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Endocrinology
Definition:-
In 2000 - 171 million people all over the world were burdened with diabetes.
Middle east and Indian subcontinent –epidemic centre for type 2 DM.
1b (Idiopathic).
Type 2 DM.
Diseases of pancreas.
Pancreatitis.
Neoplasia.
Pancreatectomy.
Endocrinopathies.
Acromegaly ,Cushing's syndrome, Pheocromocytoma, Hyperthyroidism
etc.
Drug/Chemical induced.
Glucocorticoids, Thyroid hormones, Thiazides, Beta blockers.
Infections.
CMV, Congenital rubella.
PROINSULIN
Insulin C – peptide
Actions:-
Promotes
Glycogen synthesis.
Triglyceride synthesis.
Fatty acid synthesis.
Protein synthesis.
Inhibits
Gluconeogenesis.
Glycogenolysis.
Lipolysis.
Ketogenesis.
Protein degradation.
It lowers blood glucose by suppressing Hepatic glucose production and stimulating
glucose uptake in Skeletal Muscle and Fat.
Slowly progressive.
Ethiology:-
• Genetic
• HLA (Human Leucocyte Antigen) DR3 and DR4 region on short arm of
chromosome 6.
• HLA DQA1 and DQB1 genes are also involved.
• Environmental
Lack of Insulin
Increased Glucagon,
Decreased Cortisol, Increased
Anabolism GH, Catabolism
Catecholamines
Death ?
Type 2 DM
Pathology:-
Often associated with central (visceral) obesity, hypertension and dyslipidemia (increased
LDL, TG, Cholesterol and decreased HDL).
Sedentary people without exercise are more insulin resistant than active people with the
same body weight.
Etiology:-
• Genetic
• Environmental
– Age
– Pregnancy
Polyphagia.
Polyuria.
Polydipsia.
Nocturia.
Tiredness.
Recent changes in weight.
Nausea / headache.
Pruritis vulvae.
Balanitis.
Mood changes.
Blurring of vision.
Investigations
• Urine testing
• Glucose.
– Ketones.
By Nitroprusside test.
Nowadays with ketone body sensitive dip sticks.
– Proteins.
– Dipsticks for albumin to find out the renal disease; detects if >300mg/L of
albumin is excreted through the urine.
– Blood
– Glucose.
Blood lipids.
• Total cholesterol.
• Triglycerides.
• LDL.
• HDL.
Establishing diagnosis of Diabetes.
Ketonuria Yes No
Therapeutic goals:-
Healthy diet.
Decreased alcohol consumption.
Regular exercise.
Quit smoking.
Rice Vegetables
2/5 th
Pasta 2/5th
Fruits
Bread
Potatoes
Fish
Meat
Egg
1/5th
Consumption of food with a low Glycaemic Index - as they produce a slow
gradual rise in blood glucose. eg: Pasta, Brown bread, Noodles, Beans, Whole
wheat products.
5. Sulfonylureas:-
MOA stimulate the release of insulin from the pancreatic beta cells (insulin
secretalogue). Act through a sulfonlyurea receptor situated on the beta cell
surface.
MOA insulin sensitivity and peripheral glucose uptake are increased through the
activation of a c- AMP regulated kinase in the muscle.
Also inhibits hepatic gluconeogensis and impairs the absorption of glucose from
the gut.
It does NOT increase the insulin secretion.
Usually doses of 500-3000 mg/ day can be given in divide doses ( upto 3 times
after food).
Contraindicated in
Lower the post prandial blood glucose , and is usually combined with a
sulfonylurea.
MOA bind and activate peroxisome proliferator activated receptor alpha , a nuclear
receptor present mainly in adipose tissue which regulates the metabolism and
enhances the actions of endogenous insulin.
Most effective in patients with severe insulin resistance (in central obesity). They
redistribute the fat to subcutaneous areas. However the body fat and weight is
increased.
Incretin Mimetics:-
• Before from extraction and purification from the pancreas of cows and pigs.
Insulin delivery
• Injected subcutaneously into the anterior abdominal wall , upper arms , outer
thighs and buttocks.
• Also available as Pen injectors with cartridges which are more convenient.
• Intra nasal insulin has been recently approved by FDA and will be soon
available in the market!
Twice daily regimen of a short acting and intermediate acting insulin given in
combination with breakfast and dinner is the simplest regimen followed.
2/3rd of the total dose is given in the morning and 1/3rd in the evening.
Short acting insulin taken before each meal and intermediate insulin being used at bed
time (Basal –Bolus regimen).
Hypoglycemia.
Weight gain.
Peripheral edema (as insulin causes water and salt retention in short term).
Local allergy.
Incidence:-
2 – 4 % of all pregnancies.
Risk factors:-
Any pregnant woman with one or more risk factors to be evaluated at the beginning of
third trimester (at 28 weeks).
