ACUTE DIABETIC COMPLICATIONSACUTE DIABETIC COMPLICATIONS

ByDr. Nabil Lymon

Professor of Internal MedicineMansoura University

I. Diabetic ketoacidosis

Precipitating factors

1. Neglected treatment and inadequate administration of

insulin.

2. Infections lead to increased insulin requirements.

3. Stressful conditions such as myocardial

infarction, C.V. stroke, pregnancy, trauma, emotional stress

which lead to increase in the counter-regulatory hormones of

insulin leading to increase in the insulin requirements.

4. Endocrinal disorders: cushing, thyrotoxicosis,

pheochrom- ocytosis.

5. Drugs which decrease the insulin secretion such as:

a. Steroids, Diuretics.

b. Azathioprine, Diazoxide, Phenytoin.

Pathogenesis and clinical pictureA. Severe insulin deficiency leads to

1. Impaired glucose utilization as a source of energy leads to hyperglycemia, polyurea and dehydration which lead to muscle weakness, tachycardia and hypothermia.

2. The body begin to utilize fat as a source of energy leading to increased glycerol, free fatty acids with formation of ketone bodies (acetone, acetoacetic acid, B hydroxybuteric acid) which leads to:

a. Acetone odour.

b. Acidosis which lead to air hunger (Kausmaull respiration)

c. Also ketonemia may lead to severe abdominal pain (acute abdomen)

Cont.___________________________3. Insulin deficiency leads to impaired K entery to

the cells leading to hyper K which give the following manifestations:

a. Atony of the skeletal muscles leads to muscle weakness and apathy.

b. Atony of the GIT leads to ileus and gastric dilatation. c. Arrhythmia.

B. Confusion and rarely comma may develop due to the effect of 1. Ketone bodies.2. Dehydration.3. Electrolyte disturbance.

Differential diagnosis KetoacidosisHopolycemia

Precipitating factors. Onset

See beforeSlow

See laterRapid

SkinTongue

Dry and coldDry

WetMoist

TemperatureRespirationBreath

SubnormalKausmaullAcetone odour

NormalNormalNormal

Blood pressureEffect of oral sugar

LowNo effect

Systolic pressureRapid recover

Investigations1. Blood examination

a. Hyperglycemia more than 300 mg% and ketonemia.

b. Acidosis (PH <7.3), increased FFA and triglycerides

c. Electrolyte disturbances:- hyper K, hypo Na.d. Serum urea and creatinine increase due to

hypovolemia.

2. Urine examination:- polyuria, glucosuria and ketonuria.

TreatmentA. Prevention the patient is given guidelines to

prevent this problem such as:

1.The daily dose of insulin is mandatory and its

negligence is dangerous.

2.When the patient can't follow his usual diet due to

severe illness e.g. pneumonia, he must eat or drink

whatever he can tolerate. The patient must test for

urine glucose and ketone bodies every 4 hours and if

the tests show the need for extrainsulin, we can add

20% to the original dose (e.g. if the patient's usual

dose is 40 U we can add 8 U).

B. Curative1. Fluid replacement

a. Suitable regimen is as follow:- 1 litre in the In 1/2 h, followed by 1 litre in 1 h, another 1 litre in 1 h, 1 litre in 2 h, 1 litre in 3 h, and 1 litre in 4 h.

b. 2 the total amount of the fluid deficit is given in 8 hours and the other 2 over the next 16 h.

c. Normal saline is used at the start and changed to dextrose saline when blood glucose reaches 180 mg%.

2. Insulin regimen we can use one of these two methods: a. I V. insulin infusion by the use of infusion pump:- soluble insulin

is diluted in 0.9 saline and 0.1 U/kg/h (6U/h) is given by the infusion. The infusion is continued until the patient is well enough (S.C.insulin is given before eating) and the insulin infusion is discontinued after meal.

b. IM. route (soluble insulin) :- 20 U at the start, then 6 U/h till blood glucose reaches 200 mg%.

Cont._________________________Cont._____________________________3. Electrolyte correction

a. Kcl which is given from the second hour after insulin

therapy as follow:

- 20 mmol is added to every litre saline if K level is 3-4 meq/L.

- 40 mmol is added to every litre saline if K level is less than 3

meq/L.

- It is contraindicated to add K if there is oliguria or K level > 5

meq/L.

b. Na HCO3:- 65 mmol over 30-60 min and can be

repeated every hour when the PH <7.1

4. Treatment of the precipitating factors e.g infection.

5. Treatment of the complications:- see later.

Complications1. Acute fatty infiltration of the liver.

