1-Cellular Responses OLD

What type of cells undergo hypertrophy and not hyperplasia?

Non-dividing cells like cardiac and skeletal muscle. They can't replicate, so they grow in size (hypertrophy) to meet increased demand. Non-dividing cells increase in size (hypertrophy size); Dividing cells increase in number (hyperplasia)

What are two clinical examples of pathologic hypertrophy?

Left ventricular hypertrophy due to hypertension or aortic stenosis—both conditions cause pressure overload.

Name two conditions that result in physiologic hyperplasia.

Breast tissue during lactation (hormonal) and bone marrow hyperplasia at high altitude or during anemia (compensatory).

Which virus can cause pathologic hyperplasia of the skin?

HPV (human papillomavirus) causes verruca (warts) by inducing epithelial proliferation.

Why is BPH an exception to the rule about hyperplasia and cancer risk?

Benign prostatic hyperplasia is not associated with increased risk of prostate cancer, unlike most pathologic hyperplasias.

What two molecular mechanisms drive atrophy?

Ubiquitin-proteasome pathway degrades cellular proteins; autophagy removes organelles and cytoplasm via lysosomes.

What is the pigment that accumulates in atrophic cells?

Lipofuscin—an aging-associated “wear-and-tear” pigment resulting from lipid peroxidation.

Name three causes of metaplasia and their associated cell-type changes.

Smoking - squamous metaplasia in bronchi;

GERD - glandular metaplasia in esophagus;

Vitamin A deficiency - squamous metaplasia in resp tract (Bitot's spots);

Schistoma - squamous metaplasia in bladder;

Myositis Ossificans - connective tissue metaplasia (forms bone in muscle)

What form of metaplasia involves connective tissue and does not increase cancer risk?

Myositis ossificans—bone formation in muscle post-trauma (connective tissue metaplasia).

What are the histologic features of dysplasia?

Disordered growth, pleomorphism, increased nuclear-to-cytoplasmic ratio, hyperchromatic nuclei, loss of polarity.

What are the three cervical grades of dysplasia?

CIN I (mild), CIN II (moderate), CIN III (severe/carcinoma in situ).

How does dysplasia differ from metaplasia?

Dysplasia is premalignant with atypical cells; metaplasia is a reversible change in cell type, often protective.

List the four major mechanisms that cause intracellular accumulation.

Abnormal metabolism, defective protein folding, enzyme deficiency, ingestion of indigestible material.

What histologic stain confirms glycogen, and what digestion method verifies it?

PAS stain (pink); diastase digestion removes glycogen, confirming specificity.

What disease involves lysosomal cholesterol buildup?

Niemann-Pick disease type C—a lysosomal storage disorder affecting cholesterol trafficking.

What are foam cells, and where are they found?

Lipid-laden macrophages in atherosclerotic plaques.

What are Russell bodies, and in which cells are they seen?

Eosinophilic immunoglobulin accumulations in plasma cells, seen in chronic inflammation.

What two organs are primarily damaged in α1-antitrypsin deficiency?

Liver (due to accumulated protein) and lungs (due to lack of protease inhibitor leading to emphysema).

Which pigment indicates oxidative wear and tear?

Lipofuscin—accumulates in aging cells from lipid peroxidation.

What immunohistochemical stains help identify melanin?

MART-1 and Melan A—help differentiate melanin from other brown pigments.

What stain is used to confirm hemosiderin?

Prussian blue—stains iron blue.

What disease causes Kayser-Fleischer rings?

Wilson’s disease—due to copper deposition in Descemet's membrane of cornea.

What is kernicterus, and what pigment is involved?

Neonatal brain damage from bilirubin accumulation.

What pigment appears in coal miners’ lungs?

Carbon (anthracosis)—black pigment in alveolar macrophages.

What are two signs of lead poisoning visible under the microscope and in physical exam?

Basophilic stippling of RBCs and lead line (purple-blue gum line).

What distinguishes dystrophic from metastatic calcification?

Dystrophic = damaged/dead tissue with normal calcium levels; metastatic = normal tissue with hypercalcemia.

Name three causes of metastatic calcification.

Hyperparathyroidism, renal failure, vitamin D intoxication.

Where does metastatic calcification tend to occur in the body?

Acidic sites: gastric mucosa, lungs, kidneys.

What is the earliest microscopic feature of reversible injury?

Cell swelling due to impaired Na+/K+ ATPase.

What is the sequence of nuclear changes in irreversible injury?

Pyknosis → karyorrhexis → karyolysis.

What pump fails in cell injury, leading to cell swelling?

Na+/K+ ATPase.

Define hypoxia and name four causes.

O₂ deficiency in tissues. Causes: anemia, ischemia, CO poisoning, cyanide.

What are three mechanisms of ischemia-reperfusion injury?

ROS generation, calcium influx, complement activation and inflammation.

What are the three major types of ROS?

Superoxide (O₂⁻), hydrogen peroxide (H₂O₂), hydroxyl radical (OH•).

What are four key antioxidant defenses against ROS?

Vitamins E, A, C; glutathione; catalase; superoxide dismutase.

What metals catalyze ROS formation, and what proteins bind them?

Iron and copper; bound by transferrin, ferritin, ceruloplasmin.

What type of necrosis is classically seen in infarcts outside the brain?

Coagulative necrosis.

Which form of necrosis is associated with bacterial infections and pus? Also the only type inside the brain.

Liquefactive necrosis.

What are the features and causes of caseous necrosis?

Cheesy, eosinophilic, granulomatous—seen in TB and fungal infections.

What causes fat necrosis in pancreatitis?

Lipase-mediated saponification of fat, forming chalky white areas.

What distinguishes wet gangrene from dry gangrene?

Dry = ischemic coagulative necrosis; wet = superimposed infection + liquefaction.

What kind of necrosis is associated with autoimmune vasculitis?

Fibrinoid necrosis—immune complex deposition in vessel walls.

What are psammoma bodies, and where are they seen?

Concentric calcifications found in meningiomas, papillary thyroid cancer, serous ovarian tumors.

What are three physiologic roles of apoptosis?

Embryogenesis (e.g. digit separation), involution of tissues (e.g. endometrium), and immune regulation (removal of self-reactive lymphocytes).

What molecule flips to the outer membrane to signal macrophage cleanup?

Phosphatidylserine.

What protein promotes mitochondrial-mediated apoptosis?

BAX and BAK—promote outer mitochondrial membrane permeability.

What protein blocks apoptosis and is overexpressed in cancer?

BCL-2—inhibits mitochondrial pore formation.

What process results in DNA laddering?

Endonuclease cleavage during apoptosis—produces oligonucleosomal fragments.

How do cytotoxic T cells induce apoptosis in virally infected cells?

Release perforin to form pores and granzyme to activate caspases.

What is the intrinsic trigger for apoptosis when DNA damage is irreparable?

Activation of p53 → BAX/BAK pathway.

What kinase proteins mediate necroptosis?

RIPK1 and RIPK3, leading to MLKL activation.

What cell death process involves IL-1 release and fever?

Pyroptosis—mediated by caspase-1 and inflammasomes.

What is ferroptosis dependent on, and how is it different from apoptosis?

Iron-dependent lipid peroxidation; distinct from apoptosis as it doesn't involve caspases.