis

Branching rods in oral infection

Actinomyces israelii

"Brown tumor" of bone

Hemorrhage causes brown color of osteolytic cysts: 1. Hyperparathyroidism 2. Osteitis fibrosa cystica (von Recklinghausen's disease)

Brushfield's spots
Down syndrome

Bruton's disease
X-linked agammaglobulinemia

Budd-Chiari syndrome
Posthepatic venous thrombosis

Buerger's disease
Small/medium-artery vasculitis

Burkitt's lymphoma
8:14 translocation; associated with EBV

Burton's lines
Lead poisoning

C-ANCA, P-ANCA
Wegener's granulomatosis, polyarteritis nodosa

Caf-au-lait spots on skin

Neurofibromatosis

Caisson disease
Gas emboli

Calf pseudohypertrophy
Duchenne's muscular dystrophy

Call-Exner bodies
Granulosa-theca cell tumor of the ovary

Cardiomegaly with apical atrophy

Chagas' disease

Cerebriform nuclei
Mycosis fungoides (cutaneous T-cell lymphoma)

Chagas' disease
Trypanosome infection

Chancre

1 syphilis (not painful)

Chancroid
Haemophilus ducreyi (painful)

Charcot's triad
Multiple sclerosis (nystagmus, intention tremor, scanning speech), cholangitis (jaundice, RUQ pain, fever)

Charcot-Leyden crystals
Bronchial asthma (eosinophil membranes)

Chdiak-Higashi disease
Phagocyte deficiency

Cherry-red spot on macula

Tay-Sachs, Niemann-Pick disease, central retinal artery occlusion

Cheyne-Stokes respirations
Central apnea in CHF and intracranial pressure

"Chocolate cysts"

Endometriosis (frequently involves both ovaries)

Chronic atrophic gastritis

Predisposition to gastric carcinoma

Chvostek's sign
Hypocalcemia (facial muscle spasm upon tapping)

Clear cell adenocarcinoma of

DES exposure in utero

Clue cells
Gardnerella vaginitis

Codman's triangle on x-ray

Osteosarcoma

Cold agglutinins
Mycoplasma pneumoniae, infectious mononucleosis

Cold intolerance
Hypothyroidism

Condylomata lata
2 syphilis

Continuous machinery murmur

Patent ductus arteriosus

Cori's disease
Debranching enzyme deficiency

Cotton-wool spots
Chronic hypertension

Cough, conjunctivitis, coryza

Measles

Councilman bodies
Toxic or viral hepatitis

Cowdry type A bodies

Herpesvirus

Crescents in Bowman's capsule

Rapidly progressive crescentic glomerulonephritis

Crigler-Najjar syndrome
Congenital unconjugated hyperbilirubinemia

Curling's ulcer
Acute gastric ulcer associated with severe burns

Currant-jelly sputum
Klebsiella

Curschmann's spirals
Bronchial asthma (whorled mucous plugs)

Cushing's ulcer
Acute gastric ulcer associated with CNS injury

Depigmentation of neurons in
Parkinson's disease (basal ganglia disorder--rigidity, resting tremor, bradykinesia)

Dermatitis, dementia, diarrhea

Pellagra (niacin, vitamin B3 deficiency)

Diabetes insipidus + exophthalmos +

Hand-Schller-Christian disease

Dog or cat bite

Pasteurella multocida

Donovan bodies
Granuloma inguinale

Dressler's syndrome
Post-MI fibrinous pericarditis

Dubin-Johnson syndrome
Congenital conjugated hyperbilirubinemia (black liver)

Duchenne's muscular dystrophy

Deleted dystrophin gene (X-linked recessive)

Eburnation

Osteoarthritis (polished, ivory-like appearance of bone)

Edwards' syndrome
Trisomy 18 associated with rocker-bottom feet, low-set ears, heart disease

Eisenmenger's complex
Late cyanosis shunt (uncorrected L R shunt becomes R L shunt)

Elastic skin
Ehlers-Danlos syndrome

Erb-Duchenne palsy
Superior trunk brachial plexus injury ("waiter's tip")

Erythema chronicum migrans

Lyme disease

Fanconi's syndrome
Proximal tubular reabsorption defect

"Fat, female, forty, and fertile"

Acute cholecystitis

Fatty liver
Alcoholism

Ferruginous bodies
Asbestosis

Gardner's syndrome
Colon polyps with osteomas and soft tissue tumors

Gaucher's disease
Glucocerebrosidase deficiency

Gilbert's syndrome
Benign congenital unconjugated hyperbilirubinemia

Glanzmann's thrombasthenia
Defect in platelet aggregation

Goodpasture's syndrome

Autoantibodies against alveolar and glomerular basement membrane proteins

Gowers' maneuver
Duchenne's (use of patient's arms to help legs pick self off the floor)

Guillain-Barr syndrome
Idiopathic polyneuritis

"Hair-on-end" appearance on x-ray

-thalassemia, sickle cell anemia (extramedullary hematopoiesis)

Hand-Schller-Christian disease
Chronic progressive histiocytosis

HbF
Thalassemia major

HbS
Sickle cell anemia

hCG elevated

Choriocarcinoma, hydatidiform mole (occurs with and without embryo)

Heberden's nodes
Osteoarthritis (DIP swelling 2 to osteophytes)

Heinz bodies
G6PD deficiency

Henoch-Schnlein purpura
Hypersensitivity vasculitis associated with hemorrhagic urticaria and URIs

Heterophil antibodies
Infectious mononucleosis (EBV)

High-output cardiac failure (dilated cardiomyopathy)

Wet beriberi (thiamine, vitamin B1 deficiency)

HLA-B27
Reiter's syndrome, ankylosing spondylitis

HLA-DR3 or -DR4

Diabetes mellitus type 1 (caused by autoimmune destruction of cells)

Homer Wright rosettes

Neuroblastoma

Honeycomb lung on x-ray

Interstitial fibrosis

Horner's syndrome
Ptosis, miosis, and anhidrosis

Howell-Jolly bodies
Splenectomy (or nonfunctional spleen)

Huntington's disease
Caudate degeneration (autosomal dominant)

Hyperphagia + hypersexuality + hyperorality + hyperdocility

Klver-Bucy syndrome (amygdala)

Hyperpigmentation of skin

1 adrenal insufficiency (Addison's disease)

Hypersegmented neutrophils
Macrocytic anemia

Hypertension + hypokalemia
Conn's syndrome

Hypochromic microcytosis
Iron deficiency anemia, lead poisoning

Increased -fetoprotein in amniotic fluid/maternal serum

Anencephaly, spina bifida (neural tube defects)

Increased uric acid levels

Gout, Lesch-Nyhan syndrome, myeloproliferative disorders, loop and thiazide diuretics

Intussusception
Adenovirus (causes hyperplasia of Peyer's patches)

Janeway lesions

Endocarditis

Jarisch-Herxheimer reaction
Syphilisoveraggressive treatment of an asymptomatic patient that causes symptoms due to rapid lysis

Job's syndrome
Neutrophil chemotaxis abnormality

Kaposi's sarcoma
AIDS in MSM (men who have sex with men)

Kartagener's syndrome
Dynein defect

Kayser-Fleischer rings
Wilson's disease

Keratin pearls
Squamous cell carcinoma

Kimmelstiel-Wilson nodules

Diabetic nephropathy

Klver-Bucy syndrome
Bilateral amygdala lesions

Koplik spots
Measles

Krukenberg tumor
Gastric adenocarcinoma with ovarian metastases
often precedes squamous cell carcinoma
actinic keratosis

primary adrenocortical deficiency

Addison's disease

polyostotic fibrous dysplasia, precocious puberty, cafe-au-lait spots, short stature, young girls - diagnosis?
Albright's syndrome

hereditary nephritis with nerve deafness

Alport's syndrome

anti-basement membrane antibodies diagnosis?

Goodpasture's syndrome

anticentromere antibodies - diagnosis?

scleroderma (CREST)

anti-double-stranded DNA antibodies (ANA antibodies) - diagnosis? - what hypersensitivity type?

SLE - type III hypersensitivity

anti-epithelial cell antibodies diagnosis?

pemphigus vulgaris

antigliadin antibodies - diagnosis?

celiac disease

antihistone antibodies - diagnosis?

drug-induced SLE

anti-IgG antibodies - diagnosis?

rheumatoid arthritis

antimitochondrial antibodies diagnosis?

primary biliary cirrhosis

antineutrophil antibodies - diagnosis?

vasculitis

antiplatelet antibodies - diagnosis?

idiopathic thrombocytopenic purpura

arachnodactyly - diagnosis?
Marfan's syndrome

Argyll-Robertson pupil - diagnosis?

neurosyphilis

Arnold-Chiari malformation
cerebellar tonsillar herniation

Aschoff bodies - diagnosis?

rheumatic fever

atrophy of the mammillary bodies diagnosis?

Wernicke's encephalopathy

Auer rods - diagnosis?

acute myelogenous leukemia (especially promyelocytic type)

autosplenectomy - diagnosis?
sickle cell anemia

Babinski's sign is associated with what?

UMN lesion

"bamboo spine" on x-ray

ankylosing spondylitis

basophilic stippling of RBCs - diagnosis?

lead poisoning

defective dystrophin, less severe than Duchenne's

Becker's muscular dystrophy

LMN CN VII palsy

Bell's palsy

Bence Jones proteins - possible diagnoses? - in each case, what are the proteins?
multiple myeloma - kappa or lambda light chains Waldenstrom's macroglobulinemia - IgM

IgA nephropathy - diagnosis?

Berger's disease

Bernard-Soulier disease - what is the defect?

defect in platelet adhesion

bilateral hilar adenopathy, uveitis diagnosis?

sarcoidosis

Birbeck granules on EM - diagnosis?

histiocytosis X (eosinophilic granuloma)

bloody tap on LP - diagnosis?

subarachnoid hemorrhage

"blue bloater"
chronic bronchitis

blue-domed cysts - diagnosis?

fibrocystic change of the breast

blue sclera - diagnosis?

osteogenesis imperfecta

boot-shaped heart on x-ray - possible diagnoses?

tetralogy of Fallot or RVH

Bouchard's nodes - diagnosis? - where are they located? - why do they occur?
osteoarthritis - on PIP secondary to osteophytes

boutonniere deformity - diagnosis?

rheumatoid arthritis

branching rods in oral infection diagnosis?

Actinomyces israelii

"brown tumor" of bone - possible diagnoses? - what causes the brown color?
hyperparathyroidism or osteitis fibrosa cystica (von Recklinghausen's disease) - color is due to hemorrhage in cysts

X-linked agammaglobulinemia
Bruton's disease

posthepatic venous thrombosis diagnosis?

Budd-Chiari syndrome

Buerger's disease - what size arteries does it affect?

small or medium-artery vasculitis

Burkitt's lymphoma - what is the translocation? - what virus is it associated with? - appearance on histology?
8:14 translocation EBV starry sky appearance

Burton's lines - diagnosis?

lead poisoning

what types of ANCA are associated with Wegener's granulomatosis and microscopic polyangiitis?
Wegener's - c-ANCA MPA - p-ANCA

cafe-au-lait spots on skin - diagnosis?

neurofibromatosis

calf pseudohypertrophy - diagnosis?

Duchenne's muscular dystrophy

Call-Exner bodies - diagnosis?

granulosa-theca cell tumor of the ovary

cardiomegaly with apical atrophy diagnosis?

Chagas' disease

trypanosome infection - diagnosis?

Chagas' disease

painless chancre - diagnosis?

primary syphilis

painful chancroid - cause?

Haemophilus ducreyi

Charcot's triad of multiple sclerosis

nystagmus, intention tremor, scanning speech

Charcot's triad of cholangitis

jaundice, RUQ pain, fever

Charcot-Leyden crystals - diagnosis? - what are they?

bronchial asthma - eosinophil membranes

what is the defect in Chediak-Higashi disease?

phagocyte deficiency

cherry-red spot on macula - possible diagnoses?

Tay-Sachs or Niemann-Pick disease

what are Cheyne-Stokes respirations, and in what circumstance do they occur?

central apnea in CHF and increased intracranial pressure

"chocolate cysts"
endometriosis

what does chronic atrophic gastritis predispose to?

gastric carcinoma

Chvostek's sign - what is it, and what does it indicate?

facial muscle spasm upon tapping - sign of hypocalcemia

DES exposure in utero predisposes to what?

clear cell adenocarcinoma of the vagina

clue cells - diagnosis?

Gardnerella vaginitis

Codman's triangle on x-ray - diagnosis?

osteosarcoma

cold agglutinins - possible diagnoses?

Mycoplasma pneumonia or infectious mononucleosis

cold intolerance - sign of what?

hypothyroidism

condylomata lata - diagnosis?

secondary syphilis

continuous machinery murmur indicates what?

patent ductus arteriosus

what is the defect in Cori's disease?

debranching enzyme deficiency

cough, conjunctivitis, coryza, fever diagnosis?

measles

Councilman bodies - diagnosis?

toxic or viral hepatitis

Cowdry type A bodies - caused by what?

herpesvirus

crescents in Bowman's capsule diagnosis?

rapidly progressive crescentic glomerulonephritis

what is Crigler-Najjar syndrome?

congenital unconjugated hyperbilirubinemia due to absent UDP glucuronyl transferase

acute gastric ulcer associated with severe burns

Curling's ulcer

currant-jelly sputum - diagnosis?

Klebsiella

Curschmann's spirals - diagnosis? - what are they?

bronchial asthma - whorled mucous plugs

acute gastric ulcer associated with CNS injury

Cushing's ulcer

D-dimers - diagnosis?
DIC

depigmentation of neurons in substantia nigra - diagnosis? - where is the defect? - symptoms?

Parkinson's disease - basal ganglia disorder - rigidity, resting tremor, bradykinesia

dermatitis, dementia, diarrhea diagnosis?

pellagra (niacin/vitamin B3 deficiency)

dog or cat bite - infected with?

Pasteurella multocida

what is Dressler's syndrome?

post-MI fibrinous pericarditis

what is Dubin-Johnson syndrome? - what is the defect? - what is the pathologic consequence?

congenital conjugated hyperbilirubinemia due to defective liver excretion of conjugated bilirubin, causing black liver

what is the defect in Duchenne's muscular dystrophy? - what is the inheritance pattern?
deleted dystrophin gene - X-linked recessive

eburnation - diagnosis?
osteoarthritis

trisomy 18 associated with rocker-bottom feet, low-set ears, heart disease

Edwards' syndrome

what is Eisenmenger's complex?

late cyanosis shunt (reversal of an uncorrected L-R shunt to an R-L shunt)

elastic skin - diagnosis?

Ehlers-Danlos syndrome

where and what is Erb-Duchenne palsy?

superior trunk injury to brachial plexus (C5-6) - "waiter's tip"

erythema chronicum migrans diagnosis?

Lyme disease

genetically inherited aplastic anemia

Fanconi's anemia

what is Fanconi's syndrome?

proximal tubular reabsorption defect (causes excretion of many things - leads to, among other things, rickets, metabolic acidosis, hypokalemia)

"fat, female, forty, and fertile" - at risk for?

acute cholecystitis

fatty liver - associated with?

alcoholism

ferruginous bodies - diagnosis?

asbestosis

colon polyps with osteomas and soft tissue tumors - diagnosis?

Gardner's syndrome

what is the defect in Gaucher's disease?

glucocerebrosidase deficiency

Ghon focus - diagnosis?

primary TB

what is Gilbert's syndrome? - what is the deficiency?

benign congenital unconjugated hyperbilirubinemia - due to mildly decreased UDP-glucouronyl transferase or decreased bilirubin uptake by liver

what is the defect in Glanzmann's thrombasthenia?

defect in platelet aggregation (defect in GPIIb/IIIa)

autoantibodies against alveolar and glomerular basement membrane proteins - diagnosis?

Goodpasture's syndrome

Gowers' maneuver - diagnosis? - what is the maneuver?

Duchenne's - use of patient's arms to help legs pick self off floor

idiopathic peripheral polyneuritis diagnosis?

Guillain-Barre syndrome

"hair on end" (crew cut) appearance on x-ray - possible diagnoses? - why does this happen?
beta-thalassemia or sickle cell anemia - due to extramedullary hematopoiesis

what is Hand-Schuller-Christian disease?

chronic progressive histiocytosis (Langerhans cell histiocytosis)

lots of HbF - diagnosis?

thalassemia major

HbS - diagnosis?
sickle cell anemia

conditions in which hCG is elevated

choriocarcinoma, hydatidiform mole

Heberden's nodes - diagnosis? - where are they located? - why do they occur?
osteoarthritis - DIP swelling secondary to osteophytes

Heinz bodies - diagnosis?

G6PD deficiency

hypersensitivity vasculitis associated with hemorrhagic urticaria and upper respiratory tract infections - diagnosis?
Henoch-Schonlein purpura

heterophil antibodies - diagnosis? - caused by what?

infectious mononucleosis - caused by EBV

high-output cardiac failure (dilated cardiomyopathy) is associated with what vitamin deficiency? - what is the disease called?

vitamin B1 (thiamine) deficiency - wet beriberi

HLA-B27 - associated with what diseases?

Reiter's syndrome, ankylosing spondylitis, psoriasis, inflammatory bowel disease

disease associated with HLA-DR3 or DR4 - what causes it?

diabetes mellitus type 1 - autoimmune destruction of beta cells

Homer Wright rosettes - diagnosis?

neuroblastoma

honeycomb lung on x-ray - diagnosis?

interstitial fibrosis

symptoms of Horner's syndrome

ptosis, miosis, anhidrosis

Howell-Jolly bodies - caused by what?

splenectomy or nonfunctional spleen

caudate degeneration - diagnosis? - what is the inheritance pattern?

Huntington's disease - autosomal dominant

hyperphagia, hypersexuality, hyperorality, hyperdocility - diagnosis? - what is the affected organ?

Kluver-Bucy syndrome - affects amygdala

hyperpigmentation of skin - diagnosis?

primary adrenal insufficiency (Addison's disease)

hypersegmented neutrophils - diagnosis?

macrocytic anemia

hypertension and hypokalemia diagnosis?

Conn's syndrome (aldosterone-secreting tumor)

hypochromic microcytosis - possible diagnoses?

iron deficiency anemia, lead poisoning

increased alpha-fetoprotein in amniotic fluid/maternal serum - possible diagnoses?

neural tube defects (anencephaly, spina bifida)

increased uric acid levels - possible diagnoses?

gout, Lesch-Nyhan syndrome, myeloproliferative disorders, use of loop and thiazide diuretics

Janeway lesions - diagnosis?

endocarditis

what disease is the Jarish-Herxheimer reaction associated with, and what is it?
syphilis - overaggressive treatment of an asymptomatic patient that causes symptoms due to rapid lysis

what is the defect in Job's syndrome?

neutrophil chemotaxis abnormality - due to failure of IFN-gamma production by helper T cells

Kaposi's sarcoma - associated with?

AIDS in MSM

what is the defect in Kartagener's syndrome?

dynein defect

Kayser-Fleischer rings - diagnosis?

Wilson's disease

keratin pearls - diagnosis?

squamous cell carcinoma

Kimmelstiel-Wilson nodules - diagnosis?

diabetic nephropathy

bilateral amygdala lesions - diagnosis?

Kluver-Bucy syndrome

koilocytes - diagnosis?
HPV

Koplik spots - diagnosis?

measles

gastric adenocarcinoma with ovarian metastases

Krukenberg tumor (Puneet, this one is for you)

Kussmaul hyperpnea - diagnosis?

diabetic ketoacidosis

lens dislocation, aortic dissection, joint hyperflexibility - diagnosis? - what is the defect?
Marfan's syndrome - defect in fibrillin

what is the defect in Lesch-Nyhan syndrome?

HGPRT deficiency

Lewy bodies - diagnosis?

Parkinson's disease

what is Libman-Sacks disease?

endocarditis associated with SLE

lines of Zahn - diagnosis?

arterial thrombus

Lisch nodules - diagnosis?

neurofibromatosis (von Recklinghausen's disease)

low serum ceruloplasmin - diagnosis?

Wilson's disease

Nitrates (mechanism, use, toxicity)

Cause NO release -> vasodilation (veins >>> arteries); used in angina; fast tolerance, hypotension, flushing, headache Pharmacology Cardio

Adverse effects of statins

Hepatoxicity and muscle breakdown Pharmacology Cardio decrease CRP

Niacin (mechanism, use, toxicity)

Inhibits lipolysis and reduces VLDL secretion, lowering LDL and raising HDL; hyperlipidemia; flushing and hyperuricemia Pharmacology Cardio increase Glucose level

Cholestyramine, colestipol, colesevelam (mechanism, use, toxicity)

Inhibits reabsorption of bile acids -> lower LDL with slight increase in HDL; unpigmented gallbladder stones and malabsorption Pharmacology Cardio

Ezetimibe
Prevents cholesterol reabsorption -> lower LDL Pharmacology Cardio

Fibrates (gemfibrozil + -fibrates) (mechanism, use, toxicity)

Upregulates LPL -> lower triglycerides, slightly inc. HDL and slightly dec. LDL; myositis and hepatoxicity Pharmacology Cardio

Digoxin and digitoxin (mechanism, use, toxicity)

Inhibits Na/K ATPase -> indirectly inhibits Na/Ca exchanger -> inc. calcium levels -> inc. contractility; stimulates the vagus; causes cholinergic symptoms and hyperkalemia Pharmacology Cardio

Class 1A antiarrhythmics
Quinidine, procainamide, and disopyramide; inc. AP duration and QT interval; can cause torsades de pointes, cinchonism (qunidine), procainamide (drug-induced lupus) Pharmacology Cardio in WPW blocks open channel

Class 1B antiarrhythmics
Lidocaine iv, mexiletine and tocainide oral; dec. AP duration especially in depolarized/ischemia tissue; best following MI Pharmacology Cardio blocks inactive channel

Class 1C antiarrhythmics
Flecainide, propafenone; no effect on AP, used in ventricular tachycardias; do not use postMI due to risk for arrhythmias Pharmacology Cardio blocks all na channels

Class 1 antiarrhythmics (general mechanism and toxicity)

Blocks Na channels, decreasing the slope of phase 0 depolarization; toxicity exacerbated by hyperkalemia Pharmacology Cardio

Class 2 antiarrhythmics
Beta-blockers; reduces cAMP, slowing SA and AV node activity, increases PR interval; adverse effects include impotence, asthma exacerbation, sedation Pharmacology Cardio

Class 3 antiarrhythmics
Amiodarone, ibutilide, dofetilide, sotalol (excessive b block); K channel blockers; inc. AP duration and QT interval Pharmacology Cardio

Toxicity of amiodarone
Pulmonary fibrosis, hepatotoxicity, thyroid dysfunction Pharmacology Cardio

Class 4 antiarrhythmics

Ca channel blockers; verapamil and diltiazem; dec. conduction velocity and inc. PR interval; cause constipation, flushing, and edema Pharmacology Cardio

Adeosine (mechanism, use, toxicity)

Inc. K efflux, hyperpolarizing the cell; used in supraventricular tachycardias; can cause flushing, hypotension, and chest pain Pharmacology Cardio

Magnseium (mechanism, use, toxicity)

Used in torsades de pointes and digoxin toxicity Pharmacology Cardio

Treatment for prolactinoma

Bromocriptine or cabergoline (dopamine agonists) Pharmacology Endocrine

Treatment of secondary hyperaldosteronism

Spironolactone (or other AT2 antagonist) Pharmacology Endocrine

Treatment of carcinoid syndrome

Octreotide (somatostatin analogues) Pharmacology Endocrine

Rapid-acting insulins (3)

Lispro, aspart, and glulisine Pharmacology Endocrine

Short-acting insulin (1)

Regular Pharmacology Endocrine

Intermediate-acting insulin (1)

NPH Pharmacology Endocrine

Long-acting insulins (2)

Glargine and detemir Pharmacology Endocrine

Metformin (mechanism, use, toxicity)

Biguanide; unknown mechanism; increases insulin sensitivity and glycolysis and decreases gluconeogenesis; can cause lactic acidosis (don't use in renal failure patients) Pharmacology Endocrine

Tolbutamide, chlorpropamide (mechanism, use, toxicity)

First-generation sulfonylureas; close beta-cell K channels, causing depolarization and increased insulin release; causes disulfuramlike effects Pharmacology Endocrine

Glyburide, glimepiride, glipizide (in patients with renal failure due to hepatic clearance) (mechanism, use, toxicity)
Second-generation sulfonylureas; close betacell K channels, causing depolarization and increased insulin release; causes hypoglycemia Pharmacology Endocrine

Pioglitazone, rosiglitazone (mechanism, use, toxicity)

Thiazolidinediones; activates PPAR-gamma, increasing insulin sensitivity and adiponectin levels; causes weight gain, hepatotoxicity, and heart failure Pharmacology Endocrine

Acarbose, miglitol (mechanism, use, toxicity)

Alpha-glucosidase inhibitors; prevent sugar hydrolysis and absorption, reducing blood sugar levels Pharmacology Endocrine

Pramlintide (mechanism, use, toxicity)

Amylin analog; reduces glucagon secretion; causes hypoglycemia Pharmacology Endocrine

Exenatide, liraglutide (mechanism, use, toxicity)

GLP-1 analogues; increase insulin, decrease glucagon secretion; causes pancreatitis Pharmacology Endocrine

Linagliptin, saxagliptin, sitagliptin (mechanism, use, toxicity)

DPP-4 inhibitors; increase insulin, decrease glucagon secretion; causes mild urinary/respiratory infections Pharmacology Endocrine inhibit breakdown of GLP

Propylthiouracil (mechanism, use, toxicity)

Blocks thyroid peroxidase and 5'-deiodinase; used to treat hyperthyroidism; causes agranulocytosis, aplastic anemia, hepatotoxicity Pharmacology Endocrine

Methimazole (mechanism, use, toxicity)

Blocks thyroid peroxidase; used to treat hyperthyrodism; teratogenic Pharmacology Endocrine

Levothyroxine, triiodothyronine (mechanism, use, toxicity)

Thyroid hormone analogs; causes thyrotoxicosis Pharmacology Endocrine

Oxytocin (mechanism, use, toxicity)

Used to control uterine hemhorrage Pharmacology Endocrine

Demeclocycline (mechanism, use, toxicity)

ADH antagonist used to treat SIADH; can cause photosensitivty and bone/teeth abnormalities Pharmacology Endocrine

Glucocorticoids (mechanism, use, toxicity)

Inhibits phospholipase A2 activity and expression of COX-2; used for immune suppression; can cause Cushing's syndrome, adrenal insufficiency (if withdrawn quickly) Pharmacology Endocrine

Cimetidine and ranitidine (mechanism, use, toxicity)

H2 antagonists; used to treat hyperchloridia; cimeditine is a P-450 inhibitor and has antiandrogenic effects, both reduce creatinine secretion Pharmacology GI

-prazoles (mechanism, use, toxicity)

Irreversibly inhibit the H/K pump; used to treat hyperchloridia; increased risk of C. difficile infection and hypomagnesemia Pharmacology GI

Bismuth, sucralfate (mechanism, use, toxicity)

Coats ulcer base and protects underlying tissue Pharmacology GI

Misoprostol (mechanism, use, toxicity)

PGE1 analog that decreases acid production and increases bicarb production; used to prevent NSAID ulcers; abortifacient Pharmacology GI

Octreotide (mechanism, use, toxicity)

Somatostatin analog; used to treat VIPoma and carcinoid syndrome Pharmacology GI

Toxicity of long-term antacid use

Hypokalemia Pharmacology GI

Infliximab (mechanism, use, toxicity)

Anti-TNF; used to treat IBD and RA; can cause activation of latent microbes Pharmacology GI

Sulfasalazine (mechanism, use, toxicity)

Combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (antiinflammatory); used to treat IBD; causes oligospermia Pharmacology GI

Ondansetron (mechanism, use, toxicity)

5-HT3 antagonist; used as an antiemetic Pharmacology GI chemo, headache constipation

Metoclopramide (mechanism, use, toxicity)

D2 antagonist; used to increase gut muscle activity and as an antiemetic; causes parkinson signs Pharmacology GI not in small bowel obstruction

Can be used to prevent mast cell degranulation

Cromolyn sodium Pharmacology Heme/Onc

Treatment of lead poisoning

Dimercaprol and EDTA, succimer in kids Pharmacology Heme/Onc

Heparin (mechanism, use, toxicity)

Activates antithrombin, which inactivates thrombin and Xa; used for immediate coagulation and in pregnant women; some patients develop antibodies to platelet factor 4 (HIT) Pharmacology Heme/Onc

Enoxaparin, dalteparin (mechanism, use, toxicity)

Same actions as heparin, but has a longer halflife, does not have to be monitored as closely, and has a reduced risk of HIT Pharmacology Heme/Onc

Warfarin (mechanism, use, toxicity)

Inactivated gamma-carboxylation of factors II, VII, IX, X, C, and S; used for long-term and non-immediate anticoagulation; can cause

tissue necrosis, teratogenic Pharmacology Heme/Onc

Alteplase, reteplase, tenecteplase (mechanism, use, toxicity)

Converts plasminogen to plasmin; used as a thrombolytic Pharmacology Heme/Onct

Aspirin (mechanism, use, toxicity)

Irreversibly inhibits COX-1 and COX-2; antiplatelet and anti-inflammatory; gastric ulcers, tinnitus, Reye's syndrome in childhood viral infections Pharmacology Heme/Onc

Clopidogrel, ticlodipine, prasugrel, ticagrelor (mechanism, use, toxicity)

Irreversibly blocks ADP receptors on platelets, preventing degranulation; used for acure coronary syndrome; ticlodipine causes neutropenia Pharmacology Heme/Onc

Cilostazol, dipyridamole (mechanism, use, toxicity)

Phosphodiesterase inhibitor, increases cAMP and decreases ADP, preventing platelet degranulation; nausea, headache, facial flushing, hypotension Pharmacology Heme/Onc

Abciximab, eptifibatide, tirofiban (mechanism, use, toxicity)

GPIIb/IIIa inhibitors, preventing platelet aggregation; bleeding, thrombocytopenia Pharmacology Heme/Onc

Methotrexate (mechanism, use, toxicity)

Inhibits dihydrofolate reductase, inhibiting DNA synthesis; myelosuppression, macrovesicular fatty change in liver Pharmacology Heme/Onc leukemias, lymphomas choriocarcinoma sarcomas abortion ectopic pregnancy RA, psoriasis

5-fluorouracil (mechanism, use, toxicity)

Pyrimidine analog that is activated and inhibits thymidylate synthase, inhibiting DNA synthesis; myelosuppression, photosensitivity Pharmacology Heme/Onc colon ca, basal cell, IV only

Cytarabine (mechanism, use, toxicity)

Pyrimidine analog that inhibits DNA polymerase; leukopenia, thrombocytopenia, megaloblastic anemia Pharmacology Heme/Onc leuk, lympomas

Azathioprine, 6-mercaptopurine, 6thioguanine (mechanism, use, toxicity)

Purine analogs that are activated by HGPRT and inhibit purine synthesis; toxicity is increased with allopurinol, causes bone marrow, GI, and liver toxicity Pharmacology Heme/Onc Leukemias

Dactinomycin (actinomycin D) (mechanism, use, toxicity)

DNA intercalator; used for childhood tumors; myelosuppression Pharmacology Heme/Onc Wilms Ewig Rhabdomyosarcoma

Doxorubicin (Adriamycin), daunorubicin (mechanism, use, toxicity)

Generates free radicals that cause DNA strand breaks; dilated cardiomyopathy, myelosuppression, alopecia Pharmacology Heme/Onc solid tumor leukemias lymphomas

Bleomycin (mechanism, use, toxicity)

Generates free radicals that cause DNA strand breaks; pulmonary fibrosis with minimal myelosuppression Pharmacology Heme/Onc testiclar Hodgkin

Cyclophosphamide, ifosfamide (mechanism, use, toxicity)

Crosslinks DNA (must be activated by liver); myelosuppression, hemhorragic cystitis (can be minimized with mesna) Pharmacology

Heme/Onc solid tumors, leak, breast, lymphomas some brain

Carmustine, lomustine, semustine, streptozocin (mechanism, use, toxicity) Nitrosoureas

Used to treat CNS tumors Pharmacology Heme/Onc

Busulfan (mechanism, use, toxicity)

Alkylates DNA; pulmonary fibrosis, hyperpigmentation Pharmacology Heme/Onc CML, ablation

Vincristine, vinblastine (mechanism, use, toxicity)

Block microtubule polymerization; vincristine causes neurotoxicity, vinblastine causes bone marro suppression Pharmacology Heme/Onc solid tumors leuk lymphomas

Paclitaxel (mechanism, use, toxicity)

Blocks microtubule breakdown; myelosuppression Pharmacology Heme/Onc ovarian and breast

Cisplatin, carboplatin (mechanism, use, toxicity)

Crosslinks DNA; nephrotoxicity (minimize with chloride diuresis, amifostine), acoustic n. damage Pharmacology Heme/Onc testicular bladder ovary lung

Etoposide, teniposide (mechanism, use, toxicity)

Inhibits topoisomerase II; myelosuppression, GI upset, alopecia Pharmacology Heme/Onc solid tumors leuk lymphomas

Hydroxyurea (mechanism, use, toxicity)

Inhibits ribonucleotide reductase; used in cancers and HbSS disease; bone marrow suppression Pharmacology Heme/Onc Melanoma CML Sickle , Polycythemia vera

Prednisone (mechanism, use, toxicity)

Unknown but may trigger apoptosis in dividing cells; Cushingoid symptoms Pharmacology Heme/Onc

Tamoxifen, raloxifene (mechanism, use, toxicity)

Prevents estrogen receptor binding; used in breast cancer and prevention of osteoporosis; tamoxifen increases the risk of endometrial cancer due to agonist effects Pharmacology Heme/Onc

Trastuzumab (mechanism, use, toxicity)

Antibody against HER-2 receptor; cardiotoxicity Pharmacology Heme/Onc

Imatinib (mechanism, use, toxicity)

Antibody against bcr-abl tyrosine kinase Pharmacology Heme/Onc

Rituximab (mechanism, use, toxicity)

Antibody against CD20; used to treat nonHodgkin's lymphoma and rheumatoid arthritis Pharmacology Heme/Onc

Vemurafenib (mechanism, use, toxicity)

B-raf kinase inhibitor (V600 mutation); used in metastatic melanoma Pharmacology Heme/Onc

Bevacizumab (mechanism, use, toxicity)

Antibody against VEGF Pharmacology Heme/Onc met. melanoma

Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac (mechanism, use, toxicity)

Reversible COX inhibitor; gastric ulcers, renal ischemia (due to constriction of afferent arteriole) Pharmacology Musculoskeletal

Celecoxib (mechanism, use, toxicity)

Reversible COX-2 inhibitor; antiinflammatory without damage to gastric mucosa; sulfa allergy, thrombosis Pharmacology Musculoskeletal

Acetominophen (mechanism, use, toxicity)

COX inhibitor in the CNS (not antiinflammatory); causes hepatic necrosis Pharmacology Musculoskeletal

Alendronate (mechanism, use, toxicity)

Pyrophosphate analog that inhibits osteoclasts; used to treat osteoporosis, hypercalcemia, and Paget's disease; corrosive esophagitis Pharmacology Musculoskeletal

Allopurinol (mechanism, use, toxicity)

Xanthine oxidase inhibitor, reduces production of uric acid Pharmacology Musculoskeletal

Febuxostat (mechanism, use, toxicity)

Xanthine oxidase inhibitor Pharmacology Musculoskeletal

Probenecid (mechanism, use, toxicity)

Inhibits reabsorption of uric acid in PCT Pharmacology Musculoskeletal

Colchine (mechanism, use, toxicity)

Inhibits microtubule polymerization, preventing neutrophil extravasation Pharmacology Musculoskeletal

Etanercept (mechanism, use, toxicity)

TNF-alpha receptor that binds free TNF-alpha Pharmacology Musculoskeletal

Infliximab, adalimumab (mechanism, use, toxicity)

Anti-TNF-alpha antibody Pharmacology Musculoskeletal

Latanoprost (mechanism, use, toxicity)

PGF2 analog that increases the outflow of aqueous humor; can cause darkening of the iris Pharmacology Neurology

Morphine, fentanyl, cofeine, heroin, methadone, meperidine, dextromethorphan, diphenoxylate (mechanism, use, toxicity)

Mu opioid agonists that open K channels and close Ca channels, inhibting synaptic transmission; addiction, respiratory depression, constipation, miosis Pharmacology Neurology

Butorphanol (mechanism, use, toxicity)

Mu opioid partial agonist; used to treat severe pain; causes withdrawal if being treated with full agonist Pharmacology Neurology

Tramadol (mechanism, use, toxicity)

Weak opioid agonist that inhibits serotonin and NE reuptake; increases risk for seizures Pharmacology Neurology

First-line therapy for simple partial seizures

Carbamazepine Pharmacology Neurology

First-line therapy for complex partial seizures

Carbamazepine Pharmacology Neurology

First-line therapies for tonic-clonic seizures (3)

Carbamazepine, phenytoin, valproate Pharmacology Neurology

First-line therapy for absence seizures

Ethosuximide Pharmacology Neurology

Phenytoin (mechanism, use, toxicity)

Increases Na channel inactivation and inhibits glutamate release; used for simple, complex, and tonic-clonic seizures and status epilecticus prophylaxis; nystagmus, gingival hyperplasia, hirsutism, megaloblastic anemia, teratogenic, drug-induced lupus, P450 inducer Pharmacology Neurology

Carbamazepine (mechanism, use, toxicity)

Increases Na channel inactivation; first-line for simple, complex, and tonic-clonic seizures and trigeminal neuralgia; agranulocytosis, aplastic anemia, P450 inducer, SIADH, liver toxicity Pharmacology Neurology

Lamotrigine (mechanism, use, toxicity)

Blocks Na channels; used for simple, complex, and tonic-clonic seizures; Steven-Johnson syndrome Pharmacology Neurology

Gabapentin (mechanism, use, toxicity)

Inhibits Ca channels; used for simple, complex, and tonic-clonic seizures, migraine prophylaxis, peripheral neuropathy, bipolar disorder; ataxia Pharmacology Neurology

Topiramate (mechanism, use, toxicity)

Blocks Na channels and increases GABA secretion; used for simple, complex, and tonicclonic seizures and migraine prevention; mental dulling, kidney stones, weight loss Pharmacology Neurology

Phenobarbital (mechanism, use, toxicity)

Increases GABA channel action; first-line for simple, complex, and tonic-clonic seizures in children; P450 inducer Pharmacology Neurology

Valproate (mechanism, use, toxicity)

Increases Na channel inactivation and increases GABA levels; first-line for tonicclonic seizures, used for simplex, complex, tonic-clonic, and myoclonic seizures;

hepatotoxicity, neural tube defects, weight gain, tremor Pharmacology Neurology plateletes

Ethosuximide (mechanism, use, toxicity)

Blocks thalamic Ca channels; first-line for absence seizures; GI distress, Steven-Johnson syndrome Pharmacology Neurology

Benzodiazepines (mechanism, use, toxicity)

Increases frequency of GABA channel opening; first-line for status epilepticus (diazepam, lorazepam), used for eclampsia seizures (diazepam, lorazepam), anxiety, alcohol withdrawl, sleep walking, night terrors; sedation Pharmacology Neurology

Tiagabine (mechanism, use, toxicity)

Inhibits GABA reuptake; used for simple and complex seizures Pharmacology Neurology

Vigabatrin (mechanism, use, toxicity)

Irreversibly inhibits GABA transaminase, increasing GABA concentration; used for simple and complex seizures Pharmacology Neurology

Levetriacetam (mechanism, use, toxicity)

Unknown mechanism; used for simple, complex, and tonic-clonic seizures Pharmacology Neurology

Phenobarbital, pentobarbial, thiopental, secobarbital (mechanism, use, toxicity)

Increase duration of GABA channel opening; induction of anesthesia, sedative; CNS depression, P450 inducer, contraindicated in patients with porphyrias Pharmacology Neurology

Triazolam, oxazepam, midazolam (mechanism, use, toxicity)

Short-acting benzodiazepines; more addictive potential Pharmacology Neurology

Barbituates vs. benzodiazepines (mechanism)

Increase duration vs. increase frequency Pharmacology Neurology

Zolpidem, zaleplon, eszopiclone (mechanism, use, toxicity)