2. Infectiona. Rhinocerebral infection with mucormycosis may complicate this

condition

b. Treatment with amphotricin B + necrotic tissue removal, improve the survival to about 60%.

3. Shock due to severe dehydration.

4. Vascular thrombosis due to dehydration and increased viscosity of the blood.

5. Pulmonary edema which may occur by the volume overload due to excess fluid.

6. Cerebral edema "rare but fatal"

Cause: It occurs 4-16 h. after initiation of therapy due to

rapid decrease of blood glucose level which lead to

movement of water into the intracellular space leading to

brain edema.

Cl.p.: Increased ICT leads to papilledema,

ophthalmoplegia, confusion, coma.

Prevention: Avoid the rapid decrease of blood glucose

and distribute the fluid replacement over 24 hours.

Treatment: Brain dehydrating measures e.g mannitol 1-

2 gm/kg over 20 min.

II. Hyperglycemic hyperosmolar non ketotic coma (HONK)

Pathogenesis

A. It occurs in middle aged and elderly patients

due to the presence of low level of insulin

which is sufficient for prevention of lipolysis

and ketosis and not enough to prevent

hyperglycemia.

B. The predisposing factors: see diabetic

ketoacidosis.

Clinical picture

1. Severe hyperglycemia and dehydration

which may lead to renal impairment.

2. Neurologic manifestations such as

convulsions, stupors and coma.

3. Thrombotic complications may occur

due to increased viscosity of the blood.

TreatmentTreatment

1. The same as in diabetic ketoacidosis but we

give z tonic saline to decrease the serum

osmolality which exceed 340 mosm/L (N.290

mosm/L).

2. Lower rate of insulin infusion 3U/h.

3. Lower rate of S.C. heparin to prevent

thrombosis.

III. Lactic acidosis

1. Occur with: biguanide therapy especially

phenformin.

2. The patient presents with acidosis (Kausmaull

respiration), late CNS and CVS inhibition.

3. Plasma ketostix value: < ++ exclude diabetic

ketoacidosis as a cause of metabolic acidosis.

4. Treatment:- by large amounts of bicarbonates.

IV. HypoglycemiaIV. HypoglycemiaCause:

1. Missed meal or Severe exercise after insulin or oral hypoglycemic agents.

2. Brittle diabetes mellitus.

3. Decreased elimination of insulin as in cases of renal failure.

Clinical picture:

1. Adrenergic manifestations

Begin when blood glucose < 50 mg% and leads to weakness, sweating, tremor, palpitation, irritability ,

tingling of the mouth and fingers ,hunger.

Cont._________________________Cont._____________________________2. Brain manifestations

Begin when blood glucose < 30 mg% and leads to headache hypothermia, visual disturbances, mental dullness, confusion, coma and dent

3. Masked symptoms of hypoglycemia may occur in the following conditions: a. Old age.b. During night.c. In alcoholics.d. During therapy with the following drugs:- β- blockers tranqulizers.

4. Prolonged hypoglycemia leads to irreversible brain damage.

InvestigationsLow plasma glucose level < 50 mg% in male and < 45

mg% in female.

Differential diagnosis1. From diabetic ketoacidosis:- see before.2. From other causes of hypoglycemia:- see later.

Treatment1. Adrenergic reactions:- can be treated with oral

CHO.2. If there is coma or confusion:- I.V. glucose 25-50

gm 50% followed by constant infusion of glucose till the patient is able to eat.

3. Hypoglycemia due to sulphonylurea:- may persist for a long time (days) so glucose has to be infused for a long time.

DIABETES WITH PREGNANCY

DIABETES WITH PREGNANCY

ClassificationGestational diabetes:- Impaired glucose tolerance

(IGT) during pregnancy.A:- IGT diagnosed before pregnancy and treated by

diet alone.B:- Insulin treatment (duration <10 years) before

pregnancy.C:- Insulin treatment (duration 10-20 years) before

pregnancy.D:- Insulin treatment (duration >20 years) before

pregnancy, Or the presence of chronic hypertension or simple retinopathy.

E: - The presence of diabetic nephropathy.F:- The presence of coronary artery disease.G:- The presence of proliferative retinopathy.H:- Prior renal transplantation.

The relation between diabetes and pregnancy

A. Effects of pregnancy on DM1. Increase the need for insulin due to increased anti-insulin such as human placentallactogen and progesterone.2. Decreased renal threshold for glucose.3. Increased incidence of complications e.g nephropathy.

