Hypoglycaemia

1. Hypoglycaemia Dr. Essam H. Jiffri

2. INTRODUCTION • -Hypoglycaemia is defined as a fasting venous whole-blood glucose level of less • than 2.2 mmol/L (plasma glucose <2.5 mmo1/l), when measured by a • glucose-specific ( enzymatic) method. • -Hypoglycaemia is dangerous because glucose is a vital primary fuel for the brain.

3. INTRODUCTION • -Deficiency produces disordered function and, if prolonged or severe, can cause tissue damage or death. • -In fasting, the brain still has an energy requirement equivalent to 80 g glucose 24/h, • which cannot be provided by NEFA, the immediately available alternative fuel. • -The brain can utilize ketone bodies but these are not produced rapidly enough to protect against acute hypoglycaemia.

4. Clinical Features • -Symptoms fall into two main categories: • -In early acute hypoglycaemia: include nervousness, weakness, headache, sweating, dizziness, tremor, tachycardia, palpitations, anxiety and hunger).

5. Clinical Features • -Those caused by dysfunction of the central nervous system (neuroglycopaenia), • include visual symptoms, headache, blunted mental, loss of motor function, confusion, abnormal behavior and loss of consciousness.

6. Causes • -It has been traditional to classify hypoglycaemia as conditions that produce low blood glucose levels during fasting. • -An alternative approach is based on the pathophysiology of hypoglycaemia, particularly reduced gluconeogenesis and increased utilization of glucose.

7. Causes

8. CAUSES • I-Decreased Output of Glucose • -Hypoglycaemia may result from impaired glycogenolysis or reduced gluconeogenesis. • -Gluconeogenesis may be impaired because of reduced formation from amino acids • and glycerol.

9. I-Decreased Output of Glucose • Liver Disease • -Hypoglycaemia might be expected to be a complication of liver disease because • of the role of this organ in gluconeogenesis • Alcohol Abuse • -Alcohol inhibits gluconeogenesis following alcohol ingestion.

10. I-Decreased Output of Glucose • Inherited Metabolic Disorders • - Endocrine Disease • -Deficiency of counter-regulatory hormones is common cause of hypoglycaemia. • -It occurs in cortisol deficiency, due either to: • primary adrenal failure or • secondary to adrenocorticotrophic hormone (ACTH) deficiency • -In growth hormone deficiency. • -Impaired gluconeogenesis is the most likely reason.

11. CAUSES • 2-lncreased Glucose Utilization • Reduced Fat Stores Low • -Fat stores allow only limited ketogenesis and this may contribute to hypoglycaemia • in premature infants and in malnutrition.

12. 2-lncreased Glucose Utilization • Decreased Ketone Body Production • -Continued utilization of glucose by the brain can cause hypoglycaemia when the • production of ketone bodies is defective.

13. 2-lncreased Glucose Utilization • Impaired Fatty Acid Oxidation Activated • -Long-chain fatty acids are transported by carnitine into mitochondria for oxidation, • this being facilitated by two carnitine acyltransferases, deficiency or inactivity of one of these enzymes may cause impaired oxidation of long-chain fatty acids.

14. CAUSES • 3-Decreased Output and Increased Utilization of Glucose • Insulin • -Insulin reduces blood glucose acutely, mainly by increasing cellular uptake and • utilization; therefore excess administration causes hypoglycaemia. • -Hyperinsulinaemia may also result from inappropriate endogenous production.

15. 3-Decreased Output and Increased Utilization of Glucose • Insulin • -Insulinomas, which are common causes of hypoglycaemia in adults, are tumours of pancreatic beta cells. • -Nesiodioblastosis is a diffuse increase in pancreatic endocrine cells and is an • important cause of hypoglycaemia in infancy.

16. 3-Decreased Output and Increased Utilization of Glucose • Sulphonylureas • - Sulphonylureas increase glucose-stimulated insulin release and hypoglycaemia is the most commonly observed side-effect.

17. 3-Decreased Output and Increased Utilization of Glucose • Nonpancreatic Tumour • - Some nonpancreatic tumours, particularly primary liver carcinomas, occasionally • cause hypoglycaemia.

18. 3-Decreased Output and Increased Utilization of Glucose • Postgastrectomy • - Hypoglycaemia is 2h after a meal rich in carbohydrate is common in patients with • a partial gastrectomy. • - It occurs because of rapid passage of sugar into the small intestine and enhanced release of enteric hormones which augment glucose-stimulated insulin release, this excess release of insulin causes hypoglycaemia.

19. Investigation of Hypoglycaemia in Adults • - Once the diagnosis is considered blood glucose and insulin should be measured after an overnight fast: hypoglycaemia with inappropriately high insulin levels is being demonstrated by such a protocol in over 90% of cases of insulinoma.

20. Investigation of Hypoglycaemia in Adults • - For some patients an extended fast of up to 72 h is needed, and glucose and insulin concentration should be determined every 4-6h, or when the patient has symptoms. • - Hypoglycaemia due to non-islet cell tumours is usually very severe and tuomours may be detected by physical examination or imaging techniques.

21. Hypoglacaemia in Infancy and Childhood • Hypoglycaemia often occurs at birth, as normal blood control is established after a few days of birth.

22. Investigation of Hypoglacaemia in Infancy and Childhood • - minimum investigations are: • - blood glucose • - serum insulin, and • - blood or urinary ketone bodies. • - It may be necessary to estimate: • - Growth hormone • - Cortisol • - NEFA, and • - Other intermediary metabolites

23. Hypoglacaemia in Infancy and Childhood • Most neonates with persistent hypoglycaemia have hyperinsulinism due to: • -Deficiency of counter-regulatory hormone, or • -An enzyme deficiency affecting gluconeogenisis or glycogenolysis. • - In older children hyperinsulinism, growth hormone or cortisol deficiency are important cause.