Cell Death, Intracellular Accumulation, Pathological Calcification and Cellular Aging

Flashcards covering key definitions, classification, morphology, mechanisms, and clinical correlates for Cell Death, Intracellular Accumulation, Pathological Calcification, and Cellular Aging based on the lecture notes.

What is necrosis?

A spectrum of morphological changes that follow cell death in living tissue, occurring in the setting of irreversible exogenous injury.

What enzymatic and protein processes drive the morphological appearance of necrotic cells?

Denaturation of intracellular proteins and enzymatic digestion.

What characterizes coagulative necrosis microscopically and grossly?

Preservation of tissue architecture lasting several days with a firm texture grossly, and intensely eosinophilic cells devoid of nuclei under light microscopy.

In which organ hypoxic tissue cell death does coagulative necrosis NOT occur?

The brain.

What is liquefactive necrosis and where does it typically occur?

A type of necrosis caused by enzymatic digestion resulting in a liquid viscous mass (or creamy yellow pus if initiated by acute inflammation); seen in focal bacterial or fungal infections and hypoxic brain injury.

What tissue appearance and microscopic characteristics define caseous necrosis?

A cheesy white gross appearance with amorphous granular debris enclosed by a distinctive border of granulomatous reaction, completely obliterating tissue architecture.

How do dry gangrene and wet gangrene differ?

Dry gangrene is synonymous with coagulative necrosis resulting from lost blood supply. Wet gangrene resembles liquefactive necrosis and is due to secondary infection.

What are Fournier's gangrene and Noma (Cancrum oris)?

Fournier's gangrene is gangrenous necrosis in the scrotum; Noma (Cancrum oris) is a gangrenous lesion of the vulva or mouth.

Where does fibrinoid necrosis commonly occur and in what diseases is it seen?

It occurs in blood vessel walls in immune-mediated reactions, collagen diseases (Rheumatic fever, Rheumatoid, Scleroderma, Lupus erythematosus, Polyarteritis nodosa), and malignant hypertension.

What is fat saponification and how does it occur in Acute Pancreatitis?

Pancreatic lipases liquefy fat cell membranes in the peritoneum to release fatty acids, which combine with calcium to form chalky-white calcium soaps.

Define karyolysis, pyknosis, and karyorrhexis.

Karyolysis is the fading of basophilic chromatin; pyknosis is nuclear shrinkage and increased basophilia; karyorrhexis is nuclear fragmentation.

Which laboratory markers assess cardiac, skeletal, and smooth muscle injury?

Troponin I, Troponin C, Troponin T, and Creatine kinase.

What is apoptosis?

A programmed cell death resulting from the activation of a tightly regulated intracellular suicide program, in which plasma membranes remain intact without eliciting inflammation.

List four physiological examples of apoptosis.

1) Programmed cell death during embryogenesis; 2) Hormone-dependent involution (menstrual endometrial breakdown, ovarian follicular atresia in menopause, lactating breast regression after weaning, prostate atrophy after castration); 3) Cell deletion in intestinal crypt epithelia; 4) Elimination of self-reactive lymphocytes.

Which caspase initiates the intrinsic (mitochondrial) pathway of apoptosis, and what causes its activation?

Caspase 9; triggered by signals within cells (e.g., DNA damage from radiation, toxins, free radicals) releasing pro-apoptotic proteins such as Cytochrome c from mitochondria.

Which cell surface receptors and caspases are involved in the extrinsic pathway of apoptosis?

Death receptors such as Fas-Fas Ligand and TNF-TNFR1, involving activation of Caspase 8 and Caspase 10.

Which caspases serve as executioner caspases and what enzymes do they activate?

Caspase 3 and Caspase 6, which activate DNases (for DNA fragmentation) and proteases (for cytoskeletal protein destruction).

What are Councilman bodies?

Apoptotic bodies seen in viral hepatitis.

List five diagnostic methods used to detect apoptosis.

1) Step-ladder pattern on agarose gel electrophoresis; 2) TUNEL technique; 3) H&E, Feulgen, and acridine orange staining; 4) Measurement of cytosolic cytochrome c and activated lipase; 5) Recognition of phosphatidylserine on the outer leaflet by Annexin V dye.

What is necroptosis?

A hybrid form of cell death sharing morphologic features of necrosis (ATP loss, cell swelling, ROS generation, lysosomal enzyme release) and mechanistic features of apoptosis (triggered by genetically programmed signal transduction).

What four mechanisms cause intracellular accumulation?

i) Inadequate removal of normal endogenous substances; ii) Enzyme defects or deficiencies; iii) Defects in protein folding or transport; iv) Ingestion of indigestible exogenous materials.

What specific types of lipid accumulate in Atherosclerosis, Gaucher's disease, and Tay-Sachs disease?

Atherosclerosis: Cholesterol and its esters; Gaucher's disease: Phospholipids; Tay-Sachs disease: Gangliosides.

Distinguish between Russell bodies and Mallory bodies.

Russell bodies are immunoglobulin accumulations in plasma cells seen in multiple myeloma; Mallory bodies are pinkish intermediate filament accumulations in liver cells seen in alcoholic liver disease.

What is lipofuscin?

A brownish peri-nuclear 'wear and tear' pigment that is non-injurious to cells, serving as a sign of lipid peroxidation, atrophy, and aging in the heart and liver of elderly people.

What causes Ochronosis?

Deposition of homogentisic acid in tissues (such as cartilage) caused by a deficiency of the enzyme homogentisic acid oxidase.

How do dystrophic and metastatic calcification differ in terms of tissue status and serum calcium level?

Dystrophic calcification occurs in dead or dying tissue with normal serum calcium levels; metastatic calcification occurs in normal tissue with increased serum calcium levels (hypercalcemia).

What are Psammoma bodies and in which conditions are they observed?

Concentric lamellated basophilic calcifications seen in papillary cancers (thyroid, renal, ovarian) and meningioma.

List four major causes of hypercalcemia leading to metastatic calcification.

1) Hyperparathyroidism; 2) Bone destruction (malignancies, Paget's disease, immobilization); 3) Vitamin D disorders (intoxication, sarcoidosis); 4) Renal failure.

Which gene mutations are responsible for Progeria, Werner syndrome, and Bloom syndrome?

Progeria: Lamin A gene mutation; Werner syndrome: WRN gene mutation; Bloom syndrome: BLM gene mutation.

What is cellular senescence and what drives it?

Permanent cell arrest that occurs when a cell exhausts its division capacity, driven by telomere shortening and activation of tumor suppressor genes.

What form of gangrenous necrosis is depicted in this image?

Dry gangrene.

Identify the gross pathologic finding with chalky white deposits shown in this mesentery specimen.

Fat necrosis (chalky white deposits representing foci of fat necrosis with calcium soap formation/saponification).

What intracellular immunoglobulin accumulation is labeled in this plasma cell slide?

Russell bodies.

What concentric lamellated structures are shown in this histology image of pathological calcification?

Psammoma bodies.

What genetic cellular aging condition is illustrated in this photograph of Sam Berns?

Progeria (Hutchinson-Gilford progeria syndrome).