B. Effects on the female1. Abortion.2. Premature labor.3. Toxemia of pregnancy.4. Postpartum hemorrhage.5. Puerperal sepsis.

C. Effects of DM on the baby1. High birth weight.2. Congenital anomaly especially anencephaly.3. Hyaline membrane disease.4. Hypoglycemia after birth ( due to maternal hyperglycemia over active pancreas.

TreatmentI. Pre-pregnancy planning

Tight control should be initiated before pregnancy until the glycosylated Hb is normalized, this is because diabetes related congenital malformations occur by the 5th to 8th week.

II. During pregnancy1. Diet. small frequent meals to prevent nocturnal and preprandial hypoglyce-

mia.2. Insulin treatment and avoid oral hypoglycemic agents since they cause fetal

beta cell hypertrophy and increase the tendency toward macrosomia and they have also teratogenic effects.

3. Monitor the diabetic control by:a. Home blood glucose monitoring:- keep FPG 60-110 and PPG <150 mg%.b. Glycosylated Hb every month (less than 7%).

III. During labour:- maternal blood glucose is kept within 80-100mg% during labour by an infusion of dextrose 10 gm/h +regular insulin 1/2 -2 U/h. We must be cautious with insulin adminstration because there is increased insulin sensitivity during and after delivery.

Thank Thank youyou

CHRONIC DIABETIC CHRONIC DIABETIC COMPLICATIONSCOMPLICATIONS

CHRONIC DIABETIC CHRONIC DIABETIC COMPLICATIONSCOMPLICATIONS

Diabetic neuropathyPathogenesis

1. Mononeuropathy due to ischemia of the vaso nervosa.

2. Polyneuropathy Accumulation of sorbitol: Normally 1% of glucose is

converted to sorbitol by the effect of aldose reductase enzyme. In diabetics due to increased glucose level, sorbitol is converted to fructose by the effect of sorbitol dehydrogenase. The accumulated fructose leads to increased osmolarity of the cells leading to increased water and electrolyte content of the cells and damage of the axons, myelin schwan cells.

Depletion of myoinositol: Its concentration in the peripheral nerves is 100 times than that of the plasma level. This concentration gradient is established by active transport (Na/K ATPase activity) which is defective in diabetics and this leads to disturbance of this concentration gradient.

Clinical pictureI. Mononeuropathy: Femoral, Ulnar, Median nerves,

Cranial nerves 3,4,6.II. Trunkal neuropathy: pain in the distribution of one or

more spinal nerves usually in the chest wall and the abdomen which may lead to acute chest pain or acute abdominal pain.

III. PolyneuropathyA. Sensory

1. Sensory affection is more than motor affection.2. Early there is numbness and tingling sensation more by night and

nocturnal calf spasm is common.3. Late there is glove and stock hyposthesia

B. Motor1. Diabetic amyotrophy "rare type":- bilateral asymmetrical weakness

and wasting of the pelvic girdle and thigh muscles, recovery occur.2. Diabetic neuropathic cachexia "more in elder males":- Bilateral

symmetrical peripheral neuropathy, anorexia, severe depression and weight loss which give the impression of malignancy.

IV. Autonomic IV. Autonomic neuropathyneuropathy1. Genitourinary system

a. Bladder dysfunction- Early:- straining, dribbling, reduction in the stream force.

- Late:- bladder is distended with overflow incontinence.

b. Loss of testicular sensation which is used to

differentiate organic from hysterical impotence.

c. Impotence

- Parasympathetic affection leads to failure of erection.

- Sympathetic affection leads to failure of ejaculation.

Cont._________________________Cont._____________________________2. Cardiovascular dysfunction

a. Persistent tachycardia.

b. Postural hypotension.

c. Painless myocardial infarction.

3. Gostrointestinal tracta. Gastroparesis leads to slow emptying, distension and

vomiting.

b. Intermittent bouts of diarrhea which is severe, watery, nocturnal and alternating with constipation.

c. Defects in the autonomic innervation of the internal anal sphincter leads to faecal incontinence.

Cont.___________________________4. Sweating disturbance "due to affection of the

sudomotor nerve fibres" a. Gustatory sweating.b. Night sweating.c. Anhydrosis of the feet and legs with excessive

sweating elsewhere.

5. Pupillary changes: Argyll robertson pupil (miotic, irregular and eccentric).

6. Vasomotor disturbances:a. Edema of the feet and leg due to loss of the

vasomotor tone.b. Neuropathic foot:- foot trauma leads to ulceration in

the sole which may become infected leading to bone destruction and osteomyelitis.