BZ1 subtype GABA channel agonists; used to treat insomnia Pharmacology Neurology

Ketamine (mechanism, use, toxicity)

Blocks NMDA receptor; used as an anesthetic; increases cardiac activity, hallucinations, bad dreams Pharmacology Neurology

Order of sensory loss when using local anesthetics

Pain -> temperature -> touch -> pressure Pharmacology Neurology

Succinylcholine (mechanism, use, toxicity)

ACh receptor agonist, produces sustained depolarization and desensitization; used as a paralytic; hypercalcemia, hyperkalemia, malignant hyperthermia Pharmacology Neurology

Tubocurarine, -curium drugs (mechanism, use, toxicity)

ACh antagonists; used as paralytics Pharmacology Neurology

Dantrolene (mechanism, use, toxicity)

Inhibits release of Ca from sarcoplasmic reticulum and skeletal muscle; used to treat malignant hyperthermia and neurolepticmalignant syndrome Pharmacology Neurology

Levodopa/carbidopa (mechanism, use, toxicity)

Converted to dopamine by dopa decarboxylase in CNS/inhibits peripheral dopa decarboxylase activity; used to treat parkinson symptoms; can cause arrhythmias and "on/off" phenomenon Pharmacology Neurology

Selegiline (mechanism, use, toxicity)

MAO-B (prefers dopamine for breakdown) inhibitor, inhibits dopamine breakdown; used to treat parkinson symptoms; enhances adverse effects of levodopa Pharmacology Neurology

Donepezil, galantamine, rivastigmine (mechanism, use, toxicity)

ACh esterase inhibitors; used to treat Alzheimer's disease; cholinergic symptoms Pharmacology Neurology

Sumatriptan (mechanism, use, toxicity)

Agonist at 1B/1D serotonin receptors; used to treat acute migraines and cluster headaches; coronary vasospasm Pharmacology Neurology

Trifluoperzine, fluphenazine, haloperidol (mechanism, use, toxicity)

High potency antipsychotics that antagonize D2 receptors; used to treat schizoprehnia, psychosis, mania, and Tourette's; hyperprolactinemia, anti-cholinergic symptoms (dry mouth, constipation), extrapyramidal effects (dyskinesia), neuroleptic malignany syndrome, tardive dyskinesia (haloperidol) Pharmacology Psychiatry

Chlorpromazine, thioridazine (mechanism, use, toxicity)

Low potency antipsychotics that antagonize D2 receptors; used to treat schizophrenia, psychosis, mania, and Tourette's; corneal

deposits (chlorpromazine), retinal desporits (thioridazine) Pharmacology Psychiatry

Olanzapine, clozapine, quetiapine, risperidone, aripripazole, ziprasidone (mechanism, use, toxicity)

Atypical antipsychotics with unknown mechnism; used for schizophrenia, bipolar disorder, OCD, and others; weight gain (olanzapine, clozapine), agranulocytosis (clozapine), seizures (clozapine), prolonged QT (ziprasidone) Pharmacology Psychiatry

Lithium (mechanism, use, toxicity)

Unknown mechanism; used for bipolar disorder and SIADH; tremor, sedation, edema, hypothyroidism, polyuria Pharmacology Psychiatry

Buspirone (mechanism, use, toxicity)

Agonizes 1A serotonin receptors; used for generalized anxiety disorder; no side effects with alcohol, but takes 1-2 weeks for improvement Pharmacology Psychiatry

Fluoxetine, paroxetine, sertraline, citalopram (mechanism, use, toxicity)

Block reuptake of serotonin from the synaptic cleft; depression and others; sexual dysfunction, sertonin syndrome (hyperthermia, myoclonus, flushing, diarrhea, seizures) Pharmacology Psychiatry

Venlafaxine, duloxetine (mechanism, use, toxicity)

Block reuptake of NE and serotonin from synaptic cleft; depression, diabetic neuropathy (duloxetine); hypertension Pharmacology Psychiatry

-iptyline, -ipramine, doxepin, amoxapine (mechanism, use, toxicity)

TCAs, block reuptake of NE and serotonin; depression, bewetting (imipramine), OCD

(clomipramine); convulsions, coma, arrhythmias, sedation, hypotension, anticholinergic effects Pharmacology Psychiatry

Tranylcypromine, phenelzine, isocarboxazid, selegiline (mechanism, use, toxicity)

Inhibit breakdown of NE, serotonin, and dopamine; used for atypical depression, anxiety, and hypochondriasis; hypertensive crisis (tyramine in wine/cheese), don't use with other serotonin agonists Pharmacology Psychiatry

Bupropion (mechanism, use, toxicity)

Increases NE and dopamine; used for smoking sensation, depression; seizures in bulimics Pharmacology Psychiatry

Mirtazapine (mechanism, use, toxicity)

Alpha-2 antagonist, increases NE and serotonin release, and serotonin receptor agonist; used for depression; sedation, increased appetite with weight gain; Pharmacology Psychiatry

Maprotiline (mechanism, use, toxicity)

Blocks NE reuptake; used for depression; sedation, hypotension Pharmacology Psychiatry

Trazodone (mechanism, use, toxicity)

Inhibits serotonin uptake; used for insomnia; pripism Pharmacology Psychiatry

Mannitol (mechanism, use, toxicity)

Osmotic diuretic; used to treat drug overdose and increased ICP; pulmonary edema, CHF Pharmacology Renal

Acetazolamide (mechanism, use, toxicity)

Carbonic anhydrase inhibitor; used for glaucoma, metabolic alklalosis;

hyperchloremic metabolic acidosis, ammonia toxicity, sulfa allergy Pharmacology Renal loss of NH4+

Furosemide (mechanism, use, toxicity)

Inhibits NKCC channel, preventing urine concentration; used in hypertension, CHF, hypercalcemia; ototoxicity, hypokalemia, hypocalcemia, nephritis, gout, sulfa allergy Pharmacology Renal

Ethacrynic acid (mechanism, use, toxicity)

Inhibits NKCC channel; used in patients with furosemide (sulfa) allergy; hyperuricemia Pharmacology Renal

Hydrochlorothiazide (mechanism, use, toxicity)

Inhibits NaCl reabsorption in DCT and increases Ca reabsorption; hypertension and hypercalcinuria; hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy Pharmacology Renal not in diabetics

Spironolactone, eplerenone (mechanism, use, toxicity)

Aldosterone receptor antagonists; hyperaldosteronism, CHF, hypokalemia; hyperkalemia (arrhythmias), antiandrogen effects with spironolactone Pharmacology Renal

Triamterene, amiloride (mechanism, use, toxicity)

Block sodium channels in cortical collecting duct; hyperaldosteronism, CHF Pharmacology Renal

Captopril, enalapril, lisinopril (mechanism, use, toxicity)

ACE inhibitor, leads to reduced angiotensin II levels and decreases GFR; prevents heart

remodeling, hypertension, CHF; cough, angioedema, transient creatinine increase, hyperkalemia Pharmacology Renal

Losartan, valsartan (mechanism, use, toxicity)

Angiotensin II receptor antagonists; similar to ACE inhibitors, but do not cause cough due to normal metabolism of bradykinin Pharmacology Renal

Leuprolide (mechanism, use, toxicity)

GnRH analog that acts as an agonist in pulsatile doses and an antagonist in continuous doses; used as an agonist for infertility and an antagonist for prostate cancer, fibroids, and precocious puberty; antiandrogenic Pharmacology Reproductive

Finasteride (mechanism, use, toxicity)

5-alpha reductase inhibitor; used for BPH and male-pattern baldness Pharmacology Reproductive

Flutamide (mechanism, use, toxicity)

Testosterone receptor antagonist; used in prostate cancer Pharmacology Reproductive

Ketoconazole (mechanism, use, toxicity)

Inhibits 17,20-desmolase, stopping sex steroid synthesis; used to treat polycystic ovarian syndrome Pharmacology Reproductive
Apoptosis (definition) Programmed cell death; ATP required. Mediated by caspases. Apoptosis is characterized by...? Cell shrinkage, nuclear shrinkage and basophilia (pyknosis), membrane blebbing, pyknotic nuclear fragmentation (karyorrhexis), nuclear fading (karyolysis), and formation of apoptotic bodies, which are then phagocytosed. No significant inflammation.

When does apoptosis occur? Occurs during embryogenesis, hormone induction (menstruation), immune cellmediated death, injurious stimuli (e.g., radiation, hypoxia), atrophy (e.g., endometrial lining during menopause) Necrosis (definition) Enzymatic degradation of a cell resulting from exogenous injury. Necrosis is characterized by...? Enzymatic digestion and protein denaturation, with release of intracellular components. Inflammatory. Necrosis morphologies Coagulative (heart, liver, kidney) Liquefactive (brain) Caseous (tuberculosis) Fat (pancreas) Fibrinoid (blood vessels) Gangrenous (limbs, GI tract) Characteristics of reversible cell injury Cellular swelling Nuclear chromatin clumping Decr ATP synthesis Ribosomal detachment Glycogen depletion Fatty change Characteristics of irreversible cell injury Plasma membrane damage Lysosomal rupture Ca2+ influx --< oxidative phosphorylation Nuclear pyknosis, karyolysis, karyorrhexis Mitochondrial permeability 5 Characteristic signs of inflammation Rubor (redness) Dolor (pain) Calor (heat) Tumor (swelling) Functio laesa (loss of fxn) Fluid exudation in inflammation Incr vascular permeability, vasodilation, endothelial injury. Leukocyte activation in inflammation

Emigration (rolling, tight binding, diapedesis); chemotaxis (bacterial products, complement, cytokines); phagocytosis and killing. Substances that are chemotactic for neutrophils IL-8 C5a Leukotriene B4 Kallikrein Fibrosis in inflammation Fibroblast emigration and proliferation; deposition of ECM. Acute inflammation Neutrophil, eosinophil, and Ab-mediated. Rapid onset (seconds-minutes), lasts minutes-days. Chronic inflammation Mononuclear cell mediated: Characterized by persistent destruction and repair. Associated w/ blood vessel proliferation, fibrosis. Granuloma -nodular collections of epithelioid macrophages and giant cells. Granulomatous dz's TB (caseating) Syphilis Listeria monocytogenes Wegener's granulomatosis Leprosy Bartonella Some fungal pneumonias Sarcoidosis Crohn's dz *Granuloma formation is IL-2, interferongamma mediated. Resolution of inflammation Restoration of normal structure. Granulation tissue -- highly vascularized, fibrotic. Abscess -fibrosis surrounding pus. Fistula -- abnormal communication. Scarring -- collagen deposition resulting in altered structure and fxn. Characteristics of trans udate Hypocellular Protein-poor Specific gravity > 1.012 Due to: Incr hydrostatic pressure Decr oncotic pressure Na+ retention Characteristics of ex udate Cellular Protein-rich Specific gravity < 1.020 Due to: Lymphatic obstruction Inflammation

Leukocyte extravasation Neutrophils exit from blood vessels at sites of injury and inflammation in 4 steps: 1.) Rolling 2.) Tight binding 3.) Diapedesis 4.) Migration <img src="218a.JPG" /> Rolling (step 1 in leukocyte extravasation) Mediated by E-selectin and P-selectin on vascular endothelium binding to sialyl Lewis^x on the leukocyte. <img src="218a.JPG" /> Tight binding (step 2 of leukocyte extravasation) Mediated by ICAM -1 on vascular endothelium binding to LFA-1 (integrin) on the leukocyte ("Hold on tight to your CAM era") <img src="218a.JPG" /> Diapedesis (step 3 in leukocyte extravasation) Leukocyte travels btw endothelial cells and exits blood vessel; PECAM-1 is involved. <img src="218a.JPG" /> Migration (step 4 in leukocyte extravasation) Leukocyte travels thru the interstitium to the site of injury or infxn guided by chemotactic signals (e.g., cytokines) <img src="218a.JPG" /> Things that initiate Free radical injury Radiation exposure Metabolism of drugs (phase I) Redox rxtn Nitric oxide Transition metals Leukocyte oxidative burst *Reperfusion after anoxia induces free radical production (e.g., superoxide) and is a major cause of injury after thrombolytic therapy Free radical injury induces cell injury thru...? Membrane lipid peroxidation Protein modification DNA Breakage Free radical degradation Produced thru enzymes (catalase, superoxide dismutase, glutathioe peroxidase), spontaneous decay, antioxidants (Vitamins A, C, E).

Amyloid structure Beta-pleated sheet demonstrable by apple-green birefringence of Congo red stain under polarized light; affected tissue has waxy appearance. Type of amyloid protein: Primary Protein? Derived from...? AL protein Derived from Ig L ight chains (multiple myeloma) (AL = L ight chains) Type of amyloid protein: Secondary Protein? Derived from...? AA protein Derived from serum amyloidassociated (SAA) protein (chronic inflammatory dz) (AA = A cute-phase reactant) Type of amyloid protein: Senile cardiac Protein? Derived from...? Protein = transthyretin Derived from AF (AF = old F ogies) Type of amyloid protein: DM2 Protein? Derived from...? Amylin protein Derived from AE (AE = E ndocrine) Type of amyloid protein: Medullary carcinoma of thyroid Protein? Derived from...? A-CAL protein Derived from calcitonin (A-CAL = CAL citonin) Type of amyloid protein: Alzheimer's dz Protein? Derived from...? Beta-amyloid Derived from amyloid precursor protein (APP) Type of amyloid protein: Dialysis-associated Protein? Derived from...? Beta-2 microglobulin Derived from MHC class I proteins. Hypovolemic/cardiogenic shock

Low-output failure. Findings: cold, clammy pt; low cardiac output; Incr TPR. Septic shock High-output failure; high mixed venous pressure. Findings: hot pt, dilated arterioles, decr TPR. Neoplastic progression: normal state, before anything goes wrong Normal cells w/ basal --< apical differentiation <img src="220a.JPG" /> Neoplastic progression: step 1 Hyperplasia/dysplasia Cells have increased in # (hyperplasia ) Abnormal proliferation of cells w/ loss of size, shape, and orientation (dysplasia ) <img src="220b.JPG" /> Neoplastic progression: step 2 In situ carcinoma Neoplastic cells hae not invaded basement membrane. High nuclear/cytoplasmic ratio and clumped chromatin Neoplastic cells encompass entire thickness Tumor cells are monoclonal <img src="220c.JPG" /> Neoplastic progression: step 3 Invasive carcinoma Cells have invaded basement membrane using collagenases and hydrolases Can metastasize if they reach a blood or lymphatic vessel <img src="220d.JPG" /> Neoplastic progression: step 4 Metastasis Metastasis = Spread to distant organ Must survive immune attack. "Seed and soil" theory of metastasis: Seed = tumor embolus Soil = target organ -- liver, lungs, bone, brain... Angiogenesis allows for tumor survival Decr cadherin, incr laminin, integrin receptors <img src="220e.JPG" /> Hyperplasia Incr in # of cells. Reversible.

Metaplasia 1 adult cell type is replaced by another. Often 2' to irritation and/or environmental exposure (e.g., squamous metaplasia in trachea and bronchi of smokers) Reversible. Dysplasia Abnormal growth w/ loss of cellular orientation, shape, and size in comparizon to normal tissue maturation; commonly preneoplastic. Reversible. Anaplasia Abnormal cells lacking differentiation; like primitive cells of the same tissue, often equated w/ undifferentiated malignant neoplasms. Little or no resemblance to tissue of origin. Irreversible. Neoplasia A clonal proliferation of cells that is uncontrolled and excessive. Irreversible. Desmoplasia Fibrous tissue formation in response to a neoplasm. Irreversible. Tumor grade Degree of cellular differentiation based on histologic appearance of tumor. Usually graded I-IV based on degree of differentiation and number of mitoses per high-power field; character of tumor itself. Tumor stage Degree of localization/spread based on site and size of 1' lesion, spread to regional LNs, presence of metastases; spread of tumor in a specific pt. S tage = S pread TNM staging system T = size of T umor N = N ode involvement M = M etastases

Which usually has more prognostic value, tumor stage or grade? Usually stage < grade Tumor nomenclature: Epithelium What do you call a benign tumor of this tissue? .. a malignant one? Benign: Adenoma, papilloma Malignant: Adenocarcinoma, papillary carcinoma Tumor nomenclature: Blood cells What do you call a benign tumor of this tissue? .. a malignant one? Benign: -- Malignant: Leukemia, lymphoma Tumor nomenclature: Blood vessels What do you call a benign tumor of this tissue? .. a malignant one? Benign: hemangioma Malignant: Angiosarcoma Tumor nomenclature: Smooth muscle What do you call a benign tumor of this tissue? .. a malignant one? Benign: Leiomyoma Malignant: Leiomyosarcoma Tumor nomenclature: Skeletal muscle What do you call a benign tumor of this tissue? .. a malignant one? Benign: Rhabdomyoma Malignant: Rhabdomyosarcoma Tumor nomenclature: Bone What do you call a benign tumor of this tissue? .. a malignant one? Benign: Osteoma Malignant: osteosarcoma Tumor nomenclature: Fat What do you call a benign tumor of this tissue? .. a malignant one? Benign: lipoma Malignant: liposarcoma Tumor nomenclature: < 1 cell type What do you call a benign tumor of this tissue? .. a malignant one?

Benign: mature teratoma (women) Malignant: immature teratoma and mature teratoma (men) Carcinoma vs. sarcoma Carcinoma = epithelial origin Sarcoma = mesenchymal origin (blood vessels, muscle, bone, fat, etc.) Both imply malignancy Benign Usually well-differentiated, slow growing, welldemarcated, no metastasis. Malignant May be poorlly differentiated, erratic growth, locally invasive/diffuse, may metastasize. Dz: Down syndrome What is the associated neoplasm? ALL (we ALL fall Down ) AML Neoplasm: ALL (we ALL fall Down ) AML With what dz is this associated? Down syndrome Dz: Xeroderma pigmentosum, albinism What is the associated neoplasm? Melanoma, basal cell carcinoma, and esp. squamous cell carcinomas of the skin Neoplasm: Melanoma, basal cell carcinoma, and esp. squamous cell carcinomas of the skin With what dz is this associated? Xeroderma pigmentosum, albinism Dz: Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants What is the associated neoplasm? Gastric adenocarcinoma Neoplasm: Gastric adenocarcinoma With what dz is this associated? Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants

Dz: Tuberous sclerosis (facial angiofibroma, seizures, mental retardation) What is the associated neoplasm? Astrocytoma, angiomyolipoma, and cardiac rhabdomyoma Neoplasm: Astrocytoma, angiomyolipoma, and cardiac rhabdomyoma With what dz is this associated? Tuberous sclerosis (facial angiofibroma, seizures, mental retardation) Dz: Actinic keratosis What is the associated neoplasm? Squamous cell carcinoma of the skin Neoplasm: Squamous cell carcinoma of the skin With what dz is this associated? Actinic keratosis Dz: Barrett's esophagus (chronic GI reflux) What is the associated neoplasm? Esophageal adenocarcinoma Neoplasm: Esophageal adenocarcinoma With what dz is this associated? Barrett's esophagus (chronic GI reflux) Dz: Plummer-Vinson syndrome (atrophic gastritis, esophageal webs, anemia; all due to iron deficiency) What is the associated neoplasm? Squamous cell carcinoma of esophagus Neoplasm: Squamous cell carcinoma of esophagus With what dz is this associated? Plummer-Vinson syndrome (atrophic gastritis, esophageal webs, anemia; all due to iron deficiency) Dz: Cirrhosis (alcoholic, hepatitis B or C) What is the associated neoplasm? Hepatocellular carcinoma

Neoplasm: Hepatocellular carcinoma With what dz is this associated? Cirrhosis (alcoholic, hepatitis B or C) Dz: Ulcerative colitis What is the associated neoplasm? Colonic adenocarcinoma Neoplasm: Colonic adenocarcinoma With what dz is this associated? Ulcerative colitis Dz: Paget's dz of bone What is the associated neoplasm? Secondary osteosarcoma and fibrosarcoma Neoplasm: Secondary osteosarcoma and fibrosarcoma With what dz is this associated? Paget's dz of bone Dz: Immunodeficiency states What is the associated neoplasm? Malignant lymphomas Neoplasm: Malignant lymphomas With what dz is this associated? Immunodeficiency states Dz: AIDS What is the associated neoplasm? Aggressive malignant lymphomas (nonHodgkin's) and Kaposi's sarcoma Neoplasm: Aggressive malignant lymphomas (non-Hodgkin's) and Kaposi's sarcoma With what dz is this associated? AIDS Dz: Autoimmune dz's (e.g., Hashimoto's thyroiditis, myasthenia gravis) What is the associated neoplasm? Benign and malignant lymphomas

Neoplasm: Benign and malignant lymphomas With what dz is this associated? Autoimmune dz's (e.g., Hashimoto's thyroiditis, myasthenia gravis) Dz: Acanthosis nigricans (hyperpigmentation and epidermal thickening) What is the associated neoplasm? Visceral malignancy (stomach, lung, breast, uterus) Neoplasm: Visceral malignancy (stomach, lung, breast, uterus) With what dz is this associated? Acanthosis nigricans (hyperpigmentation and epidermal thickening) Dz: Dysplastic nevus What is the associated neoplasm? Malignant melanoma Neoplasm: Malignant melanoma With what dz is this associated? Dysplastic nevus Dz: Radiation exposure What is the associated neoplasm? Sarcoma Neoplasm: Sarcoma With what dz is this associated? Radiation exposure Oncogenes Gain of fxn --< cancer. Need damage to only 1 allele. Oncogene: abl Associated tumor? CML tumor: CML What is the associated oncogene? abl Oncogene: c-myc Associated tumor?

Burkitt's lymphoma tumor: Burkitt's lymphoma What is the associated oncogene? c-myc Oncogene: bcl-2 Associated tumor? Follicular and undifferentiated lymphomas (inhibits apoptosis) tumor: Follicular and undifferentiated lymphomas (inhibits apoptosis) What is the associated oncogene? bcl-2 Oncogene: erb-B2 Associated tumor? Breast, ovarian, and gastric carcinomas tumor: Breast, ovarian, and gastric carcinomas What is the associated oncogene? erb-B2 Oncogene: ras Associated tumor? Colon carcinoma tumor: Colon carcinoma What is the associated oncogene? ras Oncogene: L -myc Associated tumor? L ung tumor tumor: L ung tumor What is the associated oncogene? L -myc Oncogene: N -myc Associated tumor? N euroblastoma tumor: N euroblastoma What is the associated oncogene? N -myc

Oncogene: ret Associated tumor? Multiple endocrine neoplasia (MEN) types II and III tumor: Multiple endocrine neoplasia (MEN) types II and III What is the associated oncogene? ret Oncogene: c-kit Associated tumor? Gastrointestinal stromal tumor (GIST) tumor: Gastrointestinal stromal tumor (GIST) What is the associated oncogene? c-kit Tumor suppressor genes Loss of fxn --< cancer; both allels must be lost for expression of dz. Tumor suppressor gene: Rb chromosome? Associated tumor? Chr. 13q Assoc.: Retinoblastoma, osteosarcoma Chr. 13q Assoc.: Retinoblastoma, osteosarcoma What is the tumor suppressor gene? Rb Tumor suppressor gene: BRCA1 chromosome? Associated tumor? Chr. 17q Assoc.: Breast and ovarian cancer Chr. 17q Assoc.: Breast and ovarian cancer What is the tumor suppressor gene? BRCA1 Tumor suppressor gene: BRCA2 chromosome? Associated tumor? Chr. 13q Assoc: breast cancer Chr. 13q Assoc: breast cancer What is the tumor suppressor gene?

BRCA2 Tumor suppressor gene: p 53 chromosome? Associated tumor? Chr. 17p Assoc: most human cancers (crap!), LiFraumeni syndrome Chr. 17p Assoc: most human cancers (crap!), LiFraumeni syndrome What is the tumor suppressor gene? p 53 Tumor suppressor gene: p 16 chromosome? Associated tumor? Chr. 9p Assoc: Melanoma ("MelaN oma is N ine") Chr. 9p Assoc: Melanoma ("MelaN oma is N ine") What is the tumor suppressor gene? p 16 Tumor suppressor gene: APC chromosome? Associated tumor? Chr. 5q Assoc: Colorectal cancer (assoc w/ FAP) Chr. 5q Assoc: Colorectal cancer (assoc w/ FAP) What is the tumor suppressor gene? APC Tumor suppressor gene: WT1 chromosome? Associated tumor? Chr. 11p Assoc: Wilms' tumor Chr. 11p Assoc: Wilms' tumor What is the tumor suppressor gene? WT1 Tumor suppressor gene: NF1 chromosome? Associated tumor? Chr. 17q Assoc: Neurofibromatosis type 1 Chr. 17q Assoc: Neurofibromatosis type 1 What is the tumor suppressor gene?

NF1 Tumor suppressor gene: NF2 chromosome? Associated tumor? Chr. 22q Assoc: Neurofibromatosis 2 ("Type 2 = 22") Chr. 22q Assoc: Neurofibromatosis 2 ("Type 2 = 22") What is the tumor suppressor gene? NF2 Tumor suppressor gene: DPC chromosome? Associated tumor? Chr. 18q Assoc: Pancreatic cancer [DPC = D eleted in P ancreatic C ancer"] Chr. 18q Assoc: Pancreatic cancer [DPC = D eleted in P ancreatic C ancer"] What is the tumor suppressor gene? DPC Tumor suppressor gene: DCC chromosome? Associated tumor? Chr. 18q Assoc: Colon cancer [DCC = D eleted in C olon C ancer] Chr. 18q Assoc: Colon cancer [DCC = D eleted in C olon C ancer] What is the tumor suppressor gene? DCC How should tumor markers be used clinically? Tumor markers should not be used as the primary tool for cancer Dx. They may be used to confirm Dx, to monitor for tumor recurrence, and to monitor response to therapy. Tumor markers: PSA Prostate-Specific Ag. Used to screen for prostate carcinoma. Can also be elevated in BPH and prostatitis. Tumor markers: Prostatic acid phospatase Prostate carcinoma.

Tumor markers: CEA Carcinoembryonic Ag. Very nonspecific, but produced by ~70% of colorectal and pancreatic cancers; also produced by gastric and breast carcinomas. Tumor markers: alpha-fetoprotein Normally made by fetus. Hepatocellular carcinomas. Nonseminomatous germ cell tumors of the testis (e.g., yolk sac tumor) Tumor markers: Beta-hCG "HCG" H ydatidiform moles C horiocarcinomas G estational trophoblastic tumors Tumor markers: CA-125 Ovarian, malignant epithelial tumors Tumor markers: S-100 Melanoma, neural tumors, astrocytomas. Tumor markers: Alkaline phosphatase Metastases to bone, obstructive biliary dz, Paget's dz of bone. Tumor markers: Bombesin Neuorblastoma, lung, and gastric cancer. Tumor markers: TRAP Tartrate-resistant acid phosphatase. Hairy cell leukemia -- a B-cell neoplasm. "TRAP the hairy animal." Tumor markers: CA-19-9 Pancreatic adenocarcinoma Sonic Hedgehog Gene Produced @ base of limbs in zone of polarizing activity. Involved in patterning along anterior/posterior axis. Produced @ base of limbs in zone of polarizing activity. Involved in patterning along anterior/posterior axis.

Sonic Hedgehog Gene Wnt-7 Gene Produced @ apical ectodermal ridge (thickened ectoderm @ distal end of each developing limb). Necessary for organization along dorsal/ventral axis. Produced @ apical ectodermal ridge (thickened ectoderm @ distal end of each developing limb). Necessary for organization along dorsal/ventral axis. Wnt-7 Gene FGF Gene Produced @ apical ectodermal ridge. Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs. Produced @ apical ectodermal ridge. Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs. FGF Gene Homeobox Gene Involved in segmental organization Involved in segmental organization Homeobox Gene Fetal Landmarks 1st week Day 0: fertilazation --< about 3d --< morula about 5d --< Blastocyst w/in wk 1 --< implantation as blastocyst Fetal Landmarks 2nd week Bilaminar disk (epiblast and hypoblast) Epiblast (ectoderm precursor) invaginates to form primitive streak --< gives rise to both intraembryonic mesoderm and endoderm. "Rule of 2's" for 2nd week of development 2 germ layers (bilaminar disk - epiblast, hypoblast) 2 cavities (amniotic cavity, yolk sac)

2 components of placenta (cytotrophoblast, syncytiotrophoblast) Fetal Landmarks Week 3 Gastrulation. Primitive streak, notochord, and neural plate begin to form. <img src="118a week 3.JPG" /> "Rule of 3's" for 3rd week of development 3 Germ layers (gastrula): 1.) Ectoderm 2.) Mesoderm 3.) Endoderm Fetal Landmarks Week 4 Heart begins to beat. Upper and lower limb buds begin to form. "Rule of 4's" for 4th week of development 4 heart chambers (heart begins to beat) 4 limb buds grow Fetal Landmarks Embryonic Period (wks 3-8) Neural tube forms, organogenesis. Extremely susceptible to teratogens. <img src="118b - week 3-8.JPG" /> Fetal Landmarks Fetal Period Week 8 (beginning of fetal period) Fetal Movement "Looks like" a baby Week 10 male/female genitalia Alar plate Dorsal plate, sensory (same position as spinal cord) Dorsal plate, sensory (same position as spinal cord) Alar plate Basal plate ventral plate, motor. (same orientation as spinal cord)

ventral plate, motor. (same orientation as spinal cord) Basal plate Surface ectoderm derivatives Adenohypophysis (anterior pituitary) Lens of eye Epithelial linings of oral cavity, eye, and nose Epidermis Salivary, sweat, and mammary glands Adenohypophysis (anterior pituitary) Lens of eye Epithelial linings of oral cavity, eye, and nose Epidermis Salivary, sweat, and mammary glands Surface ectoderm derivatives Neuroectoderm derivatives (Think "CNS + Brain") Brain: neurohypophysis (posterior pituitary), CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland Retina Spinal cord Notochord induces ectoderm to form neuroectoderm, postnatally: becomes nucleus pulposus of IV disks (Think "CNS + Brain") Brain: neurohypophysis (posterior pituitary), CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland Retina Spinal cord Notochord induces ectoderm to form neuroectoderm, postnatally: becomes nucleus pulposus of IV disks Neuroectoderm derivatives Neural Crest derivatives (ectoderm) ANS Dorsal Root ganglia Cranial nerves Celial ganglion Melanocytes Chromaffin cells of adrenal medulla Enterochromaffin cells Parafollicular (C) cells of thyroid Schwann cells Bones of skull Laryngeal cartilage Pia and arachnoid Odontoblasts Aorticopulminary septum ANS Dorsal Root ganglia Cranial nerves Celial ganglion Melanocytes Chromaffin cells of adrenal medulla Enterochromaffin cells

Parafollicular (C) cells of thyroid Schwann cells Bones of skull Laryngeal cartilage Pia and arachnoid Odontoblasts Aorticopulminary septum Neural Crest derivatives (ectoderm) Endoderm derivatives Gut tube epithelium and derivatives (e.g. lungs, liver, pancreas, thymus, parathyroid, thyroid follicular cells) Gut tube epithelium and derivatives (e.g. lungs, liver, pancreas, thymus, parathyroid, thyroid follicular cells) Endoderm derivatives Mesodermal derivatives Muscle, bone, connective tissue Serous lining of body cavities Spleen (derived from foregut mesentery) CV structures, lymphatics, blood Urogenital structures, kidneys Adrenal cortex Muscle, bone, connective tissue Serous lining of body cavities Spleen (derived from foregut mesentery) CV structures, lymphatics, blood Urogenital structures, kidneys Adrenal cortex Mesodermal derivatives Mesodermal defects "VACTERL" Vertebral defects Anal atresia Cardiac defects Tracheo-Esophageal fistula Renal defects Limb defects (in bone/muscle) "VACTERL" Vertebral defects Anal atresia Cardiac defects Tracheo-Esophageal fistula Renal defects Limb defects (in bone/muscle) Mesodermal defects Timing of teratogens Before wk 3: all-or-none Wk 3-8 (embryonic period): organogenesis, so most susceptible to insults wk <8: Affect growth/fxn Fetal Alcohol Syndrome

Leading cause of birth defects/congenital malformations and mental retardation in the US. If mom drank, increased risk of: pre- and post-natal developmental retardation microcephaly holoprosencephaly facial abnormalities Limb dislocation Heart and lung fistulas ACE-Inhibitors Renal Damage Teratogens: Renal Damage ACE-Inhibitors Cocaine Abnormal fetal development and fetal addiction. Placental abruption. Teratogens: Abnormal fetal development and fetal addiction. Placental abruption. Cocaine Diethylstilbestrol (DES) (A synthetic nonsteroidal estrogen) Vaginal clear cell carcinoma. Teratogens: Vaginal clear cell carcinoma. Diethylstilbestrol (DES) (A synthetic nonsteroidal estrogen) Iodide (lack or excess) Congenital goiter or hypothyroidism Teratogens: Congenital goiter or hypothyroidism Iodide (lack or excess) Vitamin A (excess) Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac abnormalities)

Teratogens: Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac abnormalities) Vitamin A (excess) Thalidomide Limb defects ("flipper" limbs) Teratogens: Limb defects ("flipper" limbs) Thalidomide Smoking (nicotine + CO) Preterm labor Placental problems Intra-uterine growth retardation (IUGR) ADHD Teratogens: Preterm labor Placental problems Intra-uterine growth retardation (IUGR) ADHD Smoking (nicotine + CO) X-rays, Anticonvulsants Multiple anomalies Teratogens: Multiple anomalies X-rays, Anticonvulsants Warfarin Bone deformities Fetal hemorrhage Abortion Teratogens: Bone deformities Fetal hemorrhage Abortion Warfarin Twinning timeline Before 3d: Dichorionic, diamniotic, 2 placentas Day 3: chorion forms Days 3-8: Monochorionic, diamniotic, 1 placenta Day 8: Amnion forms Day <8: monochorionic, monoamniotic, w/ 1 placenta (risk for conjoined twins) Dizygotic (fraternal) and early monozygotic twins

Monozygotes that split early (>3d) develop w/ 2 placentals, chorions, and amniotic sacs Dizygotes develop this way Monozygotic (later) twins 1 Zygote splits evenly: 2 amniotic sacs w/ shared chorion and placenta Conjoined twins: 1 chorion and 1 amniotic sac Fetal component of placenta Cytotrophoblast: inner layer of chorionic villi Syncytiotrophoblast: outer layer of chorionic villi, secretes HcG Maternal component of placenta Decidua basalis: Derived from endometrium, w/ maternal blood in lacunae Umbilical cord 2 Umbilical arteries: Return deoxygenated blood from fetal internal iliac arteries to placenta 1 Umbilical vein: supplies oxygenated blood from placenta to fetus (about 80% O2 sat) All above derive from allantosis Urachus Removes nitrogenous waste from fetal bladder (like a urethra) Connects to allantosis Umbilical cord abnormalities Single umbilical artery is associated w/ congenital and chromosomal abnormalities Vitelline fistula Fistula btw umbilicus and terminal ileum --< fecal discharge Fistula btw umbilicus and terminal ileum --< fecal discharge Vitelline fistula Urachal fistula Fistula btw umbilicus and bladder --< urinary discharge

Fistula btw umbilicus and bladder --< urinary discharge Urachal fistula truncus arteriosus Gives rise to ascending aorta and pulmonary trunk Bulbus cordis Gives rise to smooth parts (outflow tract) of LV and RV Primitive Ventricle Gives rise to trabeculated parts of LV and RV Primitive Atria Gives rise to trabeculated parts of RA and LA Sinus Venosus Left horn of sinus venosus: coronary sinus Right horn of SV: smooth part of RA Right common cardinal vein and right anterior cardinal vein Give rise to SVC Steps in forming interventricular septum 1.) Muscular ventricular septum forms --< remaining opening is the interventricular foramen . 2.) Aorticopulminary septum divides truncus arteriosus into aorta and pulmonary trunk 3.) Aorticopulminary septum meets and fuses w/ muscular ventricular septum to form a membranous interventricular septum (closing the interventricular foramen) <img src="123a IV septum development.JPG" /> Steps in interatrial septum development 1.) Foramen primum narrows as septum primum grows toward the endocardial cushions. 2.) Perforations in the septum primum form the foramen secundum (foramen primum disappears). 3.) Foramen secundum maintains

R --< L shunt while septum secundum grows. 4.) Septum secundum contains a permanent opening (the foramen ovale ) 5.) Foramen secundum enlarges as upper half of the septum primum degenerates 6.) Remaining portion of the septum primum forms the valve of the foramen ovale. <img src="124a - Interatrial septum development.JPG" /> Fetal Erythropoiesis "Young Liver Synthesizes Blood" 1.) Yolk sac (wks 3-8) 2.) Liver (wks 6-30) >overlap @ both ends 3.) Spleen (wks 9-28) 4.) Bone Marrow (wks 28+) Fetal hemoglobin (alpha)2,(gamma)2 structure Postnatal derivative(s) of: Umbilical vein Ligamentum teres hepatis (contained w/in falciform ligament) Postnatal derivative(s) of: Umbilical arteries Medial umbilical ligaments (umbiL ical arteries --< mediaL umbilical L igaments) Postnatal derivative(s) of: Ductus arteriosus Ligamentum arteriosum <img src="Ligamentum Arteriosum.JPG" /> Postnatal derivative(s) of: Ductus Venosus Ligamentum venosum <img src="Ligamentum Venosum.JPG" /> Postnatal derivative(s) of: Allantosis (urachus) allaN tosis --< mediaN umbilical ligament Urachus is part of allantoic duct between bladder and umbilicus. Urachal cyst or sinus is a remnant. Postnatal derivative(s) of: Notochord Nucleus pulposus of IV disks <img src="nucleus pulposus.JPG" />

Ductus venosus (1 of 3 fetal shunts) Blood enters fetus thru umbilical vein, conducted to ductus venosus into the IVC, thus bypassing the hepatic circulation. <img src="125a - ductus venosus.JPG" /> * becomes ligamentum venosum Foramen ovale (2 of 3 fetal shunts) Oxygenated blood reaching heart thru the IVC is diverted thru the foramen ovale and pumped to the aorta --< systemic circuit (IVC < RA < LA < LV < Ao < body) <img src="125b - Foramen Ovale.JPG" /> *becomes fossa ovalis Ductus Arteriosus (3 of 3 fetal shunts) Deoxygenated blood from SVC is expelled into pulmonary artery and ductus arteriosus to the lower body of the fetus. (RV < Pulm. Art. < Ao < Common iliac arteries < internal iliac arteries < 2 umbilical arteries < placenta) <img src="125c - Ductus Arteriosus.JPG" /> *becomes ligamentum arteriosum Events at 1st breath Decreased resistance in pulmonary vasculature This causes increased LAP vs. RAP --< the foramen ovale closes (is now the fossa ovalis) The increased [O2] leads to a drop in prostaglandins, which causes the closure of the ductus arteriosus Tx for Patent ductus arteriosus (PDA) Indomethacin (a potent NSAID) Indomethacin (a potent NSAID) Tx for Patent ductus arteriosus (PDA) To keep ductus arteriosus open (patent) Tx w/ Prostaglandins Tx w/ Prostaglandins To keep ductus arteriosus open (patent) 1st Aortic Arch

Part of the MAXillary artery [which is itself a branch of the external carotid] "1st Arch is MAXimal" 2nd Aortic Arch Stapedial Artery Hyoid Artery "Second = Stapedial" 3rd Aortic Arch C ommon C arotid artery + proximal part of internal carotid artery "C is the 3rd letter of the alphabet" (ABC --< 3rd aortic arch / C ommon C arotid) 4th Aortic Arch Left --< Aortic arch Right --< proximal part of the right sublcavian artery "4th arch = 4 limbs (systemic circuit)" 6th Aortic arch Proximal part of pulmonary arteries (On left): Ductus arteriosus "6th Aortic arch = pulmonary and pulmonary-to-systemic shunt" Prosencephalon Telencephalon Becomes cerebral hemispheres and lateral ventricles Diencephalon becomes thalami, etc. and 3rd ventricle <img src="126a embryonic CNS.JPG" /> Mesencephalon Becomes midbrain and cerebral aqueduct <img src="126a - embryonic CNS.JPG" /> Rhombencephalon Metencephalon - pons and cerebellum, 4th ventricle Myelencephalon - Medulla <img src="126a - embryonic CNS.JPG" /> Neural tube defects (generally) Associated with decreased folic acid intake during pregnancy. Elevated alpha-fetoprotein in amniotic fluid and maternal serum.

