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Hypoxic and Ischemic Encephalopathy- Pathology of Stroke

y Brain is sensitive because it works by oxidative phosphorylationy Brain has no energy stores and most injury is caused by hypoperfusiony Causes of energy shortage: ischemia, cerebral perfusion, hypoxia, hypoglycemia,

and anemia

y Usually is from cardiac arrestor shock (severe hypotension)y Traumatic brain injury or increased intracranial pressure is a cause of HIE in adults

and children

y A rise of 10 mmHg (systolic) in the brain will cause brain capillaries to collapsey There is a pump in the membrane of neurons that works against the concentration

gradients that is the source of neuronal membrane excitability (Na in and K out)

o In energy failure there is a depolarization of the membranes (fainting)o If energy failure persists then there will be permanent neuronal damageo Glu is dumped into the synaptic cleft (at toxic levels)o Na channels open which causes a mass influx into the cell which results in

cellular edema

o Ca also rushes in and there is activation of cytolytic enzymes and other freeradicals which results in cell death

o Damage- energy failure, glutamate, mitochondrial injury free radicals, lacticacidosis, edema

o Reperfusion, while maintaining brain function, allows the aforementioneddamages to occur as well

y Neurons are more sensitive than glial cells to damage because neurons have higherenergy demands

o Some neurons are more vulnerable- hippocampus, 3-5 cortical layers, purkinjecells, and striatal cells

yPathological Patterns of HIEo Hippocampal sclerosis

Patients with epilepsy or after cardiac arrest Purkinje cell sparing without hypoglycemia Segment of pyramidal layers are missing Causes Korsakoff amnesia- loss of episodic memory (long/short are

preserved)

o Laminal Cortical Necrosis (Pseudolaminar necrosis) and Thalamic injuryKorsakoff (due to dorsal nu of thal involvement) or PVS state whenwakefulness may be present but awareness is not; Diffuse cortical, thalamic, or

combined neuronal loss/white matter damage (with intact brainstem)

bilateralo Border zone (watershed) lesions- does not affect hippocampuso Total Cerebral and BrainstemDamage

Unresponsiveness, absent brainstem reflexes, no spontaneous respiration,flat EEG, no circ, non perfused brain

Imaging shows hypodesnity due to disintegration Cerebral infarcts involving brainstem

y Cerebrovascular Accident

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o Cerebral Infarct- atherosclerosis, small vessel disease (HTN), emoblism Evolution: (1) Cerebral Necrosis (2) Edema (3) Caviation (months) Micro: (1) inflammation and axonal swelling (AA and FA) (2)

neovascularization at 2 weeks; monocytes enter the infarct and disgest

neurons and turn into lipid laden macrophages (3) macrophage reaction at 3-

4 weeks (4) gemistocytic astrocytes and glial scare (2 months) Embolic infarcts can look hemorrhagic but their primary process is an infarct

(clot lyses and then causes bleeding)

Lacunar infarcts from small vessel disease (HTN/diabetes)can cause cysticproblems; affects deeper nuclei (basal ganglia/thalamus); can be just as bad

as more massive infarcts

y Cerebral Autosomal DominantArteriopathy with subcortial infarcts andischemic encephalopathy (CADASIL = notch 3 gene), coll 4A1 defects,

cerebral amyloid angiopathy

Vascular dementia (multi-infarct) Ischemic penumbra- central zone where the necrosis/death is irreversible;

surrounded by a gray zone where recovery may be possible (thissurrounding zone is the penumbra)

o Cerebral Hemorrhage- HTN, arterial aneurysms, AVM, Angiopathy, Coagulopathy Caused by small vessel disease- vessels lose elasticity so their strength is

greatly diminished since strength is due to elasticity not stiffness

Affects basal ganglia, thalamus, and lateral ventricles; also pons, cerebellum,and central white matter

Vascular lesions can cause infarction and hemorrhage Intracranial Aneurysm (Saccular/Berry Aneurysms)- located at the junction

of bifurcation of vessels

y Can enlarge and cause tumor like symptomsy Can rupture (BAD) Subarachnoid hemorrhage will cause increase in

intracranial pressure

y Risks polycystic Kidneys, coarc, and female AVM- tangle of veins and arteries that are delicate and can hemorrhage and

cause seizures/focal defecits

Cerebral Amyloid Angiopathy- parenchymal brain damage; amyloid/fibringdeposit in walls of arteries and makes them fragile

oy