Lom disordersofglucosehomeostasis2013

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Lom disordersofglucosehomeostasis2013

  1. 1. Disorders of glucose homeostasis Language of medicine 2013 Division of chemical pathology David Haarburger
  2. 2. Fuels Carbohydrates Fat(Polysaccharides) Proteins (Triacylglycerides) Fatty AcidsMonosaccharide Amino acids Glycerol Glucose Ketones Glucose Ketones Glucose
  3. 3. Glucose• Major energy substrate• Essential for some tissues – Erythrocytes – Neurons• Can be oxidised to lactate or CO2• Glucose concentration is tightly controlled between 2.5 and 8.0 mmol/L – Glycolysis – Glycogenolysis – Gluconeogenesis
  4. 4. Glucose and fat metabolism glucose glucose-6-phosphate phosphoenolpyruvate pyruvate lactate fatty acids acetyl-CoA + ketones oxaloacetate citric acid ATP
  5. 5. Metabolism during starvation triacylglycerides free fatty acidsamino acids glucose ketones glycogen
  6. 6. Hormones involved in glucose control Glucose GlucoseCounter-regulatory hormones Regulatory hormones• Glucagon • Insulin – Glycogenolysis – Gluconeogenesis – Glycogen synthesis• Adrenaline – Protein synthesis – Lipolysis – Fat synthesis – Glycogenolysis• Growth hormone – Allows glucose entry into cells – Lipolysis – Glycogenolysis• Cortisol – Proteolysis – Gluconeogenesis
  7. 7. Diabetes mellitus• Absolute or relative lack of – polyuria insulin – polydipsia• Types – polyphagia – Type I • Complications • IDDM, Juvenile-onset – Acute • Autoimmune • DKA – Type II • HONK • NIDDM, Adult-onset – Chronic • Insulin resistance • Macrovascular – Gestational DM – Coronary heart disease – Peripheral vascular disease – Secondary to exocrine disease – Stroke – Endocrinopathies • Microvascular • Cushing syndrome, Acromegaly – Retinopathy – Nephropathy• Symptoms – Neuropathy – loss of weight
  8. 8. Pathogenesis of DKA No insulin↑gluconeogenesis ↑glycogenolysis ↑lipolysis hyperglycaemia ↑ketones acidosis glycosuria loss of water andosmotic diuresis vomiting electrolytes Diagnosis ↓pH dehydration ↑Glucose ↑Ketones
  9. 9. Pathogenesis of HONK state Low insulin Diagnosis ↑Glucose ↑gluconeogenesis ↑glycogenolysis ↑Osmolarity ↓pH (no ketones) glycosuria hyperglycaemiaosmotic diuresis ↑↑ plasma osmolarity increasedloss of water and blood electrolytes viscosity cerebral dehydration thrombosis dehydration
  10. 10. Diagnosis of diabetes• Fasting plasma glucose level ≥ 7.0 mmol/l – Normal < 6.1 mmol/l• Glucose tolerance test – Plasma glucose ≥ 11.1 mmol/l two hours after a 75 g oral glucose load• Symptoms of hyperglycaemia and random plasma glucose ≥ 11.1 mmol/l• Glycated haemoglobin (Hb A1C) ≥ 6.5%
  11. 11. Hypoglycaemia• Blood glucose < 2.2 – Drug Induced mmol/L • Insulin • Alcohol• Symptoms – Neoplasms – Neuroglycopaenia • Insulinoma • Tiredness • Insulin-like growth factor • Confusion secreting tumours • Convulsions – Liver disease • Coma – Endocrine disease – Sympathetic stimulation • Addison’s disease • Palpations • Growth hormone • Tachycardia deficiency • Sweating – Sepsis• Causes

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