1 Flashcards

Question 1

Q

A/1 Causes, morphology and mechanisms of cell necrosis.

Answer

A

Necrosis is a form of cell death in which cellular membranes fall apart, and cellular enzymes leak out and ultimately digest the cell.

Causes:

Oxigen deprivation: Hypoxia, ischemia
Infectious agents
Physical agents: radiation, temperature
Immunologic ractiton
Aging: telomeres

Morphology:

Eosinophilia
Glassy appearance
Vaculated appearance
Myelin figures
Membrane fragmentation
Nuclear changes: Karyolysis, karyrorrhexis, pyknosis

Mechanisms:

ATP depletion
Mitochondrial damage
Ca⁺⁺ influx
ROS: DNA, lipids, proteins
Membrane damage
DNA damage

Types:

Coagulative
Liquifactive
Gangrenous: Sicca, Humida
Caseous: Coagulative + liquifactive
Fat: pancrease, enzymes leak out -> Fat released (chalky white appearance)
Fibrinoid: Endothil damage -> fibrin leaks out -> Ag-Ab complexes combine with it.

Question 2

Q

A/2 The causes and mechanisms of apoptosis. Apoptosis in pathologic conditions.

Answer

A

Pathway of cell death in which cells activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins.

Causes:

Physiologic:
1. Embryogenesis
2. Hormone dependent
3. Death of inflammatory cells
4. Death of proliferating cells
Pathologic:
1. DNA damage
2. Mis-folded proteins
3. Viral infection: viral (cell cycler arrest)
4. Atrophy

Mechanisms:

Intrinsic:
- Cell injury -> BH3 receptors -> Bcl2 effectors (Bak-Bak, Bax-Bax channels) -> Cytochrome C leaks out -> Pro-caspase -> Caspase -> activation of effector caspase 3,6,7.
- Regulated by Bcl-2
Extrinsic:
- Fas/TNF -> FaDD-> Pro-caspase -> Caspase -> activation of effector caspase 3,6,7.

Morphology:

Apoptotic bodies (Contain organels) -> undergo phagocytosis
Eosinophilic cytoplasm
Nuclei changes: Karyorrhexis
4.

Question 3

Q

A/3 Coagulative necrosis, organ manifestations

Answer

A

architecture is preserved. firm. denaturation of the proteins and enzymes -> coagulated. inflammatory cells migrate and digest.

Infarct: ischemic necrosis caused by occlusion of the arterial supply or the venous drainage.

white (anemic) infarct:
- Solid organs
red (hemorrhagic) infarct: occurs in:-
1. Venous occlusion
2. Loose tissues
3. Dual circulation
4. Reperfusion

Organ manifestation:

Anemic:

Kidney + spleen:
- obstraction of an end artery
- thromboemboli (usually from the heart - aneurysme/fibrilation)
- Wedge shaped, pale, necrotic area.
- Inflammatory response -> fibrotic scar
- In kidney: Might lead to hypertension (renin-angiotensin-aldosteron).
Gangrena sicca:
- Atherosclerosis in extrimities
- Mummification (might fall off)
- Claudicartion intermittans
AMI:
- .

Hemorrhagic:

AMI:
- .
Pulmonary:
- Usually from DVT
- Morphology depends on size:
  - Large -> hypoxia -> R sided HF -> death
  - Small -> damage to endothelial + pulmonary hemorrhage
- Bronchial circulation can prevent.
- Affects lower lobes
- Wedge shaped, Red-blue -> 48 Hr -> red-brown (hemosiderin)
- Final stage: fibrous replacment -> whitish scar.
Intestinal:
- Superior mesenteric-> duodenum + jejunum
- Inferior mesenteric -> no infarct
- Portal (hypercoagulability) -> entire intestine
- Transmural -> 24 hr -> Bacteria -> gangrene -> perforation
- Mural (mucosa + sub-mucosa) - > Multi focal lesions -> Edematorious thickening of the mucosa + Inflammation due to bacterial superinfection
- Mucosal -> bacterial superinfection
- Abdominal pain + bloody diarrhea

Question 4

Q

A/4 Liquefactive necrosis, organ manifestations

Answer

A

enzymes are active and digest the tissue. seen in bacterial and fungal infection. heterolysis. autolysis. the tissue transforms into a liquid viscous mass. if initiated by an acute inflammation -> pus.

