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Bethelhem Berhanu
• Two hormonal abnormalities:
– Insulin deficiency and/or resistance.
– Glucagon excess – required???
• increased secretio...
• These will result in abnormal Metabolism
of:
– Carbohydrate
– Fat
– Protein

• Inflammatory process
Normally…
Hyperglycemia

↑Insulin

↓Glucose production

↓Gluconeogenesis

↑Glucose uptake

↓Glycogenolysis

Normoglycemia
DKA
Hyperglycemia

↑Insulin

↑Glucose production

↑ Gluconeogenesis

↓Glucose uptake

↑ Glycogenolysis

Hyperglycemia
Carbohydrate contd.
• The decrease in glucose uptake alone does not
give us the degree of hyperglycemia in DKA or
HHS.
• G...
• Glucosuria helps in reducing the serum
glucose initially, but later….
Osmotic diuresis,

Volume depletion

↓GFR

↓ gluco...
On fat metabolism
• ↓insulin & ↑cathechilamines → Lipolysis
– There will be free fatty acid mobilization to the
liver
– No...
• The acidic ketone bodies will cause metabolic
acidosis.
– Dehydration from osmotic diuresis also
exacerbates the acidosi...
On protein metabolism
• There will be increased protein breakdown
and production of amino acids, which will be
used in glu...
Events
• Dehydration – 6 litres or more, 15-20% of
their weight. Why?
– Osmotic Diuresis – blood glucose exceeds the
renal...
Events contd.
• Metabolic acidosis – initially due to the excess
ketones.
– Compensatory mechanisms

(1) respiratory compe...
Events contd.
• Ionic changes –
– A general loss of electrolytes due to osmotic
diuresis.
– Potassium – intracellular buff...
• Paradoxes of DKA
– Hyperglycemia despite decreased intake
– Polyuria despite dehydration
– Catabolic state despite hyper...
DKA Vs HHS
• Degree of hyperglycemia
– HHS > DKA
• Pts with DKA present earlier due to symptoms of
ketoacidosis
• DKA pts ...
In summary….
• Hyperglycemia results from impaired glucose
utilization, increased gluconeogenesis and increased
glycogenol...
References
• Harrison, 18th Edition
• Uptodate 19.3
• The World Wide Web
DKA pathophysiology
DKA pathophysiology
DKA pathophysiology
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DKA pathophysiology

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DKA pathophysiology

  1. 1. Bethelhem Berhanu
  2. 2. • Two hormonal abnormalities: – Insulin deficiency and/or resistance. – Glucagon excess – required??? • increased secretion of catecholamines and cortisol Insulin Glucagon Epinephrine Cortisol Growth Hormone
  3. 3. • These will result in abnormal Metabolism of: – Carbohydrate – Fat – Protein • Inflammatory process
  4. 4. Normally… Hyperglycemia ↑Insulin ↓Glucose production ↓Gluconeogenesis ↑Glucose uptake ↓Glycogenolysis Normoglycemia
  5. 5. DKA Hyperglycemia ↑Insulin ↑Glucose production ↑ Gluconeogenesis ↓Glucose uptake ↑ Glycogenolysis Hyperglycemia
  6. 6. Carbohydrate contd. • The decrease in glucose uptake alone does not give us the degree of hyperglycemia in DKA or HHS. • Gluconeogenesis, why? – Providing the substrates (glycerol, alanine) – Increase in glucagon
  7. 7. • Glucosuria helps in reducing the serum glucose initially, but later…. Osmotic diuresis, Volume depletion ↓GFR ↓ glucose excretion
  8. 8. On fat metabolism • ↓insulin & ↑cathechilamines → Lipolysis – There will be free fatty acid mobilization to the liver – Normally, these would be converted into TGLs and VLDL, but the presence of glucagon alters the hepatic metabolism to form ketone bodies. Ketone bodies Acetone Acetoacetate β-hydroxbutyrate
  9. 9. • The acidic ketone bodies will cause metabolic acidosis. – Dehydration from osmotic diuresis also exacerbates the acidosis. • A second product of lipolysis, glycerol, will be used as a substrate for gluconeogenesis in the liver.
  10. 10. On protein metabolism • There will be increased protein breakdown and production of amino acids, which will be used in gluconeogenesis (alanine).
  11. 11. Events • Dehydration – 6 litres or more, 15-20% of their weight. Why? – Osmotic Diuresis – blood glucose exceeds the renal treshold (160-180mg/dl) – Vomiting – Hyperventilation – Impaired consciousness – decreased intake.
  12. 12. Events contd. • Metabolic acidosis – initially due to the excess ketones. – Compensatory mechanisms (1) respiratory compensation, (2) intracellular buffering – excess H+ goes into cells in exchange for potassium. (3) bicarbonate buffering system.
  13. 13. Events contd. • Ionic changes – – A general loss of electrolytes due to osmotic diuresis. – Potassium – intracellular buffering mechanism shifts potassium out of cells so even if there is decreased total potassium in the body, serum potassium may initially be normal or even high. This potassium is further lost through the kidneys.
  14. 14. • Paradoxes of DKA – Hyperglycemia despite decreased intake – Polyuria despite dehydration – Catabolic state despite hyperglycemia
  15. 15. DKA Vs HHS • Degree of hyperglycemia – HHS > DKA • Pts with DKA present earlier due to symptoms of ketoacidosis • DKA pts are usually younger and have a better GFR, thus excreting more glucose through urine. • Ketoacidosis – Not found in HHS….why? • Minimal insulin may be sufficient to minimise ketosis but does not control hyperglycemia
  16. 16. In summary…. • Hyperglycemia results from impaired glucose utilization, increased gluconeogenesis and increased glycogenolysis • Ketoacidosis results from lipolysis, with synthesis of ketones from free fatty acids in the liver mitochondria. • Glucose concentrations are most often lower (usually <800 mg/dL [44 mmol/L]) in DKA compared to HHS. • Insulin levels in HHS are insufficient to allow appropriate glucose utilization, but are adequate to prevent lipolysis and subsequent ketogenesis.
  17. 17. References • Harrison, 18th Edition • Uptodate 19.3 • The World Wide Web

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