Path

Module 1 Images

Renal artery stenosis ATROPHY!

ATROPHY (general deni3ons):
E3ology: workload, blood supply (stenosis/atherosclerosis), innervaEon, loss of endocrine sEmulaEon
& aging
Pathogenesis: decreased protein synthesis/increased protein degradaEon

Decrease in organ size due to decrease in cell size

RENAL ARTERY STENOSIS RENAL ATROPHY
Most common eEology of unilateral renal artery stenosis is atherosclerosis
Most common presentaEon is asymptomaEc because other kidney compensates
Most common cause of death (COD): JG cells can sense hypo-perfusion to the kidney and release renin
hypertension stroke or MI
NOTE: If it is bilateral atrophy, then there is a back-up of ltrates DECREASED URINE OUTPUT (oliguria)
GFR generalized edema
Inves3ga3on: urinalysis, Doppler Ultrasound for blood ow, BUN, Epigastric/Flank bruit (sounds upon
auscultaEon due to turbulent ow)
Complica3ons: renal failure, hypertensive changes to heart, brain, reEna
OTHER MEDICAL SCENARIOS OF ATROPHY:
Cut ulnar nerve - hand atrophies (denervaEon)
Fracture and have a cast - arm shrinks (disuse)
Alzheimers disease - cerebral hemispheres atrophy
Necrosis of pituitary and dont make TSH - thyroid gland atrophies
DIFFERENTIAL:
Hypoplasia - organ size due to incomplete development

DiGeorge syndrome

Le[ ventricular HYPERTROPHY!

E3ology:

Pathological: hypertension (most common), aorEc stenosis, valvular insuciencies

Phyiological: uterus size during pregnancy (Endometrium is hyperplasia, Myometrium is hypertrophy) or
breasts ge^ng bigger (hypertrophy and hyperplasia)

Pathogenesis: increased protein synthesis, decreased protein degradaEon

Increase in organ size due to increase in cell size!

Presenta3on: asymptoma3c unEl end-organ damage (TIA, stroke)

Inves3ga3on: echocardiogram
Complica3ons:

Angina (chest pain), shortness of breath, syncope (light headedness)

Le[ ventricular failure blood backs up into lungs and paEent cant breathe (complains of shortness of
breath WHEN THEY ARE LAYING FLAT/ orthopnea)
Arrhythmias + thrombus stroke
MOST common cause of right heart failure = le[ heart failure due to conEnuous back up of blood when
both le[ and right heart is failing, you have CONGESTIVE HEART FAILURE
CHF leads to distended jugular vein, peripheral edema, hepatomegaly, ascites (signs of right heart failure)

Note: Permanent cells (heart & CNS) can only undergo hypertrophy, not hyperplasia!

Squamous
M
etaplasia
o
f
B
ronchus
Pathogenesis: geneEc reprogramming of stem cells (always REVERSIBLE!)

SCENARIOS OF METAPLASIA:
A) Chronic smoker: pseudostra3ed ciliated columnar epithelium with goblet cells
simple squamous
Presenta3on: cough & recurrent infecEons (unable to clear mucus b/c losing goblet cells and cilia)
Inves3ga3on: bronchoscopy, biopsy
Complica3ons: squamous cell carcinoma of lung

B) BarreTs Esophagus is a type of intesEnal metaplasia due to acid reux in lower 1/3 of
esophagus (stra3ed squamous non-kera3nized tall columnar with goblet cells)
Presenta3on: waterbrush bad metallic taste in mouth d/t acid
Inves3ga3on: endoscopy, biopsy
Complica3ons: adenocarcinoma (lower 1/3) & squamous cell carcinoma (upper 2/3)

C) Cervical Metaplasia is physiological; simple columnar simple squamous at endocervix

PresentaEon: asymptomaEc
InvesEgaEon: pap smear
ComplicaEons: adenocarcinoma (endocervix) & squamous cell carcinoma (ectocervix)
NOT CAUSED BY HPV (HPV CAUSES DYSPLASIA!)

D) Squamous Metaplasia of the urinary bladder due to S. haematobium; transi3onal

squamous
Presenta3on: blood in the urine (hematuria)
Inves3ga3on: cystoscopy, biopsy
Complica3ons: squamous cell carcinoma

Metaplasia & dysplasia = reversible

Carcinoma = irreversible (broken basement membrane)

Ischemia hypoxia injury!

Reversible injury: vacuolar degenera3on

Microscopic ndings: cellular swelling (hydropic change) & nuclei are s3ll visible (DNA/RNA/ribosomes
stain blue)
Hydropic change is reversible; water goes in due to accumulaEon of Na+ inside cell
Anaerobic lacEc acid buildup pH which denatures proteins
Morphology: cell swelling, distended vacuoles, detachment of ribosomes, plasma membrane blebbing,
swollen mitochondria, myelin gures, nuclear chromaEn clumping, glycogen depleEon & fajy change

Irreversible injury: inability of mitochondria to recover

Morphology: mitochondrial permeability & vacuolizaEon, plasma membrane damage, lysosomal swelling
& rupture, nuclear condensaEon (pyknosis), fragmentaEon (karyorrhexis) & dissoluEon (karyolysis)
Ca2+ accumulates which acEvates phospholipases (membrane damage), proteases (cytoskeleton
damage) & endonucleases (cleave DNA)
Eosinophilia = b/c of denatured cytoplasmic proteins & loss of RNA

Inves3ga3ons:

Under LIGHT microscopy, nuclei are no longer visible is best indicator

Under electron microscopy, mitochondrial damage is the best indicator

Irreversible injury coagulaEve necrosis (structure is sEll intact)

Classic example: gun-shot wound leads to bleeding hypovolemic shock ischemia/

hypoxia reversible injury irreversible injury

HepaEc Steatosis

Steatosis = INTRACELLULAR accumula3on of lipid in hepatocytes

Microvesicular nucleus is central (le[ image)

Macrovesicular nucleus pushed to periphery of cell (right image)

E3ology: alcohol consump3on, metabolic syndrome (obesity, hypertension, diabetes, dyshyperlipidemia),

Reyes syndrome, CO poisoning

Both micro and macrovesicular changes are REVERSIBLE!

CCl4 in liver [ONLY irreversible faTy change due to CCl3 free radicals in SER] lipid peroxida3on

Pathogenesis: alcohol blocks -oxidaEon of FAs in mitochondria, acetyl coA & NADH [ DHAP
G3P backbone] no apolipoproteins being made FAs accumulate in liver
Presenta3on: incidental nding on autopsy/imaging is most common because its asymptoma3c unEl turns
into hepa33s [fever, vomiEng, right upper quadrant pain, jaundice]

Alcoholic hepaEEs: AST > ALT with a raEo of 2 due to alcohol & drugs

Elevated ALT viral cause

Mallory bodies (ubiquinated keraEn intermediate laments) seen in alcoholic hepaEEs

Complica3ons: fajy change (reversible) hepaEEs (reversible) cirrhosis (irreversible) hepatocellular

carcinoma (irreversible)

Other organs that can undergo these changes (fajy change) are HEART and KIDNEY

Staining for fat: Oil red O, Sudan Black, Osmic acid (electron microscopy)
Staining for glycogen: PAS

CoagulaEve Necrosis of Kidney

Coagula3ve Necrosis - almost always due to ischemia leading to hypoxia; overall

architecture of the organ is sEll preserved (see renal tubules on histology)
E3ology: anything that causes ischemia/hypoxia (atherosclerosis/embolus/gunshot wound)
Inves3ga3ons: no nuclei, eosinophilia (proteins are denatured), but overall architecture is
maintained b/c degradaEve enzymes are also denatured!
Examples:

Gangrenous necrosis ischemic coagulaEve necrosis + superimposed infecEon (wet

gangrene) seen with diabetes & vasculiEs

Renal artery stenosis

Sickle cell anemia (vaso-occlusion coagulaEve necrosis of spleen)
Volvulus in the GI
Embolus of SMA
CoagulaEve necrosis in lung by pulmonary embolism
Myocardial infarcEon

Necrosis ALWAYS accompanied by inammaEon (rst PMNs/neutrophils for rst 24 hours

& then macrophages El day 3) 7-10 days see granulaEon Essue (angiogenesis, type III
collagen) 2 weeks (type III collagen type I) broblasts laying down collagen/
cicatriza3on [chronic inammaEon] fully formed scar at 2 months!

LiquefacEve Necrosis of Brain

Liquefac3ve necrosis can be from hypoxia in the brain (stroke), or
bacterial/fungal infecEons somewhere else in the body
Architecture IS compromised!!!

BRAIN: ischemia/hypoxia microglia releasing hydrolyEc enzymes which

digest the brain parenchyma

Microglia become loaded with fat/necroEc debris form foam/giTer cells

Presenta3on: a[er 2 weeks, you see astrocytes (which are broblasts of brain)
and gliosis (brosis of brain)
Complica3ons: stroke (paralysis & slurred speech)
Brain with pyogenic bacteria (pus/neutrophils/debris) = brain abscess

LUNG: d/t pyogenic bacteria (necrosis in the lung d/t hypoxia = coagulaEve)
PresentaEon: diculty breathing, smelly sputum, cough, fever (caused by IL-1
& TNF)

Fat Necrosis

E3ology in breast: TRAUMA, non-enzymaEc, no hypocalcemia

Dystrophic calcica3on there is NORMAL calcium levels

E3ology in pancreas: ENZYMATIC, alcoholism and gallstones

Pathogenesis: pancreaEc injury release of amylase & lipase released FAs combine
with Ca2+ saponica3on (chalky white deposits on surface of pancreas)
Inves3ga3ons: interlobular space of fat upon microscopy
ComplicaEons: fever, nausea, vomiEng, epigastric pain, spasms and tetany due to decrease
in serum Ca2+

Acute pancrea33s: hypocalcemia d/t saponicaEon

Chronic pancrea33s: brosis, dystrophic calcicaEon with HYPOCALCEMIA b/c of malabsorpEon of fat
soluble vitamins no Vitamin D cant take up Ca2+

Chronic inammaEon hypocalcemia

Dystrophic calcicaEon normal calcium levels (except pancreaEEs)
MetastaEc calcicaEon hypercalcemia

Caseous Necrosis
Caseous necrosis = coagulaEve + liquefacEve
necrosis
Pathogenesis: TB inhalaEon macrophages try
to engulf microbe but cant, so they release IL-12
which converts CD4+ T cells TH1 cells TH1
cells secrete IFN gamma to acEvate macrophages
to epithelioid cells [no phagocy3c func3on/ only
secrete IL-1/TNF/TGF] GRANULOMA (complex
mixture of chronic inammatory cells and dead
Essue)

Casea3ng granuloma central area of caseous

necrosis (no nuclei in center) walled o by
chronic inammatory cells (macrophages, T cells,
plasma cells, broblast, giant cells, epitheliod cells
BUT NO PMNs!!!!)
Langhans Giant Cells (collecEon of epithelioid cells)
ONLY in TB with horseshoe shaped arrangement of
nuclei

Presenta3on: Tuberculosis (cough, low grade

fever, SOB, night sweats, weight loss)
Inves3ga3ons: acid fast & cojage cheese like
appearance due to mycolic acid
ACID FAST STAIN used to conrm diagnosis

Acute InammaEon AppendiciEs

Five cardinal signs: redness (histamine/vasodilaEon), hot (vasodilaEon), pain (bradykinin),

swelling (histamine/vasodilaEon) & loss of funcEon
Transient vasoconstric3on (neurogenic) vasodila3on by histamine vascular
permeability/exuda3on[marginaEon (rouleaux formaEon of RBCs pushes WBCs to
periphery) rolling adhesion/emigraEon via integrins (ICAM-1 & VCAM) chemotaxis/
acEvaEon]
ChemotacEc factors for PMNs/neutrophils

Complement (C5a) MOST IMPORTANT!!

Bacterial products most important chemotacEc factor for macrophages
Arachidonic acid metabolites (Leukotriene B4)
Cytokines (IL-8)

Movement of WBC from vessels to intersEEal space = diapadesis

Phagocytosis:

Recogni3on & aTachment coated with opsonins (IgG & C3b)

Engulfment formaEon of phagolysosome requires presence of Ca2+ & Mg2+
Killing/degrada3on
Oxygen dependent mechanisms:

H2O2-myeloperoxidase-halide system decient in paEents with CGD requires reacEve radical = HOCl
MPO independent killing most potent radical = OH-

Oxygen independent mechanisms: pH due to buildup of lacEc acid

Types of acute inamma3on:

Serous albumin containing exudate; seen in blister, pulmonary TB

Fibrinous contains brin; seen in rheumaEc fever (bread & buTer pericardi3s)
Suppura3ve/purulent liquefacEve necrosis caused by pyogens (pus has neutrophils); seen in acute
appendici3s
Sanguinous contains large number of RBCs; tumor invasion

Acute InammaEon

Changes in vascular permeability: intravascular hydrostaEc pressure

(vasodilaEon) or intravascular osmoEc pressure (albumin) intersEEal uid
(edema)

Endothelial cell contrac3on histamine in venules immediate transient response

Junc3onal contrac3on cytokine mediated [TNF & IL-1]
Direct endothelial injury endothelial detachment in capillaries & venules; immediate
sustained response
Leukocyte dependent endothelial injury inammatory cells release ROS causing
endothelial detachment in venules & pulmonary capillaries
Increased transcytosis in presence of VEGF vascular permeability

Mediators of vascular permeability

Cell derived vasoac3ve mediators

Arachidonic acid metabolites derived from cell membrane phospholipids

Prostaglandins = vasodilaEon & permeability
Leukotrienes = permeability & chemotacEc acEvity
PAF vasodilaEon, permeability & aggregaEon of platelets at the site of injury
Amines: vasodilaEon & vascular permeability (VENULES only)
Histamine mast cells, basophils, platelets
Serotonin platelets
Endothelins powerful vasoconstrictor

Plasma derived vasoac3ve mediators

Kinins & coagula3on cascade bradykinin (vasodilaEon, vascular permeability & PAIN!!)
Clokng system prevents infec3on spread; end product = brin
Complement system

Opsinizing bacteria = C3b; ATrac3ng leukocytes (chemotaxis) = C5b, 6, 7 complex & C5a; Mast cell
ac3vators degranulaEon & histamine release = C3a, C5a; C6-C9 = create pores in bacterial walls

Chronic InammaEon PepEc Ulcer

Pathogenesis:

Previous acute inammaEon (2 weeks)

De novo: Granulomatous inammaEon (TB) & autoimmune disease

Cell types: monocytes & macrophages, lymphocytes, plasma cells,

broblasts & endothelial cells
Hallmark is brosis by broblasts leading to loss of func3on
PMNs (neutrophils) ARE ABSENT!!

Presenta3on: NO pain normally because no more bradykinin, BUT

every chronic inammaEon can have an episode of acute ON
chronic inammaEon which causes pain
Happens in paEents with Crohns, RA, gout and psoriasis

Chronic Granulomatous InammaEon

Casea3ng granuloma central area of caseous necrosis (no nuclei in
center) walled o by chronic inammatory cells (macrophages, T cells,
plasma cells, broblast, giant cells, epitheliod cells BUT NO PMNs!!!!)

Other granuloma types:

Non-casea3ng granuloma no central area of necrosis

Crohns, Sarcoidosis & Berylliosis

Pyogenic/Suppura3ve purulent (has PMNs/neutrophils) granulomas

Cat Scratch Disease and Lymphogranuloma Venerum (LGV) STI caused by
chlamydia

Foreign Body Granuloma

Gout (monosodium uric acid crystals) & foreign body giant cells

Path Module 2 Images

Amyloidosis of the Kidney

Amyloid extracellular protein deposits found most commonly in the kidney!

Pathogenesis: protein misfolding for ALL amyloidosis

Organ is iniEally enlarged, but then atrophies due to vascular involvement

Localized: aects one organ

Kidneys aected kidney turns brown with iodine stain proteinuria, enlargement & failure
Senile Cardiac Amyloidosis & familial neuropathies transthyre3n

Liver deposits in Space of Disse hepatomegaly

Alzheimers beta amyloid plaques (extracellular)

Spleen white pulp (sago spleen); sinusoids/red pulp (lardaceous spleen) splenomegaly

See tapioca-like granules

Mul3ple myeloma w/ Bence Jones proteins AL amyloid

Chronic Inammatory Condi3ons (Crohns, Ulcera3ve Coli3s, TB, Osteomyeli3s, Rheumatoid Arthri3s) AA amyloid
Dialysis pa3ents (from -2 microglobulin)

Presenta3on:

Tau proteins/neurobrillary tangles are intracellular

Systemic: aects mulEple organs

See tapioca granules; deposits in ALL layers of the heart

Generalized edema due to loss of proteins Nephro3c Syndrome in the kidney [most common]
Amyloid in the heart usually deposits into the myocardium so you get arrhythmias

Inves3ga3ons:

Electron microscopy: non branching brils ( pleated sheets) & non-branching component made up of -1-glycoprotein
H&E stain: amorphous, glassy pink (hyaline) extracellular protein
Congo Red: salmon pink/red, subject to polarized microscopy looks like apple green birefringement

CalcicaEon of AorEc Valve

Dystrophic calcica3on: dead or dying 3ssues

Seen in: atheroscleroEc plaques, enzymaEc fat necrosis, damaged cardiac valves,
mercury poisoning, congenital CMV, aging (degeneraEve with wear & tear) &
Rheuma3c endocardi3s
Presenta3on: aorEc stenosis, repeated syncope, SOB, CHF, murmur
Inves3ga3ons:
Ca2+ levels are NORMAL

EXCEPTION = fat necrosis of pancreas (HYPOCALCEMIA!)

H&E: Ca2+ stains blue (basophilic)!!

Metasta3c calcica3on: Ca2+ levels are ELEVATED in NORMAL Essues!

