Pathology First

Question 1

When does cell injury occur?

Answer 1

When stress exceeds cell’s ability to adapt

Question 2

What’s the hallmark of reversible cell injury?

Answer 2

Cellular swelling & cell membrane and nuclear material are still intact

Question 3

What’s the hallmark of irreversible cell injury?

Answer 3

Cell membrane damage; always pathological; eventually cell death

Question 4

What is hypoxemia?

Answer 4

Reduced concentration of O2 in the blood (low pO2)

Question 5

What are the classifications of hypoxemia?

Answer 5

Normal A-a: High altitude & Hypoventilation (eg. opioids)
Increased A-a: Diffusion defect (eg. Lung fibrosis) & V/Q mismatch & Right to left shunt in heart

Question 6

What causes a decrease in O2 carrying capacity?

Answer 6

Anemia
CO poisoning
Methemoglobinemia

Question 7

What causes the cell to swell in reversible cell damage?

Answer 7

Loss of ATP-dependent ion pumps; More influx of ions (Na+); water follows

Question 8

What are some morphologic features of irreversible cell damage (necrosis)?

Answer 8

Denaturation of intracellular proteins
Digestion of cells by lysosomes

Question 9

What’s the microscopic appearance of necrotic cells?

Answer 9

• Loss of membrane integrity; leakage of intracellular components (eg. cardiac troponin) & vacuolization
• Nuclear damage; karyolysis / karyorrhexis / pyknosis (nuclear shrinkage)
• Inflammation (to remove dead cells)
• Myelin figures & calcification

Question 10

What is coagulative necrosis?

Answer 10

Ischemia of any organ except brain; Dead tissue architecture preservation (removed later by inflammatory WBCs); digestive enzymes denature before plasma membrane digestion is complete

Question 11

What is a localized area of coagulative necrosis called?

Answer 11

Infarction

Question 12

What is liquefactive necrosis?

Answer 12

• Ischemia/hypoxia of CNS or bacterial/fungal infections
• Tissues turn into (creamy/yellow; dead PMNs) liquid viscous mass
• Enzymatic proteolysis favored over coagulation; dead cells fully digested
• Results in cavity with gel material

Question 13

What happens in gangrenous necrosis?

Answer 13

• Subtype of coagulative necrosis; lower limbs ischemia (dry gangrene); bacterial superimposition causes liquefaction (wet gangrene)

Question 14

What happens in caseous necrosis?

Answer 14

• Tissue maintains a friable/cheese-like appearance
• Mainly caused by TB
• Necrotic cells (amorphic/granular/eosinophilic) surrounded by histiocytes (macrophages); forms caseating granuloma

Question 15

What happens in fat necrosis?

Answer 15

Adjacent fat broken down by lipases; causes free fatty acids + calcium = Saponification (white chalky areas)

Question 16

What happens in fibrinoid necrosis?

Answer 16

Deposit of immune complexes & fibrin in BVs (appears bright pink in H&E stain); mainly caused by vasculitis (polyarteritis nodosa)

Question 17

How could the body respond after necrosis?

Answer 17

Phagocytosis
Scarring
Regeneration
Calcification

Question 18

What cell structures are broken down during apoptosis?

Answer 18

(Apoptotic bodies) Cell’s own nuclear DNA / nuclear and cytoplasmic proteins

Question 19

What are the morphologic changes in apoptosis?

Answer 19

Cellular shrinkage / Cytoplasmic blebs / Chromatin condensation / Phagocytosis of apoptotic cells or bodies / apoptotic bodies formation (cytoplasm & tightly packed organelles ± nuclear fragments) / Intense eosinophilic or shrunken basophilic fragments surrounded by halo

Question 20

What is the mechanism of the initiation phase of apoptosis in the mitochondrial (intrinsic) pathway?

Answer 20

Cell damage (DNA damage/ER stress/GF withdrawal)
BH3-only protein activation; Inhibit Mcl-1/Bcl-2/Bcl-x (anti-apoptotic); activate Bak & Bax (pro-apoptotic); mitochondrial permeability; Cyt C leaks and binds to Apaf-1; forms apoptosome; activates caspase-9; initiates apoptosis

Question 21

What is the mechanism of the initiation phase of apoptosis in the death receptor (extrinsic) pathway?

Answer 21

Initiated by TNF receptors family; when TNF-1 binds to TNF / FasL (expressed on activated CTLs) binds to Fas; activate death receptors; cytoplasmic death domain sends signal to activate caspase-8 (apoptosis initiator)
- Usually for self-reactive lymphocyte elimination / damage by CTLs

Question 22

What is the execution phase of apoptosis?

Answer 22

Activation of caspases 3 or 6 that activate DNase (deoxyribonuclease) to break down nuclear matrix
(also cause membrane & phospholipid alterations; flipping inner leaflet to outer leaflet; expose phosphatidylserine; phagocytes recognition)

Question 23

What is amyloidosis?

Answer 23

Abnormal aggregation of misfolded proteins in insoluble beta sheet form extracellularly (in ECM); causing cell damage & apoptosis

Question 24

What causes primary amyloidosis in systemic amyloidosis?

Answer 24

Accumulation of AL amyloid (derived from Igs LC); associated with plasma cell dyscrasias (multiple myeloma; plasma cell cancer; excess plasma cells production; increase Ig LC production)

Question 25

What causes secondary amyloidosis in systemic amyloidosis?

Answer 25

Accumulation of AA amyloid; derivative of SAA (systemic amyloid-associated protein); caused by chronic inflammations & malignancies & FMF (Familial Mediterranean Fever)