2.11 PHYS - Ischemia Regulatoin of blood flow...

Question 1

Contrast the deficits from infarcts of the 1. anterior, 2. middle, and 3. posterior cerebral arteries

Answer 1

1. Anteiror: contralateral paralysis - lower limb, contralateral loss of sensation - lower limb
2. Middle: contralateral paralysis - upper limb andand face, contralateral loss of sensation of upper and lower limbs, and face, aphasia if in dominant hemisphere (usually left), hemineglect if lesion effects nondominant side (usually right)
3. Posterior: contralateral hemianopia with macular sparing

Question 2

Describe the regulation of cerebral blood flow by:

1. Pressure changes
2. Blood gases

Answer 2

1. Response to changes in mean arterial pressure:
   •Brain arterioles constrict with increased blood pressure and dilate with lowered blood pressure.
   •The size changes keep the cerebral flow constant
2. Response to changes in blood gases:
   •CO2 can increase due to a metabolic increase.
   •Raised arterial CO2 causes brain arterioles to dilate and cerebral blood flow will increase.
   •Low arterial CO2 leads to vasoconstriction and cerebral blood flow will decrease

Question 3

Describe how 1. autoregulation, 2. active hyperemia, 3. reactive hyperemia are examples of local (intrinsic) control of blood flow

Answer 3

1. Autoregulation: Flow remains constant over a range of perfusion pressures
2. Active hyperemia: Increase in flow in response to increased metabolic demand
3. Reactive hyperemia: Increase in flow in following periods of occlusion

Question 4

Describe how ischemia can lead to excitotoxicity

Answer 4

•Insufficient blood supply to cells means less oxygen and glucose getting to the cells.

• -> Anoxia leads to swelling of cells.
• -> Lack of glucose and oxygen stops ATP production and leads to failure of the Na+/K+ ATPase and thus build up of Na+ in cells

•Oxygen-deprived cells release large amounts of glutamate at nerve terminals which leads to overactivation of glutamate receptors.
•NMDA receptors have been implicated due to their ubiquity and their high Ca2+ permeability.
The active glutamate receptors leads to excessive increases in intracellular calcium

Question 5

Describe how excitoxicity can damage neurons

Answer 5

• Na+ entry into cells leading to rapid cell swelling and lysis.
• Increased Ca2+ entry leads to damage of endoplasmic reticulum and mitochondria
• The calcium activates many enzymes (phosphatases, proteases, lipases) that degrade the cell.
• Lipid peroxidation leads to free radicals which damage cellular proteins and leads to cell death.
• Possible involvement of the activation of genes for programmed cell death