• fxnal hypoxia: low partial pressure of O2
• impaired O2 carrying capacity of the blood
• inhib of O2 use by the tissue
• ischemia due to dec perfusion or obstruction of large or small blood vessels

• amount of collarteral circ
• duration of ischemia
• magnitude of rapidity of the reduction of blood flow
• these factors will determine
  • antamoic site of lesion
  • size of lesion
  • clinical deficit

• global cerebral ischemia
  • results form a general dec in cerebral perfusion such as in cardiac arrest, shock, marked hypotension, asphyxia
• Focal cerebral ischemia
  • cessation of blood flow to localized areas of the brain due to large or small blood vessel disease

• Neurons: most sensitive to hypoxia
• oligodendroglia: also sensitive
• astrocytes: also sensitive
• there are differences in regional blood flow and cellular metabolic requirements

• the outcome depends on severity of insult
• MINOR ISCHEMIA: result in trasient confusion with  no morpho or fxn derangements but at times can cause perm damage w/ permanent clinical deficits
• more SEVERE ISCHEMIA: result in variety of clinical and morph changes, many devastating
• widespread neuronal death
  • if pt survives permanent deficits
  • severe neuro impair, remain in deep coma
• BRAIN DEATH: evidence of diffuse cortical injury: flat EEG w/ brainstem damage, no resp drive, no reflexes, no cerebral perfusion
• RESPIRATOR BRAIN: necrosis, edema, widespread destruction of brain due to recurrent cycles of edema and vasocompression --> autolysis & soft brain which prevents its fixation if formalin (on resp for long time - swell, inc in kids)

• swollen brain
• wide gyri
• narrow sulci
• possible herniation (bc of swelling)
• ischemia and hemorrhage assoc w/ herniation

• Early Stage: 12-24hrs after injury produces neuronal cell change causing red nerons - cells undergo vacuolization and eosinophilia of cyto ultimately resulting in pyknosis & karyorrhexis
  • pyramidal cells of hippocampus & purkinje cells of cerebellum partic susceptible to global ischemia. eventually nphils infiltrate
• subacute changes: 24 hrs -2w includes necrosis infiltration of mphags, vascular prolif, reactive gliosis
• Repair: after 2 wk removal of necro tissue, loss of org cell structures & gliosis --> uneven destruction of the neocortex w/ preserve of some areas and involv of others called: psuedolaminar necrosis

• Cerebral arterial occlusion caused by thrombotic occlusions arising from aterosclerosis
• most common sites of primary thrombosis --> infarc are: CAROTID BIFURCATION, ORIGIN OF MCA & BASILAR A
• occlusion caused by anterograde progression of the thrombus or frag and subsequent embolization
• assoc w/ systemic dz: DM & HTN

Focal Ischemia due to vasc Inflam

• arteritis: small and large vessel inflam - syphilis, TB, immunosuppressed
• PAN & collagen vasc dz: inv cerebral vessels-->single or mult infarcts
• primary angiitis of CNS: inv small to med sized parenchymal & subarachnoid vessels w/ infilt by chronic inflam & giant cells
• hypercoag states: PCV, sickle cell
• dissect aneurysm of extracranial A, esp in neck
• drug abuse: partic stim like meth & cocain, heroin

• Cerebral Autosomal Dominant Arteriopathy w/ subcortical infarcts & leukoencephalopathy
• Assoc w/ mut in Notch 3
• characterized by recurrent strokes and dementia
• abnorm of white matter & concentric narrow of adventitia and media of leptomeningeal arteries
• rare hereditary form of stroke

• much more common cause of ischemia and infarct
  • cardiac mural thrombi
  • MI
  • valv dz
  • Afib
  • cartoid artery atherosclerosis
  • fat, air, tumor emboli
• area of distribution of the MCA, direct extensionof Int Carotid A,
• emboli lodge at bifurcation of arteries
• location of embolus cant be ID'd at autopsy bc lysis
• fat emboli:fracture of long bones w/ release of bone marrow & fat occur in MVA, widespread white matter hemorrhage & generalized cerebral dysfxn
• air emboli: penetrating injury to cervical vessels, IV injection of air, divers, sex
• tumor emboli many sarcomas and some CA can emboli

• suffocation
  • air cant get in
  • entrapment/env: inadequate O2, autopsy alone will not give COD
  • smother: occlude ext airway, minimal autopsy findings
  • choke: occlusion int airway
    • nat: epiglottitis, homicidal: movement of gag, Accident: inhale food, foreing obj
  • positional asphyxia: usu accident, drugs/alc, trapped in position which impair breath, congestion cyanosis, petechiae
  • traumatic asphyxia: heavy weight compresses chest/upper abd, congestion petechia, BURKING, overlaying - baby sleep w/ parents
  • mech asphyxia: compression of body
  • suffocating gases: displace O2
• strangulation
  • hanging, ligature strangulation, manual strangulation
• chemical asphyxiation

• colorless, odorless, tasteless -
• compete w/ o2 for binding sites on o2 carrying proteins.
•  cherry red discolors of tissues.
•  necrosis of globus pallidus, cerebral cortex, hippocampus

• produces cell hypoxia by competing w/ ferric iron atom of intracell cytochrome oxidase
• seen in suicides gas chambers
• death is not usu instantaneous
• smell of almonds
• burns of gastric mucosa
• pink discolorationof tissues

• produced by fermentation of organic matter
• found in sewers and cesspools
• low doses have rotten egg smell
• high doses paralyze olfactory nerves
• high doses cause rapid death

• gases displace oxygen from the atmosphere
• carbon dioxide and methane most common
• reduction of atmosphereic O2 in less than 25% causes unconsciousness in seconds and death in minutes
• no specific autopsy findings