Carbohydrate metabolism disorders Carbohydrate carbohydrate is the major

Carbohydrate metabolism (disorders)

Carbohydrate Ø carbohydrate is the major component of human diet. Ø Important source of body energy. Ø Carbohydrate is stored in the body but it is limited (liver 10% its wet weight, muscles 0. 5%). Ø All tissues can utilize GLUCOSE. Ø Glucose is almost exclusive carbohydrate circulating in blood Ø Brain the most important glucose consumer, followed by RBC, WBC, platelets Ø Kidney (oxidize fatty acids and ketone) Ø Liver synthesize glucose from a. a (alanine) this is defined as gluconeogenesis.

Carbohydrates metabolism Ø Plasma glucose is derived from the hydrolysis of dietary starch and polysaccharides, from the conversion of other dietary hexoses into glucose, from the synthesis of glucose from a. a or pyruvate (gluconeogenesis). Ø GLYCOGENESIS Ø GLYCOGENOLYSIS Ø GLYCOLYSIS ( oxidative phosphorylation)

Glycolysis (glyco = sugar , lysis = breaking ) Break glucose down to form two pyruvates All life on earth performs glycolysis In the cytoplasm Glycolysis produces 4 ATP's and 2 NADH, but uses 2 ATP's in the process for a net of 2 ATP and 2 NADH

The Oxidation of Pyruvate to form Acetyl Co. A 2 NADH's are generated (1 per pyruvate) 2 CO 2 are released (1 per pyruvate)

Anaerobic Respiration Alcohol Fermentation Occurs in yeasts in many bacteria The product of fermentation, alcohol, is toxic to the organism

Lactic Acid Fermentation

Regulation of blood glucose Ø Hormones play an important role in regulation of plasma glucose concentration: 1. 2. 3. 4. 5. 6. Insulin by pancreatic β- cells. Growth hormone by anterior pituitary. Epinephrine by adrenal medulla. Cortisol by adrenal cortex. Glucagon by pancreatic α–cells. Thyroxine by thyroid gland.

Decrease of blood glucose • Insulin • Lowering a blood glucose by several mechanisms: 1. By increasing the entry of glucose into muscles and adipose tissue cells. 2. By promoting liver glycogenesis and thus converting glucose to glycogen. 3. By promoting glycolysis which accelerate glucose utilization. 4. By promoting lipid synthesis from glucose in adipose tissue. 5. By promoting amino acid synthesis from glucose intermediates. • Excess of insulin secretion cause hypoglycemia. • Deficiency of insulin secretion cause hyperglycemia.

Increase of blood glucose • Growth hormone Ø Its action antagonistic to insulin. It raises the blood glucose concentration by : 1. Inhibiting entry of glucose into muscle cells. 2. Inhibiting glycolysis 3. Inhibiting the formation of triglycerides from glucose. The secretion of growth hormone is stimulated by lowered blood glucose concentration(hypoglycemia)

• Epinephrine (adrenaline) • Epinephrine and norepinephrine raise the blood glucose by causing the rapid breakdown of liver glycogen to glucose. Epinephrine section is stimulated by physical or emotional stress which is neurogenic. • Glucagon raises blood glucose by promoting hepatic glycogenolysis. • Glucagon secretion is stimulated by hypoglycemia and suppressed by hyperglycemia.

• cortisol (hydrocortisone) Ø cortisol raises blood glucose : 1. Promoting gluconeogenesis from the breakdown of protein. 2. Decreasing the entry of glucose into muscle cells. Cortisol is an insulin antagonist. • Thyroxine Ø Thyroxine promotes the conversion of liver glycogen to glucose and accelerates the absorption of glucose from intestine during meals.

Disorders associated with hyperglycemia Ø Hyperglycemia is harmful to the body, it increase the extracellular osmotic pressure causes cellular dehydration and that’s led to brain coma. Ø Acidosis and dehydration Ø Hemoglobin becomes glycosylated (Hb. A 1 C), a nonenzymatic reaction, glucose binds to the terminal valine of hemoglobin A beta chain. Ø Electrolytes imbalance.

Diabetes Mellitus Ø Diabetes mellitus is the most important disease affecting carbohydrate metabolism

Ø Many pathogenic changes are associated with chronic form of diabetes: 1. Vascular lesions in capillaries small veins cause changes in the retina and kidney (nephrosclerosis). 2. Atherosclerosis (hardening of the arteries). 3. Coronary vascular disease. 4. Neurologic defects (neuropathy). • Many physiologic abnormalities: 1. Hyperglycemia. 2. Hyperlipidemia and hypercholesterolemia. 3. ketosis (ketonemia). Ketone bodies ( acetoacetate, acetone and β –hydroxyburate). 4. Ketonuria. 5. Acidosis (the blood p. H falls). 6. Loss of electrolytes urine. 7. Glucosuria or glycosuria and polyuria.

Disorders associated with hypoglycemia • The clinical symptoms of hypoglycemia resemble those of cerebral anoxia include : 1. Faintness. 2. Weakness. 3. Dizziness. 4. Anxiety. 5. Hunger 6. Palpitation of heart. 7. Cold sweat. 8. There may even be mental confusion and motor incoordination.

Tests for the detection of hyperglycemia Ø Normal range plasma glucoe: 70 -110 mg/dl Ø Fasting blood sugar(FBS): 70 -110 mg/dl Ø Random blood sugar: < 180 mg/dl Ø Postprandial blood sugar(PPBS): < 120 mg/dl Ø Glucose tolerance test (GTT): < 140 mg/dl

Glucose Tolerance Test (GTT) Ø The usual procedure of GTT is to determine the level of blood glucose un fasting state and at various interval after 75 g glucose load. Administer orally a solution of pure glucose (75 g) should be dissolved in 250 -350 ml of water and should be asked to drink within 2 -3 minutes. Children 1. 75 g glucose/kg body weight. Ø Determine the blood glucose at interval of 30, 60, 120, and 180 minutes. Ø Urine sample also should be collected.

Glucose tolerance curves A. Diabetes mellitus C. Normal B. Hyperthyroidism D. Addison's disease or hypothyroidism or hyperinsulism