STEPTRACKERGENERAL PRINCIPLES | PATHOLOGY | HIGH-YIELD REVIEW

Reversible vs Irreversible Injury

Causes: hypoxia, toxins, infection, immune attack, genetic and nutritional defects, physical agents — all converge on the same cell changes.

FOCUS ON
Low ATP drives reversible injury, and its hallmark is cell swelling. Membrane damage marks the point of no return: plasma membrane (enzymes leak into serum), mitochondrial membrane (cytochrome c leaks) and lysosomal membrane (the cell digests itself).
FEATURE
REVERSIBLE INJURY
IRREVERSIBLE INJURY
EXAM SIGNAL
Hallmark
the one-line answer
Cellular swelling — Na⁺/K⁺-ATPase fails, Na⁺ and water enter
Membrane damage — plasma, mitochondrial, lysosomal
Swelling = reversible · enzyme leak = irreversible
Plasma membrane
Blebbing, loss of microvilli, myelin figures may appear
Rupture → intracellular enzymes enter blood; Ca²⁺ floods in
↑ troponin, CK-MB, AST/ALT, lipase in serum
Mitochondria
Swelling, ↓ oxidative phosphorylation
Membrane damage → loss of ETC, cytochrome c release; large flocculent densities on EM
Cytochrome c in cytosol → intrinsic apoptosis
Nucleus
Chromatin clumping (↓ pH from lactic acid)
Pyknosis (shrinks) → karyorrhexis (fragments) → karyolysis (fades)
Nuclear changes = cell is dead
ER & ribosomes
ER swells; ribosomes detach → ↓ protein synthesis
Lysosomes rupture → hydrolytic enzymes digest the cell
Lysosomal enzymes = autolysis
Cytoplasm
Hydropic (vacuolar) change; fatty change in hepatocytes
↑ eosinophilia (lost RNA, denatured protein)
Pink, glassy cytoplasm = dead myocyte
Calcium
Cytosolic Ca²⁺ begins to rise
High cytosolic Ca²⁺ activates phospholipases, proteases, endonucleases, ATPases
Ca²⁺ in mitochondria → more permeability, more injury
Outcome
Full recovery if O₂ / stimulus restored
Necrosis (groups of cells, inflammation) or apoptosis (single cells, no inflammation)
See pages 1.03 and 1.04

Mechanism — what low ATP does

Hypoxia↓ oxidative phosphorylation
→
↓ ATPPumps fail
→
Na⁺/K⁺ pump ↓Swelling, blebs
→
Glycolysis ↑Lactic acid, ↓ pH, chromatin clumps
→
Ca²⁺ ↑ + membrane damagePoint of no return

Ribosome detachment cuts protein synthesis at the same time. Each step before membrane damage can still recover.

Leaked enzymes → which tissue died

MARKER
TISSUE
NOTE
Troponin I/T
Myocardium
Most sensitive and specific for MI
CK-MB
Myocardium
Falls fast — useful for reinfarction
AST, ALT
Liver
ALT more liver-specific; AST:ALT > 2 suggests alcohol
Lipase, amylase
Pancreas
Lipase more specific
CK-MM
Skeletal muscle
Rhabdomyolysis, crush injury
LDH
Many tissues
Nonspecific; high in hemolysis

How it's tested

COMMON CONFUSIONMitochondrial swelling alone is reversible. Flocculent densities and leaked cytochrome c are not.
THE TRAPThe stem lists "elevated troponin" or "rising ALT" without naming injury type. Any enzyme in serum means membrane damage, so the injury is already irreversible.
YOUR APPROACHAn energy (ATP) problem points to reversible injury. A membrane problem points to irreversible injury. Nuclear dissolution means the cell is already dead.

If you see… think…

Swollen cells with surface blebs, membranes intact → reversible injury (Na⁺/K⁺-ATPase failure)
Fat droplets in hepatocytes after a binge → reversible fatty change
Chest pain + rising troponin → irreversible myocyte membrane damage
Pyknosis, karyorrhexis, karyolysis → dead cell (necrosis)
Cytochrome c in cytosol → mitochondrial membrane damage → apoptosis
Flocculent mitochondrial densities on EM → irreversible injury
Crush injury, dark urine, ↑ CK → skeletal muscle necrosis (rhabdomyolysis)
Clumped chromatin in a hypoxic cell → ↓ intracellular pH from lactic acid
Intensely eosinophilic myocytes → irreversible injury