Anemic

Gangrene humida:

infection superimposed the necrotic tissue.
No immune.
Microbe’s enzymes digest the tissue

Cerebral infarct:

Thrombosis / Embolism (carotid atheroscelrosis / heart)
Morphology:
- Encephalomalacia alba: anemic progress to:
- Encephalomalacia flava: liquifactive necrosis
- Cysta post encephalomalacia: astrocytes around the cyst

Pulmonary abscesses:

suppurative necrosis -> formation of cavities with pus surrounded by inflammatory cells.
Morphology:
- Aspiration -> Right: Upper lobe/upper part of lower lobe
- Pneumonia / Bronchial obstraction -> Multiple, basal and diffusely scattered.
- Septic / hematogenous spread -> multiple and everywhere
Bloody and purulent sputum
Consequences:
- Rapture to the A.W
- Bronchopleural fistula -> pneumotorax + empyema

Hemorrhagic:

Encephalomalacia Rubra due to:
- Reperfusion
- thromb us in a vein
- border line necrosis

Question 5

Q

A/5 Acute myocardial infarction

Answer

A

Pathgenesis:

Fixed coronaries + dynamic changes
- Fixed coronaries - 70-75% due to atherosclerosis
- Dynamic changes - disruption of the plaque (intra plaqueal hemorrhage, erosion, rapture) -> Platelet AAA -> ADP, TXA2, serotonin -> Vasospasem -> occlusion => ischemia
ischemia -> ATP decrease -> pH decrease -> loss of contractility + reversible changes. (after 30_min -> irreversible)
“Wavefront theory”: subendocardial affeceted first (Higher pressure & contrasction compresses capillaries) => transmural in 3-6 hours (theraputic window)

Morphology:

According to the
0-0.5:
- EM - swollen myofibers and swollen mitochondria
0.5-4:
- EM - swollen myofibers and swollen mitochondria
- Diaphorase reaction (DH)
4-12:
- Coagulative necrosis starts -> Eosinophilia
- Pale myocardium
12-24:
- Nuclear changes
- Dissociation of the organelles
2-3 day:
- Reddish border line -> migration of PMNI
- Macrophage system -> starts to dissolve the tissue
3-7 days:
- Yellow myocardium (lipid deliberation)
- Myomalacia (weakening of the texture of the myocardium)
7-30 days:
- Regeneration, capillary proliferation.
- fibroblasts ingrow from the capillaries and collagen deposits
- Scar formation (firm whitish tissue)

Reperfusion methoods: ballon (w/wo stent), thrombolysis (tPA, streptokinase), bypass

Reperfusion injuries: ROS, Ca⁺⁺ influx, Hemorrhage.

Clinical features:

Substernal crushing pain + radiation - not relived by nitroglycerin. dyspnea, diaphoretic.
ECG - ST elevation, Q-wave
Serum levels of: CK-MB, Troponin T, Troponin I.

Consequnces: (CAMP CART)

Cardiogenic shock
Arrythmias
Myocardial apture
Pericarditis
CIHD
Aneurysm
Reinfarction
Thrombos formation

Question 6

Q

A/6 The morphology and mechanisms of reversible cell injury, examples

Answer

A

Morphology and Mechanisms:

Cellular swelling:
- ATP decrease -> pump function decrease -> swelling
- Vacuoles of pinched-off segments of ER.
Fatty changes:
- Accumulation of TAG
- Fat vacuoles appear around the nucleus, pushon it aside
- Reasons:
  - Starvation: increase fat mobilization
  - Hypoxia: Decrease oxidation
  - Alcohol: Decrease NAD⁺ (decreased oxidation)
  - Obesity
- Microscopic changes:
  - Plasma membrane alterations
  - Mitochondrial swelling (phospholipid-rich amorphous densities)
  - Dilation of ER + ditachment of ribosomes
  - Clumping of chromatin

Examples:

Hepatic steatosis:
- Diffused
- Reduced NAD; imparied lipoproteins.
- Alcohol is the main reasone; DM (insulin resistance -> Fat intake)
- Morphology: Vacules, displace the nucleus; enlarged liver (4-6kg), soft, yellowish, tense capsule.
- Revarsible until fibrosis developes, start, around the central vein -> cirrhosis (oblitiration of the nodules creats scar tissue)
- Nutmeg liver
  - Spotty, not diffused
- Tiger heart
  - Hypoxia
  - Due to anemia, CO, COPD
- Fatty heart
  - Fat arround the cells (in the Right side)

Question 7

Q

A/7 Pathomorphology and complications of atherosclerosis

Answer

A

Chronic inflammatory response due to non denuding endothelial injury.

