Disorders of Carbohydrate Metabolism PDF

Disorders of carbohydrate metabolism GNK689 (MBCHB VI) Dr EM Madingwana Chemical Pathology January 2024 Overview A. Physiology of glucose homeostasis B. Hyperglycemia and its investigation C. Hypoglycaemia and its investigation D. Clinical...

Disorders of carbohydrate metabolism GNK689 (MBCHB VI) Dr EM Madingwana Chemical Pathology January 2024 Overview A. Physiology of glucose homeostasis B. Hyperglycemia and its investigation C. Hypoglycaemia and its investigation D. Clinical cases A. Physiology of glucose homeostasis Glucose is the most important energy substrate Dietary carbohydrate Only energy source for some tissues e.g., RBC, CNS Oxidized to CO2 and water in the presence of oxygen Can also be oxidized to lactate only (anaerobic metabolism) Lactate can be converted back to glucose (Cori cycle) A. Physiology of glucose homeostasis Blood glucose concentration depends on equilibrium between inflow of glucose into the circulation and uptake into tissue Controlled by homeostatic mechanisms Normal glucose: 3.5 – 5.5 mmol/L Glucose is stored as glycogen in muscle and liver cells Stored glucose can be released through um gluconeogenesis glycogenolysis Glucose can be endogenously synthesized from other substrates through gluconeogenesis A. Physiology of glucose homeostasis Control of blood glucose concentration is achieved through hormones  Insulin: ↓ blood glucose  Glucagon: ↑ blood glucose Other counter-regulatory hormones that ↑ blood glucose:  Catecholamines (adrenaline)  Growth hormone  Cortisol Insulin Polypeptide hormone secreted by β-cells of the pancreatic islets of Langerhans pro-insulin is cleaved to form insulin and C-peptide Stimulated by ↑ blood glucose Also stimulated by incretin hormones (gut hormones) during food intake  Glucagon-like peptide 1 (GLP 1)  Glucose-dependent insulinotropic peptide (GIP) Biosynthesis of insulin Insulin  Insulin Insulin ↑ cellular uptake of potassium, phosphate, magnesium Electrolyte changes in insulin deficiency:  Hyperkalaemia  Hyperphosphataemia Electrolyte changes during insulin therapy:  Hypokalaemia  Hypophosphataemia  Hypomagnesaemia  Glucagon Polypeptide hormone secreted by ꭤ-cells of the pancreatic islets Stimulated by ↓ blood glucose Actions:  ↓ Insulin  ↑ Liver glycogenolysis  ↑ Gluconeogenesis  ↑ Lipolysis  ↑ Ketone synthesis  B. Hyperglycaemia and its investigation Diabetes mellitus – chronic hyperglycaemic state due to a defect in insulin secretion or action  Can be caused by chronic pancreatic disease, chronic pancreatitis, haemochromatosis  Endocrine cause of DM: conditions with ↑ cortisol (Cushing syndrome) or ↑GH (acromegaly)  There are two distinct types  Type 1: destruction of pancreatic cells eventually leading to cessation of insulin secretion.  Type 2: defective and delayed insulin secretion and resistance to its actions. Pathophysiology of diabetes Long term complications of diabetes Microvascular complications  Retinopathy  Neuropathy  Nephropathy Macrovascular complications  Atherosclerosis  Ischaemic heart disease &  Stroke Strict glucose control ↓ microvascular complications Diagnosis of diabetes  2h oral glucose tolerance test (OGTT) Evaluates post-prandial glucose handling by the body Used to diagnose impaired glucose tolerance (pre-diabetes) Procedure: Overnight fast 8 – 14h 75 g oral glucose load (children 1.75 g/kg) in 250ml water Take bloods at baseline and after 60 min and 120 min  HbA1c Marker of average glycaemic status over the past 2 – 3 months Glucose attaches to N-terminal valine residue of Hb beta chain Used for diagnosis and monitoring of diabetes HbA1c persists in the RBC for the lifetime of the RBC 50% of HbA1c is contributed by glucose over previous 30 days Reported as % (NGSP units) and mmol/mol (IFCC units) Diagnostic cutoff: >6.5% (48 mmol/mol) Normal: 320 mOsm/kg No or minimal metabolic acidosis No or mild ketones 15% mortality Treat with rehydration and low-dose IV insulin Thrombosis prophylaxis C. Hypoglycaemia and its investigation Blood glucose 60 prerenal)  Persistent hypoglycaemia after IV glucose bolus  Fasting hypoglycaemia found in chronic liver disease  Will persist food intake restored  Must stay on dextrose 10% IVI until food intake is restored Insulin and C-peptide appropriately suppressed due to hypoglycaemia, confirms hypoglycaemia is secondary Thank you Questions- [email protected]