Treatment

1. Non steroidal anti-inflammatory drugs.

2. Phenytoin or Carbamazepine.

3. Tricyclic antidepressant.

4. Topically applied capsiacin "derived

from red pepper".

5. Aldose reductase inhibitors.

Cardiovascular disordersA. Microangiopathy: retinal renal vasa nervosa.

B. Macroanqiopathy due to astherosclerosis

1. Cerebral:- thrombosis and ischemia.

2. Coronary astherosclerosis which differ from non diabetic in the following:

a. Atypical anginal symptoms are more.

b. Diffuse distal lesion + proximal lesion.

c. Silent myocardial infarction.

d. Complications of myocardial infarction are more.

3. Peripheral vessels:- intermittent claudications.

4. Renal:- renovascular hypertension due to renal artery asthersclerosis.

C. Cardiomyopathy:- due to myocardial hypertrophy and fibrosis due to deposition of mucopolysaccharide in the wall of the arterioles and capillary B.M.

D. Blood pressure:- hypertension, postural hypotension.

RetinopathyRetinopathy1. Simple retinopathy.

2. Proliferative retinopathy.

3. Other diabetic complications affecting vision

a. Changes in refraction "temporary changes"

- Hyperglycemia leads to myopia.

- Hypoglycemia leads to hypermetropia.

b. Glaucoma is more frequent in diabetics.

c. Senile cataract "occur at an earlier age".

NephropathyI. Glomerular injury (Diabetic glomerulosclerosis)

PathogenesisIt occurs in long standing DM (type I and type II) especially poorly controlled diabetes after about 10-20 years.There are two main types: A. Nodular glomerulosclerosis "Kimmelsteil-Wilson syndrome"

1. It is the classic lesion, constitute about 25% of cases.2. There is deposition of glycoprotein in between and inside the

glomerular capillaries. 3. Microaneurysms of small blood vessels with hyalinization of

the afferent arterioles.

B. Diffuse glomerulosclerosis1. The commonest form, constitute about 75% of the cases. 2. Diffuse thickening of the basement membrane. 3. Hyalinization of the afferent and efferent arterioles .

Stages

A. Incipient nephropathy (good metabolic control can regress the lesion)

- Stage I:- hypertrophy and hyperf i Iteration leads to increased GFR >40%.

- Stage II:- hyper fiIteration + microalbuminuria on exercise.

- Stage III:- hyper fiIteration + constant microalbuminuria (excretion of > 50 mg/24 h). This stage may remain silent for up to 10-15 years.

B. Overt nephropathy- Stage IV:- Proteinuria >500 mg/24 h (rarely the proteinuria

exceed 5 gm/24 h). The GFR is decreased and hypertension is common.

- Stage V:- End stage CRF. This azotemic period need long time to develop in diabetics, about 15 years from the onset of diabetes.

TreatmentTreatment1. Diabetic control can reverse the microalbuminuria.

2. Hypertension has to be treated aggressively to delay the progression of the disease by ACE inhibitors which decrease albuminuria even in normotensive patients.

3. Low protein diet delay the progression.

4. Treatment of end stage CRFa. Conservative measures in old age.

b. Continuous ambulatory peritoneal dialysis.

c. Transplantation is the treatment of choice in young patients.

II. Interstitial injury

Acute pyelonephritis, acute necrotizing papillitis.

Other complications

I. Limited joint mobility

1. It is present in 15-30% of IDDM and NIDDM.

2. It may be a marker for increased risk for developing

late diabetic complications in IDDM.

3. Tight waxy skin and limited full extension of the 5th

finger followed by the other fingers can be found

II. Skin complications

1. Diabetic dermopathy:- Brown areas with depressed scar on healing.

2. Necrobiosis hipodica diabeticorum:- Plaque with raised erythematous border and depressed brownish c

3. Bullosis diabeticorum:-Tense blister which may ulcerate.

4. Acanthosis nigricans:- Skin with velvety appearance.5. Eruptive exanthomas:-Yellow to red papules that may

occur in response to trauma (Koebner phenomenon). More in uncontrolled diabetics who have severe hypertrig lyceridemia.

6. Lipodystrophy:-At the sites of insulin injection.7. Scleroderma:- Hardening of the skin over the face,

neck, upper limb.

III. Infections

- Skin infection: candida, staph., fungus e.g mucormycosis.

- Chest infections: especially tuberculosis which follow diabetics like their shadows.

- Renal infections: pyelonephritis, papillary necrosis.