Primary hyperparathyroidism: PTH bone resorpEon, hydroxylaEon of Vitamin D, &

reabsorpEon of calcium in renal tubule with the excreEon of phosphates
Sarcoidoisis: non-caseaEng granuloma; acEvate Vit D precursors which increases renal
& intesEnal absorpEon of Ca2+ as well as bone resorpEon
Chronic renal failure
Vitamin D intoxicaEon

Acute
G
out
Idiopathic e3ology is unknown

Pre-disposing factors: obesity, red wine, red meat, alcohol, Lesch Nyhan (HGPRT
deciency), thiazides
Hyperuricemia (high uric acid levels) does not ALWAYS lead to gout, but to get gout, you must have had
high uric acid levels
Primary (90%) unknown enzyme defect + HGPRT deciency
Secondary (10%) - NA turnover, chronic renal disease, inborn errors of metabolism

Pathogenesis: macrophages engulf uric acid crystals complement acEvaEon brings in

neutrophils (signs of acute inammaEon)
Acute gout edematous so[ Essue with acute inammatory inltrate (PMNs & macrophages with
phagocyEzed urate crystals)

Inves3ga3on: joint aspiraEon/atherocentesis

Yellow, negaEve birefringerence under plane polarized light

Gout

Monosodium urate crystals

Loves rst metatarsal joint
NegaEvely birefringement
Needle shaped crystals
Yellow crystals

Pseudogout

Calcium Pyrophosphate crystals

Loves the knee
Posi3ve birefringement
Rhomboid crystals
Blue crystals

Chronic Gout

Loss of func3on
No bradykinin, no pain

NO pain normally BUT every chronic inammaEon can have an

episode of acute ON chronic inammaEon which causes pain

No histamine no swelling or redness

Foreign body granuloma (with foreign body giant cells)
broblasts deposit collagen joint becomes brosed
reduced ROM
Tophaceous deposits in sow 3ssues: ear, nasal carElages and
skin of ngerEps
Most commonly aected Essues = joints & kidney (urate
nephropathy)

Cholestasis accumula3on of bilirubin in

bile canaliculi of hepatocytes!

Components of bile: bilirubin, bile salts, phospholipids, cholesterol &

electrolytes
Due to: obstrucEon of bile duct, cholecysEEs, bile duct collapse, liver
failure, gall stones (cholelithiasis), biliary atresia
Conjugated/direct bilirubin (product of hemoglobin catabolism)
Endogenous pigment found extracellularly
Skin (yellow), gallbladder (green) & intes3ne (brown)

Presenta3on: jaundice (icterus), steatorrhea (pale b/c no stercobilin), dark

urine & malabsorpEon of fat soluble vitamins

Vitamin A (causes night blindness)

Vitamin D (causes hypocalcemia/arrhythmias),
Vitamin E (no anEoxidants)
Vitamin K (causes bleeding)

Inves3ga3ons = conjugated bilirubin

Hemosiderin deposits
Endogenous pigment from catabolism of hemoglobin

Denatured form of ferri3n

Normally stored in RES (spleen, bone marrow & Kuper cells of the liver)

Pathogenesis:

Excess intracellular iron (hemosiderosis) due to:

Excess intes3nal iron absorp3on
Hemolysis of RBCs
Blood transfusions

Hemochromatosis extreme iron overload

Le[ ventricular hypertrophy le[ heart failure blood backs up into alveolar space
pulmonary edema at 2 weeks, hemosiderin laden macrophages in alveolar space
(heart failure cells) with alveolar brosis (due to collagen)

Presenta3on: dyspnea, SOB, orthopnea b/c uid in alveolar space when lying
down, paroxysmal nocturnal dyspnea
Inves3ga3ons: Stain blue on Prussian Blue & golden-brown on H&E b/c
hemosiderin contains iron

Hemochromatosis
Primary hemochromatosis

C282Y muta3on of HFE gene [regulates iron absorpEon]

Test with Real Time PCR & RFLP

Secondary hemochromatosis

Excess intes3nal iron absorp3on

Hemolysis of RBCs
Blood transfusions

Pathogenesis: excessive absorpEon of iron saturaEon of iron binding protein

deposi3on of hemosiderin in 3ssue
Heart cardiac failure
Liver hepa3c cirrhosis

risk of hepatocellular carcinoma

Pancreas diabetes
Skin bronze appearance
Kidney kidney failure

Treatment = phlebotomy (removal of blood)

Pulmonary Antharcosis

Exogenous pigment
E3ology: inhalaEon of coal dust or carbon parEcles
Pathogenesis: phagocyEzed by alveolar macrophages/dust
cells [incapable of digesEng the pigment] travels to
regional lymph nodes & accumulates!
Presenta3on: asymptomaEc/no inammaEon
Seen in urban dwellers, smokers & coal miners

Complica3ons: Coal workers develop pneumoconiosis (black

lung) if carbon is mixed with silica

Tajoos

E3ology: injecEon of insoluble metallic vegetable

pigments into skin
Pathogenesis: engulfed by dermal macrophages
unable to digest pigments remain in the dermis
for life

Melanin & Lipofuscin

Melanin endogenous pigment produced by
melanocytes & stored in melanosomes
ProtecEve barrier of skin (absorbs UV light)
Can accumulate in basal epithelial cells of skin
(freckles), nevus cells & dermal macrophages
Heavy concentraEons malignant melanoma
(aggressive & metastasize rapidly)

Lipofuscin wear & tear pigment

Insoluble pigment produced due to free radical induced
damage associated with aging
Stored in lysosomes
Most visible in liver, heart & brain

Path Module 5 Images

Biology of Tumor Growth

Transforma3on monoclonal proliferaEon

AddiEonal mutaEons over Eme can lead to subclones

resistance to chemotherapy

Tumor growth requires 30 doubling 3mes for clinical

signicance

Angiogenesis via FGF, PDGF, VEGF to maintain blood supply

Local invasion - [resistant Essues mature carElage & elasEc

Essue in arteries]

Detachment of tumor by downregula3ng E-cadherin & muta3on

of catenins
ATachment to ECM proteins laminins, integrins, bronec3n
ECM protein degrada3on type IV collagenase, cathepsin B
Genera3on of new sites - MMP2 & MMP9 secreted by tumor
Movement through ECM proteins autocrine mo3lity factors

Distant metastasis - via lympha3cs, hematogenously, or

seeding

Grading vs. Staging

Grading level of dieren3a3on (well, moderately, or
poorly dierenEated), mitoses & character of tumor
Graded I-IV based on histological appearance
Problems with variaEon of histology of various areas and
observer variaEon

Stage extent of spread; of greatest prognos3c value

Clinical staging based on evidence acquired before
treatment
Pathological staging obtained at surgery via examinaEon
of Essues
Size of the primary tumor (T)
Extent of spread to regional lymph nodes (N)
Presence or absence of metastases (M)

Cervical Dysplasia Carcinoma

Pathogenesis: Squamous dysplasia from HPV 16 and 18 strains incorpora3ng in host genome express E6
and E7; E6 inac3vates p53, E7 inac3vates Rb

Three stages asymptomaEc in ALL stages!! Pap smear to screen; biopsy to diagnose!

CIN I (mild/at condyloma) lower 1/3 of epithelium is dysplasEc and upper 2/3 has koilocyEc change

CAUSE GENITAL WARTS [totally benign] but can sEll do koilocyEc change (indicates the presence of HPV)

Metaplasia (columnar squamous) Dysplasia Invasive cervical cancer (invade BM)

Most imp predisposing factor for cervical cancer history of mul3ple sexual partners!
Most common symptom = post-coital bleeding!

Smaller nucleus = most mature/largest = supercial cells (these are the cells you want to do a pap smear for)
Biggest nucleus/mito3cally ac3ve = least mature/smallest = parabasal cells

Schillers test tests for non-glycogen/highly mito3c areas site of carcinoma

HPV 6 & 11 dont incorporate in the host genome do not cause dysplasia or carcinoma

Increased nucleus to cytoplasmic ra3o

Nuclear hyperchromasia (blue/basophilic)
Nuclear pleomorphism (di sizes & shapes)
Cellular pleomorphism
Enlargement, irregularity & loss of polarity (orientaEon of cells doesnt make sense)

Naturally in the cervix, squamous cells mature from boTom to top as they accumulate glycogen

CIN II (moderate) lower 2/3 is dysplasEc and upper 1/3 has koilocyEc change
CIN III (severe dysplasia/carcinoma in situ) enEre epithelium is dysplasEc no koilocyEc change; basement membrane is INTACT (not
carcinoma yet)

ALL FORMS OF DYPLASIA ARE REVERSIBLE - 5 features of dysplasia/atypia are:

KoilocyEc change = perinuclear halo and nuclear hyperchromasia

Also have dyspyrunia (painful intercourse); white vaginal discharge (leukorrhea)

Malignant squamous cells with kera3n pearls = well dierenEated in funcEon b/c making keraEn pearls!!

Colonoscopy, mammogram & digital rectal exam are examples of screening tests for cancer like the pap smear

Oncogenic Viruses
DNA VIRUSES

RNA VIRUSES/
RETROVIRUSES (contain
reverse transcriptase)

VIRUS

ASSOCIATED CANCER

HHV-8 (Kaposis sarcoma

associated virus)

Kaposis sarcoma, body

cavity fluid B cell lymphoma

HPV (Human Papilloma

virus)

Cervical carcinoma
(16,18), penile/anal
carcinoma

EBV (Ebstein- Barr virus)

Burkitts lymphoma,
nasopharyngeal carcinoma

HBV, HCV (Hepatitis

viruses)

Hepatocellular carcinoma
(most common cancer
prevented by
immunisation)

HTLV-1 (Human T cell

Leukaemia virus -1)

Adult T cell leukaemia

viral Tax protein causes
mutation

Endemic in the Caribbean

and Japan. Only RNA
virus implicated in human
cancer.

Anaplasia
Anaplasia de-dierenEated or lack of dierenEaEon in
structure and funcEon
Rapid cell growth & hallmark of malignancy
Immunohistochemical stains for anaplasia
Epithelial origin carcinoma cytokera3n stain
Disseminate via lympha3cs

Mesenchymal origin sarcoma vimen3n stain

Disseminate hematogenously via venous drainage
Liver & lung are frequent sites

Muscle origin desmin stain

Black areas = tumor giant cells [mul3nucleated]b/c anaplasEc

tumors divide at a very fast rate
KI67 is the stain for rapidly dividing tumor cells

Benign Neoplasm Lipoma

Lipoma slow growing benign tumor of adipose

(mesenchymal origin)
Well dierenEated, well demarcated & smooth borders
No hemorrhage, necrosis or ulceraEons
Lipoma has a true capsule

E3ology unknown; painless

Most common in back
Histology mature white fat cells with no pleomorphism!
0% chance of malignant transformaEon stays benign
forever

Hemangioma
Capillary hemangioma type of hamartoma (disorganized
Essue in normal locaEon)
Histology disorganized blood vessels
Very common in children < 3 years old
Regress about age of 7-10 years

Strawberry raised lesions (usually on bujcheek of newborn)

0% chance of malignant transformaEon
Do NOT do biopsy!

Chorisotoma (normal Essue in an abnormal place)

Aka: ectopic or heterotopic rest

Meckels diverEculum (gastric and pancreaEc Essue in the ileum)

Leiomyoma/uterine broid tumors

Pathogenesis: fast growing benign tumors in myometrium (smooth muscle - mesenchymal)

No necrosis or hemorrhage; clear demarcaEon, localized & pseudocapsule

E3ology: unknown; asymptomaEc; no chance of malignancy

Presenta3on:

Most common in nulliparous African American women (never had children)

Heavy periods (menorrhagia) iron deciency anemia le[ ventricular hypertrophy le[ ventricular
failure pulmonary edema at 2 weeks hemosiderin laden macrophages in alveolar space (heart failure
cells) with alveolar brosis (due to collagen)
Uterus grows big and presses on bladder (urinary urgency/frequency) and presses on rectum
(consEpaEon)

Histology = well dierenEated - whorling bundles smooth muscle cells

Complica3ons:
Estrogen makes the broids grow bigger but does not CAUSE them
Pregnancy & oral contracepEves causes the broids to grow bigger
Menopause causes the broids to grow smaller

If the broids become too big for the blood supply, they undergo coagulaEve necrosis and then a RED
INFARCT

Benign Mixed Tumor of ParoEd Gland

Pleomorphic (mixed benign) adenoma of salivary gland
E3ology: unknown
Pathogenesis: arises from 1 germ layer that undergoes divergent dieren3a3on;
monoclonal origin
Presenta3on: painless lumpy mass in the jaw;
ComplicaEons:

Small chance of malignant transformaEon metastasize compression of facial nerve

Bells palsy
High chance of recurrence

InvesEgaEons:

Biopsy: see both mesenchymal [amorphous bromyxoid stroma] & epithelial cells
[serous acini]!
Both are benign

Tumor of the Colon

Polyp an outgrowth of mucosal 3ssue

Can be pedunculated (has visible stalk/FAP) or sessile (at with no stalk/HNPCC)

Familial Adenomatous Polyposis (FAP) geneEc, tubular adenoma, numerous benign polyps (>100) on lew side of colon
(sigmoid, descending); BENIGN TUMOR WITH DYSPLASTIC CELLS AND HENCE CAN BECOME CANCER!
Gene = APC (tumor suppressor gene) which requires 2 hits inherit 1 bad hit and get second hit later in life POLYPS
mutaEons in KRAS & p53 adenocarcinoma!

NEVER BORN WITH POLYPS B/C BORN WITH ONLY ONE HIT
AsymptomaEc screen with sigmoidoscopy (screen at age 12)
Can bleed and give iron deciency anemia Le[ heart failure
Diameter of le[ colon is smaller than right easier to obstruct

Hereditary Non Polyposis Colon Cancer (HNPCC) no benign polyps; cancer on right side of colon

DNA mismatch repair genes: MLH1, MSH2 and MSH6 & PMS2
Microsatellite instability [start screening with colonoscopy at age of 25]
Lynch Syndrome = family history of cancers in breast, right sided colon, endometrium & ovaries

Adenoma-carcinoma sequence excepEon to rule where benign tumors stay benign; chance of happening = 100% so resecEon of colon
is necessary!

MutaEons in DNA mismatch repair genes

Colon cancer mostly sporadic!

Predisposing factors: FAP, high fat diet, low ber, rich in rened carbs, low in Vitamins A, C, & E, UC & Crohns
E3ology: unknown
Symptoms: depend on side

Lew bright red blood in stool, mucus, intesEnal obstrucEon and le[ lower quadrant pain
Right iniEally no symptoms (b/c occult bleeding) iron deciency anemia due to chronic blood loss

Iron deciency anemia in an elderly male right sided colon cancer unEl proven otherwise!!!!

Tumor marker: Carcino-embryonic an3gen (CEA) useful for follow-up to treatment, not diagnosis
Immunohistochemical stain: cytokera3n
Spread of cancer from colon: lymph liver lung

Osteosarcoma

Malignant tumor of osteoblasts [derived from mesenchyme]

Pathogenesis:

MutaEon in Rb gene (child would present with both eyes removed at a young age due to reEnoblastoma)

Presenta3on: seen in children (12-20)

Painful enlarged mass (swelling) around the knee (metaphyseal plate of long bones b/c
this is site of con3nuous cell replica3on)
Pathological fractures

Inves3ga3ons:

Histology: malignant osteoblasts, hemorrhage, necrosis, invasiveness & lack of

demarcaEon
X-ray: Codmans triangle (periosteal elevaEon) & sun burst appearance (reacEve bone
formaEon)

Complica3ons:

Invade venous channels cough with blood and sputum (hemoptysis) b/c metastasize
to lung via the blood
Most sarcomas end up in liver and lung (b/c organs with most blood ow)

Metastasis
Metastasis of carcinoma is via lympha3cs

All carcinomas eventually end up in blood due to the emptying of lymph in thoracic duct

Homing organ ajracts malignant tumors to itself by chemokines and cytokines

Ovarian & gastric carcinomas spread through direct seeding through the
omentum!
Hematogenous spread - liver (via portal vein) and lung (via vena cava) have largest
capillary bed, which pre-disposes to sarcomas
Paraneoplas3c syndrome [things that dont make sense]

Squamous cell carcinoma of lung giving you hypercalcemia - tumor releases a PTH
related pepEde mimic PTH causes bone resorpEon and reabsorpEon from kidneys
and hydroxylaEon of Vitamin D
Small cell carcinoma of lung secreEng ACTH causes adrenal cortex to release corEsol
Cushing syndrome

Endometrial Adenocarcinoma

Endometrial carcinoma - hormone producing cancer

E3ology: post-menopausal women taking estrogen replacement therapy, paEents
taking tamoxifen for breast cancer (antagonist in breast and antagonisEc in
endometrium), obesity, diabetes mellitus, nulliparous & POD
MutaEon in mismatch repair gene PTEN [Cowdens syndrome]

Pathogenesis: Unopposed estrogen (estrogen without progesterone) atypical

endometrial hyperplasia [precursor lesion] endometrial carcinoma
Estrogen is a DIRECT cause!!

Presenta3on: vaginal bleeding in post-menopausal women & leukorrhea (white

vaginal discharge)
Inves3ga3ons:
Histology: malignant endometrial glands invading the myometrium
Immunohistochemical stain: cytokera3n

Spread via lymph nodes, seeding via peritoneal cavity to peritoneal tubes,
invasion of myometrium and HEMATOGENOUS spread!

Gastric Adenocarcinoma

Irregular, headed up margins, necroEc, hemorrhagic

E3ology: H. pylori (gram negaEve), Japanese, smoked foods
(have nitrosamines)
H. pylori also associated with B cell lymphoma (MALToma)

Precursor lesion: chronic atrophy gastri3s

Presenta3on: epigastric pain, early saEety, hematemesis,
iron deciency anemia, melena (dark tarry stools), enlarged
Virchows node [le[ supraclavicular lymph nodes]
Inves3ga3ons:
Tumor marker = CEA

Nonspecic used for CLuBS [colon, lung, breast & stomach cancers!]

