Hemorrhagic Stroke: Pathogenesis and clinical findings
Authors: Andrea Kuczynski Oswald Chen Reviewers: Sina Marzoughi Usama Malik Anjali Arora Ran (Marissa) Zhang Mao Ding Michael D Hill* Gary Klein* * MD at time of publication
Primary Intracerebral Hemorrhage (~75%)
Secondary Intracerebral Hemorrhage (~25%)
Amyloid Angiopathy
Amyloid deposits in blood vessels and weakens vessel walls
Hypertension
Lipohyalinosis (lipid and protein aggregation in arterial walls) weakens blood vessels
Unknown
Aneurysm
Dilation of a weakened blood vessel
Drugs (e.g., cocaine, crystal meth, decongestants, anticoagulants)
Vascular Malformations
Note: the pathophysiology and exact mechanism is not well known
Release of toxic blood plasma components (coagulation factors, immunoglobins)
Red blood cell lysis
Cytotoxic hemoglobin (heme, iron) release
Fenton-type free radical generation (Fe(II) + H2O2 → Fe(III) + OH− + OH•)
Oxidative damage to carbohydrates, lipids, nucleic acids, and proteins in brain
Necrosis of hypoxic brain tissue
Neurological signs: focal motor weakness, aphasia, vision loss, sensory loss, imbalance/incoordination, altered LOC
Rupture of blood vessel(s) Accumulation of blood → hematoma formation
↓ Cerebral tissue perfusion (↓ O2 availability)
↓ Mitochondrial oxidative phosphorylation (final step in aerobic glucose metabolism)
↓ Adenosine triphosphate (ATP) production
↑ Anaerobic glucose metabolism → ↑ Cerebral lactate production
Cerebral lactic acidosis Impaired cellular metabolism Death of neurons and glia
Microglia clear debris and release inflammatory markers (TNFα, IFγ, IL-1β)
↑ Endothelial cell apoptosis and ↑ blood-brain barrier permeability
Cerebral edema
Increased intracranial pressure: papilledema, sudden headache, non-reactive pupils, ↓ level of consciousness (LOC), nausea/vomiting
Astrocytes release glutamate (main excitatory neurotransmitter)
Activation of neuronal metabotropic glutamate receptors
↑ Ca2+ influx into neurons
Excitotoxicity (excess stimulation of glutamate receptors leading to neuronal death)
Dysfunction of Na+/K+ ATPase pump (moves 3 Na+ out of cell and 2 K+ into cell) on neurons
↓ Na+ efflux and ↓ K+ influx
Neuronal membrane potential becomes less negative (closer to threshold potential)
Neurons depolarize → ↑ Glutamate release
General findings: Seizures, lethargy
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
First published June 6, 2018, updated February 28, 2023 on www.thecalgaryguide.com