Behavioral Science: Statistical distribution:

Positive skew = meAn>meDian>mOde Positive skew = alphabetical from greatest to least

Reportable diseases: It was reported that studly Mr. Shigella ate salmon, chicken, and liver: It was REPORTED that STuDly MMR SHIGELLA aTB Salmon, Chicken, and Liver

STDs: AIDs, Gonorrhea, Syphilis, Chlamydia (*NOT HIV!) MMR: Measles, Mumps, Rubella Shigella TB Salmonella Chicken Pox Hepatits A, B, C

Health care payment:

CARE for the Elderly, AID the destitute Medicare - elderly, Medicaid - low income people

Early developmental milestones:

# of blocks stacked = age in years * 3 2 word sentences at 2 pee at three; tricycle at three four-square at four = can hop at four drawings:

o o o o o

3yo = circle 4yo = + 5yo = square 6yo = triangle See reference:

Biochemistry:

Stop codons: UGA, UAA, UAG U Go Away, U Are Away, U Are Gone EXpress EXons, INtrons are IN the way Proto-oncogenes: Mikes sis returned with her two new breasts she was able to grow because of herbs. MYCs SIS RETurned with HER2Neu breasts she RAS ABLe To-Grow BCl of hERBs.

Myc sis ret Her2/neu ras abl TGFalpha bcl2 ERB-B1, B2

Collagen: The higher the number, the smaller and softer it gets

Type 1 - bone (skin) - Osteogenesis Imperfecta (failed glycosylation and formation of procollagen triple helix with ER) Type 2 - cartilage - death in utero Type 3 - blood vessels - Ehlers-Danlos (failure of cross-linking by lysyl oxidase to make collagen fibrils outside fibroblasts), berry aneurysms Type 4: basement membrane - Alports nephritis (+ deafness and vision problems; cant see, cant pee, cant hear)

Blotting procedures: SNOW DROP

S/D: Southern blot = DNA sample identified with DNA probe N/R: Northern blot = RNA sample identified with DNA probe O/O W/P: Western blot = protein sample identified with antibody probe

Model systems:

Imprinting:

Knock out = take a gene OUT Knock in = INsert a gene Knock down = knock down the expression of the gene via complementary mRNA antagonist

Prader-Willi = Paternal deletion AngelMans = Maternal deletion

Genetics: Autosomal Dominant: have familial or hereditary in name + A Brainy Dwarf named Marfan von Hippel-Lindau hired MEN to Hunt for Potatoes.

Brainy = Neurofibromatosis1, 2 Dwarf = Achondroplasia Marfan von Hippel-Lindau MEN1, 2a, 2b Huntingtons Potato = Tuberous sclerosis

X-linked recessive: Duke Fabrys Brutal Gopher Hunter, Lesch, Was-Actually a Fragile Albino Hemophiliac.

Duke = Duchennes Fabry Brutal = Brutons Gopher > G6Pher = G6PD deficiency Hunter = Hunters Lesch-Nyhan Was-Actually = Wiskott-Aldrich Fragile X ocular Albinism Hemophilia A, B

Fragile X = Xtra large testes, jaws, ears

FraGile X = cGg trinucleotide repeat myoTonic dystrophy = cTg trinucleotide repeat

Autosomal trisomies: Pat Ed Down = 13, 18, 21 Puberty at 13, Election at 18, Drinking at 21 Down syndrome is associated with ALL (and AML) and ALzheimers and decreased ALpha-fetoprotein > ALL fall DOWN; also associated with:

Duodenal Atresia (failure to recanalize = blind duodenum > bilious vomiting with first feed; double-bubble) Celiac Disease (associated with dermatitis herpetiformis) Annular Pancreas Hirschprung congenital megacolon (failure of neural crest cell migration: no Auerbach or Meissners plexus > constipation/meconium ileus)

Edwards: watch 99 balloons Pataus: rocker bottom Pedals/feet, cleft lip/Palate, holoProsencephaly (sonic hedgehog deficiency), Polydactyly Williams syndrome: Will Farrell in Elf: elfin faces, mental retardation, well-developed verbal skills, extreme friendliness DiGeorge syndrome: CATCH-22

Cleft palate Abnormal facies Thymic aplasia (T-cell deficiency) Cardiac defects Hypocalcemia (secondary to parathyroid aplasia; remember third pharyngeal pouch: inferior parathyroids are grown with thymus and descend together) microdeletion at chromosome 22q11

Vitamin B1: Thiamine Thiamine pyrophosphate (TPP) is needed for a number of enzymes, but is rarely required alone. Whenever you need B1, you usually need FAD (B2), NAD (B3), CoA (B5), and Lipoic Acid, so just group them together: B1,2,3,5+LA. Enzymes that use B1, 2, 3, 5 + LA:

Glycolysis/TCA: PDH (X = lactic acidosis; Tx: ketogenic Leucine, Lysine + high fat diet) TCA: alphaKGDH HMP: transketolase branched chain AADH (X = Maple Syrup Urine Disease > severe CNS defects, MR, and death)

Related problems:

Lipoic acid is antagonized by Arsenic, which causes rice water diarrhea and garlic breath. B1 deficiency in alcoholics > Wernicke-Korsakoff, beriberi PDH deficiency/dysfunction > inability to continue TCA > diversion to lactic acidosis; brain starves for energy > neurologic defects. To keep brain from starving, Tx with ketogenic amino acids LEUCINE and LYSINE and high fat diet (beta oxidation of fats will produce acetyl CoA > TCA/ketogenesis).

Vitamin B6: Pyridoxine Major pathways that use B6: 1. 2. 3. Glycogenolysis RLS: Glycogen > G1P via glycogen phosphorylase Heme synthesis RLS: Succinyl CoA (TCA) + Glycine > delta aminolevulinic acid (ALA) via deltaaminolevulinic acid synthase Cysteine synthesis: Homocysteine + Serine > Cystathione via Cystathione synthase (X = homocysteinuria: Marfanoid Sx+MR+atherosclerosis) Note: Cystinuria due to PCT reabsorption defect > staghorn cystine kidney stones; Tx: acetazolamide to alkalinize urine ALT/AST transamination: Alanine+alphaKG(TCA)<ALT>Pyruvate(glycolysis)+glutamate Aspartate(Urea cycle)+alphaKG(TCA)< AST>OAA(TCA)+glutamate Amino acid production (hydroxylation, decarboxylation reactions): 1. tyrosine hydroxylation> dopa decarboxylation> dopamine 2. tryptophan to niacin/B3 (no B6 = no B3 = Pellagra) 3. histidine to histamine 4. glycine to porphyrin (in heme production; no B6 = hypochromic, microcytic anemia) 5. glutamate to GABA (no B6 = loss of GABA = increased excitation > convulsions/seizures)

4.

5.

Vitamin B12: Cobalamin Cofactor when you see Meth in product or substrate: 1. 2. METHylmalonylCoA > Succinyl CoA via methylmalonylCoA isomerase homocysteine + N-METHylTHF > METHionine + THF via homocysteine methyltransferase

Absorbed in the ileum (Crohns, gastric bypass, sprue, Diphyllobothrium latum) with IF (pernicious anemia); use Schilling test to determine if its intake/absorption or lack of IF problem. B12 stores last for YEARS. Deficiency causes an increase in methylmalonic acid (peripheral neuropathy) and homocysteine (megaloblastic anemia). Other causes of megaloblastic anemia = folate deficiency (incr. homocysteine but not methylmalonic acid, so no neuropathy) and chronic alcoholism. Vitamin B7: Biotin While Vitamin B6 is needed for DEcarboxylation reactions (amino acid production), B7 is needed for CARBOXylation reactions: 1. 2. 3. PropionylCoA(oddchainFA/branchedchainAA metab) >MethylmalonylCoA via proprionylCoA carboxylase (which goes on to form succinyl CoA of TCA with methylmalonylCoA isomerase and B12) Pyruvate(glycolysis)>OAA (TCA) via pyruvate carboxylase AcetylCoA(TCA)>MalonylCoA(FA synthesis RLS)

Avidin in egg-whites Avidly binds B7. Vitamin C: Ascorbic Acid 1. 2. 3. Iron absorption and Fe2+ state maintenance Collagen synthesis: hydroxylation of proline and lysine within fibroblast ER < SCURVY dopamine > NE via dopamine beta hydroxylase, blocked by Reserpine

Vitamin D: the longest name with a 1: (1,25-(OH)2D3) Calcitriol = active form (PTH stimulates conversion of livers 25OHvitamin D to 1,25-(OH)2D3 in kidney by 1alpha hydroxylase) Vitamin E: E is for Erythrocytes; its an antioxidant that prevents hemolytic anemia and neurodysfunction Vitamin K: inject newborns with it to make sure theyre oK (prevent hemorrhage); deficiency = normal bleeding time, but increased PT and aPTT Note:

platelet dysfunction > BT extrinsic (shorter) pathway > PT (shorter name); VII; monitor w/ Warfarin intrinsic (longer) pathway > PTT (longer name); monitor w/ Heparin

Carbamoyl phosphate synthetase: UP 1, 2.

Urea cycle RLS: CPS1 Pyrimidine synthesis RLS: CPS2

HMGCoA ___:

You always want to REDUCE your CHOLESTEROL: HMGCoA reductase = RLS for cholesterol synthesis vs. HMGCoA synthase = ketogenesis (your brain wants to SYNTHESIZE KETONES when theres no glucose)

Regulation by F2,6BP: 2 supports 1:

PFK2 supports PFK1 > glycolysis F26BP supports F16BP > glycolysis

MOA: insulin > decreases cAMP > decreases PKA > dephosphorylated FBPase2 = PFK2 > F6P to F26BP > stimulates PFK1 > incr F6P to F16BP (glycolysis) Note: glucose > decreases cAMP > decreases CAP-cAMP binding of lac operon = RNA polymerase cant bind to promoter Glycolytic enzyme deficiency: RBCs solely depend on glycolysis for energy so no Pyruvate Kinase/Phosphoglycerate Kinase (ATP generating steps) = decreased ATP > cant maintain membrane gradient > cell swells > hemolytic anemia HMP shunt/Pentose Phosphate Pathway:

NADPH: 1. 2. 3. 4.

G6P > Ribulose5P + 2NADPH via RLS G6PDH Ribulose5P > Ribose5P > purine synthesis

fatty acid and steroid synthesis oxidative burst (NADPH oxidase; X = Chronic Granulomatous Disease) p450 glutathione reductase AKA RBC antioxidation

G6PD deficiency = (x-r) > no NADPH = no glutathione reductase = oxidative damage = hemolytic anemia (bite cells - RBCs partially eaten by macrophages (M0s), Heinz bodies - oxidized Hb that precipitated in RBCs) Drugs that cause hemolytic anemia in G6PD deficiency: Prima had to take Aspirin when she INHaled her I.B.Professor Dapsones Sulfurous Fava bean NitroFarts.

