Ischemia: Causes and Effects

• Ischemia is a decrease in blood supply to a tissue or part, caused by an occlusion of its arterial supply

Types of Ischemia

• Sudden (acute) ischemia
• Gradual (chronic) ischemia

Causes of Sudden (Acute) Occlusion:

• Thrombosis or embolism in the lumen
• Surgical ligature of the artery or arterial vasospasm in certain poisoning in the wall

Causes of Gradual (Chronic) Arterial Occlusion:

• Tumor, enlarged lymph nodes, or fibrosis exert pressure on the artery
• Atherosclerosis in the wall of the artery

Effects of Acute Ischemia:

• Tissues with end arteries experience infarction or gangrene
• Tissues with efficient collateral supply experience almost no damage
• Permanent cells like neurons undergo necrosis easily (brain cells die after 20 minutes)
• Connective tissue cells tolerate ischemia longer (cardiac muscle cells die after 6 hours, bone cells die after 12-48 hours)
• Low oxygen content in the blood due to severe anemia or CHF leads to already low oxygen delivery to body cells

Chronic Ischemia

• Gradual ischemia allows collaterals to open up
• Efficient collaterals prevent tissue damage
• Inefficient collaterals lead to necrosis and replacement fibrosis

Infarction

• Infarction is an area of coagulative necrosis (liquefactive in the brain) due to acute ischemia in an organ with end-arteries (brain, retina, heart, spleen, kidney, and intestine)

Common Sites of Infarction:

• Myocardial, cerebral, pulmonary, intestinal infarction
• Ischemic necrosis of distal extremities (gangrene)

Types of Infarction:

• Red (hemorrhagic) infarct occurs in soft and vascular organs like the lung
• Red infarcts also occur in tissues with dual circulations like the lung and small intestine
• Red infarcts occur when blood flow is restored to an area of infarction
• The red color is due to hemorrhage in the infarct substance from dilated marginal vessels
• When hemolysis occurs in RBCs and its products are removed, the infarct may become pale
• Pale (anemic) infarct occurs with arterial occlusions in solid organs with end-arterial circulations (firm and less vascular) like the heart, spleen, and kidney

General Features of Infarction:

• The size of the infarct area is related to the size of the obstructed artery and the tissue's susceptibility to ischemia such as the brain
• Infarcts are wedge-shaped (pyramidal) due to the fan-like distribution of arteries
• The base is directed towards the surface of the organ, and the apex is deep
• The infarct is subcapsular (raised when recent due to edema, depressed when healed due to fibrosis)
• Serofibrinous inflammation of the overlying serosa occurs
• It is surrounded by a red zone of inflammatory hyperemia
• It is firm (soft in the brain)

Microscopic Examination of Infarction:

• Early on, cells show post-necrotic changes
• Structural details are lost, but outlines are preserved
• Necrotic tissue appears as granular pink debris
• The infarct is surrounded by a zone of acute inflammation (hyperemia, edema, neutrophils, and macrophages)
• Repair follows inflammation beginning at the margins
• Most infarcts are replaced by scar

Fate of Infarct:

• Small infarcts: Necrotic tissue is removed by macrophages, and the defect is filled by granulation tissue followed by fibrosis
• Large infarcts: Surrounded by a fibrous capsule; substances may show dystrophic calcification
• In the brain, high lipid content leads to a cavity filled with clear fluid and surrounded by gliosis

Clinical Manifestations of Infarction:

• Heart failure, arrhythmia, acute failure, or shock can occur
• Hematuria can occur
• Hemiplegia can occur

Gangrene

• Gangrene is defined as necrosis with putrefaction

Causes of Gangrene:

• Necrosis is caused by acute ischemia or bacterial infection
• Putrefaction is caused by saprophytic bacteria active in necrotic tissue

Types of Gangrene:

• Dry gangrene and moist gangrene

Dry Gangrene:

• Occurs especially in the toes and feet of elderly patients with gradual arterial occlusion (artery occlusion alone while veins and lymphatics remain patent)
• There is minimal fluid due to patent venous and lymphatic drainage and evaporation from the surface
• The putrefactive process is slow with mild toxemia
• There is a line of demarcation (area of inflammation) between the gangrenous and healthy part

Wet (Moist) Gangrene:

• Occurs in internal organs, especially the intestine in strangulated hernias, in diabetic patients, or with crush injuries
• It stems from occlusion of both arteries and veins
• There is excess tissue fluid (moist)
• The putrefactive process is rapid with severe toxemia
• There is no line of demarcation

Dry vs. Wet Gangrene:

• Site: Dry typically in extremities; wet in internal organs.
• Cause: Dry from gradual arterial obstruction; wet from sudden arterial and venous obstruction.
• Progress: Dry is slow; wet is rapid.
• Line of Demarcation: Dry has demarcation; wet has none.
• Gangrenous Part: Dry is black, dry, and mummified; wet is swollen and edematous with ulcerated skin.
• Putrefaction: Dry has minimal putrefaction due to lack of fluids; wet has maximal putrefaction.

Bed Sores:

• A type of gangrene occurring with prolonged confinement to bed (paralysis, senility, etc.)
• Continuous pressure from the bed mattress, especially over bony prominences, causes blood stagnation with thrombosis and necrosis
• Dead tissue is cast off leaving a sore (superficial ulcer)
• Underlying bone may be exposed
• Secondary bacterial infection can be present