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2011-1, 2010-2, 2005-1
What are the effects of insulin deficiency?
-
Intracellular glucose deficiency w/
extracellular excess
Derangement of the glucostatic function of the liver
Hyperglycaemia with no decrease in
gluconeogenesis
Secondary osmotic diuresis with dehydration
Electrolyte and calorie loss
Catabolism of protein and fat
Ketosis => acidosis
2011-1
Please name the principal Ketone bodies.
- Acetoacetate, β hydroxybutyrate, Acetone
How are the Ketone bodies produced and how are they metabolised?
- Fatty acids (β oxidation) => acetyl-CoA => citric acid cycle => high output of energy (c.f. CHOs)
- Occurs in the mitochondria in the liver and other tissues
- Acetyl-CoA will condense => acetoacetyl-CoA (and aceyl-CoA + acetoacetyl-CoA = HMG-CoA)
- In the liver from these (via deacyclase and HMG-CoA) acetoacetate <=> β hydroxybutyrate
(irreversible, the enzyme for acetoacetate => acetyl-CoA is not found in liver cells)
- These products are water soluble (unlike fatty acids and triglycerides) and are exported from the
liver to extraheaptic tissues (esp. brain, skeletal and cardiac muscle) for ultilisation
- They convert the β-HB => acetoacetate => acetoacetyl-CoA => acetyl-CoA for ulilisation
- The acetone is formed from the spontaneous decarboxylation of acetoacetate cannot be
converted back to acetyl-CoA and is excreted in urine and the lungs
In which clinical situations do they accumulate in the body?
- Insulin inhibits and glucagon stimulates there production
- This pathway is most active during extended periods of fasting
- A rise is seen during sleep, starvation, high fat/low carb diet
- Also seen in diabetes when there is insulin deficiency and glucagon excess
- Also alcoholic ketosis can occur: alcohol blocks the first step of gluconeogenesis
- Normally the levels of β-HB and acetoacetate will be much higher than acetone, but still very low
due to utilization in the tissues
What are the physiological and clinical consequences of excess ketones?
- When production exceeds ultilisation (and excretion of acetone) there is a buildup (ketosis)
- Acetoacetate and β-HB are acids: normally buffered, but when the mechanisms are exceeded a
metabolic acidosis develops
- The kidneys and lungs initially compensate
- The acidosis is exacerbated by the hyperglycaemia in DKA causing dehydration