Spina bifida occulta Failure of bony spinal canal to close, w/o structural herniation. Dura intact. <img src="127a - Spina Bifida Oculta.JPG" /> Meningocele Meninges herniate thru the spinal canal defect (subarachnoid space protrudes) <img src="127b - Meningeocele.JPG" /> Myelomeningocele Meninges and spinal cord both herniate thru the spinal canal defect <img src="127c Myelomeningeocele.JPG" /><img src="myelomenigocele.JPG" /> Anencephaly Forebrain anomaly. Malformation of the anterior end of the neural tube: no brain/calvarium. Increased alpha-fetoprotein (AFP) Polyhydramnios (b/c no brain = no swallowing center) Forebrain anomaly. Malformation of the anterior end of the neural tube: no brain/calvarium. Increased alpha-fetoprotein (AFP) Polyhydramnios (b/c no brain = no swallowing center) Anencephaly Holoprosencephaly Forebrain anomaly: decreased separation of hemispheres across the midline --< cyclopia Associated w/ Patau's syndrome and severe Fetal Alcohol Syndrome Forebrain anomaly: decreased separation of hemispheres across the midline --< cyclopia Associated w/ Patau's syndrome and severe Fetal Alcohol Syndrome Holoprosencephaly Chiari type II malformation Posterior fossa malformation: cerebellar tonsillar herniation thru the foramen magnum

w/ aqueductal stenosis and hydrocephaly. Often presents w/ syringomyelia, thoracolumbar myelomeningocele. <img src="127c Syringomyelia.JPG" /> Posterior fossa malformation: cerebellar tonsillar herniation thru the foramen magnum w/ aqueductal stenosis and hydrocephaly. Often presents w/ syringomyelia, thoracolumbar myelomeningocele. <img src="127c Syringomyelia.JPG" /> Chiari type II malformation Dandy-Walker malformation Posterior fossa malformation: large posterior fossa Absent cerebellum w/ cyst in its place Posterior fossa malformation: large posterior fossa Absent cerebellum w/ cyst in its place Dandy-Walker malformation Syringomyelia Enlargement of the central canal of the spinal cord: crossing fibers of spinothalamic tract are damaged --< "cape-like" bilateral loss of pain and temperature sensation in upper limbs w/ preservation of touch sensation. Often presents w/ Chiari II type malformation Most common @ C8-T1 <img src="127c - Syringomyelia.JPG" /> Enlargement of the central canal of the spinal cord: crossing fibers of spinothalamic tract are damaged --< "cape-like" bilateral loss of pain and temperature sensation in upper limbs w/ preservation of touch sensation. Often presents w/ Chiari II type malformation Most common @ C8-T1 <img src="127c - Syringomyelia.JPG" /> Syringomyelia Branchial (aka pharyngeal) apparatus Composed of: 1.) Branchial Clefts aka Branchial Grooves (from ectoderm) 2.) Branchial Arches (from mesoderm --< muscle, arteries, and neural crest cells --< bones, cartilage) 3.) Branchial Pouches (derived from endoderm) "CAP covers from the outside" (outside) Clefts <

Arches < Pouches (inside) <img src="128a Branchial apparatus.JPG" /> Branchial Arch 1 nerves Supplied by CN V2 and V3 --< Chewing (nerves also derive from arch 1) Branchial Arch 1 structures Meckel's cartilage (M andible, M alleus, incus, sphenoM andibular ligament) Muscles : M uscles of M astication (temporalis, M asseter, lateral and M edial pterygoids) M ylohyoid Anterior belly of digastric Tensor tympani Tensor veli palatini Anterior 2/3rds of the tongue Treacher Collins Syndrome 1st Arch neural crest fails to migrate: Mandibular hypoplasia and facial abnormalities Branchial arch 2 nerve(s) CN VII (facial expression) Branchial arch 2 structures Reichart's Cartilage (St apes, St ylohyoid process, lesser horn of hyoid, St ylohyoid ligament) Muscles : Muscles of facial expression St apedius St ylohyoid Posterior belly of digastric Branchial Arch 3 nerve(s) CN IX (glossopharyngeal) Branchial arch 3 structures Cartilage: greater horn of hyoid Muscle: stylopharyngeus "Think of the pharynx: stylopharyngeus innervated by the glossopharyngeal nerve" Congenital Pharyngocutaneous Fistula Persistence of 3rd branchial cleft and pouch: Fistula between tonsillar area, cleft in lateral neck.

Persistence of 3rd branchial cleft and pouch: Fistula between tonsillar area, cleft in lateral neck. Congenital Pharyngocutaneous Fistula Branchial arches 4-6 nerve(s) CN X Arch 4 = swallowing --< superior laryngeal branch Arch 6 = speaking --< recurrent laryngeal branch Branchial arches 4-6 structures Cartilage: thyroid, cricoid, arytenoids, corniculate, cuneiform Muscles: 4th - most pharyngeal constrictors, cricothyroid (responsible for pitch), levator veli palatini 6th all intrinsic muscles of larynx except the cricothyroid Arch 5: no major contributions to adult structures Branchial arches and the tongue Posterior 1/3rd: branchial arches 3 and 4 Anterior 2/3rds: branchial arch 1 1st Branchial Cleft Gives rise to the external auditory meatus Gives rise to the external auditory meatus 1st Branchial Cleft 2nd thru 4th branchial clefts Give rise to temporary cervical sinuses (obliterated by proliferation of the 2nd arch mesenchyme) Give rise to temporary cervical sinuses (obliterated by proliferation of the 2nd arch mesenchyme) 2nd thru 4th branchial clefts Persistent cervical sinus A branchial cleft cyst w/in the lateral neck A branchial cleft cyst w/in the lateral neck Persistent cervical sinus

1st branchial pouch Gives rise to endoderm-lined structures of the ear: Middle ear cavity Eustachian tube Mastoid air cells Gives rise to endoderm-lined structures of the ear: Middle ear cavity Eustachian tube Mastoid air cells 1st branchial pouch 2nd Branchial Pouch Gives rise to epithelial lining of the palatine tonsil Gives rise to epithelial lining of the palatine tonsil 2nd Branchial Pouch 3rd Branchial Pouch Dorsal wings: give rise to inferior parathyroids Ventral wings: give rise to thymus 3rd pouch = 3 structures (L and R inferior parathyroid, and thymus) 3rd pouch structures end up below 4th pouch structures* 4th Branchial Pouch Dorsal wings: develop into the superior parathyroids Dorsal wings: develop into the superior parathyroids 4th Branchial Pouch DiGeorge Syndrome Aberrant development of the 3rd and 4th branchial pouches: T-cell deficiency/thymic aplasia Hypocalcemia (due to failure of parathyroid development) Ear development: 1st and 2nd branchial arches 1st Arch: Bones --< malleus, incus Muscles --< tensor tympani (and its innervation via V3) 2nd

Arch: Bone --< stapes Muscle --< stapedius (and its innervation via CN VII) Ear development: 1st branchial cleft, membrane, and pouch 1st cleft: External auditory meatus 1st membrane: tympanic membrane 1st pouch: Eustachian tube, middle ear cavity, mastoid air cells Anterior 2/3rds of tongue 1st branchial arch (sensation via CN V3) -<Taste via CN VII --<Motor to all of the tongue is via CN XII <img src="130a - Innervation of tongue.JPG" /> Posterior 1/3rd of tongue 3rd and 4th arches: sensation and taste mainly via CNIX (extreme posterior via CN X) All motor to tongue is via CN XII <img src="130a - Innervation of tongue.JPG" /> CN's involved in taste, pain, and motor innervation of the tongue Taste: CN VII, IX, and X (solitary nucleus) Pain: CN V3, IX, X Motor: CN XII (note: muscles of the tongue are derived from occipital myotomes) Cleft Lip Failure of fusion of the maxillary and nasal processes (formation of the primary palate ) <img src="131b - cleft lip.JPG" /> Cleft Palate Failure of fusion of the lateral palatine processes and/or the median palatine processes (formation of the secondary palate ) <img src="131c - partial cleft palate.JPG" /> Diaphragm derives from... "Several Parts Build Diaphragm" S eptum transversum --< central tendon P leuroperitoneal folds B ody wall D orsal mesentery of the esophagus --< crura <img src="131d - Diaphragm embryology.JPG" />

Diaphragm innervation Diaphragm descends during development, but maintains innervation from above. "C3, 4, 5: keep the diaphragm alive" Diaphragmatic hernia When abdominal contents herniate into the thorax b/c of incomplete development. Leads to: hypoplasia of thoracic organs due to space compression, scaphoid abdomen, cyanosis. When abdominal contents herniate into the thorax b/c of incomplete development. Leads to: hypoplasia of thoracic organs due to space compression, scaphoid abdomen, cyanosis. Diaphragmatic hernia gram positive cocci Staphylococcus, Streptococcus gram neg cocci Neisseria gram positive bacilli Clostridium, Corynebacterium, Bacillus, Listeria, Mycobacterium (acid fast) gram positive branching filaments Actinomyces, Nocardia (weakly acid fast) Spiral spirochetes: Leptospira, Borrelia (Giemsa), Treponema bacteria with unusual cell membranes/walls Mycoplasma - sterols, no cell wall Mycobacteria - mycolic acid. High lipid content Bugs that do not gram stain well TRMMLC - These Rascals May Microscopically Lack Color Treponema (too thin, dark field, fluorescent Ab), Rickettsia (intracellular) Mycobacteria (acid

fast), Mycoplasma (no cell wall), Legionella pneumophilia (intracellular, silver stain), Chlamydia (intracellular, no muramic acid) Giemsa Stain Gee These Bad Puns are Cheesy Giemsa, Trypanosomes, Borrelia, Plasmodium, Chlamydia PAS stain PASs the whipped cream & sugar glycogen, mucopolysaccharides, diagnose Whipple's Ziehl-Neelsen stain Acid-fast (RED) India Ink stain Cryptococcus neoformans (stains everything else black - clear crypto bubble!) Silver stain Fungi, Legionella Obligate aerobes Nagging Pests Must Breathe Nocardia Pseudomonas Aeruginosa Mycobacterium Tuberculosis Bacillus Obligate Anaerobes Anaerobes Can't Breathe Air Clostridium, Bacteroides, Actinomyces Obligate intracellular Really Cold Rickettsia Chlamydia Facultative Intracellular Some Nasty Bugs May Live FacultativeLY Salmonella, Neisseria, Brucella, Mycobacterium, Listeria, Francisella, Legionella, Yersinia Pestis

Catalase positive orgs SSPACE for your Cats S. aureus, Serratia, Pseudomonas, Actinomyces, Candida, E. coli, Catalase Urease positive orgs PUNCH-K Proteus, Ureaplasma, Nocardia, Cryptococcus, H. pylori, Klebsiella Pigment-producing bacteria Actinomyces israelii - Israel has yellow sand S. aureus - yellow pigment "golden" Pseudomonas AERUGinosa- blue-green AERUGula is green Serratia marcescens - red pigment - Red maraschino cherries IgA protease orgs Enzyme that cleaves IgA SHiN - S. pneumoniae, H. influenza type B, Neisseria Endotoxin features Outer cell membrane of gram negs Lipopolysaccharide - structural part of bacteria, released when lysed Bacterial chromosome Fever, Shock Induces TNF and IL-1 Meningococcemia, sepsis by gram neg Endotoxin efx Endotoxin (esp Lipid A) 1)Activates Macrophages: IL-1->fever TNF->fever, hemorrhagic tissue necrosis Nitric Oxide->Hypotension (shock) 2)Activates complement (alt. pathway): C3a>hypotension, edema C5a->neutrophil, chemotaxis 3)Act. Hageman factor: Coagulation cascade>DIC Identification gram pos cocci

on the STAPH retreat, there was NO StRESs Staphylococci NOvobiocin- Saprophyticus is Resistant; Epidermidis is Sensitive Streptococci OVeRPaSs Optochin-Viridans is Resistant; Pneumoniae is Sensitive size B-BRAS Bacitracin- group B strep are Resistant; group A strep are Sensitive Alpha hemolytic green apple Strep pneumoniae - op sens; quellung pos Strep viridans - op res; bile growth Optochin- OVeRPaSs Beta hemolytic Because we need space -clear space Staph aureus - cat and coag pos Strep pyogenes - grpA - bacitracin sens Strep agalactiae- grpB - bacitracin res Listeria monocytogenes (tumbling, newborn meningitis, unpast. milk) Strep pneumoniae S. pneumoniae MOPS are Most OPtochin Sensitive Meningitis, Otitis media, Pneumonia, Sinusitis Lancet shaped, gram pos diplococci, encapsulated IgA protease "rusty" sputum, sepsis in sickle cell anemia and splenectomy Staph aureus Gram pos cocci in clusters Protein A (vir) bind Fc-IgG, inhibits complement fixation and phagocytosis TSST superantigen that binds MHC II T cell receptor, T cell activation Causes acute bacterial endocarditis, osteomyelitis Strep viridans

alpha hemolytic dental caries (S. mutans) and endocarditis (S. sanguis) Strep pyogenes (groups A strep) PHaryngitis can result in rheumatic PHever and glomerulonePHritis No "rheum" for SPECCulation: Subcutaneous plaques, Polyarthritis, Erythema marginatum, Chorea, Carditis Bacitracin sens, Abs to M protein, ASO titer Strep agalactiae (group B streptococci) B for Babies Bacitracin res; Beta hemolytic; CAMP factor pneumonia, meningitis, sepsis in babies Penicillin prophylaxis in Pregnancy Enterococci (group D strep) UTI and subacute endocarditis Grow in salt and bile VRE Vancomycin Resistant Enterococci Corynebacterium diphtheriae Pseudomembranous pharyngitis w/ lympahenopathy ABCDEFG ADP ribosylation (inh protein synth), Betaprophage (exotoxin), Corynebacterium, Diptheria, Elongation Factor 2, Granules (blue & red) Clostridia gram pos, spores, obligate anaerobe rods TETanus is TETanic paralysis (Tetanospasmin blocks glycine & GABA release) from Renshaw cells in spinal cord BOTulinium from BOTtles of food & honey (flaccid paralysis heat-labile toxin inh ACh at nm junc) PERFringens PERForates a gangrenous leg (myonecrosis and hemolysis) DIfficile DIarrhea. (enterotoxin & cytotoxin) metronidazole or oral Vancomycin. Anthrax

Bacillus antracis, gram pos, spores, capsule of D-glutamate Cutaneous- black painless ulcer bacteremia and death Pulmonary- inhale spores flulike fever, pulm hemorrhage, mediastinitis, shock Woolsorter's dz Listeria monocytogenes Facultative intracellular, milk/cheese, vaginal, tumbling motility Amnionitis, septicemia, abortion in preg Meningitis: neonate & immunocomp Gastroenteritis rx: Ampicillin Actinomyces vs Nocardia SNAP: Sulfa for Nocardia; Actinomyces use Penicillin Actinomyces israelii- oral/facial abscess Nocardia asteroides- soil, pulm infxn Mycobacteria Acid Fast; fever, night sweats, wt loss, hemoptysis M. tuberculosis: TB, M. kansasii: TB-like sx M. avium-intracellulare: AIDS prophyl: Azithromycin Leprosy Mycobacterium leprae, acid-fast, cool temp Hansen's Dz: 1. Lepromatous- diffuse, cell mediated, Th2 response 2. Tuberculoid- few plaques, cell mediated, Th1 resp Treat: long-term oral Dapsone; toxicity hemolysis and methemoglobinemia Other: Rifampin w/Clofazimine & Dapsone Lactose Fermenting Enterics pink colonies on MacConkey's agar Lactose is KEE test w/ MacConKEE'S Citrobacter, Klebsiella, E. coli, Enterobacter, Serratia

Neisseria MeninGococci ferment Maltose & Glucose Gonococci ferment Glucose gram neg diplococci, make IgA proteases N. Gonorrhoeae- dx: Ceftriaxone N.Meningitidis- vaccine (no B) dx: Ceftri or Penicillin G; Rifampin prophylaxis Haemophilus Influenzae haEMOPhilus Epiglottitis, Meningitis, Otitis media, Pneumonia Go to the five (factor V NAD+) and dime (X hematin) to buy Chocolate (agar) small gram neg rod, IgA protease Dx meningitis w/ Ceftriaxone. Rifampin prophylaxis Legionella pneumophila Legionnaire's dz- severe pneumonia & fvr Pontiac fvr- flu-like, mild French legionnaire w/silver helmet at campfire (charcoal) w/iron dagger- he's no sissy (cysteine) Silver stain, charcoal yeast w/Fe & cysteine Dx: Erythromycin Pseudomonas aeruginosa PSEUDOmonas - wound and burn infxn Pneumonia (CF), Sepsis (black lesions), External otitis (swimmer's ear), UTI, Drug use, Diabetic Osteomyelitis, hot tub folliculitis AERuginosis-AERobic aerobic, gram+ rod, non-lactose, oxidase positive, Pyocyanin(blue-green) pigment, grape odor, water source Endotoxin and Exotoxin A (inact. EF2) Dx: Aminoglycoside+ super penicillin (piperacillin, ticarcillin) Escherichia Coli Fimbriae- cystitis and pyelonephritis K capsule- pneumonia, neonatal meningi LPS- septic shock EIEC - Invasive; dysentary ETEC- Traveler's diarrhea (watery) EPEC- children (Peds)

EHEC- O157:H7 shiga-like toxin (dysentary) & Hemolytic-uremic syndrome (anemia, thrombocytopenia, renal failure) *Does not ferment SORBITOL (distinguish) Klebsiella 4 A's: Aspiration pneumonia, Abscess in lungs and liver, Alcoholics, di-A-betics red currant jelly sputum polysaccharide capsule Spirochetes BLT. B is Big Borrelia (big), Leptospira, Treponema Treponema dark-field microscopy Lyme disease BAKE a key Lyme pie: Bell's palsy (bilateral), Arthritis, Kardiac block, Erythema migrans ("bull's eye rash") Borrelia burgdorferi, tick IXODES, rx: Doxycycline, Ceftriaxone Syphilis Spirochete Treponema pallidum rx: Penicillin G Primary: painless chancre Second: Secondary syphilis = Systemic disseminated, maculopapular rash, condylomata lata Third: Gummas, aortitis, neurosyphilis, Argyll Robertson Congenital: Saber shins, saddle nose, CN VIII deafness Gardnerella vaginalis I don't have a CLUE what I smell FISH in the VAGINA GARDEN Vaginosis; gray discharge, fishy smell clue cell: covered w/ bacteria rx: Metronidazole Rickettsial Rickettsia on the wRists, Typhus on the Trunk; Triad: headache, fever, rash R. Rickettsii RMSF (tick); obligate intracellular

orgs need CoA & NAD+ Typhus: Endemic (fleas)- R. typhi; Epidemic (human body louse) R. prowazekii (central rash spreads out) rx: Doxycycline Rash on palm and sole you drive CARS using PALMS & SOLES PALM and SOLE rash is seen in Coxsackievirus A infection Rocky Mtn spotted fever, Syphilis Chlamydiae 1. Elementary body is Enfectious and Enters cells via Endocytosis 2. Reticulate body Replicates in cell; fission Giemsa or fluorescent antibody dx: Azithromycin or Doxycycline C. trachomatis: arthritis, conjunctivitis, urethritis, PID C pneumoniae & C psittaci: atypical pneu Histoplasmosis Histo Hides (within macs) & Flys Midwest Pneumonia Mississippi and Ohio river valleys Bird or Bat droppings rx: Fluconazole/ Ketoconazole or Amphotericin B Blastomycosis Blasto Buds (Broadly) Broad based budding East US and C. America Inflammatory lung dz - diss. to skin and bone Granulomatous nodules rx: Fluconazole/ Ketoconazole or Amphotericin B Coccidioidomycosis Coccidio Crowds, Confuses, Coughs, Quakes. Inc after earthquakes San Joaquin Valley "valley fever", SW US, CA Pneumonia & Meningitis->bone, skin Spherule filled with endospores

rx: Fluconazole/ Ketoconazole or Amphotericin B Paracoccidioidomycosis Paracoccidio Parasails (budding yeast) with the CAPTAIN'S WHEEL (appearance) to Latin America rx: Fluconazole/ Ketoconazole or Amphotericin B Systemic mycoses Mycosis twins cough conazole and (amp) B all over you Pneumonia and disseminate. Dimorphic fungi rx: Fluconozole or Ketoconazole (local) Amphotericin B (systemic) Tinea versicolor Malassezia furfur hyper-, hypopigmented patches Hot and humid weather "spaghetti and meatballs" on KOH prep dx: Topical miconazole, selenium sulfide Encapsulated bacteria Qulleng rx: capsular swellung SHiN SKiS (B): Sterptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Salmonella, Klebsiella pneumoniae, group B Strep gram pos rods Clostridium (anaerobe), Corynebacterium, Listeria (beta hemolytic), Bacillus (aerobe) branching filaments Actinomyces, Nocardia Lysogeny, specialized transduction ABCDE shigA-like toxin, Botulinum, Cholera toxin, Diphtheria toxin, Erythrogenic toxin of S. pyogenes

gamma hemolytic gram pos cocci Enterococcus (bile & NaCl) S. bovis (in bile, not NaCl) cows like bile, but not salt Spore forming Soil: Bacillus anthracis, Clostridium perfringens, C. tetani other: B. cereus, C botulinum, Coxiella burnetii Salmonella bloody diarrhea, flagella, hematogenous, produce H2S, monocytic resp rx: antibiotics prolong illness Salmonella typhi Typhoid fever Rose spots on abdomen, fever, headache, diarrhea Gallbladder carrier state Shigella non-lactose fermenting, bloody diarrhea Campylobacter jejuni Bloody diarrhea (esp kids) Fecal-oral, poultry, meat, milk Comma or S shaped, grows at 42 deg, oxidase pos Guillain-Barre Vibrio cholerae rice-water diarrhea via toxin> Act Gs> Inc cAMP; Comma-shape, oxidase pos, alkaline media Yersinia enterocolitica pet feces, milk, pork diarrhea in daycare Mesenteric Adenitis (mimic IBD) Helicobacter Pylori

Triple Therapy 1 PPI 2 Clarithromycin 3 Amoxicillin or Metronidazole gastritis & 90% duodenal ulcers gastric adenocarcinoma & lymphoma Gram neg rod, urease pos, alkaline env Leptospira interrogans question-mark shaped, water (animal urine), surfers Flulike, jaundice, photophobia w/conjunctivitis Weil's dz: severe form jaundice & azotemia liver & kidney dysfunction, fever, anemia, hemorrhage Rickettsial w/ no rash Ehrlichiosis (tick): Granulocytes w/ berry cluster orgs Q fever Coxsiella brunetii; Pneumonia; (aerosol, tick feces & cow placenta) Q fever is Queer cuz no rash rx: Doxycycline Mycoplasma pneumoniae atypical pneumonia gold aglutinins; Eaton's agar, no cell wall, *Only bacteria w/ cholesterol military & prison rx: Tetracycline or Erythromycin

Gives rigid support, protects against osmotic pressure; Sugar backbone w/ cross-linked peptide side chains. (function; chemical composition)
Bacterial Structures: Peptidoglycan

Major surface Ag; Peptidoglycan for support. Teichoic acid induces TNF and IL-1. (function; chemical composition)

Bacterial Structures: Cell wall / cell membrane (G+'s)

Site of endotoxin (LPS), major surface Ag; Lipid A induces TNF and IL-1 Polysaccharide is the Ag (function; chemical composition)

Bacterial Structures: Outer membrane (G-)

Site of oxidative and transport enzymes; Lipoprotein bilayer (function; chemical composition)
Bacterial Structures: Plasma membrane

Protein synthesis; 50S and 30S subunits (function; chemical composition)

Bacterial Structures: Ribosome

Space btw the cytoplasmic membrane and the outer membrane in G- bacteria; Contains may hydrolytic enzymes, including beta-lactamases (function; chemical composition)
Bacterial Structures: Periplasm

Protects against phagocytosis; Polysaccharide (except in Bacillus anthracis , which contains D-glutamate) (function; chemical composition)
Bacterial Structures: Capsule Function? Structure? (... and exception?)

Mediate adherence of bacteria to cell surface, sex pilus forms attachment btw 2 bacteria during conjugation; Glycoprotein (function; chemical composition)
Bacterial Structures: Pilus/fimbria

Motility; Protein (function; chemical composition)

Bacterial Structures: Flagellum

Provides resistance to dehydration, heat, and chemicals; Keratin-like coat, dipiclonic acid (function; chemical composition)
Bacterial Structures: Spore

Contains a variety of genes for ABX resistance, enzymes, toxins; DNA (function; chemical composition)
Bacterial Structures: Plasmid

Mediates adherence to surfaces, especially foreign surfaces (e.g. indwelling catheters); Polysaccharide (function; chemical composition)
Bacterial Structures: Glycocalyx

Teichoic acid Cell wall <img src="138b cell wall.JPG" />

Structures unique to gram (+) organisms

Flagellum, pilus, capsule, PDG, cytoplasmic membrane <img src="138a cell walls.JPG" />
Structures common to Gram +/- organisms

Endotoxin/LPS (outer membrane) Periplasmic space (location of many beta-lactamases) <img src="138c - cell wall gram neg.JPG" />
Features unique to G(-) organisms

Mycoplasma: contain sterols and have no cell wall Mycobacteria: Contain mycolic acid. High lipid content.
Bacteria w/ unusual cell membranes/walls

Staphylococcus Streptococcus
G(+) cocci

Neisseria
G(-) cocci

My cobacterium (acid-fast) List eria B acillus C lostridium C orynebacterium What happened when you were sending that email to Gram + Rod ? My List B ecame CC 'd

G(+) Rods

G(+) Rods
My cobacterium (acid-fast) List eria B acillus C lostridium C orynebacterium What happened when you were sending that email to Gram + Rod ? My List B ecame CC 'd

H ave Y ou E ver L istened to GNR (Guns n' Roses = Gram (-) Rods)? I like B oy B ands. B esides, Fran kly, I P refer Garden s to jungles. Haemophilus Yersinia Enterics (separate card) Legionella (silver stain) Bordatella Brucella Bartonella Francisella Pasteurella Gardnerella (gram variable)
G(-) Rods

G(-) Rods
H ave Y ou E ver L istened to GNR (Guns n' Roses = Gram (-) Rods)? I like B oy B ands. B esides, Fran kly, I P refer Garden s to jungles. Haemophilus Yersinia Enterics (separate card) Legionella (silver stain) Bordatella Brucella Bartonella Francisella Pasteurella Gardnerella (gram variable)

Actinomyces Nocardia (weakly acid-fast)

Branching Filamentous bacteria (G+)

Branching Filamentous bacteria (G+)

Actinomyces Nocardia (weakly acid-fast)

Rickettsiae Chlamydiae (Giemsa stain)

Pleomorphic (G-) bacteria

Pleomorphic (G-) bacteria

Rickettsiae Chlamydiae (Giemsa stain)

Leptospira Borrelia (Giemsa stain) Treponema

Spirochetes (G-)

Spirochetes (G-)
Leptospira Borrelia (Giemsa stain) Treponema

Mycoplasma
Neither G+ nor G- (b/c no cell wall)

These Rascals May Microscopically Lack Color Treponema (too thin to be visualized) Rickettsia (intracellular parasite) Mycobacteria (high-lipidcontent cell wall requires acid-fast stain) Mycoplasma (no cell wall) Legionella pneumophilia (primarily intracellular) Chlamydia (intracellular parasite; lacks muramic acid cell wall)
Bugs that won't Gram stain

Darkfield microscopy and fluorescent Ab staining

Visualizing Treponemes

Acid-fast stain
Visualizing Mycobacteria

Silver stain
Visualizing Legionella

use for: Borrelia Plasmodium Trypanosomes Chlamydia

Giemsa's stain is used to visualize...?

stains glycogen, mucopolysaccharides; Used to diagnose Whipple's dz (PASs the sugar)

PAS (periodic acid-Schiff) stain

Use to stain Acid-fast bacteria

Ziehl-Neelsen stain

used to visualize Cryptococcus neoformans

India ink

used to visualize: fungi, Legionella

Silver stain

Chocolate agar w/ factors V (NAD) and X (hematin) (Media used for isolation)
Media/Special culture requirements for: H. influenzae

H. influenzae

Chocolate agar w/ factors V (NAD) and X (hematin)

Thayer-Martin media (Chocolate agar based, w/ various ABX) (Media used for isolation)
Media/Special culture requirements for: N. gonorrheae

N. gonorrheae
Thayer-Martin media (Chocolate agar based, w/ various ABX)

Bordet-Gengou (potato) agar (Media used for isolation)

Media/Special culture requirements for: B. pertussis

B. pertussis
Bordet-Gengou (potato) agar

Tellurite plate, Loffler's media (Media used for isolation)

Media/Special culture requirements for: C. diphtheriae

C. diphtheriae
Tellurite plate, Loffler's media

Lowenstein-Jensen agar (Media used for isolation)

Media/Special culture requirements for: M. tuberculosis

M. tuberculosis
Lowenstein-Jensen agar

Eaton's agar (Media used for isolation)

Media/Special culture requirements for: M. pneumoniae

M. pneumoniae
Eaton's agar

Eosin-methylene Blue (EMB) agar (blueblack colonies w/ metallic sheen) (Media used for isolation)
Media/Special culture requirements for: E. coli

E. coli

Eosin-methylene Blue (EMB) agar (blue-black colonies w/ metallic sheen)

Pink colonies on MacConkey's agar (Media used for isolation)

Media/Special culture requirements for: Lactose-fermenting enterics

Lactose-fermenting enterics
Pink colonies on MacConkey's agar

Charcoal yeast extract agar buffered w/ increased iron and cysteine (Media used for isolation)
Media/Special culture requirements for: Legionella

Legionella
Charcoal yeast extract agar buffered w/ increased iron and cysteine

Sabouraud's agar (Media used for isolation)

Media/Special culture requirements for: Fungi

Fungi
Sabouraud's agar

E. coli Shigella Salmonella Yersinia Klebsiella Proteus Enterobacter Serratia Vibrio Campylobacter Helicobacter Pseudomonas Bacteroides
G(-) Enterics (rod-shaped)

Use an O2-dependent system to generate ATP Examples: (Nagging Pests Must Breathe) Nocardia Pseudomonas Mycobacterium tuberculosis (w/ prediliction for apices of lungs, where PO2 is highest) Bacillus Also: to help remember Pseudomonas aeruginosa AERuginosa is an AERobe
Obligate aerobes

P. AERuginosa is an AERobe seen in burn wounds, nosocomial pneumonia, and pneumonias in cystic fibrosis pts.
Pseudomonas aeruginosa O2 tolerance? Where does it show up?

Lack catalase and/or superoxide dismutase, and thus are susceptible to oxidative damage. Generally foulsmelling (short-chain FA's), are difficult to culture, and produce gas in tissue (CO2 and H2). Normal flora in GI tract, pathogenic elsewhere. Examples: (anaerobes Can't Breathe Air) Clostridium Bacteroides Actinomyces
Obligate Anaerobes

AminO2 glycosides are ineffective against anaerobes b/c these ABX require O2 to enter into the bacterial cell.
Aminoglycosides and anaerobes

Rickettsia, Chlamydia (Stay inside [cells] when it's R eally C old) *Can't make their own ATP
Obligate intracellular bugs

Some Nasty Bugs May Live FacultativeLY Salmonella Neisseria Brucella Mycobacterium Listeria Francisella Legionella Yersinia
Facultatively intracellular bugs

Postive quellung: If encapsulated bug is present, the capsule swells when specific anti-capsular antisera are added (Quellung = capsular swellung)
Quellung Reaction

Capsule is Ag for vaccines (e.g. Pneumovax, H. influenzae B, meningococcal vaccines) Conjugation w/ protein increases immunogenicity and Tcell dependent response
Capsule and vaccines

Encapsulated (Some Nasties Have Kapsules) Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae (esp. type B) Klebsiella pneumoniae Polysaccharide capsule is an antiphagocytic virulence factor for above bacteria.
Quellung (+) Bacteria

Particular Kinds Have Urease Proteus Klebsiella H. pylori Ureaplasma

Urease (+) bugs

S. aureus --> yellow pigment (Auerus is Latin for gold) Pseudomonas aeruginosa --> blue-green pigment (AERUGula is green) Serratia marcescens --> red pigment (Think of red maraschino cherries)
Pigment-producing bacteria

Promote evasion of host immune response

Virulence factors

protein A: Binds Fc region of Ig, disrupts opsonization and phagocytosis. IgA protease: Enzyme that cleaves IgA. Polysaccharide capsules also inhibit phagocytosis. [*also TSST-1, but I don't think it's technically a virulence factor]
Important virulence factors in S. aureus

Polysaccharide capsules also inhibit phagocytosis. [*also TSST-1, but I don't think it's technically a virulence factor] Important virulence factors in S. aureus
protein A: Binds Fc region of Ig, disrupts opsonization and phagocytosis. IgA protease: Enzyme that cleaves IgA.

Secreted by S. pneumoniae, H. influenzae, and Neisseria to prevent phagocytosis

IgA protease Who secretes it?

IgA protease Who secretes it?

Secreted by S. pneumoniae, H. influenzae, and Neisseria to prevent phagocytosis

M protein: Helps prevent phagocytosis

Group A streptococcus virulence factors

Group A streptococcus virulence factors

M protein: Helps prevent phagocytosis

Certain species of some G(+) and G(-) organisms; Outer cell membrane of most G(-) bacteria and Listeria (Exo ; Endo)
Exotoxin vs. Endotoxin: Source

Yes; No (Exo ; Endo)

Exotoxin vs. Endotoxin: Secreted from cell?

Polypeptide; Lipopolysaccharide (structural part of the bacteria. Released when lysed) (Exo ; Endo)
Exotoxin vs. Endotoxin: Chemistry

Plasmid or bacteriophage; bacterial chromosome (Exo ; Endo)

Exotoxin vs. Endotoxin: Location of genes

High (fatal dose on the order of 1 microgram); Low (fatal dose on the order of hundreds of micrograms) (Exo ; Endo)
Exotoxin vs. Endotoxin: Toxicity

Various; Fever, shock (Exo ; Endo)

Exotoxin vs. Endotoxin: Clinical effects

Various; Includes TNF and IL-1 (Exo ; Endo)

Exotoxin vs. Endotoxin: Mode of action

Induces high-titer Abs called antitoxins ; Poorly antigenic (Exo ; Endo)

Exotoxin vs. Endotoxin: Antigenicity

Toxoids useful as vaccines; No toxoids formed and no vaccine available (Exo ; Endo)
Exotoxin vs. Endotoxin: Vaccines

Destroyed rapidly at 60C (except staphylococcal enterotoxin); Stable at 100C for 1 hour (Exo ; Endo)

Exotoxin vs. Endotoxin: Heat stability

Tetanus, botulism, diphtheria; Meningococcemia, sepsis by G(-) rods (Exo ; Endo)

Exotoxin vs. Endotoxin: Typical diseases

Bind directly to MHCII and T-cell receptor simultaneously, activating large numbers of T-cells to stimulate release of IFN-gamma and IL-2
Superantigens

Organism, toxin function: S. aureus SuperAg that causes toxic shock syndrome (fever, rash, shock).
Toxins: TSST-1

TSST-1
S. aureus SuperAg that causes toxic shock syndrome (fever, rash, shock).

Organism, toxin function: S. aureus Causes staphylococcal scalded skin syndrome

Toxins: Exfoliatin

Exfoliatin
S. aureus Causes staphylococcal scalded skin syndrome

Organism, toxin function: S. aureus (and others) Cause food poisoning

Toxins: Enterotoxins

Enterotoxins
S. aureus (and others) Cause food poisoning

Organism, toxin function: S. pyogenes SuperAg that causes toxic shock-like syndrome
Toxins: Scarlet fever-erythrogenic toxin

Scarlet fever-erythrogenic toxin

S. pyogenes SuperAg that causes toxic shocklike syndrome

Interfere w/ host cell function. B (binding) component binds to a receptor on the surface of the host cell, enabling endocytosis. A (active) component then attaches an ADP-ribosyl to a host cell protein (ADP ribosylation), altering protein function.
ADP ribosylating exotoxins

Organism, toxin function: Corynebacterium diphtheriae ADPribosylating A-B exotoxin that inactivates EF-2 (similar to Psudomonas exotoxin A) Causes pharyngitis and pseudomembrane in throat.
Toxins: Diphtheria exotoxin

Diphtheria exotoxin
Corynebacterium diphtheriae ADPribosylating A-B exotoxin that inactivates EF2 (similar to Psudomonas exotoxin A) Causes pharyngitis and pseudomembrane in throat.

Organism, toxin function: Vibrio Cholerae ADP ribosylation of G-protein stimulates adenylyl cyclase Increased pumping of Cl- into gut and decreased Na+ absorption Water moves into gut lumen Causes voluminous rice-water diarrhea
Toxins: Cholera toxin

Cholera toxin
Vibrio Cholerae ADP ribosylation of G-protein stimulates adenylyl cyclase Increased pumping of Cl- into gut and decreased Na+ absorption Water moves into gut lumen Causes voluminous rice-water diarrhea

Organism, toxin function: E. coli ADPribosylating A-B toxins Heat-labile: stimulates Adenylyl cyclase Heat-stabile: stimulates Guanylate cyclase Both: cause watery diarrhea Labile like the A ir, Stable like the G round
Toxins: Heat-labile toxin, Heat-stabile toxin

Organism, toxin function: Bordetella pertussis ADP-ribosylating A-B toxin that increases cAMP by inhibiting Galpha1 Causes whooping cough Inhibits chemokine receptor --> causes lymphocytosis
Toxins: Pertussis toxin (PT)

Organism, toxin function: Clostridium perfringens Causes gas gangrene Get double zone of hemolysis on blood agar
Toxins: alpha toxin

alpha toxin
Clostridium perfringens Causes gas gangrene Get double zone of hemolysis on blood agar

Organism, toxin function: C. tetani Blocks the release of inhibitory neurotransmitters GABA and glycine Causes lockjaw
Toxins: Tetanus toxin (tetanospasmin)

Tetanus toxin (tetanospasmin)

C. tetani Blocks the release of inhibitory neurotransmitters GABA and glycine Causes lockjaw

Organism, toxin function: C. botulinum Blocks release of ACh Causes anticholinergic symptoms, CNS paralysis (especially cranial nerves) Spores found

in canned food, honey (causes floppy baby)

Toxins: Botulinum toxin (aka Botox)

Botulinum toxin (aka Botox)

C. botulinum Blocks release of ACh Causes anticholinergic symptoms, CNS paralysis (especially cranial nerves) Spores found in canned food, honey (causes floppy baby)

Organism, toxin function: Bacillus anthracis Edema factor, part of the toxin complex, is an adenylate cyclase
Toxins: Anthrax toxin

Organism, toxin function: Shigella, and E. coli O157:H7 Cleaves host cell rRNA (inactivates 60S ribosome) Enhances cytokine release, causing HUS
Toxins: Shiga toxin

Shiga toxin

Shigella, and E. coli O157:H7 Cleaves host cell rRNA (inactivates 60S ribosome) Enhances cytokine release, causing HUS

Organism, toxin function: S. pyogenes a hemolysin. Ag for ASO Ab, which is used in Dx of rheumatic fever
Toxins: Streptolysin O

Streptolysin O
S. pyogenes a hemolysin. Ag for ASO Ab, which is used in Dx of rheumatic fever

Vibrio cholerae B. pertussis E. coli Bacillus anthracis Cholera, pertussis, and E. coli toxins act via ADP ribosylation to permanently activate endogenous adenylate cyclase (increasing cAMP), While anthrax edema factor is itself an adenylate cyclase

cAMP inducers (list)

Toxin permanently activates Gs, Causing rice-water diarrhea (Cholera turns the on on)
Vibrio Cholerae toxin and cAMP

Pertussis toxin permanently disables Gi, causing whooping cough (Pertussis toxin turns the off off) *Pertussis toxin also promotes lymphocytosis by inhibiting chemokine receptors.
B. pertussis and cAMP

Heat-labile toxin stimulates adenylyl cyclase

E. coli and cAMP

Anthrax toxin includes edema factor, a bacterial adenylate cyclase (increases cAMP)
Bacillus anthracis and cAMP

A Lipopolysaccharide found in the cell wall of G(-) bacteria N-dotoxin is an integral part of the gram-Negative cell wall *Endotoxin is heat stable
Endotoxin

Activates Macs: IL-1 causes fever TNF causes fever, hemorrhagic tissue necrosis NO causes hypotension (shock) <img src="144a - endotoxins.JPG" />
Endotoxin and Macrophages

Activates the complement (alternative pathway): C3a causes hypotension, edema C5a causes PMN chemotaxis <img src="144a - endotoxins.JPG" />
Endotoxin and complement

Activates Hageman factor This activates coagulation cascade, causing DIC <img src="144a - endotoxins.JPG" />
Endotoxin and Hageman factor (factor XII)

Lag phase: metabolic activity w/o division Log phase: rapid cell division Stationary phase: nutrient depletion slows growth. Spore formation in some bacteria. Death phase: prolonged nutrient depletion and buildup of waste products leads to death. <img src="144b - bacterial growth curve.JPG" />
Bacterial growth curve

DNA taken up directly from environment by competent prokaryotic and eukaryotic cells. Any DNA can be used
Transformation

F+ plasmid contains genes for conjugation process. Bacteria w/o this are termed F-. Plasmid is replicated and transferred through pilus from the F+ cell. Plasmid DNA only, no transfer of chromosomal genes.
F+ x F- Conjugation

F+ plasmid can become incorporated into bacterial chromosomal DNA, now termed Hfr cell. Replication of incoporated plasmid DNA may include some flanking chromosomal DNA. Transfer of plasmid and chromosomal genes.
Hfr x F- Conjugation

Lytic phage infects bacterium, leading to cleavage of bacterial DNA and synthesis of viral proteins. Parts of bacterial chromosomal DNA may become packaged in viral capsid. Phage infects

another bacterium, transferring these genes.