Prima = Primaquine Aspirin INH (Isoniazid) I.B.Professor = Ibuprofen Dapsone Sulfurous = Sulfonamides Fava bean NitroFarts = Nitrofurantoin

CGD (chronic granulomatous disease, Dx: negative Nitroblue tetrazolium reduction) = NADPH oxidase deficiency > susceptible to Catalase+ organisms: The recoiling Red Asp wasnt Sorry towards the moaning Cat because it had Noheart.

recoiling = E.coli red = Serratia Asp = Aspergillus Sorry = S. Aureus moaning = Pseudomonas Cat = Catalase + organism NoHeart = Nocardia

Disorders of __ metabolism: __-kinase is the enzyme that immediately follows the breakdown of __:

Glucose > G6P via Gluco(Hexo)kinase Fructose > F1P via Fructokinase Galactose > Gal1P via Galactokinase

Deficiencies of Fructo and Galactokinases causes MILD symptoms (respective sugars are present in urine). The SEcond steps cause SEvere symptoms (AldolaseB and Uridyl transferase, respectively). Watch out when you see ALDO- because it means something bad is going to happen:

Glucose > Sorbitol via Aldose Reductase + NADPH (CATARACTS) Note: Sorbitol > Fructose via SorbitolDH Galactose > Galactilol via Aldose Reductase + NADPH (CATARACTS) Fructose1P > Glyceraldehide and DihydroxyacetoneP via Aldolase B (FRUCTOSE INTOLERANCE)

Essential amino acids: TV FILM HWRK (Threonine(T), Valine(V), PHENYLALANINE(F), Isoleucine(I), Leucine(L), Methionine(M), Histidine(H), TRYPTOPHAN(W ), ARGININE(R), LYSINE(K)) Negatively charged amino acids: Negative experience to be burned by Acid: Aspartic acid and glutamic acid Note: Aspartate and Glutamate (as N-acetyl glutamate) are involved in Urea cycle elimination of ammonia Amino acids with three titratable H+: Ricky Cant Hate ED RKY C H ED

Arginine(R) - 12.5 Lysine(K) - 10.5 Tyrosine(Y) - 10.1 Cysteine(C) - 8.2 Histidine(H) - 6 Aspartic acid(E) - 4.3 Glutamic acid(D) - 3.7

The numbers arent important except for Histidine. Just know the order and that it goes in descending pHs. FYI: COO-=2, NH3+=9.5 KNOW: Ketogenic amino acids: Leucine and Lysine > USED TO TREAT PDH DEFICIENCY Cycles: Urea cycle and TCA overlap:

OAA(TCA) + Glutamate <AST> Aspartate(Urea) + alphaKG(TCA) Aspartate(Urea) + Citrulline(Urea) > Arginosuccinate(Urea) > Arginine(Urea) + Fumarate(TCA)

Urea cycle enzyme deficiency > decreased TCA intermediates > TCA INHIBITION + HYPERAMMONEMIA (b/c decreased NH4+ excretion). Sx: asterixis, slurred speech, somnolence, blurry vision, vomiting Tx: less protein in diet + Benzoate/Phenylbutyrate (bind a.a.>excrete) OTC = major urea cycle enzyme: Ornithine + carbamoyl-phosphate > Citrulline via OTC OTC deficiency (x-r) = shunting of carbamoyl phosphate from urea cycle to pyrimidine synthesis: carbamoyl phosphate + aspartate > orotic acid Orotic Aciduria > decreased BUN + hyperammonemia Amino acid derivatives:

Phenylalanine (Phenylalanine hydroxylase + THB + NADPH via Dihydropterin reductase)> Tyrosine(X = PKU (a-r): screened by Guthrie test 2-3 days after birth; Tx: decr Phen, incr Tyr diet): o > Fumarate via Homogentinsic acid oxidase (X = Alkaptonuria) o > Thyroxine o (Tyrosine hydroxylase/B6, blocked by Metyrosine)> Dopa:

> Melanin (X = Albinism: decreased pigment) (Dopa decarboxylase/B6, blocked by Carbidopa)> Dopamine (Dopamine Hydroxylase/VitC, blocked by Reserpine)> NE (PNMT/SAM)>Epinephrine

Tryptophan(X in Hartnups): o (B6)> Niacin=B3 > NAD+/NADP+ (X = Pellagra) o (BH4)> Serotonin > Melatonin (sleep)

Lysosomal storage diseases:

Tay-SaX = HeXosaminidase A > incr GM2: no hepatosplen; cherry macula, onion skin lysosomes Fab-Gal is into Ceramics Fabrys = alphaGALactosidase A > incr Ceramide trihexose: peripheral neuropathy, angiokeratoma, CV/renal disease Gauched out my femur when I was on a sugar high Gaucher, Femur Necrosis, Sugar High = GlucoCerebrosidase Gauchers = betaGlucocerebrosidase > incr glucocerebroside: aseptic femur necrosis, hepatosplenomegaly, crumpled tissue paper cytoplasm Blind Intelligent Intergalactic Crab Intelligent Intergalactic = Galactocerebroside Krabbes = Galactocerebrosidase > incr galactocerebroside: blindness, peripheral neuropathy, developmental delay, globoid cells Niemann Picks his nose with hisphinger Niemann-Pick = Sphingomyelinase > incr Sphingomyelin: cherry macula with hepatosplenomegaly, neurodegeneration, foam cells Sulfur tides are multicolored Sulfur tide = Sulfatide Multicolored = Metachromic Metachromic leukodystrophy = Aryl sulfatase A > incr Sulfatides: central and peripheral demyelination with ataxia, dementia

Mucopolysaccharidoses:

HurLers = alpha-L-iduronidase > incr heparan sulfate, dermatan sulfate: corneal clouding, gargoylism, airway obstruction Hunters = iduronate sulfatase > incr heparan sulfate, dermatan sulfate: NO CORNEAL CLOUDING because Hunters need to see clearly

Major apolipoproteins: II:LL C-II = cofactor for Lipoprotein Lipase Treat abetalipoproteinemias (deficient apoB100, B48 > night blindness, acanthocytes (spiky RBC), steatorrhea, ataxia) with Vitamin E Embryology: Important Genes for Embryogenesis:

Sonic the Hedgehog fights a One-Eyed Monster: Sonic Hedgehog mutation > Holoprosencephaly FGF gene = Fibroblast Growth Factor: Growth Factor lengthens limbs FGF mutation > Achondroplasia (A-D dwarfism) HOX (Homeobox) gene: Boxes help with organization organizes/determines limb location (Vitamin A toxicity alters HOX expression > cleft palate, cardiac abnormalities, spontaneous abortion)

Rules of Early Development:

Week 2: 2 germ layers (epiblast, hypoblast), 2 cavities (amniotic, yolk sac), 2 placental components (cytotrophoblast, syncytiotrophoblast) Week 3: 3 germ layers (ectoderm, mesoderm, endoderm) Week 4: 4 heart chambers, 4 limb buds Note: neural tube closes by week 4: def. folic acid> spina bifida, etc. neural tube defect has incr alpha-fetoprotein+AChesterase (**Gastroschisis and Omphalocele, pretty much ANY internal organ extrusion results in incr alpha-fetoprotein)

SAD DAVE:

SAD: Sensory = Alar Plate/Afferent nerves = Dorsal DAVE: Dorsal=Afferent, Ventral=Efferent

Embryologic derivatives:

Ectoderm:

o o o o o o o

Surface: what you see (epidermis, hair, nails, teeth enamel, eye lens) + anterior pituitary(Rathkes pouch) Neuro: everything connected to the CNS (brain, spinal cord, oligodendocytes, posterior pituitary, retina, pineal gland) + pupillary muscles Neural crest: skull and PNS stuff (skull, head muscles, dentine, pia/arachnoid, Schwann cells, DRG, cranial nerves, celiac ganglion, parafollicular C cells of thyroid) + adrenal medulla (chromaffin cells) + melanocytes (last to migrate) Paraxial: axial stuff (axial skeleton, skeletal muscles, connective tissue and dermis) + dura mater Intermediate: urogenital ridge (kidneys and ureters, vas deferens, gonads, uterus and uterine tubules) Lateral: non-skeletal muscle and blood-related organs (visceral muscle and connective tissue, blood, lymph, spleen, cardiovascular system) + adrenal cortex Note: spleen = mesoderm, but supplied by celiac artery of the foregut MESODERMAL DEFECTS = VACTERL: Vertebral defects, Anal atresia, Cardiac defects,Tracheo-Esophageal fistulas, Renal defects, Limb defects

Mesoderm:

Endoderm: ear/mouth to anus hollow lining and organs + bladder and vagina o tympanic cavity/auritory tube, tonsils, thymus, thyroid, parathyroid o larynx, trachea, bronchi, lungs o GIT, liver, gallbladder, pancreas o urinary bladder, urethra, lower 2/3 vagina (this explains how patients can still have a vagina even if the paramesonephric ducts fail to develop) Notochord > nucleus pulposus of intervertebral disk

Teratogens:

Amina couldnt hear because she was too absorbed in her reading. Aminoglycosides prevent mRNA reading by interfering with 16S of 30S and cause CNVIII ototoxicity (Note: Congenital Syphilis also causes CNVIII ototoxicity + Saber shins + Saddle nose + Hutchinsons teeth + Mulberry Molars + frontal bossing) Maternal Diabetes: hyperglycemia > incr fetal insulin > decr lung development = cant breathe; mermaids also cant breathe air > maternal diabetes causes ARDs and sirenomelia/anal atresia (also, transposition of great vessels)

Umbilical cord:

Allantois: 2 arteries, 1 vein (arteries is 2x as long as vein) AllaNtois (urachus)> mediaN umbilical ligament UmbiLical artery > mediaL umbilical ligament Umbilical vein - ligamentum teres hepatis

Allantois > Urachus (wk3): urachus failure to obliterate = bladder to navel connection: umbilical urination or bladder outpouching Omphalomesenteric duct > Vitelline duct (wk7): duct failure to obliterate = colon to navel connection: umbilical meconium or Meckels diverticulum Heart embryology:

Primitive __ > trabeculated (rough) portion of __ Smooth atrium = sinus venosus Smooth ventricle = bulbus cordis SVC = right common and anterior cardinal veins Aorta/Pulmonary artery = truncus arteriosus, separated by spiraling neural crest migration (X = Transposition of Great Vessels, Tetralogy of Fallot)

PGA open: PG keeps DA open (decr PG > close DA with Indomethacin, NSAIDs) Aortic arch derivatives: left side of body to right side, top to bottom

I: maxillary artery (external carotid) - @ face II: hyoid/stapedial artery - @ midline throat III: common and internal carotid arteries - @ midline neck IV: right subclavian artery and aortic arch - @ right/middle chest VI: pulmonary artery (inc. ductus arteriosus connection to aorta) - @ right side of heart

Neural tube defects: The longer the name, the worse the symptoms:

Occulta: spinal canal opening but no herniation, tuft of hair Meningocele: herniation of meninges Meningomyelocele: herniation of spinal cord

Pharyngeal/Branchial CAP:

Cleft = ectoderm (~external hollow spaces) Arches = mesoderm (~muscles) Pouches = endoderm (~immune organs above the neck)