Biopsy: malignant glands invading basement membrane!

Bilateral Ovarian Tumor

Metastases to both ovaries from a primary site = Krukenberg

Histology: Signet ring cells [malignant cells coming from primary
tumors]
Filled with mucins that push nuclei to the periphery
Mucin has glycogen -- stain with PAS

Three primary sites:

Stomach (gastric adenocarcinoma)

Colon
Breast

Present with symptoms of primary tumor

Poor prognosis paEents die within a year
Tumor marker = CA 125

Mature CysEc Teratoma

Teratoma derived from 2 or more germ layers

Only occurs in ovaries and testes b/c arising from to3potent germ cells

Mature teratoma = BENIGN DERMOID CYST well-dierenEated

Immature teratoma = malignant!

Presenta3on: teeth & hair (from ectoderm), sebaceous secreEons

(from mesoderm)
Usually no symptoms incidental nding of calcied tooth on x-ray!

Four complica3ons: inferElity, rupture, torsion, malignant

transformaEon to invasive squamous cell carcinoma (from
ectodermal component)
NOT A MIXED TUMOR [tumor from 1 germ layer makes 2 dierent cell
types via divergent dierenEaEon]

Wilms Tumor

Nephroblastoma [malignant mixed tumor] in children 2-5yr

Pathogenesis: DIVERGENT DIFFERENTIATION!!

MutaEon in WT-1 and WT-2 tumor suppressor genes

Sporadic (unilateral) & familial (bilateral)
Tendency to metastasize early, especially to the lungs
Precursor lesion = nephrogenic rests (abnormally persistent clusters of
embryonal cells)

Presenta3on: palpable abdominal mass, abdominal pain, tumor

compresses renal vessels JG cells secrete renin and lead to hypertension
Histology: triphasic all three are malignant
Blastemal small, immature blue cells with high nuclear: cytoplasmic raEo
Stromal/mesenchymal spindle-shaped cells
Epithelial defecEve tubules/glomeruli

Do a nephrectomy or may metastasize to lungs!

ReEnoblastoma
ReEnoblastoma around age 2
Pathogenesis:

MutaEon in Rb tumor suppressor gene needs 2 hits

Sporadic (unilateral) & familial (bilateral)
Familial type leads to osteosarcoma later in life

Presenta3on: visual impairment (running into walls), leukocoria (cats eye

reex) causes pupil to look white with pupillary light reex
Histology: Flexner-Wintersteiner roseTes (malignant cells arranged around
a central lumen)
Treatment: take out eye and chemotherapy
PseudoroseTes: NOT arranged around central lumen
Seen in neuroblastoma

Cancer CharacterisEcs
No chance of malignancy
Lipoma
Capillary hemangioma
Leiomyoma

Small chance of malignancy

Salivary gland adenoma (mixed tumor)

Benign dermoid cyst (teratoma)

100% chance of malignancy

Familial Adenomatous Polyposis (FAP)

HNPCC
Osteosarcoma
Wilms tumor (mixed tumor)
ReEnoblastoma

Sites of Metastasis for Primary Cancers

SITE OF
METASTASIS

SITE OF PRIMARY
CANCER

MNEMONIC

BRAIN

Lung, Breast, Skin

(melanoma), Kidney
(renal cell carcinoma),
GI

Lots of Bad Stuff Kills

Glia

LIVER
(AFP is tumor marker
for hepatocellular
carcinoma)

Colon, Stomach,
Pancreas, Breast, Lung

Cancer Sometimes
Penetrates Benign Liver

BONE

Prostate and breast

are the most common.
Also thyroid, testes,
lung and kidney

PROTOONCOGENES

ONCOGENE

PATHOGENESIS

ASSOCIATED
TUMOUR

Abl

t9:22 translocation of abl formation

of bcr-abl fusion gene on ch. 22
(Philadelphia chromosome) increased
tyrosinase activity

Chronic myelogenous
leukaemia

c-myc

t8:14 translocation of c-myc. EBV

causes polyclonal stimulation of B cells
and increases the chances of this
translocation*

Burkitts lymphoma*

bcl-2

t14:18 translocation of B cell Ig heavy

chain close to bcl-2 gene on ch 18
Overexpression of bcl-2 gene product
Inactivates apoptosis gene *

B cell follicular*
lymphoma

erb-B2/neu
(HER-2)

Overexpression of erbB2

Invasive ductal
carcinomas

ras

Point mutation reduction of GTPase

activity and RAS is trapped in an
activated bound state via MAP kinase
pathway activates transcription.

30% of human cancer

including lung, colon,
pancreas and leukaemia
(acute myelogenous

(tyrosine kinase

activity)

Protooncogenes (continued)
ONCOGENE

PATHOGENESIS

ASSOCIATED
TUMOUR

L-myc

Amplification

Lung tumour

N-myc

Amplification

Neuroblastoma

ret

Point mutation

Multiple Endocrine
Neoplasia (MEN) types
I and II

c-kit

Gastrointestinal
stromal tumour (GIST)

TUMOUR SUPPRESSOR GENES

GENE

NORMAL FUNCTION

PATHOGENESIS ASSOCIATED
TUMOUR

Rb

Prevents cells from

entering S phase

Majority of
tumour
suppressor genes
are inactivated
by point mutation

BRCA1

BRCA2

DNA repair

Retinobastoma
Osteosarcoma
Breast and ovarian
cancer (+colon and
prostate)
Breast cancer

NF1/NF2

NF1= Encodes GTPase

activating protein

Neurofibromatosis
1 and 2

P53

Inhibits activated cyclinDcdk complex hence

preventing progression
from GI to S phase

Most human
cancers, LiFraumeni
syndrome,
oncogenesis in
HPV(USMLE)

TUMOUR SUPPRESSOR GENES CONTINUED

GENE

ASSOCIATED TUMOUR

P16

Melanoma

APC

Familial adenomatous polyposis

syndrome, Gardners syndrome

WT1

Wilms tumour

DPC (deleted in
pancreatic cancer)

Pancreatic cancer

DCC (deleted in colon)

Colon cancer

RADIATION INDUCED CANCERS

UV RADIATION

Formation of thymidine dimers

that distort the DNA molecule
UVB- light induced cancers
include:
Basal cell carcinoma (most
common type)
Squamous cell carcinoma
Malignant melanoma

Xerdoma pigementosum
AR disease
Deficiency of DNA repair enzymes
cannot splice out damage to
DNA
Extreme photosensitivity with a
x2000 fold risk of skin cancers

IONISING RADIATION (alpha and

beta particles, gamma-rays, xrays)

Hydrolyses water into free

hydroxyl radicals mutagenic to
DNA
Ionising radiation induced cancers
include:
Leukaemia

Increased in radiologists and

atomic bomb victims

Papillary carcinoma of the

thyroid
Osteogenic sarcoma
Others: Lung, breast and liver
cancers

LABORATORY DIAGNOSIS OF CANCER

MORPHOLOGIC METHODS
METHOD

PURPOSE

Frozen section

For immediate results e.g. in the middle of surgery in

the histological examination of lymph nodes and mass
lesions

Fine needle aspiration

Aspiration of cells from a mass followed by

cytological examination usually for palpable lesions
though modern techniques may permit examination of
deeper structures

Cytologic (papanicolaou smears

Cervical cancer detection but now also for other

neoplasms

Flow cytometry

Used in the classification of leukaemias and

lymphomas by detecting DNA ploidy by staining with
fluorescence labelled surface markers for DNA and
sorting out as to size and fluorescence intensity

Immunocytochemistry

Detects nuclear or cytoplasmic protein with the aid of

a specific antibody. Used in tumour diagnosis to detect
the origin of a cell

Molecular Diagnostic
techniques

PCR based for diagnosis, prognosis, and detection of

hereditary predisposition

TUMOUR MARKERS
Good for screening and follow-up but not diagnosis
TUMOUR MAKER

ASSOCIATED NEOPLASM

Prostate specific antigen (PSA)

Prostate carcinoma

Prostatic acid phosphatase

Prostate carcinoma

Carcinoembryonic antigen (CEA)

Very non specific but produced by

70% of colorectal and pancreatic
cancers and by gastric and breast
carcinomas

Alpha foetoprotein (AFP)

Hepatocellular carcinomas;
Embryonal cell carcinoma

PARANEOPLASTIC SYNDROMES
SYNDROME

CAUSE

ASSOCIATED
NEOPLASMS

Cushings Syndrome ACTH or ACTH-like peptide

Small cell lung carcinoma

SIADH

ADH

Small cell lung carcinoma,

intracrainial carcinoma

Hypercalcaemia

PTH-related peptide, TGFBeta, TNF, IL-1

Squamous cell lung

carcinoma, renal cell
carcinoma, breast
carcinoma

Polycythemia

Erythropoietin

Renal cell carcinoma,

haemangioblastoma

Lambert-Eaton
syndrome (muscle
weakness)

Antibodies against
presynaptic Ca2+ channels at
neuromuscular junction

Thymoma, small cell lung

carcinoma

Gout, urate
nephropathy

Hyperuricaemia due to
excess nucleic acid turnover
(i.e. cytotoxic therapy

Leukaemias and
Lymphomas

CANCER EPIDEMIOLOGY
INCIDENCE

MORTALITY

MALE

FEMALE

Prostate (32%)

Breast (32%)

Lung (16%)

Lung (13%)

Colon and rectum (12%)

Colon and rectum (13%)

Lung (33%)

Lung (23%)

Prostate (13%)

Breast (18%)

Path Module 3 Images

Hyperemia
Ac3ve increase in blood volume due to arteriolar
dila3on mediated by histamine
Physiological: blushing, exercise
Pathological: acute inammaEon reacEon of meningiEs
preceding formaEon of purulent exudate
Only Eme you see exudate in the lung = INFECTIONS!

Acute & Chronic CongesEon of Lung

due to Le[ Heart Failure

Always passive & pathological; accompanied by edema

Hypertension/aorEc stenosis L heart failure pulmonary edema

Caused by impaired venous ow VENULES are predominantly aected

Before 2 weeks, see transudate (less protein, less inammatory cells &
lower specic gravity) due to increased hydrosta3c pressure engorged
capillaries dyspnea
PresentaEon: coughing up frothy sputum

Lung ( 2 weeks):

Hemosiderin laden macrophages [heart failure cells]

Fibrosis of the alveolar walls
Presenta3on: SOB, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, pink
frothy sputum, PULMONARY edema!

Chronic CongesEon due to Right Heart

Failure
Causes of Right Heart Failure: Le[ heart failure, pulmonary valve stenosis,
asbestosis, pulmonary brosis, right ventricular hypertrophy, silicosis,
recurrent pulmonary emboli
Symptoms of Right Heart Failure: distended jugular veins, peripheral
edema, ascites, hepatosplenomegaly
Nutmeg liver at 2 weeks:

Due to RIGHT heart failure (cardiac cirrhosis) or stenosis of hepa3c vein (Budd
Chiari)
Coagula3ve necrosis red infarct
Zone 1: closest to hepaEc artery in portal triad (receive more O2) reversible faTy
change in liver (steatosis) pale areas
Zone 3: furthest from hepaEc artery/closest to central vein in portal triad coagulaEve
necrosis (centrilobular necrosis) with hemosiderin in Kuppfer cells b/c central porEon is
the last to receive blood seen as red areas in image

Disseminated Intravascular CoagulaEon

Widespread small thrombi in the microcirculaEon throughout the body accompanied by

simultaneous bleeding
Manifests as:

Petechiae pin point hemorrhages

Purpura 1mm 1cm diuse supercial hemorrhage
Ecchymoses - >1cm large supercial hemorrhage
Waterhouse Friderichsen Syndrome DIC + sep3c shock + bilateral adrenal hemorrhages

Destruc3on of adrenal cortex Addisons disease

E3ology
Diuse endothelial injury
Gram nega3ve sepsis (endotoxic) acEvate monocytes which release IL-1 & TNF IL-1 & TNF act on
endothelial cell surface & the expression of 3ssue factor & the expression of thrombomodulin
Injured endothelial cells induce platelet aggregaEon & acEvaEon of intrinsic pathway by exposure of collagen

Viral, ricketssiae
Immunologic injury (type II, III, SLE)

Release of thromboplas3c agents in circula3on acEvaEon of coagulaEon

Amnio3c uid embolism, fat embolism, snake bite, promyelocy3c leukemia, extensive 3ssue necrosis &
burns, mucin, proteoly3c enzymes from carcinoma

Eects of DIC
Essue perfusion shock, lacEc acidosis, microinfarcts
Bleeding consumpEve coagulopathy

Diagnosis: FDPs, D-dimers

Management: heparin to prevent formaEon of thrombi & replace platelets

Thrombus

Occur INSIDE a vessel & aTached to a wall; platelets involved in formaEon

Lines of Zahn (indicate blood ow)

Arterial thrombi (pale b/c high velocity of blood) most commonly due to endothelial injury

Propagate RETROGRADE to blood ow (b/c always moving towards the heart)

Venous thrombi (red b/c slow velocity of blood) - most commonly due to stasis

Pale: platelets & brin

Dark: RBCs

Propagate ANTEROGRADE to blood ow (90% in deep veins of the legs)

Virchows triad

Turbulent blood ow stasis (allows buildup of platelets & coagulaEon factors)

Endothelial injury
Hypercoagulability

Factor V leiden muta3on pre-disposes to thrombus because Proteins C & S cannot cleave/inhibit mutated factor V (pro-coagulant)
Acquired syndromes: cancer (Trousseaus syndrome), heart failure, severe burns, trauma

4 fates of thrombus:

Trousseau unexplained, recurrent thrombophlebi3s look for underlying abdominal malignancy like pancrea3c cancer [release of pro-
coagulants]

Propagate accumulate platelets & obstruct vessel

Embolize dislodge/fragment and carried by blood to a distant site
Dissolu3on removed by brinolyEc acEvity (by Tissue Plasminogen Ac3vator)
Reorganiza3on/ Recanaliza3on induce inammaEon & brosis (organizaEon) re-estblish some degree of ow
(recanalizaEon)

Thrombus in LV embolizes most commonly to lower limbs and brain (CVA)

Post-mortem Clot
NO Lines of Zahn & do not aTach to vessel
Lines of Zahn ONLY seen in thrombus
Fibrin + trapped cells

Transverse secEon of an artery

Superior: yellow chicken fat appearance of coagulated

plasma (supernatant)
Inferior: currant jelly appearance of enmeshed RBCs
(sediment) due to gravity

Platelets not involved in formaEon of clot

Occurs OUTSIDE a vessel (test tube/hematomas) or
post-mortem!

Pulmonary Artery Embolism

Most common origin = from deep leg veins (femoral, popliteal, iliac)
Classica3on
Massive (saddle embolus) straddles the bifurcaEon of the pulmonary
arteries; caused by DVT
Sudden death & no 3me to develop infarc3on
Example: hospitalized paEents who get out of bed 1st Eme

Major (medium vessels) present with dyspnea, pleuriEc chest pain &
hemoptysis & V/Q mismatch
If bronchial arteries are intact pulmonary hemorrhage, NO necrosis
If bronchial arteries are compromised red infarct!
Usually in LOWER LOBES!

Minor (small vessels) asymptomaEc

If you have a series of recurring minor embolisms marginate on the walls of the
pulmonary artery ow encounters resistance pulmonary HTN right heart
failure WITHOUT lew heart failure!!!

Fat Embolism

Due to long bone fractures (yellow bone marrow) , trauma to

subcutaneous Essue, burns
Pathogenesis: fat globules enter circulaEon mechanical blockage as
platelets adhere to fat globules biochemical injury as FFAs released from
adipose damage endothelial cells of vessels recruit coagulaEon factors
DIC, clogging of pulmonary & systemic arteries
Symptoms: 1-3 days a[er fracture
Pulmonary insuciency (dyspnea, tachypnea, tachycardia)
Neurological symptoms (irritability, restlessness, delirium, coma)
Anemia & thrombocytopenia ( petechiae)

Diagnosis: fat globules in urine & sputum

Post-mortem: frozen sec3on (fat will dissolve if processed rouEnely with

alcohol)

FAT STAINS: sudan IV (stains red), oil red (stains red), osmium/osmic acid
(stains black)

Bone Marrow Embolism

In small pulmonary vessels - aggressive CPR
Injury to at bones of the ribs (red bone marrow)

NOT cause of death, incidental nding

Morphology: fat and hematopoe3c cells

AmnioEc Fluid Embolism

Morphology: squames, hair, meconium in pulmonary vessels

Pathogenesis: entry of amnio3c uid into maternal circula3on via a tear in the
placental membrane & rupture of the uterine veins
Symptoms: dyspnea w/in 1 hour, pulmonary edema, diuse alveolar damage
usually fatal!

If paEent survives, the release of thrombogenic agents (mucin) from the amnioEc uid
leads to DIC!
platelets & clokng factors PT/PTT

Diseases with Swirls on Histology:

Silicosis swirls of collagen, no nuclei, eosinophilic

Amnio3c uid embolus swirls of squames/hair/meconium in pulmonary artery
(nuclei are present)
Leiyomyoma swirls of smooth muscle (criss cross formaEon)
Malignant HTN (hyperplasEc) 'onion looking
Cervical carcinoma looks like keraEn pearls
Squamous cell carcinoma keraEn pearls

Atheromatous Emboli
Clews = cholesterol crystals, foam cells
(macrophages) & debris
MOST common presentaEon is ASYMPTOMATIC &
incidental nding on autopsy unless there is
COMPLETE occlusion of the vessel
Most commonly aected vessels peripheral
arteries
Iliac, femoral & posterior Ebial arteries

Systemic Thromboembolism
Travel in arterial circulaEon
Sites of origin: heart (mural 80%), aorta
(ulcerated atheroscleroEc plaques), & venous
circula3on (paradoxical through ASD, VSD)
Eect: embolize to the lower extremiEes and
brain block an end artery INFARCT!

