Hypoglycemia brain. Loose. 2008. JVECC

Question 1

What percentage of the cardiac output goes to the brain?

Answer 1

15 % of the CO

Question 2

What percentage of the total body oxygen is consumed by the brain at rest?

Answer 2

20%

Question 3

What percentage of the total body glucose is utilized by the brain at rest?

Answer 3

25%

Question 4

Where are glucosensing receptors located?

Answer 4

in the brain

• ventromedial hypothalamus –> at BBB

and the peripheray

• intestinal tract, hepatoportal region, carotid body

Question 5

What happens when hypoglycemia stimulates glucosensing neurons?

Answer 5

they stimulate the release of glucagon, epinephrine, and norepinephrine –> leads to astrocyte and hepatic glycogenolysis + cardiovascular changes that promotes cerebral blood flow –> more glucose delviered to the brain

Question 6

True/False: Insulin is required for the brain cells to uptake glucose

Answer 6

false, the brain does not require insulin for glucose uptake

Question 7

How high is the brain’s interstitial glucose concentration compared to plasma glucose?

Answer 7

20-30% lower

Question 8

What are clinical signs seen at plasma glucose cc < 65 mg/dL?

Answer 8

• nervousness
• tremors
• cardiac palpitations
• weakness

Question 9

What are clinical signs that can be seen at plasma glucose concentrations < 18 mg/dL?

Answer 9

• seizure activity
• severe brain damage
• coma
• death

Question 10

What clinical conditions have been associated with neurologic signs from hypoglycemia in dogs and cat?

Answer 10

• iatrogenic or endogenous hyperinsulinemia
• septicemia
• neonatal hepatopathy
• portosystemic shunting
• paraneoplastic syndrome
• hypoadrenocorticism
• xylitol toxicosis

Question 11

What are the 3 systemic compensatory mechanisms again hypoglycemia? in what order do they occur?

Answer 11

1. decrease in insulin secretion + increased in glucagon concentration and secretion –> glucagon –> induces hepatic glycogenolysis and gluconeogenesis
2. release of epinephrine and norepinephrine –> decreases peripehral glucose uptake –> more glucose available for the brain
3. (after hours of hypoglycemia) secretion or cortisol and growth hormone

Question 12

What are the intracranial compensatory mechanisms for hypoglycemia?

Answer 12

• increase of GLUT transporters in the brain (GLUT1 at the luminal side of the BBB –> increased glucose extraction from the blood, and GLUT3 on neurons –> increased glucose uptake from ECF into the neurons
• cerebral blood flow increases
• shift towards pyruvate and lactate production (use neuronal glycogen stores)

Question 13

How does hypoglycemic neuronal injury occur?

Answer 13

reduction in cerebral ATP

• dysfunction of the Na-K-ATPase pump –> increases IC Na in neurons –> cell swelling and glutamate uptake by astrocytes

cellular swelling and membrane disruption

• causes release of excitatory neurotransmitters (=glutamate and aspartate) into brain interstitium

glutamate uptake by astrocytes

• astrocytes depolarize –> opening ion channels –> influx of Ca, K, and Cl

glutamate in brain interstitium

• glutamate activates NMDA and AMPA receptors of excitatory neurons –> increased IC Ca + nitric oxide synthase –> neuronal death

high IC Ca

• causes mitochondrial membrane megachannel (MMC) to open –> causes mitochondrial permeability transition (MPT) –> cell swelling + ROS release –> cell death

intraneuronal zin accumulation

• mediates glutamate excitotoxicity, activates free radicals, cell death

Question 14

What is “hypoglycemic unawareness”?

Answer 14

impaired compensatory responses to hypoglycemia from:

• decreased glucagon release
• decreased hepatic responsiveness to epinephrine
• lower systemic blood glucose levels are tolerated/not noticed in patients because compensatory responses are not initiated
• caused by previous hypoglycemic episodes