Branchial CLEFT - ectoderm: ~external hollow spaces

Cleft 1: external auditory meatus Clefts 2-4: temporary cervical sinus (fail to obliterate = lateral neck branchial cleft cyst)

Branchial cleft cyst (lateral neck) vs Thyroglossal duct cyst (midline neck, moves with swallowing because attached to tongue) Branchial ARCH - mesoderm: ~muscles The nerves that supply the branchial arches are all BOTH motor and sensory: Some(I) Say(II) Marry(III) Money(IV) But(V) My(VI) Brother(VII) Says(VIII) Big(IX) Brains(X) Matter(XI) Most(XII) (S = sens ory, M = motor, B = both) **LOOK AT THE NERVES TO FIGURE OUT WHICH MUSCLES MAKE UP WHAT ARCH** or use the following mnemonic: Chewing made me grimace so I swallowed, choked, then called for help.

chewing = arch 1 (V2,3) = muscles of mastication, ant. 2/3 tongue + malleus/incus/tensor tympani grimace = arch 2 (VII) = facial expression + stapes/stapedius (defect = Treacher Collins mandibular hypoplasia and facial abn ormalities) swallowed = arch 3 (IX)= stylopharyngeus (defect = fissure from neck to tonsils) choked = arch 4 (X, sup laryngeal)= pharyngeal constrictors and cricothyroid called for help = arch 6 (X, inf laryngeal)= intrinsic larynx muscles except cricothyroid

Note: Arch 4&6 make up post. 1/3 tongue Branchial POUCH - endoderm: ~immune organs above the neck + middle ear

Pouch 1 = auditory tube, middle ear, mastoid air cells Pouch 2 = tonsils and tonsillar sinus Pouch 3 = inferior parathyroid + thymus (they descend together) Pouch 4 = superior parathyroid + parafollicular C cells of thyroid

Failure of 3rd and 4th Pouch = DiGeorges: no thymus (= T cell deficiency), no parathyroids (= hypocalcemia > tetany) C3, 4, 5 keeps the diaphragm alive. Kidney embryology: main player = Metanephros:

Ureteric Bud = ureter>pelvis>collecting ducts JOINS Metanephric Mesenchyme = glomerulus>DCT

Defective ureteric bud = renal agenesis; B/L renal agenesis > oligohydramnios > Potters: pulmonary hypoplasia + face/limb deformities **MC site of obstruction = Ureteropelvic junction with kidney > fetal hydronephrosis Genital embryology:

Male = Mesonephric Pemale = Paramesonephric

Men are Wolves = Wolffian ducts > SEVEN in SEVEN UP (Seminal vesicles, Epididymis, Vas deferens, Ejaculatory duct, N = nothing) Women Mull over past arguments = Mullerian ducts > fallopian tubes, uterus, and upper 1/3 of vagina (lower 2/3 from urogenital sinus of endoderm)

Female = default genitals Hormone overview:

Prolactin stimulates Dopamine inhibits Prolactin Prolactin inhibits GnRH GnRH > incr FSH, LH L in LH and Leydig: LH stimulates Leydig cells to produce testosterone > develop Wolffian duct S in FSH, Sertoli, and Sperm: FSH stimulates Sertoli cells to produce Sperm, Inhibin, and Mullerian inhibiting factor (MIF); MIF inhibits female paramesonephric duct development

Genital homologues:

Urogenital sinus: o Bulbourethral glands = Bartholins greater vestibular glands o proState gland = Skene urethral and paraurethral glands

Extrophy of bladder is associated with Epispadias (faulty positioning of genital tubercle) vs. Hypospadias = more common, failure of urethral fold closure, incr risk of UTI Microbiology: Encapsulated organisms: (+Quellung reaction: quell makes capsules swell) Claustrophobic Pastor Salmon Echoed Back: Yersinful Crypt-dark Strip Clubs are Pseudo-Homes to Nice Men Francis and Bruce.

Claustrophobic = Clostridium Pastor = Pasturella Salmon = Salmonella Echoed = E.coli Back = Bacillus anthracis (D-glutamate) Yersinful = Yersinia Crypt-dark = Cryptococcus (India Ink, narrow-based budding in meningitis) Strip = Streptococcus Clubs = Klebsiella Pseudo = Pseudomonas Homes = Haemophilus Nice men = Neisseria meningitidis Francis = Francisella Bruce = Brucella

BAD - Bacillus Anthracis unique capsule contains D-glutamate Staff of grapes = Staphylococcus is in clusters VS. Streptococcus = pairs/chains

Spirochetes: Spiraling Boris Lept then Tripped

Spiraling = Spirochetes Boris = Borrelia (Giemsa stain = aniline dye; relapsing fever = result of antigenic variation) Lept = Leptospira Tripped = Treponema (Dark Field Microscopy, VDRL cardiolipin screening, FTA-ABS confirmation)

Mycoplasma vs Mycobacteria

Stains:

Bacteria have cell walls (Mycobacteria have mycolic acid in their cell walls that stain acid-fast) Plasma membranes have sterols (Mycoplasma have sterols and no cell wall)

GiemsA stains BorreliA, MalariA, ChlamydiA, TrypanosomA PASs the sugar and whip cream (PAS stains glycogen and Dx Whipples disease) Legions who Sustained injuries get Silver stars: Legionella, grow with Cysteine, silver stain; water source

Special Culture:

Nice Homes have chocolate: Neisseria and Haemophilus grow on Chocolate agar +: o Neisseria = Thayer Martin media: Vancomycin (vs G+), Polymyxin (vs g-), Nystatin (vs fungi) o Haemophilus = V (NAD+) and X (hematin) If I Tell-U the Corny joke Right, youll Laugh: o TellURight = tellurite agar o Corny = Corynebacterium o Laugh = Lofflers media TB and J: M. tuberculosis on lowenstEIN-Jensen agar (takes 3-4 weeks to grow, but diagnostic)

Obligate aerobes: If No AER, Anthrax and TB cant survive!

No = NOcardia Aer = pseudomonas AERuginosa Anthrax = B. anthracis TB = M. tuberculosis

Microaerophils = bacters: Campylobacter, Helicobacter Obligate anaerobes: These BACTERia ACTIN CLOSTRophobic enviroments (non-healing ulcers):

BACTERia = Bacteroides (E.G., B. fragilis) ACTIN = Actinomyces CLOSTRophobic = CLOSTRidium

Obligate Intracellular: REACh for My COX if you want me INSIDE you.

R = Rickettsia E = Ehrlichia A = Anaplasma Ch = Chlamydia My = Mycoplasma Cox = Coxiella Inside = intracellular

Facultative intracellular: Legions of Salmon, Rabbits, N Cows Tumble IN My yard.

Legions = Legionella Salmon = Salmonella Rabbits = Francisella N = Neisseria Cows = Brucella Tumble = Listeria In = intracellular My = Mycobacterium

Note: intracellular pathogens require cell-mediated immunity (CMI), so neonates are at risk (E.G., Listeria > neonatal meningitis: tumbles, has endotoxin, and a narrow zone of beta hemolysis) Bacterial virulence factors:

protein A for staph. Aureus: binds Fc of Ig to prevent opsonization and phagocytosis M protein (prevents phagocytosis) > strep. pyogenes rheuMatic fever (Sx: subcutaneous plaques, polyarthritis, erythema marginatum, chorea, carditis) IgA protease (to colonize respiratory mucosa) + antiphagocytic capsule (infects ASPLENIC patients b/c decr M0 and IgM/complement C3 activation (E.G., Sickle Cell autosplenectomy)) + causes meningitis = SHiN Note: can also undergo transformation (pick up DNA from environment) o Strep pneumo o H. influenza type B (B polysaccharide) o Neisseria meningitidis

Exotoxin vs Endotoxin:

EXotoxin = from EXogenous source (plasmid or bacteriophage) and EXcreted from bacteria, EXtremely toxic (even small dose), EXact effects (different toxins produce different symptoms); ~heat-labile ENDOtoxin (Lipid A)- ENDOgenous (made from bacterial chromosome, ENtegral to outer membrane of most g-Neg bacteria (and Listeria(G+))); heat stable; causes gENeral fever, shock/sepsis via direct MACROPHAGE response (binds CD14-M0 marker) > release TNF and IL-1 (no Th involvement) o M0 activation: IL1 = Fever TNF alpha = fever, hemorrhagic tissue necrosis Nitric oxide = hypotension/shock alternate complement pathway: C3a = Anaphylaxis (basophil and mast cell degranulation > hypotension, edema)

o o

C5a = neutrophil chemotaxis Hageman factor: coagulation cascade> DIC/microthrombi

Exotoxin subclass: SUPERANTIGENS: bind directly to MHCII and TH1(CD4) > explosive release of IFNgamma and IL2 (non-specific immune response):

S. aureus = TSST-1 > Toxic Shock Syndrome (fever, rash, shock) S. pyogenes = Erythrogenic toxin > Scarlet fever with Toxic-Shock-like symptoms Note: S. pyogenes also has Streptolysin O (lyses RBC); Dx: Rheumatic Fever with anti-Streptolysin-O antibody (ASOAb)

E. coli ADP ribosylating A-B toxin: Labile like Air, Stable like Ground:

heat-Labile toxin stimulates Adenylate cyclase heat-Stable toxin stimulates Guanylate cyclase

Both cause watery diarrhea. Bacterial Toxins Envoded in Lysogenic Phage: ABCDE

ShigA-like toxin - EHEC 0157:H7 - cleaves host cell rRNA/inactivates 60S; also, incr cytokines > HUS Botulinum toxin - inhibits ACh vesicle release from presynaptic neuron > flaccid paralysis Cholera toxin - activates Gs > incr cAMP > incr Cl- secretion into gut = decr Na+ absorption > watery diarrhea

Diptheria toxin - ADP-ribosylating A-B toxin (like Pseudomonas exotoxin A) - B binds, A enters and ribosylates EF2 > no more protein synthesis > cell death; pseudomembrane formation Erythrogenic (superantigen) toxin of Strep. pyogenes > Scarlet Fever - activates both TH1(CD4) and MHCII > incr INFgamma + IL2 > incr M0 and T-cell non-specific immune response > ~Toxic Shock

Gram Positives: crystal violet + iodine = blue

Coag negative Staph: SENsitive: Staph. Epi = Novobiocin SENSITIVE (VS. Staph. saprophyticus = Novobiocin resistant) alpha hemolytic Strep: OVeRPasS: Optochin Viridans Resistant, Pneumonia Sensitive Note: Strep pneumonia is bile soluble (= cant be cultured in bile, unlike gamma hemolytic Strep) beta hemolytic Strep: BBBR: Beta hemolytic, group B strep (Strep agalactiae), Bacitracin Resistant (VS. group A strep (Strep. pyogenes) = bacitracin sensitive) OR B-BRAS - Bacitracin: group B = resistant, group A = sensitive gamma hemolytic Strep: grows in bile; stomach is used to salty foods = Enterococci grows in 6.5%NaCl (VS. Strep. bovis > does NOT grow in 6.5%NaCl)

Exposure/PRIMARY TB:

Ghon complex = Ghon focus of LOWER lobe + peri-hilar lymph nodes You think they are Ghon but theyre just waiting to become secondary TB (fibrocaseous cavitary lesion of UPPER lobe)

gram negative: acetone + saffranin = pink

N. Meningities ferMents Maltose, has a capsule, and vaccine (gonorrhea doesnt; NOTE**: gonorrheas pilus protein undergoes antigenic variation!!) Note: -N. meningitidis = respiratory/oral spread > meningococcemia and Waterhouse-Friderichsen adrenal hemorrhage (hypotension and DIC) -N. gonorrhea = STD> high fever, septic arthritis, neonatal conjunctivitis, PID, Fitz-Hugh-Curtis (cervicitis>salpingitis>liver capsule infection) Enterobacteriae: CAPSULE = VIRULENCE FACTOR, all ferment glucose o Lactose fermenters (pink on MacConkey, blue on Eosin-Methylene blue) = SEEK: Serratia, Enterobacter, E. coli (blue-black metallic sheen), Klebsiella o Non-lactose fermenters = PSSY: Proteus, Salmonella, Shigella, Yersinia o H2S producing (black on Hektoen Agar) + motile (flagellar H antigen): Proteus (swarming, urease+, staghorn ammonium struvite stones), Salmonella o Note: Salmonella and Shigella both invade mucosa > bloody diarrhea; Salmonella is motile (w/ 2 flagellar antigen variants) and produces H2S, S. typhi of Typhoid fever causes abdominal rose spots and can remain chronically in gallbladder; Shigella is more virulent, moves by actin polymerization and 60S deactivating toxin induces HUS.

oxidase + organisms: when you go Camping at a quiet Pasture youd Moan More with Nice Vibrators

Camping = Campylobacter Pasture = Pasturella Moan = Pseudomonas More = Moraxella Nice = Neisseria Vibrators = Vibrio

VDRL false positives: VDRL

V = viruses: EBV, hepatitis D = drugs R = Rheumatic fever (Dx w/ S. pyogenes ASO titers) L = Lupus and Leprosy

Chlamydia: Dx via Giemsa stain (ChlamydiA, MalariA, BorreliA + TrypanosomA)

Elementary body is Enfectious and Enters cells via Endocytosis Reticulate body Replicates in cell by fission

Tricky Dick: TRIC = serotypes DK: o > MC PID, cervicitis, ectopic pregnancy o > Fitz-Hugh-Curtis liver capsule infection (from spread of PID) + violin string adhesions of parietal peritoneum to liver o > neonatal pneumonal/conjunctivitis o > REITERS: Cant see, cant pee, cant climb a tree = conjunctivitis, urethritis, arthritis VS. trAChoma = serotypes A-C > blindness VS. L1-L3 = Lymphogranuloma venerum: ulcers > lymphadenopathy, rectal strictures mistaken for PID

Tx: mothers and infants with Chlamydia with Erythromycin estolate, though there is a risk of maternal acute cholestatic hepatitis

Atypical (walking) pneumonias: My Clammy Legion walked; Tx: macrolides

Fungi:

My = Mycoplasma (IgM = cold agglutinins > agglutinate or lyse RBCs; grown on Eatons agar; Tx: tetracycline or macrolide) Clammy = Chlamydia (Tx: tetracycline or macrolide) Legion = Legionella (Tx: macrolide)

Dimorphic: cold = mold, heat = yea(s)t + Blast His Cock = East Coast to West Coast (Tx: Ketoconazole)

Blast = Blastomycosis = east of Mississippi River His = Histoplasmosis = Mississippi River and Ohio river Cock = Coccidiomycosis = Southwest US: CA, AZ

His Woodpecker Blasted Wood into Dust:

His Woodpecker = Histoplasmosis from bird/bat droppings = macrophage filled with round yeast; Histo Hides within macrophages Blasted Wood = Blastomycosis in wood = Broad-Based-Budding fungi; the handle of a baseball bat looks like its budding off the shaft) Dust = Coccidiomycosis = large spherule filled with endospores; barrel-shaped arthroconidia; Cock is filled with Sperm, Coccidio is filled with Spores

Actinomyces = Acute Angles, Septate (VS. Mucormycosis/Rhizopus = Wide angles, non-septate; ~in Diabetics) Helminth drugs:

Worms = Bendazole Praziquantel = foods: Pork, Fish, Crab, Snails o Pork = Taenia o Fish = Diphyllo, Clonorchis o Crab = Paragonimus o Snails = Schistosoma

Antigenic shift vs. drift: SPED

Vaccines:

Shift (reassortment via segmented viruses) = Pandemic Epidemic = Drift (random mutations)

Live: See MMR. Sabins small yellow chickens live. o MMR = Measles, Mumps, Rubella o Sabin (Polio, oral) o small pox o yellow fever o chicken pox/shingles Killed: RIP Always

o o o o

Rabies Influenza Polio (SalK = Killed, injected) Adenovirus

Recombinant: H_V o Worms = Bendazole o Praziquantel = foods: Pork, Fish, Crab, Snails

Viruses: DNA viruses: HeHe PoPa ParAde: first three = enveloped

He = Herpes He = HepaDNA (HBV; carries special RT: DNAdDNAp) Po = Pox (smallpox, molluscum contagiosum; carries DNAdRNAp and replicates in cytoplasm) Pa = Papilloma (HPV: (6,11): condylomata acuminata/genital warts, koilocytes=squamous cell with perinuclear cytoplasmic halo; (16,18): CIN; anal squamous cell CA) + Polyoma (JC, PML demyelinating encephalopathy) Par = Parvo = B19/Erythema infectiosum (ssDNA) Ade = Adenovirus (swimming pool conjunctivitis, gastroenteritis)

Herpes: 2 Simple Chickens Barred Sight from Rose Patches

2 Simple = HSV1,2 Chickens = HHV3: Chicken pox (truncal rash > extremities; lesions of different age)/shingles Barred = HHV4: EBV (mono, Burkitts, large cell non-Hodgkins @ Waldeyers ring, nasopharyngeal CA, hairy leukoplakia on lateral tongue; infects B cells via CD21-EBV receptor) Sight = HHV5: CMV (retinitis, negative mono-spot mono, TORCH; both intranuclear owl-eye and cytoplasmic inclusion bodies) Rose = HHV6: Roseola/Erythema subitum (high fever > rash) Patches = HHV8: Kaposi-sarcoma

RNA viruses: +RNA = PiToFlaCoCa: middle 3 = enveloped

Pi = PicoRNA = PECoRnA: o P = Polio (both colonizes nasopharynx and causes meningitis like Hib > myalgia and paralysis) o E = Echovirus: swimming pool aseptic meningitis/myocarditis o C = Coxsackie: aseptic meningitis/myocarditis, hand-foot-mouth (palm and sole vesicular rash also seen in secondary syphilis and Rickettsial Rocky Mountain Spotted Fever) o Rn = RHINOvirus (stuffy NOSE from common cold) o A = HAV To = Toga

o o o

Togas Rubelled against Germany with TORCHs = Togavirus, Rubella, German Measles (post-auricular occipital lymphadenopathy, fine truncal rash), TORCH infection (blueberry muffin rash, deaf, cataracts, PDA) VS. Rubeola: a PARA Ruby weasles caught SSPEcial measles = Paramyxo, Rubeola, SSPE complication, Measles VS. Roseola: HHV6 (high fever/seizures > truncal rash)

Fla = Flavi (HCV, yellow, dengue, St. Louis, West Nile) o yellow fever causes yellowing skin (jaundice) and black vomit Co = Corona (common cold, SARS) Ca = Calici = Norwalk, CA Cruises (gastroenteritis from cruises)

-RNA = all enveloped + RNAdRNApol

Reovirus = dsRNA, segmented: ROTAvirus = right out the anus (childhood winter gastroenteritis) HepEvirus = HEV (water epidemic, only dangerous if pregnant) Orthomyxo: O for octo = 8 segments > reassortment = Influenza pandemic (Ag shift) Paramyxo = PaRaMyX2o: o P or PARA = Parainfluenza = croup

o o

R = RSV; Tx: Ribavirin (vs. IMPDH of purine synthesis; AE: hemolytic anemia, teratogen) or RSVP Liz where P Liz = Palivizumab which binds Paramyxo F protein, preventing respiratory epithelial syncytia formation Mx2 = Measles and Mumps:

Measles: A PARA RUBY weasles caught SSPEcial Measles = paramyxo, rubeola, SSPE complication, Measles 3 Cs = cough, coryza, conjunctivitis + Koplik spots; rash from head down like Rubella Mumps: parotitis, orchitis, aseptic meningitis

Segmented viruses: BOAR

Hepatitis:

B = Bunya (Hanta hemorrhagic fever) O = Orthomyxo (Influenza) A = Arena (mouse Lassa encephalitis) R = Reovirus (right out the anus childhood diarrhea)

HAV = Picorna (+RNA); fecal-oral (ice cubes, shellfish) HBV = HepaDNA (env, dsDNA); blood (renal dialysis, needle stick), sex, mother; Dx: PCR HCV = Flavi (env, +RNA); blood (IVDA, transfusion); Dx: RT-PCR HDV = Delta (defective env, -RNA); infects with HBV HEV = HepEvirus (+RNA); fecal-oral (water epidemic)

ToRCHS: hepatosplenomegaly, jaundice, thrombocytopenia, growth retardation

T = Toxoplasma: ToxoTriad: intracranial calcifications, chorioretinitis, hydrocephalus = SAME TRIAD AS CMV!!; from cat feces, ringenhancing brain abscess); Tx: Sulfadiazine+Pyrimethamine R = Rubella (Togavirus, +RNA): PDA, cataracts, deaf, blueberry muffin rash; maternal rash and arthritis C = CMV: Toxoplasma triad (intracranial calcification, chorioretinitis, hydrocephalus) + UNILATERAL hearing loss, seizures H = HSV (+HIV): temporal lobe encephalitis, herpetic lesions (fingers) S = Syphilis: hydrops fetalis stillbirth > Hutchinson teeth, saddle nose, saber shins

Note: B19 also causes hydrops fetalis Bactericidal drugs (all else = bacteriostatic): Sephiroth Met Vancouver Penpal Amina in Florida, then KILLED HER D:

Seph(iroth) = Cephalosporin Met = Metronidazole Vancouver = Vancomycin Penpal = Penicillin Amina = Aminoglycosides Florida = Fluoroquinolones

Antimicrobial drugs: 1. inhibits PG cross-linking > no cell wall: Ceph Chills-in Nam watching PG movies: 1. Ceph = Cephalosporin 2. Chills-in = cillins (binds PBP, block transpeptidase cross-linking; Penicillin = endocarditis prophylaxis (before surgery/dental), syphilis prophylaxis) 3. Nam = AztreoNAM (binds PBP3 for Pencillin-allergy pts; vs SEEK Pseudomonas- Serratia, E.coli, Enterobacter, Klebsiella, Pseudomonas), MeropeNEM and ImipeNEM+Cilastatin (Merpenem/Imipenem vs. everything, esp. Enterobacter, but causes SEIZURES; Cilastatin inhibits renal dihydropeptidase I to inhibit renal tubule Imipinem inactivation) blocks PG synthesis: 1. Bacitracin (vs. S. pyogenes (GAS)) 2. Vancomycin (binds D-Ala-D-Ala and interferes with PG-elongating transglycosylase 1. vs. resistant G+ inc, MRSA and C.diff!! 2. TON of AEs: T = thrombophlebitis, O = ototoxic, N = nephrotoxic + Red Man (slow infusion and pretreat with antihistamine to prevent)) vs. g- by disrupting cell membranes: Polymyxins (neosporin) - detergent vs cell membrane; AE: neurotoxicity, acute renal tubular necrosis vs. G+/g- by blocking folate > no nucleotide synthesis (megaloblastic anemia): 1. Sulfonamides (comp inhibit PABA for dihydropteroate synthetase > no DHF synthesis; AE: infant kernicterus (avoid in pregnancy), SJ, nephrotox, G6PD hemolysis) 1. Sulfamethoxazole-Trimethoprim (TMP-SMX) vs UTI, P. jirovecii prophylaxis in AIDS

2.