Generalized transduction

Lysogenic phage infects bacterium; viral DNA incorporated into bacterial chromosome. When phage DNA is excised, flanking bacterial gnees may be excised w/ it. DNA is packaged into phage viral capsid and can infect another bacterium.
Specialized transduction

Segment of DNA can jump (excision and reincorporation) from one location to another, can transfer genes from plasmid to choromosome and vice versa. When excision occurs, may include some flanking chromosomal DNA, which can be incorporated into a plasmid and transferred to another bacterium.
Transposition (transposons)

ABCDE ShigA -like toxin B otulinum toxin (certain strains) C holera toxin D iphtheria toxin E rythrogenic toxin of Streptococcus pyogenes

5 bacterial toxins encoded in a lysogenic phage

Clostridium (anaerobe) Corynebacterium Listeria Bacillus

Gram (+) | Rods | ?

Staphylococcus aureus
Gram (+) | Cocci | Catalase (+), in clusters (Staphylococcus) | Coagulase (+) | ?

Novobiocin sensitive: Staphylococcus epidermidis Nobobiocin resistant: Staphylococcus saprophyticus

Gram (+) | Cocci | Catalase (+), in clusters (Staphylococcus) | Coagulase (-) | ?

(+) Quellung (has capsule), Optochin sensitive, Bile soluble: Streptococcus pneumoniae (-) Quellung (no capsule), Optochin resistant, not bile soluble: Streptococcus viridans
Gram (+) | Cocci | Catalase (-), in chains (Streptococcus) | partial hemolysis (green alpha hemolysis) | ?

Bacitracin sensitive: Group A Strep (GAS) aka Streptoccus pyogenes Bacitracin resistant: Group B strep aka Streptococcus agalactiae
Gram (+) | Cocci | Catalase (-), in chains (Streptococcus) | Complete hemolysis (clear, beta-hemolysis) | ?

Enterococcus (E. faecalis) Peptostreptococcus (anaerobe)

Gram (+) | Cocci | Catalase (-), in chains (Streptococcus) | No hemolysis (gamma hemolysis) | ?

NO vobiocin - S aprophyticus is R esistant; E pidermidis is S ensitive On the office's staph retreat, there was NO S tRES
Identifying Staphylococci w/ Novobiocin (once you know it's a G(+)/catalase(+) coccus in clusters)

O ptochin: V iridans is R esistant P neumoniae is S ensitive (OVRPS = overpass) B acitracin: group B strep are R esistant group A strep are S ensitive (B-BRAS )
Identifying Streptococci (once you know it's a G(+)/catalase(-) coccus in chains)

Form a green ring around colonies on blood agar. Include: 1.) Streptococcus pneumoniae (catalase (-) and optochin

sensitive) <img src="Strep pneumo.JPG" /> 2.) viridans streptococci (catalase (-), optochin resistant)
alpha-hemolytic bacteria

Form a clear area of hemolysis on blood agar. Include: 1.) Staphylococcus aureus (catalase and coagulase positive) 2.) Streptococcus pyogenes - GAS (catalase negative and bacitracin sensitive) 3.) Streptococcus agalactiae - GBS (catalase negative and bacitracin resistant) 4.) Listeria monocytogenes (tumbling motility, meningitis in newborns, unpasteurized milk)
Beta-hemolytic bacteria

Catalase degrades H2O2, an antimicrobial product of PMNs. H2O2 is a substrate for myeloperoxidase.
Catalase

Staphylococci make catalase, whereas Streptococci do not S. aureus makes coagulase, whereas S. epidermidis and S. saprophyticus do not. (Staph make catalase b/c they have more staff. Bad staph (aureus, b/c epidermidis is skin flora) make coagulase and toxins.)
Catalase/Coagulase in G(+) cocci

Virulence factor of Staphylococcus aureus Binds Fc-IgG, inhibiting complement fixation and phagocytosis
Protein A (virulence factor)

In Staph aureus A superAg that binds MHCII and the TCR, resulting in polyclonal T-cell activation
TSST (@ molecular level)

<img src="147a - S aureus.JPG" /><img src="Staph aureus (1).JPG" /> 1.) Inflammatory Dz - skin infxns, organ abcesses, pneumonia 2.) Toxin-mediated dz - Toxic shock syndrome (TSST-1), scalded skin syndrome (exfoliative toxin), rapid-onset food poisoning (preformed enterotoxins) 3.) MRSA (methicillin-resistant S. aureus) infxn: important cause of serious nosocomial and community-acquired infxns. Resistant to beta-lactams due to altered penicillin-binding proteins. 4.) Misc. acute bacterial endocarditis, osteomyelitis
Dzs caused by Staphylococcus aureus

Infects prosthetic devices and catheters. Component of normal skin flora. Contaminates blood cultures.
Staphylococcus epidermidis

Encapsulated. Has IgA protease. Most common cause of: Meningitis Otitis media (in children) Pneumonia Sinusitis (S. pneumoniae MOPS are M ost OP tochin S ensitive) Associated w/ rusty sputum, sepsis in sickle cell anemia and splenectomy.
Streptococcus pneumoniae (the pneumococcus)

Immunoglobulin MOA, Clinical uses, Administration MOA - IgG (prepared from pooled human serum or plasma) binds to virus, blocking its attachment to the receptor/host cell Clinical uses: Given pre-exposure to prevent infection/disease or post-exposure to abort infection/modify disease course (eg., postexposure prophylaxis for Hepatitis A) Virusespecific hyperimmunoglobulin available for some diseases (HBIG, VZVIG, RIG) Administration - Parenteral

Amantadine, Rimantadine MOA, Clinical uses, Side Effects, Administration, Resistance MOA - Inhibit entry and uncoating of Influenza A virus by preventing acidification of the endosome (interfere w/M2 protein of influenza A) Clinical Uses - Prophylaxis and treatment of influenza A virus infection (specific for influenza A) Side Effects: Amantadine - Elevated concentrations (usually seen with reduced renal function (elderly) - renally excreted) -< ataxia, dizziness, slurred speech (CNS effects) Rimantadine - low risk of CNS effects (met by liver, doesn't cross BBB), some GI sx Administration - well absorbed oral Resistance single aa change in M2 (emerges very quickly) Fomiversen MOA, Clinical Uses, Administration MOA - Antisense oligonucleotide (21nucleotides long, complementary to mRNA from the major immediate-early transcriptional unit of CMV) inhibiting synthesis of essential proteins for CMV infection Clinical Use - CMV retinitis in AIDS pts who cannot take other meds (intolerance/contraindication) Administration Intravitreal injection Interferons MOA, Clinical Use, Side Effects, Administration MOA: (Bind cell receptor and induce multiple effects) Induce synthesis of antiviral proteins (including RNase and protein kinase) that protect the cell against subsequent challenges by both RNA and DNA viruses Clinical Use: IFN-a chronic hepatitis B and C (pegylated ifn + ribavirin), Kaposi's sarcoma, leukemias, malignant melanoma IFN-b - MS IFN-g NADPH oxidase deficiency (Chronic Granulomatous Disease) Side Effects: Influenzalike sx (esp. in first wk) BM suppression (neutropenia) Depression Fatigue, myalgia, wt loss and increases susceptibility to bacterial infection Administration - parenteral (once/wk dose due to long half life w/PEG) Ribavirin MOA, Clinical Use, Side Effects

MOA - Synthetic nucleoside analog that inhibits viral RNA synthesis by altering the nucleotide pools and normal mRNA formation (competitively inhibits IMP dehydrogenase) (needs to be phosphorylated in cell to become active) Clinical Use: Given orally in combo w/aIFN for chronic Hep C Aerosol tx for RSV pneumonia and bronchiolitis in infants Unlabeled uses include tx of other viral infections (influenza A and B, West Nile Virus, Lassa fever, Hantavirus Hemorrhagic fever w/renal syndrome) Side Effects: BM suppression (anemia) Teratogenic (pregnancy should be avoided for at least 6mo after termination of tx) Acyclovir MOA, Clinical Use, Side Effects, Administration, Resistance MOA - Guanosine analog, rapidly phosphorylated by virus-specific thymidine kinase (only slowly by phosphorylated by host thymidine kinase) to monophosphate (further phosphorylated by host cell to triphosphate). Preferentially inhibits viral DNA polymerase by chain termination. Clinical Use: HSV (oral) used for HSV induced mucocutaneous and genital lesions as well as for encephalitis, prophylaxis in immunocompromised VZV - Can treat chickenpox or shingles, decrease posherpetic neuralgia No effect on latent forms of HSV/VZV Side Effects: (well tolerated) Local irritation/burning (topical) Rare Nephrotoxicity due to crystallization in renal tubules Administration - Given PO, IV, topical (topical not very effective) Resistance (usually in immunocompromised) - No viral thymidine kinase (most common), mutation that affect acyclovir affinity/phosphorylation by thymidine kinase Famciclovir MOA, Clinical Use, Side Effects MOA - Rapidly converted to active compound, penciclovir, by enzymes in the intestinal wall and liver, then same MOA as acyclovir (monophosphorylated by virus, triphosphate formed by cell, preferential DNA pol inhibitor) Clinical Use - Preferred over Acyclovir for VZV (decreases new lesions, shedding, duration of

pain and postherpetic neuralgia), can also be used for HSV (but no more effective and more expensive than acyclovir) Side effects - well tolerated (mild headache, nausea, diarrhea) Valacyclovir MOA, Clinical Use, Side Effects MOA - Rapidly converted to active compound, acyclovir, by enzymes in the intestinal wall and liver, then same MOA as acyclovir (monophosphorylated by virus, triphosphate formed by cell, preferential DNA pol inhibitor) Clinical Use - Preferred over Acyclovir for VZV (decreases new lesions, shedding, duration of pain and postherpetic neuralgia), can also be used for HSV (but no more effective and more expensive than acyclovir) Side effects - well tolerated (mild headache, nausea, diarrhea) Ganciclovir MOA, Clinical Use, Side Effects, Administration, Resistance MOA - Phosphorylated to monophosphate by protein kinase in herpes virus, then triphosphate by host cell enzymes. Preferentially inhibits viral DNA polymerase. Clinical Use: Active vs. all Herpes viruses (but no better activity than acyclovir for HSV/VZV) - used for CMV CMV retinitis in AIDS pts Prevention of CMV disease in immunocompromised (transplant recipients) Side Effects: Neutropenia, Thrombocytopenia, Leukopenia Renal toxicity Teratogen, carcinogen, mutagen (only use if life or sight threatening infection) Administration - PO or IV Resistance - mutated CMV DNA polymerase or lack of viral kinase Foscarnet MOA, Clinical Use, Side Effects, Administration, Resistance MOA - Pyrophosphate analogue that acts as a noncompetitive inhibitor or viral DNA polymerase (no activation required by viral kinase) Clinical Use: Ganciclovir-resistant CMV Acyclovir-resistant HSV or VZV Side Effects Nephrotoxicity (usually reversible but may cause renal failure), electrolyte imbalances Administration - infused in large volumes of fluid Resistance - Mutated DNA polymerase

Zanamivir, Oseltamivir MOA, Clinical Use, Administration MOA - Inhibit influenza neuraminidase, decreasing release of progeny virus (NA is essential for release of newly assembled virions) Clinical Use - Influenza A and B Administration: Zanamivir - aerosol (low PO bioavailability) Oseltamivir - PO Maraviroc MOA, Clinical Use MOA - CCR5 antagonist that interferes w/necessary interaction w/co-receptor molecules Clinical Use - HIV (pts must have virus that uses CCR5 as coreceptor) Enfuvirtide Class, MOA, Clinicla Use, Side Effects, Adminstration, Resistance Class - Fusion inhibitor MOA - Peptide that binds viral gp41 subunit and inhibits conformational change required for fusion w/CD4 cells, blocking entry and replication. Clinical Use - HIV (used in pts w/persistent viral replication despite antiretroviral therapy) Side Effects - hypersensitivity reaction, reactions at injection site, increase risk of bacterial pneumonia Adminsitration - SubQ injection Resistance - Develops due to mutations in envelope protein Zidovudine (AZT) Class, MOA, Clinical Use, Side Effects, Resistance Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use HAART, used for general prophylaxis and during pregnancy to reduce risk of fetal transmission Side Effects: BM suppression reversed w/G-CSF and EPO Megaloblastic anemia Lactic acidosis (mt toxicity) GI intolerance, Headache Resistance enhancement of chain terminator removal Didanosine (DDI) Class, MOA, Clinical Use, Side Effects, Resistance Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA

chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Peripheral neuropathy Pancreatitis Lactic acidosis (mt toxicity) Resistance - enhancement of chain terminator removal or steric hindrance Stavudine (D4T) Class, MOA, Clinical Use, Side Effects, Resistance Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Peripheral neuropathy Pancreatitis Lactic acidosis (mt toxicity) Resistance - enhancement of chain terminator removal or steric hindrance Lamivudine (3TC) Class, MOA, Clinical Use, Side Effects, Resistance Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use HAART, HBV Side Effects: (no serious side effects) BM suppression - reversed w/G-CSF and EPO Lactic acidosis (mt toxicity) Resistance steric hindrance Tenofovir (TDF) Class, MOA, Clinical Use, Side Effects Class - Nucleotide RTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use - HAART - (paired w/ FTC or FTC+efavirenz in single pill regimen) Side Effects: (well tolerated) BM suppression reversed w/G-CSF and EPO Occasional nephrotoxicity Abacavir (ABC) Class, MOA, Clinical Use, Side Effects, Resistance Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA

chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Rash, anaphylactic reaction Lactic acidosis (mt toxicity) Resistance enhancement of chain terminator removal or steric hindrance Emtricitabine (FTC) Class, MOA, Clinical Use, Side Effects, Resistance Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3' OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use HAART Side Effects: (no serious side effects) BM suppression - reversed w/G-CSF and EPO Lactic acidosis (mt toxicity) Resistance - steric hindrance Nevirapine Class, MOA, Clinical Use, Side Effects, Resistance Class - NNRTI MOA - Binds to RT at allosteric site (different site than NRTIs) Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Rash (occasional SJS) Hepatotoxicity Resistance - single aa substitution in RT Efavirenz Class, MOA, Clinical Use, Side Effects, Resistance Class - NNRTI MOA - Binds to RT at allosteric site (different site than NRTIs) Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Rash (occasional SJS) CNS toxicity (sedation, weird dreams) Resistance single aa substitution in RT Etravirine Class, MOA, Clinical Use, Side Effects, Resistance Class - NNRTI MOA - Binds to RT at allosteric site (different site than NRTIs) Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Rash (occasional SJS) Hepatotoxicity Resistance - muation to RT (can tolerate more than 1aa mutation)

Raltegravir Class, MOA Class - Integrase inhibitor MOA - Binds active site of integrase and chelate metal ions required for catalysis of DNA strand transfer reaction Saquinavir , Ritonavir , Indinavir , Nelfinavir , Amprenavir Class, MOA, Clinical Use, Side Effects, Resistance Class - Protease Inhibitor (PI) MOA Binds enzyme active site and resists cleavage, preventing proteolytic processing of Gag and Gag-pol required to produce infectious virions Clinical Use - HAART Side Effects: Lipodystrophy GI upset Hyperlipidemia, Hyperglycemia Thrombocytopenia, Sicca syndrome (Indinavir) Resistance: Primarily steric hindrance (exclusion of drug from active site) Mutations also exist Ritonavir (acts as booster) + other PI can help overcome resistance Beviramat Class, MOA, Resistance Class - viral maturation inhibitors MOA Prevents cleavage of viral core polyprotein at the CA/SP-1 cleavage site, blocking viral maturation Resistance - polymorphisms at 3aa sites greatly compromise activity of compound (clinical development has been difficult) Adefovir dipivoxil MOA, Clinical Use, Side Effects MOA - Nucleotide analog of adenosine monophosphate that can inhibit RT and DNA polymerase activity Clinical Use: Originally for HIV but too toxic b/c high dose required HBV with evidence of active viral replication (based on persistence elevation of ALT/AST or histo evidence) Side Effects - Nephrotoxicity (monitor renal function) Entecavir MOA, Clinical Use, Side Effects MOA - Guanosine nucleoside analog with selective activity vs. HBV. Intracellular phophorylation to triphosphate, which competes for HBV DNA pol binding site. Side Effects nonspecific (headache, fatigue, nausea)

Delaviridine Class, MOA, Clinical Use, Side Effects Class - NNRTI MOA - Binds to RT at allosteric site (different site than NRTIs) Clinical Use HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Rash (occasional SJS) CNS toxicity (sedation, weird dreams) HAART When Initiated, Drugs used Initiated when patient presents with (any one of the below): 1. AIDS-defining illness 2. Low CD4 cell count (>350 cells/mm3) 3. High viral load Drugs used (select either regimen): 1. 2 NRTIs + PI 2. 2 NRTIs + NNRTI

CNS/PNS origins: Neuroectoderm (gives rise to what?)

CNS neurons Ependymal cells (inner lining of ventricles, make CSF) Oligodendrocytes Astrocytes

CNS/PNS origins: Neural Crest (gives rise to what?)

Schwann cells PNS neurons

CNS/PNS origins: Mesoderm (gives rise to what?)

M icroglia, like M acrophages, originate from M esoderm

Neurons
Comprise nervous system. Permanent cells -do not divide in adulthood. Large cells w/ prominent nucleoli.

Nissl substance
RER found in cell body and dendrites, but not axon of neurons.

Astrocytes
Physical support, repair, K+ metabolism, removal of excess NT. Maintenance of BBB.

Reactive gliosis in response to injury. <img src="392a Astrocyte.JPG" />

Astrocyte marker?
GFAP

Microglia
CNS phagocytes. Mesodermal origin. Not readily discernible in Nissle stains. Have small, irregular nuclei and relatively little cytoplasm. <img src="392b Microglia.JPG" />

What happens to microglia in the presence of tissue damage?

Microglia --(tissue damage)--< large ameboid phagocytic cells

What happens to HIV-infected microglia?

HIV-infected microglia fuse to form multinucleated giant cells in the CNS

Oligodendria
Each oligodendrocyte myelinates multiple CNS axons (up to 30 each). In Nissle stains, they appear as small nuclei with dark chromatin and little cytoplasm. <img src="392c oligodendroglia.JPG" />

What is the predominant type of glial cell in white matter?

Oligodendrocytes.

What cells are destroyed in multiple sclerosis?

Oligodendrocytes.

What do oligodendrocytes look like on H&amp;E?

"Fried Eggs" <img src="555a oligodendrocytes.JPG" />

Schwann cells

Each Schwann cell myelinates only 1 PNS axon. Also promote axonal regeneration. Derived from neural crest.

What are the cells that are destroyed in Guillain-Barr syndrome?

Schwann cells.

An acoustic neuroma is a type of...? Where is it located?

Acoustic neuroma is a type of Schwannoma. It is typically located in internal acoustic meatus (CN VIII)

Sensory receptors/corpuscles: Free nerve endings (C, A-delta fibers) Location? Senses?
In all skin, epidermis, some viscera. Senses pain and temperature. <img src="393a free nerve endings.JPG" />

Sensory receptors/corpuscles (location and senses): In all skin, epidermis, some viscera. Senses pain and temperature. <img src="393a free nerve endings.JPG" /> Which is this?
Free nerve endings (C, A-delta fibers)

Sensory receptors/corpuscles: Meissner's corpuscles Location? Senses?

In glabrous (hairless) skin. Senses dynamic fine touch (e.g., manipulation), adapt quickly. <img src="393b Meissners Corpuscles.JPG" />

Sensory receptors/corpuscles (location and senses): In glabrous (hairless) skin. Senses dynamic fine touch (e.g., manipulation), adapt quickly. <img src="393b Meissners Corpuscles.JPG" /> Which is this?
Meissner's corpuscles

Sensory receptors/corpuscles: Pacinian corpuscles Location? Senses?

In deep skin layers, ligaments, and joints. Sense vibration, pressure. <img src="393c Pascinian corpuscle.JPG" />

Sensory receptors/corpuscles (location and senses): In deep skin layers, ligaments, and joints. Sense vibration, pressure. <img src="393c Pascinian corpuscle.JPG" /> Which is this?
Pacinian corpuscles

Sensory receptors/corpuscles: Merkel's disks Location? Senses?

(cup-shaped, unencapsulated) In hair follicles. Sense static touch (e.g., shapes, edges, textures), adapt slowly. <img src="393d Merkels disk.JPG" />

Sensory receptors/corpuscles (location and senses): (cup-shaped, unencapsulated) In hair follicles. Sense static touch (e.g., shapes, edges, textures), adapt slowly. <img src="393d Merkels disk.JPG" /> Which is this?
Merkel's disks

Peripheral nerve layers: Endoneurium

Invests a single nerve fiber (Endo = inner) <img src="393e Peripheral nerve layers.JPG" />

Peripheral nerve layers: Perineurium

(P erineurium is the P ermeability barrier) Surrounds a fascicle of nerve fibers. (Peri = around) Must be rejoined in microsurgery for limb reattachment. <img src="393e Peripheral nerve layers.JPG" />

Peripheral nerve layers: Epineurium

Dense connective tissue that surrounds entire nerve (fasicles and blood vessels) (Epi = outer)

<img src="393e Peripheral nerve layers.JPG" />

Neurotransmitters: NE Change in dz? Location of synthesis?

Increased in anxiety, decreased in depression. Made in the locus ceruleus.

Increased in anxiety, decreased in depression. Made in the locus ceruleus. What NT is this?
NE

Neurotransmitters: Dopamine Change in dz? Location of synthesis?

Increased in schizophrenia, decreased in Parkinson's. Made in the ventral tegmentum and SNc

Increased in schizophrenia, decreased in Parkinson's. Made in the ventral tegmentum and SNc What NT is this?
Dopamine

Neurotransmitters: 5-HT Change in dz? Location of synthesis?

Decreased in anxiety, depression. Made in the raphe nucleus

Decreased in anxiety, depression. Made in the raphe nucleus What NT is this?

5-HT

Neurotransmitters: ACh Change in dz? Location of synthesis?

Decreased in Alzheimer's, Huntington's. Made in the basal nucleus of Meynert.

Decreased in Alzheimer's, Huntington's. Made in the basal nucleus of Meynert. What NT is this?
ACh

What 3 structures form the blood-brain barrier (BBB)?

1.) Tight junctions btw nonfenestrated capillary endothelial cells 2.) Basement membrane 3.) Astrocyte processes <img src="394a BBB.JPG" />

Besides the BBB, what are 2 similar barriers?

1.) Blood-testis barrier 2.) Maternal-fetal blood barrier of placenta

What happens at the BBB w/ infarction?

Infarction destroys endothelial cell tight junctions, leading to vasogenic edema

Glucose and amino acids at the BBB

Cross slowly by carrier-mediated transport mechanism.

Nonpolar/lipid-soluble substances at the BBB

Cross rapidly via diffusion.

Specialized brain regions w/ fenestrated capillaries and no BBB

Allow molecules in the blood to affect brain function (e.g., area postrema - vomiting center after chemo, OVLT - osmotic sensing) or neurosecretory products to enter circulation (e.g., neurohypophysis - ADH release)

Hypothalamus functions
The hypothalamus wears TAN HATS : T hirst and water balance A denohypophysis control N eurohypophysis releases hormones from hypothalamus H unger A utonomic regulation T emperature regulation S exual urges

Inputs to the hypothalamus

OVLT (senses change in osmolarity) Area postrema (responds to emetics)

Supraoptic nucleus of the hypothalamus

Area that makes ADH.

Area that makes ADH.

Supraoptic nucleus of the hypothalamus

Paraventricular nucleus of the hypothalamus

Area that makes oxytocin.

Area that makes oxytocin.

Paraventricular nucleus of the hypothalamus

Lateral area of the hypothalamus

Controls hunger: destruction leads to anorexia. ("If you zap the lateral nucleus, you shrink laterally ") Inhibited by leptin.

Ventromedial area of the hypothalamus

Controls satiety: destruction leads to hyperphagia. ("If you zap your ventromedial nucleus, you grow ventrally and medially .") Stimulated by leptin.

Anterior hypothalamus
Cooling (Anterior = cooling, or A/C). A nterior is pA rasympathetic.

Posterior hypothalamus

Heating (posterior = get fired up / heating). Sympathetic. If you zap your P osterior hypothalamus, you become a P oikilotherm (cold-blooded, like a snake)

Septal nucleus of the hypothalamus

area responsible for sexual urges

area responsible for sexual urges

Septal nucleus of the hypothalamus

Suprachiasmatic nucleus of the hypothalamus

Circadian rhythm. ("You need to sleep to be charismatic [chiasmatic]").

Posterior pituitary (neurohypophysis)

Receives hypothalamic axonal projections from supraoptic (ADH) and paraventricular (oxytocin) nuclei. Oxytocin: oxys = quick; tocos = birth.

Anterior pituitary aka...?

A nterior pituitary = A denohypophysis

Thalamus
Major relay for ascending sensory information that ultimately reaches the cortex. <img src="395a Thalamus.JPG" />

Blood supply to the thalamus

posterior communicating, posterior cerebral, and anterior choroidal arteries.

Lateral geniculate nucleus (LGN) of thalamus <img src="395b Thalamus without labels.JPG" />
(hint: "L ateral for L ight") area of thalamus for visual information.

area of thalamus for visual information.

Lateral geniculate nucleus (LGN) of thalamus <img src="395b Thalamus without labels.JPG" /> (hint: "L ateral for L ight")

Medial geniculate nucleus (MGN) of the thalamus <img src="395b Thalamus without labels.JPG" />

(hint: M edial for M usic) Area of the thalamus responsible for auditory information

Area of the thalamus responsible for auditory information

Medial geniculate nucleus (MGN) of the thalamus <img src="395b Thalamus without labels.JPG" /> (hint: M edial for M usic)

Ventral posterior nucleus, lateral part (VPL) -- of thalamus <img src="395b Thalamus without labels.JPG" />
part of the thalamus responsible for body sensation (proprioception, pressure, pain, touch, vibration via dorsal columns, spinothalamic tract).

part of the thalamus responsible for body sensation (proprioception, pressure, pain, touch, vibration via dorsal columns, spinothalamic tract).
Ventral posterior nucleus, lateral part (VPL) -of thalamus <img src="395b Thalamus without labels.JPG" />

Ventral posterior nucleus, medial part (VPM) -- of the thalamus <img src="395b Thalamus without labels.JPG" />
(hint: you put M akeup on your face, and sensory info is relayed through the VPM ) Area of thalamus responsible for facial sensation (via CN V)

Area of thalamus responsible for facial sensation (via CN V)

Ventral posterior nucleus, medial part (VPM) - of the thalamus <img src="395b Thalamus without labels.JPG" /> (hint: you put M akeup on your face, and sensory info is relayed through the VPM )

Motor and sensory locations in the thalamus

Motor is anterior to sensation in the thalamus, just like the cortex. <img src="395a Thalamus.JPG" />

Limbic system: Includes what? Responsible for what?

Includes cingulate gyrus, hippocampus, fornix, and mammillary bodies. Responsible for F eeding, F leeing, F ighting, F eeling, and sex (....) (The famous 5 F's )

Input to the cerebellum

Receives contralateral cortical input via middle cerebellar peduncle and ipsilateral proprioceptive information via inferior cerebellar peduncle. Input nerves = climbing and mossy fibers.

Output from the cerebellum

Provides stimulatory feedback to contralateral cortex to modulate movement. Output nerves = Purkinje fibers output deep to nuclei of cerebellum, which in turn output to cortex via superior cerebellar peduncle.

Deep nuclei of the cerebellum

Lateral to medial: D entate, E mboliform, G lobose, F astigial ("D on't E at G reasy F oods")

Lateral cerebellum
area of the cerebellum responsible for voluntary movement of extremities

area of the cerebellum responsible for voluntary movement of extremities

Lateral cerebellum

Medial cerebellum
Area of cerebellum responsible for balance, truncal coordination.

Area of cerebellum responsible for balance, truncal coordination.

Medial cerebellum

Basal ganglia (overall function)

Important in voluntary movements and making postural adjustments. Receives cortical input, provides negative feedback to cortex to modulate movement.

Important in voluntary movements and making postural adjustments. Receives cortical input, provides negative feedback to cortex to modulate movement.
Basal ganglia (overall function)

Excitatory pathway of the basal ganglia

Substantia Nigra pars compacta's (SNc's) dopamine binds to D1 receptros in the excitatory pathway, stimulating the excitatory pathway (incr motion). Therefore, loss of dopamine in Parkinson's inhibits the excitatory pathway (decr motion). <img src="396a Excitatory and inhibitory pathways.JPG" /> Key: Grey = stimulatory || Black = inhibitory SNc = Substantia nigra pars compacta GPe = Globus pallidus externus GPi = Globus pallidus internus STN = Subthalamaic nucleus D1 = Dopamine D1 receptor (excitatory) D2 = Dopamine D2 receptor (inhibitory)

Inhibitory pathway of the basal ganglia

SNc's dopamine binds to D2 receptros in the inhibitory pathway, inhibiting the inhibitory pathway (incr motion). Therefore, loss of dopamine in Parkinson's dz excites (i.e., disinhibits) the inhibitory pathway (decr motion). <img src="396a Excitatory and inhibitory pathways.JPG" /> Key: Grey = stimulatory || Black = inhibitory SNc = Substantia nigra pars compacta GPe = Globus pallidus externus GPi = Globus pallidus internus STN = Subthalamaic nucleus D1 = Dopamine D1 receptor (excitatory) D2 = Dopamine D2 receptor (inhibitory)

Parkinson's disease
Degenerative disorder of CNS associated w/ Lewy bodies (composed of alpha-synuclein)

and depigmentation of the substantia nigra pars compacta (loss of dopaminergic neurons). Rare cases have been linked to exposure to MPTP, a contaminant in illicit street drugs. ("TRaP = T remor (at rest), cogwheel R igidity, a nd P ostural instability. You are TRaP ped inside your body.")

Degenerative disorder of CNS associated w/ Lewy bodies (composed of alphasynuclein) and depigmentation of the substantia nigra pars compacta (loss of dopaminergic neurons). Rare cases have been linked to exposure to MPTP, a contaminant in illicit street drugs. ("TRaP = T remor (at rest), cogwheel R igidity, a nd P ostural instability. You are TRaP ped inside your body.")
Parkinson's disease

Hemiballismus
Sudden, wild flailing of 1 arm. Characteristic of contralateral subthalamic nucleus lesion. Loss of inhibition of thalamus through globus pallidus. ("Hemiballismus = Half ballistic -like throwing a baseball")

Huntington's dz
Autosomal-dominant trinucleotide repeat d/o. Chromosome 4. Atrophy of caudate nucleus (loss of GABAergic neurons) leads to enlarged lateral ventricles on CT. <img src="397a HDAtrophy of caudate nucleus.JPG" /> Chorea, depression, progressive dementia. Sx manifest in affeccted indvls btw ages 20-50. (Expansion of CAG repeats: "C audate loses A Ch and G ABA")

Autosomal-dominant trinucleotide repeat d/o. Chromosome 4. Atrophy of caudate nucleus (loss of GABAergic neurons) leads to enlarged lateral ventricles on CT. <img src="397a HDAtrophy of caudate nucleus.JPG" />

Chorea, depression, progressive dementia. Sx manifest in affeccted indvls btw ages 20-50. (Expansion of CAG repeats: "C audate loses A Ch and G ABA")
Huntington's dz

Chorea
Sudden, jerky, purposeless movements. Characteristic of basal ganglia lesion (e.g., Huntington's disease) (Chorea = dancing (Greek). Think choral dancing or choreography)

Athetosis
Slow, writhing movements, especially if fiingers. Characteristic of basal ganglia lesion (e.g., Huntington's dz) (Athetos = not fixed (Greek). Think snakelike.)

Essential/postural tremor
Action tremor, autosomal dominant. Essential tremor pts often self-medicate w/ alcohol, which decreases the tremor. Tx: beta-blockers.

Resting tremor

Not noticeable distally. Seen in Parkinson's ("pill-rolling" tremor)

Intention tremor
Slow, zigzag motion when pointing twd a target; associated w/ cerebellar dysfunction.

Cerebral cortex: where are the Sylvian fissure vs. Central sulcus?
A: Sylvian fissure is above temporal lobe; central sulcus divides frontal and parietal lobes. <img src="398a Cerebral cortex fxns.JPG" />

Cerebral cortex: What is the arcuate fasciculus?

Connection between Associative auditory cortex (Wernicke's area; dominant hemisphere) and Motor speech area (Broca's area; dominant hemisphere) <img src="398a Cerebral cortex fxns.JPG" />

Cerebral cortex: Where is the primary auditory cortex (Heschel's gyrus)? The primary motor area? The primary sensory area? The premotor area (part of extrapyramidal circuit)?
<img src="398a Cerebral cortex fxns.JPG" />

Frontal lobe functions

"Executive functions" Planning, inhibition, concentration, orientation, language, abstraction, judgment, motor regulation, mood. Lack of social judgment is most notable in frontal lobe lesion. ("D amage = D isinhibition" - e.g., Phineas Gage)

Homonculus: What is it? What is it used for? What reaches into the Sylvian fissure? The longitudinal fissure?
Topographical representation of sensory and motor areas in the cerebral cortex. Used to localize lesion (e.g., in blood supply) leading to specific defects. For example, lower extremity deficit in sensation or movement indicates involvement of anterior cerebral artery. <img src="399a Motor homonculus.JPG" />

Brain lesion in: Broca's area

(hint: BRO ca's is BRO ken speech.) Consequence: Motor (nonfluent/expressive) aphasia w/ good comprehension.

Motor (nonfluent/expressive) aphasia w/ good comprehension. Where is the lesion?

Broca's area (hint: BRO ca's is BRO ken speech.)

Brain lesion in: Wernicke's area

(hint: W ernicke's is W ordy but makes no sense.) Consequence: Sensory (fluent/receptive) aphasia w/ poor comprehension, neologisms.

Sensory (fluent/receptive) aphasia w/ poor comprehension, neologisms. Where is the lesion?

Wernicke's area (hint: W ernicke's is W ordy but makes no sense.)

Brain lesion in: Arcuate fasciculus (connects Wernicke's to Broca's area)

Consequence: Conduction aphasia; good comprehension, fluent speech, but poor repitition.

Conduction aphasia; good comprehension, fluent speech, but poor repitition. Where is the lesion?
Arcuate fasciculus (connects Wernicke's to Broca's area)

Brain lesion in: Amygdala (bilateral)

Consequence: Kluver-Bucy syndrome (hyperorality, hypersexuality, disinhibited behavior)

Kluver-Bucy syndrome (hyperorality, hypersexuality, disinhibited behavior) Where is the lesion?

Amygdala (bilateral)

Brain lesion in: Frontal lobe

Consequence: Personality changes and deficits in concentration, orientation, and judgment; may havve reemergence of primitive reflexes.

Personality changes and deficits in concentration, orientation, and judgment; may havve reemergence of primitive reflexes. Where is the lesion?
Frontal lobe

Brain lesion in: Right parietal lobe

Consequence: Spatial neglect syndrome (agnosia of the contralateral side of the world)

Spatial neglect syndrome (agnosia of the contralateral side of the world) Where is the lesion?
Right parietal lobe

Brain lesion in: Reticular activating system (midbrain)

Consequence: Reduced levels of arousal and wakefulness (e.g., coma)

Reduced levels of arousal and wakefulness (e.g., coma) Where is the lesion?
Reticular activating system (midbrain)

Brain lesion in: Mammillary bodies (bilateral)

Consequence: Wernicke-Korsakoff syndrome (confusion, confabulation, ophthalmoplegia, ataxia)

Wernicke-Korsakoff syndrome (confusion, confabulation, ophthalmoplegia, ataxia) Where is the lesion?

Mammillary bodies (bilateral)

Brain lesion in: Basal ganglia

Consequence: May result in tremor at rest, chorea, or athetosis

May result in tremor at rest, chorea, or athetosis Where is the lesion?

Basal ganglia

Brain lesion in: Cerebellar hemisphere

(hint: cerebellar hemispheres are laterally located, so they affect the lateral limbs) Consequence: Intention tremor, limb ataxia; Damage to the cerebellum results in ipsilateral deficits; Fall toward side of lesion

Intention tremor, limb ataxia; Damage to the cerebellum results in ipsilateral deficits; Fall toward side of lesion Where is the lesion?
Cerebellar hemisphere (hint: cerebellar hemispheres are laterally located, so they affect the lateral limbs)

Brain lesion in: Cerebellar vermis

(hint: vermis is centrally located, so it affects the central body) Consequence: Truncal ataxia, dysarthria.

Truncal ataxia, dysarthria. Where is the lesion?

Cerebellar vermis (hint: vermis is centrally located, so it affects the central body)

Brain lesion in: Subthalamic nucleus

Consequence: Contralateral hemiballismus

Contralateral hemiballismus Where is the lesion?

Subthalamic nucleus

Brain lesion in: Hippocampus

Consequence: Anterograde amnesia -inability to make new memories

Anterograde amnesia -- inability to make new memories Where is the lesion?

Hippocampus

Brain lesion in: Paramedian pontine reticular formation (PPRF)

Consequence: Eyes look away from side of lesion

Eyes look away from side of lesion Where is the lesion?

Paramedian pontine reticular formation (PPRF)

Brain lesion in: Frontal eye fields

Consequence: Eyes look toward lesion.

Eyes look toward lesion. Where is the lesion?

Frontal eye fields

Aphasia (definition) vs. Dysarthria (definition)

Aphasia is a higher-order inability to speak. vs. Dysarthria is a motor inability to speak.

Broca's aphasia
Nonfluent aphasia w/ intact comprehension. Broca's area -- inferior frontal gyrus. ("Bro ca's Bro ken Boca " [boca = mouth in Spanish])

Wernicke's aphasia

Fluent aphasia with impaired comprehension. Wernicke's area -- superior temporal gyrus. ("W ernicke's is W ordy but makes no sense." or "W ernicke's = W hat?")

Global aphasia
Nonfluent aphasia w/ impaired comprehension. Both Broca's and Wernicke's areas affected.

Conduction aphasia
Poor repitition but fluent speech, intact comprehension. Arcuate fasciculus -- connects Broca's and Wernicke's areas.

Anterior cerebral artery: what areas of cortex does it supply?

Supplies anteromedial surface of brain [darkest grey] <img src="400a Cerebral arteries.JPG" />

Middle cerebral artery: what areas of cortex does it supply?

Supplies lateral surface of brain [White areas below] <img src="400a Cerebral arteries.JPG" />

Posterior cerebral artery: what areas of cortex does it supply?

