6/16- CV Pathology and Pathophysiology Flashcards
What are Watershed zones?
Where is the worst?
Areas supplied by multiple arteries (but the very end of these arteries)
- Infarcts may result from hypotension
Worst = high posterior parietal cortex (“triple border zone area”)
What is the leading cause of ischemic strokes?
Atherosclerosis spawning emboli or thrombus formation (may be intracranial or extracranial)
What is this?
Carotid endarterectomy
- Atherosclerosis with complicated plaques
What is a “complicated” plaque?
What does it cause?
When an atherosclerotic plaque erodes through the endothelium
- Causes thrombogenesis
- May lead to emboli or breaking off or local thrombosis with occlusion of the vessel
What is a non-atherosclerotic cause of stroke?
Carotid dissection
- Blood leaves vessel, gets stuck within adventitia, and then compresses vessel lumen
Where do dissections usually occur?
Areas of trauma to the vessel
- e.g. struck in neck with baseball
- damage to back of throat (near carotid)
What are some symptoms seen in hypotensive ischemic injury?
“Watershed” or arterial border zone infarcts
- Dorsolateral aspects of the cerebral hemispheres
- “Man in a barrel” weakness
- Rims of the cerebellar hemispheres
If sufficiently severe, global damage with atrophy of neuron containing structures:
- Laminar necrosis
- Basal ganglia shrinkage
- Hydrocephalus ex vacuo
What is this?
Watershed infarct of high posterior parietal cortex (although can involve motor strip)
- Infarct = loss of tissue due to ischemia
- Enlarged sulci with shrunken gyri
What is this?
Result of global hypoperfusion
- Not much cortex left (innermost layers go first- laminar necrosis)
- No thalamus, caudate….
- Hydrocephalus ex vacuo
- Person would be unconscious; persistent vegetative state
What is this?
Sulcal depth discoloration seen in relative watershed
- Depth of sulcus is relatively less well perfused than surface
- Opposite of contusions (affect surface of gyri more)
Which cells are most vulnerable to ischemia?
Neurons >> Glia > Endothelium
- Purkinje cells of cerebellum
- Pyramidal neurons of CA1 (Sommer’s sector of the hippocampus)
- Middle layers of the cerebral cortex- laminar necrosis
Secondary mechanism of damage following ischemia?
Major contribution from excitotoxicity secondary to release of aspartate and glutamate
What is this?
Shows selective ischemic vulnerability of the neurons in the hippocampus
- Memory problems
What is this?
Acute Middle Cerebral Artery Infarct
- Discoloration in MCA territory
- Ventricular effacement
- Cingulate herniation
- Probably pretty proximal block, because so much area affected
- Pt’s life is endanger from brain swelling (may need hemi-craniectomy)
What is this?
Acute PCA stroke
- Posterior cerebral artery territory infarcts (mesial surface of temporal lobe)
- May result from emboli or thrombosis
Histopathology of Infarction: Temporal Evolution
- Day 1:
- Day 2- weeks:
- Weeks- months:
Day 1:
- Red neuron and rarefaction of neuropil (first sign/change that can be seen of infarction; light microscopy)
Day 2-weeks:
- Neuronal drop out
- Rarefaction of neuropil
- Influx of macrophages and fewer lymphocytes and poly’s
- Astrogliosis
- Vascular proliferation (beware of contrast ehancement!)
Weeks-months:
- Cystic cavity containing macrophages then CSF
- Wall of reactive astrocytes (reactive gliosis)
What is this?
Acute infarct with red neurons
- Earliest light microscopic change in CNS infarct
- Red cytoplasm
- No good Nissl substance anymore
What is this?
How long after stroke?
Remote middle cerebral artery infarct
Several months later
- Neurons/tissue cleared out by macrophages
- Large ventricle compensating for volume loss
- If this hits motor strip, person will probably be hemiparetic (face and arm worse than leg b/c ACA still okay)
What is this?
Wall of remote infarct cavity
- Macrophages (foamy cytoplasm)
- Rarefied tissue- not many cells
- Reactive astrocytes (big, bottom right) in wall; much cytoplasm- doing their best to wall off the cyst
What does this show?
Cerebral peduncle and medullary pyramid atrophy following MCA infarct
- Due to loss/degeneration of axons
What is this?
Remote pontine infarct (cystic infarct)
- Near midline, so mesial/medial perforating infarct of the pons from arteries from the basilar coming straight in
What is this?
Multiple hemorrhagic emoblic infarcts
- Often come from heart valves/dysfunctional wall
- Possible from atherosclerosis in carotids
- Most emboli go ipsilateral
In addition to atherosclerosis and carotid dissection, what else can cause a stroke?
Vasculitis- inflammation of the wall of the blood vessel (entire thickness)
- May be part of systemic vasculitis or may be confined to CNS
- Inflammatory infiltrate MUST involve the entire thickness of the vessel wall; transmural inflammation
- May cause multifocal strokes
What is this?