3. 4.

5. 6. 7.

2. Sulfadiazine+Pyrimethamine vs Toxoplasma 3. Sulfadoxin+Pyrimethamine vs Malaria 2. Trimethoprim, Pyrimethamine (DHFXdihydrofolate reductase>THF like Methotrexate) vs. URIs (S. pneumo), UTIs, GITIs, and Pseudomonas by blocking topoII (DNA gyrase) and IV: Fluoroquinolones (AE: cartilage/tendon rupture, incr QT, G6PD hemolysis) vs. Mycobacterum, prophylaxis for Hib and N.men by blocking DNAdRNAp = no transcription: Rifampin Protein synthesis inhibitors: Quinn get in Line and take 50MCs to 30ST: 1. Quinn, Line 50MCs = Quin-Dalfo, Linezolid, Macrolides, Chloramphenicol/Clindamycin block 50S 1. Quin-Dalfo (streptogramins): Quinupristin prevents elongation, Dalfopristin changes 50S conformation for better Quin-binding 2. Linezolid: binds 50S P-site and blocks 70S assembly Tx: Quin-Dalfo and Linezolid is good for ALL RESISTANT BACTERIA: VRE, MRSA 3. MACrolidEs (ACEmycin = Azithro, Clarithro, Erythromycin): MacroLIDEs prevent sLIDing of mRNA = inhibit translocation by binding to 23S of 50S 1. Tx: PUS - atypical Pneumonia, URIs, STDs 2. AE: PROLONG QT, acute cholestatic hepatitis, incr serum concentration of warfarin 3. resistance via METHYLATION OF drug binding site on 50S rRNA Note: Azithromycin = AIDS MAC prophylaxis Chloramphenicol: ChLorAMPS Peptidyltransferase - prevents peptide bond formation; Tx: meningitis (H. flu, N. men, Strep. pneumo); AE: aplastic anemia and gray baby; resistance via ACETYLATION 5. Clindamycin: also blocks peptide bond formation at 50S; vs. ANAEROBES (B. fragilis, C. perfringens) like Metronidazole; AE: Pseudomembranous colitis like Ampicillin 30ST = Streptomycin (aminoglycosides), Tetracycline block 30S 1. Amina didnt hear the GNATS because she was busy reading: Aminoglycosides (GNATS = Genta, Neo, Amikacin, Tobra, and Stretomycins) cause ototoxicity (and nephrotox) and act by binding to 16S and causing mRNA misreading; vs. g- rods; REQUIRES O2 UPTAKE so ineffective against anaerobes; resistance via modification of 30S (acetylation, etc) 2. Tetracyclines block TRNA from binding A-site and discolors Teeth/bones 1. caTion-chelator, do NOT take with antacids, milk, or iron-containing prep! 2. AE: photosensitivity (SAT for photo - sulfonamides, amiodarone, TETRACYCLINE) 3. vs. VACUUM TH BedRoom - Vibrio, acne, Chlamydia, ureaplasma, urealyticum, Mycoplasma pneumonia, Tularemia, H. pylori, Borrelia, Rickettsia 4. resistance via decr uptake, incr export 4. NOTE: DEMECLOCYCLINE = DIURETIC = ADH ANTAGONIST (Tx: SIADH)

2.

Ampicillin and Amoxicillin are Anti-G+ Aminopenicillins that HELPS kill Pseudomonas with Sulbactam/Clavulanic acid (beta lactamase inhibitor):

H = Haemophilus E = E. coli L = Listeria P = Proteus S = Salmonella

Note: Ampicillin = intrapartum injection, GBS prophylaxis TCP Takes Care of Pseudomonas:

Ticarcillin Carbenicillin Piperacillin

Cephalosporins:

1st generation (cefa): G+ + PEcK: Proteus, E.coli, Klebsiella 2nd generation (fur fox fotetan): G+ + HEN-PEcKS: Haemophilus, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella, Serratia o Fur cap - Cefuroxime for Community Acquired Pneumonia o Linda Brought a Fragile Fox foTito - Clindamycin, B. fragilis, Cefuroxime, Cefotetan 3rd generation (trix tax taz): Meningitis, Gonorrhea, Typhoid fever (Salmonella) o Ceftriaxone = #1 o CefTAZidime is for Pseudomonas like TAZobactam+Piperacillin (but causes neutropenia) 4th generation (Cefepime) = G+ + pseudomonas

Metronidazole: forms toxic metabolite that damages DNA; Tx: GET GAP on the METRO

G = Giardia E = Entamoeba histolytica (liver abscess) T = Trichomonas G = Gardnerella A = Anaerobes (B. fragilis, C. difficile) P = H. Pylori (+ bismuth + amoxicillin/tetracycline)

Anti-TB: INH-SPIRE: AE: hepatotoxic

Antifungal:

INH = Isoniazid (inactivates mycolic acid synthesis enzymes enoyl-acyl carrier protein reductase (InhA overexpression = resistance) and betaketoacylACPsynthase (KasA); KatG gene encodes catalase peroxidase that activates INH); solo-TB prophylaxis; AE: hepatotoxicity, neurotoxicity (prevented by B6), drug-induced lupus (anti-histone Ab) S = Streptomycin (aminoglycoside vs 30S mRNA reading) P = Pyrazinamide - active in acidic pH, inhibits mycobacterial growth in M0; AE: hyperuricemia/gout (I = INH) R = Rifampin - inhibits DNA-dRNAp = no transcription (rapid resistance) AND blocks packaging and assembly of viruses; induces cyp450; prophylaxis for N. men and Hib; AE: red secretions, stop therapy with purpura, bone marrow suppression E = Ethambutol - AE: optic neuropathy (red green colorblindness)

Amphotericin B: o AmphoTEARicin TEARS holes in fungal membrane (binds ergosterol and forms pores) o AmphoTERRible: AE: fever/chills, hypotension, nephrotox, arrhythmia, anemia, IV phlebitis

Antiviral:

ARM2 cure A FLU = Amantadine Rimantidine block M2 protein (viral uncoating) vs. Influenza A; AE: AtaxiA Herpes = Cyclovirs (virally activated guanosine analogs) + Trifluridine (thymidine analog) CMV = Cids Gang loved seeing Foamy Scarlet = Cidofovir (Cytosine analog + Probenicid to prevent excretion), Ganciclovir (intraocular implant), Fomivirsen (intraocular injection, anti-sense RNA therapy), FOScarnet (unlike ganciclovir, doesnt require thymidine kinase activation; pyroFOSphate analog that directly inhibits DNApol)

HIV therapy:

Protease inhibitors = navirs (AE: GI intolerance, hyperglycemia, lipodystrophy, cyp450 inhibitor) NRTIs: Abe Did Embark on a L-AZy Start o Abacavir o Didanosine o Emtriciabine o Lamivudine o AZT (Zidovudine) o Stavudine NNRTIs: Move to Delaware? Effin Never! o Delavirdine o Efavirenz o Nevirapine FUsion inhibitor = enFUvirtide (gp41 binder)

Interferons: activates NK cells; AE: Neutropenia

IFNalpha - alpha B C > Tx: HBV, HCV IFNbeta - PMS sounds like BMS > Tx: Multiple Sclerosis NOTE**: alpha and beta IFNs decr viral replication and incr antiviral protein synthesis that impairs viral mRNA translation IFNgamma - G in gamma is for cGd > Tx: Chronic Granulomatous Disease (NADPH oxidase deficiency) NOTE**: IFNgamma incr MHCI and II expression, activates M0 > TNFalpha, IL1, IL6

Immunology:

B-cells are always found in (white) Follicles closer to the outside of the LN or spleen VS. T-cells are found in the deeper medulla(LN)/PALS(spleen) Lymph drainage:

rectum above pectinate line = internal iliac umbilicus to legs (inc, superficial genitals and anal canal below pectinate line) = superficial inguinal testes = para-aortic

MHC I and II: Rule of 8s

1*8 = MHCI x CD8 = 8 2*4 = MHCII x CD4 = 8

Natural Killer cells: detects MHCI

Gotta KIL to survive (KIR + KIL = survive) KIR only = release perforins and granzymes > apoptosis

Antibody cleavage:

Papain cleaves Ab into 3 pieces: Pa Pa In (evenly splits into 3) Protease cleaves Ab into 2 pieces: Prot Ease (evenly splits into 2; complement can still bind hinge)

Cytokines: Hot T-Bone stEAk

IL1 (and IL6): hot = fever; secreted by M0 IL2: T = T-cell proliferation; secreted by Th1 IL3: Bone = Bone marrow stimulation (acts like GM-CSF); secreted by T cells IL4: E = IgE (and IgG) class switching; secreted by Th2 IL5: A = IgA (and eosinophil) production; secreted by Th2

Neutrophil chemotaxis: CILK: C5a, IL8, LTB4, Kallikrein

IL8: 8 looks like multilobed nucleus of neutrophil = PMN chemotaxis LTB4s B also looks like neutrophil multilobed nucleus

Immunosuppression Rx vs. IL2: (IL)2 Pro-Cyclists Secreted Tacks in Response to Serious/Sirius Dax; prevent transplant rejection

vs. production: Cyclosporin (via inhibit calcineurin) vs. secretion: Tacrolimus (via binding FK-protein) vs. response to: Sirolimus (via MTOR) vs. receptor: Daclizumab

**NOTE: MCC SCID = defective IL2 receptor > ADA deficiency; decr T > decr B activation: all types of recurrent infections (viral/bacterial/fungal) Rx vs TNF: Tx: Rheumatoid arthritis

vs. TNF: Infliximab vs. TNF receptor: Adalimumab fake TNF receptor: Etanercept

Complement:

C_a for anaphylaxis (histamine release > edema > hypotension, anaphylaxis)

