Pathology First Flashcards
(26 cards)
When does cell injury occur?
When stress exceeds cell’s ability to adapt
What’s the hallmark of reversible cell injury?
Cellular swelling & cell membrane and nuclear material are still intact
What’s the hallmark of irreversible cell injury?
Cell membrane damage; always pathological; eventually cell death
What is hypoxemia?
Reduced concentration of O2 in the blood (low pO2)
What are the classifications of hypoxemia?
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
What causes a decrease in O2 carrying capacity?
Anemia
CO poisoning
Methemoglobinemia
What causes the cell to swell in reversible cell damage?
Loss of ATP-dependent ion pumps; More influx of ions (Na+); water follows
What are some morphologic features of irreversible cell damage (necrosis)?
Denaturation of intracellular proteins
Digestion of cells by lysosomes
What’s the microscopic appearance of necrotic cells?
- 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
What is coagulative necrosis?
Ischemia of any organ except brain; Dead tissue architecture preservation (removed later by inflammatory WBCs); digestive enzymes denature before plasma membrane digestion is complete
What is a localized area of coagulative necrosis called?
Infarction
What is liquefactive necrosis?
- 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
What happens in gangrenous necrosis?
- Subtype of coagulative necrosis; lower limbs ischemia (dry gangrene); bacterial superimposition causes liquefaction (wet gangrene)
What happens in caseous necrosis?
- Tissue maintains a friable/cheese-like appearance
- Mainly caused by TB
- Necrotic cells (amorphic/granular/eosinophilic) surrounded by histiocytes (macrophages); forms caseating granuloma
What happens in fat necrosis?
Adjacent fat broken down by lipases; causes free fatty acids + calcium = Saponification (white chalky areas)
What happens in fibrinoid necrosis?
Deposit of immune complexes & fibrin in BVs (appears bright pink in H&E stain); mainly caused by vasculitis (polyarteritis nodosa)
How could the body respond after necrosis?
Phagocytosis
Scarring
Regeneration
Calcification
What cell structures are broken down during apoptosis?
(Apoptotic bodies) Cell’s own nuclear DNA / nuclear and cytoplasmic proteins
What are the morphologic changes in apoptosis?
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
What is the mechanism of the initiation phase of apoptosis in the mitochondrial (intrinsic) pathway?
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
What is the mechanism of the initiation phase of apoptosis in the death receptor (extrinsic) pathway?
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
What is the execution phase of apoptosis?
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)
What is amyloidosis?
Abnormal aggregation of misfolded proteins in insoluble beta sheet form extracellularly (in ECM); causing cell damage & apoptosis
What causes primary amyloidosis in systemic amyloidosis?
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)