Nitrogen Embolism/ The Bends/

Caissons Disease
E3ology: deep sea diving without Caissons chamber or
deeper than 10m
Pathogenesis: O2, N2 dissolve in high amounts in blood &
Essues due to high pressure sudden resurfacing releases
N2, O2 O2 reabsorbed, N2 bubbles out ruptures 3ssues &
forms emboli in vessels platelets adhere to N2, form
secondary thrombi & aggravate ischemia

Brain (death), muscles, joints (bends), lungs edema, hemorrhage

(chokes)

Caissons disease persistent (chronic) gas emboli in bones

necrosis in femur, Ebia & humerus
Treatment: pressure chamber slow decompression

Air Embolism
150 ml of air in venous circula3on through neck
wounds, thoracentesis, cut jugular vein,
hemodialysis, child birth, aborEon
Air bubbles coalesce & obstruct ow of blood in right
ventricle, lungs, & brain
Frothy mixture in right ventricle ineecEve ejecEon
may occlude large vessels

White Infarct

Occur in solid organs with SINGLE blood supply

Arterial occlusion O2 supply white infarct (wedge shaped)

ischemic COAGULATIVE necrosis!

Heart usually due to coronary atherosclerosis with

superimposed thrombi
LAD is most commonly aected
Elevated Troponin I & CK-MB

Kidney

Unilateral asymptomaEc
Bilateral - urine output

Spleen

Common eEology: sickle cell disease

Red Infarct

Loose 3ssues with collateral/dual blood supply (lungs,

small bowel, tes3cles)
Lung usually due to MAJOR pulmonary embolus
(from DVT) + compromised bronchial artery
hemorrhage/congesEon red infarct coagulaEve
necrosis!
Watershed area in GI: splenic exure (where SMA
ends, IMA begins) most vulnerable to hypoxia
Small intes3ne infarct caused by volvulus, obstrucEon or
intersuscepEon (proximal bowel goes into the distal bowel)

Cerebral Infarct
Usually atherosclerosis with superimposed thrombosis in
vertebro-basilar artery
Thrombo-emboli in the internal caroEd/MCA are less common

12 hours: coagulaEve necrosis/ hemorrhage due to

reperfusion
48 hours: microglia engulf necroEc material GiTer cells
Later: LIQUEFACTIVE necrosis & gliosis of surrounding areas

Path Module 4 Images

GRAM POSITIVE

PATHOGENESIS

GRAM NEGATIVE
PATHOGENESIS

EXOTOXINS Toxic shock

syndrome mediated by superantigens

of staph, aureus
Intravaginal tampon if left too long
leads to growth of staph release
of exotoxins in circulation rash,
conjunctivitis and vomiting

ENTEROTOXINS Food poisoning

EXOFOLIATINTOXIN Scalded
skin syndrome

ORGANISMS
1. Staphylococci
2. Streptococci
3. Corynebacteria diptherae
4. Actinomyces Israelii

RELEASE ENDOTOXINS

Possess a Lipopolysaccharide wall

(LPS wall). Bacteria lysis leads to
large amounts of LPS in the blood
Binds with Lipopolysaccharide
Binding protein (LBP) forming an
LPS-LBP complex LPS-LBP is
picked by macrophages that release
TNF damage of endothelium
PMNs bind onto damaged epithelium
release of IL-1 procoagulant
factor DIC

ORGANISMS
1. N. meningitides
2. N. Gonorrhoea
3. Salmonella Typhi
4. Klebsiella, E.coli, Pseudomonas
(bronchopneumonia)
5. Bartonella henslae

Furuncle & Carbuncle

Skin inammatory lesions:

Furuncle single infected hair follicle + accessory gland

Carbuncle mulEple communicaEng furuncles

Commonly found at nape of the neck

More common in diabe3c pa3ents b/c dont heal properly and have a lot of glucose that
bacteria feeds on

Most common cause: S. aureus and S. pyogenes

Pathogen: direct damage via enzymes (streptokinase, hyaluronidase)

Spread of infec3on: skin infecEon abscesses lymphaEcs venous &

other organs

Presenta3on: cardinal signs of acute inammaEon

Diagnosis: history and physical; no biopsy
Histology: liquefacEve necrosis or pus with PMNs, macrophages &
necroEc cells
Course: healing with brosis

ImpeEgo
Type III hypersensi3vity immune complex mediated
Very common in children (on the face)

E3ology: S. aureus & S. pyogenes

Contact with fomites, pts with poor hygiene

Presenta3on: honey colored crusts of face

Direct damage via enzymes [hyaluronidase, collagenase] and
spreads by fomites
Supercial skin infecEon aecEng only epidermis COMPLETE
RESOLUTION (no brosis)

S. pyogenes impeEgo 2 weeks a[er can have hematuria and urinary

output (oliguria) post-streptococcal glomerulonephri3s

Bacterial MeningiEs

Inamma3on of leptomeninges (pia and arachnoid)

InhalaEon of respiratory droplets spreads directly to brain via sinuses to meninges

but can also spread via blood
InammaEon does NOT spread to brain parenchyma due to BBB

Presenta3on: headache, fever, sE neck, photophobia

Inves3ga3on: fundoscopy if papilledema dont do lumbar puncture or would get
uncal herniaEon
CSF= turbid, proteins, PMNs & glucose

Types
Bacterial
Viral
Fungal
Tuberculous

Protein

Glucose

/normal

Leukocytes
(PMNs)
(lymphos)
(lymphos)
(PMNs/MACs

Age group

Bacterial agent

Neonates up to
2 months

Strep. Agalactiae (Group B),

E.coli, Listeria monocytogenes

Infancy and
childhood

Strep. Pneumoniae, N.
meningitides, H. influenzae

Adolescence

N. meningitides

20-60 years

Strep pneumoniae, N.
meningitides, Listeria
monocytogenes, gram negative
bacilli

Meningococcal SepEcemia

Unregulated hemosta3c process: DIC

LOS endotoxin (of N. meningi3dis) binds LBP engulfed by macrophage TNF

endothelial acEvaEon/injury PMNs sEck IL-1 [pro-coagulaEon] 3ssue factor
& an3-coagulants uncontrolled coagulaEon brin clots ischemia/Essue
damage
DEPLETED COAGULATION FACTORS THROMBOCYTOPENIA hemorrhage!

DIC purpura sepEcemia [bacteria mulEplying in blood] mulEple organ

failure
Commensal gram nega3ve bacteria = E. coli, H. inuenza, P. aeruginosa, Klebsiella,
Proteus, SerraEa!
Inves3ga3ons: D-dimers,bleeding Eme, PT and PTT
Fibrinogen and platelet count are low

Waterhouse Friderichsen Syndrome DIC + sep3c shock + bilateral adrenal

hemorrhages

Fulminant meningococcemia!

Lobular Bronchopneumonia

Caused by: Klebsiella, E.coli, Pseudomonas, Staph

URT infecEon acute bronchiEs spread of inammatory exudate to adjacent
alveoli destruc3on of bronchioles & alveoli
No macrophages in bronchioles to clean up the debris scarring

Can coalesce to involve the enEre lobe [like lobar pneumonia]

Children, elderly, bedridden, immunocompromised, hospitalized
May lead to abscesses, empyema [rare in lobar pneumonia]
Caused by Klebsiella followed by S. aureus

Presenta3on: fever, pleuriEc chest pain worse on inspiraEon, dyspnea, producEve

cough with bloody sputum
Chest x-ray: patchy consolida3on
Sputum sample: gram stain or culture
Complica3ons: Sepsis, DIC , lung abscess/empyema, pleural brosis

Lobar Pneumonia

Streptococcal pneumonia causes lobar pneumonia in healthy young adult

exposed to cold, strain, exhausEon
Pathogenesis:
Acute conges3on: exudate rich in brin, RBC, a few PMN in alveolar lumen
Spreads through alveolar pores of Kohn to involve enEre lobe; alveolar walls
NOT damaged!
Red hepa3za3on (exudate rich in RBCs, brin & more PMNs controlled
infec3on!) grey hepa3za3on (congesEon & brin disappear, PMNs replaced
by macrophages) macrophages clear debris few days later with help of
anEbioEcs
COMPLETE RESOLUTION = 10-14 days

Presenta3on: Cough, fever, chest pain, bloody sputum

Same as bronchopneumonia

Chest x-ray: lobar consolidaEon aecEng enEre lobe of the lung

LOBAR PNEUMONIA VS. BRONCHOPNEUMONIA

LOBAR PNEUMONIA

BRONCHOPNEUMONIA

90% of cases are caused by

Streptococcus Pneumonia

Caused by a various organisms

including Klebsiella, E.coli,
Pseudomaonas and Staph

X-ray: Consolidation appears opaque

Multiple opaque nodules

Occurs in the healthy

Occurs in the setting of weak

immunity

Triggered by cold stress and

exhaustion

History of previous upper respiratory

infection

Infection begins in the alveoli and

spreads via the pores of Kohn and
spreads to involve entire lobe

Infection begins in the bronchi and

spreads to the alveoli

Presence of macrophages in alveoli

- exudates are enzymatically
digested leaving the basic
architecture intact resolution and
no scarring

No macrophages in the bronchi to

clean up the debris leading to scarring

Pathogenesis:

Diphtheria

Corynebacterium diphtheria gram posiEve bacillus

Severe throat infecEon in children [usually not vaccinated]
Pseudomembrane = necro3c cells, PMNs & bro3c exudate

Presenta3on:

Fever, sore throat, malaise, pseudomembrane [should NOT be scraped o]

Bull neck (massive cervical lymphadenopathy) may lead to respiratory distress & require tracheotomy
Most common cause of death

3 weeks heart failure (myocardi3s) & spinal nerve damage (peripheral neuropathy) due to powerful
exotoxin [ADP ribosyla3on inhibits protein synthesis]

ImmunizaEon [DTaP] can prevent the disease

Clostridium dicile gram posiEve bacillus

Broad spectrum an3bio3cs eliminate normal ora of the gut that normally provide protecEon severe
mucosal suppuraEve inammaEon pseudomembrane coli3s [seen on colonoscopy]

AcEnomycosis
Causa3ve agent = Ac3nomyces israelii (commensal bacteria in normal ora of
mouth)
Histology: colonies of organism (sulfur granules) lying in a pool of PMNs/pus
Four types
Cervico-facial oral cavity

Through breach in oral mucosa sinus tracts

Going to den3st/dentures/poor oral hygiene
Present with fever, painful lumpy jaw, squeeze abscess and see sulfur granules with PMNs, debris
and organism!
Peculiar chronic response: brosis occurs even with PMNs present!

Thoracic pneumonia
AspiraEon

Abdominal Direct inoculaEon in surgery

Pelvic Contaminated intrauterine devices

Cytomegalovirus (HHV-5)

Contracted via body uids (transplacental, saliva, urine, breast milk, blood
transfusions) and organ transplant or ver3cally transmiTed
Immunocompromised AIDS pa3ents (CD4 <50)
Most commonly aected re3na (CMV re3ni3s) coTon wool appearance

Can also aect lungs (inters33al pneumonia), GI (esophagiEs), gastriEs, duodeniEs,

coliEs
Transplant of kidney/liver nephriEs/hepaEEs

Presenta3on depends on organ

Tropism for endothelial cells

Polyclonal B cell ac3vator
Immunocompetent infecEous mononucleosis (but usually with EBV)

Inves3ga3on urine sample, PCR for virus DNA, anEbody Eters

Cytopathic eects cytomegalo (enlarged cell & nucleus), formaEon of intranuclear

basophilic inclusions [Owls eye], intracytoplasmic inclusions which are mostly
basophilic; see marginated chroma3n

Herpes Zoster
Pathogenesis: inhalaEon of respiratory droplets
chicken pox varicella zoster dormant in DRG
acEvates when immunocompromised
Unilateral painful vesicles which follow a single dermatome

Inves3ga3on: Tzanck smear scrape vesicle and stain

with Giemsa to visualize Tzanck cells (MulEnucleated
giant cells) in syncy3a forma3on
Intranuclear eosinophil inclusions = Cowdry type A

Rabies

RNA virus - bite by bat, dogs, raccoons, foxes, skunks

Prognosis: based on site of bite (distance from bite site to
brain determines prognosis)
Leg bite has bejer prognosis than neck bite!

Virus spreads from PNS to CNS via retrograde axonal

transport
Presenta3on: loss of consciousness/stupor, hydrophobia,
spasms of pharyngeal muscles, respiratory failure
Deni3ve diagnosis: made on autopsy (Negri bodies
intracytoplasmic eosinophilic inclusions found in neurons)

Viral MyocardiEs

Presenta3on: u-like or asymptomaEc

Inves3ga3on: PCR a[er endomyocardial biopsy
Common outcome: COMPLETE RESOLUTION
Complica3ons:
Dilated cardiomyopathy
Arrhythmias and heart failure if aects
conducEon bers

Viral Mycocardi3s

Myocardial Infarc3on

E3ology: Coxsackie A or B

E3ology: atheroscleroEc plaque with

superimposed thrombosis

Pathogenesis:
Pathogenesis:
No ischemia
Ischemia hypoxia
CombinaEon of direct damage by virus &
InltraEon of PMNs, macrophages &
damage via immune response/lymphocyEc
sheets of necrosis
inltraEon
InammaEon necrosis

Necrosis inammaEon

Patchy necrosis

Necrosis of region of myocardium supplied

by that artery

Rocky Mountain Spojed Fever viral!

E3ology: RickeTsia rickeTsii (obligate intracellular bacteria)

Transmijed by 3ck bites (seen mainly in campers/hikers)

PredilecEon for endothelial cells & smooth muscle of arterioles
Perivascular inammatory inltrate macrophages, lymphocytes & plasma cells

Epidemiology: GOAT regions Georgia, Oklahoma Arkansas Tennessee

Presenta3on (1 week a[er bite): fever, headache, myalgia and vasculi3c rash (starts from
extremi3es and moves inward/proximal)
Can go to lung or brain and cause endothelial damage thrombus
Skin hypoxia ischemia gangrene
Brain stroke/red infarct
Lung red infarct

RickeTsia: Posi3ve Weil-felix test & skin biopsy with immunouorescent staining [most
accurate]

Dieren3al:

R. prowazeki causes epidemic typhus (via lice)

Loves endothelial cells and causes thrombosis

Dierence in rash starts from trunk and spreads out

Coxiella Burnek (Q-fever) Nega3ve Weil-felix test but immunouorescent!

No skin rash & ring granuloma on liver biopsy [fat surrounded by epithelioid cells]

Candida albicans (moniliasis)

Usually supercial oral thrush, vagina, mucocutaneous
Mouth oral thrush which is easily scraped o
Esophageal
Vaginal causes yeast infecEon

Squamous epithelium stain with PAS, silver stain or mucicarmime,

budding yeast with pseudohyphae (chinese lejer appearance)
InltraEon of PMNs + lymphocytes + monocytes + giant cells [mixture of
acute & chronic in all fungi]
Opportunis3c - diabeEc paEents, immunocompromised and paEents on
broad spectrum anEbioEcs
Invasive form can disseminate abscesses

PneumocysEs jiroveci
Opportunis3c AIDS pa3ents (CD4 <200)
Presenta3on: fever, dyspnea on exerEon, dry cough (b/c
produces coTon candy EXUDATE in alveolar space - not
able to produce sputum) & intersEEal pneumonia/
inamma3on & thickening of alveolar wall w/ sparse
mononuclear inltrate
InltraEon of PMNs + lymphocytes + monocytes + giant cells
[mixture of acute & chronic in all fungi]
Inves3ga3on: bronchoalveolar lavage & stain with silver
stain black cup shaped cyst

Aspergillus

InhalaEon of aspergillus (mycelial form)

No eect in immunocompetent
A. avus = aatoxin & A. fumigatus = gliotoxin

Opportunis3c fungi in immunocompromised

Aspergilloma (fungal ball) colonize a pre-exisEng cavity from TB or lung abscess

Allergic bronchopulmonary aspergillosis type I and type III hypersensi3vity

See in pts with bronchial asthma inhale colonizes causes wheezing, dyspnea, producEve
cough and fever exacerba3on of asthma
Looks like asthma Curschman spiral, Charcot-Leyden crystals & eosinophils BUT SEE HYPHAE

Disseminated aspergillosis angio-invasive ONLY in immunocompromised!

Invades blood vessel wall thrombosis coagulaEve necrosis
Most common organs brain and lung necro3zing pneumonia and stroke

Stain with PAS, silver, mucicarmine

Slender organisms, septate hyphae that branch at acute angles

InltraEon of PMNs + lymphocytes + monocytes + giant cells [mixture of acute &

chronic in all fungi]

Mucormycosis

Zygomycetes: Mucor, Rhizopus & Absidia

OpportunisEc fungi in immunocompromised

Prevalent in pa3ents with diabe3c ketoacidosis b/c low pH favors growth of
organism & availability of glucose

Pathogenesis: InhalaEon of spores tropism for endothelial cells of

blood vessels angio-invasive disseminated endothelial damage
thrombosis ischemia hypoxia
Most common in cerebral hemispheres red infarct
Lung, GI, sinuses

Presenta3on: sero-sangrenous nasal discharge, fever, pain and headache &

rhino-facial-palatal necrosis
Inves3ga3ons: stain sputum or nasal discharge with silver stain/PAS
Broad organisms with non-septate hyphae branching at right angles

Cryptococcus neoformans (Torulosis)

E3ology: opportunisEc infecEon in immunocompromised HIV pa3ents (CD4 <100)
Pathogenesis: spores in pigeon droppings inhalaEon granulomas with giant
cells
Usually involve lungs & brain
Inammatory reac3on is ABSENT due to inert capsule
If disseminated meningiEs!