- Genital infections in females leading to severe pruritis vulvae.

TreatmentTreatmentTreatment of diabetes mellitus

I. control

A. Amount of calories calculated "caloric adjustment aim to control the body wt"- Heavy workers:- 35 K cal/kg IBW.

- Moderate active persons:- 30 Kcal/kg IBW.

- Mild active persons:- 25 K cal/kg IBW.

- For boys 1 year old:- 1000 Kcal/ day, add 100 Kcal for each year of age.

B. Proportion of food elements - CHO:- 2-3gm/ kg. Supply the body by 50% of the calories.

- Protein:- 1-29m/ kg. Supply the body by 20% of calories.

- Fat:- 1gm/ kg. Supply the body by 30% of calories.

Cont._________________________Cont._____________________________C. Distribution of calories: The patient is given 3

main meals and 3 snacks.D. Precautions as regard the diet

1. Avoid simple sugars and give fine fibers (non absorbable polysaccharides) as bran which delay the absorption of other CHO so the increase in blood glucose is gradual.

2. Type of protein which can be given:-fish, poultry and skimmed milk.

3. Give plenty of vegetables.

E. What is the value of weight reduction ?1. Decrease Hepatic glucose production. 2. Decrease insulin resistance. 3. Increase B-cell function.

II. Oral therapy

A. Sulphonylurea group

Mechanism of action

1. Stimulate insulin secretion (main action).

2. Decrease hepatic glucose production.

3. Increase sensitivity of insulin receptors.

4. Reverse the post binding defect of insulin

action.

Preparations1. Old generationDoseDuration

Acetohexamide250-1500 mg twice14 hours

Chloropropamide100-500 mg onceup to 60 hours

Tolzamide100-1000 mg once or twice14 hours

Tolbutamide500-3000 mg 2-3 times 6-12 hours

2. New generation

Glibenclamide1.25-20 mg once or twiceup to 24 h

Glipizide2.5-40 mg once or twiceup to 24 h

Gliclazide80-480 mgup to 12 h

Glimepiride (amaryl)1-8 mgup to 24 h

Metabolism1. Acetohexamide, glibenclamide and glipizide are metabolised in the liver

and kidney.

2. Chloropropamide and gliclazide are metabolised only in the kidneys.

3. Tolzamide and tolbutamide are metabolised only in the liver.

Side effects

1. Hypoglycemia which may be severe and prolonged especially with chloropropamide.

2. HypoNa due to increased ADH by chloropropamide.

3. Hepatitis and bone marrow depression (rare).

4. Skin reactions.

Drug interactions:- The hypoglycemic effect is:

- Increased by:- NSAIb, sulphonamide, BB, H2 receptor antagonists.

- Decreased by:- corticosteroids estrogen rifampicin diuretics, barbiturates.

B. Biguanide group

Mechanism of action1. Decrease plasma glucose by reduction of

gluconeogenesis. 2. Increase sensitivity of insulin receptors. 3. Decrease intestinal glucose absorption. 4. Decrease body weight through its anorexogenic

effect.

Preparations and dosage1. Phenformin: may induce lactic acidosis.

2. Metformin: 500-1000 mg tab are available. It should be used with caution in the elderly and contraindicated in patients with renal impairment.

Side effects

1. Mild self limited diarrhea, nausea, and

anorexia.

2. Some patients complain of metallic taste in

their mouth and abdominal discomfort.

3. Many of these side effects are transient and

dose related and can be minimized by

taking metformin with meals and titrating the

dose and by decreasing the dosage.

C. Alpha glucosidose inhibitors "miglitol, acarbose"Mechanism

They slow down the breakdown of disaccharides and polysaccharides and other complex CHO into monosaccharides on the brush border of the small intestine leading to delayed glucose absorption.

Side effects1. Flatulence, soft stools and mild abdominal discomfort.2. They are dose related and transient, occuring during the 1st few weeks

of therapy.Advantages

1. They don't cause hypoglycemia.2. It is safer than sulfonylurea and biguanides in patients with kidney

diseases and in the elder population.3. It is also effective in patients with gestational diabetes manifested mainly

by postprandial hyperglycemia.4. It decrease the insulin requirements by 40% in patients with type I

diabetes. 5. Decrease the daily fluctuation in blood glucose values.

Dose: 50-100 mg orally twice with meals. Acarbose must be titrated up very slowly in order to avoid side effects (start by 25 mg/day and increase by 25 mg/w).

