Cell Injury and Death

Hypoxia

No oxygen + nutrition due to artery blockage, lung disease, or anaemia

Toxins (cause of cell injury)

Air pollutants, insecticides, CO, asbestos, cigarette smoke, ethanol, drugs/therapeutic drugs

Infectious agents (cause of cell injury)

Viruses, bacteria, fungi, parasites

Immunologic reactions (cause of cell injury)

Autoimmune reactions, allergies, excessive/chronic immune response → inflammation → tissue damage

Genetic abnormalities (cause of cell injury)

Chromosomal abnormalities/mutations → congenital malformations (Down syndrome, sickle cell anaemia), damaged DNA/misfolded proteins

Nutritional imbalances (cause of cell injury)

Protein-calorie insufficiency, vitamin deficiency, excessive dietary intake

Physical agents (cause of cell injury)

Trauma, extreme temperature, radiation, electric shock, sudden atmospheric pressure changes

Cellular response to injury depends on what factors?

Type of injury, duration, and severity

Outcome of cell injury depends on what factors?

Cell type, metabolic state, adaptability, genetic makeup

Cell injury usually results in what?

Functional + biochemical abnormalities in essential cellular components

Most common morphologic change in reversible cell injury?

Cellular swelling

Gross appearance of cellular swelling in organ

Pallor, increased turgor, increased organ weight

Microscopic appearance of cellular swelling

Small clear vacuoles in cytoplasm (hydropic change/vacuolar degeneration)

Hydropic change

vacuolar degeneration due to cellular swelling

Fatty change definition

Triglyceride-containing lipid vacuoles in cytoplasm

Organs most affected by fatty change

Organs involved in lipid metabolism (especially liver)

Gross appearance of fatty liver

Liver becomes whiter than normal due to fat accumulation

Plasma membrane changes in reversible injury

Blebbing, blunting/distortion of microvilli, loosening of intercellular attachments

Mitochondrial changes in reversible injury

Swelling + appearance of phospholipid-rich amorphous densities

ER changes in reversible injury

Dilation of ER + ribosome detachment + polysome dissociation

Nuclear changes in reversible injury

Clumping of chromatin

Myelin figures in injury

Whorled phospholipid masses seen in cytoplasm during cell injury

Necrosis definition

Accidental rapid uncontrollable cell death indicating a pathologic process

Main causes of necrosis

Severe O2/nutrient loss, toxins, trauma

Necrosis outcome

Severe irreversible damage beyond repair and survival

Most common necrosis type due to ischemia in solid organs (except brain)

Coagulative necrosis

Pathophysiology of coagulative necrosis

Protein + enzyme denaturation → limits proteolysis of dead cells

Sites of coagulative necrosis

Liver, kidney, myocardium, skeletal muscle

Gross appearance of coagulative necrosis

Firm pale wedge-shaped area (infarct)

Microscopy of coagulative necrosis

Preserved tissue architecture with “ghost cells”

Key cell appearance in coagulative necrosis

Eosinophilic anucleate cells persisting days to weeks

Nuclear change in coagulative necrosis

Karyolysis (loss of nuclei)

Necrosis type in CNS infarction

Liquefactive necrosis

Liquefactive necrosis mechanism

Enzymatic digestion of dead cells → tissue liquefies

Liquefactive necrosis causes

Hypoxic death in CNS or microbial infection

Liquefactive necrosis sites

Brain, abscess

Gross appearance of liquefactive necrosis

Soft liquid pus-filled cavity

Microscopy of liquefactive necrosis

Complete digestion, loss of structure, many neutrophils

Pus composition in liquefactive necrosis

Creamy yellow viscous liquid from digested tissue

Caseous necrosis definition

Cheese-like necrosis classically seen in TB

Cause of caseous necrosis

TB infection with hypersensitivity reaction to lipopolysaccharide in TB cell wall

Site of caseous necrosis

Lung (TB)

Gross appearance of caseous necrosis

Friable yellow-white “cheese-like” necrotic area

Microscopy of caseous necrosis

Amorphous granular pink debris of fragmented/lysed cells

Granuloma definition

Macrophages + inflammatory cells surrounding caseous necrosis

Fat necrosis definition

Focal fat destruction due to enzymatic digestion and saponification

Main causes of fat necrosis

Abdominal trauma or acute pancreatitis

Fat necrosis pathogenesis

Pancreatic enzymes leak → digest fat → fatty acids bind Ca → chalky white lesions

Sites of fat necrosis

Pancreas, breast, mesentery

Gross appearance of fat necrosis

Chalky white deposits (calcium soap formation)

Saponification

Calcium soap formation at sites of fat breakdown

Microscopy of fat necrosis

Shadowy fat cells + calcium deposits

Fibrinoid necrosis definition

Bright pink fibrin-like necrosis in vessel walls

Cause of fibrinoid necrosis

Immune complexes deposition or severe hypertension damaging vessels

Site of fibrinoid necrosis

Blood vessels

Gross appearance of fibrinoid necrosis

Not obvious grossly

Microscopy of fibrinoid necrosis

Bright pink amorphous eosinophilic material in vessel wall

Gangrenous necrosis definition

Coagulative necrosis affecting multiple tissue layers in specific sites

Dry gangrene cause

Loss of blood supply → coagulative necrosis

Wet gangrene cause

Superimposed bacterial infection on ischemic tissue

Common sites of gangrene

Lower limbs, appendix, gall bladder, intestines

Gross appearance of dry gangrene

Black and shrivelled

Gross appearance of wet gangrene

Swollen and foul-smelling

Microscopy of gangrene

Coagulative necrosis (dry) ± liquefactive necrosis (wet infection)

Apoptosis definition

Programmed regulated cell death without host reaction/inflammation

Key feature of apoptosis

Occurs via defined genes and biochemical pathways

Apoptosis can occur in healthy tissue?

Yes, not necessarily associated with pathologic injury

Physiologic role of apoptosis

Eliminates unwanted cells during development + maintains constant cell numbers

Pathologic trigger of apoptosis

DNA/protein damage beyond repair

Nuclear morphology in apoptosis

Chromatin condensation, aggregation, and karyorrhexis

Cell morphology in apoptosis

Cell shrinkage + cytoplasmic budding

Apoptotic bodies

Cell fragments formed from apoptosis that may be histologically undetectable

Appearance of apoptotic body

Round/oval intensely eosinophilic cytoplasm with nuclear chromatin fragments