NO FEVER OR NECK STIFFNESS, but will see headache, intracranial pressure, projecEle vomiEng,
photophobia

Diagnos3c:

PAS, silver stain, mucicarmine (stains organism red in perivascular space)

CysEc spaces containing soap bubble lesions
CSF add India ink stains polysaccharide capsule of Cryptococcus organisms appear as
clear halo NEGATIVE staining!
Latex agglu3na3on test using anEbodies most specic
Lumbar puncture: mixed acute & chronic inammatory cells (sparse), glucose (normal
or ) & protein ()

Tuberculosis

Most important risk factor = HIV

Immunocompetent with 1st 3me infec3on (Asia, Africa) inhalaEon of M. tuberculosis

Try to wall it o caseous central necrosis (Gohns focus in lower part of upper lobe or upper part of
lower lobe/subpleural locaEon) casea3ng granuloma [TYPE IV HYPERSENSITIVITY]
Primary caseous necrosis is very mild, inammaEon spreads to regional lymphaEcs and hilar lymph
nodes primary complex (Gohns focus, regional lympha3cs, hilar lymph nodes)
Contained in the lung & can heal via brosis b/c caseaEon is very mild

Langhans giant cells & periphery has broblasts become broEc and dystrophic calcicaEon
Presenta3on: fever, night sweats, weight loss ,cough with hemoptysis (in 2 TB)
Inves3ga3on:
3 samples of early morning sputum stain with acid fast
Pleural biopsy look for caseaEng granuloma

Immunocompetent with reinfec3on

Extensive caseous necrosis with cavita3on secondary TB in apex of upper lobe

Immunocompetent immunocompromised with reac3va3on

Secondary TB gets into blood secondary progressive TB miliary TB

SEll get secondary TB

Milet sized lesions b/c immunocompromised cant form granulomas no caseaEon/cavitaEon/

brosis; ONLY EXTENSIVE NECROSIS
MulEplies in lung brain (encephaliEs), spleen and liver, pancytomegaly, testes, ovaries (inferElity),
iliocecal brosis (intesEnal obstrucEon), kidney (renal failure)

Primary progressive

Immunocompromised gets TB for rst Eme dont contain it in lung b/c cant form a granuloma (no
Gohns complex)
Becomes disseminated and miliary TB

Tuberculosis

Complica3ons: pneumonia, lung abscess, empyema, pleural

thickening, aspergilloma (b/c preexisEng cavity), late complicaEon
(AA amyloidosis), PoTs disease (cold abscess of the spine
ruptures into paravertebral so[ Essue)
Tuberculin (PPD) test measure extent of hyperemia with
injecEon of tubercle protein
>5mm = HIV+, history of recent contact, chest x-ray with old TB scar
>10mm = IVDA, homeless, born in countries with high incidence, health
care workers, nursing home residents
>15mm = EVERYONE!

Dimorphic Fungi
Coccoides immi3s thick walled, non budding
spherules
Largest pathogenic fungus
Southwestern & Western US
Valley fever

Blastomyces derma3dis round

Broad-based budding
Endemic area overlaps with Histoplasma

Histoplasma capsulatum

Histoplasmosis

E3ology: inhalaEon of spores in bird and bat droppings [caves]

Ohio, Appalachia, Mississippi River Valley

Acute in immunocompetent paEents

Contained in the lungs; see PMNs
AsymptomaEc or u like

Chronic presents exactly like TB

Fever, weight loss, cough with hemoptysis

Immunocompetent caseaEng granuloma (like TB) mostly in upper lobe
Dierence on chest x ray mulEple foci (buckshot dystrophic calcica3on)
TB only has one focus but x-ray is idenEcal to that of miliary TB

Immunocompromised pa3ents disseminated b/c cannot form a granuloma to contain

it in the lungs
Go to cells of RES lymphadenopathy, splenomegaly, hepatomegaly, bone marrow suppression
(pancytopenia)

Inves3ga3on: Histoplasma anEgens in blood and urine by PCR

Biopsy: intracellular organism

Acute in PMNs
Chronic - budding yeast in macrophages - pH to survive

Cat Scratch Disease

E3ology: gram negaEve bacteria Bartonella henselae

Immunocompetent face or upper limbs; self-limiEng

2 weeks wall o infecEon, suppura3ve granuloma in lymph nodes

Type IV hypersensi3vity reacEon

Presenta3on: fever, headache, malaise, tender, suppuraEve, warm axillary/

cervical lymph nodes
Lymph node biopsy see suppuraEve granuloma (PMNs and debris)

Epithelioid cells arranged around a stellate area of necrosis composed of dead/dying

PMNs

Immunocompromised

No granuloma disseminates see gram negaEve organisms in macrophages

Bone osteomyeliEs, thrombocytopenia
Brain encephaliEs

Not self limi3ng die

Tuberculoid
L
eprosy
E3ology: inhalaEon of intracellular, acid fast M. leprae

Aects cooler areas of body distal extremiEes, ear lobe, peripheral nerve and testes
Found within macrophages or Schwann cells

Tuberculoid

Lepromatous

Good CD4 immunity

Form casea3ng granuloma
Poor CD4 immunity
No granuloma & Leonine facies

Lepromin test: (+) = tuberculoid and (-) = lepromatous b/c looking for CD4 immunity
Presenta3on: skin lesions - less in tuberculoid than lepromatous

Auto-amputaEons of digits very disguring

Peripheral neuropathy paresthesia, atrophy
InferElity - especially in men
Dont die OF leprosy but die from secondary bacterial infecEons sepsis

Biopsy of skin or nerve

Tuberculoid see granuloma

Lepromatous more skin lesions, no granuloma, Virchow cells/foamy cells/lepra cells (acEvated
macrophages containing organism + lipid)

Pulmonary Lab Slides

Airway Histology
Bronchi

Bronchioles

Epithelium
Ciliated columnar cells
Goblet cells
Basal cells
Neuroendocrine cells

Epithelium
Ciliated columnar cells
Clara cells

Basement membrane

Basement membrane

Smooth muscle

Smooth muscle

Seromucinous glands

-----------

Car3lage

-----------

Vasculature & lymphaEcs

Vasculature & lymphaEcs

Obstruc3ve Lung Diseases (COPD) - 4th

Restric3ve Lung Diseases contrac3on
leading COD in US; M=F
atelectasis due to brosis!
TLC, RV, FRC
FEV1: FVC normal ra3o & peak ow
FEV1: normal FVC ra3o & peak ow
Hypoxia, hypercapnea & resp acidosis
Emphysema

Acute Respiratory Distress Syndrome

Chronic BronchiEs

Fibrosing
UIP/IPF [cobblestone appearance]
Accelerated form: AIP/Hamman Rich
NSIP [chicken-wire appearance]
COP/BOOP [ground glass; Masson body]
Collagen Vascular Disease
Lymphoid IntersEEal Pneumonia
Pneumoconiosis

Asthma

Eosinophilic
Loeer syndrome
Drug/Allergy related
Chronic eosinophilic pneumonia

Bronchiectasis

Granulomatous
Sarcoidosis
HypersensiEvity pneumonia/EAA
Smoking-related
DesquamaEve intersEEal pneumonia
RB intersEEal lung disease
Pulmonary Langerhans Cell Histocytosis

Atelectasis
Lung collapse O2 shortness of breath

Resorp3on obstruc3on of the bronchial lumen; REVERSIBLE

AspiraEng a peanut, tumor obstrucEon (sq. cell carcinoma, small cell carcinoma &
bronchial carcinoid) & chronic bronchiEs (mucus plugs)
X-ray: trachea deviates in same direc3on as the collapse

Compression - REVERSIBLE

Pneumothorax, hemothorax, pneumohemothorax, chylothorax (lymph), empyema (pus),

pleural eusion
X-ray: Trachea deviates to opposite side

Contrac3on IRREVERSIBLE due to pulmonary brosis

Trachea in either direcEon or central

Caused by all restric3ve lung diseases which lead to brosis

AIP, UIP, IPF, COP, sarcoidosis, honeycomb lung, asbestosis, silicosis, coal workers pneumoconiosis

FEV1: FVC raEo is normal but TLC & RV

DAD/ARDS/Hyaline Membrane Disease/Shock Lung

Direct causes: pulmonary contusion (bruise) due to blunt force trauma to chest, near drowning experience or
aspiraEon pneumonia
Indirect causes: acute pancrea33s (enzymes causing damage to lung), uremia, sepsis, burns
Pathogenesis: imbalance of pro & an3-inammatory response

Damage to type II pneumocytes and/or endothelial cells

Pulmonary edema due to acute inammaEon releasing histamine

Acute (exuda3ve ) phase: 0-7 days neutrophils, necroEc debris, brin

Heavy & rm lungs, intersEEal & intra-alveolar edema/hemorrhage, necrosis & sloughing of alveolar epithelial cells
See hyaline membranes made up of debris and brin diusion barrier

Chronic inammaEon = pulmonary brosis contracEon atelectasis

Cor pulmonale R heart failure secondary to lung disease

Diagnosis: sudden onset, ground glass appearance on x-ray, bilateral diuse inters33al inltrates, pulmonary
edema with normal pulmonary capillary wedge pressure (non-cardiogenic/no heart failure which wedge
pressure) & refractory hypoxemia (even with supplemental oxygen/posiEve pressure oxygen - sEll cyanoEc due
to hyaline membranes)

ExudaEve pulmonary edema - lots of cells & proteins

Organizing (prolifera3ve) phase: 1-3 weeks - proliferaEon of Type II pneumocytes & broblasts which lay down collagen
organizaEon of brin exudates brosis & alveolar septal thickening

Alveolar capillary membrane compromise (disrupts gas exchange),vascular permeability, loss of diusion & surfactant

Sudden onset SOB, tachypnea, tachycardia, cyanosis

Complica3ons: respiratory failure, pulmonary edema if survive up to 2 weeks: pulmonary brosis,

contracEon atelectasis & cor pulmonale, nutmeg liver (chronic passive congesEon)

NOTE:
Neonatal RDS - no hyaline
membranes b/c no
inammaEon/ neutrophils
due to damaged endothelial
cells or type I pneumocytes

Emphysema
Permanent destruc3on & dilata3on of airways distal to terminal bronchioles without

brosis (excepEon: irregular type);

Centroacinar respiratory bronchioles & upper lobes

Have to be a smoker b/c normal levels of A1AT but elastase overwhelms the A1AT

Panacinar enEre acinus from respiratory bronchioles to the alveolar ducts; lower lobes
Deciency of A1AT PiZZ homozygous recessive on chromosome 14
As a child, pt. had cirrhosis of liver b/c liver makes A1AT
Dont have to be a smoker but smoking will make it occur earlier

Irregular (paracicratricial) only one with brosis & contrac3on atelectasis

Usually asymptomaEc

Septal (distal acinar) - ruptures into pleural space bullae & pneumothorax compression atelectasis

Presenta3on: skinny (compensaEng and using accessory muscles), barrel chested (b/c
obstrucEve lung disease), hunched over & breathing through pursed lips
Pink puers compensaEng early to prevent cyanosis & hypoxia

Kidney makes more EPO which drives erythropoiesis secondary polycythemia

FEV1: FVC; TLC & RV

ABG O2, normal pH and normal CO2 (later stages pH drops and CO2 increases)
X-ray hyperlucent, hyperinated lungs with aTened domes of diaphragm and narrow medias3num

Complica3ons: respiratory failure and cor pulmonale (right heart failure secondary to
pulmonary hypertension)
A[er 2 weeks, liver cirrhosis/nutmeg liver (zone 3: coagulaEve necrosis & zone 1: fajy change)

Chronic
B
ronchiEs
Produc3ve cough of foul smelling, purulent sputum for 3 consecu3ve months for 2

consecu3ve years; clinical diagnosis

E3ology: Cigare3e smoking
Pathogenesis:

Bronchus squamous metaplasia, goblet cell hyperplasia, thickened BM, hypertrophy of bronchial
smooth muscle & hypertrophy/hyperplasia of seromucinous glands
HYPERSECRETION OF MUCUS!

Reid index (raEo of thickness of submucosal gland to overall bronchial wall) elevated >50%
Bronchioles brosis of the bronchiolar wall luminal narrowing, metaplasia of goblet cells
BronchioliEs obliterans (obliteraEon of lumen of bronchioles)
Only place where you see brosis in chronic bronchiEs

Presenta3on:

Blue bloaters b/c decompensate early, cor pulmonale ascites and peripheral edema
Get right heart failure and respiratory failure early

FEV1: FVC ra3o & TLC & RV

X-ray: see pneumonia b/c no cilia & resorpEon atelectasis b/c of mucus plugs blocking the bronchial
lumen
ABG: hypoxia, hypercapnea, respiratory acidosis
Peripheral chemoreceptors detect PO2, not PCO2 so cant give O2 b/c pt stops breathing

Complica3ons: respiratory failure early, cor pulmonale early, cardiac cirrhosis/nutmeg liver,
resorpEon atelectasis, recurrent pneumonia lung abscess bronchiectasis

Atopic Bronchial Asthma

Asthma the only reversible obstrucEve airway disease; bronchoconstricEon

Atopic extrinsic; geneEc/family history; EPISODIC
Triad: bronchial asthma, allergic rhiniEs, eczema
Type I hypersensi3vity

1st exposure, anEgen presentaEon to mast cells IL-4 causes IgE producEon
2nd exposure, cross-linking on surface of mast cell mast cell degranulaEon histamine & leukotrienes edema/
exudate/neutrophils

IL-4 sEmulates IgE producEon IgE coats mast cells which degranulate w/ anEgen exposure
C5a, IL-8- chemotacEc for neutrophils
IL-13 mucus producEon
IL-5 chemotacEc for eosinophils

Presenta3on: expiratory wheeze, chest Eghtness, producEve cough, SOB

Inves3ga3ons:

Sputum cytology Curschmann spirals (shred ding of bronchial epithelial cells) & Charcot Layden crystals
(MBP & eosinophilic caEonic protein)
X-ray hyperinated lung elds
Flow meter peak ow rate
Blood CBC lots of eosinophils eosinophilia
Pulmonary func3on tests FEV1: FVC ra3o & TLC & RV

DestrucEon of pseudostraEed columnar epithelium, goblet cell hyperplasia causes mucus

plugs, thickening of BM, hypertrophy of bronchial smooth muscle, hypertrophy of
seromucinous glands (normal Reid index) , lots of neutrophils & eosinophils
Mucus plugs in bronchial lumen similar to chronic bronchiEs without squamous metaplasia

Non-atopic Bronchial Asthma

Non-atopic Intrinsic; Aspirin and viral infecEons
Aspirin: inhibits COX & favors lipooxygenase
leukotrienes bronchoconstricEon

Aspirin triad = nasal polyps, intrinsic asthma, allergic rhini3s

Viral: lowering the threshold for sub-epithelial vagal

receptors acetylcholine binding PS response
bronchoconstricEon
Albuterol (-2 agonist) sEmulate sympatheEcs
bronchodilaEon
No IgE, NO eosinophils, no family history & NO Charcot
Leyden crystals
Do see Curschman spirals & neutrophils

Status asthma3cus common in extrinsic

Do not respond to medicaEons/beta 2 agonists

Require intubaEon

Bronchiectasis

Permanent/ irreversible dila3on of bronchi to pleural

surface
Pathogenesis: obstrucEon & recurrent infecEons [S.
aureus, Klebsiella] aects the lower lobes
Cause: CysEc brosis, Kartegeners syndrome (sinusiEs,
bronchiectasis, inferElity in males, situs inversus/
dextrocardia), chronic bronchiEs (mucus plugs), allergic
bronchopulmonary aspergeillosis, TB, centrally located
lung tumors (squamous carcinoma of lung, small cell
carcinoma of lung & bronchial carcnoid)
Presenta3on: High spike fevers, halitosis, producEve
cough with foul smelling sputum, nger clubbing (due to
hypoxia), hemoptysis
Inves3ga3ons:
Sputum cytology mixed ora of anaerobes (make it foul
smelling) & aerobes
Chest X-ray train track appearance because there is
dilataEon all the way to pleural surface

Complica3ons: Can lead to respiratory failure, cor

pulmonale, FEV1:FVC, TLC & RV, metasta3c
abscesses (from lung to brain), sepsis if travels to blood,
resorp3on atelectasis due to obstrucEon of bronchial
lumen & AA amyloidosis due to chronic inammatory
condiEon restric3ve cardiomyopathy!