D. TroglitazoneD. Troglitazone "insulin sensitizer":- it acts by "insulin sensitizer":- it acts by

improving the insulin receptors.improving the insulin receptors.

III. Insulin therapy

IndicationsIndications

1.1. All type I (IDDM) patients. All type I (IDDM) patients.

2.2. Patients with type Patients with type IIII (NIDDM) in the following (NIDDM) in the following

conditions:conditions:

a. Not responding to diet and oral hypoglycemic agents.a. Not responding to diet and oral hypoglycemic agents.

b. During pregnancy and operations. c. During severe b. During pregnancy and operations. c. During severe

infection.infection.

3.3. Patients with diabetic ketoacidosis Patients with diabetic ketoacidosis

PreparationsA. Type of insulin

TypePreparationOnset

(hours)PeakDuration

1. Short actingNeutral (regular)Semilente

1/21

33

6-86-8

2.Intermediate actingIsophane (NPH)3816-24

3. Long actinga. Lente2824

b. Protamine zinc61224

c. Ultralente4-612-1630

4. BiphasicRapitard,mixtard

1/28-1216-24

B. Origin of insulin1. Animal origin eg. bovine type.

2. Purified monocomponent which is non antigenic.

3. Human insulin prepared by genetic engineering by the recombinant DNA technology.

Insulin regimen1. Conventional insulin therapy

a. Two injections, 2/3 the dose before breakfast and 1/3 before lunch.

b. 2/3 the dose intermediate insulin and 1/3regular insulin.

c. Begin by 20-30 U/day‘ and increase guided by the' response

2. Multiple subcutaneous insulin injection (MSII)

a. 25% of the dose is given as intermediate insulin before sleep.

b. 75% of the dose is given as regular insulin before the three main

meals.

3. Continous subcutaneous insulin infusion (CSII)

a. Small pump that deliver insulin SC.

b. 40% of the total daily dose is given as the basal rate and the

remainder as preprandial doses.

c. It is indicated in the following conditions:

- Pregnancy.

- Renal transplantation.

- Most patients with IDDM

Side effects1. Insulin allergy which may be local or systemic reactions.2. Hypoglycemia.3. Insulin antibodies.4. Insulin hpodystrophy: atrophy and displacement of S.C. fat at

sites of insulin injections.5. Insulin resistance due to:

a. Obesity.b. Antibodies against insulin preparation.c. Antibodies against insulin receptors.

6. Somogi phenomenon: overdose of insulin given at night leads to hypoglycemia with night sweat and

headache leading to increase in the counter regulatory hormones which may lead to hyperglycemia. This condition is treated by reduction of the evening insulin dose.

What do you know about dawn phenomenon? It refere to 'an early morning rise in plasma glucose requiring increase in the amount of insulin to maintain euglycemia.- Insulin analogues which may be:

a. Short acting:- act within 5 minutes of its adminstration and last only for 2-3 hours.b. Long acting:- which resemble to great extent

the basal insulin released in the body.- Oral insulin, nasal insulin, and rectal insulin are

under trials.- Pancreatic transplantation.- Islet cell transplantation.

HYPOGLYCEMIA CausesI. Fasting hypoglycemia

1. Increased Glucose utilization1. With hyperinsulinemia:-

a. Insulin.b. Exogenous insulin, sulphonylurea.

2. No hyperinsulinemia:-a. Extrapancreatic tumors:- may be due to high

level of insulin like growth factors from mesodermal tumors as fibroma sarcoma.

b. Systemic carnitine enzyme deficiency (an enzyme which is essential for carrying FFA to

the mitochondria to be oxidized) so that all tissues become obligate glucose consumers.

2. Hepatic disorders

a. Severe liver diseases: cirrhosis, fulminant

hepatic failure.

b. Enzyme defects: glycogen storage disease.

3. Hormonal deficiency:- hypopituitarism ,

Addison disease,hypothyroidism.

4. Substrate deficiency:- severe malnutrition, late

pregnancy.

5. Drugs which lead to decreased glucose

production: alcohol, BB, salicylates.

II. Postprandial hypoglycemia

1. Alimentary hypoglycemia: gastrectomy, gastrojejuno-

stomy lead to rapid gastric emptying, brisk glucose

absorption and excessive insulin release.

2. Early type II diabetes mellitus (I&T): the peak value of

insulin occur after 2 hours or later when the absorption

of CHO from the intestine has been completed.

