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![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.](https://image.slidesharecdn.com/dkamajor-140225104009-phpapp01/75/DKA-pathophysiology-18-2048.jpg)
Uploaded byBethelhem Berhanu
DKA pathophysiology
Insulin deficiency and excess glucagon lead to abnormal carbohydrate, fat, and protein metabolism resulting in diabetic ketoacidosis (DKA). Specifically: 1) Impaired glucose utilization and increased gluconeogenesis and glycogenolysis cause hyperglycemia. 2) Increased lipolysis and synthesis of ketone bodies in the liver from free fatty acids causes ketoacidosis and metabolic acidosis. 3) Glucose levels are usually lower in DKA compared to hyperosmolar hyperglycemic state (HHS) due to greater urinary glucose excretion in DKA patients, who are usually younger with better kidney function. Insulin levels are sufficient to prevent ketogenesis in H
In this document
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Introduction of the speaker, Bethelhem Berhanu.
Focus on hormonal issues: insulin deficiency/resistance, glucagon excess, and stress hormones affecting metabolism.
Discusses abnormal metabolism involving carbohydrates, fats, proteins, and related inflammatory processes.
Outlines the normal metabolic response to hyperglycemia, leading to normoglycemia through hormonal regulation.
Describes metabolic changes in DKA, including increased glucose production and hyperglycemia due to hormonal imbalances.
Examines effects of glucose uptake decrease and gluconeogenesis in DKA and the role of glucagon.
Impact of glucosuria on serum glucose levels, including osmotic diuresis and volume depletion effects.
Details on lipolysis leading to ketone body production and altered fat metabolism due to hormonal changes.
Discusses the role of ketone bodies in metabolic acidosis and their relation to dehydration effects.
Focuses on increased protein breakdown and amino acid production for gluconeogenesis in DKA.
Describes severe dehydration (6L+ loss), causes like osmotic diuresis, vomiting, and hyperventilation.
Details compensatory mechanisms for metabolic acidosis caused by excess ketones and buffered changes.
Discusses electrolyte loss in DKA due to osmotic diuresis and potassium shifts affecting serum levels.
Identifies paradoxical scenarios in DKA, such as hyperglycemia with decreased intake and altered catabolism.
Differences between DKA and HHS regarding hyperglycemia, symptoms, patient demographics, and ketosis.
Summarizes key points on hyperglycemia, ketoacidosis, and the roles of insulin in DKA versus HHS.
Cites references used for the presentation including Harrison and Uptodate sources.
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DKA pathophysiology
- 1.
- 2. • Two hormonalabnormalities: – Insulin deficiency and/or resistance. – Glucagon excess – required??? • increased secretion of catecholamines and cortisol Insulin Glucagon Epinephrine Cortisol Growth Hormone
- 3. • These willresult in abnormal Metabolism of: – Carbohydrate – Fat – Protein • Inflammatory process
- 4.
- 5. DKA Hyperglycemia ↑Insulin ↑Glucose production ↑ Gluconeogenesis ↓Glucoseuptake ↑ Glycogenolysis Hyperglycemia
- 6. Carbohydrate contd. • Thedecrease 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. • Glucosuria helpsin reducing the serum glucose initially, but later…. Osmotic diuresis, Volume depletion ↓GFR ↓ glucose excretion
- 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. • The acidicketone 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. On protein metabolism •There will be increased protein breakdown and production of amino acids, which will be used in gluconeogenesis (alanine).
- 13. 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.
- 14. Events contd. • Metabolicacidosis – 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.
- 15. Events contd. • Ionicchanges – – 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.
- 16. • Paradoxes ofDKA – Hyperglycemia despite decreased intake – Polyuria despite dehydration – Catabolic state despite hyperglycemia
- 17. 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
- 18. In summary…. • Hyperglycemiaresults 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.
- 19. References • Harrison, 18thEdition • Uptodate 19.3 • The World Wide Web