Idiopathic Pulmonary Fibrosis (UIP)

Usual Inters33al Pneumoni3s (UIP) pajern seen on histology

DOES NOT ALWAYS LEAD TO IPF

Diagnosis of exclusion b/c cause is unknown (idiopathic)

Males over 60; smokers
Presenta3on: dry cough with dyspnea on exerEon, nger clubbing, pulmonary brosis,
geographic & temporal heterogeneity

Progressive & relentless need lung transplanta3on

Geographic heterogeneity favors lower lobe rst
Temporal heterogeneity coexisEng of old (anucleated, acellular, pink) & new brosis (broblast foci, has
cells)
Cobblestone pleural surface honeycomb lung (pockets of airspaces contain mucus and lined by Type II
pneumocytes)
X-ray bilateral re3culo-nodular shadows mainly lower lobes with honeycomb lung

RestricEve - Normal FEV1: FVC, TLC & RV

Respiratory failure, contracEon atelectasis, cor pulmonale due to HTN & right heart failure,
nutmeg liver/cardiac cirrhosis

AIP = Diuse Alveolar Damage without a cause

UIP + DAD = AIP (accelerated version of IPF)

Non-specic IntersEEal Pneumonia

Idiopathic, bejer prognosis, younger ppl
Histopathology
Uniform brosing process [chicken-wire]
Two variants
Cellular (inltraEon of lymphocytes) more inammaEon
Fibrosing more brosis

Lacks honeycomb change, broblast foci &

heterogeneity

Cryptogenic Organizing Pneumonia

(BronchioliEs Obliterans Organizing Pneumonia)
Idiopathic
X-ray: patchy peribronchial/sub-pleural
consolida3on
Histopathology:
Masson bodies polypoid plugs of loose CT in
alveolar ducts, alveoli & bronchioles
Alveolar architecture NOT destroyed!
Recover spontaneously/with steroids

Collagen Vascular Disease

Pulmonary manifesta3ons:
Lupus
Rheumatoid arthriEs
Systemic sclerosis
DermatomyosiEs-polymyosiEs
Sjorgens syndrome

Pleural involvement:
PleuriEs
Pleural nodules
Pleural eusion

Lymphoid IntersEEal Pneumonia

Idiopathic
Expansion of the inters33um by sheets of
lymphoid cells
Associated with
CT diseases
Autoimmune diseases
HIV

May transform to lymphoma

Coal Workers Pneumoconiosis

Inhala3on of Coal dust Black Lung Disease

Seen in urban dwellers, tobacco smokers, & coal workers
Black pigment (from carbon) deposits in lungs Antharcosis
Types of CWP:
Asymptoma3c accumulaEon of carbon in perilymphaEc regions & LNs
Simple AggregaEons of carbon-laden macs in nodules & macules
Occurs in upper lobes
Macules macrophages containing coal
Nodules mulEple macules w/ brosis, more common
May cause dilaEon of alveoli Focal dust emphysema
Complicated Progressive massive brosis
Coalescence of modules into brous scars
Large blackened scars
Signicant respiratory impairment
Carbon alone is inert & not brogenic gives Pulmonary antharcosis Asymptoma3c CWP
Macs not killed
InhalaEon of Carbon w/ impuri3es results in Fibrosis Honeycomb Lung
HIGHER RaEo of carbon to other materials higher risk of CWP
Dust cells (Alveolar macs) engulf coal (carbon w/ impuriEes) secrete TGFB AcEvates broblast release
Collagen Fibrosis
May migrate to hilar lymph nodes, or
Accumulate in connecEve Essue along lymphaEcs
Signs/Symptoms: dyspnea on exerEon & non-producEve cough
Inves3ga3ons:
Spirometry FEV/FVC normal, TLC low (RestricEve disease)
Complica3ons:
ContracEon atelectasis d/t brosis
Cor pulmonale

Silicosis

Commonly d/t Sandblas3ng/stone cu^ng/hard rock mining Inhale of Silica (silicon dioxide)
Crystalline form (quartz) most brogenic
Seen in miners, glass manufacturers, quarry workers, stone cuTers
Slow, progressive nodular & brosing pneumoconiosis (not granulomatous) 10-20 yrs Chronic silicosis
Nodular lesions may undergo central cavitaEon
Starts at UPPER lobes
Mac engulfs crystalline silica (w/ SiOH) H bonds w/ proteins & phospholipids of mac damage cell membrane and
kills Macs
Release TGF beta produce collagen whorls of collagen nodules (surrounded by lymphos & macs)
PresentaEon
DOE
Non-producEve cough
InvesEgaEon:
CXR eggshell calcica3on in hilar LN (thin rims of calcicaEon in hilar LN)
Stain w/ polarized microscopy weakly birefringent
Birefringent par3cles in polarized light white par3es of silica glowing
Spirometry restric3ve FEV1/FVC normal, TLC low
ComplicaEons
Fibrosis w/ dystrophic Ca2+ ContracEon atelectasis
Respiratory failure
Cor pulmonale
Increase risk of Pulmonary TB d/t increase use of macs to digest silica none available to form
granulomatous inammatory response (poor granuloma formaEon)
Depressed cell-mediated immunity

Asbestosis

Inhala3on of Asbestos bers, common in:

Mining, Shipyard worker, Ship builders, Construc3on workers, Home insula3on, Milling
Two types:
Amphobole s3, straight more dangerous, penetrates lower lobes
Crysto3le curly exible less pathogenic more easily removed by mucociliary apparatus
Causes DIFFUSE INTERSTITIAL FIBROSIS (not nodular) in LOWER lobes around bronchioles, alveolar ducts, intersEEum
Gross honeycomb lung brosis
Thickening of the pleura
See thickening of RV hypertrophy Cor pulmonale
Asbestos in the lymph nodes bilateral hilar lymphadenopathy Carcincoma
Large pleural mass in the recess obliteraEon of pleural space
ALL indicaEons of MESOTHELIOMA
MS Asbestos body Ferruginous bodies Macs + asbestos ber
Macs ajempt to phagocyEze asbestos ber Macs coat ber w/ iron (from their own ferriEn) Ferric state beaded-structures w/
translucent center
H&E Golden-Brown
Prussian blue Blue
Sign/Symptoms: dry cough & dyspnea on exerEon
InvesEgaEon
PFT restricEve, normal FEV1/FVC, low TLC
Sputum see Asbestosis bodies (golden/brown or blue) as described
ComplicaEons
HC lung Fibrosis (RestricEve) Contrac3on atelectasis
Peribronchiolar brosis, respiratory failure & cor pulmonale
Increased risk of cancer:
Bronchogenic carcinoma (most common)
Common cancer d/t smoking cigarejes
Smoking + Asbestosis Increased risk by 55x
Mesothelioma (unique)
Pleural cancer d/t asbestosis
NeoplasEc mesothelial cells lung unsheated w/ yellow-white rm (gelaEnous) layer of tumor
May obliterate pleura space, fuse parietal and visceral pleura
Manifests years a[er exposure 25-50 yrs
PresentaEon wasted & anemic
Pleural plaques well-circumscribed plaques of dense collagen and Ca2+ Dystrophic calcicaEon
Found on anterior and posterolateral parietal pleura (NOT visceral) & domes of the diaphragm
Flat or nodular; does not contain Asbestos bodies

Sarcoidosis

Idiopathic, diagnosis of exclusion

African american, Danish, and Swedish; higher incidence in non-smokers & young females
Pathogenesis: Type IV hypersensi3vity with non-casea3ng granulomas w/ lymphange3c distribu3on

Incidental nding of bilateral hilar lymphadenopathy

RestricEve cardiomyopathy, facial nerve paralysis , paroEd & lacrimal glands (sicca syndrome) , Milkulicz syndrome,
uveiEs, hepatosplenomegaly, renal failure & erythema nodosum on skin painful rash on shin

Epitheliod cells acEvate vitamin D hypercalcemia (metasta3c calcica3on)

ACE is elevated used monitor response to treatment
Normal FEV1: FVC, TLC & RV
Polyclonal hypergammaglobulinemia dysregulaEon of T cells
Cutaneous anergy - develop sarcoidosis following TB, use all T cells and epithelioid cells to form non-caseaEng
granulomas no cells to mount response to PPD become PPD (-)
Complicaitons: mulE-organ problems, pulmonary failure, cor pulmonale, contracEon atelectasis,
hypercalcemia
Biopsy of hilar lymph node see non-caseaEng granuloma!

Giant cells of granuloma Schaumann body (laminated calcium concreEons due to metastaEc calcicaEon)
Asteroid bodies proteinaceous inclusions in giant cells

Presenta3on: dry cough & dyspnea on exerEon

Starts in the lung BUT mulEsystemic!

Eventually leads to honey comb lung with pulmonary brosis

Lung transplant sarcoidosis recurs in 75% pa3ents!

Other non-casea3ng granulomas: berryliosis, Crohns, drug reacEons to methotrexate

HypersensiEvity Pneumonia (Extrinsic

Allergic AlveoliEs)
EEology

Inhaled organic anEgens damage at level of alveoli

restricEve lung disease diusion capacity, lung
compliance & total lung volume

Pathogenesis:

Immune complex mediated (Type III) & cell-mediated

(Type IV) hypersensiEvity reacEon to an extrinsic an3gen

Histopathology:

Airway centered process

Chronic inammatory inltrate
Organizing pneumonia
Giant cells & poorly formed non-necro3zing granuloma!

DesquamaEve IntersEEal Pneumonia

Rare pneumonia; seen in smokers
Prominent lling of alveolar spaces by
alveolar macrophages
Minimal intersEEal brosis

Respiratory BronchioliEs IntersEEal

Lung Disease
Seen in smokers; in 40s & 50s
AccumulaEon of smokers macrophages
within the lumen of respiratory bronchioles
Associated with peribronchiolar brosis
Responds to steroids & smoking cessa3on

Pulmonary Langerhan Cell HisEocytes

(Eosinophilic Granuloma)

Almost exclusively in smokers

Culprit cell = Langerhans cell
Contain Birbeck granules on EM
tennis racket appearance

Typical Pneumonia
Lobar young immunocompetent
Streptococcus pneumoniae
COMPLETE RESOLUTION
Spreads via the pores of Kohn

Architecture stays intact

Conuent consolida3on of en3re lobe!
Bronchi are NOT involved

Bronchopneumonia patchy lung; bronchi & bronchioles are damaged

Klebsiella alcoholics, diabeEcs > aspiraEon
Red currant jelly sputum

Pseudomonas CF, venElators, burns, lung abscesses

Klebsiella & pseudomonas both cause necroEzing pneumonia b/c angio-invasive
endothelial damage
S. aureus following viral infec3on causes bronchopneumonia
Legionella contaminated water sources/ACs
Extrapulmonary symptoms confusion, diarrhea, abdominal pain, liver & kidney compromise,
vomiEng
Look for urinary anEgen

Community Acquired Acute

Pneumonia

Symptoms: high fever, shaking chills, pleuriEc chest pain

S. pneumoniae most common; lower lobe or right middle lobe

H. inuenzae most common cause of COPD exacerba3on

Malnourished, chronic alcoholics, diabe3cs

Red currant jelly sputum

P. aeruginosa

A[er viral respiratory illness secondary (measles in children, inuenza in adults)

Hospitalized paEents primary nosocomial infec3on abscess, empyema
IVDA right sided endocardi3s
Penicillin resistance via beta lactamases MRSA

K. pneumoniae extensive destrucEon

Elderly individuals

S. aureus most likely to cause abscesses

Underlying chronic diseases: COPD, cysEc brosis, bronchiectasis

Capsule B present targeted by vaccine

Moraxella catarrhalis 2nd most common cause of COPD exacerba3on

Underlying chronic diseases: CHF, COPD, DM

PaEents with splenic func3on [sickle cell, liver cirrhosis] give vaccine

Progressive necroEzing pneumonia in cys3c brosis & burn pa3ents

Extensive destrucEon, abscess formaEon
Green colored agar smells like grapes

L. pneumophilia prevents phagosome fusion

Aqua3c environments: water cooling towers or tubing of portable water

Community Acquired Atypical

Involves INTERSTITIUM! Pneumonia

E3ology: obligate intracellular bacteria walking pneumonia

Most common = Mycoplasma

Chlamydia (psijaci, pneumoniae) & Coxiella burnek (from sheep; no rash in Q fever)
Viruses CMV, parainuenza

Pathogenesis: alveolar spaces are free/empty, inammaEon in alveolar wall

(thickened septae) cough is DRY
Presenta3on: mild symptoms in the beginning (dry cough & low grade fever), DAD
(hyaline membrane)
Inves3ga3ons:

No dullnesss on percussion b/c alveolar spaces are empty

Worse than what x-ray shows
X-ray inters33al inltrates; ground glass opacity
Serology IgM, IgG Eters most accurate

ComplicaEons ARDS hyaline membranes on autopsy

No neutrophils. Only edema, lymphocytes & monocytes

Lung Abscess

AspiraEon lung abscess

Predisposing factors: alcoholics, stroke paEents ( gag reex), intubated, seizure,

Alzheimer's or any hospital bedridden paEents
Aspirate more common on right side!
Standing bojom of right lung (right bronchus is nearly verEcal)
Laying down top of right lung

MulEple lung abscesses in IV drug abusers due to dirty needles introduces S.

aureus right heart infec3ve endocardi3s in tricuspid sepEc emboli
mul3ple lung abscesses
SepEcemia can also cause mulEple lung abscesses

Presenta3on: produc3ve cough, halitosis, hemoptysis, nger clubbing

X-ray: cavity with air uid level; liquefacEve necrosis due to pyogenic bacteria
Sputum: mixed ora

Complica3ons: empyema, compression atelectasis, bronchopleural stula,

sepEcemia, AA amyloidosis
Aspergilloma (fungal ball) in cavity formed by abscess

Other causes of lung abscess:

Lymphomatoid Granulomatosis associated with EBV & necroEzing granulomas

Wegeners granulomatosis
Churg Strauss

Cardiogenic Pulmonary Edema

E3ology: le[ heart failure (dyspnea, orthopnea, paroxysmal dyspnea, pink frothy
sputum)
Pathogenesis:
<2 weeks transudate due to hydrosta3c pressure
2 weeks alveolar wall brosis; heart failure cells

Presenta3on:

pulmonary capillary wedge pressure

No hyaline membrane
At 2 weeks, hemosiderin layden macrophages/heart failure cells

Complica3ons:

Can lead to pulmonary HTN right heart failure

Will NOT lead to cor pulmonale (b/c due to cardiac problem)

Non-cardiogenic pulmonary edema

E3ology: ARDS, high alEtude, neurogenic, pulmonary thromboembolism

Pulmonary Embolism

E3ology: DVT, stasis caused by long ights, birth control pills (estrogen is
pro-coagulant), adenocarcinoma (produces mucins/procoagulants) &
Factor V leiden muta3ons
Most commonly seen in popliteal, iliac femoral veins at or above knee;
usually unilateral
Pathogenesis of DVT:
Virchows triad:

Hypercoagulability
Endothelial injury
Turbulence of blood ow

Presenta3on:

Massive saddle embolisms at bifurcaEon of pulmonary trunk - sudden death/

no eect on lung
Major with CHF dyspnea, pleuriEc chest pain, hemoptysis, coagulaEve
necrosis in the lung
CHF compromises the bronchial artery red infarct

Major with intact bronchial circula3on pulmonary hemorrhage

Minor asymptomaEc

Recurrent minor --> pulmonary hypertension right heart failure (cor pulmonale) &
nutmeg liver awer 2 weeks
Before 2 weeks transudate in both liver AND lung

Inves3ga3on spiral CT/pulmonary angiogram

Pulmonary
H
ypertension
Mean PA pressures > systemic pressure

E3ology: secondary to cross-sec3onal area of blood ow

Primary mutaEon in BMPR2 (bone morphogenic protein receptor) binds TGF
Causes hyperplasia & vascular resistance
Common in young females 20-40
Long standing/chronic severe plexiform lesions vasculature channels within the inEma

Small capillaries cant take extreme pressure & undergo brinoid necrosis, dilaEons & hemorrhage

Secondary

Pulmonary: obstrucEve & restricEve lung diseases except bronchial asthma

Cardiac: L R shunt (ASD, VSD, PDA)
PresentaEon: syncope, angina & dyspnea (SAD)
Loud P2 [pulmonary valve makes a sound when it closes]

Most accurate test cardiac catheterizaEon to measure pressures of heart

Complica3ons right heart failure nutmeg liver

Pulmonary capillary wedge pressures will be elevated

Pi^ng peripheral edema, ascites, distended jugular edema, hepatosplenomegaly

Pulmonary trunk atherosclerosis atheroma due to pressure

Medium vessels inEmal cell & smooth muscle cell proliferaEon wall thickening
Small vessels thickening, medial hypertrophy, reduplicaEon of the IEL & EEL

Diuse Pulmonary Hemorrhagic Syndromes

AcEve bleeding into lungs & broEc thickening of alveolar septa

Triad:

Coexistence of old (hemosiderin laden macrophages) and new hemorrhage with alveolar
wall brosis temporal heterogeneity
Goodpastures young men; Type II hypersensiEvity [prototype]

Iron deciency anemia,

Cough with hemoptysis &
Pulmonary inltrates on x-ray

Wegeners

AnEbodies ajacking glomerular & pulmonary BM [collagen type IV]

See triad but also aects kidney so glomerular nephriEs hematuria
NEVER see URT no nasal ulceraEon or sinusiEs
An3-glomerular basement membrane (GBM) an3bodies to the alpha 3 chain of Type IV collagen &
linear deposits of IgG and C3
URT nasal ulceraEon & sinusiEs
LRT cough with hemoptysis
Causes glomerular nephriEs hematuria
cANCA and PR3 an3bodies
Renal biopsy & immunouorescence see nothing [pauci-immune]

Idiopathic pulmonary hemosiderosis no renal involvement/no hematuria

Children > adults
Self-limiEng and resolves on its own

Adenocarcinoma (30-35%)

E3ology: KRAS [smokers], EGFR [women, non-smokers, Asian] & ALK [signet
adenocarcinoma in non-smokers]
Common in non-smoker females <45 yrs old

Pathogenesis:

Cell of origin = bronchioloalveolar stem cell/clara cell

Precursor lesion: Atypical Adenomatous Hyperplasia (AAH)
Peripherally located - coin lesion on x-ray

Presenta3on: dyspnea, cachexia (b/c of TNF alpha), nger clubbing (all lung cancers)
Biopsy: malignant glands invading stroma

Produce lots of mucin well dierenEated in funcEon

PosiEve for cytokeraEn & PAS; diastase resistant b/c no glycogen
Immunohistochemical stains: TTF-1, cytokera3n 7, napsin-A
Prominent nucleus & nucleolus and dispersed chromaEn

Complica3ons:

Paraneoplas3c syndromes hematological all due to MUCIN [DIC, nonbacterial

thrombo3c endocardi3s/maren3c endocardi3s & trousseaus recurrent migratory
thromboEc phlebiEs]

LocaEon makes it easy to cause pleural eusions compression atelectasis

Le[ side pericardial eusion pericardial tamponade (hypotension, distended jugular veins &
mued heart sounds Becks triad)

Trousseus thrombus in supercial vein vein is red, hot, swollen and painful recurrent and migratory
Sterile vegeta3ons on heart valves = nonbacterial endocardiEs marenEc (?)
Aor3c valve aorEc regurg diastolic murmur

Adenocarcinoma in-situ
Non-invasive
Same cell of origin and precursor lesion
Present like lobar pneumonia
ProducEve cough with a lot of sputum
SOB, pleuriEc chest pain
No coin lesion
Consolida3on of the lobe on x-ray

Lepidic paTern on biopsy bujery on fence

PaEent dies from respiratory failure due to
overproducEon of mucin

Squamous Cell Carcinoma (25-30%)

E3ology: smoking, asbestosis

Smoking + asbestosis highest risk

Men > women

Pathogenesis: PseudostraEed squamous

Precursor lesion squamous dysplasia

Presenta3on: dyspnea, cachexia (b/c of TNF alpha), nger clubbing (all lung
cancers), hemoptysis
Kera3n pearls well dierenEated in funcEon, intercellular bridges
CytokeraEn posiEve
Immunohistochemical stains: P63, cytokera3n 5/6, cytokera3n 903

Complica3ons: centrally located blocks bronchial lumen and no cilia

Mucus trapped recurrent pneumonia lung abscess bronchiectasis

Gets bigger and compresses esophagus (dysphagia), trachea, recurrent laryngeal nerve
(hoarseness), bilateral hilar lymphadenopathy
Superior Vena Cava syndrome: edema of face and upper extremiEes, distended jugular
veins, dusty cyanosis & compression of central structures

Central, Cavi3es, CigareTes, hyperCalcemia

Can do METASTATIC calcica3on b/c secretes PTH-releasing pep3de

Large Cell Carcinoma (10-12%)

Undieren3ated epithelial malignancy
Lacks features of small cell & no glandular or squamous
dierenEaEon

Two types:
Large cell carcinoma (undierenEated)
Large cell neuroendocrine carcinoma
Neuroendocrine markers: chromogranin, synaptophysin, CD56

Pathogenesis:
3p deleEon
P16/CDKN2a

ParaneoplasEc syndrome gynecomas3a!