3. Idiopathic type: which occur after large CHO meal.

4. Insulinoma.

III. Artifactual causes of III. Artifactual causes of hypoglycemiahypoglycemia1. Pseudohypoglycemia:- Occurs in certain chronic

leukemias when the leukocyte counts are markedly

sample collection or storage or confusion between whole

blood and plasma glucose values. The plasma glucose is

about 15% higher than corresponding whole elevated.

This reflect utilization of glucose by leukocytes after the

blood sample has been drawn, such condition is not

associated with symptoms.

2. Other artifactual hypog/ycemias may be seen with:-

Improper blood glucose values.

Clinical picture

Refere to diabetic hypoglycemia.

Investigations

1. Fasting plasma glucose level less than 50 mg% in males and <

45 mg% in females.

a. If the amount of glucose required to correct the manifestations

of hypoglycemia is less than 10 gm, the cause of fasting

hypoglycemia is decreased production of glucose.

b. If > 10 gm, the cause will be increased utilization of glucose.

2. The ratio of insulin (uU/ml) / plasma glucose (mg/dl) a. Normally

less than 0.4 b. In patients with insulinoma, it is higher.

3. Determination of the plasma level of insulin, cortisol, thyroxine.

4. Liver and kidney function tests.

5. Abdominal ultrasonography or C.T for solid tumors

TreatmentI. Fasting hypoglycemia

A. The acute attack: see diabetic hypoglycemia.

B. insulinoma

1. Surgical: resection of the tumor is the treatment of choice, if the tumor can't be localized stepwise pancreatectomy (from tail to head) is done.

Resection is stopped once blood glucose rises.

2. Medical: in cases of preoperative preparation , and in non surgical cases.

a. Diazoxide: 300-1200 mg/day ,IV or orally.

b. Octreotide: 150-450 mg/day , 5C.

c. Cytotoxic drugs: doxorubcin and streptozotocin for metastatic insulinoma.

II. Post-prandial (reactive hypoglycemia)

1. Diet (the main line of treatment) small frequent meals and avoid simple CHO.

2. Drugs

a. Probanthine: 7.5 mg 2 h before meals.

b. Phenytoin: 100-200 mg. It inhibits insulin secretion.

c. Propranolon: 10 mg 2 h before meals.

3. Surgery inhibition of rapid entry of glucose into the intestine by putting a reversed jejunal segment near the gastric outlet. This is done Incases refractory to the previous measures.

DIABETES DIABETES INSIPIDUSINSIPIDUS

(DI)(DI)

DIABETES DIABETES INSIPIDUSINSIPIDUS

(DI)(DI)

Physiology1. Vasopressin (A.D.H.) is secreted by the supraoptic muceli in the

hypothalamus and migrate along the axons of these nuclei to the posterior pituitary.

2. Actions of A.D.H.a. Increased Absorption of H2 0 in the collecting tubules to maintain osmolality and volume of body fluids constant.b. Increased A.C. T.H. release from the anterior pituitary.c. It may enhance memory and learning.d. Constrict the arteriolar smooth ms.

3. Control of secretiona. Increased plasma osmolality: stimulate the osmoreceptor in the hypothalamus leading to increased A.D.H. secretion.b. Decreased blood volume: decrease inhibitory impulses .of the left atrium

(which passes via the vagus) on A.D.H. release leads to increased A.D.H. secretion.

c. Decreased blood pressure: stimulate the baroreceptors in the carotid sinus and aortic arch leading to increased A.D.H. secretion.d. Neural regulation:

- Cholinergic and R- adrenergic stimuli :- stimulate A.D.H.- Atropine and a- adrenergic stimuli :- inhibit A.D.H.

CausesI. Central D.I.

4 types of central DI are- Complete central DI : inability to secrete ADH.- Partial central Dl: ADH is secreted at a normal

osmotic threshold but in subnormal amounts.- Defective osmoreceptor DI : AbH is not released

in response to plasma osmolality but released in response to hypovolemia.

- Reset osmoreceptor D.L : A.D.H. is released at a higher than normal osmotic threshold.

A. Familial1. Dominant or recessive inheritance.2. DIDMOAD "wolfram syndrome"

(DI., D.M., optic atrophy, nerve deafness).

B. AcquiredB. Acquired1. 1. TraumaTrauma2. 2. Tumors:Tumors: large pituitary tumors. large pituitary tumors.3. 3. Infections: meningitis, encephalitis. meningitis, encephalitis.4. 4. Infilteration:Infilteration: sarcoidosis sarcoidosis5. 5. Infarction:Infarction: sheehan syndrome. sheehan syndrome.6. 6. Idiopathic:Idiopathic: most common cause. most common cause.

