Energy Merabolism in the CNS Flashcards
The human brain lacks any capacity to? Therefore it is extremely vulnerable to?
Store energy; interruptions in nutrient supply
the human brain has a very active?
Very active metabolism;
The human brain has an extremely high? How does the brain accomplish this?
Flux; High enzymatic concentration that allows a rapid response to increase in available glucose
the brain is biased towards what over what? This means that?
the brain is biased towards glycolysis over gluconeogenesis. This means that little is stored as carbohydrates
There are very low amounts of what and what?
Low amounts of glycolytic and TCA cycle intermediates
The brain has a vulnerability due to? This means it must reline on?
High metabolic rate and limited energy stores; leads to an absolute reliance on blood for O2 and energy substrates
The brain has a critical dependence on?
aerobic glucose metabolism
any supply interruption to the brain leads to? This can be a shortage of ?
Encephalopathy; ether glucose or O2
the brain is extremely vulnerable to?
Hypoxia; Hypoglycaemia; disorders of glucose metabolising enzymes
how can an insulin overdose lead to coma?
overdose of insulin drives available glucose into the periphery; this leads to low levels of glucose getting to the brain which leads to coma
in case of starvation how is the brains energy demands met? Why do you not see the immediate effects like in an insulin overdose?
Because glucose fails slowly in starvation the body has time to begin to make ketone bodies from the break down of fat
what are some consequences of hypoglycaemic encephalopathy?
Neurological impairment progressing through confusion to seizures coma and ultimately death (cessation of spontaneous EEG potentials)
At the pre-terminal stages of hypoglycaemia the cerebral metabolic rate for what falls more rapidly then? This suggests that?
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
during hypoglycaemic encephalopathy what are some substrates that can support the brain? How long can these stories support the brain?
TCA cycle intermediates (very small pool) amino acids (glutamate and glutamine); these stories only last for approx.. 15 min
what are the 2 compensatory mechanisms for low 02 levels in the brain?
Cerebral blood flow increases; ATP Production switch’s to anaerobically (this can lead to acidosis)
where does the energy provide to the brain go to?
most (90%) goes to maintaining ion gradients; some (10%) dependent enzymes
Neurotransmitter synthesis requires?
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
the glia cells support role includes?
Maintain ionic balance( incl. acid/base); Blood-brain barrier (BBB) ; Scavenge (neurone death ? gliosis)
all glia cells have?
High membrane potential
what are the 2 types of neurones (releasing) that comprise the largest two sets in the cortex?
Glutamate- and GABA-releasing neurones
Released transmitter is mainly taken up by? It is returned as?
Released transmitter is mainly (most commonly) taken up into nearby astrocytes; and returned as (physiologically neutral) glutamine
Transient or permanent reduction in cerebral blood flow is? In general what is the mortality rate?
Stroke; 30%
in a stroke what happens to the infarcted area (in terms of metabolism); what about in the penumbra?
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
Describe what happens to glutamate during a stroke?
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
what are the two major types of stroke?
Haemorrhage and ischaemic stroke
what is the only licensed treatment for stroke? What is the general mechanism? What is the therapeutic window?
tissue-plasminogen activator (rt-PA) ; serine protease; converts plasminogen to plasmin -> plasmin breaks down fibrin; Therapeutic window is <3 hrs.
