First Aid: Pathology + Pharm Flashcards

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1
Q

What are two absolute requirements for apoptosis to occur?

A

ATP and Caspases

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2
Q

Bcl 2 and BAX are key factors involved in the intrinsic apoptosis pathway. What would occur if either were overexpressed? What is the key step leading to apoptosis in this pathway?

A

Changes in pro/anti-apoptotic factors can lead to INCR MT permeability and cytochrome c release –> activates caspases

INCR Bcl2--> Apaf 1 over inhibitition, DECR. caspase activation --> tumorigenesis (e.g. follicular lymphoma)
INCR BAX (BAK) --> Pro-apoptotic
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3
Q

What are the two pathways of the extrinsic apoptosis pathway? What happens if there is a defect in one of these?

A
  1. Ligand receptor interactions (FasL binding to Fas [CD95] –> crosslinking –> coalesce –> death domain binding site –> FADD –> activates caspases)
  2. Immune cell (cytotoxic T-cell release of perforin and granzyme B)

A defect especially in Fas-FasL binding –> autoimmune disorders (this process responsible for thymic negative selection)

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4
Q

Match the type of necrosis with main associated characteristics and/or pathologies/locations:

  1. Coagulative
  2. Liquefactive
  3. Caseous
  4. Fatty
  5. Fibrinoid
  6. Gangrenous
A
  1. Heart, liver, kidney (protein denaturation then enzymatic degradation)
  2. Brain (CNS), bacterial abscess (lysosomal enzyme release)
  3. TB, systemic fungi, Nocardia
  4. Enzymatic (pancreatitis-saponification) or nonenzymatic (breast trauma)
  5. Vasculitides, malignant HTN
  6. Dry (ischemic coagulative) and wet (infection); limbs and GI tract
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5
Q

A cell is swollen and also exhibits MT swelling. You also notice nuclear chromatin clumping and fatty change on gross specimen. Are these changes reversible? When would they not be reversible?

A

Yes, with proper oxygenation

Irreversible - PLasma membrane damage, lysosomal rupture, MT peremeability

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6
Q

Match the Organ with areas of ischemic susceptibility:

  1. Brain
  2. Heart
  3. Kidney
  4. Liver
  5. Colon
A
  1. ACA/MCA/PCA boundary areas
  2. Subendocardium (LV)
  3. Medulla: Straight segment of proximal tubule and thick ascending limb
  4. Area around central vein (zone III)
  5. Splenic flexure, rectum
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7
Q

Where would you see red infarcts? Pale infarcts?

A

Red - areas w/ lots of blood supplies and loose tissue –> Lungs, liver, intestine

Pale - solid tissue –> Heart, kidney, spleen

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8
Q

A patient presents with tachycardia, low BP, and warm dry skin. you determine they are in a state of shock and have high cardiac output. What type of shock could this be and would IV fluids help increase the BP?

A

Septic, neurogenic or anaphylactic shock

-IV fluids would not increase BP
Could give Epi

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9
Q

What mediates acute inflammation and how long does this last? What about chronic inflammation? What are the outcomes of each?

A

Acute - PMNs, eosinophils and antibodies (rapid onset in seconds/minutes, can last minutes/days)
outcome - complete resolution or abscess formation

Chronic - Mononuclear cell (lymphocyte, monocyte, macrophages) and fibroblast mediated (onset in 2-3 days, can last long time)
outcome - granuloma, scarring and amyloidosis

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10
Q

What characteristics define a granuloma?

A

Epithelioid Histiocytes

Giant cells and rim of lymphocytes can also be present, but may not be

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11
Q

What is chromatolysis?

A

Process involving cell body after axonal injury –> Round cell swelling, displace nuclease to periphery, dispersion of Nissl substance in cytoplasm

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12
Q

What is chromatolysis?

A

Process involving cell body after axonal injury –> Round cell swelling, displace nuclease to periphery, dispersion of Nissl substance in cytoplasm

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13
Q

What is dystrophic calcification and where is it seen? What would serum calcium levels reveal?