Supplies posterior and inferior surfaces [medium grey areas below] <img src="400a Cerebral arteries.JPG" />

Anterior cerebral artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What does it supply?
[Right anterior cerebral artery is labeled below -- top/left] <img src="401a Circle of Willis with labels.JPG" /> Supplies medial surface of the brain, leg-foot area of motor and sensory cortices.

Middle cerebral artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What does it supply?
[Labeled below at top/left, just beneath right anterior cerebral art.] <img src="401a Circle of Willis with labels.JPG" /> Supplies lateral aspect of brain, trunk-arm-face area of motor and sensory cortices, Broca's and Wernicke's speech areas (on dominant hemisphere), optic radiations.

What deficit occurs w/ problems in the middle cerebral artery?

Contralateral face and arm paralysis and sensory loss, aphasia (dominant sphere), leftsided neglect.

Posterior cerebral artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What does it supply?

[labeled below along middle/right] <img src="401a Circle of Willis with labels.JPG" /> Supplies the visual cortex.

What deficit is associated with problems in the posterior cerebral artery?

Contralateral homonymous hemianopia with macular sparing.

Anterior communicating artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What is associated with this artery?
[labeled below along top/right] <img src="401a Circle of Willis with labels.JPG" /> Most common site of circle of Willis aneurysm; lesions may cause visual field defects.

Posterior communicating artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What is associated with this artery?
[labeled below along middle/left] <img src="401a Circle of Willis with labels.JPG" /> Common area of aneurysm; Causes CN III palsy.

Lateral striate: Where are they? <img src="401b Circle of Willis without labels.JPG" /> What do they supply?
[labeled below along middle/right] <img src="401a Circle of Willis with labels.JPG" /> Divisions of the middle cerebral artery that supply the internal capsule, caudate, putamen, and globus pallidus.

What deficit is associated with the lateral striate?

"Arteries of stroke"; infarct of internal capsule causes pure motor hemiparesis.

Watershed zones of the circle of Willis

Between anterior cerebral/middle cerebral, posterior cerebral/middle cerebral arteries. Damaged in severe hypotension --< upper leg/upper arm weakness, defects in higherorder visual processing.

Posterior Inferior Cerebellar Artery (PICA): Where is it? <img src="401b Circle of Willis without labels.JPG" /> What deficits are associated with an infarct here?
[labled below at bottom/right] <img src="401a Circle of Willis with labels.JPG" /> Infarcts cause Wallenberg's syndrome (aka lateral medullary syndrome) (nystagmus, ipsilateral ataxia, nausea, vomiting, Horner's syndrome)

Basilar artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What would an infarct here cause?
[labeled below along middle/left] <img src="401b Circle of Willis without labels.JPG" /> Infarct causes locked-in syndrome.

In general, strokes of the anterior circle of Willis vs. the posterior circle of Willis
stroke of the anterior circle : General sensory and motor dysfunction, aphasia. stroke of the posterior circle : Cranial nerve deficits (vertigo, visual deficits), coma, cerebellar deficits (ataxia)

Anterior spinal artery: Where is it? <img src="401b Circle of Willis without labels.JPG" /> What defects are associated?
[at bottom of picture, below] <img src="401a Circle of Willis with labels.JPG" /> Medial

medullary syndrome: contralateral hemiparesis (lower extremities), medial lemniscus (decr proprioception), ipsilateral paralysis of hypoglossal nerve

Anterior Inferior Cerebellar Artery (AICA) Where is it located? <img src="401b Circle of Willis without labels.JPG" /> What deficits are associated?

[labeled below in lower right] <img src="401a Circle of Willis with labels.JPG" /> Lateral inferior pontine syndrome: ipsilateral facial paralysis, ipsilateral cochlear nucleus, vestibular (nystagmus), ipsilateral facial pain and temperature, ipsilateral dystaxia (MCP, ICP)

Berry aneurysms: Where do they occur? What is the most common complication?
<img src="554a Berry aneurysms.JPG" /> Occur at the bifurcations in the circle of Willis. Most common site is bifurcation of the anterior communicating artery. Rupture (most common complication) leads to hemorrhagic stroke/subarachnoid hemorrhage.

PO2 SaO2 Cyanosis Oxygen Hypoxia Ischemia Respiratory acidosis Ventilation defect

driving force for diffusion of O2 into tissue percent heme groups occupied by O2 decreased O2 saturation (SaO2); O2 content electron acceptor in oxidative pathway inadequate O2 leads to ATP depletion decreased arterial (or venous) blood flow retention of CO, always decreases PaO2 impaired delivery of O2 to alveoli; intrapulmonary shunting of blood (e.g.,

RDS) Perfusion defect absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus) O2 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis) SaO2; heme Fe+3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue cyanosis not corrected by O2; chocolate colored blood SaO2; left-shift O2 binding curve; inhibits cytochrome oxidase car exhaust, space heaters, smoke inhalation headache; cherry red color skin inhibits cytochrome oxidase; systemic asphyxiant 2, 3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia 2, 3 BPG, high altitude, acidosis, fever respiratory alkalosis enhances glycolysis; synthesis 2,3 BPG damages membrane and drains off protons; alcohol, salicylates drain off protons; dinitrophenol, thermogenin (brown fat) hyperthermia impaired Na+/K+ ATPase pump

Diffusion defect

Methemoglobin Clinical methemoglobinemia Carbon monoxide Causes carbon monoxide poisoning S/S carbon monoxide poisoning Cyanide

Carbon monoxide + cyanide poisoning house fires Left-shifted O2 curve Right-shifted O2 curve High altitude Mitochondrial poisons Uncoupling agents in mitochondria Complication mitochondrial poisons/uncoupling agents Decreased ATP

(cellular swelling); reversible Anaerobic glycolysis Irreversible injury hypoxia Mitochondrial damage Irreversible injury hypoxia Free radicals Free radicals Superoxide dismutase Glutathione Catalase Lipofuscin Reperfusion injury in heart Mitochondrial injury SER hyperplasia Complications SER hyperplasia Chediak-Higashi Chediak-Higashi I cell disease Rigor mortis ATP synthesis in hypoxia; lactate intracellular pH, denatures proteins membrane/mitochondrial damage release cytochrome c activates apoptosis cytosolic Ca2+ activates phospholipase, proteases, endonuclease unpaired electron in outer orbit; damage cell membranes and DNA superoxide, hydroxyl, peroxide, drugs (acetaminophen) neutralizes superoxide neutralizes peroxide, drug FRs neutralizes peroxide indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage superoxide FRs + calcium cytochrome c in cytosol initiates apoptosis alcohol, barbiturates, phenytoin increases drug metabolism (e.g., oral contraceptives); low vitamin D membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles AR; giant lysosomes absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes stiff muscles after death due to ATP

depletion Fatty change in liver Fatty change in liver Causes fatty change Fatty change in kwashiorkor Ferritin Hemosiderin Atrophy Brain atrophy Exocrine gland atrophy in CF Labile cells Stable cells Permanent cells Hypertrophy LVH RVH Bladder smooth muscle hypertrophy Removal of kidney Hyperplasia MCC alcohol (increase in NADH); DHAP G3P TG VLDL pushes nucleus to side synthesis TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL synthesis of apoproteins primary iron storage protein; soluble in blood; serum level reflects marrow storage iron insoluble ferritin degradation product visible with Prussian blue stain reduction in cell/tissue mass by either loss or cell shrinkage ischemia; Alzheimers duct obstruction by thick secretions stem cells (skin, marrow, GI tract) in G0 phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones) cannot replicate; cardiac/striated muscle; neurons increase in cell size (structural components, DNA) increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis) pulmonary hypertension prostate hyperplasia constricts urethra hypertrophy of remaining kidney increase in number of cells

Endometrial hyperplasia RBC hyperplasia Prostate hyperplasia Gynecomastia Metaplasia Squamous metaplasia in bronchus Intestinal metaplasia in stomach Squamous metaplasia bladder Barretts esophagus Dysplasia Squamous dysplasia in cervix Squamous dysplasia in bronchus Necrosis Coagulation necrosis Infarction Liquefactive necrosis Caseous necrosis Granulomas Epithelioid cells

unopposed estrogen (obesity, taking estrogen) increased EPO (blood loss, ectopic secretion, high altitude) increased dihydrotestosterone (DHEA) hyperplasia male breast tissue; normal in newborn, adolescent, elderly one adult cell type replaces another cell type smoking Paneth cells, goblet cells; H pylori chronic atrophic gastritis Schistosoma hematobium infection glandular metaplasia of distal esophagus; due to GERD atypical hyperplasia and metaplasia are precursors for cancer human papilloma virus smoking death of groups of cells preservation of structural outline (due to lactic acid) pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene brain infarct, bacterial infections; wet gangrene variant coagulation necrosis; granulomas due to TB/systemic fungi activated macrophages (epithelioid cells); multinucleated giant cells; CD4 TH1 cells -interferon released by CD4 T cells activates macrophages

Multinucleated giant cells Granulomas Enzymatic fat necrosis Fibrinoid necrosis Postmortem necrosis Dystrophic calcification Dystrophic calcification Metastatic calcification Nephrocalcinosis S/S nephrocalcinosis Apoptosis Signals activating apoptosis Signal modulators of apoptosis BCL-2 genes

fusion of epithelioid cells type IV hypersensitivity associated with pancreatitis; soap formation (Ca2+ + fatty acids) necrosis of immune reactions (immune vasculitis/endocarditis) autolysis; no inflammatory reaction calcification of damaged tissue; normal serum calcium pancreatitis; atherosclerotic plaque calcification of normal tissue; increased serum calcium or phosphorus metastatic calcification of collecting tubule basement membranes polyuria due to nephrogenic diabetes insipidus; renal failure gene regulated individual cell death mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal TP53 suppressor gene, BCL-2 genes anti-apoptosis gene; prevents cytochrome c from leaving mitochondria responsible for enzymatic cell death in apoptosis; proteases and endonucleases eosinophilic cytoplasm, pyknotic (ink dot) nucleus loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells key chemical in acute inflammation;

Caspases Markers of apoptosis Apoptosis Histamine

mast cell; arteriole vasodilation; venular permeability Rubor acute inflammation Calor acute inflammation Tumor acute inflammation Dolor acute inflammation Acute inflammation Initial vessel events Neutrophil rolling acute inflammation Integrins CD11/CD18 Endothelial cell adhesion molecules ICAM VCAM Activation neutrophil adhesion molecules Activation neutrophil adhesion molecules Chemotaxis Opsonizing agents Neutrophils, monocytes, macrophages O2-dependent MPO system ProductionofsuperoxidefromO2 redness; arteriole vasodilation (histamine) heat; arteriole vasodilation (histamine) swelling; vessel permeability (histamine) pain; bradykinin, PGE neutrophil dominant; IgM transient vasoconstriction arteriolar vasodilation venular permeability due to selectins neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination markers for integrins activated by IL-1 and TNF intercellular adhesion molecule vascular cell adhesion molecule Leukocyte adhesion molecule defect neutrophilic leukocytosis; corticosteroids neutropenia; endotoxins directed movement; C5a and LTB4 IgG, C3b; enhance phagocytosis receptors for IgG, C3b most potent microbicidal system; neutrophils, monocytes NADPH oxidase with NADPH cofactor; produces respiratory burst

Nitro blue tetrazolium (NBT) Superoxide dismutase Myeloperoxidase Microbicidal defects Chronic granulomatous disease Chronic granulomatous disease Chronic granulomatous disease Myeloperoxidase deficiency Opsonization defect Phagocytosis defect COX inhibitors PGE2 PGI2 Nitric oxide IL-1 and TNF IL-6 Acute phase reactants Bradykinin

test for respiratory burst converts superoxide to peroxide lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl) chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR) absent NADPH oxidase; no respiratory burst Staphylococcus aureus not killed (catalase positive) Streptococcus killed (catalase negative) AR; respiratory burst present; no bleach produced Brutons agammaglobulinemia (XR, decreased IgG) Chediak-Higashi (see cell injury); also has defect in microtubule polymerization non-steroidals (non-selective), selective COX-2 inhibitors vasodilation, fever vasodilator; prevent platelet aggregation vasodilator; FR gas from conversion arginine to citrulline fever, synthesis acute phase reactants in liver, leukocytosis stimulated by IL-1; stimulates synthesis of acute phase reactants fibrinogen, ferritin, C-reactive protein kinin produced in conversion of factor

XII to factor XI Bradykinin Anaphylatoxins Prostaglandin I2 Lipoxygenase Zileuton Zafirlukast, montelukast LTC4, -D4, -E4 TXA2 Dipyridamole Corticosteroids Corticosteroids Fever Chronic inflammation Granuloma Positive PPD Suppurative inflammation Cellulitis pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors C3a and C5a; directly stimulate mast cell release of histamine synthesized by endothelial cells; vasodilator, inhibits platelet aggregation hydroxylation of arachidonic acid inhibits lipoxygenase block lipoxygenase receptor bronchoconstrictors synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction inhibits thromboxane synthase inhibits phospholipase A2, activation neutrophil adhesion molecules neutrophilic leukocytosis, lymphopenia, eosinopenia right shift OBC; hostile to bacterial/viral replication monocyte/macrophage; IgG; repair by fibrosis cellular immunity; macrophages interact with TH1 class cells (memory cells) Langerhans cells process PPD and interact with TH1 class cells abscess; Staphylococcus aureus (coagulase) subcutaneous inflammation; Streptococcus pyogenes

(hyaluronidase) Pseudomembranous inflammation Cell cycle TP53 and RB suppressor genes BAX gene Extracellular matrix Complete restoration Scar tissue Collagen Collagen Type I collagen Type II collagen Type IV collagen Type X collagen Laminin Fibronectin Angiogenesis in repair Key event in wound repair Granulation tissue Collagenases toxins from Corynebacterium diphtheriae, Clostridium difficile key checkpoint G1 to S phase arrests cell in G1 phase for DNA repair or apoptosis stimulates apoptosis; activated by TP53 suppressor gene if too much DNA damage basement membrane, interstitial matrix cell must be capable of duplication, no damage to basement membrane end-product of repair by connective tissue triple helix of cross-linked chains cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength bones, tendons early wound repair basement membrane epiphyseal plate key basement membrane glycoprotein key interstitial matrix glycoprotein basic fibroblast growth factor, vascular endothelial growth factor granulation tissue formation; fibronectin responsible becomes scar tissue zinc cofactor (metalloprotease); type III collagen replaced by type I collagen

Tensile strength of healed wound Inhibition wound healing Ehlers-Danlos syndrome Scurvy Keloid Pyogenic granuloma Healing by primary intention Healing by secondary intention Liver injury Lung injury CNS injury WBC alterations in acute inflammation Erythrocyte sedimentation rate C-reactive protein Polyclonal gammopathy Total body water Osmosis

80% original strength infection (MCC S. aureus), zinc deficiency, DM defects in collagen synthesis and structure; hyperelasticity collagen tensile strength by decreasing cross-links at points of hydroxylation excessive type III collagen; common in blacks exuberant granulation tissue; bleeds when touched clean wound; appose wound margins with suture infected wound; leave wound open; myofibroblasts important regenerative nodules; abnormal cytoarchitecture type II pneumocyte repair cell astrocyte and microglial cell repair cells; gliosis neutrophilic leukocytosis, left shift, toxic granulation increased fibrinogen enhances rouleaux indicator of acute inflammation and inflammatory atheromatous plaque diffuse of -globulins; IgG; chronic inflammation ECF (plasma, interstitial fluid) + ICF (cytosol) H20 shift between ECF and ICF; controlled by serum Na+ and glucose

Edema

increased fluid in interstitial space or body cavities; transudate, exudate, lymph protein and cell-poor fluid in interstitial space/body cavity; alteration Starlings forces oncotic pressure (albumin) keeps fluid in vessels, hydrostatic pressure pushes fluid out decreased oncotic pressure and/or increased hydrostatic pressure pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension hydrostatic pressure and oncotic pressure cardiac output (activation RAA system), primary renal disease kwashiorkor; nephrotic syndrome; cirrhosis oncotic pressure, hydrostatic pressure protein and cell rich (pus); acute inflammation with vessel permeability radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor) endothelial injury, stasis, hypercoagulability fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis) anticoagulants that prevent venous clot formation

Transudate

Starlings forces Pitting edema Hydrostatic pressure Renal retention sodium and water Causes of renal retention of sodium/water Oncotic pressure (hypoalbuminemia) Ascites in cirrhosis Exudate

Lymphedema Thrombus Venous thrombus Heparin/warfarin

Arterial thrombus Aspirin Pulmonary thromboembolism Systemic thromboembolism Fat embolus Amniotic fluid embolism Diving Decompression sickness Dyspnea, chest pain underwater Dyspnea, chest pain rising to surface Hypovolemic shock (blood loss) Cardiogenic shock Septic shock Kidneys Shock complications Tumors Benign tumors

endothelial injury; platelets held together by fibrin prevents platelet thrombus in arteries femoral vein site of origin majority from left heart long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia DIC; lanugo hair in maternal pulmonary arteries 1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue release of N2 gas from tissue with rapid ascent; ischemic damage pulmonary embolus spontaneous pneumothorax CO and LVEDP; PVR CO; LVEDP and PVR CO ( venous return); PVR (vasodilation) most susceptible organ in shock; straight portion proximal tubule most susceptible ischemic ATN, multiorgan failure, AG metabolic acidosis parenchyma neoplastic component epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma) epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma

Carcinoma

Basal cell carcinoma Squamous cell carcinoma Adenocarcinoma Transitional cell carcinoma Sarcoma Liposarcoma Embryonal rhabdomyosarcoma Teratoma Hamartoma Choristoma Mixed tumor Leukemia Lymphoma Extranodal lymphoma sites Malignant tumors Upregulate telomerase Monoclonality E-Cadherin Malignant cells

invades but does not metastasize lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix distal esophagus colon, kidney, liver, pancreas, prostate, breast, lung, endometrium renal pelvis, ureter, bladder malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone) MC sarcoma in adults MC sarcoma in children ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp normal tissue aberrant tissue location; pancreatic tissue stomach wall different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid malignancy of stem cells in bone marrow malignancy of lymph nodes stomach (MC), Peyers patches invade and metastasize; benign tumors do not increases telomere length; found in all neoplastic cells key finding in neoplastic vs. normal cells intercellular adhesion; lose adhesion in malignant cells receptors for laminin (basement

membrane), fibronectin (ECM) Invasion enzyme Angiogenesis Metastasis Carcinoma Vessel invading carcinomas Sarcoma Seeding type IV collagenase (basement membrane) basic fibroblast growth factor, vascular endothelium growth factor lymphatic, hematogenous, seeding; often more common than primary cancer lymph node -> hematogenous renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma hematogenous ovarian cancer, periphery lung, CNS via spinal fluid

Sites where metastasis more common lung, bone, brain, liver, adrenal primary cancer Sites where primary cancer more common than metastasis Bone metastasis Bone sites metastasis Osteoblastic metastasis Osteolytic metastasis EM neurosecretory granules EM thin and thick myofilaments EM Birbeck granules Primary prevention Cancers in children GI tract, kidney, urogenital osteoblastic (radiodense); osteolytic (radiolucent) vertebra MC (Batson venous plexus) prostate cancer; increased serum AP, hypercalcemia breast cancer carcinoid tumors, small cell carcinoma, neuroblastoma rhabdomyosarcoma histocytic neoplasms (Langerhans histiocytosis) stop smoking; sun screen; high fiber diet leukemia (MC), CNS tumors, Burkitts, Ewings, neuroblastoma

Cancer vaccine Cancer incidence men Cancer incidence women Cancer mortality men Cancer mortality women Gynecologic cancers Cervical Pap smear Malignant melanoma Southeast China Southeast Asia Japan Africa Squamous dysplasia oropharynx, larynx, bronchus, cervix Chronic irritation sinus orifices, third degree burn scars Actinic (solar) keratosis Glandular metaplasia of esophagus (Barretts) Endometrial hyperplasia Glandular (intestinal) metaplasia of stomach (Helicobacter) Chronic ulcerative colitis Villous adenoma of rectum Tubular adenoma of colon Scar tissue in lung Regenerative nodules in cirrhosis

hepatitis B vaccine; prevents hepatocellular carcinoma prostate lung colorectal breast lung colorectal lung prostate colorectal lung breast colorectal endometrium ovary cervix decreased incidence of cervical cancer; detects cervical dysplasia fastest increasing in world nasopharyngeal carcinoma (EBV) hepatocellular carcinoma (HBV + aflatoxin) stomach cancer Burkitts lymphoma, Kaposi sarcoma (HHV-8) risk for squamous cell carcinoma (SCC) risk for SCC risk factor for SCC risk factor for adenocarcinoma risk factor for adenocarcinoma risk factor for adenocarcinoma risk factor for adenocarcinoma risk factor for adenocarcinoma risk factor for adenocarcinoma risk factor for adenocarcinoma risk factor for hepatocellular

carcinoma Complete hydatidiform mole Dysplastic mole UVB light HHV-8 EBV Polycyclic hydrocarbons Asbestos Polycyclic hydrocarbons Barretts esophagus H. pylori Tubular adenoma, villous adenoma HBV and HCV Vinyl chloride Gallstones, porcelain gallbladder Polycyclic hydrocarbons Polycyclic hydrocarbons Polycyclic hydrocarbons HPV + lack of circumcision Age risk factor for choriocarcinoma MC risk factor for malignant melanoma MC risk factor for BCC, SCC, melanoma MC risk factor for Kaposis sarcoma MC risk factor for nasopharyngeal carcinoma MC risk factor for larynx (SCC), lung cancers MC risk factor for mesothelioma MC risk factor for oral cavity, midesophagus SCC MC risk factor for distal esophagus adenocarcinoma MC risk factor for stomach adenocarcinoma and lymphoma MC risk factors for colon adenocarcinoma MC risk factors for hepatocellular carcinoma MC risk factor for liver angiosarcoma MC risk factor for gallbladder adenocarcinoma MC risk factor for pancreas adenocarcinoma MC risk factor for renal cell carcinoma MC risk factor for urinary bladder MC risk factor for penis SCC MC risk factor for prostate adenocarcinoma

Cryptorchid testis Age >50 with excess estrogen exposure HPV 16/18 DES Nulliparity Complete mole Turner syndrome (XO) Turner syndrome (XO/XY) Ionizing radiation Family history (MEN IIa/IIb) Hashimotos thyroiditis Ionizing radiation EBV Ionizing radiation EBV HTLV-1 Bacterial causes of cancer Parasitic causes of cancer Carcinogenesis

MC risk factor for seminoma MC risk factor for breast and endometrial carcinoma MC risk factor for vulva, vagina, cervix SCC MC risk factor for vagina/cervix clear cell carcinoma MC risk factor for surface derived ovarian cancer MC risk factor for choriocarcinoma MC risk factor for dysgerminoma of ovary gonadoblastoma of ovary MC risk factor for papillary cancer of thyroid MC risk factor for medullary carcinoma thyroid MC risk factor for malignant lymphoma thyroid MC risk factor for osteogenic sarcoma MC risk factor for primary CNS lymphoma in AIDS and Burkitts lymphoma MC risk factor for acute/chronic myelogenous leukemia MC risk factor for Burkitts lymphoma MC risk factor for T cell leukemia/lymphoma H. pylori (stomach adenocarcinoma and lymphoma) S. hematobium (SCC bladder), C. sinensis (cholangiocarcinoma) mutations involving regulatory genes

Regulatory genes Types mutations

proto-oncogenes, suppressor genes, anti-apoptosis genes point mutation MC, translocation, amplification ( copies), overexpression ( activity) Burkitts t(8;14); CML t(9;22); follicular lymphoma t( 14;18); APL leukemia t( 15;17) TP53 suppressor gene, RAS protooncogene inactivates suppressor genes (e.g., TP53), activates proto-oncogenes (e.g., RAS) activates ERB-B2 enhances activity of BCL-2 function-growth factor synthesis; mutation-overexpression function growth factor receptor; activation bad prognostic sign for breast carcinoma function-GTP signal transduction; point mutation; 30% of all human cancer function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML function nuclear transcription; translocation (8; 14) causing Burkitts lymphoma majority are point mutations; loss of suppression two hit theory; two separate point mutations of RB suppressor gene on one hit theory; one already inactivated in germ cells

Translocations Key cancer genes Point mutation Amplification Overexpression S/S POC ERB-B2 POC

RAS POC

ABL POC

MYC POC Inactivation suppressor genes Sporadic retinoblastoma AD retinoblastoma

TP53 suppressor gene functions Inactivation TP 53 suppressor gene RB suppressor gene function Inactivation RB suppressor gene APC suppressor gene function Inactivation APC suppressor gene BRCA1/2 suppressor genes function BRCA 1/2 suppressor genes BCL-2 function

G,-S phase inhibition, DNA repair, activation BAX apoptosis gene inactivation causes majority of human cancers G1-S phase inhibition retinoblastoma, osteogenic sarcoma prevents nuclear transcription by catenin familial polyposis (FAP) DNA repair Inactivation breast, ovarian cancers anti apoptosis gene (keeps cytochrome c in mitochondria) t(14;18) translocation of heavy chain causes overexpression; follicular B cell lymphoma [think t(14;18) = t(l4;lB) for foLLicular B] AR; defect in DNA repair enzymes; risk for UVB light cancers AD; inactivation DNA mismatch genes; colorectal cancer AR; susceptibility to DNA damage; leukemias, lymphomas Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar) key chemical carcinogen (cigarette smoke) produced from Aspergillus; hepatocellular carcinoma

BCL-2 gene

Xeroderma pigmentosum Hereditary non-polyposis syndrome (HNPCC) Chromosome instability syndromes Examples chromosome instability

Carcinogens Polycyclic hydrocarbons Aflatoxins

Asbestos Thorium dioxide Aniline dyes Vinyl chloride Benzene Cyclophosphamide EBV HBV and HCV HPV HHV-8 UVB cancers Key host defense Cachexia Most common anemia Most common coagulopathy Most common COD in cancer Acanthosis nigricans, seborrheic keratoses; possible markers for gastric adenocarcinoma Clubbing

lung cancer, mesothelioma hepatocellular carcinoma, cholangiocarcinoma transitional cell carcinoma angiosarcoma of liver leukemia transitional cell carcinoma of bladder Burkitts; CNS lymphoma (AIDS); Hodgkins mixed cellularity; nasopharyngeal carcinoma hepatocellular carcinoma cervical, penis, and anorectal squamous cancers Kaposi sarcoma basal cell carcinoma, squamous cell carcinoma, malignant melanoma cytotoxic CD8 T cells (type IV hypersensitivity) due to tumor necrosis factor- anemia chronic disease hypercoagulability gram negative infection

possible marker for lung cancer

Non-bacterial thrombotic endocarditis possible marker for pancreatic cancer mitral valve TNM staging AFP metastasis more important than nodal involvement hepatocellular carcinoma, yolk sac tumors

PSA CEA BJ (Bence-Jones) protein -human chorionic gonadotropin Calcitonin Small cell carcinoma lung Renal cell carcinoma Hepatocellular carcinoma Medullary carcinoma of thyroid Squamous cell carcinoma of lung Erythropoietin Reticulocyte count Extramedullary hematopoiesis Newborn physiologic anemia Pregnancy Anemia MCV MCHC MCHC Thalassemias

prostate cancer recurrence colorectal cancer multiple myeloma choriocarcinoma medullary carcinoma thyroid; hypocalcemia ADH (hyponatremia), ACTH (ectopic Cushings) EPO (polycythemia), PTH-related peptide (hypercalcemia) EPO (polycythemia), insulin-like factor (hypoglycemia) calcitonin (hypocalcemia), ACTH (ectopic Cushings) PTH-related peptide (hypercalcemia) synthesized in peritubular capillaries measure of effective erythropoiesis; correct for degree of anemia hematopoiesis outside bone marrow (e.g., spleen) drop in Hb due to replacement of HbF RBCs with HbA Hb and Hct decreased; greater increase in plasma volume than RBC mass normal O2 saturation and arterial PO2 average volume of RBCs; useful for anemia classification average Hb concentration in RBCs in microcytic anemias; in spherocytosis MCV, RBC count

RDW Mature RBC Total iron binding capacity % Saturation Serum ferritin

RBC size variation; iron deficiency; normal in other microcytic anemias anaerobic glycolysis; no mitochondria or HLA antigens iron deficiency; anemia chronic disease, sideroblastic anemia iron deficiency, anemia chronic disease; sideroblastic anemia iron deficiency; anemia chronic disease, sideroblastic anemia; normal thalassemia iron deficiency MC, anemic chronic disease, thalassemia, sideroblastic anemia MCC Meckels diverticulum MCC menorrhagia MCC peptic ulcer disease MCC colon cancer ferritin; Fe and % saturation, TIBC; normocytic then microcytic anemia MC anemia in malignancy and alcoholics AR; two -globin gene deletions; normal Hb electrophoresis three -globin gene deletions; hemolytic anemia; four -globin chains four -globin gene deletions; four globin chains AR; DNA splicing defect; HbA2 and F; HbA nonsense mutation with stop codon; hemolytic anemia; HbF, HbA2

Microcytic anemias Iron deficiency child Iron deficiency woman < 50 Iron deficiency man < 50 Iron deficiency men/woman > 50 Stages iron deficiency Anemia chronic disease -Thalassemia trait HbH disease Hb Barts disease -Thalassemia minor -Thalassemia major

Sideroblastic anemia Causes sideroblastic anemia Pb poisoning

defect in mitochondrial heme synthesis producing ringed sideroblasts alcohol, pyridoxine deficiency (isoniazid Rx of TB), Pb poisoning inhibition ferrochelatase, daminolevulinic acid dehydrase, ribonuclease growth retardation; Pb in epiphyses (lead lines); abdominal colic; encephalopathy peripheral neuropathy; proximal renal tubule damage (Fanconis syndrome) coarse basophilic stippling RBCs; MCV; blood Pb; d-aminolevulinic acid animal products; requires intrinsic factor for reabsorption in terminal ileum transfers methyl group to homocysteine binds with B12 in mouth, removed by pancreatic enzymes in small intestine involved in propionate metabolism; end-product succinyl CoA vegan, pernicious anemia MC, fish tapeworm, pancreatitis, bacterial overgrowth, Crohns disease autoimmune destruction parietal cells; chronic gastritis body/fundus; achlorhydria; gastrin alcohol MCC, poor diet, drugs, malabsorption, pregnancy, goat milk alcohol, OC, phenytoin, methotrexate, trimethoprim, 5-fluorouracil

S/S Pb poisoning children S/S Pb poisoning adult Lab Pb poisoning

Vitamin B12 Vitamin B12 R factor Vitamin B12 Causes B12 deficiency

Pernicious anemia Causes folate deficiency Drugs and folate deficiency

Intestinal conjugase in folate metabolism

inhibited by phenytoin

Jejunal uptake of monoglutamate form inhibited by alcohol and OC of folate Dihydrofolate reductase Thymidylate synthetase Folate deficiency Lab in B12/folate deficiency Lab findings unique to B12 deficiency B12 reabsorbed absorbed after administration of intrinsic factor B12 reabsorbed absorbed after administration of antibiotics B12 reabsorbed absorbed after administration of pancreatic extract Acute blood loss Aplastic anemia Lab findings aplastic anemia Anemia in renal disease Extravascular hemolysis Intravascular hemolysis Congenital spherocytosis Blood findings in spherocytosis inhibited by methotrexate, trimethoprim inhibited by 5-fluorouracil MCC of increased serum homocysteine pancytopenia; hypersegmented neutrophils; homocysteine gastrin (pernicious anemia), methylmalonic acid PA bacterial overgrowth chronic pancreatitis initially normal Hb and Hct; 0.9% saline uncovers RBC deficit drugs (e.g., phenylbutazone); infection (e.g., parvovirus); benzene pancytopenia; hypocellular bone marrow normocytic; decreased EPO macrophage phagocytosis of RBCs; unconjugated bilirubin and urine UBG serum haptoglobin; hemoglobinuria; hemosiderinuria AD; defect in spectrin; extravascular hemolysis; splenomegaly normocytic anemia; dense RBCs,

MCHC, osmotic fragility PNH missing decay accelerating factor; complement destruction RBCs, neutrophils, platelets pancytopenia; hemoglobinuria; positive sugar water test and acidified serum test AR; missense mutation (valine for glutamic acid 6th positive -globin chain) deoxyhemoglobin (hypoxemia, acidosis); HbS > 60% inhibits sickling; hydroxyurea HbF vasoocclusive crises, hemolytic anemia (extravascular) dactylitis (6-9 months); Streptococcus pneumoniae sepsis (dysfunctional spleen) Salmonella paratyphi aplastic crisis (parvovirus B-19), acute chest syndrome, autosplenectomy, calcium bilirubinate gallstones, priapism, aseptic necrosis microhematuria from sickling in renal medulla; renal papillary necrosis HbAS-HbA 55-60%, HbS 40-45%; HbSS-HbS 90-95%, HbF 5-10% sickle cells; target cells; Howell-Jolly bodies (nuclear remnants) XR; oxidant damage (peroxide) to Hb (e.g., primaquine; dapsone; fava beans) Heinz bodies (denatured Hb; special stain); bite cells

S/S PNH

HbSS Causes of sickling HbF Pathophysiology HbSS HbSS children HbSS osteomyelitis HbSS complications

HbAS Hb electrophoresis Blood findings in HbSS G6PD deficiency Blood findings G6PD deficiency

Pyruvate kinase deficiency Warm type AIHA Cold type AIHA Penicillin

ATP; RBCs dehydrated; 2,3-BPG (right-shifted OBC) IgG; extravascular hemolysis; e.g., SLE, drugs IgM intravascular hemolysis; e.g., CLL, Mycoplasma IgG antibody against penicillin attached to RBC (type II hypersensitivity) drug alters Rh antigens; IgG antibody against Rh antigens (type II hypersensitivity) drug-IgM IC; intravascular hemolysis; type III hypersensitivity positive direct Coombs; spherocytes mechanical damage causing intravascular hemolysis aortic stenosis (MCC), DIC, TIP, HUS

Methyldopa Quinidine Lab findings AIHA Micro-macroangiopathic hemolysis Causes of micro/macro hemolysis

Peripheral blood findings micro/macro schistocytes; iron deficiency from hemolysis hemoglobinuria Malaria Leukemoid reaction Leukoerythroblastic reaction intravascular hemolysis correlates with fever; falciparum-ring forms and gametocytes exaggerated WBC response to infection; usually due to infection marrow infiltrative disease peripheralizes myeloblasts/nucleated RBCs type I hypersensitivity (e.g., penicillin reaction); invasive helminthic infection mononucleosis; CMV; toxoplasmosis; viral hepatitis; phenytoin

Causes of leukoerythroblastic reaction bone metastasis MCC, myelofibrosis Eosinophilia

Helminthes not producing eosinophilia pinworms, adult worms in ascariasis Atypical lymphocytes

Mononucleosis Clinical findings mono

due to EBV; EBV attaches to CD21 receptors on B cells exudative tonsillitis, generalized lymphadenopathy, hepatosplenomegaly atypical lymphocytosis; IgM heterophile antibodies against horse RBCs T cell deficiencies (HIV); combined B/T deficiency (adenine deaminase deficiency) viral infections, whooping cough lymphopenia, eosinopenia, neutrophilia neoplastic stem cell disorder; splenomegaly; marrow fibrosis; risk for leukemia polycythemia vera, myelofibrosis and myeloid metaplasia plasma volume; RBC count; normal RBC mass RBC count and RBC mass hypoxic stimulus for EPO to generate RBCs lung disease, cyanotic heart disease, high altitude normal plasma volume; RBC mass; SaO2; EPO no hypoxic stimulus for EPO ectopic secretion EPO, polycythemia vera plasma volume and RBC mass; normal SaO2; EPO normal plasma volume; RBC mass;

Lab findings mono

Lymphopenia Lymphocytosis Corticosteroids Chronic MPD Examples of MPD Relative polycythemia Absolute polycythemia Appropriate polycythemia Causes of appropriate absolute polycythemia Appropriate absolute polycythemia Inappropriate absolute polycythemia Causes of inappropriate polycythemia Polycythemia vera Ectopic EPO (renal cell carcinoma)

normal SaO2; EPO Myelofibrosis myeloid metaplasia Lab findings in myelofibrosis Essential thrombocythemia Myelodysplastic syndrome Benzene Leukemia by age Acute vs. chronic leukemia AML Acute promyelocytic leukemia Acute monocytic leukemia CML marrow fibrosis; extramedullary hematopoiesis; splenomegaly tear drop RBCs; dry bone marrow aspirate (marrow fibrosis) MPO with increase in abnormal appearing platelets severe anemia in elderly; 30% develop leukemia; ringed sideroblasts aplastic anemia; acute leukemia ALL, newborn-14; AML, 15-60; CML, 40-60; CLL, >60 acute, blasts >30% in bone marrow; chronic, blasts <10% in bone marrow Auer rods in myeloblasts t(15;17); defect in retinoic acid; Rx retinoic acid ( maturation); DIC gum infiltration t(9;22) of ABL POC; Philadelphia chromosome 22; alkaline phosphatase score early pre-B (80%); CALLA (CD10) and TdT positive; CNS and testicle involvement t(12;21) offers good prognosis B cell neoplasm; -globulins; MCC generalized lymphadenopathy patients> 60-yrs-old HTLV-1; CD4 T cells; skin infiltration; lytic bone lesions with hypercalcemia positive TRAP stain; splenomegaly; Rx with purine nucleosides germinal follicles, B cells; paracortex,

ALL ALL CLL Adult T cell leukemia Hairy cell leukemia Nodal sites

T cells; sinuses, histiocytes Testicular cancer Stomach cancer Phenytoin Cat scratch disease Follicular B-cell lymphoma Burkitt lymphoma Extra nodal lymphomas Mycosis fungoides Sezary syndrome Polyclonal gammopathy Monoclonal gammopathy Confirmatory tests Bence Jones protein Multiple myeloma MGUS Findings in MGUS Waldenstroms macroglobulinemia metastasizes to para-aortic nodes metastasizes to left supraclavicular nodes (Virchow node) atypical lymphocytosis Bartonella henselae; granulomatous microabscesses t(14;18); overexpression of BCL-2 anti-apoptosis gene t(8;14); EBV association; common childhood NHL; starry sky appearance risk factors H. pylori (stomach); Sjogrens syndrome CD4 T cell neoplasm; skin lesions with Pautriers microabscesses leukemic phase of mycosis fungoides sign of chronic inflammation M component (spike); sign of plasma cell disorder serum and urine immunoelectrophoresis; bone marrow aspirate light chains in urine; predictive of a malignant plasma cell disorder M spike; lytic bone lesions; pathologic fractures; hypercalcemia; renal failure MC monoclonal gammopathy; may progress to myeloma elderly patient; no BJ protein; no malignant plasma cells lymphoplasmacytic lymphoma; IgM M spike; hyperviscosity

Hodgkins lymphoma Lymphocyte predominant Hodgkins Nodular sclerosing Hodgkins Mixed cellularity Hodgkins Hodgkins prognosis Alkylating agents in Rx of Hodgkins Langerhans histiocytes Letterer-Siwe disease Hand-Christian-Christian disease Eosinophilic granuloma Mast cells Urticaria pigmentosum Amyloid Primary amyloidosis Secondary amyloidosis Alzheimers disease Gauchers disease

neoplastic component, Reed Stemberg (RS) cell; CD15 CD30 positive infrequent classic RS cells female dominant; supraclavicular nodes + anterior mediastinal nodes male dominant; numerous RS cells; EBV association stage of disease and type of Hodgkins most important factors risk for second malignancies (leukemia; NHL) CD1 positive; Birbeck granules malignant histiocytosis <2 yrs old; diffuse eczematous rash; organ involvement malignant; lytic skull lesions, diabetes insipidus, exophthalmos benign histiocytosis; lytic bone lesions with pathologic fractures release histamine (pruritus; swelling); metachromatic granules positive with toluidine blue localized mastocytosis; skin lesions swell and itch with scratching twisted -sheet; apple green birefringence with Congo red AL amyloid derived from light chains; plasma cell disorders AA amyloid derived from serumassociated amyloid; chronic infections amyloid precursor protein gene product chromosome 21; amyloid- macrophages have fibrillary

appearance; deficiency glucocerebrosidase Niemann Picks disease Hypersplenism Splenic dysfunction Anticoagulants Heparin Protein C/S Procoagulants Protein C and S von Willebrand factor Platelets GpIb GpIIb:IIIa Extrinsic system factor Intrinsic system factors Final common pathway factors Factor XIII Vitamin K-dependent factors macrophages have soap bubble appearance; deficiency sphingomyelinase splenomegaly; peripheral blood cytopenias; portal hypertension MCC Howell Jolly bodies; susceptible to Streptococcus pneumoniae sepsis tissue plasminogen activator, heparin, PGI2 ATIII, protein C/S enhances ATIII activity (neutralizes all factors except V, VIII, fibrinogen) neutralize V and VIII coagulation factors, thromboxane A2 (platelet aggregation, vasoconstrictor) inactivate factors V and VIII; enhance fibrinolysis complexes with factor VIII to enhance VIII:C activity; platelet adhesion receptors for von Willebrand factor and fibrinogen; synthesize thromboxane A2 platelet receptor for von Willebrand factor platelet receptor for fibrinogen VII XII, XI, IX, VIII X, V, prothrombin (II), fibrinogen (I) cross-links insoluble fibrin; strengthens fibrin clots prothrombin, VII, IX, X, protein C and S

