ch 1 patho

Cellular adaptation definition?

Reversible changes in cell size, number, or function to survive stress

What is homeostasis?

Stable internal environment maintained by continuous physiological adjustment

When does cell injury occur?

When stress exceeds adaptive capacity or is inherently harmful

Define reversible injury

Mild injury where cell can recover after removal of stimulus

Define irreversible injury

Point of no return leading to cell death

Most important causes of cell injury?

Hypoxia, toxins, infections, immune reactions, genetic defects, nutritional imbalance, physical agents

Define hypoxia

Reduced oxygen supply to tissues

Define ischemia

Reduced blood flow causing hypoxia + nutrient deprivation

Which is more severe: hypoxia or ischemia?

Ischemia

Most sensitive organ to hypoxia?

Brain (neurons)

Time for irreversible neuronal death after ischemia?

3–5 minutes

What are the hallmarks of reversible injury?

Cell swelling and fatty change

Why does cell swelling occur?

Na⁺/K⁺ ATPase failure → Na⁺ + water influx

What is fatty change (steatosis)?

Triglyceride accumulation in cytoplasm (mainly liver)

What defines irreversible injury?

Mitochondrial dysfunction + membrane damage + DNA damage

What is the “point of no return”?

Loss of mitochondrial ATP production and membrane integrity

What happens in ATP depletion?

Na⁺/K⁺ pump failure, lactic acidosis, ribosome detachment, cell swelling

Why does lactic acidosis occur in hypoxia?

Anaerobic glycolysis → lactic acid accumulation → ↓ pH

What does mitochondrial damage cause?

ATP loss + cytochrome c release → apoptosis

What does lysosomal rupture cause?

Release of hydrolases → autodigestion

Define ROS

Reactive oxygen species causing lipid, protein, and DNA damage

Most dangerous ROS?

Hydroxyl radical (•OH)

Main effect of ROS?

Lipid peroxidation, protein damage, DNA breaks

Name antioxidant enzymes

Superoxide dismutase, catalase, glutathione peroxidase

Function of SOD

Superoxide → H₂O₂

Function of catalase

H₂O₂ → H₂O + O₂

Function of glutathione peroxidase

Detoxifies H₂O₂ using glutathione

What causes ischemia-reperfusion injury?

ROS burst + inflammation + Ca²⁺ overload after reoxygenation

What does Ca²⁺ overload activate?

Phospholipases, proteases, endonucleases, ATPases

Causes of membrane damage?

ROS, Ca²⁺ activation, ↓ phospholipids, cytoskeletal damage

What is ER stress?

Accumulation of misfolded proteins in endoplasmic reticulum

What is UPR? unfolded protein response

↑ chaperones, ↓ protein synthesis, ↑ degradation of misfolded proteins

What happens if UPR fails?

Apoptosis via intrinsic (mitochondrial) pathway

Define autophagy

Lysosomal degradation of organelles for survival

Function of autophagy

Energy recycling + removal of damaged organelles

Define necrosis

Unregulated cell death with inflammation

Define apoptosis

Programmed cell death without inflammation

Hallmark of necrosis

Membrane rupture + inflammation

Hallmark of apoptosis

Intact membrane + apoptotic bodies + no inflammation

What is pyknosis?

Nuclear shrinkage + chromatin condensation

What is karyorrhexis?

Nuclear fragmentation

What is karyolysis?

Nuclear dissolution

Nuclear sequence in necrosis?

Pyknosis → Karyorrhexis → Karyolysis

Coagulative necrosis occurs in?

Infarcts of solid organs (except brain)

Liquefactive necrosis occurs in?

Brain infarct or abscess

Caseous necrosis is seen in?

Tuberculosis

Fat necrosis is seen in?

Pancreatitis

Fibrinoid necrosis is seen in?

Vasculitis (immune-mediated vessel injury)

Gangrenous necrosis occurs in?

Limb ischemia (dry = coagulative, wet = infection)

Intrinsic apoptosis pathway?

Mitochondrial cytochrome c → caspase-9 activation

Extrinsic apoptosis pathway?

Fas/TNF receptor → caspase-8 activation

Executioner caspases?

Caspase-3, 6, 7

Function of BCL-2?

Anti-apoptotic → prevents mitochondrial permeabilization

Function of BAX/BAK?

Pro-apoptotic → form mitochondrial pores

What happens in apoptosis?

Cell shrinkage + apoptotic bodies + phagocytosis without inflammation

Function of Fas ligand?

Activates extrinsic apoptosis via Fas receptor

Function of p53?

DNA repair or apoptosis if damage is severe

What happens if p53 is mutated?

Cancer due to survival of damaged cells

Causes of DNA damage?

Radiation, ROS, toxins, chemotherapy

What checkpoint does p53 arrest?

G1 phase cell cycle arrest

Define hypertrophy

Increase in cell size

Define hyperplasia

Increase in cell number

Define atrophy

Decrease in cell size and number

Define metaplasia

Reversible replacement of one cell type with another

Example of physiologic hypertrophy!

Uterus in pregnancy

Example of pathologic hypertrophy

Left ventricular hypertrophy in hypertension

Example of physiologic hyperplasia

Breast in pregnancy, liver regeneration

Example of pathologic hyperplasia

Endometrial hyperplasia, BPH

Causes of atrophy

Disuse, denervation, ischemia, malnutrition, hormone loss, aging

Example of metaplasia

Squamous metaplasia in smokers

Barrett esophagus definition

Columnar metaplasia of distal esophagus due to GERD

What is steatosis?

Fat accumulation in liver cells

Effect of alcohol on liver

Fatty liver due to impaired lipid metabolism

What are foam cells?

Lipid-laden macrophages in atherosclerosis

Glycogen accumulation occurs in?

Diabetes mellitus and glycogen storage diseases

What is lipofuscin?

“Wear and tear” pigment from lipid peroxidation

What is hemosiderin?

Iron storage pigment (Prussian blue positive)

What is melanin?

UV-protective pigment

Dystrophic calcification occurs in?

Dead or damaged tissue (normal serum Ca²⁺)

Metastatic calcification occurs in?

Normal tissue due to hypercalcemia

Causes of hypercalcemia?

Hyperparathyroidism, bone destruction, vitamin D excess, renal failure

Main ROS sources?

Mitochondria, inflammation, radiation

What is respiratory burst?

Neutrophil ROS production via NADPH oxidase

Function of VEGF?

Stimulates angiogenesis in hypoxia

Function of HIF?

Activates hypoxia survival genes (VEGF, glycolysis)

Main ATP-dependent pump?

Na⁺/K⁺ ATPase

Mechanism of CCl₄ toxicity?

Lipid peroxidation → hepatocyte necrosis

Mechanism of diphtheria toxin?

Inhibits protein synthesis (EF-2)

Mechanism of mercury toxicity?

Binds sulfhydryl groups → enzyme inhibition

How are apoptotic cells cleared?

Phosphatidylserine exposure → macrophage phagocytosis

Define necroptosis

Regulated necrosis (TNF-mediated)

Define pyroptosis

Inflammatory caspase-mediated cell death with IL-1 release

Define ferroptosis

Iron-dependent lipid peroxidation cell death