A

Calcium deposition secondary to necrosis

Localized (e.g. heart valves) - TB (lungs/pericardium), liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis, Monckeberg arteriolosclerosis, congenital CMV + toxoplasmosis, psammoma bodies

Normocalcemic in serum test

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14
Q

What is metastatic calcification and where is it seen? What would you see on serum exam?

A

Widespread deposition secondary to hypercalcemia (primary hyperparathyroidism, sarcoidosis, hypervitaminosis D) or high calcium-phosphate product (e.g. chronic renal failure + 2nd hyperPTH, long term dialysis, calciphylaxis, warfarin)

Calcium mainly in interstitial tissues of kidney, lungs and gastric mucosa (high pH favors deposits)

High serum calcium

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15
Q

What is metastatic calcification and where is it seen? What would you see on serum exam?

A

Widespread deposition secondary to hypercalcemia (primary hyperparathyroidism, sarcoidosis, hypervitaminosis D) or high calcium-phosphate product (e.g. chronic renal failure + 2nd hyperPTH, long term dialysis, calciphylaxis, warfarin)

Calcium mainly in interstitial tissues of kidney, lungs and gastric mucosa (high pH favors deposits)

High serum calcium

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16
Q

What are the 4 key steps to leukocyte extravasation and what are the factors involved on the cell and endothelium? Where does this process occur?

A

Extravasation is at POSTCAPILLARY VENULES

  1. Margination and rolling - Vasodilation allows for margination, E-selectin P-selectin GlyCAM-1/CD34 on vasculature bind Sialyl-LewisX and L-selectin on leukocyte
  2. Tight biding - ICAM1/VCAM on vasc. to CD11/18 integrins and VLA4 INTEGRINS on leukocyte.
  3. Diapedesis - travel between endothelial cells, PECAM1 on both
  4. Migration - travel to site of injury via chemotactic products
17
Q

What are some important chemotactic products that can draw a leukocyte to the site of injury or infection?

A

Bacterial products, C5a, IL8, LTB4, kallikrein, platelet-activating factor

18
Q

Which key factors enhance phagocytosis by PMNs?

A

C3b and IgG

19
Q

What are three key ways free radicals can incite cell damage?

A

membrane lipid peroxidation

protein modification

DNA breakage

20
Q

What are some ways free radicals can be eliminated in the cell?

A
  1. Enzymes - catalase, superoxide dismutase, glutathione peroxidase
  2. Spontaneous decay
  3. Antioxidants - e.g. Vitamins A, C, E
21
Q

Name some key free radical pathologies:

A
  1. Retinopathy/prematurity
  2. Bronchopulmonary dysplasia
  3. Carbon tetrachloride –> liver necrosis (fatty change)
  4. Acetaminophen overdose –> fulminant hepatits, renal papillary necrosis
  5. Iron overload –> hemochromatosis
  6. Reperfusion injury (e.g. superoxide), like after thrombolytic therapy
22
Q

How does granulomatous disease occur?

A

Th1 cells secrete gamma-interferon activating macrophages

Macrophages release TNF-alpha

TNF-alpha induce and maintain granuloma

23
Q

What is one of the leading causes of death from toxic agents in children? How does this lead to death? Symptoms?

A

Iron poisoning –> Cell death from peroxidation of membrane lipids

Acute sx –> N/V, gastric bleed, lethargy
Chronic sx –> Met Acidosis, Scarring –> GI obstruction

24
Q

What does lipofuscin staining indicate?

A

Normal aging (Yellow-brown intracellular “wear and tear” pigment)

25
Q

Name the CYP 450 live enzyme inducers and inhibitors:

A

INDUCERS: Chronic Alcohol abuse, Carbamazepine, Phenobarbitol, Phenytoin, Rifampin, Griseofulvin

INHIBITORS: Acute alcohol abuse, Cimetidine, Ciprofloxacin, Erythromycin, Azole antifungals, Grapefruit juice, Isoniazid, and Ritonavir (protease inhibitors)