Cellular Adaptation, Injury and Death

Hypertrophy

Increase in cell size → increased organ size due to ↑ cellular protein synthesis

Hyperplasia

Increase in number of cells due to growth factor/hormone-driven proliferation

Atrophy

Decrease in organ size due to ↓ cell size + ↓ cell number

Metaplasia

Reversible replacement of one differentiated adult cell type by another via stem cell reprogramming

Dysplasia

Disordered epithelial growth with loss of uniformity + loss of architectural orientation (premalignant, not true adaptation)

Key difference: hypertrophy vs hyperplasia

Hypertrophy

Which tissues can undergo hyperplasia

Labile and stable tissues (must be capable of division)

Permanent cells response to stress

Hypertrophy only (cannot divide)

Classic example of hypertrophy

Skeletal muscle growth in weightlifters

Pathologic hypertrophy example

Left ventricular hypertrophy in chronic hypertension/aortic stenosis

Pregnant uterus enlargement

Both hypertrophy + hyperplasia (smooth muscle)

Breast enlargement in pregnancy

Physiologic hyperplasia of glandular/lobular epithelium

Compensatory hyperplasia example

Liver regeneration after partial hepatectomy

Pathologic hyperplasia definition

Excessive/inappropriate hormonal or growth factor stimulation

Pathologic hyperplasia cancer risk

Creates a “fertile soil” for malignancy

Physiologic atrophy example

Uterus shrinking after childbirth

Major causes of pathologic atrophy

Disuse, denervation, ischemia, malnutrition, loss of endocrine stimulation, pressure, aging

Main mechanism of atrophy

↓ protein synthesis + ↑ protein degradation (ubiquitin-proteasome pathway)

Autophagy

Cell digests its own organelles during starvation to survive

Metaplasia mechanism

Stem cell reprogramming to a new differentiation pathway

Smoking effect on bronchus

Columnar epithelium → squamous metaplasia

Barrett oesophagus

Squamous epithelium → intestinal-type columnar metaplasia

Metaplasia significance

Adaptive but increases risk of dysplasia and carcinoma

Dysplasia key histologic idea

Loss of normal cell polarity and uniformity

Carcinoma in situ

Full thickness dysplasia with intact basement membrane (non-invasive)

Dysplasia reversibility

Mild/moderate dysplasia can be reversible if stimulus removed

Labile cells

Continuously dividing cells (e.g., skin epidermis, GI epithelium)

Stable cells

Quiescent but can divide after injury (e.g., hepatocytes, renal tubules)

Permanent cells

Cannot divide after injury (e.g., neurons, cardiac myocytes)

Main causes of cell injury

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

Ischemia vs hypoxia

Ischemia

Most common cause of cell injury

Hypoxia/ischemia

Core mechanisms of cell injury

ATP depletion, membrane damage, biochemical pathway disruption, DNA damage

Most important early mechanism in ischemic injury

ATP depletion

ATP depletion causes

Failure of Na+/K+ pump → Na+ and water influx → cell swelling

Reversible cell injury definition

Cell can recover and return to normal if stimulus removed

Most common reversible injury morphology

Cellular swelling (hydropic change)

Hydropic change microscopic appearance

Clear cytoplasmic vacuoles due to water accumulation

Fatty change definition

Triglyceride vacuoles in cytoplasm (esp liver)

Early reversible injury organelle changes

Membrane blebs, loss of microvilli, mitochondrial swelling, ER dilation + ribosome detachment, chromatin clumping

Reversible injury key concept

Membranes remain intact enough for recovery

Necrosis definition

Uncontrolled cell death with membrane rupture and inflammation

Apoptosis definition

Programmed regulated cell death without inflammation

Key difference necrosis vs apoptosis

Necrosis

Necrosis gross outcome

Often triggers inflammation and tissue damage extension

Apoptosis gross outcome

Cell fragments removed cleanly with minimal tissue reaction

Necrosis cytoplasmic features

Increased eosinophilia, glassy cytoplasm, vacuolated “moth-eaten” appearance

Necrosis nuclear change sequence

Pyknosis → karyorrhexis → karyolysis

Most diagnostic irreversible injury finding

Nuclear dissolution (karyolysis)

Coagulative necrosis hallmark

Preserved tissue architecture with eosinophilic anucleate cells

Coagulative necrosis typical cause

Ischemia/infarction in solid organs (except brain)

Coagulative necrosis typical organs

Heart, kidney, liver, skeletal muscle

Myocardial infarction necrosis type

Coagulative necrosis

Liquefactive necrosis hallmark

Complete enzymatic digestion → tissue becomes liquid/viscous

Liquefactive necrosis typical causes

Brain infarction and bacterial infections

Abscess definition

Localized collection of pus due to liquefactive necrosis

Brain infarct necrosis type

Liquefactive necrosis

Gangrenous necrosis definition

Clinical term for ischemic necrosis of limb/bowel (usually coagulative)

Dry gangrene

Coagulative necrosis due to ischemia (no infection)

Wet gangrene

Gangrene with superimposed bacterial infection → liquefaction component

Caseous necrosis hallmark

Cheese-like friable yellow-white necrosis; amorphous granular pink debris microscopically

Caseous necrosis classic disease

Tuberculosis

Granuloma definition

Collection of activated macrophages surrounding chronic inflammation (seen around caseous necrosis)

Fat necrosis hallmark

Chalky white deposits due to saponification

Fat necrosis mechanism

Pancreatic lipase releases fatty acids → bind Ca2+ → calcium soaps

Fat necrosis classic setting

Acute pancreatitis or abdominal trauma

Fibrinoid necrosis hallmark

Bright pink fibrin-like material in vessel walls on H&E

Fibrinoid necrosis mechanism

Immune complex deposition + plasma protein leakage into vessel wall

Fibrinoid necrosis seen in

Immune vasculitis and severe hypertension

Most common necrosis pattern in TB

Caseous necrosis

Most common necrosis pattern in MI

Coagulative necrosis

Most common necrosis pattern in cerebral infarct

Liquefactive necrosis

Lipofuscin

Brown-yellow “wear-and-tear” intracellular pigment (aging heart/liver)

Lipofuscin significance

Marker of past free radical injury/aging (benign)

Haemosiderin

Iron storage pigment from breakdown of hemoglobin (hemorrhage/hemolysis)

Melanin

Brown-black pigment produced by melanocytes

UV radiation DNA damage

Formation of pyrimidine (thymine) dimers

Why UV predisposes to cancer

DNA mutation accumulation if repair fails

Apoptosis morphology

Cell shrinkage, chromatin condensation, nuclear fragmentation, apoptotic bodies

Apoptotic bodies

Membrane-bound fragments containing cytoplasm and nuclear material

Why apoptosis does not cause inflammation

Cell contents not leaked; apoptotic bodies rapidly phagocytosed

Physiologic apoptosis roles

Embryogenesis, removal of unwanted immune cells, involution of hormone-dependent tissues

Pathologic apoptosis triggers

Severe DNA damage, misfolded proteins (ER stress), viral infections

Key apoptosis regulatory proteins

BCL2 (anti-apoptotic) vs BAX (pro-apoptotic)

Necrosis exam trigger words

inflammation + swelling + membrane rupture

Apoptosis exam trigger words

shrinkage + apoptotic bodies + no inflammation