Transcript Clinical biochemistry (4) Carbohydratex

Carbohydrate metabolism
(disorders)
Carbohydrate
 carbohydrate is the major component of human diet.
 Important source of body energy.
 Carbohydrate is stored in the body but it is limited
(liver 10% its wet weight, muscles 0.5%).
 All tissues can utilize GLUCOSE.
 Glucose is almost exclusive carbohydrate circulating
in blood
 Brain the most important glucose consumer, followed
by RBC, WBC, platelets
 Kidney (oxidize fatty acids and ketone)
 Liver synthesize glucose from a.a (alanine) this is
defined as gluconeogenesis.
Carbohydrates metabolism
 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).
GLYCOGENESIS
GLYCOGENOLYSIS
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 CoA

2 NADH's are generated (1 per pyruvate)

2 CO2 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

occurs in humans and other mammals
o The product of Lactic Acid fermentation, lactic acid, is toxic to mammals
o This is the "burn" felt when undergoing strenuous activity
Regulation of blood glucose
 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
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
• Glucagon raises blood glucose by promoting
hepatic glycogenolysis.
• Glucagon secretion is stimulated by hypoglycemia
and suppressed by hyperglycemia.
•
cortisol (hydrocortisone)
 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
 Thyroxine promotes the conversion of liver
glycogen to glucose and accelerates the absorption
of glucose from intestine during meals.
Disorders associated with hyperglycemia
 Hyperglycemia is harmful to the body, it increase
the extracellular osmotic pressure causes cellular
dehydration and that’s led to brain coma.
 Acidosis and dehydration
 Hemoglobin becomes glycosylated (HbA1C), a
nonenzymatic reaction, glucose binds to the
terminal valine of hemoglobin A beta chain.
 Electrolytes imbalance.
Diabetes Mellitus
 Diabetes mellitus is the most important
disease affecting carbohydrate metabolism
 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 pH 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
 Normal range plasma glucoe:70-110mg/dl
Fasting blood sugar(FBS): 70-110mg/dl
Random blood sugar: < 180mg/dl
Postprandial blood sugar(PPBS): < 120mg/dl
Glucose tolerance test (GTT): < 140 mg/dl
Glucose Tolerance Test (GTT)
 The usual procedure of GTT is to determine the
level of blood glucose un fasting state and at
various interval after 75g glucose load.
Administer orally a solution of pure glucose (75g)
should be dissolved in 250-350ml of water and
should be asked to drink within 2-3 minutes.
Children 1.75g glucose/kg body weight.
Determine the blood glucose at interval of 30,60,
120,and 180 minutes.
Urine sample also should be collected.
Glucose tolerance curves
A. Diabetes mellitus
C. Normal
B. Hyperthyroidism
D. Addison's disease or hypothyroidism or hyperinsulism