CARBOHYDRATES- source of energy for human body- aldehyde/ ketone w/ 2+ hydroxyl groups- mono, di, polysaccharide- D-glucose

D-glucose- principal & almost exclusive CHO circulating in blood- blood glucose from hydrolysis of dietary starch, conversion of other

dietary hexose into glucose by liver, & from synthesis of glucose from AA, FA & lactate

- principal fuel for peripheral tissues- maintained by metabolic processes & hormonal control

Hormonal Regulation1. Insulin

- small peptide (ß-cells of Islets of Langerhans of pancreas): high BG

- ONLY hormone that lowers blood glucose- Inc membrane permeability: bind to receptors on cell surface

entry to liver, muscle & adipose tissue- Enhance synthesis of glycogen, lipid & CHON- Inc BG: secreted; dec BG: inhibited

2. Glucagon- polypeptide (α-cells of Islets of Langerhan of pancreas): low BG - principal hormone: RAPID increase of BG in blood- stimulates hepatic glycogenolysis & gluconeogenesis

3. Epinephrine- adrenaline- inc glucose by:

stimulating glycogenolysis & lipolysis while inhibiting release of insulin

4. Thyroxine- thyroid gland- promotes glycogenolysis deplete glycogen stores in liver

5. Growth Hormone- somatotropin (anterior pituitary)- inhibits glucose uptake by tissues- stimulates liver glycogenolysis raise glucose conc

6. Adrenocotricotropin (ACTH)- stimulates release of cortisol (adrenal gland) inc glucose

7. Cortisol- stimulates gluconeogenesis

8. Somatostatin9. Somatomedins

Disorders of CHO1. Hyperglycemia2. Hypoglycemia3. Inborn errors of CHO metabolism

- normal or dec plasma glucose, excretion of a nonglucose reducing sugar in urine

HYPERGLYCEMIA: Diabetes Mellitus- MOST IMPT--hyperglycemia- Deficiency of insulin secretion, complications overtime

TYPE 1 DM- severe DM- absolute deficiency of insulin (autoimmune destruction of ß-cells)- viral or chemical, genetic- islet cell, insulin autoantibodies- abrupt onset of symptoms following viral infection, ketosis- REQUIRE insulin treatment: prevent ketosis & sustain life- History of rapid weight loss, polyphagia, polydipsia & polyuria- Neurologic: confusion, disorientation & loss of consciousness- Any age, frequently juvenile- 10% of all DM; Asian/ African descent Lab findings

- hyperglycemia- polyuria, inc urine & serum osmolarity, inc specific gravity,

ketonemia, ketonuria, acidosis, electrolyte imbalance Pathophysiology

Low insulin: impaired entry of glucose HIGH BG

High BG exceed renal reabsorptive capacity Glycosuria/ Glucosuria

Water is excreted w/ glucose Thirsty & hungry Polydipsia (H2O) & Polyphagia (desire for eating)

Increase glucagons a. Inhibited: Glycolysis

b. Stimulated: Glycogenolysis, lipolysis & gluconeogenesis

Catabolism of AA & FA-> inc acetyl CoA (cholesterol or ketoacid. Acetoacetic acid. ß-hydroxybutyric acid & acetione) KETOSISa. ketonemia (blood)b. ketonuriac. sweet “organic” odor (acetone)

Overproduction of ketoacids acidosis/ low blood pH dec HCO3 [CO2 & H2O]

Depletion of HCO3 metabolic acidosis

Respiratory center stimulated rapid, deep breathing & increased excretion of CO2 by lungs coma

TYPE 2 DM- milder DM- relative deficiency of insulin activity due to insulin resistance (normal

BUT insufficient peripheral response) & secretory defect- inc amyloid deposition in tissue (starchlike-CHONS-CHO complex)- env factors: excessive calories, lack exercise- no relationship to viruses- not prone to ketosis; doesn’t require insulin- inc risk of developing vascular complications & hyperosmolar coma- obese, 40+, progess slowly- most common DM: 80-90% Pathophysiology

Hyperglycemic hyperosmolar nonketotic coma- urinary losses of H2O, glucose & electrolytes (osmotic diuresis) w/o

sufficient fluid replacement DEHYDRATION high BG coma

Elderly patients Treatment

Dietary measures

Insulin/ oral hypoglycemic agents Complications (w/in 10-15 yrs)

Retinopathy (blindness)

Nephropathy

Neuropathy

Microvascular/ macrovascular disease

Heart attack & strokes (vascular complications)

