Porth's Essentials of Pathophysiology, 4e

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Disorders of Brain Function

C h a p t e r 3 7

Other Types of Dementia Vascular Dementia

Neurocognitive Disorders Alzheimer Disease Pathology Manifestations

Frontotemporal Dementia Wernicke-Korsakoff Syndrome Huntington Disease

Diagnosis and Treatment

weight, it receives one sixth of the resting cardiac output and accounts for 20% of the body’s oxygen consump- tion. 2 By definition, hypoxia denotes a deprivation of oxygen with maintained blood flow, whereas ischemia represents a situation of greatly reduced or interrupted blood flow. The cellular effects of hypoxia and ischemia are quite different, and the brain tends to have different sensitivities to the two conditions. Hypoxia interferes with the delivery of oxygen, whereas ischemia interferes with the delivery of oxygen and glucose as well as the removal of metabolic wastes. Hypoxia usually is seen in conditions such as expo- sure to reduced atmospheric pressure, carbon monox- ide poisoning, severe anemia, and failure of the lungs to oxygenate the blood. Contrary to popular belief, hypoxia is fairly well tolerated, particularly in situations of chronic hypoxia. Neurons are capable of substantial anaerobic metabolism and are fairly tolerant of pure hypoxia, in which case it produces listlessness, drowsi- ness, and impaired problem solving. Unconsciousness and convulsions may occur when hypoxia is sudden and severe. However, the effects of severe hypoxia on brain function seldom are seen because the condition rapidly leads to cardiac arrest and ischemia. Ischemia is seen in conditions of low blood flow. Cerebral ischemia can be focal, as in a stroke due to cerebral artery occlusion, or global, as in cardiac

arrest. 3 Cerebral artery occlusion leads to focal isch- emia, and if sustained, to infarction (death) of brain tissue in the distribution of the affected vessel. The location of the infarct and extent of tissue damage that results is determined by modifying variables, of which collateral blood flow is the most important. The collat- eral circulation may even provide sufficient blood flow to the borders of the focal ischemic region to maintain a low level of metabolic activity, thereby preserving tis- sue integrity. Within the brain, certain regions and cell popula- tions are more susceptible than others to ischemic injury 4 (Fig. 37-1). Areas of the brain located at the border zones between the overlapping territories sup- plied by the major cerebral arteries, sometimes called the watershed areas, are extremely vulnerable to ischemia. During events such as severe hypotension, these distal territories undergo a profound lowering of blood flow, predisposing to ischemia and infarc- tion of brain tissues. As a consequence, areas of the cortex that are supplied by the major cerebral arter- ies usually regain function on recovery of adequate blood flow, whereas infarctions may occur in the watershed strips, resulting in focal neurologic deficits. Laminar necrosis refers to short, creeping segments of necrosis that occur within and parallel to the cerebral cortex, in areas supplied by the penetrating arteries

Anterior cerebral artery

Middle cerebral artery

FIGURE 37-1. Consequences of global ischemia. A global insult induces lesions that reflect the vascular architecture (watershed infarcts, laminar necrosis) and the sensitivity of individual neuronal systems (pyramidal cells of the Sommer section, Purkinje cells). (FromTrojanowsi JQ, Kenyon L.The central nervous system. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 5th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2008:1191. Courtesy of Dmitri Karetnikov, artist.)

Watershed zone of infarction Short penetrating arteries

Necrosis in Sommer sector of hippocampus

Laminar necrosis

Necrosis of Purkinje cells of cerebellum