Energy Merabolism in the CNS

Question 1

The human brain lacks any capacity to? Therefore it is extremely vulnerable to?

Answer 1

Store energy; interruptions in nutrient supply

Question 2

the human brain has a very active?

Answer 2

Very active metabolism;

Question 3

The human brain has an extremely high? How does the brain accomplish this?

Answer 3

Flux; High enzymatic concentration that allows a rapid response to increase in available glucose

Question 4

the brain is biased towards what over what? This means that?

Answer 4

the brain is biased towards glycolysis over gluconeogenesis. This means that little is stored as carbohydrates

Question 5

There are very low amounts of what and what?

Answer 5

Low amounts of glycolytic and TCA cycle intermediates

Question 6

The brain has a vulnerability due to? This means it must reline on?

Answer 6

High metabolic rate and limited energy stores; leads to an absolute reliance on blood for O2 and energy substrates

Question 7

The brain has a critical dependence on?

Answer 7

aerobic glucose metabolism

Question 8

any supply interruption to the brain leads to? This can be a shortage of ?

Answer 8

Encephalopathy; ether glucose or O2

Question 9

the brain is extremely vulnerable to?

Answer 9

Hypoxia; Hypoglycaemia; disorders of glucose metabolising enzymes

Question 10

how can an insulin overdose lead to coma?

Answer 10

overdose of insulin drives available glucose into the periphery; this leads to low levels of glucose getting to the brain which leads to coma

Question 11

in case of starvation how is the brains energy demands met? Why do you not see the immediate effects like in an insulin overdose?

Answer 11

Because glucose fails slowly in starvation the body has time to begin to make ketone bodies from the break down of fat

Question 12

what are some consequences of hypoglycaemic encephalopathy?

Answer 12

Neurological impairment progressing through confusion to seizures coma and ultimately death (cessation of spontaneous EEG potentials)

Question 13

At the pre-terminal stages of hypoglycaemia the cerebral metabolic rate for what falls more rapidly then? This suggests that?

Answer 13

At the pre-terminal stages of hypoglycaemia the cerebral metabolic rate for GLUCOSE falls more rapidly O2; This suggests that alternative substrates are being oxidized

Question 14

during hypoglycaemic encephalopathy what are some substrates that can support the brain? How long can these stories support the brain?

Answer 14

TCA cycle intermediates (very small pool) amino acids (glutamate and glutamine); these stories only last for approx.. 15 min

Question 15

what are the 2 compensatory mechanisms for low 02 levels in the brain?

Answer 15

Cerebral blood flow increases; ATP Production switch’s to anaerobically (this can lead to acidosis)

Question 16

where does the energy provide to the brain go to?

Answer 16

most (90%) goes to maintaining ion gradients; some (10%) dependent enzymes

Question 17

Neurotransmitter synthesis requires?

Answer 17

TCA Cycle is required for the synthesis of important neurotransmitters; The acetyl moiety of acetylcholine is derived from acetyl-CoA; Excitatory (glutamate) and inhibitory (GABA) amino acid transmitters are derived from à-ketoglutarate

Question 18

the glia cells support role includes?

Answer 18

Maintain ionic balance( incl. acid/base); Blood-brain barrier (BBB) ; Scavenge (neurone death ? gliosis)

Question 19

all glia cells have?

Answer 19

High membrane potential

Question 20

what are the 2 types of neurones (releasing) that comprise the largest two sets in the cortex?

Answer 20

Glutamate- and GABA-releasing neurones

Question 21

Released transmitter is mainly taken up by? It is returned as?

Answer 21

Released transmitter is mainly (most commonly) taken up into nearby astrocytes; and returned as (physiologically neutral) glutamine

Question 22

Transient or permanent reduction in cerebral blood flow is? In general what is the mortality rate?

Answer 22

Stroke; 30%

Question 23

in a stroke what happens to the infarcted area (in terms of metabolism); what about in the penumbra?

Answer 23

In the infarcted area; complete lack of glc and O2 leads to metabolism result halting; in the penumbra (Area around the infarct) lack of O2 but low residual glc leads to anaerobic metabolism -> lactic acidosis

Question 24

Describe what happens to glutamate during a stroke?

Answer 24

ATP is required to keep glutamate inside neurones by ?active transport? against its concentration gradient;
Loss of ATP -> glutamate leakage [the transporter can
work in reverse if pH falls]
Extracellular glutamate excites most neurones;
exacerbating the ATP loss as pumps work to maintain
membrane potentials

Question 25

what are the two major types of stroke?

Answer 25

Haemorrhage and ischaemic stroke

Question 26

what is the only licensed treatment for stroke? What is the general mechanism? What is the therapeutic window?

Answer 26

tissue-plasminogen activator (rt-PA) ; serine protease; converts plasminogen to plasmin -> plasmin breaks down fibrin; Therapeutic window is <3 hrs.