C_b for binding bacteria (opsonizes and forms pores)

low 3 causes 3: C3 deficiency causes HSRIII (immune complex deposit), seen especially in glomerulonephritis; susceptible to S. pneumo and Hib > severe recurrent pyogenic sinus and respiratory tract infections **Remember SHiN: S(trep. pneumo) + Hi(b) = C3 deficiency; N(eisseria) = C5-C9/MAC deficiency Passive immunity: To Be Healed Rapidly - Tetanus Botulism HBV, Rabies/(RSV in premies every winter month) Immune deficiencies:

Brutons agammaglobulinemia = (x-r) Boys with BTK (tyrosine kinase) defect > Blocked B-cell differentiation: recurrent Bacterial infection after 6 months (when moms IgG disappears) b/c no Igs Selective Ig(A) deficiency: milk Allergies, blood product Anaphylaxis, giardiA infections; IgA is missing in mucus so recurrent sinus and lung infections **Note: IgA deficiency also seen in Ataxia-Telangiectasia:defective DNA repair enzymes, sensitive to ionizing radiation, cerebellar atrophy > ataxia, spider angiomas (telangiectasias); assoc. w/ lymphomas and acute leukemias Hyper-IgE/Jobs Syndrome: Im Hyper Excited for my FATEd Job o Hyper Excited = Hyper IgE o F = coarse Facies o A = cold, noninflamed Staph Abcesses o T = retained primary Teeth o E = Eczema o Job = Jobs Chediak-Higashi (a-r): Grandpa Al couldnt eat Eastern food with his fingers. o Grandpa = Gram positive cocci infections: Staph and Strep o Al = partial albinism o couldnt eat = defective microtubules = defective phagocytosis and lysosomal fusion o Eastern = Higashi (higashi means East in Japanese) o with his fingers = peripheral neuropathy

Pathology: Proto-oncogenes: tumor promoters; damage one allele > gain of function (VS. tumor suppressors need to damage both alleles to lose function) Mikes sis returned with her2new breasts that she was able to-grow-faster b/c of herbs.

Mike = myc: C-myc - Burkitts, N-myc - adrenal Neuroblastoma, L-myc - small cell lung CA sis: astrocytoma, osteosarcoma returned = ret: MENII her2new = Her2/neu: breast cancer was = ras: colon, bladder, lung, pancreas, renal CA able = abl: CML, ALL (ALL able CaMeLs are from Philadelphia t(9;22)) to-grow-faster = TGF: astrocytoma, HCC b/c = bcl2: follicular lymphoma herbs = ERB-B1,2: ERB-B1 - lung squamous cell CA, ERB-B2 - breast, ovarian, gastric CA

Psammoma bodies: concentric Ca2+ spheres; looks like thumbprint; PSaMMoma:

P = papillary thyroid tumor S = serous cystadenocarcinoma of ovary M = mesothelioma M = meningioma

ESR (marker of inflammation): inflammatory product fibrinogen coats RBC causing aggregation > weight pulls RBC down = fall at faster rate in test tube

incr/faster ESR = inflammation: infection, cancer, pregnancy, SLE decr/slower ESR = de-prESsed Heart is Sick from Too Much Blood. o Heart = CHF o Sick = Sickle Cell o Too Much Blood = Polycythemia

Pharmacology: Kompetitive inhibitors incr Km, decrease affinity/potency (amount of drug needed for effect); sigmoid effect curve shifts right; Lineweaver-Burke lines cross at Y-axis (VS non-competitive inhibitors decr Vm, decrease efficacy (maximal effect of drug); sigmoid effect curves vertical maximum effect is reduced; Lineweaver-Burke lines join at X-axis) Zero-order elimination: constant amount of drug eliminated per unit time = PEA - Phenytoin, Ethanol, Aspirin Urine pH and drug elimination: medicine gets trapped in opposite urine pH:

acid (phenobarb, MTX, TCA, aspirin) trapped in basic bicarbonate **Note: Acetazolamide alkalinizes urine by getting rid of bicarbonate; Tx: cysteine stones and altitude sickness (hyperventilation > respiratory alkalosis) base (amphetamine) trapped in acidic ammonium chloride

Phase I vs Phase II metabolism: 1 red ox went 2 conjugate polar bears.

Phase 1: cyp450 red-ox (+ hydrolysis); geriatrics lose phase 1 first Phase 2: conjugation (acetylation, glucuronidation, sulfation) > yields very polar renally excreted inactive metabolites

Therapeutic index: TILED with TI= LD#/ED# and the #s adding up to 100; safer drugs have higher TIs G-protein-linked 2nd messenger:

Gs = adenylyl cyclase > ATP-to-cAMP > PKA > cascade Gi = inhibit adenylyl cyclase > decr cAMP > decr PKA Gq = phospholipase C > lipids-to-PIP2 > IP3 incr intracellular Ca2+, DAG stim PKC > cascade

Kiss and Kick til youre Sick of Sex QISS QIQ SIQ SQS

Gq = alpha 1: SM contraction, mydriasis; incr Systolic and Diastolic BP Gi = alpha 2: decr SNS, decr insulin Gs = beta 1: incr heart rate and contractility, incr renin, incr lipolysis Gs = beta 2: decr Diastolic BP, vaso/bronchodilation, incr heart rate, contractility, incr lipolysis, incr insulin release (think Beta2 stimulates Beta islet cells of pancreas), decr uterine tone Gq = M1: CNS, enteric nervous system Gi = M2: decr HR, decr atrial contractility Gq = M3: incr secretions, peristalsis, miosis, accommodation (ciliary muscle contraction) Gs = D1: renal perfusion (renal artery dilation) Gi = D2: brain neurotransmitter Gq = H1: pruritus/pain, incr nasal/bronchial mucus, contract bronchioles Gs = H2: incr gastric acid secretion (inhibited by -idines) Gq = V1: incr vascular SM contraction Gs = V2: incr H2O reabsorption in kidneys CD (ADH action)

Signaling pathways:

cAMP (Gs, Gi): FLAT CHAMP + calcitonin + glucagon o F = FSH o L = LH o A = ACTH o T = TSH o C = CRH o H = hCG o A = ADH (V2) o M = MSH o P = PTH

o o

calcitonin glucagon (incr cAMP > activates PKA > incr F16BPase > gluconeogenesis RLS)

IP3 (Gq): hIP3othalamic GGOAT o GHRH o GnRH o oxytocin o ADH (V1) o TRH cGMP: vasodilators o ANP o NO (NO venodilates decreasing preload VS beta-blockers arteriodilate and reduce afterload) tyrosine kinase: the TyK Grows In Milk o GH o IGF-1 o FGF o PDGF o Insulin o Prolactin steroid receptor: cytoplasmic (except thyroid hormone = intranuclear) o (Adrenal cortex:) Aldosterone, Glucocorticoid, Testosterone, Estrogen o Progesterone o Vitamin D o T4/T3 (intranuclear receptor)

Glaucoma drugs: AABBCDF

AA = Alpha Agonist: vasoconstriction > decr aq humor synthesis (not for closed angle glaucoma) BB = Beta Blocker (Timolol): decr aq humor secretion C = Cholinomimetic (Carbachol, Pilocarpine; Phys is for the Eyes Physostigmine, Echothiophate): incr outflow (contract ciliary m uscle and open trabecular meshwork into canal of Schlemm) D = Diuretic: Acetazolamide (carbonic anhydrase inhibitor), Mannitol: decr aq humor secretion F = PGF2alpha (Latanoprost): incr uveoscleral outflow; AE: dyes irises brown

Cholinomimetics:

Bethanechol: Give Beth-ann-a-call if you want your PNS stimulated: Tx: post-op neurogenic ileus and urinary retention Anticholinesterases = -stigmines + Edrophonium + Echothiophate

Organophosphate poisoning: DUMBBELSS: Tx: Atropine, Pralidoxime

Diarrhea Urination Miosis Bradycardia Bronchospasm Excitation of skeletal muscle and CNS Lacrimation Salivation Sweating

Atropine poisoning: what would happen if you got lost in the desert: Hot, Dry, Red, Blind (cycloplegia), Mad (delirium), urinary retention(/constipation) Hexamethonium: Put a Hex on reFLEX bradycardia - Hexamethonium prevents NE reflex bradycardia by blocking all Nicotinic receptors (ganglion blocker inhibits Na/K ligand-gated channels) ACh receptors:

Nicotinic = Na/K ligand-gated channels (ANS and NMJ) (Hexamethonium/Mecamylamine blocks these)

Muscarinic = G-coupled receptors; M1,2,3=QIQ (Atropine blocks these)

Specific antidontes:

DeFERoxamine Txs Fe (iron) Children Suck on Lead pencils: Succimer Txs Lead poisoning in children (Tx is CaEDTA in adults) DiMERcaprol Txs MERcury, arsenic, gold Copper Penny: Copper, arsenic, gold Tx w/ PENIcillamine NITRoprusside turns into Cyanide which is Txd w/ NITRite, hydroxocobalamin, and thiosulfate METHylene blue and VitC Txs METHemoglobin ETHANOL Txs mETHANOL poisoning Heparins H looks like a Proton: PROTamine Txs Heparin toxicity

Drug reactions:

TCAs 3 Cs: Cardiotoxicity, Convulsions, Coma Cutaneous flushing: VANC = Vancomycin, Adenosine, Niacin, Ca2+ channel blockers Dilated cardiomyopathy = Doxorubicin and Daunorubicin Torsades de Pointes: The Method to get 31Awesome QTs is to wear a Halo and Risper that you bought a Macro-PIe from Quinn. o Method = Methadone o 31Awesome = Class III, Class Ia antiarrhythmics o Halo = haloperidol o Risper = risperidone o Macro = macrolide o PI = HIV protease inhibitors o Quinn = Chloroquine/Mefloquine Aplastic anemia: Chlora SAID Ptuey to Meth: o Chlora = Chloramphenical o SAID = NSAID o PTUey = PTU (antithyroid) o Meth = Methimazole (antithryoid) Hemolysis in G6PD: Prima had to take Aspirin after INHaling her I.B.Professor Dapsones Sulfurous Fava Bean Nitrofarts o Primaquine o Aspirin o INH o Ibuprofen o Dapsone o Sulfonamides o Fava bean o Nitrofurantoin Pseudomembranous colitis makes you want to ClAmp your ass: CLindamycin, AMPicillin Photosensitivity: SAT for a Photo: o S = Sulfonamides o A = Amiodarone o T = Tetracyclines Stevens-Johnson rash: Seizures, Sulfas, and Cillins + Allopurinol o Seizure drugs: ethosuximide, lamotrigine, carbamazepine, phenobarbital, phenytoin o Sulfa drugs o Penicillin o Allopurinol SLE-like syndrome: SHIPP o Sulfonamides o Hydralazine (Hydras neck Loops (Lupus) around in circles) o INH o Phenytoin o Procainamide Disulfiram-like reaction: Drunk Ceph said he was Pro-Car (okay to drive) at Night, but to avoid a Gruesome accident, Chlora made him Suffer the Metro. o Ceph = Cephalosporin o Procar = Procarbazine o Night = Nitrofurantoin

o o o o

Gruesome = Griseofulvin Chlora = Chloramphenicol Suffer = Sulfonylureas Metro = Metronidazole