Small (Oat) Cell Carcinoma (20-25%)

Cell of origin = Kulchitsky (neuroendocrine) cells

Neuroendocrine marker Synaptophysin, Chromogranin, CD56

Centrally located carcinoma
99% are associated with cigareje smoking

Worst prognosis already metastasized

Order of metastasis 1 lymph node blood adrenal glands liver brain

bone kidneys
Cannot be resected need chemotherapy/radiotherapy

Pathogenesis

Myc amplica3on, p53, pRB

3p dele3on

Inves3ga3ons:

Biopsy salt and pepper appearance

Histology bronchial carcinoid looks EXACTLY the same b/c same cell of origin
Cytology shows nuclear molding (NOT in bronchial carcinoid)
KeraEn stain: classic rim & dot staining; rim = cytoplasm & dot = golgi apparatus

Paraneoplas3c syndromes

SIADH (diluEonal hyponatremia) which leads to cerebral edema and papilledema

Gonadotropins (FSH - gynecomasEa, LH problems ovulaEng leads to inferElity,
amenorrhea & hirsuEsm)
Cushing syndrome (bualo hump, purple striae, moon face)

Malignant Mesothelioma
1 malignancy of pleura, peritoneum or
pericardium
Strong associaEon with asbestos
rind-like encasement of the lung

Three primary paTerns

Epithelial
Sarcomatoid
Mixed (biphasic)

Stain for calre3nin

Lung Cancer X-rays

Lew image: Centrally located tumors (bronchial carnoid, small cell lung
carcinoma and squamous cell carcinoma)

ResorpEon atelectasis
Compression of esophagus & hilar lymph nodes
Widening of medias3num
Compression of recurrent laryngeal nerve, le[ phrenic nerve
Tracheal deviaEon to the RIGHT
SVC syndrome cant get blood back to right heart red face

Right picture: pancoast tumor/superior sulcus tumor

Right cervical sympatheEc syndrome ipsilateral horner syndrome

(anhydrosis, miosis, ptosis, endopthalmos sunken)
Was3ng of thenar eminence b/c compressing brachial plexus
Recurrent laryngeal nerve paralysis & dysphagia (compressed esophagus)
Right side SVC syndrome
Le[ side - compress thoracic duct chylothorax compression atelectasis

Metastasis from Lung Cancer

Common sites of lung metastasis
Adrenal glands (50%) can cause Addisons [rare]
Liver, brain, bone, kidney
Most common to metastasize:
Small Cell Lung Carcinoma > Adenocarcinoma >
Squamous cell carcinoma > Bronchial Carcinoid

Bronchial carcinoid has the best prognosis

Finger Clubbing
Pulmonary causes all causes of bronchiectasis,
empyema, lung abscess, lung cancers,
mesothelioma (pleural cancer), idiopathic
pulmonary brosis
Bronchial asthma, COPD, chronic bronchi3s &
emphysema = no nger clubbing
Cardiovascular causes sub-acute infecEve
endocardiEs, atrial myxoma and all R L shunts

Bronchial Carcinoid

Cell of origin = Kulchitsky (neuroendocrine) cells

IdenEcal to Small Cell Lung Carcinoma on histology
Same neuroendocrine markers

Best prognosis b/c it rarely metastasizes

Central, well dieren3ated & nested
Centrally located can lead to resorpEon atelectasis

Carcinoid syndrome episodic ushing, wheezing

and diarrhea due to serotonin
Urine look for 5HIAA

Solitary Pulmonary Nodule

Coin lesion - ONLY chest X-ray nding
Possible causes- adenocarcinoma (invasive rapid
rate of growth), sarcoidosis, TB, histoplasmosis,
pulmonary hamartoma (benign)
Ask paEent for previous x-rays to compare rate of
growth or do serial x-rays

Pulmonary Hamartoma
Asymptoma3c and benign
ONLY coin lesion with popcorn calcica3on
Capillary hemangioma also a hamartoma
Incidental nding

MetastaEc Deposits in the Lung

Metasta3c lung cancer TO THE LUNG FROM
BREAST/COLON CANCER is more common
than primary lung cancer (adenocarcinoma)

Drugs
Benet from anE-EGFR treatment ONLY if KRAS is
NOT mutated
EGFR-TKIs [getnib, erlo3nib] treat EGFR-TK
mutaEons, not RAS
EML4 + ALK fusion in NSCLC treat with ALK
inhibitor [crizo3nib]
Premetrexed adenocarcinoma/unspecic
NSCLC > squamous cell carcinoma
Bevacizumab dont use w/ squamous cell
carcinoma b/c can lead to hemorrhage

CVS Lab Slides

IntroducEon
Characteris3cs of a dysfunc3onal endothelial cell:
Prothrombo3c surface
Increased leukocyte adhesivity [VCAM-1/ICAM]
Does NOT produce nitric oxide constricEon!

Kaposis Sarcoma (HHV-8) AIDS paEent with purple

lesion on skin
Angiosarcoma exposure to vinyl chloride

Atherosclerosis
(disease of inEma)

Modiable predisposing factors: hypercholesterolemia, hypertension (60%), smoking, diabetes

Non-modiable risk factors: age (40-60 yrs = 5 fold) , gender (M > F), gene3c predisposi3on
Other risk factors: homocys3nuria, lipoprotein a, PA-1 inhibitor, CRP, estrogen & C. pneumoniae
3 main components of a bro-faTy plaque (atheroma):

Pathogenesis:

3 main factors make it stable: thick brous cap (pluripotent smooth muscles that travel from media to inEma deposit
collagen) protects lipid core from lumen, less lipid core and less inammatory cells (foam cells)

Unstable usually rupture li[s o the cap and exposes core to lumen

Fajy dots with macrophage foam cells fajy streaks with lipid laden macrophages cholesterol plaques
(asymptoma3c) can embolize during vascular procedures (ex: ANGIOGRAM), ulceraEon, hemorrhage ( 2 weeks
hemosiderin), ssures (deep ulcers), aneurysms, dystrophic calcicaEon & rupture (most dangerous)

Stable inEma has thickened (brous cap and lipid core)

Cells (macrophages, smooth muscle cells, T cells)

ECM (collagen, elasEc bers, proteoglycans)
Lipids

Moderately steno3c (50-75%), thinner brous cap, core rich in lipids, less smooth muscle proliferaton & ECCENTRIC!
If core gets in contact with lumen superimposed thrombosis (made up of brin, platelets and RBCs) get stroke,
MI, gangrene

Presenta3on asymptomaEc
Angiogram has high risk of emboliza3on
ORDER OF LIKELIHOOD: Infra-renal abdominal aorta (turbulence) proximal coronary arteries
branches of abdominal aorta [thoracic aorta, femoral, popliteal] internal caroEd artery Circle of Willis
[vertebral, basilar & middle cerebral]

Monckebergs Medial Calcic Sclerosis

Dystrophic calcica3on in tunica media
Does NOT encroach on the vessel lumen!
AsymptomaEc - found on x ray
Usually in elderly paEents due to wear and tear

Arteriolosclerosis (small vessel/ full

thickness) - Hypertension
Normal: < 130/85

Stage I: 140-159/90-99
Stage II: >160/100
Malignant: >210/120

Hyaline chronic benign hypertension aects only AFFERENT arteriole

AsymptomaEc
Signicant luminal narrowing renal failure
Pathogenesis: endothelial damage leakage of plasma proteins exudate

Hyperplas3c chronic malignant hypertension

Concentric, laminated thickening of the walls onion skin

Hematuria, oliguria
Hypertensive aor3c dissec3on (chest pain radiaEng to back), hemorrhagic
stroke, papilledema, reEnal hemorrhage,

Fibrinoid necrosis due to sudden malignant hypertension necro3zing

arterioli3s

Giant Cell (Temporal) ArteriEs

Pathogenesis:

Medium to large arteries aected - Temporal, ophthalmic and vertebral arteries

Giant cells, in3mal thickening, fragmenta3on of IEL
NOT transmural only aects in3ma and inner media
Granulomatous vasculi3s CD4+ mediated

Presenta3on:

M/F >50 year old

Jaw claudicaEon and facial pain
Polymyalgia rheuma3ca (muscle and joint pain)

Inves3ga3ons:

Markedly elevated ESR nonspecic marker of inammaEon

Temporal artery biopsy focal and skips so need to take a segmental biopsy so you
dont miss the lesion
NegaEve biopsy doesnt rule out disease

Treat with IV steroids to prevent blindness/reduce inammaEon on ophthalmic

artery
Takayasu arteri3s has same pathogenesis but its in <40, aects arch of aorta &
causes weak pulses in upper limbs

PolyarteriEs Nodosa
Pathogenesis:

Transmural & aects small to medium arteries but the LUNG is spared!
Capillaries, venules and arterioles are UNAFFECTED
String of pearls appearance

Distribu3on of lesions in descending order: kidney, heart, liver, GI

Renal artery thrombosis (but doesnt cause glomerular nephriEs so no
hematuria) ischemia hypoxia acute tubular necrosis renal
failure
HTN b/c sEmulates JG cells due to hypoxia

Coronary artery causes MI

Liver infarcts
GI red infarct

Vaso navorum common bular nerve foot drop

Displaced temporal heterogeneity old (brosis) and new
(neutrophils and brinoid necrosis) inammatory changes
Associated with Hepa33s B

Microscopic PolyangiiEs
Necro3zing vasculi3s (like PAN) BUT:
Smaller vessels (GN hematuria)
Lung (pulmonary capillaries hemoptysis)
Lesions of same stage/age in vessels
MPO-ANCA/P-ANCA (70%)

Churg Strauss
Aects small vessels
Allergic granulomatosis & angii3s
Symptoms: asthma, allergic rhiniEs, lung
inltrates, peripheral eosinophilia,
extravascular necroEzing granulomas
Cutaneous, GI, renal & lung involvement
MPO-ANCA/P-ANCA
Death due to cardiac involvement

Kawasaki Syndrome (Mucocutaneous

Lymph Node Syndrome)
Large, medium & small arteries
Causes coronary aneurysms MI

Japanese children < 4 years old

Presenta3on: fever, conjuncEval & oral
erythema, edema of hands & feet, skin rash,
enlargement of cervical lymph nodes
Treatment: high doses of ASA and IVIG

Breugers Disease (ThromboangiiEs obliterans)

Pathogenesis:

Small to medium arteries

Granulomatous vasculiEs with microabscesses - Type IV hypersensi3vity
ONLY one that eventually extends to veins and nerves involves the enEre
neurovascular bundle!

Aects 3bial and radial (distal peripheral arteries)

6Ps (paresthesia, pain, pallor, paralysis, poikilothermia (cold temp b/c no

perfusion) & pulselessness)

Presenta3on

Young (<35) male smokers of Japanese, Indian or Jewish descent

Stop smoking does NOT reverse condiEon but stops progression

IniEally intermiTent claudica3on (pain on walking, relieved at rest),

Reynauds phenomenon, phlebiEs, ulcers, gangrene, pain at rest (once the
nerves are aected )

Anterior biopsy thrombus in the lumen

 Presenta3on:

Wegeners

More common in males about 40

URT symptoms naso-mucosal ulcera3on, sinusiEs
LRT necro3zing pneumonia, granulomatous vasculiEs that does NOT spare
the lung lung abscess
Pneumonia not ge^ng bejer with anEbioEcs (like adenocarcinoma in situ) b/c
necroEzing pneumonia (needs steroids and immunosuppressants)

Pulmonary AND renal involvement with neutrophil microabscesses!

Aects kidneys renal infarcts and aects glomeruli capillaries too (glomerular
nephriEs [crescent shape] hematuria renal failure)
Pulmonary hemorrhage
Iron deciency anemia
Cough with hemoptysis
Bilateral inltrates

Limited Wegeners doesnt involve kidney

Inves3ga3ons:

C-ANCA in blood PR3 an3bodies

Dont see anything with immunouorescence = pauci-immune

Pulmonary and capillary involvement dierenEate it from PAN

Abdominal (AtheroscleroEc) AorEc

Aneurysm (AAA)

TRUE aneurysm involves ALL three layers of vessel wall

Common loca3on infrarenal abdominal aorta
Predisposing factor atherosclerosis
PresentaEon most commonly asymptoma3c

Incidental nding of a pulsa3le and expansile abdominal mass or

on ultrasound/CT

Complica3ons:

CriEcal size: >5cm has high risk for rupture hypovolemic shock
Mural thrombus due to stasis downstream ischemia
Compress vertebrae (back pain), ureter (hydronephrosis
retrograde ow of urine which leads to dilataEon of renal pelvis
and calyces)

Pseudoaneurysm broken through inEma & media but sEll

conned by advenEEa usually following vascular procedures

Thoracic
A
neurysm
Common cause = ter3ary syphilis

Pathogenesis: starts in vaso vasorum which supplies media oblitera3ve end arteri3s
lymphocytes, plasma cells & mononuclear cells in advenEEa occlusion of vaso vasorum
due to thrombus necrosis of media ischemia causes loss of elasEc bers chronic
inammaEon brosis vessel becomes weakened aneurysm
Presenta3on:

Tree bark appearance due to in3mal wrinkling

Compresses central structures (esophagus, le[ recurrent, trachea, etc)
InammaEon can spread to aorEc roots where coronary arteries originate ischemia of myocardium
MI
Can lead to aorEc regugitaEon/insuciency/incompetency ge^ng blood from both le[ atrium AND
aorta volume overload cor bovinum le[ heart failure pulmonary edema (most common cause
of death) Right heart failure from le[ heart failure
Most common cause of death = heart failure due to aor3c regurgita3on!