Risk factors

Environmental than genetic
Multiplication effect - exponential increse
Major constitutional (non modifiable)
- Age (40-60)
- Sex (female premenopausal)
- Genetics
Major Modifiable
- Hyperlipidemia
- Smoking 1pack/day * 200
- Hypertension
- Diabetes
Additional
- Obesity
- Lack of exercise
- Stressful life

Pathogenesis

Non denuding EC injury -> ROS -> LDL oxidation -> Oxidzed LDL-scavenger receptor -> Macrophage become foam cells -> recruit more monocytes + ROS + release PDGF -> SMC (plaque stabilization) -> Fatty streak

Morphology

Fatty streak - Lipid filled foam cells
Primary plaque -
- Lipid core - Cholesterol chrystals, foam cells, EMC, Cell debris, Calcium
- Fibrous cap - SMC, EC, Collagen, neovascularization.
- 2 shoulders - vulnerable areas of the plaque
Secondary (complicated) plaque - THE CAR
- Thrombus
- Hemorrhage
- Embolism
- Calcification
- Anurysem
- Rupture

Prevention

Primary prevention - exercise, hypertension control, diet, stop smoking
Secondary prevention - Statins, aspirin, Beta blockers, Bypass.

Question 8

Q

A/8 Amyloidosis

Answer

A

Extracellular deposits of fibrillar proteins responsible for the tissue damage (aggregation of misfolded proteins)

Proteins can be accumulated in the following way:

Excess protein is presented to the cell (proteinuria)
Increased protein synthesis (plasma cells)
Cell injury. Alcohol (Mallory bodies)
Abnormal folding of proteins (problems with chaperons)

Pathogenesis

Misfolded proteins -> fibrilis -> 4-6 fibrils in β pleated configuration form an amyloid (resembles starch)

Important amyloid types:

AL - precursor is immunoglobulin light chains, monoclonal B cell proliferation.
AA - precursor is SAA normally synthesized in the liver
Aβ - Cerebral lesions of Alzheimer disease (APP is the precursor)
Transthyretin - binds thyroxine and retinol, deposits in the heart (Senile systemic amyloidosis)

Clasification of amyloidosis: RELIFA

Reactive: AA type, systemic
Endocrine: APUD-OMAs
Localized: plasma cytoma
Immunologic: Multiple myloma, AL type, systemic
Falmilial: Familiar mediterinian fever, AA type, systemic
Aging: TTR, Senile, systemic

Morphology

Can be seen macroscopically when painted with iodine and sulfuroc acid
Microsocpic staining - congo red
Kidney - deposits in the peritubular area
Spleen - Tubular or nodular
Liver - Disses space, sinuses
Heart - subendocardial elevations
GI - is good for biopsy (Rectum, oral)

Clinical correlation

Difficult to recognize (non-specific symptoms)
Kidney failure
Conduction disturbances
1 - 3 yr after diagnosis
Amyloid can not be removed
primary is the most common

Question 9

Q

A/9 Exogenous and endogenous pigments

Answer

A

Exogenous: Tattoo, Carbon, Silicium

Carbon:
- Urbanic life
- antraxosis
Silicium -> pneumoconiosis
- Phagocytosed by macrophages -> kill the macrophages -> leakage of lysosomal enzymes -> necrosis -> fibrosis -> increased lung resistance -> cor pulmonale -> Right sided heart failure
- Types:
  - asymptomatic anthracosis
  - sCWP - little to no pulmonary disfunction (coal macules and nodules; upper lobe and upper of lower lobe)
  - cCWP - excessive fibrosis, lung function is compromised (Coalescence of the coal nodules)