Ototoxicity/Nephrotoxicity: Mice use Platinum earring Loops to crawl into your Ear and make you deaf o Mice = -mycins = aminoglycosides and vancomycin o Platinum = Cisplatin o Loops = Loop diuretics p450 interactions: o p450 inducers: Queen Barbs riFamily induced Saint John to eat a Pheny-looking Greasy Carb

Queen = Quinidine Barbara = Barbiturate riFamily = Rifampin induced Saint John = Saint Johns Wort Pheny-looking = Phenytoin (AE: gingival hyperplasia) Greasy = Griseofulvin Carb = Carbamazepine See reference:

p450 inhibitors: Without a Key, Kim was inhibited from PIES and Juice

Key = Ketoconazole Kim = Cimetidine inhibited PI = HIV Protease Inhibitors E = Erythromycin S = Sulfonamides Juice = grapefruit juice

See reference:

Toxicity bear: Cumulatively Toxic Drugs and their Rescues o Asparagine: neurotoxicity o Cisplatin: ototoxic/nephrotoxic; Tx: Amifostine o Vincristine/Vinblastine: Christ my nerves, Blast my bones - Vincristine = peripheral neuropathy, Vinblastine = myelosuppression o Bleomycin: pulmonary fibrosis o Doxorubicin: cardiotoxic; Tx; Dexrozoxane (for cardiotoxicity), Dimethyl-sulphoxide (for ROS ulcers) o Cyclophosphamide: Acrolein = nephro/bladder toxic (Tx: Mesna); also SIADH effects (Tx: Demeclocycline) o Methotrexate: nephrotoxic (Tx: Leucovorin), myelosuppression (Tx; Filgrastim) o See reference:

Cardiovascular: Contractility decreases with: ABBCCC:

A = Acidosis BB = Beta blocker CCC = hyperCO2, CHF, non-DHP Ca2+ channel blockers

Heart murmurs:

MR. ASS and MS. ARD = o MR = mitral regurg o AS = aortic stenosis o S = systolic murmurs o and o MS = mitral stenosis o AR = aortic regurg o D = diastolic murmurs holosystolic = all regurgs + VSD murmurs that increase with breathing: o rIght murmurs increase with Inspiration o lEft murmurs increase with Expiration

Wolf = Lone Canis - Wolff-Parkinson-White is treated with amiodaRONE and ProCAINamide AV blocks: First, a girl stays out til 12 even though her curfew is 10. Then, the teenager stays out later and later, til her mom throws a fit. Afterwards, despite the teenager being good, the mom throws random fits probably because of menopause. Finally, the young woman is old enough to whatever she wants separately from her parents.

1st degree: increased PR 2nd degree: o Type 1 Wenckebach: incr PR until QRS drop o Type 2: random QRS drop 3rd degree: PR and QRS = independent rates; seen in Lyme disease

DiGeorge Tets: TETralogy of Fallow + TETany from hypocalcemia (lack of parathyroids) (also, truncus arteriosus) PGA open: PGE kEEps PDA open (PGE1 analogs: Alprostadil, Misoprostol); close with Indomethacin Evolution of MI: 4 and death are both pronounced shi in Japanese

Initially: nothing 4 hours-4days later: PMNs, coagulative necrosis, risk of arrhythmia (esp. V-fib) 4-10 days later: M0s thinned walls > increased risk of rupture and tamponade >10 days: risk for ventricular aneurysm (bulging scar because fibrosis made it lose its ability to contract) <ventricular remodeling can be prevented with ACE-Is

Bacterial endocarditis: FROM JANE:

Fever Roth spots: round retinal white spots surrounded by hemorrhage Oslers nodes: tender raised red lesions on fingers and toe pads Murmur (new) Janeway lesions: non-tender small red lesions on palms and soles Anemia Nail-bed (splinter) hemorrhage Emboli

IVDA = right-sided bacterial endocarditis: dont TRI drugs (tricuspid valve) SLE causes LSE (Libman Sacks endocarditis with warty sterile vegetations on both sides of valve, assoc. w/ mitral regurg) Rheumatic heart disease of S. pyogenes (beta-hemolytic, bacitracin-sensitive Strep): AAAAAA

group A Strep autoimmune (Ab to antiphagocytic M protein > MVP > Mitral Stenosis), fever Aschoff bodies (granulomas with giant cells) = subcutaneous nodules

Anitschkow cells (activated histiocytes) elevated ASO titers and ESR migratorypolyArthritis

+ Erythema martginatum, Syndenhams/St. Vitus chorea (of face, tongue, and upper limb) ACE-inhibitors are ACEs at controlling HTN:

essential hypertension HTN+CHF (decreases both preload and afterload) HTN+DM (protective against Diabetic nephropathy)

Antihypertensive therapy: ABCD:

ACE-I/ARBs Beta blockers Calcium channel blockers Diuretics (LOOps LOOse Calcium, Thiazides retain calcium)

Aden Diaz is Mine OK?: Adenoxine, Diazoxide and Minoxidil Open K+ channels Antiarrhythmics: No Bad Boy Keeps Clean

Type I: Na+ blocker (incr QT) Type II: Beta blocker (incr PR); Tx OD w/ Glucagon Type III: K+ blocker (incr QT) Type IV: Ca2+ blocker (incr PR); Tx coronary and cerebral vasospasms

Type I antiarrhythmics:

Ia: The Queen Werewolf Disappeared Quinidine, Procainamide, Disopyramide (incr AP) Ib: To Funny Little Mexico Tocainide, Phenytoin, Lidocaine, Mexiletine (decr AP) Ic: Properly Fleeing Endangerment Propafenone, Flecainide, Encainide

Type III: Amiodarone: check PFTs, LFTs, and TFTs

pulmonary fibrosis hepatotoxicity hypo/hyperthyroidism (amiodarone = mostly iodine, resembles thyroid hormone) + photodermatitis (SAT for a photo)

Endocrine: Adrenal cortex: GFR: The deeper you go, the sweeter it gets.

salt: zona Glomerulosa: aldosterone sugar: zona Fasciculata: cortisol sex: zona Reticularis: androgens

Adenohypophysis = Anterior pituitary (RAthkes pouch of ectoderm): FLAT PEG

FSH LH

ACTH TSH Prolactin endorphins (share POMC origin with ACTH and MSH) GH

Basophilic = B-FLAT: Basophilic-FSH, LH, ACTH, TSH (VS Acidophils-Prolactin, GH) Neurohypophysis = Posterior pituitary (Neural tube of ectoderm): secretes hypothalamic substances: A Pair of Ox were Supra Dehydrated

Paraventricular nucleus - Oxytocin Supraoptic nucleus - Vasopressin (ADH)

Adrenal steroids: In an enzyme deficiency, if the first digit is a 1, then the patient will be hypertensive. If the second digit is a 1, then the patient will look male.

17alpha hydroxylase deficiency: HTN, feminine 21 hydroxylase deficiency (MC): hypotension, masculine 11 beta hydroxylase deficiency: HTN, masculine

PTH = phosphate trashing hormone (note: decreased free serum Mg2+, decreases PTH secretion; common causes of decr Mg2+ = alcohol, aminoglycosides, diarrhea, diuretics) Calcitonin = from parafollicular C cells of thyroid = neural Crest derivative, secreted in medullary thyroid Cancer (MENII) (Signaling pathway mnemonics were covered earlier) Thyroid hormone functions: T3 = 5Bs

Brain (CNS) maturation (defect = mental retardation seen in Cretinism) Bone growth (synergism with GH; defect = Cretinism) Beta1 adrenergic effects (Thyroid Storm: incr HR, contractility > arrhythmia; Tx with propanolol or PTU (OK in pregnant)) incr BMR incr Blood sugar: glycogenolysis, gluconeogenesis, lipolysis

Pheochromocytoma (PCC): Rule of 10s

10% malignant 10% bilateral 10% extra-adrenal 10% calcify 10% kids 10% familial

Neuroblastoma (MCC adrenal medulla tumor in children) = N-myc oncogene, stain = Neurofilaments, tumor marker = Bombesin

see Homer-Wright pseudorosettes and incr HVA (Dopamine derivative) in urine scenario: ~2yo with retroperitoneal ab mass presents with HTN hypotonia, myoclonus, and non-rhythmic conjugate eye movements (opsoclonus-myoclonus) mass may invade into an intervertebral epidural space and look like a dumbbell

HypOthyroidism = cOld intolerance; HypErthyroidism = hEat intolerance CHIMPANZEES cause Hypercalcemia:

Calcium ingestion (incr antacids > milk-alkali syndrome)

Hyperparathyroid/Hyperthyroid Iatrogenic: Thiazides Multiple myeloma Pagets disease (when patients are immobilized, normally normocalcemic) Addisons disease Neoplasms (e.g., breast cancer = osteolytic) Zollinger-Ellison syndrome (pancreatic tumor > incr gastrin; associated with MENI (parathyroid tumor) Excess vitamin D Excess vitamin A (incr bone resorption > incr Ca2+) Sarcoidosis (or granulomatous disease)

Hyperparathyroidism:

Primary: Osteitis fibrosa cystica = stones, bones, and groans = kidney stones, brown bone tumors, w eakness and constipation; incr cAMP in urine VS Secondary: Renal osteodystrophy = renal disease > decr Vit D > decr Ca2+ > incr PTH > bone lesions

Hypocalcemia signs:

C = Chvostek sign = Cheek tapping > facial muscle Contraction T = Trosseaus sign = Tight BP cuff > hand Tetany (spasm)

Dexamethasone vs Demeclocycline vs Desmopressin:

Dexamethasone = steroid to Dx ACTH disease/syndrome DemecloCYCLine = tetracycline ADH antagonist vs CYCLophosphamide-induced SIADH; Tx: SIADH DesmoPRESSIN = vasoPRESSIN (ADH) analog; Tx: central Diabetes insipidus (Note: nephrogenic DI is treated by hydrochlorothiazide (Ca2+ sparing diuretic), indomethacin (decr renal blood flow), or amiloride (K+ sparing aldosterone receptor antagonist diuretic that closes Na+ channels that also reabsorbs Li to Tx Li-induced DI)

Multiple endocrine neoplasias (MEN): (A-D)

MENI (Wermers): 3Ps o pancreatic - ~Zollinger-Ellison gastrinoma - peptic ulcers o parathyroid - incr PTH - hypercalcemia o pituitary - ~prolactin or GH - amenorrhea, lactation MENIIa (Sipples): 2Ps o parathyroid - incr PTH - hypercalcemia o PCC - incr catecholamines (Epi/Nor), urine VMA and Metanephrine o medullary thyroid (parafollicular C) - polygonal, incr calcitonin - hypocalcemia MENIIb: 1P o PCC - incr catecholamines, urine VMA/metanephrine o medullary thyroid (parafollicular C) - incr calcitonin - hypocalcemia o Marfans habitus + oral/intestinal mucosal neuromas Note: MENIIs are associated with ret oncogene Also, the II in MENII stands for the 2Cs in PCC

Diabetic drugs:

Metformin Glitters in Sunny Gliptin Tides o Metformin = incr glucose uptake in muscle and fat via GLUT4 (aka incr insulin sensitivity in peripheral tissue) and decr liver glucose production via incr AMPK and decr PEPCK (OAAtoPEP) and decr G6Pase (G6PtoGlucose) production o -Glitazones = incr insulin sensitivity via PPARgamma/adiponectin o Sulfonamides = incr pancreatic insulin production via blocking ATP-dep. K+ efflux o -Gliptins, -Tides = incr insulin, decr glucagon, decr gastric motility (incr satiety) o + Acarbose/Miglitol = decr starch hydrolysis and glucose GI uptake

Diabetes drugs mechanisms of action:

PPARazzi camera flashes GLITA - PPARgamma -Glitazones GULP TIDES - GLP1 -Tides Dr.PPer and Lipton - DPP4 inhibitor -Gliptins Acarbose - Alpha glucosidase

Remember:

insulin > decreases cAMP > decreases PKA > dephosphorylated FBPase2 = PFK2 > F6P to F26BP > F26BP stimulates PFK1 > incr F6P to F16BP (glycolysis) glucose > decreases cAMP > decreases CAP-cAMP binding of lac operon = RNA polymerase cant bind to promoter

Gastrointestinal: Retroperitoneal structures: I ASK DR. PC

Primary retroperitoneal (never pushed into sac): o IVC o Ab aorta o Suprarenal glands o Kidneys/Ureters Secondary retroperitoneal (pushed into sac, but escaped): o Duodenum (2, 3, 4) o Rectum o Pancreas (head, body) o Colon (ascending, descending)

OR SAD PUCKER = suprarenal, abdominal aorta, duodenum, pancreas, ureter, colon, kidney, esophagus, rectum Digestive tract histology: Brunch DIP:

Brunners (submucosal, alkaline mucus secreting) glands = Duodenum Ileum = Peyers Patches (M cells take up antigen; also location of IgA -secreting plasma cells) Note: Shigella is taken up by the M-cells of Peyers Patches; viruses like Adenovirus may invade Peyers Patch es and cause intussusception; Sabin (live Polio vaccine) increases IgA immunity

Enteric nerve plexuses: AUerbach is on the AUtside, MeiSSners is SSubmucosal

Auerbachs = Myenteric = coordinates Motility by being wedged between the inner/circular and outer/longitudinal muscles Meissners = Submucosal = regulates Secretions, blood flow, and absorption between mucosa and inner/circular muscles

Defect in Auerbachs causes Achalasia Lack of both Auerbach and Meissners due to failure of neural crest cell migration causes Hirschsprungs Congenital Megacolon, assoc. with Down Syndrome (see failure to pass meconium, like in Cystic Fibrosis) Portosystemic anastomoses: The mnemonic is from Systemic (IVC) to Portal (Celiac, SMV, IMV) veins: MI Superiors an Ass. He makes me feel Inferior about my Superficial appearance by poking near my Belly-button so I Eat Less.

Rectal anastomoses: (X=hemorrhoids) MI Superior is an Ass: Systemic: Middle and Inferior Rectal to Portal: Superior Rectal Umbilical anastomoses: (X=caput medusae) Inferior about my Superficial appearance by poking near my Belly-button: Systemic: Inferior, Superficial Epigastric to Portal: Paraumbilical Esophageal anastomoses: (X=esophageal varices) Eat Less: (X = esophageal varices) Systemic: Esophageal (azygos)

to Portal: Left Gastric Liver anatomy: 1ABC

1ABC:

o o o

Zone 1 = Apical surface of hepatocytes face Bile Canaliculi = periportal zone Also, when you think of ABC, you should think of Hepatitis A, B, C Zone 1 = first affected by viral hepatitis because closest to hepatic artery (Remember: Portal triad = bile duct, hepatic artery, and portal vein)

The 3rd letter in the alphabet = C: o Zone 3 = Centrilobular (periCentral vein) = where blood drains into the hepatic vein o because its so far from the hepatic artery, its the first place to suffer from ischemia o also, since blood pools in veins, you can think of drugs/poisons pooling there, too Bottom line: Zone 1 = susceptible to viruses, Zone 3 = susceptible to drugs/ischemia

Femoral region: NAVEL with the Venous near the Penis

Lateral to medial: Nerve, Artery, Vein, Empty space, (deep inguinal) Lymphatics/Lacunar ligament Note: femoral sheath does not contain femoral nerve

Inguinal canal: INternal (deep) inguinal ring = INdirect hernia that may go INto the scrotum = lateral to inferior epigastric vessels VS. an alien Directly bursting from your stomach = direct hernia = protrudes from abdominal wall medial to inferior epigastric vessels:

or MDs dont LIe: Medial = Direct, Lateral = Indirect Fem-Fem: femoral hernias occur more often in females (and is the leading cause of bowel incarceration) GI secretory products:

IF you PARTY too hard, youll vomit out a lot of GASTRIC ACID.: Parietal cells secrete IF (intrinsic factor) and HCl (gastric acid) Pep-pep to the Chief: Chief cells make Pepsin

Vitamin/Mineral absorption:


Bilirubin:

Duodenum: FED = Fe (iron) in Duodenum Jejunum: The Jester is a Fat Fool = Jejunum absorbs most Fats and Folate Ileum: The ileum is the last part of the small intestine; its where you say Bye Bye to the SI: Byle acid, B12/IF is reabsorbed in the Ileum

Rules of thumb: o The two-named diseases dont go together o The one named diseases are milder INdirect = UNconjugated = water INsoluble: Crigler-Najjar, Gilbert = KING KONG > CING CUNG > Criggler-Indirect/Unconjugated-Najjar-Gilbert You get Crigler-Najjar/Gilberts when youre unable to conjugate bilirubin into a water -soluble/excretable form ~ Glucuronyl transferase deficiency Direct = conjugated = Water soluble: Dubin-Johnson, Rotors = Dubin-Johnson called Rotor-rooter to fix his WaterPipes. You get direct bilirubinemia when theres a problem with bile Pipes/excretion (E.G., biliary tree obstruction) Note: Dubin-Johnson is worse than Rotors in that the liver is pigmented black

Achalasia: AABBCC

Achalasia loss of Auerbachs myenteric plexus Birds beak on Barium swallow associated with Chagas and CREST

Boerhaave syndrome = Been-Heaving; transmural complication of Mallory-Weiss BARRetts esophagus = Becomes Adenocarcinoma, Results from Reflux Esophageal cancer risk factors: ABCDEFGH

Alcohol, Achalasia Barretts esophagus Cigarettes Diverticuli (e.g., Zenkers) Esophageal web (e.g., Plummer-Vinson), Esophagitis Familial GERD Hot dogs (nitrosamines)

Esophageal cancer epidemiology and locations:

Gastritis:

Squamous cell = Spread out worldwide (most prevalent worldwide); upper 2/3s (where striated muscle can be found) Adenocarcinoma = most prevalent in America (lower 1/3, location of pure smooth muscle)

Acute gastritis (erosive): o Burned by Curling iron: Curlings ulcer = stress ulcer from burns: decr plasma volume > sloughing of gastric mucosa o Cushion the brain: Cushings ulcer = stress ulcer from head injury: incr ICP > incr vagal stimulation > incr ACh > incr H+) Chronic gastritis (non-erosive): AB-pairing o Type A (fundus/Body) = Autoimmune/Anemia: AutoAb to parietal cells, pernicious anemia (Ab to IF), achlorhydria o Type B (Antrum) = Bacterial: H.pylori infection (duodenal > stomach ulcer), increased risk of MALT lymphoma

Peptic ulcer disease:

Gastric ulcer pain = Greater with food Duodenal ulcer pain = Decreases with food (will see hypertrophy of Brunners glands and clean punched out margins un like carcinoma raised/irregular margins)

Inflammatory bowel disease (IBD): Crohns vs Ulcerative Colitis

Crohns: A Creepy Fat old Crone (Granny) went Skipping on Cobblestones while pumping her Arthritic Fist in the air. o Creepy Fat = Creeping fat o Crone = Crohns disease o (Granny) non-caseating Granulomas o Skipping = transmural Skip lesions o Cobblestone = Cobblestone mucosa o Arthritic = Migratory polyarthritis o Fist = Fistulas o Gum to Bum lesions and extraintestinal manifestations (systemic) like erythema nodosum (~shins), ankylosing spondylitis, and uveitis o Note: this is disordered response to intestinal bacteria Ulcerative colitis: If you have a Lead Pipe jammed up your Rectum, youll get Bloody Diarrhea. o Lead Pipe = loss of haustra leads to lead pipe appearance on imaging o Rectum = UC always involves the rectal mucosa/submucosa and procedes continuously up unlike Crohns which tends to spare the rectum o Bloody diarrhea (another trait not shared with Crohns) o Note: this is autoimmune o UC is also associated with friable pseudopolyps, pyoderma gangrenosum, and primary sclerosing cholangitis

Meckels diverticulum: Rule of 2s

2 inches long 2 feet from ileocecal valve 2% of population 2yo (or younger) 2 types of ectopic epithelia: gastric or pancreatic

Colonic polyps: VILLous = VILLainOUS because villous polyps are more likely to be malignant (villous > tubulovillous > tubulous) Colorectal cancer (CRC):

Familial adenomatous polyposis (FAP): polyposis = thousands of polyps; FAPCancer involves APC gene; always involves rectum VS. HNPCC/Lynch which doesnt have many polyps and involves the PROXIMAL colon Gardners syndrome = Gardeners Grow all kinds of things: Gardners = FAP + osteomas + lipomas/soft tissue tumors + retinal hyperplasia Turcots syndrome: TURcot = TURban; FAP + malignant CNS tumor (medulloblastoma)

Presentation of CRC: Think of the colon as a funnel that shrinks towards the anus (and also that visceral nerves dont have as many localized pain receptors as the anus):

distal colon (left side, near anus) = obstruction, sharp colicky pain, hematochezia proximal colon (right side) = iron deficiency anemia, dull pain, fatigue

CRC: Apple core lesion on barium enema x-ray, CEA tumor marker Molecular pathogenesis of CRC: alphabetical order lose APC (decreased intercellular Adhesion) then mutate kRAS (unregulated signal transduction MAPK) then lose p53 (no apoptosis) Wilsons disease (hepatolenticular degeneration): a-r inadequate copper excretion, treated with penicillamine (copper penny): ABCDEF

Asterixis, Ataxia, Anemia (hemolytic) Basal ganglia degeneration (Parkinsonism) decr Ceruloplasmin, Cirrhosis, Corneal deposits, Cancer (HCC) Dementia

Encephalopathy Fanconis Syndrome: defective PCT reabsorption

Gallstones (cholelithiasis): Risk factors = 4Fs:

Fat Fertile Female Forty

Acute pancreatitis causes: GET SMASHED > DIC, ARDS

Gallstones Ethanol Trauma Steroids Mumps Autoimmune disease Scorpion Sting Hypercalcemia, Hyperlipidemia ERCP Drugs (E.G., Sulfa drugs)

Antacid adverse effects:

Al = AluMINIMUM amount of feces: constipation Mg = Must Go to the bathroom: diarrhea