Stasis in heart causes mural thrombosis

Arrhythmias + mural thrombosis embolic stroke

Infec3ve endocardi3s superimposed infecEon on damaged valves

ECG, angiogram, FTA-Abs test (Fluorescent Treponemal An3body Absorp3on Test)

Thoracic aneurysms aect adven33a media

AtheroscleroEc aneurysms aect inEma media

AorEc DissecEon

Pathogenesis: in3mal tear (from hypertension) + defec3ve media

(Marfans syndrome Fibrillin gene on chromosome 15 and Ehlers Danlos)
Ascending worse prognosis
Rupture backward into the pericardial space pericardial tamponade
Becks triad (low BP, distended neck veins, mued heart sounds)
Rupture forward & compromise: common caro3d (stroke), coronary (MI),
subclavian (uneuqual BP and pulse in upper extremiEes) anterior spinal
arteries (myeliEs) and renal arteries (renal failure)
Chest pain radia3ng to back
X-ray: widening of medias3num b/c blood collects in the media
Histology: blood dissects media into inner 2/3 and outer 1/3
Double barrel aorta two inEmal tears; another inEmal tear that lets the
blood go back into lumen and keeps paEent alive

Descending aects lower extremiEes; bejer prognosis

Iliac and femoral

Berry Aneurysm
Predisposing factors: Marfans syndrome & Ehler Danlos due to cysEc
medial degenera3on/necrosis easy for blood to dissect media
Associated with Autosomal dominant polycys3c kidney disease
Common loca3on: between anterior cerebral and anterior communica3ng
Presenta3on: asymptomaEc
Rupture subarachnoid hemorrhage (presents like meningiEs) thunder-
clap headache, photophobia, neck sEness, fever, seizures due to irritaEon
of the meninges
Inves3ga3ons: Do CT and check CSF
Before 12 hours blood (RBCs)
Awer 12 hours bilirubin (yellow) xanthochromia

Complica3ons:

Vasospasm of cerebral artery ischemic stroke

Fibrosis of arachnoid villi communica3ng hydrocephalus

MycoEc (InfecEous) Aneurysm

Weakening of vessel wall by microbial
infecEon
Endocardi3s with a sep3c embolism
On tricuspid goes to lung and usually good at
clearing
On mitral worse b/c can go to aorta/brain

Can also be caused by tuberculosis or bacterial

abscess

Myocardial InfarcEon

Superimposed thrombus on an atheroscleroEc plaque thats unstable/ruptures

Most commonly aected: right coronary, lew circumex, LAD

Two types:

Presenta3on: sharp substernal chest pain radiaEng to arm, diaphoresis

Inves3ga3on:

Complica3ons: mostly between 3-7 days b/c macs have engulfed debris & myocardium is
so[ and vulnerable to rupture

Transmural full thickness of ventricular wall; associated with plaque disrupEon & superimposed
thrombosis; more serious
Subendocardial inner 1/3 ventricular wall; gunshot wound bleeding out hypotension,
hypoxia

Do EKG ST eleva3on
Troponin I rise in 2-4 hours, PEAK at 48 hours, disappears 7-10 days
CK-MB rise in 2-4 hours, PEAK at 24 hours, disappears in 3 days (72 hours); use to check for re-infarcEon

Rupture of free wall of myocardium pericardial temponde (diastolic dysfuncEon) Becks Triad
IV septum rupture (le[ to right shunt ) VSD, pulmonary edema

Pansystolic murmur loudest in lew lower sternal border

Only Eme that right ventricle has oxygenated blood oxygen saturaEon from right atrium to right ventricle

Papillary muscle rupture severe mitral regurgitaEon pulmonary veins pulmonary edema
Pansystolic murmur loudest at apex (at the mitral valve)

Months later lew ventricular aneurysm a[er fully formed scar

Stasis mural thrombus arrhythmia + embolism stroke
Most common place legs, brain

Cardiogenic shock, brinous pericardi3s (bread & bujer), Dresslers autoimmune pericardi3s (> 2 wks)
Any pericardiEs - Chest pain when you lie at, relieved when you sit forward due to fricEon rub

DaEng of Myocardial Infarct

Gross:

Old white
New tan

Histology:

1-4 hours: wavy bers

12-24 hours: coagula3ve necrosis, contrac3on bands [need
ATP to relax & reperfusion brings in Ca2+]
1-3 days: heavy neutrophilic inltra3on
3-7 days: MACROPHAGES
10-14 days: acEve granula3on 3ssue
Angiogenesis & Type III collagen

2 weeks: Type III Type I collagen [circatriza3on]

2 months: scarring complete [fully formed Type I]

Acute RheumaEc Fever

Prominent in developing countries children 10-15 years old

Repeated S. pyogenes pharyngi3s Type II hypersensiEvity

Jones criteria: erythema marginatum, nodules, Sydenham chorea, migratory polyarthri3s

& pancardi3s [ACCNE]

Cross-reacEng anEbodies to M protein of S. pyogenes cross reacEng with anEgens of valves and joints
molecular mimicry

Minor manifesta3ons: fever, atralgia (joint pain) , ESR & CRP and prolonged PR interval

Pancardi3s

Myocardi3s arrhythmia; Ascho bodies around arteries (perivascular) & granuloma-like (combinaEon
of CD4+ lymphocytes & acEvated macrophages/Anitshkow cells)
Anitshkow cells nuclei look like owls eye on transverse secEon; caterpillar appearance on longitudinal secEon

Pericardi3s brinous pericardiEs (bread & buTer) - fricEon rub

Endocardi3s regurgita3on of mitral valve

Pansystolic murmur loudest at apex

Sterile vegetaEons with brin b/c organism is no longer there verrucae endocardiEs regurgitaEon

ASO and DNAse B 3ter in blood

Chronic RheumaEc Heart Disease

E3ology: recurrent ajacks of rheumaEc fever

Complica3ons:
Fibrosis of heart valves

Order of aected valves mitral, aor3c, tricuspid

Fibrosis of the mitral valve shmouth/bujonhole appearance

Irregular thickening & calcica3on of the leaets, with fusion of the

commissures & the chordae tendinae
Systolic AND diastolic murmur
Le[ atrium enlarges [compresses central structures] le[ atrium fails blood
backs up in lung pulmonary edema pulmonary HTN right heart failure
and nutmeg liver!
Le[ atrium failure stasis mural thrombus + arrhythmia embolic stroke!
Damaged mitral valve superimposed infec3ve endocardi3s

InvesEgaEons: ECG look for brosis of heart valve

AorEc Stenosis

Dystrophic calcica3on from wear and tear can shear RBCs produce
schistocytes & jaundice
Presenta3on:
Usually in paEents over 60 years
Congenital bicuspid aor3c valve occurs earlier in life (40 years)
SAD [syncope, angina, death due to CHF/arrhythmias]

Complica3ons:

Le[ ventricular hypertrophy protein synthesis or protein degradaEon

Lew heart failure pulmonary edema pulmonary HTN right heart failure
Transudate unEl 2 weeks
A[er 2 weeks brosis and hemosiderin laden macrophages

stroke volume & cardiac output

Less supply, increase demand

Ischemia and infarcEon of myocardium MI

Mural thrombus + arrhythmia embolic stroke

AorEc valve is damaged infec3ve subacute endocardi3s (S. viridans)

Inves3ga3on: ECG
Dieren3ate from Rheuma3c Heart Disease aects mitral rst, then aorEc!

Mitral Valve Prolapse

Presenta3on:

Young women between 20-40

Marfans syndrome or Ehlers Danlos syndrome
AsymptomaEc and incidental nding of mid systolic click

Pathogenesis: accumula3on of GAGs in spongiosa

layer [myxoid degenera3on of valve]
Complica3ons:

Rupture of chordae tendinae mitral regurgita3on le[

heart failure pulmonary edema
Pansystolic murmur at apex

RegurgitaEon of mitral valve infec3ve endocardi3s

InfecEve EndocardiEs
Acute endocardi3s

Sub-acute endocardi3s

High fever, no splenomegaly & no nger clubbing

Low-grade fever, splenomegaly & nger clubbing

S. aureus in normal valves death

S. viridans in ABnormal valves good prognosis w/

anEbioEcs

HACEK group Hemophilus, AcEnobacillus,
Cardiobacterium, Eikenella & Kingella

Large vegetaEons w/ minimal neutrophils b/c valves Small vegetaEons, granulaEon Essue, brosis,
are avascular
plasma cells, macrophages, broblasts
Dystrophic calcica3on
IVDA using dirty needles tricuspid valve

SPLINTER HEMORRHAGES UNDER FINGERNAILS!

Syphilis, RheumaEc heart disease, calcicaEon of

mitral valve & mitral valve prolapse!

Abnormal valve + dental work bacteremia due to
S. viridans

Complica3ons:
Complica3ons:
Sepsis sepEc emboli lungs mulEple lung Sepsis sepEc emboli legs, brain
abscesses
GlomerulonephriEs Type III HypersensiEvity
Ring abscess in myocardium arrhythmia
[immune complex]!

Inves3ga3on: Serial blood cultures & ECG

ProstheEc Valve EndocardiEs

Tissue valve: pig valve bioprostheEc
Metallic valve: mechanically ruptures RBCs as they
pass through schistocytes (helmet cells) so
conjugated bilirubin (jaundice)
Microangiopathic hemoly3c anemia

Most common cause = S. epidermidis

Other causes: gram negaEve bacilli & fungi (C. albicans)

Fever + heart murmur

Non-bacterial ThromboEc EndocardiEs

(MaranEc)
Sterile vegeta3ons mostly on mitral valve
Pathogenesis

Endothelial abnormaliEes
Hypercoaguable states
Adenocarcinomas (MUCIN) hypercoaguability!

NO bacteria
NO inammaEon or brosis

Libman-Sacks Endocardi3s sterile vegetaEons

on BOTH valve surfaces in paEents with SLE

Viral MyocardiEs
Most common cause: Coxsackie virus
Pathogenesis:

Direct damage by virus + CD8+ mediated damage

Inamma3on [inltraEon of lymphocytes] necrosis
(patchy) of myocytes

Outcome: COMPLETE RESOLUTION

Similar to lobar pneumonia & impeEgo

Complica3on:

Flu-like symptoms
Arrhythmias heart failure and dilated cardiomyopathy

Valvular Heart Disease

Cardiomyopathies

Dilated most common cardiomyopathy; eccentric hypertrophy

Idiopathic, but common causes include: muta3ons in dystrophin gene, viral myocardi3s, alcoholics due
to thiamine deciency (wet beri beri), peri-partum cardiomyopathy (before and a[er birth) and
hemochromatosis
Presenta3on: combinaEon of R and L heart failure b/c both ventricles are dilated (like CHF)
Hear S3 sound [gallop rhythm] SYSTOLIC [CONTRACTILE] DYSFUNCTION!
Displaced apex beat due to dilaEon at 5th intercostal space mid-clavicular line pushed to mid-axillary line

Inves3ga3on:

Echocardiogram dilated heart chambers with low ejec3on frac3on due to systolic dysfuncEon
Endomyocardial biopsy hypertrophy of myocytes with intersEEal brosis

ComplicaEon arrhythmia + mural thrombus (due to stasis) embolize lower limb or brain (stroke)

Hypertrophic concentric hypertrophy

Due to mutaEon in gene that codes for beta myosin heavy chain
Hypertrophy Haphazard/disarray of myocardial bers
PresentaEon sudden death from arrhythmias (athlete that collapses and dies)

DIASTOLIC DYSFUNCTION
le[ ventricular end diastolic volume & stroke volume normal ejec3on frac3on
IV septum asymmetric hypertrophy makes contact with the anterior leaet of mitral valve during systole

ECG banana shaped lew ventricle (very small)

Complica3ons: arrhythmias, infecEve endocardiEs of mitral valve, le[ heart failure, right heart failure,
mural thrombus due to stasis that can embolize and give stroke, infarcts of the septum (small supply but
increased demand ischemia)

Restric3ve

E3ology: endomyocardial brosis, hemochromatosis, amyloidosis, sarcoidosis, Loeers (eosinophilia)

DIASTOLIC DYSFUNCTION [loss of ventricular compliance] & SYSTOLIC DYSFUNCTION (not forceful);
MOST inters33al brosis
Complica3ons arrhythmias and heart failure

Congenital Heart Defects

R L shunt [cyano3c]
Tetralogy of Fallot

VSD, pulmonary stenosis, overriding aorta, R ventricle hypertrophy

Truncus arteriosus single great artery for both ventricles

Tricuspid atresia hypoplasEc RV
Total anomalous pulmonary venous connec3on
Pulmonary veins fail to join le[ atrium

Transposi3on of great vessels - aorta o RV & pulmonary artery o LV

IncompaEble with life unless a shunt (VSD, PDA) is present
Give exogenous prostaglandins to maintain patency

L R shunt [acyano3c]

ASD
VSD
PDA conEnuous, machine-like murmur

Open with Prostaglandin E; close with indomethacin

Matenal rubella infecEon

Tetralogy of Fallot
Features: right ventricle hypertrophy, VSD, overriding aorta, pulmonary stenosis
(most important)
Pathogenesis: antero-superior displacement of the infundibular septum
Presenta3on:

Becomes apparent 6 months awer birth - fetal Hb decreases [holds onto more oxygen
due to higher anity] nger clubbing
Tet spells [squa^ng] - a[er load to reverse the shunt (L R) cyanosis transiently
improves

Complica3on:

DVT (paradoxical embolism bypasses pulm circulaEon and goes to systemic

circulaEon),
Jet lesions (right to le[ ventricle lands on endocardial surface and damages it
dental work get infecEve endocardiEs)

Inves3ga3on:

Cardiac catheterizaEon or ECG

Boot shaped heart

VSD

Membranous VSD most common congenital heart disease [asymptomaEc]

L R shunt but most close up with age
Associated with Trisomy 21, 13, 18
Incidental nding on ECG

Eisenmengers syndrome pulmonary HTN reversal of shunt [R L]

cyanoEc/symptomaEc
Inves3ga3on: cardiac catheterizaEon
Complica3ons:

Pulmonary HTN right heart failure, nutmeg liver, jet lesions (le[ to right in the
beginning damaging right ventricle sub-acute infecEve endocardiEs embolizes
and goes through lungs pulmonary HTN shunt reversal [R L] jet lesions on le[
ventricle embolizes and goes to systemic
Paradoxical embolus a[er the switch (pulmonary HTN)

Pt with VSD gets a DVT and embolizes lungs

Would end systemically a[er pulm HTN

Pansystolic murmur loudest at le[ lower sternal border

ASD
Lew to right shunt; asymptomaEc

Most common congenital disease later in life

Fix spli^ng of second heart sound [split S2]

Three types:

Os3um primum associated with Downs syndrome

Os3um secundum most common
Sinus venosus

Eisenmenger syndrome - a[er pulmonary HTN

Complica3ons:
Pulmonary HTN

Can have paradoxical emboli

NO jet lesions [due to lower pressures]

PericardiEs
PericardiEs viruses (Coxsackie),
TB, metastaEc cancer, radiaEon,
lupus, MI, rheumaEc

Uremia most common systemic

disorder associated with pericardiEs
Also causes ARDS in lungs

Post MI:

2-3 days brinous pericardi3s

2 weeks Dresslers auto-immune

ALL PERICARDITIS: Chest pain

when you lie at, relieved when
you sit forward due to pericardial
fric3on rub
Complica3on: massive pericardial
eusion cardiac tamponade
(Becks triad)
Get ST elevaEon with pericardiEs

ObstrucEve Congenital AbnormaliEes

Coarcta3on of the aorta

Associated with Turner syndrome

50% cases associated with bicuspid aorEc valve
Two types:
Preductal (infan3le) has PDA
Cyanosis of lower extremiEes

Postductal (adult) ductus arteriosus closed

No cyanosis
Hypertension of upper & hypotension in lower extremiEes
Notching of ribs due to collaterals

Pulmonary stenosis & atresia

HypoplasEc RV and ASD
Blood reaches lung via PDA

Aor3c stenosis & atresia hypoplasEc le[ heart syndrome; need

PDA
Valvular
Subvalvular
Supravalvular

Tumors of the Heart

Most common are metasta3c neoplasms
Cardiac myxomas asymptomaEc
Most common primary tumor
Most common in le[ atrium
MulEnucleated stellate cells in an edematous
mucopolysaccharide stroma

Triple Coronary Artery Bypass

Internal thoracic artery most commonly used
Can hold up under high pressures

Long saphenous vein less common

Lead Poisoning

Sources: leaded gas, old aking paints, toys, furniture, bajeries, foundries
Mainly accumulates in bones and teeth (80-85%)
5-10% in blood, 5-10% in so[ Essues
Children more suscep3ve than Adults
PresentaEon depends on organs
Blood
Iron has high anity for sulydryl (SH) groups, Inhibits 2 enzymes in erythropoiesis impairs heme synthesis
Delta aminolevulinic acid (ALA) dehydratase (d-ala dehydrase)
Ferrochelatase
Inhibits iron incorporaEon into RBC No heme synthesis
Increased iron in blood but not in Hb Func3onal iron decient anemia
FuncEonal d/t available iron but cannot be used
Peripheral blood smear
Microcy3c hypochromic anemia w/ mild hemoly3c anemia TWO types of anemia
Normally central 1/3 pallor, but now > 1/3 pallor
Microcy3c RBC is smaller than nuclei of lymphocytes (normally same size)
Shut down of Na/K-ATPase pump in cell membrane inow of Na+ followed by H2O swelling hemoly3c
anemia
Basophilic s3ppling clustering of ribosomes d/t inhibiEon of ribonuclease
Bone lead lines (black arrows)
Lead is divalent like calcium Both complete w/ each other to bind phosphates in bone interferes w/ remodeling of calcifying
carElage in bones
Carpal bones are not calcied in child so they are translucent in the x-ray
If deposiEon is equal throughout the epiphyseal plate growth is retarded
If not equal abnormal growth of bone
HyperpigmentaEon of gyms blue gums/lines
CNS lead leads to demyelina3on
Children aects CNS learning & cogniEve disabiliEes, mental retardaEon, seizures, encephalopathy
Even low concentra3ons cause illness
Adults aects PNS wrist drop and foot drop
Requires high concentra3ons for illness
Aects radial, common bular never
Kidneys acute renal tubular necrosis
Intranuclear inclusions in RT epithelium (insoluble protein)
Damages PCT Fanconi syndrome
GI colicky abdominal pain & cons3pa3on excruciaEng abdominal pain
Inves3ga3on
Venous whole blood level - measure lead levels
Increased Zinc and free erythrocyte protoporphyrin IX
Treatment ChelaEng agent EDTA & Dimer Caprol (BAL)

Reye Syndrome

Not very common, rare fatal childhood hepatoencephalopathy

Associated w/ children viral infec3ons treated w/ aspirin
Never give aspirin to children w/ viral infecEons
Seen w/ Chicken pox or viral u treated w/ aspirin
Aspirin metabolites decrease B-oxidaEon by reversible inhibiEon of mitochondrial enzymes
Mitochondria dysfuncEon in the liver Disrupts UREA Cycle increase Ammonia buildup

Brain Ammonia is toxic to brain Cytotoxic Cerebral Edema

Non-inammatory hepa3c encephalopathy
Starts in the liver, ends in the brain,
NO Acute inammaEon brain swells due to Ammonia

Liver microvesicular faTy change

DilaEon of ER
Damaged mitochondria but can mitochondria can recover
Resolves w/ supporEve treatment

Signs/Symptoms:
Neurological symptoms Seizures, Confusion
N/V
Hypoglycemia
Hepatomegaly
Inves3ga3on:
Blood ammonia levels
Liver FuncEon Test elevated liver enzymes
Complica3ons:

Coma, death

Carbon Monoxide Poisoning

Common:
Automobile exhaust in enclosed environment
Incomplete combusEon of furnace and water heaters
Fires, automobiles, stoves in closed spaces

Presents w/ Flu-like symptoms

Cherry-red discolora3on of the skin d/t Carboxyhemoglobin
CO binds to Hb 3ghter than O2

Diagnosis measure CO levels

O2 satura3on Normal

ComplicaEon:
Brain Globus Pallidus necrosis (arrow), only seen if the paEent survives long enough
Seen to have Parkinsonian symptoms
Heart MI due to hypoxia

Treatment
High ow O2
Hyperbaric Chamber