Vasculitis (must have transmural inflammation)
What is this?
Granulomatous vasculitis
- Giant cell
What is this? Symptoms?
Lacunar infarct
- Infarct in area of tiny lenticulostriate artery (?)
Symptoms
- Typically asymptomatic
- May have huge effect in internal capsule
What is this?
Thickened tortuous small vessel with hemosidiren staining due to long standing HTN
- Kind of curvy
- Compromised/thickened wall
What are the therapeutic principles in ischemic strokes: thrombotic?
- Thrombolysis (TPA) if under 4.5 hrs of Sx onset and no hemorrhagic component (activates endogenous system to break down clots)*
- Vigorous supportive care (do not allow hypotension; protect airway if level of consciousness decreased; DVT prophylaxis)
- Anti-platelet treatment (baby aspirin, 86 mg)
*Not eligible if person woke up with a stroke and doesn’t know timeline
What are the therapeutic principles in ischemic strokes: embolic?
- Remove source if possible
- Consider anti-coagulation (warfarin/heparin)
- Direct thrombin inhibitors
What is this?
Hypertensive hemorrhage
What is this?
Catastrophic hypertensive hemorrhage
What is this?
Cerebellar hemorrhage
- One of the few hemorrhages that surgery may help (remove hematoma)
What is this? Results?
Pontine hemorrhage
- Loss of reticular activating system, loss of consciousness…
- Usually lethal
What is the underlying cause of hypertensive hemorrhage?
Microaneurysms of Charcot-Bouchard
Is death more common with ischemic stroke or hemorrhagic?
Hemorrhagic
What is a major cause of lobar hemorrhage in elderly patients?
Amyloid angiopathy
What is this?
Amyloid angiopathy
What is this?
Multiple hemorrhages in metastatic tumors
Therapeutic principles in intracerebral hemorrhage (ICH)?
- Vigorous supportive care; NO ASA
- Surgical evacuation of cerebellar hemorrhage; data does not support evacuation of ICH at other sites
- Ventricular drainage if the hemorrhage extends into ventricles
- Activated Factor VII being evaluated to see if ICH expansion can be slowed or stopped by increasing coagulation and that this impacts impact– mixed results
________ are the major cause of non-traumatic subarachnoid hemorrhage (SAH)?
Berry aneurysms are the major cause of non-traumatic subarachnoid hemorrhage (SAH)
- Up to `15% of pts have multiple
Different types of aneurysms?
Saccular or berry aneurysms (most)
- 15-20% may be multiple
- Proximal
Mycotic aneurysms
- Also on anterior circulation
- Distal
- Bacterial or fungal (infectious)
What caused this? Symptoms?
Rupture aneurysm (“giant” on top left, smaller mid-right)
- Worst headache of life
- May not have focal deficit
- May lose consciousness
Treatment for aneurysm?
Coiling- place and pass electrical current to trigger thrombosis; leave coil
What is this?
Cavernous sinus anuerysm
(direct arterial-venous shunting)
- Can take down CN 3, 4, 5, 6
- Bruit over eyeball
Different types of vascular malformations?
Where are these found?
What do they result in?
- Ateriovenous malformation (AVM)**
- Cavernous angioma**
- Venous angioma
- Capillary telangectasia
These are in the brain parenchyma, but are so close to the surface, they can cause subarachnoid bleeds (?)
**Clinically significant
What are AVMs (arteriovenous malformations) made of?
- Composed of anastomosed abnormal arteries and veins (no intervening capillary bed)
- Arterial component contains internal elastic lamina (elastic stain)
- Intervening neuropil is gliotic (sometimes with Rosenthal fibers)- reactive, abnormal tissue between vessels
- Hemosiderin deposition and granular bodies
Potential of AVMs for significant _____ = ___?
Potential of AVMs for significant hemorrhage = 2-4%
What is this?
Big AVM in temporal lobe
- Some on surface
- Brownish = hemosiderin staining
On micro see different vascular calibers
- Tissue seen between vessels
Cavernous angioma (cavernous hemangioma or cavernoma) made of what?
Microscopic and gross features?
Genetics?
- Cluster of vascular channels with hyalinized walls
- Varying caliber
- May contain fibrin thrombi
- No intervening neuropil
- No arterial component
- “Popcorn” appearance on MR with hemosiderin deposition
- CCM1: krit mutation (AD)
What is this?
Cavernous malformations in pons and temporal lobe
Grossly: popcorn
Therapeutic principles in aneurysms and vascular malformations?
Prevent additional hemorrhage (neurosurgical or endovascular therapy)
- Clip or coil aneurysm
- Remove or glue vascular malformation
- Not all vascular malformations require treatment
Subarachnoid blood causes vasospasm that may lead to ischemia
- Vasospasm maximal 2-14 days after SAH
- Intervene early if possible, otherwise will have to wait
- Treat/prevent vasospasm