Factors consumed in a clot Plasmin Bleeding time Aspirin Tests for vWF PT PTT Fibrinolysis tests S/S platelet dysfunction Idiopathic thrombocytopenic purpura (ITP) Chronic autoimmune thrombocytopenic purpura Heparin PF4 HIV TTP

fibrinogen, prothrombin, V, VIII; fluid is called serum cleaves fibrinogen and insoluble fibrin into degradation products evaluates platelet function (adhesion, release reaction, aggregation) MCC of a prolonged bleeding time ristocetin cofactor assay; vWF antigen assay; agar electrophoresis evaluates extrinsic pathway to fibrin clot evaluates intrinsic pathway to stable fibrin clot fibrin(ogen) degradation products; Ddimers (cross-linked insoluble fibrin) cannot form temporary plug; epistaxis; petechiae; bleeding from scratches children; antibodies against GpIIb:IIIa; no splenomegaly SLE; antibodies against GpIIb:IIIa receptors thrombocytopenia due to IgG antibody against heparin attached to PF4 on platelets heparin neutralizing factor thrombocytopenia MC hematologic abnormality; similar to ITP platelet thrombi develop in areas of endothelial damage in small vessels; consumption of platelets fever, thrombocytopenia, renal failure, hemolytic anemia with schistocytes, CNS deficits thrombocytopenia, prolonged bleeding

S/S Lab findings TTP

time, normal PT and PTT HUS similar to TTP; endothelial injury from Shiga-like toxin of 0157:H7 E. coli in undercooked beef no stable fibrin clot-late rebleeding; menorrhagia; GI bleeding; hemarthroses XR; hemarthroses; prolonged PTT, factor VIII activity, normal VIII antigen AD; platelet adhesion defect + factor VIII deficiency vWF, VIII antigen, and VIII:C; prolonged bleeding time Rx of choice for mild von Willebrands disease and hemophilia A antibodies destroy coagulation factors prolonged PT and/or PTT corrected with mixing studies epoxide reductase activity ( function vitamin K); hemorrhagic diathesis; PT antibiotics MC, newborn, malabsorption, warfarin activation coagulation system from release of tissue thromboplastin and/or endothelial cell damage consumption coagulation factors by fibrin clots; patient also anticoagulated septic shock MCC, rattlesnake bite, massive trauma, amniotic fluid bleeding from all scratches, holes, needle sites thrombocytopenia, PT and PTT, Ddimers (best test), anemia

S/S factor deficiency Hemophilia A von Willebrands disease Lab findings in VWD Desmopressin acetate Circulating anticoagulants Lab finding in circulating anticoagulant Vitamin K deficiency Causes vitamin K deficiency DIC DIC Causes S/S Lab findings DIC

Antiphospholipid antibodies Warfarin Warfarin Warfarin Rx warfarin over anticoagulation Heparin OC Factor V Leiden ATIII deficiency Hemorrhagic skin necrosis M cells

lupus anticoagulant and anticardiolipin antibodies; vessel thrombosis inhibits epoxide reductase; PT best test but PTT also prolonged full anticoagulation in 3 days when carboxylated prothrombin disappears ingredient in rat poison; danger to children in households with grandparents on warfarin intramuscular vitamin K (6-8 hrs), fresh frozen plasma (immediate) enhances ATIII; PTT best test but PT also prolonged estrogen coagulation factor synthesis and ATIII; predisposes to thrombosis MC hereditary thrombosis; resistant to degradation by protein C/S no prolongation of PTT with administration of heparin post-warfarin therapy in patient with heterozygote protein C deficiency specialized cells that transfer foreign antigens to lymphocytes in Peyers patches some patients have anti-AB-IgG antibodies; increased incidence duodenal ulcers increased incidence of gastric carcinoma do not have natural blood group antibodies at birth (e.g., anti-A-lgM) may lose natural blood group antibodies; no hemolytic reaction to mismatched blood

Blood group O Blood group A Newborns Elderly

Rh antigens Atypical antibodies Duffy antigen Antibody screen Cytomegalovirus Hepatitis C Major crossmatch Universal donor Universal recipient Packed RBC transfusion Cryoprecipitate Fresh frozen plasma Allergic transfusion reaction Febrile transfusion reaction Intravascular HTR Extravascular HTR Positive direct Coombs test

inherited in autosomal codominant fashion; Rh antigens include D, C, c, E, e antibodies against Rh or non-Rh blood group antigens (e.g., anti-D) receptor for Plasmodium vivax; blacks often lack Duffy antigen indirect Coombs test; detects atypical antibodies in serum MC infection transmitted by blood transfusion; MC antibody MCC of post-transfusion hepatitis patient serum reacted against donor RBCs; does not guarantee RBC survival blood group O; no antigens on the surface of RBCs blood group AB; no natural blood group antibodies in serum raises Hb by 1 gm/dL and Hct by 3% fibrinogen and factor VIII replacement for multiple factor deficiencies (e.g., cirrhosis, DIC) type I IgE-mediated hypersensitivity reaction recipient anti-HLA antibodies react against donor leukocytes transfusion of ABO incompatible blood (e.g., A person receives B blood) antibody attaches to donor RBCs; macrophage phagocytosis and hemolysis present in both types of hemolytic transfusion reactions

S/S ABO HDN

jaundice, no increase in Hb, hemoglobinuria mother O and baby A or B; transplacental passage of maternal anti-AB-IgG positive direct Coombs test; spherocytes; MCC unconjugated hyperbilirubinemia first 24 hrs mother Rh (D antigen) negative and fetus Rh (O antigen) positive no hemolysis in first Rh incompatible pregnancy maternal anti-D crosses placenta; potential for hydrops fetalis; high risk for kernicterus anti-D; coats D antigen site on fetal RBCs in maternal circulation positive direct Coombs; severe anemia and hyperbilirubinemia protects mother from Rh sensitization (development of anti-D antibodies) A+ cells destroyed by mothers anti AlgM converts unconjugated bilirubin in skin into harmless water soluble dipyrrole apex left parasternal border right 2nd intercostal space left 2nd intercostal space closure MV and TV closure AV and PV split in A2 and P2; due to increased blood in right side of heart

ABO HDN Rh HDN Rh HDN Rh HDN Rh immune globulin Rh HDN lab ABO HDN O Rh negative mother with A Rh positive baby Blue fluorescent light MV auscultation TV auscultation AV auscultation PV auscultation S1 S2 Inspiration

S3 Causes S3 S4 Causes S4 Murmurs Inspiration Expiration Stenosis murmurs Regurgitation murmurs Valves opening in systole Valves opening in diastole Valves closing in systole Valves closing in diastole LDL VLDL Familial hypercholesterolemia (type II) Type III hyperlipoproteinemia Type IV hyperlipoproteinemia Apo B deficiency

abnormal; due to blood entering volume overloaded ventricle in early diastole valve regurgitation; congestive heart failure abnormal; due to blood entering noncompliant ventricle with atrial contraction in late diastole volume overloaded ventricle, hypertrophy stretching valve ring or damage to valve increases right sided abnormal heart sounds and murmurs increases left sided abnormal heart sounds and murmurs problem in opening valve problem in closing valve AV and PV MV and TV MV and TV AV and PV primary vehicle for carrying cholesterol primary vehicle for carrying liversynthesized triglyceride AD; deficiency of LDL receptors; LDL deficiency apo E; remnants (chylomicron, intermediate density) VLDL; alcoholics deficiency apo B48 (chylomicrons) and B100 (VLDL); CH and TG

Clinical findings in apo B deficiency Atherosclerosis Risk factors Cells involved Fibrous plaque C-reactive protein Inflammatory atheromatous plaque Increased plasma homocysteine Hyaline arteriolosclerosis

malabsorption; hemolytic anemia reaction to injury of endothelial cells smoking, LDL, homocysteine, Chlamydia pneumoniae infection platelets, macrophages, smooth muscle cells, T cells with cytokine release pathognomonic lesion of atherosclerosis marker of an inflammatory atheromatous plaque predisposes to platelet thrombosis vessel thrombosis; folate (MC)/vitamin B12 deficiency small vessel disease of DM and hypertension; excess protein in vessel wall

Mechanisms hyaline arteriolosclerosis non-enzymatic glycosylation in DM Non-enzymatic glycosylation glucose attaches to amino acids in BM; causes permeability to protein

Mechanisms hyaline arteriolosclerosis pressure pushes proteins into vessel in hypertension wall Abdominal aortic aneurysm rupture Syphilitic aneurysm Aortic dissection Cystic medial degeneration Intimal tear in aorta due to atherosclerosis; flank pain, hypotension, pulsatile mass vasculitis of vasa vasorum of aortic arch; aortic regurgitation due to hypertension and collagen tissue disorders (e.g., Marfan) elastic tissue degeneration creates spaces filled with mucopolysaccharides due to wall stress from hypertension and structural weakness

Types of dissection S/S proximal aortic dissection Marfans

proximal (MC); distal or combination of both chest pain radiating to back, lack of pulse; cardiac tamponade MC COD AD; fibrillin defect; aortic regurgitation/dissection; lens dislocation; MVP with sudden death stasis of blood flow; deep veins below knee MC site emboli originate from femoral veins absent radial pulse with positional change lymphedema hands/feet in newborn; preductal coarctation arteriovenous fistula; due to hyperestrinism (cirrhosis, pregnancy) regress with age; do not surgically remove HHV-8; vascular malignancy; MC cancer in AIDS Bartonella henselae; vascular infection in AIDS palpable purpura; e.g., Henoch Schonlein purpura vessel thrombosis with infarction; e.g., classical polyarteritis nodosa absent pulse, stroke pulseless disease; young Asian woman temporal artery granulomatous vasculitis; ipsilateral blindness

MC COD Marfans and Ehlers Danlos aortic dissection Phlebothrombosis Pulmonary thromboembolism

Superficial migratory thrombophlebitis sign of carcinoma of head of pancreas Thoracic outlet syndrome Turners syndrome Spider telangiectasia Capillary hemangioma in newborn Kaposis sarcoma Bacillary angiomatosis Small vessel vasculitis Muscular artery vasculitis Elastic artery vasculitis Takayasus arteritis Giant cell arteritis

(ophthalmic artery) Classical polyarteritis nodosa Path findings S/S Diagnosis Kawasakis disease muscular artery vasculitis with vessel thrombosis infarction vessel inflammation at different stages; aneurysms from vessel weakness infarctions in kidneys, skin, GI tract, heart; HBsAg in 30% angiography identifies aneurysms and thrombosis coronary artery vasculitis/thrombosis/aneurysms in children chest pain; desquamating rash; swelling hands/feet; cervical lymphadenopathy IV -globulin smokers digital vasculitis; digital infarction digital vasculitis in PSS and CREST syndrome digital pain; white-blue-red color changes protein gels in cold temperature; Raynauds syndrome; HCV association acral cyanosis relieved by coming indoors association with c-ANCA; sinusitis, lung infarction, crescentic GN palpable purpura; crescentic GN; association with p-ANCA IgA-anti-IgA ICs; palpable purpura buttocks/legs; arthritis; IgA GN

S/S Rx Buergers disease (thromboangiitis obliterans) Raynauds syndrome S/S Cryoglobulinemia S/S Wegeners granulomatosis Microscopic polyangiitis Henoch-Schnlein purpura

Serum sickness vasculitis Rocky Mountain spotted fever Rickettsia infection; vasculitis causes petechia on palms trunk Meningococcemia Essential HTN blacks Renovascular HTN S/S Endocrine HTN Hypertension Afterload Preload Concentric LVH LVH with dilation/hypertrophy LHF Systolic dysfunction Diastolic dysfunction RHF

e.g., horse antivenin in Rx of rattlesnake envenomation tick borne

sepsis causes petechia/ecchymoses; potential for Waterhouse Friderichsen syndrome defect in renal excretion of sodium; plasma volume, PRA atherosclerosis renal artery in men; fibromuscular hyperplasia renal artery women epigastric bruit; PRA affected kidney, PRA unaffected kidney 1 HPTH, Graves/hypothyroidism, Cushings, 1 aldosteronism, phaeochromocytoma LVH MC complication; AMI MC COD followed by stroke and renal failure resistance ventricles contract against volume ventricles must eject increased afterload; e.g., essential HTN, aortic stenosis increased preload; e.g., valve regurgitation; left to right shunts forward failure; pulmonary edema, pillow orthopnea, paroxysmal nocturnal dyspnea LHF due to decreased ventricular contractility (ischemia) LHF due to decreased ventricular compliance (hypertrophy) backward failure; venous hydrostatic

pressure; neck vein distention, hepatomegaly, edema ACE inhibitors Diuretics in CHF Non-pharmacologic Rx in CHF AMI decrease afterload and preload in heart failure reduce preload restrict salt and water MC COD in United States; left anterior descending coronary artery thrombosis MCC coronary artery atherosclerosis; subendocardial ischemia; ST depression coronary artery vasospasm; transmural ischemia; ST elevation death within 1 hr of symptoms severe coronary artery atherosclerosis; absence of occlusive thrombosis anterior portion left ventricle, anterior 2/3rds IVS posterior portion left ventricle and papillary muscle, inferior 1/3rd IVS, right ventricle rupture of inflammatory plaque produces platelet thrombus MC COD in AMI no gross changes until 24 hrs retrosternal pain radiating down arms, diaphoresis 3rd-7th day MC type; LAD thrombosis; cardiac tamponade RCA thrombosis; mitral regurgitation

Exertional angina Prinzmetals angina Sudden cardiac death Path findings LAD coronary artery RCA AMI Ventricular fibrillation AMI S/S AMI AMI ruptures Anterior wall rupture Posteromedial papillary muscle

rupture IVS rupture Mural thrombus Pericarditis S/S Ventricular aneurysms Right ventricular infarction Diagnosis of AMI LDH isoenzymes Reinfarction ECG findings in AMI Ejection fraction By-pass surgery Angioplasty complication Umbilical vein Ductus arteriosis in fetus Ductus arteriosus in newborn Eisenmengers syndrome VSD

with LHF LAD thrombosis; left to right shunt; RHF anterior AMI; danger embolization first week in transmural AMI; 6 wks later autoimmune friction rub; leaning forward relieves pain late manifestation of AMI; precordial systolic bulge; CHF MC COD RCA thrombosis; hypotension, RHF, preserved left ventricular function CK-MB and troponins; CK-MB absent by 3 days; troponins last 7-10 days no longer used; LDH 1/2 flip indicates AMI reappearance CK-MB after 3 days inverted T waves; ST elevation; Q waves EF = stroke volume/left ventricular end-diastolic volume; 80/120 = 0.66 use internal mammary artery and saphenous veins (arterialize after 10 yrs) localized dissection with thrombosis highest O2 saturation shunts blood from pulmonary artery to aorta; PGE keeps it open closes and becomes ligamentum arteriosum cyanosis due to reversal of left to right shunt MC congenital heart disease; SaO2

right ventricle (RV), pulmonary artery (PA) ASD Down syndrome PDA Tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot Complete transposition Complications cyanotic heart disease Pre-ductal coarctation Post-ductal coarctation S/S Acute rheumatic fever Acute rheumatic fever patent foramen ovale; SaO2 right atrium (RA), RV, PA; MC adult congenital heart disease endocardial cushion defect (combined ASD and VSD) machinery murmur; close with indomethacin; SaO2 PA degree of pulmonic stenosis determines if cyanosis is present left ventricle, aorta ASD and PDA are cardioprotective cyanosis; aorta empties RV; PA empties left ventricle 2 polycythemia; infective endocarditis; metastatic abscesses Turners syndrome constriction distal to ligamentum arteriosum upper extremity HTN; claudication; ribnotching; activation RAA also causes HTN type II hypersensitivity; group A streptococcus pharyngeal infection sterile vegetations mitral valve (regurgitation); myocarditis with Aschoff nodule polyarthritis (MC), carditis, erythema marginatum, rheumatoid nodules, chorea chronic rheumatic fever; opening snap followed by mid-diastolic rumble left atrial dilation hypertrophy - atrial

S/S Mitral stenosis Mitral stenosis

fibrillation, thrombus, pulmonary edema, RHF MVP myxomatous degeneration of mitral valve; common in Marfan syndrome, Ehlers Danlos mid-systolic click followed by a murmur; palpitations, chest pain, rupture of chordae decrease preload (stand, Valsalva, anxiety) increase preload (supine, squat, clench fist) pansystolic murmur; S3 and S4 common LHF, infective endocarditis, acute rheumatic fever systolic ejection murmur; syncope and angina with exercise; hemolytic anemia worsens obstruction and increases murmur intensity decreases obstruction and decreases murmur intensity bicuspid aortic valve; age-related sclerosis bounding pulses; early diastolic blowing murmur diastolic murmur; regurgitant flow on anterior leaflet mitral valve sign for AV replacement essential HTN, infective endocarditis, acute rheumatic fever, dissection pansystolic murmur intensity with inspiration

S/S MVP click/murmur close to S1 MVP click/murmur close to S2 Mitral regurgitation Causes Aortic stenosis Aortic stenosis murmur increased preload Aortic stenosis murmur decreased preload Causes Aortic regurgitation Austin Flint murmur Significance Austin Flint murmur Causes aortic regurgitation Tricuspid regurgitation

Causes Carcinoid heart disease Infective endocarditis (IE) IE prosthetic heart valve IE ulcerative bowel disease S/S Lab findings Coxsackievirus Parasitic cause myocarditis Pericardial effusion S/S Dx and Rx Pulsus paradoxus Constrictive pericarditis Congestive cardiomyopathy Causes Hypertrophic cardiomyopathy

endocarditis IV drug abuse; RHF; carcinoid heart disease tricuspid regurgitation, pulmonic stenosis Streptococcus viridans MCC; Staphylococcus aureus MCC IVDA Staphylococcus epidermidis (coagulase negative) Streptococcus bovis IC vasculitis-Roth spot, splinter hemorrhages; regurgitant murmurs; metas1atic abscesses positive blood culture Libman Sacks endocarditis MCC of myocarditis (lymphocyte infiltrate in myocardium) and pericarditis leishmania in Chagas disease all chamber pressures are uniformally increased muffled heart sounds, pulsus paradoxus, inspiratory neck vein distention echocardiogram, pericardiocentesis, respectively drop in blood pressure >10 mmHg with inspiration TB MCC worldwide; pericardial knock generalized chamber enlargement; low ejection fraction postpartum, cardiotoxic drugs, hypothyroidism, alcohol MCC of sudden death in young person (due to conduction defects)

Site of obstruction Effect decreased preload on systolic murmur Effect increased preload on systolic murmur Restrictive cardiomyopathy Causes Cardiac myxoma Cardiac rhabdomyoma U wave Peaked T wave ST depression ST elevation Atrial fibrillation Ventricular premature beats Ventricular fibrillation Anterior AMI Inferior AMI Wolff-Parkinson-White Alveolar O2 calculation Increased A-a gradient

anterior leaflet mitral valve drawn against asymmetric thickened IVS worsens obstruction and increases murmur intensity reduces obstruction and decreases murmur intensity decreased compliance iron, amyloid, glycogen; sarcoidosis; tropical endocardial fibrosis benign tumor left atrium; embolization; syncope childhood tumor; association with tuberous sclerosis hypokalemia; MCC diuretic therapy (e.g., thiazides; loop diuretics) hyperkalemia; MCC renal failure subendocardial ischemia (e.g., classical angina pectoris) transmural ischemia (e.g., AMI), pericarditis, ventricular aneurysm MC chronic arrhythmia; absent P waves; danger for embolization wide QRS complexes; MC arrhythmia in coronary care unit MCC of death in an AMI Q waves in I and V1-V4 Q waves in II, III, and aVF; right coronary artery thrombosis. short PR interval with normal P wave; delta wave on upstroke of R wave % O2 breathing (713) - PCO2/0.8 primary lung disease; left to right shunts in heart

Forced vital capacity Forced expiratory volume/1 second (FEV1) Choanal atresia Nasal polyps Nasal polyp in a child Triad asthma Obstructive sleep apnea (OSA) S/S

total amount of air expelled after a maximal inspiration amount of air expelled in I second after maximal inspiration cyanotic when breast feeding; turns pink when crying allergic (MC; adults only), aspirin, cystic fibrosis requires sweat test to exclude cystic fibrosis patient on aspirin (pain syndrome) with nasal polyps, asthma snoring with intervals of apnea (respiratory acidosis with hypoxemia) danger cor pulmonale; requires sleep test; Rx. O2 with continuous positive airway pressure maxillary sinusitis MC in adults; ethmoiditis MC in children; S. pneumoniae MC association with EBV; metastasize to cervical nodes smoking MCC; hoarseness; squamous cell carcinoma MCC of fever 24-36 hours after surgery percussion; absent fremitus, breath sounds; inspiratory lag; elevated diaphragm decreased production surfactant; airway collapse; hyaline membranes synthesize surfactant (lecithin, phosphatidylcholine); stored in lamellar bodies

Sinusitis Nasopharyngeal carcinoma Laryngeal carcinoma Resorption atelectasis S/S RDS Type II pneumocytes

Surfactant Causes RDS Maternal diabetes

reduces surface tension in airways; synthesis cortisol, thyroxine; synthesis insulin prematurity, maternal diabetes, Csection maternal hyperglycemia fetal hyperglycemia fetal insulin which surfactant O2 FR injury (blindness, bronchopulmonary dysplasia); necrotizing enterocolitis Streptococcus pneumoniae MCC bronchopneumonia, lobar pneumonia productive cough; consolidation - percussion, tactile fremitus interstitial pneumonia; Mycoplasma pneumoniae MCC low grade fever, non-productive cough, no signs consolidation Pseudomonas, aeruginosa MCC (respirators); others - S. aureus, E. coli MCC common cold; hand to mouth transmission MCC pneumonia and bronchiolitis in child MCC croup in child; trachea area of obstruction basophilic intranuclear inclusion surrounded by halo superimposed pneumonia with S. aureus increases mortality Warthin-Finkeldey multinucleated

Complications RDS Typical community acquired pneumonia Typical pneumonia S/S Atypical community acquired pneumonia S/S Nosocomial pneumonia Rhinovirus Respiratory syncytial virus Parainfluenza virus Cytomegalovirus Influenza Rubeola

giant cells Chlamydia pneumoniae Chlamydia trachomatis Coxiella burnetii Mycoplasma pneumoniae pneumonia Streptococcus pneumoniae pneumonia Staphylococcus aureus pneumonia Corynebacterium diphtheriae Haemophilus influenzae Inspiratory stridor child Pseudomonas aeruginosa Klebsiella pneumoniae Legionella pneumophila Mycobacterium tuberculosis Candida albicans Cryptococcus immitis Aspergillus fumigatus Mucor species atypical pneumonia; association with coronary artery disease pneumonia in newborns; staccato cough; wheezing only rickettsia without a vector crowded condition; cold agglutinins; azithromycin gram positive diplococcus; azithromycin tension pneumatocysts in children with cystic fibrosis toxin produces ADP ribosylation of elongation factor 2 exacerbation chronic bronchitis; acute epiglottis in children croup, epiglottitis MCC of pneumonia and death in cystic fibrosis; green sputum mucoid sputum in alcoholic silver stain; water coolers/mist (grocery produce, restaurants, zoo rain forest) strict aerobe; MC COD due to infectious disease worldwide vessel invader; yeasts and pseudohyphae pigeon excreta; narrow-based bud septate hyphae with fruiting body; fungus ball, extrinsic asthma, vessel invader non-septate; vessel invader; frontal lobe abscess in diabetic ketoacidosis

Coccidioides immitis S/S Histoplasma capsulatum H. capsulatum Blastomyces dermatitidis Pneumocystis carinii Primary TB Primary TB Reactivation TB Mycobacterium avium intracellulare (MAI) CF

Southwest deserts; inhale arthrospores in dust; spherule with endospores erythema nodosum (painful nodules lower legs) Ohio/central Mississippi river valley; excreta bats (spelunker), chickens simulates TB; yeasts phagocytosed by macrophages overlaps histoplasmosis; broad-based buds; skin lesion simulates cancer cysts and trophozoites; pneumonia in HIV; Rx. trimethoprim/sulfamethoxazole upper portion lower lobe, lower portion upper lobe Ghon focus (subpleural caseation); Ghon complex (spread to hilar nodes) cavitating lesion in upper lobe; kidney MC extrapulmonary site atypical TB; MC TB in AIDS AR; 3 nucleotide deletion chromosome 7; defective CFTR (degraded in Golgi apparatus) pneumonia, malabsorption, males sterile; + sweat test; P. aeruginosa pneumonia MC COD MCC aspiration oropharyngeal material (mixed aerobe/anaerobe); xray - air/fluid level posterobasal segment right lower lobe superior segment right lower lobe right middle lobe, posterior segment

S/S

Lung abscess Aspiration sitting Aspiration supine Aspiration right side

right upper lobe Pulmonary thromboembolism Bronchial artery Saddle embolus S/S pulmonary infarction Dx Pain on inspiration most derive from femoral vein branch of aorta/intercostal artery; protects against developing pulmonary infarction sudden death due to acute right heart strain dyspnea and tachypnea; pleuritic chest pain; pleural effusion ventilation/perfusion scan; respiratory alkalosis; hypoxemia pleuritic inflammation; pulmonary embolus, pneumonia, pneumothorax

Pathogenesis pulmonary hypertension hypoxemia and respiratory acidosis (PH) Hypoxemia + respiratory acidosis Causes PH Cor pulmonale S/S Restrictive lung disease Restrictive lung disease (RLD) ARDS ARDS Causes vasoconstriction pulmonary vessels; vasodilation cerebral vessels 1 lung disease (COPD, restrictive), recurrent emboli, mitral stenosis, OSA, left-right shunts PH + RVH dyspnea; accentuated P2 (PH); parasternal heave (RVH) compliance, elasticity; interstitial fibrosis/edema all volumes and capacities; FEV1sec/FVC ratio RLD; non-cardiogenic pulmonary edema due to alveolar injury neutrophil destruction of type I and II pneumocytes; hyaline membranes septic shock (MC), aspiration gastric contents, severe trauma

Pneumoconiosis Caplan syndrome Coal workers Silicosis Sources asbestos Ferruginous bodies Asbestosis Mesothelioma Sarcoidosis S/S Lab findings Kveim test Farmers lung Silo fillers disease Byssinosis Goodpastures syndrome

inhalation mineral dust causing interstitial fibrosis; particles <0.5 m to reach alveoli pneumoconiosis + rheumatoid nodules in lungs black lung disease; progressive massive fibrosis; no increased incidence cancer or TB quartz; nodular opacities; foundry workers; incidence cancer and TB roofing material, old buildings (9/11), pipe-fitter shipyard asbestos fiber coated by iron benign pleural plaques (MC); bronchogenic carcinoma (MC cancer); mesothelioma malignancy of serosa; no smoking association RLD; MC non-infectious lung and liver granulomatous disease dyspnea, hilar adenopathy (noncaseating granulomas), uveitis, nodular skin lesions ACE, hypercalcemia (macrophages synthesize 1--hydroxylase) intradermal injection sarcoid antigens causes skin reaction RLD; lung reaction against thermophilic bacteria in moldy hay RLD; reaction against nitrogen dioxide in fermenting corn RLD; reaction against cotton, linen, hemp products in textile industry RLD; anti-BM antibodies; begins in

lungs and ends in renal failure Collagen vascular RLD Drugs RLD Obstructive lung disease Obstructive lung disease Obstructive lung disease Asthma S/S Charcot-Leyden crystals Lab findings Emphysema Respiratory unit Radiograph emphysema Pathogenesis Centriacinar emphysema Panacinar emphysema SLE, rheumatoid arthritis, systemic sclerosis amiodarone, bleomycin, busulfan, cyclophosphamide, methotrexate, nitrofurantoin compliance, elasticity RV, TLC; TV, VC; FEV1sec and FVC; FEV1sec/FVC ratio asthma, emphysema, chronic bronchitis, bronchiectasis extrinsic (type I hypersensitivity) and intrinsic types expiratory wheezing (inflamed terminal bronchioles); LTC4,-D4,-E4 bronchoconstrictors derive from crystalline material in eosinophil granules initial respiratory alkalosis; respiratory acidosis requires intubation destruction elastic tissue respiratory unit; lung hyperinflation; smoking MCC; pink puffer respiratory bronchiole, alveolar duct, alveoli AP diameter; depressed diaphragms; vertical heart AAT, neutrophil destruction of elastic tissue destruction/distention respiratory bronchioles upper lobe in smokers; THINK destruction/distention entire respiratory unit lower lobes; AAT

deficiency Paraseptal emphysema Lab findings Chronic bronchitis Site of obstruction Lab findings Bronchiectasis Causes Immotile cilia syndrome Central lung cancers Peripheral lung cancers Squamous lung cancer Small cell carcinoma Bronchioloalveolar carcinoma Scar carcinoma Bronchial carcinoid Metastatic lung cancer Pancoast tumor upper lobe destruction/distention alveolar ducts, alveoli; pneumothorax normal to decreased PCO2 (respiratory alkalosis) productive cough 3 months/2 consecutive years; blue bloater (cyanosis) terminal bronchioles (proximal to respiratory unit) respiratory acidosis/hypoxemia obstruction/infection key causes; dilated bronchioles extend to periphery CF MCC, TB, immotile cilia syndrome absent dynein arm in cilia; sinusitis, infertility, bronchiectasis, situs inversus squamous cancer and small cell cancer; men > women adenocarcinoma; women > men cavitate; secrete PTH-related protein neuroendocrine tumor; secrete ACTH and ADH no smoking relationship; lung consolidation resembling pneumonia usually adenocarcinoma developing in old TB scar low grade malignant; hemoptysis; rare cause carcinoid syndrome more common than primary cancer; breast cancer MCC squamous carcinoma posterior

mediastinum; destruction superior cervical ganglion S/S Solitary coin lesion Superior vena caval syndrome Anterior mediastinal masses Posterior mediastinal masses Myasthenia gravis Horners syndrome - lid lag, miosis, anhydrosis; lower brachial plexus injury granuloma MCC primary lung cancer obstructs vessel; venous congestion thymoma; nodular sclerosing Hodgkins; teratomas usually neurogenic tumors of ganglia B cell hyperplasia of thymus MC abnormality; association with thymoma association with hypogammaglobulinemia, autoimmune disease, pure RBC aplasia transudates or exudates; CHF MCC rupture subpleural or intrapleural bleb; air/pleural cavity pressure same pleuritic chest pain, dyspnea, tracheal shift ipsilateral side, absent breath sounds flap-like pleural tear; increased pleural cavity pressure; compression atelectasis as above except tracheal shift to opposite side failure of fusion of facial processes multinucleated giant cell with acidophilic intranuclear inclusions on Tzanck prep EBV glossitis; pre-AIDS defining

Thymoma Pleural effusions Spontaneous pneumothorax S/S

Tension pneumothorax S/S Cleft lip/palate Herpes labialis Hairy leukoplakia

lesion; not precursor to cancer Mumps Diphtheria Congenital syphilis Actinomycosis S/S Exudative tonsillitis Oral thrush Dental caries Peutz-Jeghers syndrome Leukoplakia/erythroleukoplakia Squamous cell carcinoma Smokeless tobacco Gum hyperplasia Pleomorphic adenoma Mucoepidermoid carcinoma Dysphagia for solids only Plummer-Vinson syndrome bilateral parotitis; unilateral orchitis; amylase pseudomembrane pharynx and trachea with cervical lymphadenopathy notched central incisors anaerobic gram + filamentous bacteria; complication extracted dental abscess draining sinuses with sulfur granules majority are viral; 20% group A streptococcus common in newborn; pre-AIDS defining lesion; yeasts and pseudohyphae Streptococcus mutans mucosal pigmentation; hamartomatous polyps biopsy to rule out squamous dysplasia or cancer smoking and alcohol association; lower lip MC site verrucoid squamous cell carcinoma phenytoin, pregnancy, scurvy MC benign tumor of salivary glands; parotid MC site MC malignant tumor major and minor salivary glands lesion obstructing esophagus; e.g., cancer, web iron deficiency anemia causes esophageal web, glossitis,

achlorhydria ( HCl in gastric acid) Dysphagia for solids and liquids TE fistula motor abnormality; e.g., achalasia MCC, PSS or CREST syndrome polyhydramnios; proximal esophagus ends blindly; distal esophagus derives from trachea vertebral abnormalities, anal atresia, TE fistula, renal disease/radius abnormality MC pulsion diverticulum of esophagus; halitosis (stinky breath, food gets stuck); near UES relaxation of lower esophageal sphincter (LES) with acid reflux MCC nocturnal cough and asthma Candida MC, CMV, HSV glandular metaplasia distal esophagus in GERD precursor for adenocarcinoma, stricture dilated left gastric vein; sign of portal hypertension due to cirrhosis tear of distal esophagus from retching in alcoholic or bulimic rupture of distal esophagus from retching; pneumomediastinum pneumomediastinum (air in subcutaneous tissue) contain VIP - relaxes LES failure of LES relaxation (no VIP); absent ganglion cells in the myenteric plexus aperistalsis/dilation of esophagus; regurgitation of undigested food at

VATER syndrome

Zenkers diverticulum GERD GERD AIDS esophagitis Barretts esophagus Complications of Barretts Esophageal varices Mallory Weiss syndrome Boerhaaves syndrome Hammans mediastinal crunch LES ganglion cells Achalasia S/S

night X-ray achalasia Acquired achalasia Distal adenocarcinoma esophagus Squamous cell carcinoma of esophagus Melena Hematemesis Congenital pyloric stenosis Acute hemorrhagic (erosive) gastritis Mucous barrier stomach Type A chronic gastritis Type B chronic gastritis H. pylori birds beak appearance Chagas disease; leishmania destroy ganglion cells MC primary cancer; due to Barretts esophagus smoking MCC; alcohol also causes sign of upper GI bleed; acid changes Hb to hematin; peptic ulcer disease MCC vomiting blood; peptic ulcers MCC hypertrophy pyloric muscle; vomiting non-bile stained fluid in 2-4 weeks NSAIDs MCC maintained by PGE; misoprostol PGE analog due to PA; achlorhydria with serum gastrin due to H. pylori; involves pylorus and antrum curved rod; urease producer; MCC PUD, adenocarcinoma, gastric lymphoma lesser curvature pylorus and antrum; poor defense against acid; food aggravates pain never malignant; acid production; food relieves pain air under diaphragm causes pain in left shoulder giant rugal hyperplasia; protein loss from increased mucus

Gastric ulcer Duodenal ulcer Perforated peptic ulcer Menetriers disease

Zollinger-Ellison syndrome S/S Hypergastrinemia Leiomyoma Intestinal type adenocarcinoma Diffuse type adenocarcinoma Gastric lymphoma Malabsorption Causes bile salt deficiency D-xylose screen Calcification of pancreas Celiac disease Celiac disease Whipples disease S/S Invasive diarrhea Secretory diarrhea

malignant islet cell tumor secreting gastrin; part of MEN I syndrome PUD in usual locations; sometimes multiple ulcers ZE, achlorhydria, gastric distention, H2 or proton blockers; renal failure MC benign tumor of stomach H pylori related; incidence; lesser curvature pylorus/antrum linitis plastica; signet ring cells; Krukenberg tumors ovaries stomach MC site for extranodal lymphomas; H. pylori associated steatorrhea; chronic pancreatitis, bile salt deficiency, small bowel disease liver disease, bile salt resins, cholestasis, bacterial overgrowth, Crohns failure to reabsorb xylose indicates small bowel disease chronic pancreatitis cause of malabsorption autoimmune disease; antibodies against gliadin in gluten; flat villi association with dermatitis herpetiformis systemic infection; foamy macrophages with bacteria (PAS+ inclusions) in small bowel submucosa fever, polyarthritis, skin pigmentation Campylobacter jejuni MCC; positive fecal smear for leukocytes loss isotonic fluid; enterotoxins from E. coli and V. cholerae

Osmotic diarrhea Rotavirus Norwalk virus Cytomegalovirus Staphylococcus aureus Bacillus cereus Clostridium botulinum (adult) Clostridium botulinum (child) Clostridium difficile Shigella sonnei Salmonella enteritidis Salmonella paratyphi Salmonella typhi Carrier state site M. tuberculosis

hypotonic loss fluid; laxatives, lactase deficiency MCC diarrhea in children MCC diarrhea in adults common cause diarrhea in AIDS; MCC cholecystitis and pancreatitis in AIDS preformed toxin causes food poisoning; culture food preformed toxin in fried rice and tacos; gram positive rods in stool preformed neurotoxin (blocks acetylcholine release); paralysis and mydriasis colonization of bowel with release of neurotoxin; eating honey pseudomembranous colitis; postantibiotics; toxin assay stool; Rx metronidazole produces dysentery (bloody diarrhea); associated with HUS gastroenteritis; animal reservoirs poultry, turtles sepsis; osteomyelitis in HbSS typhoid fever; human transmission; bradycardia, neutropenia, splenomegaly gallbladder MCC intestinal TB in United States (swallow TB); Peyers patch site of infection secretory diarrhea (travelers diarrhea); toxin stimulates guanylate cyclase

Enterotoxigenic E. coli

Vibrio cholerae Oral Rx cholera Yersinia enterocolitica Entamoeba histolytica Cryptosporidium parvum Giardia lamblia Trichuris trichiura Enterobius vermicularis Ascaris lumbricoides Necator americanus Strongyloides stercoralis Diphyllobothrium latum Signs of small bowel obstruction Radiograph small bowel obstruction MCC small bowel obstruction Duodenal atresia Hirschsprung disease S/S

secretory diarrhea; toxin stimulates adenylate cyclase to produce cAMP solution must contain glucose to reabsorb Na+ (co-transport) mesenteric lymphadenitis; sepsis in iron overload states dysentery; trophozoites phagocytose RBCs; liver abscess; Rx metronidazole MCC diarrhea in AIDS; acid-fast oocysts MC protozoal cause of diarrhea; cause of malabsorption; Rx metronidazole rectal prolapse in children anal pruritus; urethritis in girls; no eosinophilia intestinal obstruction due to adult worms; no eosinophilia hookworm; iron deficiency anemia rhabditiform larvae in stool not eggs fish tapeworm; vitamin B12 deficiency colicky pain; constipation and obstipation air-fluid levels on x-ray adhesions from previous surgery vomiting bile-stained fluid at birth; double bubble sign; Down syndrome absent ganglion cells in submucosal/myenteric plexus rectosigmoid proximal bowel dilated but peristalses; no stool in rectal vault

Hirschsprung association Intussusception Meconium ileus Indirect inguinal hernia Gallstone ileus Volvulus Direct inguinal hernia Umbilical hernia Sigmoid colon Small bowel infarction Causes small bowel infarction Ischemic colitis Mesenteric angina Angiodysplasia Hematochezia Meckels diverticulum S/S Meckels diverticulitis Sigmoid diverticulum

