Ischemia, Infarcts & Free Radical Injury

Rapid Review·General Pathology

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CELLULAR INJURY

T2High yield

P206

Focus on

Which specific tissue regions die first when perfusion drops, and why restoring blood flow paradoxically makes the damage worse.

Key takeaways

Ischemia and the zones that die first

Ischemia = inadequate blood supply for demand.

↓ arterial perfusion (atherosclerosis), ↓ venous drainage (testicular torsion, Budd-Chiari), or systemic shock.

Vulnerable regions (memorize the table below)

within every organ there is one zone that is perfused last and therefore dies first.

The watershed zone in each organ
Organ	Susceptible Region
Brain	ACA/MCA/PCA boundary (watershed) zones; Purkinje cells of cerebellum; pyramidal cells of hippocampus and neocortex (layers 3, 5, 6)
Heart	Subendocardium of the LV (last field perfused, highest wall tension)
Kidney	Straight segment of the PCT and thick ascending limb (both medullary)
Liver	Zone III, around the central vein, furthest from the portal triad
Colon	Splenic flexure (Griffith point) and rectosigmoid junction (Sudeck point)

Red vs pale infarcts

Red (hemorrhagic) infarct

occurs in venous occlusion, in tissues with dual or collateral blood supply (liver, lung, intestine, testes), and with reperfusion (post-angioplasty). Blood re-enters loose necrotic tissue.

Pale (anemic) infarct

occurs in solid organs with a single end-arterial supply (heart, kidney, spleen). There is no collateral to bleed in.

Red (hemorrhagic) infarct of the lung: blood re-enters loose necrotic tissue in an organ with a dual blood supply.

Pale (anemic) infarct of the heart: sharply demarcated area of necrosis (arrow) in an end-arterial organ.

Red vs. pale infarct, decided entirely by the blood supply
Feature	Red Infarct	Pale Infarct
Blood supply	Dual/collateral, or venous occlusion	Single end-arterial
Organs	Lung, liver, intestine, testes	Heart, kidney, spleen
Setting	Venous occlusion, reperfusion	Arterial occlusion
Mechanism	Blood re-enters loose necrotic tissue	No collateral to bleed in

Free radical injury

Free radicals damage cells three ways: membrane lipid peroxidation, protein modification, and DNA strand breakage.

Generated by radiation, phase I drug metabolism (P-450), redox reactions, NO, transition metals (iron and copper via the Fenton reaction), and the neutrophil/macrophage oxidative burst.
Eliminated by scavenging enzymes (catalase, superoxide dismutase, glutathione peroxidase), antioxidants (vitamins A, C, E), spontaneous decay, and metal carrier proteins (transferrin, ceruloplasmin).

Classic free-radical diseases

O₂ toxicity in newborns: retinopathy of prematurity and bronchopulmonary dysplasia.
Reperfusion injury after thrombolysis or stenting.
Acetaminophen overdose, and carbon tetrachloride (P-450 → CCl₃• → fatty liver via ↓ apolipoprotein synthesis plus centrilobular necrosis).
Metal overload: hemochromatosis (iron) and Wilson disease (copper).

After a prolonged episode of hypotension, a patient's liver enzymes rise sharply. Which part of the liver lobule is injured first, and why?

Zone III, around the central vein. It is furthest from the portal triad, so it receives the least oxygenated blood and is the first to die when perfusion falls.

How it's tested

After a severe hypotensive episode (shock, GI bleed, cardiac arrest), transaminases spike into the thousands. This is ischemic hepatic necrosis localized to Zone III (centrilobular), because zone III is furthest from the oxygenated blood of the portal triad.

Separately, the paradox question: cardiac enzymes rise further immediately after successful stenting or thrombolysis. This is reperfusion injury, where restored O₂ delivery fuels a free-radical burst, plus Ca²⁺ overload and neutrophil influx, that kills myocytes the original ischemia had merely stunned.

Go deeper

First Aid "Ischemia" + "Free radical injury"; Pathoma Ch. 1; Boards & Beyond. Anchor the ischemia-sensitive cells (hippocampal/Purkinje neurons, cardiac subendocardium, renal PCT straight segment + TAL) and free-radical mechanisms — lipid peroxidation, reperfusion injury, and the antioxidant scavengers.

High-yield images2

Pale (anemic) infarct of the heart: sharply demarcated area of necrosis (arrow) in an end-arterial organ.

Red (hemorrhagic) infarct of the lung: blood re-enters loose necrotic tissue in an organ with a dual blood supply.

Flashcards for this page

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What type of free radical injury is of greatest concern in a patient who has recently undergone thrombolysis for acute limb ischemia?

(...) injury

PreviousNecrosis NextIonizing Radiation

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