Endogenous: Lipofuscin, hemosiderin, melanin

Lipofuscin
- Wear an tear, Brownish color perinuclear
- Brown atrophy of the heart:
  - Heart is small, sharp edge, pointing downward; apical shortening, coronary are curly; brown color is seen. (this is a side affect)
Hemosiderin
- Hemoglobin derived granular pigment, yellow-brown, accumulates when there is a systemic/local excess of iron.
- apoferrtin
- stored in macrophages in the bone marrow, spleen and liver.
- Prussian blue -> blue color
- Local:
  - פנס בעין
  - Heart failure cells
- Systemic:
  - general hemolysis
    - autoimmune hemolytic anemia
    - Toxic
  - All the organs become brown
- free iron has a toxic effect (produce free radicals)
- Hemochromatosis
  - Autosomal recessive (HFE gene on chromoosome 6)
  - lipid peroxidation, collagen formation, DNA damage
  - Morphology:
    - Liver -> cirhosis
    - Pancrease fibrosis -> DM
    - Heart -> cardiac dysfunction
    - joints -> atypical arthritis
    - Skin -> pigmentation
Melanin:
- Brown-black
- thyrosinase enzyme
- Alterations:
  - Frackels
  - Melasma: pregnant woman in the sun
  - Vetiligo
    - hereditary: thyrosinase enzyme
    - Autoimmune: Autoantibodies against melanocytes
  - Melanocyte nevus:
    - Benign congenital / acquired neoplasm
    - Junctional -> compound -> Dermal.
    - transformation leads to melanoma.

Question 10

Q

A/10 Pathologic calcifications

Answer

A

Abnormal deposition of calcium salts + iron / magnesium

Dystorphic calcification
- associated with necrosis + aging
- Pathogenesis:
  - Extracellular:
    - Membrane bound vesicles with Ca⁺⁺ inside -> membrane bound phosphatase -> phosphatase ions generation -> phosphate ions bind Ca⁺⁺ -> Crystal formation -> more and more (propagation)
  - Intracellular:
    - initiated in the mitochondria of dead/dying cells
  - Morphology:
    - grossly - white granules or clumps
    - Somtimes tuberculous lymph -> radio-opaque stone.
- Diseases:
  - Calcifing aortic stenosis
  - arteficial valves
  - Atherosclerosis
  - Neoplasm
  - Infectious disease (tuberculosis)
Metastatic calcificartion
- Increased Ca⁺⁺ serum levels due to:
  - Neoplastic disease (multiple myloma _{osteoclast activation})
  - Increased PTH
  - VItamin D related
  - Renal faliure (increased phosphate retention)
- Morphology:
  - Everywhere but principally affects the lung, vasculature, kidney, gastric mucosa.

Question 11

Q

A/11 Stone formation

Answer

A

Gallstone (cholelithiasis)

Risk factors:
- Age, Gander (Women), Ethnic, heredity, decreased motility

Cholesterol stones

Crystalline choloesterol monohydrate crystal
Conditions for stone formation:

supersaturation
nucleation
hypomobility
Mucus hypersecretion

Risk factors (more specific):
- Demogrophy
- Females (estrogen)
- Obesity (weight reduction)
- Hyperlipidemia
Morphology:
- Exclusively in the gallbladder (50-100% cholesterol):
  - Pure: yellow
  - Mixed with Ca⁺⁺-carbonate, phosphate, bilirubin: gray-white-blck
- Firm. 80% radiolucent (Ca⁺⁺-carbonate are radio opaque)

Pigment stones:

uCB
Risk factors (more specific):
- Asian
- Chronic hemolytic syndrome
- Biliary infection
- GI disorders (chron, CF …)
Morphology:
- Black: sterile gallbladder, small in large quantities, crumble easily, 50-75% radiopaque.
- Brown: Infected ducts, singly/small quantitie, soft, radiolucent

Clinical features:

70-80% asymptomatic throughout life
Symptoms: pain, GB inflammation, empyema obstructive cholestasis, pancreatities.

Renal stone:

Urolithiasis
Types:
- 80% - Calcium oxalate
  - 50% - Idiopathic hyperclciuria
  - 10% - Hypercalcemia -> hypercalcuria
  - 20% - Hyperuricosuria
  - High pH
- 10% struvite (Mg, NH₃, PO₄^-3)
  - UTIs
- 6-7% uric acid
  - Hyperuricemia (gout / leukemias)
  - Low pH
- 1-2% cystine
Increased urine concentration of the stone’s constituent
Morphology:
- Unilateral in 80%
- Staghorn calculi: branching
Clinical features:
- Large stone -> asymptomatic
- Small stone may pass the urether -> intense pain, hematouria
- If blocks urine flow -> ulceration and bleeding
- Patient is exposed to bacterial infection
- Diagnosed radiologically

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