Down syndrome; Chagas disease terminal ileum telescopes into cecum; obstruction plus bloody diarrhea complication of cystic fibrosis second MCC of small bowel obstruction; common in weight lifting obstruction of small bowel with gallstone + air in biliary tree MC due to sigmoid colon twisting around mesentery protrudes through center of triangle of Hesselbach; no obstruction common in black children; may entrap bowel in adults MC site for polyps, cancer, diverticula diffuse abdominal pain with bloody diarrhea embolism (atrial fibrillation), thrombosis SMA or SMV splenic flexure pain with bloody diarrhea pain in splenic flexure 30 minutes after eating submucosal dilation of venules in cecum; cause of hematochezia massive loss of blood per rectum; diverticulosis MCC persistence omphalomesenteric duct bleeding MC (iron deficiency in children), diverticulitis mimics acute appendicitis; cannot differentiate without radionuclide scan diverticulitis MC complication; MCC

hematochezia and fistula formation Diverticulitis Ulcerative colitis S/S UC associations left-sided acute appendicitis mucosal/submucosal ulceration; starts in rectum; crypt abscess; risk adenocarcinoma left lower quadrant crampy pain with bloody diarrhea primary sclerosing cholangitis, seronegative HLA B27 + spondyloarthropathy transmural inflammation; terminal ileum involved 80%; granulomas; skip lesions colicky pain and diarrhea; fistulas (anal, bowl to bowel) appendix MC site; terminal ileum MC site for carcinoid syndrome liver metastasis; flushing/diarrhea due to serotonin; increased urine 5-HIAA precursor lesion colon cancer; size and number determine risk of malignancy greatest risk for colon cancer (30%); secrete mucus rich in protein and potassium AD with 100% penetrance for developing colon cancer AD, polyposis plus osteomas and desmoid tumors AD, polyposis plus brain tumors second MC cancer and cancer killer in adults obstruct; MC location rectosigmoid bleed

Crohns disease S/S Carcinoid tumor Carcinoid syndrome Tubular adenomas

Villous adenoma Familial polyposis Gardners syndrome Turcots syndrome Colorectal cancer Left-sided colorectal cancer Right-sided colorectal cancer

Acute appendicitis External hemorrhoids Internal hemorrhoids Urobilinogen (UBG) UBG Alcoholic liver disease Viral hepatitis Cholestasis markers Unconjugated bilirubin Conjugated bilirubin (CB) % CB <20% (unconjugated) Gilberts disease Physiologic jaundice newborn % CB 20-50% % CB >50% Negative urine bilirubin + trace urobilinogen Positive urine bilirubin, absent urobilinogen Positive urine bilirubin + increased urobilinogen Negative urine bilirubin + increased urobilinogen

due to lymphoid hyperplasia in children and obstruction by fecalith in adults thrombose bleed; prolapse out of rectum breakdown product CB in bowel (color of stool) enterohepatic circulation to liver and kidney (color of urine) serum AST>ALT; serum GGT serum ALT>AST serum AP and GGT macrophage degradation of heme; lipid soluble; never in urine water soluble; never normal in urine Gilberts, spherocytosis, physiologic jaundice newborn, ABO/Rh HDN AD; uptake and conjugation; bilirubin increases with fasting unconjugated hyperbilirubinemia; begins on day three viral/alcoholic hepatitis bile duct obstruction (intra or extrahepatic); carcinoma head of pancreas normal urine obstructive jaundice hepatitis extravascular hemolytic anemia

Markers of severity of liver disease Hepatitis A

albumin, PT protective antibodies; day care centers, jails, homosexuals, traveling; not chronic protective antibodies; accidental needle stick, IVDA; hepatocellular carcinoma no protective antibodies; posttransfusion hepatitis; chronic state; hepatocellular carcinoma no protective antibodies; requires HBsAg to replicate vaccination recovered from HBV acute HBV/chronic HBV infective carrier if >6 months serologic gap; not infective chronic HBV healthy carrier viral hepatitis and acetaminophen MCCs E. coli in adults; S. pneumoniae in children; complication of ascites TB MC bacteria Entamoeba histolytica; flash shaped ulcers in cecum; liver abscess; Rx Echinococcus granulosis; sheep dog definitive host; man intermediate host Schistosoma mansoni; adult worms in portal vein; pipe stem cirrhosis Clonorchis sinensis; ingesting encysted larvae in fish; cholangiocarcinoma nutmeg liver; RHF MCC

Hepatitis B

Hepatitis C Hepatitis D Anti-HBs alone Anti-HBs + anti-HBc-IgG HBsAg + HBeAg + HBVDNA + antiHBc-IgM Anti HBc-IgM alone HBsAg + anti-HBc-IgM Fulminant hepatic failure Spontaneous peritonitis Granulomatous hepatitis Amebiasis Echinococcosis Schistosomiasis Clonorchiasis Congestive hepatomegaly

(centrilobular necrosis) Hepatic vein thrombosis Portal vein thrombosis Alcohol related disorders Hypertriglyceridemia in alcoholics Hypoglycemia in alcoholics Ketoacidosis in alcoholics Primary biliary cirrhosis Primary sclerosing cholangitis Extrahepatic biliary atresia Drugs causing hepatitis Anabolic steroids Estrogen/oral contraceptives Methotrexate Liver angiosarcoma Hemochromatosis S/S Lab Wilsons disease Budd-Chiari syndrome; painful hepatomegaly; ascites; portal hypertension ascites, portal hypertension, no hepatomegaly fatty change; alcoholic hepatitis; cirrhosis synthesis of glycerol 3P (substrate for TG synthesis) gluconeogenesis ( NADH causes pyruvate to convert to lactate) lactate, OHB (acetyl CoA converted to AcAc and then OHB) granulomatous destruction triad bile ducts; anti-mitochondrial antibody association with ulcerative colitis; MCC of cholangiocarcinoma neonatal cholestasis acetaminophen, isoniazid, halothane intrahepatic cholestasis intrahepatic cholestasis; hepatic adenoma (intraperitoneal hemorrhage) liver fibrosis, fatty change vinyl chloride AR; increased iron reabsorption; liver target organ cirrhosis; bronze diabetes - skin pigmentation + destruction of islet cells; malabsorption serum ferritin, iron, % saturation; TIBC AR disease; defect in copper excretion

in bile and synthesis of ceruloplasmin S/S Lab HELLP syndrome cirrhosis, movement disorder (necrosis in putamen), Kayser Fleisher ring (Descemets membrane) ceruloplasmin (causes total copper); serum/urine free copper pre-eclampsia; Hemolytic anemia, ELevated transaminases, Low Platelets AR, cannot secrete AAT from liver cell; cirrhosis; hepatocellular carcinoma coma and microvesicular fatty change post viral infection; increased ammonia irreversible fibrosis; regenerative nodules; portal hypertension alcohol (MC), HBV/HCV, hemochromatosis, Wilsons, AAT deficiency, 1 biliary mental status changes; serum ammonia ascites; varices; splenomegaly; hemorrhoids; caput medusae portal hypertension; hypoalbuminemia; secondary aldosteronism use aldosterone blocker (acidosis increases loss ammonium in stool) gynecomastia; spider angiomas; female hair distribution BUN, glucose, sodium, potassium, calcium ( vitamin D); PT estrogen related (steroids, oral contraceptives); intraperitoneal

AAT deficiency in child

Reye syndrome Cirrhosis Causes cirrhosis Hepatic encephalopathy Portal hypertension Cause of ascites Rx Hyperestrinism in men Lab findings cirrhosis Liver cell adenoma

hemorrhage Liver cancer Hepatocellular carcinoma Cholangiocarcinoma Pathogenesis of cholesterol stones Black pigment stones Acute cholecystitis Chronic cholecystitis Gallbladder cancer Acute pancreatitis S/S Sentinel loop Pancreatic pseudocyst Chronic pancreatitis Pancreatic cancer S/S First sign tubule cell dysfunction Fixed specific gravity metastasis MC cancer; lung cancer MC primary site chronic HBV and HCV MCC; AFP; hepatic/portal vein invasion primary sclerosing cholangitis MCC, C.C sinensis bile with too much cholesterol and too little bile salts sign of extravascular hemolytic anemia (spherocytosis, HbSS) stone impacted in cystic duct; right upper quadrant colicky pain with radiation to shoulder chemical inflammation risk factors - cholelithiasis and porcelain gallbladder causes - alcohol and gallstones; amylase and lipase (more specific) epigastric pain with radiation into back localized ileus of duodenum due to acute pancreatitis abdominal mass; persistence of serum amylase >1 week alcohol abuse, CF; malabsorption, pain, type I diabetes smoking MCC jaundice/acholic (gray/pale) stools; palpable gallbladder; superficial migratory thrombophlebitis (Trousseau's sign); CA 19-9 inability to concentrate urine chronic renal failure; cannot

concentrate or dilute urine Negative urine bilirubin + trace urobilinogen Positive urine bilirubin, absent urobilinogen Positive urine bilirubin + increased urobilinogen Negative urine bilirubin + increased urobilinogen Positive urine nitrite + positive urine leukocyte esterase Sterile pyuria Prerenal azotemia Renal azotemia Postrenal azotemia Serum BUN:creatinine ratio BUN 80 mg/dL:creatinine 8 mg/dL BUN 80 mg/dL:creatinine 2 mg/dL Creatinine clearance Proteinuria RBC casts WBC casts Fatty casts with Maltese crosses Hyaline casts normal urine obstructive jaundice hepatitis extravascular hemolytic anemia urinary tract infection positive urine leukocyte esterase but negative standard culture; TB, C. trachomatis BUN and creatinine; renal blood flow (e.g. heart failure, hypovolemia) BUN and creatinine due to intrinsic renal disease (acute tubular necrosis) BUN and creatinine due to obstruction to urine flow <15:1 (renal failure); >15:1 (prerenal or postrenal azotemia) ratio 10/1 - renal failure ratio 40/1 - prerenal azotemia or postrenal azotemia measures GFR important sign of renal dysfunction nephritic type of glomerulonephritis acute pyelonephritis, acute tubulointerstitial nephritis nephrotic syndrome normal unless associated with proteinuria

Renal tubular cell casts Waxy or broad casts Cystinuria Horseshoe kidney Renal dysplasia Maternal oligohydramnios Adult polycystic kidney disease Visceral epithelial cells Glomerular BM Nephritic syndrome Nephrotic syndrome Immunofluorescence IgA GN

acute tubular necrosis chronic renal failure hexagonal crystals Turners syndrome; lower poles fused MC childhood cystic disease; abnormal development; flank mass fetal juvenile polycystic kidney disease; Potters facies in newborn AD; hypertension MC sign; cerebral berry aneurysms synthesize basement membrane negative charge due to heparan sulfate oliguria; RBC casts; hypertension; mild to moderate proteinuria proteinuria >3.5 g/day; ascites and pitting edema; fatty casts; fusion of podocytes linear (anti-glomerular BM antibodies); granular (IC deposition) MC GN; usually nephritic; episodic hematuria; mesangial IC (lgA-anti-IgA) deposits nephritic; subepithelial deposits; skin/pharyngeal infections; antiDNAase B nephritic; subendothelial deposits; anti-DNA antibodies crescents from parietal cell proliferation; worst GN; Goodpastures, Wegeners nephritic; anti-BM antibodies (glomerular + pulmonary capillary); crescentic GN

Post-streptococcal GN SLE type IV GN Crescentic GN

Goodpastures

S/S Minimal change disease (lipoid nephrosis) Lipoid nephrosis Focal segmental glomerulosclerosis Membranous GN Causes membranous GN Type I MPGN Type II MPGN DM nodular glomerulosclerosis DM glomerulosclerosis ACE inhibitors Alports syndrome Ischemic ATN Ischemic ATN Nephrotoxic ATN Nephrotoxic ATN Oliguria

young male with hemoptysis progressing to renal failure MCC childhood nephrotic syndrome podocyte fusion; loss of negative charge in glomerular BM nephrotic syndrome; AIDS and IV heroin abuse MCC adult nephrotic syndrome; subepithelial deposits; epimembranous spikes HBV, ACE inhibitors, cancer nephrotic; subepithelial deposits; HCV association; tram tracks nephrotic; C3 nephritic factor; intramembranous ICs (dense deposit disease) microalbuminuria first sign nodules with collagen in mesangium; hyaline arteriolosclerosis of arterioles inhibit angiotensin II vasoconstriction of efferent arterioles XD hereditary nephritis with sensorineural hearing loss prerenal azotemia MCC; renal tubular cell casts; BUN:creatinine ratio <15:1 disruption of BM in proximal tubule and thick ascending limb aminoglycosides, IVP dye, Pb/mercury poisoning proximal tubule dysfunction; intact BM prerenal azotemia, ATN, glomerulonephritis, postrenal azotemia

Acute pyelonephritis Chronic pyelonephritis Drug-induced tubulointerstitial nephritis S/S Analgesic nephropathy Myeloma kidney Urate nephropathy CRF Renal osteodystrophy CRF Renal osteodystrophy CRF Renal osteodystrophy CRF S/S CRF

vesicoureteral reflux with ascending infection; WBC casts, fever, flank pain U-shaped scars overlying blunt calyces type I/IV reaction; e.g., penicillin ARF, fever, rash, eosinophilia, eosinophiluria, WBC casts aspirin plus acetaminophen; renal papillary necrosis; IVP with ring defect BJ protein produces foreign body reaction in tubules prevent by giving allopurinol prior to chemotherapy fixed specific gravity; BUN:creatinine <15:1; waxy and broad casts hypovitaminosis D (no 1-hydroxylase); produces osteomalacia osteoporosis from metabolic acidosis secondary HPTH with increased osteoclastic activity pericarditis, prolonged bleeding time, normocytic anemia, pathologic fractures kidney of hypertension; shrunken kidneys due to hyaline arteriolosclerosis renal failure; encephalopathy; BP >210/120 mm Hg; IV nitroprusside necrotizing arteriolitis; flea bitten kidney; hyperplastic arteriolosclerosis pale infarcts; hematuria; common in polyarteritis nodosa renal stone MCC; atrophy of

Benign nephrosclerosis Malignant hypertension Renal findings Renal infarction Hydronephrosis

cortex/medulla; postrenal azotemia Renal stones S/S Staghorn calculus Angiomyolipoma Renal cell carcinoma most contain calcium (calcium oxalate/phosphate); hypercalciuria MC risk factor colicky pain radiating into groin, hematuria; x-ray usually shows stone due to urease producing organisms (Proteus); alkaline urine pH; ammonia smell hamartoma; associated with tuberous sclerosis smoking MCC; invasion renal vein/vena cava; lung, bone mets; yellow colored flank mass, hematuria; ectopic hormones (EPO, PTH related peptide), left-sided varicocele smoking MCC, phenacetin, aniline dyes, cyclophosphamide hypertension, unilateral abdominal mass in child; aniridia/hemihypertrophy in AD types persistent urachus produces hydronephrosis abdominal wall defect + epispadias most commonly due to prostatic hyperplasia with urethral obstruction E. coli; females > males; no fever, flank pain, or WBC casts smoking MCC, aniline dyes, cyclophosphamide; papillary hematuria; hydronephrosis risk factors persistent urachus, extrophy

S/S Renal pelvis transitional cell carcinoma Wilms tumor Urine draining from umbilicus Retroperitoneal fibrosis Bladder extrophy Bladder diverticula Acute cystitis Bladder transitional cell carcinoma S/S Bladder adenocarcinoma

Bladder squamous cell carcinoma Hypospadias Epispadias Peyronies disease Priapism Squamous cell carcinoma penis Cryptorchidism Orchitis Epididymitis S/S Varicocele Varicocele Hydrocele Torsion of testicle Testicular cancer Risk factors Seminoma

Schistosoma hematobium infection ventral opening on penis due to failure closure of urethral folds dorsal opening on penis due to defect in genital tubercle painful curvature penis due to fibromatosis persistent/painful erection; HbSS HPV and lack of circumcision most important risk factors undescended testis; risk for seminoma applies to cryptorchid testis and normal testis mumps usually unilateral (infertility uncommon) <35 - N. gonorrhoeae, C. trachomatis; >35 - E. coli, P. aeruginosa scrotal pain relieved by elevation of scrotum (Prehns sign) left-sided scrotal mass; spermatic vein drains into left renal vein; infertility common may be due to invasion of left renal vein by renal cell carcinoma persistent tunica vaginalis; scrotum transilluminates testicle high in canal; absent cremasteric reflex unilateral painless mass that does not transilluminate cryptorchid testis, Klinefelters, testicular feminization MC cancer; radiosensitive; large cells with lymphoid infiltrate; small

percentage have hCG Spermatocytic variant Embryonal carcinoma Yolk sac tumor Choriocarcinoma Teratoma Teratocarcinoma Malignant lymphoma Prostate Prostatitis Benign prostatic hyperplasia S/S Prostate cancer PSA Kallmanns syndrome Impotence Erection Ejaculation Leydig cell failure >65 yrs of age hemorrhage/necrosis; hematogenous spread before lymphatic; AFP, hCG MC testicular cancer in boys; AFP most aggressive testicle cancer; hCG more often benign in children than adult teratoma + embryonal carcinoma MC type in elderly; metastasis not primary cancer DHT derived stimulation embryo; periurethral area - hyperplasia; peripheral area - cancer perineal pain, fever; WBCs at end of voiding DHT/estrogen-mediated; glandular/smooth muscle hyperplasia all men develop; urethral obstruction MC (hesitancy, dribbling, nocturia), hematuria, dysuria Rx DHT-mediated; palpable with rectal exam; osteoblastic metastasis ( AP) sensitive but not specific for prostate cancer; in hyperplasia absent GnRH, anosmia, absence of taste failure to sustain an erection; psychogenic in most cases (erections present at night) parasympathetic response sympathetic response LH; testosterone, sperm count;

normal FSH Seminiferous tubule failure Leydig and seminiferous tubule failure Y chromosome Testosterone What component is unique to gram positive cell walls? What component is unique to gram negative cell walls? FSH (inhibin); sperm count; normal LH and testosterone FSH and LH; testosterone and sperm count determines genetic sex develops seminal vesicles, epididymis, vas deferens Techoic acid Lipopolysaccharide (LPS); Endotoxin

Treponema do not gram stain well, so Darkfield microscopy and fluorescent what method would be used to antibody staining visualize this bacteria? Mycobacteria do not gram stain well so what method is used to visualize them? Legionella do not gram stain well so what method is used to visualize them? What is more fatal, exotoxin or endotoxin? Acid fast

Silver stain exotoxin

What induces high-titer antibodies and is used in vaccines, exotoxin or exotoxin endotoxin? Which is NOT secreted from the cell, exotoxin or endotoxin? Binds directly to MHC-II and T-cell receptor activating T cells to release IFN-gamma and IL-2 Responsible for toxic shock syndrome? endotoxin Superantigens; TSST-1 TSST-1 released by Staph. aureus; Strep. pyogenes can also cause toxic shock-like symptoms

Most common cause of meningitis, otitis media (children), pneumonia, and sinusitis ADP-ribosylating toxin of this organism inactivates EF-2 leading to pseudomembranous pharyngitis? ADP ribosylating toxin of these organism leads to G protein stimulation of adenylyl cyclase. B component has a preference for intestinal epithelium.

Streptococcus pneumonia; "MOPS" Corynebacterium diptheriae (Pseudomonas also inactivate EF-2 but more closely related to burn victims not pharyngitis) Vibrio cholerae; E. coli has a heat labile toxin that works in a similar manner to cause watery diarrhea

This organisms heat stable toxin stimulates guanylate cyclase (instead E. coli of adenylate cyclase like its heat labile counterpart) ADP ribosylating toxin stimulates adenylate cyclase to cause whooping Bordetella pertussis cough? The alpha-toxin of this organism causes gas gangrene and double zone of hemolysis on blood agar. Toxin of this organism blocks the release of inhibitory neurotransmitter glycine? Toxin of this organism blocks the release of acetylcholine? Toxin of this organism kills enterocytes resulting in pseudomembranous colitis? This toxin cleaves host cell rRNA? The toxin of this organism is a hemolysin? Endotoxin activates release of what factors from macrophages? Clostridium perfringens

C. tetani; causes "lockjaw" C. botulinum; causes flaccid paralysis "floppy baby" C. difficile, often secondary to the antibiotic clindamycin or ampicillin Shiga toxin produced by shigella (also produced by some strains of E. coli) streptolysin O of S. pyogenes(Beta hemolytic) IL-1 (fever), TNF (fever, hemorrhagic tissue necrosis), NO (hypotension)

Endotoxin activates which members of the complement pathway? Endotoxin activates what factor to cause DIC? How would you differentiate between N. meningitidis and N. gonorrhoeae (lab test)? How would you differentiate between the cocci staphylococcus and streptococcus? What are 3 common gram positive rods? This coccoid rod requires chocolate agar with factor V and X for isolation.

C3a and C5a Hageman factor Meningitidis ferments maltose and gonorrhoeae does not Staph is catalase positive and strep is catalase negative Clostridium, listeria, bacillus, corynebacterium Haemophilus influenzae

This obligate aerobe requires a M. tuberculosis Lowenstein-Jensen agar for isolation? PAS positive macrophages are found Whipple's disease in this disease. This organism is identified by india ink. This two organisms are difficult to gram stain because they can't make their own ATP. How would you distinguish strep pneumonia from viridans streptococci? Cryptococcus neoformans Rickettsia and chlamydia, intracellular organisms Both are catalase negative (strep) and alpha hemolytic; pneumo is optochin sensitive and viridans is optochin resistant

Ingestion of this gram positive cocci's preformed toxin is a common cause of Staphylococcus aureus food poisening. This organisms of normal flora can cause subacute endocarditis? This organism of normal flora can infect prosthetic devices, catheters, and contaminate blood cultures. Viridans streptococci (often as dental procedure sequelae) Staphylococcus epidermidis

This gram positive, spore forming bacilli produces an alpha toxin that can cause myonecrosis, gas gangrene, or hemolysis.

C. perfringens

Gram positive, spore forming bacilli that can cause painless ulceration on Bacillus anthracis skin contact or progressive pulmonary problems on inhalation. Treatment for gram-positive rods forming long branching filaments resembling fungi. The outer membrane layer of these organisms inhibit entry of penicillin G and vancomycin. Which variant of Neisseria has a polysaccharide capsule? Can cause epiglottitis, meningitis, otitis media, and pneumonia. Actinomyces israelii and Nocardia asteroides; SNAP (Sulfa for Nocordia, Actinomyces use Penicillin) Gram negative bugs; some may however be susceptible to derivatives of penicillin G such as ampicillin Meningococci Haemophilus influenze; does not cause the flu however

This organism causes pneumonia in alcoholics, and diabetics, with a red Klebsiella; 3 A's: aspiration pneumonia, currant jelly sputum. Also cause of abscess in lungs, alcoholics nosocomial UTI's 3 lactose-fermenting enteric bacteria? Gram negative cocci? Gram negative "coccoid" rod which requires NAD and hematin for culture? Coccoid rod with an ADP ribosylating toxin? Klebsiella, E.coli, Enterobacter; grow pink colonies on MacConkeys agar Neisseria H. influenzae; NAD is factor V and hematin is factor X Bordetella pertussis

Lactose non-fermenting rod, oxidase pseudomonas positive? Lactose non-fermenting rod, oxidase Salmonella; "salmon swim" negative, bloody diarrhea, motile?

Lactose non-fermenting rod, oxidase Shigella positive, bloody diarrhea, immotile? This organism can cause bloody diarrhea, and mimic Crohn's or a "pseudoappendicitis". Causes food poisoning through contaminated seafood? Causes food poisoning through reheated rice? Causes food poisoning in meats. (4 organisms) These 3 viruses cause watery diarrhea? This organism causes bloody diarrhea and pseudomembranous colitis? This protozoan can cause bloody diarrhea. These protoza can cause watery diarrhea, but one strikes campers and the other the immunocomprimised. This organism can cause watery diarrhea and gas gangrene? This organisms toxin permanently activates Gs causing rice water diarrhea? This organisms toxin disables Gi, causing a whooping cough? The toxin of this organism is composed of a bacterial adenylate cyclase (edema factor) which increases cAMP. This organism requires silver stain and has an aerosol transmission Yersinia enterocolitica Vibrio parahaemolyticus and V. vulificus Bacillus cereus S. aureus, C perfringens (reheated meat), E.coli, Salmonella rotavirus, adenovirus, norwalk virus C. difficile Entamoeba histolytica Giardia (campers) cryptosporidium (immunocompromised) C. perfringens Vibrio cholerae Pertussis

Bacillus anthracis

Legionella

from environmental water source. (No person to person transmission) This organism is associated with wound and burn infection and a common cause of pneumonia in those with cystic fibrosis. This urease positive organism is associated with 90% of duodenal ulcers pseudomonas aeruginosa

H. pylori

Borrelia burgdorferi in lyme disease This bacteria is commonly spread by (francisella tularensis is also spread by tick bite? tick bite) This bacteria is associated with flea Yersinia pestis; plaque bite? This bacteria is the cause of cellulitis Pasteurella multocida with dog and cat bites. In vaginosis, greenish, vaginal discharge with fishy smell, what would be expected under the microscope? What are common presentations of pseudomonas aeruginosa? Gardnerella vaginalis; clue cells, or vaginal epithelial cells covered with bacteria Burn and wound infections and "PSEUDO" Pneumonia (esp in CF), Sepsis (black lesions on skin), External otitis (swimmers ear), UTI, Diabetic osteomyelitis 1)bismuth, metronidazole, and TTC or amoxicillin 2) Metronidazole, omeprazole, clarithromycin (expensive) Brucella aminoglycoside plus extended-spectrum penicillin (piperacillin, ticarcillin)

What is the treatment of H. pylori? This organism causes an undulant fever and is often acquired from dairy products. What is the treatment for pseudomonas aeruginosa? What is the treatment for G. vaginalis?

What is the treatment for legionella? Erythromycin Metronidazole

What is the treatment for H. influenzae?

ceftriaxone (meningitis), rifampin (prophylaxis in close contacts)

What are the 3 causes of a positive Current infection, past exposure, BCG PPD test? (excluding false positive) vaccination What is the Ghon complex? TB granulomas with lobar (usually lower) and perihilar lymph node involvement. Reflects primary infection. Extrapulmonary TB of the spine that presents as a sort of arthritis of the intervertebral joints. fever, night sweats, weight loss, and hemoptysis Leprosy; mycobacterium leprae Rickettsiae; classic triad of fever, headache and rash. Others my apply but if this is all you get, think Ricketts!

What is Pott's disease? What are the most commmon symptoms of TB? Patients presents with loss of eyebrows, nasal collapse, a deformed earlobe, and multiple lesions of the face. Diagnosis? Patient presents with fever, headache, and rash. Diagnosis?

What is the treatment for all forms of TTC Rickettsiae? Patient presents with rash on palms Rocky mountain spotted fever of hand and soles of feet. What is (Rickettsia), syphillis, Coxsackie A the differential? (Hint: 3 of them) (Hand, foot, and mouth disease) What is the Weil-Felix reaction? What is the classic cause of "walking" pneumonia? (insidious onset, headache, nonproductive cough, diffuse interstitial infiltrate) What is the treatment for mycoplasma pneumoniae? What are the two forms of chlamydia? antirickettsial antibodies, usually positive for rocky mountain spotted fever and typhus Mycoplasma pneumoniae

tetracycline or erythromycin Elementary body which is extracellular form that enters cell by endocytosis; Reticulate body which replicates in cell

by fission What are the 3 spirochetes? Borrelia, leptospira, and treponema

Patient presents with a red rash with central clearing that looks like an expanding "bull's eye". Diagnosis? What is the treatment for lyme disease? Patient presents with painless chancre, if left untreated what further symptoms can be expected?

Lyme disease; borrelia burgdorferi Tetracycline Condylomata lata and maculopapular rash (palms and soles)

When the pupil constricts for What is the Argyll Robertson pupil and accomodation but is nonreactive to what is it pathognomonic for? light; pathognomonic for tertiary syphillis What is the best test for treponemas? AIDS patient presents with white patches in the mouth. Diagnosis? This dimorphic fungi is a mold in soil and spherule in tissue. This organism is associated with bird or bat droppings. This mold with septate hyphae that branch at a V shape is a cause of allergic bronchopulmonary disease? FTA-ABS Oral thrush or candidiasis; candida albicans Coccidiomycosis Histoplasmosis Aspergillosis; Aspergillus fumigatus

Heavily encapsulated yeast that stains Cryptococcus neoformans w/ india ink? This yeast causes diffuse interstitial pneumonia, most commonly in the immunosuppressed (HIV). This fungus is usually introduced by trauma, typically by a thorn (rose gardener's disease), causing local pustule or ulcer with nodules along Pneumocystis carinii

Sporothrix schenckii

draining lymphatics. This protozoa causes bloody diarrhea (dysentery). Common cause of severe diarrhea in AIDS patients. What is the treatment for E. histolytica? What is the treatment for G. lamblia? What is the treatment for Plasmodium? What is the treatment for trichomonas vaginalis? Entamoeba histolytica; do not confuse with G. lamblia which causes watery diarrhea Cryptosporidium Metronidazole Metronidazole Chloroquine, sulfadoxine + pyrimethamine, mefloquine, quinine Metronidazole

What is the treatment for Toxoplasma? Sulfadiazene + pyrimethamine

What is the treatment for trypanosoma Nifurtimox cruzi? This organism can cause brain abscess in HIV patients? Toxoplasma

Patient presents with cyclic fever, headache, anemia, and splenomegaly. Malaria; p. falciparum is severe Diagnosis? Vaginitis caused by protozoa. Diagnosis? These organisms found in undercooked pork have larvae that can cause mass lesions in the brain. Trichomonas vaginalis cystircercosis; Taenia solium

These organisms which use snails as a host, penetrate the skin and cause Schistosoma granulomas, fibrosis, and inflammation of spleen and liver. This organism found in undercooked fish can cause inflammation of the biliary tract? Clonorchis sinensis

Larvae of this organism penetrate skin Ancylostoma duodenale; hookworm

of feet leading to intestinal infection and can cause anemia. This organism causes an intestinal infection and their eggs are visible in the feces. This organims causes an intestinal infection and causes anal pruritis (the scotch tape test) What is the treatment of hookworm, pinworm, roundworm, and strongyloides?

(strongyloides stercoralis is similar but does not cause anemia) Ascaris lumbricoides; giant roundworm Enterobius vermicularis; pinworm All are treated by Mebendazole/pyrantel pamoate except strongyloides, which is treated with Ivermectin/thiabendazole

This organism transmitted by ingested Echinococcus granulosus dog feces can cause cysts in liver? This organism can lead to a B12 deficiency by absorbing the vitamin, but often requires many years before apparent. This schistosoma is related to hematuria and bladder cancer. This schistosoma is related to portal hypertension Diphyllobothrium latum

Schistosoma haematobium Schistosoma mansoni

What is the treatment for schistosoma Praziquantel infection? What is the treatment for taenia solium Praziquantel/niclosamide; albendazole for cysircercosis

what is the treatment for Echinococcus Albendazole granulosus?

What are the DNA viruses? What is the only single stranded DNA virus family? What are the two non-linear DNA

HHAPPPy viruses!; Hepadna, herpes, adeno, pox, parvo, papova Parvo Papovavirus and Hepadna

viruses? What is the only DNA virus that is not icosahedral? What is the only DNA virus that does not replicate in the nucleus? What are the 3 naked DNA virus families? What are the 3 naked RNA virus families? What is the only RNA virus that is not single stranded? What are the viruses in the picornavirus family? What are the viruses in the herpesvirus family? Pox; complex structure Pox; carries its own DNA-dependent RNA polymerase PAP; Parvo, adeno, papova CPR; Calicivirus, Reovirus, picornavirus Reovirus "PERCH on a peak (pico)"; Polio, Echo, Rhino, Coxsackie, HAV HSV, VZV, EBV, CMV, HHV6, HHV8

From what families do the hepatitis B, hepadna; A, picorna; C, Flavi; D, Delta; viruses come from? E, Calici This virus is a common cause of conjunctivitis. "pink eye"; adenovirus

This virus causes aplastic crises in sickle cell disease, "slapped B19 parvovirus cheeks" rash (erythema infectiosum, and hydrops fetalis. These HPV and JCV belong to this Papovavirus viral family This virus is can cause molluscum contagiosum in the Poxvirus immunosuppressed. Norwalk virus belongs to this family, along with HEV Colorado tick fever and rotavirus belong to this family of virus. This is the #1 cause of fatal diarrhea in children. Calicivirus Reovirus Rotavirus; remember only 3 viruses cause diarrhea (rotavirus, norwalk, and adeno)

Yellow fever, dengue, St. Louis encephalitis, and West nile virus all belong to this family of virus.

Flavivirus

This family of virus include rubella, eastern and western equine Togavirus encephalopathies These viruses have reverse transcriptase? Retroviruses and HBV

This family of viruses are generally Coronavirus; (rhinovirus is also a cause of attributed with the common cold the common cold but belongs to pico and SARS. family) The influenza virus are within this family of virus. Orthomyxoviruses

This family of viruses include parainfluenza, RSV, measles, and paramyxoviruses mumps. Rabies family of viruses. This family includes Ebola and marburg hemorrhagic fever. Rhabdovirus Filoviruses

This disease is associated with progressive multifocal JCV leukoencephalopathy (PML) in HIV patients. This virus is not a retrovirus but has reverse transcriptase. These viruses must transcribe negative strand to positive using RNA polymerase. This virus is the cause of the common cold. Patient presents with parotitis, orchitis, and aseptic meningitis. Diagnosis? Patient presents with bluish-gray HBV Negative-stranded viruses; Arena, Buny, Paramyxo, Orthomyxo, Filo, Rhabdo (Always Bring Polymerase Or Fail Replication!) Rhinovirus; 100 serotypes (Coronavirus is also cause of common cold) Mumps virus Measles virus

spots on buccal mucosa. Diagnosis? Drift is minor changes based on random mutation, this is the cause of epidemics; Shift is reassortment of viral genomes (such as human flu A recombines with swine flu A), this is the cause of pandemics and is much worse. Amantadine and rimantidine for influenza A; Zanamivir and oseltamivir (neuraminidase inhibitors) are useful for both A and B Rabies

What is genetic drift and genetic shift, and which is worse?

What is the treatment for influenza? Negri bodies (cytoplasmic inclusions in neurons) are often found in this fatal encephalitis.

Patient presents with fever, black vomitus, and jaundice. Councilman Yellow fever; jaundice makes you yellow, bodies (acidophilic inclusions) may "Flavi" means yellow in latin. be seen in liver. Patient presents with fever, hepatosplenomegaly, pharyngitis, and lymphadenopathy in posterior auricular nodes. Positive monospot test. What is the Tzanck test? How is HAV transmitted? How is HBV transmitted? How is HCV transmitted? How is HEV transmitted? Which hepatitis variants predispose to cirrhosis, hepatitis, and hepatocellular carcinoma? EBV; mononucleosis, monospot test is heterophil antibodies detected by agglutination of sheep RBC's (used to distinguish EBV from CMV in mono) Smear of an opened skin vesicle to detect multinucleated giant cells in HSV-1, HSV2, and VZV fecal-oral transmission Parenteral, sexual, and maternal-fetal routes primarily via blood enterically and causes water-borne epidemics HBV and HCV

This hepatitis variant requires HBV HDV; requires HBsAg as envelope coinfection This from of hepatitis is particularly HEV fatal in pregnant women. This hepatitis is chronic and generates the most carriers. HCV; chronic, cirrhosis, carriers

This is a marker for active hepatitis IgM HAVAb A infection. This marker indicates HBV carrier state. This marker indicates immunity to HBV. This marker indicates recent HBV infection. This hepatitis marker indicates high transmissibility. Both acute HBV and chronic carriers of HBV have positive HBsAg and HBcAb and negative HBsAb. How are the two distinguished? What tests are used to determine HIV infection? What is PCR used for in HIV patients? What mutation conveys HIV immunity? What mutation conveys a rapid progression to AIDS? What oppurtunistic infections frequent the brain in AIDS patients? HBsAg HBsAb HBcAb HBeAg (e antigen is a second core antigen, antibodies to HBeAb, indicate lower transmissibility) Active disease has HBcAb of the IgM variety, whereas chronic carriers have IgG HBcAb (also carriers actually have HbsAb, but it's all bound to HBsAg) ELISA (high false pos, low threshold) followed by Western blot (high false neg, high threshold) Monitor viral load, used to follow drug therapy in patients CCR5 homozygotes (heterozygotes follow a slower course) CXCR1 mutation cryptococcus, toxoplasmosis, CMV, and JCV (PML)

What oppurtunistic infections affect CMV retinitis

the eyes in AIDS patients? What oppurtunistic infections affect Pneumocystis carinii, TB, histoplasmosis the lungs of AIDS patients? What oppurtunistic infections affect VZV (shingles), and HHV-8 (Kaposis the skin of AIDS patients? sarcoma), Pox (molluscom contagiosum)

MOA mannitol clinical uses of mannitol side effects of mannitol contraindications of mannitol how is mannitol administered? MOA spironolactone

creates an osmotic diuresis because it can't leave the tubule inhibits Na and Cl reabsorption in PC and ascendin loop to decrease intractranial pressure or intraocular pressure through volume depletion can cause pulmonary edema d/t extracellular volume expansion, pulling water out of cells hypernatremia CHF pulmonary edema anuria severe renal failure severe dehydration parenterally (poorly absorbed PO) K sparing diuretic, antagonizes aldosterone in the DCT, inhibiting Na reabsorption

what effect does decreases serum Ca levels by directly inhibiting spironolactone have on Ca its transport in the DCT clinical uses of spironolactone side effects of spironolactone HTN pulmonary edema edema from CHF or cirrhosis, nephrotic syndrome primary hyperaldosteronism gynecomastia (and other anti-androgenic effects) hyperkalemia hyponatremia hypochlroemic acidosis (blocks aldosterone's effect on Na/H antiporter) K sparing diuretic, directly inhibits Na reabsorption, independent of aldosterone increased Ca reabsorption treats ca stones MOA similar, but triampterene has shorter t1/2

MOA amiloride uses of amiloride differences between

amiloride and triamterene? MOA furosemide loop diuretic, blocking NKCC increased urinary excretion of K, Mg, Ca increases RBF without altering GFR

edema to increase urine output in ARF (although clinical uses for furosemide it doesn't alter the course of ARF) hypercalcemia hyperkalemia side effects of furosemide why does hyperuricemia result from furosemide use? contraindication of furosemide which is the only loop diuretic without a sulfa group? MOA HCTZ? clinical uses of HCTZ? contraindication of HCTZ side effects of HCTZ K wasting metabolic alkalosis Mg depletion ototoxicity hyperuricemia increases urate reabsorption d/t increased proximal Na reabsorption sulfa allergy ethacrynic acid block NaCl transport at the DCT Enhanced Ca reaborption (because Na and Ca compete for ATP dependent reabsorption at DCT) HTN edema DI (by inducing mild volume depletion) to stop recurrent renal calcium stones sulfa allergy hyperglycemia hyperlipidemia hyperuricemia hypercalcemia melabolic alkalosis Mg depletion Carbonic anhydrase inhibitor so it inhibits the reabsorption of HCO3- in PCT also CA is in ciliary body of eye and in choroid plexus cells, so it decreases aqueous humor production and increases CSF production acute altitude sickness glaucoma treatment for alkalosis facilitate eexcretion of weak acid (as seen in tumor lysis syndrome) encephalopathy (from decreased excretion of NH3 in urine) renal stones b/c calcium phosphate

MOA acetazolamide

uses for acetazolamide side effects of acetazolamide

is less soluble in alkaline urine hyperchloremic metabolic acidosis contraindications of acetazolamide what effect does furosemide have on the following serum levels: K HCO3 Ca Mg urate what effect does thiazide have on the following serum levels: K HCO3 Ca Mg urate sulfa allergy hepatic or renal dz hyperchloremic acidosis hyponatremia hypokalemia decreased increased decreased decreased increased

decrease increase increased decreased increased

what effect does spironolactone have on the increased decreased decreased none none following serum levels: K HCO3 Ca Mg urate what effect does amiloride have on the following increased decreased increased none none serum levels: K HCO3 Ca Mg urate what effect does acetazolamide have on the decreased decreased none none none following serum levels: K HCO3 Ca Mg urate which diuretics decrease Mg? which diuretics increase urate? contraindication of spironolactone MOA nitroprusside clinical uses of nitroprusside furosemide HCTZ furosemide HCTZ acute renal failure vasodilation of arteries and veins contact with RBC --> decomposition of drug and release of NO NO, via activation of guanylate cyclase --> vasodilation HTN crisis aortic dissection (must be given with B blocker) CHF

side effects of nitroprusside contraindications for nitroprusside

hypotension reflex tachy CN release known inadequate cerebral circulation hepatic/renal dz (increases thiocyanate toxicity) via guanylate cyclase --> increase cGMP which activates cAMP protein dependent kinases and leads to dephosphorylation of myosin light chains and decreased intracellular Ca --> relaxation of veins and increased venous capacitance treats angina (decresae coronary asospasm) CHF HTN hypotension, tachycardia, throbbing HA from meningeal arterial dilation ACE inhibitor blocks formation of AII and degradation of bradykinin so, inhibits constriction of efferent arteriole, and potentiates vasodilation caused by bradykinin also causes venous vasodilation HTN CHF ischemic heart disease decreases proteinuria and progression of nephropathy in diabetics cough from increased bradykinin can cause renal insufficiency b/c GFR is not increased in low volume states renal insufficiency bilateral renal artery stenosis AII receptor blocker HTN CHF no cough can't maintain GFR by vasodilation of efferent arterioles inhibits PDE III --> dilation of arteries and veins PDE III inactivates cAMP, so this process is inhibited --> increased Ca reflux in myocardium, with increased cardiac contractility refractory CHF can increase mortality, and should