50 gram glucose challenge test , measuring blood glucose one hour later.
If any two out of three values are met or exceeded the diagnosis of G.D.M is made.
F.B.S > 5.3 mmol/L.
1 hour value >10.6 mmol/L.
2 hour value > 8.9 mmol/L.
Effects on Fetus
Management:-
Wide anion gap metabolic acidosis (pH <7.3 and/or HCO3 <15) plus possible
secondary respiratory alkalosis due to Kussmaul’s respirations; can also have
metabolic alkalosis from vomiting and dehydration.
Monitor degree of ketoacidosis with anion gap and not blood glucose or ketone
level.
Rehydration
1L over 1 hour.
1 L over 2 hours.
When blood glucose <15mmol/L (270mg/dl) switch to 5% dextrose, 1 litre over 8 hours.
Insulin
When bd. Glucose falls < 15 mmol/L insulin reduced to 3 units/hr (0.05 U/Kg/hr).
Potassium
Avoid hypokalemia.
K+ is lost from cells due to insulin deficiency and general catabolic state.
Blood levels will not reflect the total body losses which might be about 400-500
mEq.
K+ falls during treatment due to rehydration and insulin (drives K+ into cells).
Bicarbonate
Treatment of the precipitating causes and patient education to prevent further DKA
episodes.
Prognosis:-
Etiology:-
Lab findings:-
Blood glucose is often > 55 mmol/L ; but is not a good indicator of the severity.
Electrolytes may show false hyponatremia ( because fall of 3 mEq/L of Na+ for
every 10mmol/L increase of blood glucose).
Same lab findings can be due to some other acute conditions such as
sepsis, renal failure, Lactic Acidosis.
Treatment:-
• Insulin
Usually given I.V. at the rate of 3 units/ hour.
• Intravenous Fluids
Rate of replacement regulated with Central Venous Pressure (CVP) and plasma Sodium
concentration.
Patient will be very ill and over-breathing (but without acetone smell as in case
of other hyperglycemic coma’s).
Plasma HCO3- and pH markedly reduced; (H+ > 63mmol/L , pH < 7.2).
Treatment
Associated with high mortality rate of about 50% in spite of best treatment !
Hypoglycemia
Definition:-
as the plasma glucose level < 2.5 to 2.8 mmol/L (<45 to 50 mg/dl).
Clinical features:-
Adrenergic symptoms
Neuroglycopenic symptoms
• Fasting Hypoglycaemia.
If conscious.
Carbohydrates (a glass of fruit juice , aerated soft drinks, chocolate, glucose powder,
Jam, honey etc ).
Macroangiopathies.
Microangiopathies.
Types:-
Maculopathy
Exudation, hemorrhage, ischemia of the macula.
Sight threatening.
Proliferative Retinopathy
Pre retinal hmgs, neovascularisation, fibrosis, exudative maculopathy.
Sight threatening.
Pathogenesis:-
Hyperglycemia increases retinal blood flow and metabolism and has direct effects on
retinal endothelial cells and pericyte loss, leading to impairment of vascular auto
regulation.
Leads to chronic retinal hypoxia, new vessel formation, and increased vascular
permeability.
Clinical features :-
Microaneurysms.
Hemorrhages usually blot hmgs (in deeper retinal layers).
Exudates.
Cotton wool spots.
Intraretinal microvascular abnormalities.
Neovascularisation.
Venous changes.
Rubeosis iridis formation of new vessels on the anterior surface of iris and can lead
to 2 0 glaucoma.
Prevention and management :-
11. Photocoagulation.
To destroy areas of retinal ischemia, to seal leaking microaneurysms and reduce macular
edema, to gliose new vessels directly on the retinal surface.
Epidemiology:-
Pathology:-
Nodular deposits.
Glomerulosclerosis.
Presentation :-
Initially increased G.F.R (Glomerular Filtration Rate) upto 140 % , enlarged kidneys,
microalbuminuria.
Management :-
A.C.E inhibitors.
Ca2+ blockers.
Pathophysiology:-
Somatic.
Polyneuropathy.
Mononeuropathy.
Visceral (autonomic).
CVS.
GIT.
Genitourinary.
Vasomotor.
Pupillary.
Clinical features:-
Diminished vibration perception in the distal parts of the body (Glove and Stocking
type).
Severe and progressive weakness and wasting of proximal muscles of the lower
limbs.
Severe pain.
3. Autonomic neuropathy.
Postural hypotension.
Resting tachycardia.
Dysphagia.
Diarrhoea / constipation.
Difficulty in micturition / urinary incontinence / recurrent infection due to atonic
bladder.
Nocturnal sweats.
Dependent edema.
Cold feet.
Decreased pupil size.
Erectile dysfunction.
Management:-