Arteriosclerosis diminished BF to legs gangrene

Susceptibility to infection Lab Dx 3 criteria:

Symptoms of DM + RPG >200mg/dL (11.1 mmol/L)

FPG >126mg/L (7mmol/L)

OGTT: 2 hours after oral glucose load >200mg/L 1. Casual (Random) Plasma Glucose (RPG)

- irrespective of last meal/ time of day- presumptive DM: >200mg/L

2. Fasting Plasma Glucose (FPG)- 8hr+ fasting- DM: >126mg/L

3.Urine Glucose - screening test- 160-180mg/dL (8.9-80mmol/L)

4.Two-hour postprandial plasma glucose - 2 hours after Px consumes std load of glucose (75g)- DM: >200mg/dL

5.Oral Glucose Tolerance Test (OGTT) - unlimited physical activity & unrestricted diet (150g CHO) for 3

days- test: morning after fasting 10-16 hrs (H2O is permitted)- fasting glucose- nonpregnant: 75g flavored sol - pedia: 0.75g/kg body weight- pregnant: 100g- drink ingested 15 minutes- plasma glucose measured every 30 mins (2 hrs)- Px seated throughout test- Samples collected in NaF; w.in 4 hrs- Factors that affect: illness, trauma, stress, some drugs

- Normal: rise 150mg/L or higher w.in 30-60 mins normal in 3 hrs

- Diabetic: higher for a longer period of time- Gestational Diabetic:

a. fasting: >105mg/Lb. 1 hr glucose: >190mg/Lc. 2 hr: >165mg/Ld. 3 hr: >145mg/L

6.Glycated Hb - glycosylated Hb; Hb A1c- determine compliance w/ therapy; extent to w/c diabetic ctrl

has been achieved- more convenient than OGTT- only 1 blood sample

7.Self-monitoring of BG - capillary whole blood- serum/ plasma higher than WB

GESTATIONAL- pregnancy: hormonal & metabolic changes- family history of diabetes, recurrent monilial infection/ large babies

(>4K g), infants w/ congenital anomalies- maternal symptoms mild; fetus: devastating (congenital

malformation & perinatal mortality)- after delivery: normal or DM in later life IGT (Impaired glucose tolerance)

- plasma glucose level following oral glucose load: not normal but not sufficiently abnormal to be DM

IFG (impaired fasting glucose)- plasma glucose level following an 8-hour fast: greater than

normal but not sufficiently high to be DMHYPOCGLYCEMIA

- low glucose: <50mg/L- reactive hypo: excessive administration of insulin- factitious hypo: other hypoglycemic agent- ethanol ingestion: reduction of gluconeogenesis- fasting/ spontaneous hypo: uncommin- rapid fall in plasma glucose release of epinephrine & symptoms

caused by epinephrine:a. weakness, sweat, shakiness, trembling, nausea,

lightheadedness, rapid pulseb. adregenergic symptoms

- gradual fall in plasma glucose: <20 or 30 mg/L:a. impairement of CNS functionb. neuroglycopenia: headache, confusion, lethargy,

unconsciousness Lab : samples drawn every 4 hrs

INBORN ERRORS OF CARBOHYDRATES METABOLISM1. Glycogen Storage Disease

- inheritable disorders: deficiency of 1 or more enzymes involved in metabolism of glycogen

- liver, heart or musculoskeletal system2. Type I (Von Gierke’s)

- more common type- short stature & huge abdomen (massive enlargement of liver)- severe hypoglycemia, inc plasma lactic acid, hyperlipidemia- caused by deficiency or absence of enzyme glucose 6-

phosphate in liver (needed for final step in formation of glucose from hepatic glycogen)

3. Galactosemia- rare genetic disorder- inability to metabolize galactose - develop vomiting, diarrhea, cirrhosis of liver, cataracts & mental

retardation4. Hereditary Fructose Intolerance

- deficiency of fructose-1-phosphate aldolase - vomiting, hypoglycemia, hepatomegaly, failure to thrive

5. Mucopolysaccharide storage disease- structural components of cartilage, bone, skin & other CT- mucopolysaccharidoses- hereditary disorders- glycosaminoglycans: accumulate in various tissues & excreted

in urine- dermatan sulfate, heparin sulfate & keratin sulfate

6. Hurler’s syndrome- severe progressive disorder characterized by corneal clouding &

death (before age 10)

- coarse facies, skeletal abnormalities, developmental delay. hepatosplenomegaly