MOA nitroglycerine

uses of nitroglyceride side effects of nitroglycerine

MOA captopril

uses of captopril

side effects of captopril contraindications of captopril MOA losartan uses of losartan side effects of losartan

MOA milrinone uses of milrinone

ONLY be used if diuretics, digoxin, and vasodilators have failed a-fib side effects of milrinone ventricular arrhythmias hypotension hepatotoxicity blocks PDE V action (thus potentiating the action of cGMP dependent kinases that activate phosphatases that encourage the relaxation of smoooth muscle) also decreases the Ca concnetration --> smooth muscle relaxation blocks the Na-K pump --> increased Na intracellularly this inhibits the Na concentration gradient from forming, blocking the Ca from leaving the cells this improves cardiac contractility also slows the conduction through AV node CHF a fib, a flutter (slows conduction through AV node) narrow therapeutic window visual disturbances, nausea, blurred vision a-tac and AV block can result

MOA sildenafil

MOA digoxin

uses of digoxin side effects of digoxin

hypokalemia 2nd/3rd degree heart block WPW contraindication of digoxin who develop a-fib --> increased impulses through accessory pathway --> VF what abnormalities can be incresaed PR, decreased QT, scooping of ST seen on the EKG on a segments, T wave inversion person taking digoxin

MOA phenytoin MOA carbamazepine MOA lamotrigine MOA gabapentin MOA topiramate MOA phenobarbital MOA valproic acid MOA ethosuxamide

Increases Na channel inactivation Increases Na channel inactivation blocks voltage gated Na channels increases GABA release Blocks Na channels, increases GABA release increases GABA increases GABA, blocks Na channels blocks ca channels in thalamus

MOA benzos uses for phenytoin usees for lamotrigine uses for carbamazepine uses for gabapentin uses for topirimate uses for phenobarbital uses for valproic acid uses for ethosuxamide which anti-epileptic drugs are 1st line in pregnancy and children which epi drug is 1st line for trigeminal neuralgia which drug is used to treat peripheral neuropathy which drug is used to treat myoclonic seizures which drug is used to treat seizures in eclampsia which epileptic drug --> sedation, tolerance, and dependence?

increases GABA everything but absence seizures. status epilepticus prophylaxis everything but absence and status everything but absence and status all seizures except absence and status peripheral neuropathy everything but absence and status everything but absence and status everything but status absence

uses for benzos in epilepsy acute status phenobarbital carbamazepine gabapentin valproic acid MgSO4 (1st line) benzos benzos

which epileptic drug --> aplastic anemia, liver carbamazepine toxicity, and teratogenesis? which epileptic drug --> diplopia, ataxia? which epileptic drug --> GI distress, lethargy, carbamazepine phenytoin ethosuxamide

headache? which epileptic drugs --> ethosuxamide lamotragine stevens johnson syndrome which epileptic drug --> nystagmus, gingival hyperplasia, hirsutism? which epileptic drug --> SLE like sydnrome which epi drug --> spina bifida and other NTDs which epi drug --> kidney stones which epilepsy drug --> malignant hyperthermia? how do you treat OD of barbiturates? how do you treat OD of benzos? other than for epilepsy, what can phenytoin be used for? phenytoin phenytoin valproic acid topiramate phenytoin symptom management flumazenil (competitive antagonist at GABA receptor) anti-arrhythmic

which is more dangerous in barbiturates (longer t1/2 and more respiratory/cv overdose: benzos or depression) barbiturates? MOA l-dopa l dopa crosses bbb (dopamine doesn't) so it is converted to dopamine by dopa decarboxylase in CNS peripheral decarboxylase inhibitor in order to increase bioavailability in brain and decrease peripheral side effects (since the conversion to dopamine won't occur peripherally) arrhythmias from peripheral conversion of DA dyskinesia following lt admin akinesia between doses selectively inhibits MAO-B, increasing availability

carbidopa

toxicity of l-dopa? MOA selegiline

of DA use of selegiline toxicityy of selegeliene MOA sumatriptan use of sumatriptan what type of drug is bethanechol? what type of drug is carbechol what type of drug is pilocarpine what type of drug is methacholine what is the difference between direct cholinergic agonsts and indirect? uses of bethanechol uses of carbechol uses of pilocarpine uses of methacholine action of methacholine class: neostigmine class pyrodostigmine class: edrophonium class: physostigmine class: echothiophate uses for neostigmine uses for pyridostigmine adjunctive to l-dopa in parkinsons enhances l-dopa toxicity 5-HT1D agonist --> vasoconstriction acute migraine cluster headache attacks direct cholinergic agonist direct cholinergic agonist direct cholinergic agonist direct cholinergic agonist direct directly stimulate cholinergic receptors and indirect inhibit their breakdown via AChE activates bladder and bowel smooth muscle (used post-op for ileus and urinary retention) glaucoma pupillary contraction release of intraocular pressure potent stimulator for saliva, sweat, and tears challenge test for asthma dx stimulates muscarinic receptors in airway indirect cholinomimetic indirect cholinomimetic indirect cholinomimetic indirect cholinomimetic indirect cholinomimetic post-op and neurogenic ileus and uriNAry retention MG reversal of NM junction blockade MG

uses for edrophonium uses for physostigmine uses for echothiophate

to dx MG glaucoma and atropine OD glaucoma

which indirect ACh agonist physostigmine penetrates CNS

what are the symptoms of organophosphate poisoning antidote to organophosphate poisoning what is pralidoxime MOA of epi in tx of glaucoma

DUMBBELSS Diarrhea Urination Miosis Bradycardia Bronchospasm Excitation of skel muscle Lacrimation Sweating Salivation atropine + pralidoxime antagonist used to regenerate active cholinesterase increases outflow of aqueous humor

MOA brimonidine in tx of (alpha agonist) decreases aqueous humor synth glaucoma MOA beta blockers in tx of glaucoma decreases aqueous humor secretion

MOA acetazolamide in tx decreas aqueous humor secretion d/t decreaed of glaucoma HCO3 MAO cholinomimetics in tx of glaucoma which drug should be used in a glaucoma emergency MOA latanoprost in tx of glaucoma which glaucoma drugs decrease the synth of aqueous humor? which glaucoma drugs increase outflow of increased outflow of aqueous humor pilocarpine (direct ACh mimetic) PGF-alpha, increases outflow of aqueous humor beta-blockers brimonidine acetazolamide epi cholinomimetics PGF2alpa (latanoprost)

aqueous humor? MOA atropine toxicity of atropine muscarinic antagonist dry as a bone hot as a hare mad as a hatter red as a beet blind as a bat

Effects Nitrates have on: EDV BP Contractility HR down down up (reflex) up (reflex) down down Ejection time MV O2 Effects B-blockers have on: EDV BP Contractility up down down down up down HR Ejection time MV O2 effects b-blockers + nitrates have on: EDV BP no effect, or down down little, no effect down Contractility HR Ejection little/no effect down a lot! time MV O2 MOA CCBs In decreasing effect, which CCBs have most effect on vascular smooth muscle? in decreasign effeect, which CCBs have most effect on heart? block voltage dependent ca channels of cardiac and smooth muscle, reducing muscle contractility nifedipine > diltiazem > verapemil

verapamil > diltiazem > nifedipine

which CCB can't be used nifedipine for arrhythmias? toxicity of CCBs which CCB is most similar to nitrates in effect? which CCB is most similar to b-blockers in effect? MOA statins? cardiac depression flushing peripheral edema dizziness constipation nifedipine (makes sense... nifedipine works most strongly on vascular smooth muscle) verapamil (makes sense... verapamil works most strongly on heart) HMG-CoA reductase inhibitors blocks formation of cholesterol from HMG-CoA

MOA niacin MOA bile resins MOA ezetimibe

blocks the export of cholesterol from the hepatocyte to the blood binds cholesterol in the gut so they can't get to the hepatocytes cholesterol absorption blocker so, prevents cholesterol from entering hepatocytes from gut increases action of lipoprotein lipase, encouraging the breakdown of VLDL --> LDL also decreases hepatic synthesis and secretion of VLDL increases HDL by decreasing TG (results from decreased VLDL) --> decresaed exchange of cholestreryl esters from HDL

MOA fibrates

which cholesterol agents affect endogenous fibrates niacin lovastatin production of cholesterol? which cholesterol agents affect absorption of ezetimibe bise acid resins exogenous cholesterol effects of statins on: LDL down A LOT up down HDL TGs effects of niacin on LDL HDL TGs down a lot (not as much as statins) up A LOT down

effects of bile acid resins down a lot (not as much as statins) none slightly on LDL HDL TGs UP effects of ezetimibe on LDL HDL TGs effects of fibrates on: LDL HDL TGs down a lot (not as much as statins) none none down a little up DOWN A FRIGGIN TON!

what 2 cholesterol drugs, if taken concurrently, will statins and fibrates cause rhabdomyolysis which cholesterol drugs increase LFTs? your lft's are not SEF (safe) statins ezetimibe fibrates

which cholesterol drug -- bile acid resins

> GI discomfort antidote to dig toxicity MOA of class I antiarrhythmics class II? class III? class Iv? which drugs are in class Ia anti-arrythmics? anti-dig Fab fragment s slowly normalize K lidocaine cardiac pacer Na channel blockers B-blockers K channel blockers CCBs Quinidine Amiodarone Procainamide Disopyramide

which drugs are in the I Be with my Lid To Mex(ico) lidocaine tocainide class Ib anti-arrhythmics? mexiletine which drugs are in the class Ic anti-arrythmics? MOA class IA antiarrhythmics? uses for class IA antiarrhythmics MOA for class IB antiarrhythmics use for class IB antiarrhythmics MOA for class IC antiarrhythmics uses for class IC antiarrhythmics toxicity of quinidine toxiciyt of procainamide toxicity of IB antiarrhythmics? toxicity of IC antiarrhythmics receptor selectivity for epi? See (C)! And Can't (EnCain) We FLEe if we PROP up PHENOMS? encainide flecainide propafenone increased AP duration increased ERP increased QT interval atrial and ventricular arrhythmias (esp reentrant and ectopic) SVT and VT decreases AP duration acute ventricular arrhythmias, esp post MI no effect on AP VT --> FV inretractable SVT LAST resort cinchonism (HA, tinnitus, thrombocytopenia, torsades de pointes from increased QT interval) SLE-like syndrome (reversible) local anesthetic CNS stimulation/depression CV depression pro-arrhythmic (esp post-MI) prolongs refractory period all are equal

receptor selectivity for NorE receptor selectivity for isoproteronol receptor selectivity for DA receptor selectivity for dobutamine receptor selectivity for phenylephrine receptor selectivity for albuterol receptor selectivity for terbutaline

a1 = a2 > b1 B1=b2 d1 = d2 > B > a b1 > b2 a1 > a2 b2 > b1 b2 > b1

MOA amphetamine MOA epehderine MOA cocaine MOA clonidine uses for epi uses for norE uses for isoproterenol uses for DA uses for dobutamine uses for amphetamines uses for ephedrine

indirect general sympathetic agonist releases stored catecholamines indirect and direct sympathomimetic stimulates release of NE from sympathetic neurons blocks reuptake of NorE and DA centrally acting alpha agonist decreased central adregnergic outflow anaphylaxis glaucoma asthma hypotension hypotension (but decreases renal perfusion) rare... AV block shock (increases renal perfusion) heart failure shock heart failure cardiac stress testing narcolepsy obesity ADD nasal decongestion urinary incontinence hypotension

uses for phenylephrine uses for albuterol uses for terbutaline uses for cocaine uses for clonidine examples of inhaled anesthetics MOA inhaled anesthetics effects of inhaled anesthetics toxicity of halothane toxicity of methoxyflurane toxicity of enflurane toxicity of any inhaled anesthetic types of drugs used as IV anesthetics which barbiturate is commonly used as an IV anesthetic? uses of thiopental

pupil dilator vasoconstriction nasal decongestion asthma asthma vasoconstriction local anesthetic HTN (esp with renal dz b/c it doesn't decrease blood flow to kidney) halothane enflurane isoflurane (-ane) unknown myocardial depression respiratory depression n/v increased cerebral blood flow decreased cerebral demand hepatotoxicity nephrotoxicity pro-convulsant malignant hyperthermia (rare) BB King on optiates proposes foolishly Barbiturates benzos Ketamine (arylclohxamines) opiates Propofol thiopental induction of anesthesia short surgical procedures

which is the most common midazolam gaseous anesthetics and anesthetic used for endoscopy? narcotics what is it administered with? side effects of midazolam how is the respiratory depression from midazolam treated? post-op respiratory depression hypotension amnesia flumezanil

side effects of arylcyclohexamines benefit of propofol what is combined with opiates during general anesthesia? MOA local anesthetics examples of atypical antipsychotics examples of typical antipsychotics MOA typical antipsychotics MOA atypical antipsychotics clinical uses of typical antipsychotics clinical uses for atypical antipsychotics clinical uses for olanzapine toxicity associated with typical antipsychotics

bad dreams CV stimulation disorientation hallucinations increased cerebral blood flow less post-op nausea than thiopental other CNS depressants block Na channels by binding to specific receptors in inner portion of channel olanzapine clozapine risperidone thioridazine haloperidol fluphenazine chlorpromazine block D2 receptor blocks dopamine and 5HT receptors schizophrenia psychosis acute mania Tourette's schizophrenia (+ and - sx) OCD anxiety d/o depression mania Tourette EPS endocrine effects anti-muscarinic effects (dry mouth) hypotension (from blocking alpha receptors), sedation (from blocking histamine receptors) NMS tardive dyskinesia stereotypical oral-facial movements d/t blocking DA receptors rigidity myoglobinuria autonomic instability hyperpyrexia dantrolene and DA agonists

what is tardive dyskinesia what is NMS tx of NMS

toxicity associated wiht atypical less EPS and anti-cholinergic effects antipsychotics Clozapine --> agranulocytosis uses for lithium toxicity of lithium bipolar blocks relapse and acute manic events LMNOP movement (tremor) nephrogenic DI

hypOthyroidism Pregnancy problems MOA buspirone uses of buspirone benefits of buspirone examples of ssri's clincical uses for ssri examples of tricyclic antidepressants MOA TCA uses for TCAs which TCA is used for bedwetting which TCA is used for OCD examples of heterocyclic antidepressants examples of MAOIs stimulates 5HT1a receptors anxiolysis for GAD doesnt cause sedation or addiction doens't interfere with alcohol fluoxetine sertraline paroxetine citalopram OCD endogenous depression eating d/o imipramine amitriptyline desipramine nortiptyline clomipramine doxepin blocks reuptake of NorE and 5HT major depression bedwetting (imipramine) OCD (clomipramine) imipramine clomipramine you need BUtane in your VEINs to MURder for a MAP of alcaTRAZ buproprion venlafaxine mirtazapine maportiline trazodone phenelzine tranylcypromine

Abdominal pain, ascites, hepatomegaly Budd-Chiari syndrome (posthepatic venous thrombosis) Achilles tendon xanthoma Familial hypercholesterolemia ( LDL receptor signaling) Adrenal hemorrhage, hypotension, DIC Waterhouse-Friderichsen syndrome (meningococcemia) Anterior drawer sign Anterior cruciate ligament injury

Arachnodactyly, lens dislocation, aortic dissection, hyperflexible joints Marfan syndrome (fribrillin defect) Athlete with polycythemia 2 to erythropoietin injection Back pain, fever, night sweats, weight loss Pott disease (vertebral TB)

Bilateral hilar adenopathy, uveitis Sarcoidosis (noncaseating granulomas) Blue sclera Osteogenesis imperfecta (type I collagen defect) Bluish line on gingiva Burton line (lead poisoning) Bone pain, bone enlargement, arthritis Paget disease of bone ( osteoblastic and osteoclastic activity) Bounding pulses, diastolic heart murmur, head bobbing Aortic regurgitation Butterfly facial rash and Raynaud phenomenon in a young Female - Systemic lupus erythematosus Caf-au-lait spots, Lisch nodules (iris hamartoma) Neurofribromatosis type I (+ pheochromocytoma, optic gliomas) Caf-au-lait spots, polyostotic fribrous dysplasia, precocious puberty, multiple endocrine abnormalities McCune-Albright syndrome (mosaic G-protein signaling mutation) Calf pseudohypertrophy Muscular dystrophy (most commonly Duchenne): X-linked recessive deletion of dystrophin gene Cherry-red spots on macula Tay-Sachs (ganglioside accumulation) or Niemann-Pick (sphingomyelin accumulation), central retinal artery occlusion Chest pain on exertion Angina (stable: with moderate exertion; unstable: with minimal exertion) Chest pain, pericardial effusion/friction rub, persistent fever following MI Dressler syndrome (autoimmune-mediated post-MI fribinous pericarditis, 112 weeks after acute episode) Child uses arms to stand up from squat Gowers sign (Duchenne muscular dystrophy) Child with fever later develops red rash on face that spreads to body Slapped cheeks (erythema infectiosum/frifth disease: parvovirus B19) Chorea, dementia, caudate degeneration Huntington disease (autosomal dominant CAG repeat expansion) Chronic exercise intolerance with myalgia, fatigue, painful cramps, myoglobinuria - McArdle disease (muscle glycogen phosphorylase defriciency) Cold intolerance - Hypothyroidism Conjugate lateral gaze palsy, horizontal diplopia Internuclear ophthalmoplegia (damage to MLF; bilateral [multiple sclerosis], unilateral [stroke])

Continuous machine-like heart murmur PDA (close with indomethacin; open or maintain with misoprostol) Cutaneous/dermal edema due to connective tissue deposition Myxedema (caused by hypothyroidism, Graves disease [pretibial]) Infant with hypoglycemia, failure to thrive, and hepatomegaly Cori disease (debranching enzyme deficiency) or Von Gierke disease (glucose-6-phosphatase deficiency, more severe) Infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect Edwards syndrome (trisomy 18) Jaundice, palpable distended non-tender gallbladder Courvoisier sign (distal obstruction of biliary tree) Large rash with bulls-eye appearance Erythema chronicum migrans from Ixodes tick bite (Lyme disease: Borrelia) Lucid interval after traumatic brain injury Epidural hematoma (middle meningeal artery rupture) Male child, recurrent infections, no mature B cells Bruton disease (X-linked agammaglobulinemia) Mucosal bleeding and prolonged bleeding time Glanzmann thrombasthenia (defect in platelet aggregation due to lack of GpIIb/IIIa) Muffled heart sounds, distended neck veins, hypotension Beck triad of cardiac tamponade Multiple colon polyps, osteomas/soft tissue tumors, impacted/ supernumerary teeth Gardner syndrome (subtype of FAP) Myopathy (infantile hypertrophic cardiomyopathy), exercise intolerance Pompe disease (lysosomal -1,4-glucosidase deficiency)

Neonate with arm paralysis following difficult birth Erb-Duchenne palsy (superior trunk [C5C6] brachial plexus injury: waiters tip) No lactation postpartum, absent menstruation, cold intolerance Sheehan syndrome (pituitary infarction) Nystagmus, intention tremor, scanning speech, bilateral internuclear ophthalmoplegia Multiple sclerosis Oscillating slow/fast breathing Cheyne-Stokes respirations (central apnea in CHF or intracranial pressure) Painful blue fingers/toes, hemolytic anemia Cold agglutinin disease (autoimmune hemolytic anemia caused by Mycoplasma pneumoniae, infectious mononucleosis) Painful, pale, cold fingers/toes Raynaud phenomenon (vasospasm in extremities) Painful, raised red lesions on pad of fingers/toes Osler nodes (infective endocarditis, immune complex deposition) Painless erythematous lesions on palms and soles - Janeway lesions (infective endocarditis, septic emboli/ microabscesses) Painless jaundice Cancer of the pancreatic head obstructing bile duct Palpable purpura on buttocks/legs, joint pain, abdominal pain (child), hematuria Henoch-Schnlein purpura (IgA vasculitis affecting skin and kidneys) Pancreatic, pituitary, parathyroid tumors - MEN 1 (autosomal dominant) Periorbital and/or peripheral edema, proteinuria, hypoalbuminemia, hypercholesterolemia - Nephrotic syndrome Pink complexion, dyspnea, hyperventilation Pink puffer (emphysema: centriacinar *smoking+, panacinar - *1-antitrypsin deficiency])

Polyuria, renal tubular acidosis type II, growth failure, electrolyte imbalances, hypophosphatemic rickets - Fanconi syndrome (proximal tubular reabsorption defect)

Thyroid and parathyroid tumors, pheochromocytoma MEN 2A (autosomal dominant ret mutation) Thyroid tumors, pheochromocytoma, ganglioneuromatosis MEN 2B (autosomal dominant ret mutation) Toe extension/fanning upon plantar scrape Babinski sign (UMN lesion) Unilateral facial drooping involving forehead Facial nerve (LMN CN VII palsy) Urethritis, conjunctivitis, arthritis in a male Reactive arthritis associated with HLA-B27 Vascular birthmark (port-wine stain) Hemangioma (benign, but associated with Sturge-Weber syndrome) Vomiting blood following gastroesophageal lacerations Mallory-Weiss syndrome (alcoholic and bulimic patients) Weight loss, diarrhea, arthritis, fever, adenopathy Whipple disease (Tropheryma whipplei) Worst headache of my life Subarachnoid hemorrhage Anticentromere antibodies Scleroderma (CREST) Antidesmoglein (epithelial) antibodies Pemphigus vulgaris (blistering) Antiglomerular basement membrane antibodies Goodpasture syndrome (glomerulonephritis and hemoptysis) Antihistone antibodies Drug-induced SLE (hydralazine, INH, phenytoin, procainamide) Anti-IgG antibodies Rheumatoid arthritis (systemic inflammation, joint pannus, boutonnire deformity) Antimitochondrial antibodies (AMAs) 1 biliary cirrhosis (female, cholestasis, portal hypertension) Antineutrophil cytoplasmic antibodies (ANCAs) Microscopic polyangiitis and Churg-Strauss syndrome (MPO-ANCA/p-ANCA); granulomatosis with polyangiitis (Wegener; PR3-ANCA/c-ANCA) Antinuclear antibodies (ANAs: anti-Smith and anti-dsDNA) SLE (type III hypersensitivity)

Antiplatelet antibodies Idiopathic thrombocytopenic purpura Anti-topoisomerase antibodies Diffuse systemic scleroderma Anti-transglutaminase/anti-gliadin/anti-endomysial antibodies Celiac disease (diarrhea, distention, weight loss) Apple core lesion on abdominal x-ray Colorectal cancer (usually left-sided) Azurophilic peroxidase and myeloblasts Auer rods (AML, especially the promyelocytic [M3] type) Bacitracin response Sensitive: Streptococcus pyogenes (group A); resistant: Streptococcus agalactiae (group B) Bamboo spine on x-ray Ankylosing spondylitis (chronic inflammatory arthritis: HLA-B27) Basophilic nuclear remnants in RBCs Howell-Jolly bodies (due to splenectomy or nonfunctional spleen) Heterophile antibodies Infectious mononucleosis (EBV) Hexagonal, double-pointed, needle-like crystals in bronchial secretions Bronchial asthma (Charcot-Leyden crystals: eosinophilic granules) High level of d-dimers DVT, PE, DIC Hilar lymphadenopathy, peripheral granulomatous lesion in middle or lower lung lobes (can calcify) Ghon complex (1 TB: Mycobacterium bacilli) Honeycomb lung on x-ray or CT Interstitial pulmonary fibrosis granular inclusions in granulocytes

Hypercoagulability (leading to migrating DVTs and vasculitis) Trousseau syndrome (adenocarcinoma of pancreas or lung) Hypersegmented neutrophils Megaloblastic anemia (B12 deficiency: neurologic symptoms; folate deficiency: no neurologic symptoms) Hypertension, hypokalemia, metabolic alkalosis Conn syndrome Hypochromic, microcytic anemia Iron deficiency anemia, lead poisoning, thalassemia (fetal hemoglobin sometimes present) Increased AFP in amniotic uid/maternal serum Dating error, anencephaly, spina bifida (neural tube defects) Increased uric acid levels Gout, Lesch-Nyhan syndrome, tumor lysis syndrome, loop and thiazide diuretics Intranuclear eosinophilic droplet-like bodies Cowdry type A bodies (HSV or CMV) Iron-containing nodules in alveolar septum Ferruginous bodies (asbestosis: chance of mesothelioma) Keratin pearls on a skin biopsy Squamous cell carcinoma Large lysosomal vesicles in phagocytes, immunodeficiency Chdiak-Higashi disease (congenital failure of phagolysosome formation) Lead pipe appearance of colon on barium enema x-ray Ulcerative colitis (loss of haustra) Linear appearance of IgG deposition on glomerular basement membrane Goodpasture syndrome Low serum ceruloplasmin Wilson disease (hepatolenticular degeneration) Lumpy bumpy appearance of glomeruli on immunouorescence Poststreptococcal glomerulonephritis (immune complex deposition of IgG and C3b)

Lytic (hole punched) bone lesions on x-ray Multiple myeloma Mammary gland (blue domed) cyst Fibrocystic change of the breast Monoclonal antibody spike Multiple myeloma (usually IgG or IgA) Monoclonal gammopathy of undetermined significance (MGUS consequence of aging) Waldenstrm (M protein = IgM) macroglobulinemia Primary amyloidosis Mucin-filled cell with peripheral nucleus Signet ring (gastric carcinoma) Narrowing of bowel lumen on barium x-ray String sign (Crohn disease) Necrotizing vasculitis (lungs) and necrotizing glomerulonephritis Granulomatosis with polyangiitis (Wegener; PR3-ANCA/ c-ANCA) and Goodpasture syndrome (antibasement membrane antibodies) Needle-shaped, negatively birefringent crystals Gout (monosodium urate crystals) Nodular hyaline deposits in glomeruli Kimmelstiel-Wilson nodules (diabetic nephropathy) Novobiocin response Sensitive: Staphylococcus epidermidis; resistant: Staphylococcus saprophyticus Nutmeg appearance of liver Chronic passive congestion of liver due to right heart failure

ClassiC/relevant treatments: Absence seizures Ethosuximide Acute gout attack NSAIDs, colchicine Acute promyelocytic leukemia (M3) All-trans retinoic acid ADHD Methylphenidate, amphetamines Alcohol use disorder AA + disulram, naltrexone, or acamprosate for patient. Al-

Anon for patients family Alcohol withdrawal Benzodiazepines Anorexia Nutrition, psychotherapy Anticoagulation during pregnancy Heparin Arrhythmia in damaged cardiac tissue Class IB antiarrhythmic (lidocaine, mexiletine, tocainide) B12 deciency Vitamin B12 supplementation (work up cause with Schilling test) Benign prostatic hyperplasia Tamsulosin, nasteride Bipolar disorder Lithium, valproate, carbamazepine, lamotrigine (mood stabilizers) Breast cancer in postmenopausal woman Aromatase inhibitor (anastrozole) Buerger disease Smoking cessation Bulimia nervosa SSRIs Candida albicans Amphotericin B (systemic), nystatin (oral thrush), azoles (vaginitis) Carcinoid syndrome Octreotide Chlamydia trachomatis Doxycycline (+ ceftriaxone for gonorrhea coinfection), erythromycin eye drops (prophylaxis in infants) Chronic gout Probenecid (underexcretor), allopurinol (overproducer), febuxostat Chronic hepatitis IFN- Chronic myelogenous leukemia Imatinib Clostridium botulinum Antitoxin Clostridium difcile Oral metronidazole; if refractory, oral vancomycin Clostridium tetani Antitoxin + vaccine booster + diazepam CMV Ganciclovir

Crohn disease Corticosteroids, iniximab, methotrexate, azathioprine Cryptococcus neoformans Fluconazole (prophylaxis in AIDS patients) Cyclophosphamide-induced hemorrhagic cystitis Mesna Depression SSRIs (rst-line) Diabetes insipidus DDAVP (central); hydrochlorothiazide, indomethacin, amiloride (nephrogenic) Diabetes mellitus type 1 Dietary intervention (low sugar) + insulin replacement Diabetes mellitus type 2 Dietary intervention, oral hypoglycemics, and insulin (if refractory) Rapid Review ` ClassiC/relevant treatments SeCTiON iii 625 ConDition Common treatment(s) Diabetic ketoacidosis Fluids, insulin, K+ Enterococci Vancomycin/ampicillin + aminoglycoside Erectile dysfunction Sildenafil, vardenafil ER breast cancer Tamoxifen

Ethylene glycol/methanol intoxication Fomepizole (alcohol dehydrogenase inhibitor) Haemophilus inuenzae (B) Rifampin (prophylaxis) Generalized anxiety disorder Buspirone Granulomatosis with polyangiitis (Wegener) Cyclophosphamide, corticosteroids Heparin toxicity (acute) Protamine sulfate HER2/neu breast cancer Trastuzumab

Hyperaldosteronism Spironolactone Hypercholesterolemia Statin (first-line) Hypertriglyceridemia Fibrate Immediate anticoagulation Heparin Infertility Leuprolide, GnRH (pulsatile), clomiphene

Inuenza Rimantadine, oseltamivir Legionella pneumophila Erythromycin Long-term anticoagulation Warfarin Malaria Chloroquine/meoquine (for blood schizont), primaquine (for liver hypnozoite) Malignant hyperthermia Dantrolene Medical abortion Mifepristone Migraine Sumatriptan MRSA Vancomycin Multiple sclerosis -interferon, immunosuppression, natalizumab Mycobacterium tuberculosis RIPE (rifampin, INH, pyrazinamide, ethambutol) Neisseria gonorrhoeae Ceftriaxone (add doxycycline to cover likely concurrent Chlamydia) Neisseria meningitidis Penicillin/ceftriaxone, rifampin (prophylaxis) Neural tube defect prevention Prenatal folic acid Osteomalacia/rickets Vitamin D supplementation Osteoporosis Bisphosphonates; calcium and vitamin D supplementation Patent ductus arteriosus Indomethacin Pheochromocytoma -antagonists (e.g., phenoxybenzamine) Pneumocystis jirovecii TMP-SMX (prophylaxis in AIDS patient) Prolactinoma Bromocriptine (dopamine agonists) Prostate cancer/uterine fibroids Leuprolide, GnRH (continuous) Prostate carcinoma Flutamide 626iii NOiTCeSRapid Review ` Key assoCiations ConDition Common treatment(s)

Pseudomonas aeruginosa Antipseudomonal penicillin + aminoglycoside Pulmonary arterial hypertension (idiopathic) Sildenafil, bosentan, epoprostenol Rickettsia rickettsii Doxycycline, chloramphenicol (associated with aplastic anemia) Ringworm infections Terbinafine, griseofulvin, imidazole Schizophrenia (negative symptoms) 5-HT2A antagonists (e.g., 2nd-generation antipsychotics) Schizophrenia (positive symptoms) D2 receptor antagonists (e.g., 1st- and 2nd-generation antipsychotics) SIADH Demeclocycline, lithium, vasopressin receptor antagonists Sickle cell anemia Hydroxyurea ( fetal hemoglobin) Sporothrix schenckii Oral potassium iodide Stable angina Sublingual nitroglycerin Staphylococcus aureus MSSA: nafcillin, oxacillin, dicloxacillin (antistaphylococcal penicillins); MRSA: vancomycin Streptococcus bovis Penicillin prophylaxis; evaluation for colon cancer if linked to endocarditis Streptococcus pneumoniae Penicillin/cephalosporin (systemic infection, pneumonia), vancomycin (meningitis) Streptococcus pyogenes Penicillin prophylaxis Temporal arteritis High-dose steroids Tonic-clonic seizures Phenytoin, valproate, carbamazepine Toxoplasma gondii Sulfadiazine + pyrimethamine Treponema pallidum Penicillin Trichomonas vaginalis Metronidazole (patient and partner) Trigeminal neuralgia (tic douloureux) Carbamazepine

Ulcerative colitis 5-ASA, iniximab, colectomy UTI prophylaxis TMP-SMX Warfarin toxicity Fresh frozen plasma (acute), vitamin K (chronic) K` ey assoCiations Disease/FinDinG most Common/imPortant assoCiations Actinic (solar) keratosis Precursor to squamous cell carcinoma Acute gastric ulcer associated with CNS injury Cushing ulcer ( intracranial pressure stimulates vagal gastric secretion) Acute gastric ulcer associated with severe burns Curling ulcer (greatly reduced plasma volume results in sloughing of gastric mucosa) Alternating areas of transmural inammation and normal colon Skip lesions (Crohn disease) Aneurysm, dissecting Hypertension Rapid Review ` Key assoCiations SeCTiON iii 627 Disease/FinDinG most Common/imPortant assoCiations Aortic aneurysm, abdominal and descending aorta Atherosclerosis Aortic aneurysm, arch 3 syphilis (syphilitic aortitis), vasa vasorum destruction Aortic aneurysm, ascending Marfan syndrome (idiopathic cystic medial degeneration) Atrophy of the mammillary bodies Wernicke encephalopathy (thiamine deficiency causing ataxia, ophthalmoplegia, and confusion) Autosplenectomy (fibrosis and shrinkage) Sickle cell anemia (hemoglobin S) Bacteria associated with gastritis, peptic ulcer disease, and stomach cancer H. pylori

Bacterial meningitis (adults and elderly) Streptococcus pneumoniae Bacterial meningitis (newborns and kids) Group B streptococcus/E.coli (newborns), S. pneumoniae/ Neisseria meningitidis (kids) Benign melanocytic nevus Spitz nevus (most common in 1st two decades) Bleeding disorder with GpIb deficiency Bernard-Soulier syndrome (defect in platelet adhesion to von Willebrand factor) Brain tumor (adults) Supratentorial: metastasis > astrocytoma (including glioblastoma multiforme) > meningioma > schwannoma Brain tumor (kids) Infratentorial: medulloblastoma (cerebellum) or supratentorial: craniopharyngioma Breast cancer Infiltrating ductal carcinoma Breast mass Fibrocystic change, carcinoma (in postmenopausal women) Breast tumor (benign) Fibroadenoma Cardiac 1 tumor (kids) Rhabdomyoma, often seen in tuberous sclerosis Cardiac manifestation of lupus Libman-Sacks endocarditis (nonbacterial, affecting both sides of mitral valve) Cardiac tumor (adults) Metastasis, 1 myxoma (4:1 left to right atrium; ball and valve) Cerebellar tonsillar herniation Chiari II malformation Chronic arrhythmia Atrial fibrillation (associated with high risk of emboli) Chronic atrophic gastritis (autoimmune) Predisposition to gastric carcinoma (can also cause pernicious anemia) Clear cell adenocarcinoma of the vagina DES exposure in utero Compression fracture Osteoporosis (type I: postmenopausal woman; type II: elderly

man or woman) Congenital adrenal hyperplasia, hypotension 21-hydroxylase deficiency Congenital cardiac anomaly VSD Congenital conjugated hyperbilirubinemia (black liver) Dubin-Johnson syndrome (inability of hepatocytes to secrete conjugated bilirubin into bile) Constrictive pericarditis TB (developing world); SLE (developed world) Coronary artery involved in thrombosis LAD > RCA > LCA Cretinism Iodine deficit/hypothyroidism 826iii NOiTCeSRapid Review ` Key assoCiations Disease/FinDinG most Common/imPortant assoCiations Cushing syndrome Iatrogenic Cushing (from corticosteroid therapy) Adrenocortical adenoma (secretes excess cortisol) ACTH-secreting pituitary adenoma Paraneoplastic Cushing (due to ACTH secretion by tumors) Cyanosis (early; less common) Tetralogy of Fallot, transposition of great vessels, truncus arteriosus Cyanosis (late; more common) VSD, ASD, PDA Death in CML Blast crisis Death in SLE Lupus nephropathy Dementia Alzheimer disease, multiple infarcts Demyelinating disease in young women Multiple sclerosis DIC Severe sepsis, obstetric complications, cancer, burns, trauma, major surgery Dietary deRapid Review ` Key assoCiations SeCTiON iii 629

Disease/FinDinG most Common/imPortant assoCiations Holosystolic murmur VSD, tricuspid regurgitation, mitral regurgitation Hypercoagulability, endothelial damage, blood stasis Virchow triad (results in venous thrombosis) Hypertension, 2 Renal disease Hypoparathyroidism Accidental excision during thyroidectomy Hypopituitarism Pituitary adenoma (usually benign tumor) Infection 2 to blood transfusion Hepatitis C Infections in chronic granulomatous disease Staphylococcus aureus, E. coli, Aspergillus (catalase Intellectual disability Down syndrome, fragile X syndrome Kidney stones Calcium = radiopaque Struvite (ammonium) = radiopaque (formed by urease organisms such as Proteus vulgaris or Staphylococcus) Uric acid = radiolucent Late cyanotic shunt (uncorrected left to right becomes right to left) Eisenmenger syndrome (caused by ASD, VSD, PDA; results in pulmonary hypertension/polycythemia) Liver disease Alcoholic cirrhosis Lysosomal storage disease Gaucher disease Male cancer Prostatic carcinoma Malignancy associated with noninfectious fever Hodgkin lymphoma Malignancy (kids) ALL, medulloblastoma (cerebellum) Metastases to bone Prostate, breast > lung > thyroid Metastases to brain Lung > breast > genitourinary > melanoma > GI Metastases to liver Colon >> stomach, pancreas )

Mitochondrial inheritance Disease occurs in both males and females, inherited through females only Mitral valve stenosis Rheumatic heart disease Mixed (UMN and LMN) motor neuron disease Amyotrophic lateral sclerosis Myocarditis Coxsackie B Nephrotic syndrome (adults) Focal segmental glomerulosclerosis Nephrotic syndrome (kids) Minimal change disease Neuron migration failure Kallmann syndrome (hypogonadotropic hypogonadism and anosmia) Nosocomial pneumonia Klebsiella, E. coli, Pseudomonas aeruginosa Obstruction of male urinary tract BPH Opening snap Mitral stenosis Opportunistic infection in AIDS Pneumocystis jirovecii pneumonia Osteomyelitis S. aureus Osteomyelitis in sickle cell disease Salmonella Osteomyelitis with IV drug use Pseudomonas, S. aureus Ovarian metastasis from gastric carcinoma or breast cancer Krukenberg tumor (mucin-secreting signetring cells) Ovarian tumor (benign, bilateral) Serous cystadenoma 036iii NOiTCeSRapid Review ` Key assoCiations Disease/FinDinG most Common/imPortant assoCiations Ovarian tumor (malignant) Serous cystadenocarcinoma Pancreatitis (acute) Gallstones, alcohol Pancreatitis (chronic) Alcohol (adults), cystic Rapid Review ` equation review SeCTiON iii 631 Disease/FinDinG most Common/imPortant assoCiations Tumor in women Leiomyoma (estrogen dependent, not precancerous)

Tumor of infancy Hemangioma (usually regresses spontaneously by childhood) Tumor of the adrenal medulla (adults) Pheochromocytoma (usually benign) Tumor of the adrenal medulla (kids) Neuroblastoma (malignant) Type of Hodgkin Nodular sclerosis (vs. mixed cellularity, lymphocytic predominance, lymphocytic depletion) Type of non-Hodgkin Diffuse large cell UTI E. coli, Staphylococcus saprophyticus (young women) Viral encephalitis affecting temporal lobe HSV-1 Vitamin deficiency (U.S.) Folate (pregnant women are at high risk; body stores only 3- to 4-month supply; prevents neural tube defects)