IIII. Nephroqenic D.I.. Nephroqenic D.I.A. A. familial:familial: X- linked X- linkedB. B. AcquiredAcquired

1. 1. Electrolyte disturbance:Electrolyte disturbance: hypok or hyperca. hypok or hyperca.2. 2. Chronic renal failureChronic renal failure..3. 3. Drugs:Drugs: demethylchlortetracycline, lithium. demethylchlortetracycline, lithium.4. 4. SystemicSystemic: multiple myeloma, amyloidosis.: multiple myeloma, amyloidosis.

Clinical picture

1. Polyuria and polydepsia: urine volume > 2.5

L/day and may reach to 20 L/day.

2. Severe dehydration leads to weakness,

psychic disturbance, prostration and death.

3. Rarely: insomnia, exhaustion, depression and

constipation. May be weight loss in chronic

cases with signs of dehydration.

4. Features of the underlying etiology.

InvestigationsI. Urine ex

1. Polyuria with low specific gravity (1001- 1004).

2. No pathological constituents.

II. Localization of the site of the lesion

1. Dehydration test

1. Prevent the patient from drinking water for 4 - 18 h.

2. Follow up every hour for specific gravity and body weight.

3. We proceed to the next step if the patient lose 5% of his body weight during the test (to prevent hypotension) or i urine specific gravity becomes nearly

stable in 3 successive samples.

4. Aquous A.D.H 5 U. is given S.C. and urine specific gravity is measured after one hour.

5. Interpretation:

- Psychogenic polydepsia:- urine specific gravity increase at the end of the test and doesn't increase further after A.D.H. administration.

- Central D.I.: urine specific gravity doesn't increase at the end of the test but increase after A.D.H.

- Nephrogenic D.I.: no increase in the specific gravity at the end of the test or after A.D.H. adminstration.

2. Nicotine test

1. Normally 1-3 mg nicotine tartarate stimulates the hypothalamus to release A.D.H. leading to oliguria.

2. The response is -ve in hypothalamo-hypophyseal axis lesion.

3. Plain X- ray, C T, MRT on the sella turcica to exclude pituitary tumors.

4. Hypertonic Na cl

1. Normally 2.5 cc 2.5% solute/kg stimulate the osmoreceptors in the hypothalamus leading to oliguria.

The response is -ve in osmoreceptor defects.

5. Blood ex. for urea, creatinine, K., Ca.

6. Plasma osmolality

a. Increases in cases of diabetes insipidus.

b. Decreases in cases of psychogenic polydepsia.

Differential diagnosisFrom other causes of polyuria :see later

TreatmentI. Central D.I.

A. Hormone replacement1. Aquous vasopressin 5 U/S.C./6h.2. Vasopressin tannate in oil 5 U I.M./48h.3. Desmopressin (minirine) 10-20 ug intra-nasal/ 12-24 h.

B. Non hormonal agents (stimulate A.D.H) 1. Chloropropamide 500mg/ day. 2. Clafibrate 500mg / 4 times / day. 3.

Carbamazepine 500mg / day.

II. Nephroqenic D.I.Hydrochlorothiazide or chlorothalidone 50 mg/ day. Na has to be

restricted from the diet. So hypo Na occur leading to decreased amount of Na delivered to the loop of Henle and decreased water excretion.

SYNDROME OF SYNDROME OF INAPPROPRIATE ADH INAPPROPRIATE ADH

SECRETIONSECRETION

SYNDROME OF SYNDROME OF INAPPROPRIATE ADH INAPPROPRIATE ADH

SECRETIONSECRETION

CausesI. Tumors release ADH

1. Oat cell carcinoma of the lung.2. Cancer pancreas.3. Hodgkin's lymphoma.4. Thymoma.

II. Non tumorous tissue release ADH or stimulate ADH release from the pituitary

A. Chest disorders1.Tuberculosis.2. Lung abscess.3. Pneumonia.4. Empyema.5. C.O.P.D.6. +ve pressure respiration

B. C. N. S. disorders

1. Skull fracture.

2. Subdural hematoma.

3. Subarachnoid Hge.

4. Acute encephalitis.

5. Tuberculous meningitis.

6. Purulent meningitis.

7. Drugs: chloropropamide, carbamazepine.

DiagnosisSymptoms Weight gain, weakness, lethargy, mental confusion,

convulsions and coma.Laboratory findings

a. Low BUN, creatinine, uric acid, albumin.b. Serum Na < 130 mmol/ L.c. Urine is almost always hypertonic in comparison to plasma and

urinary Na > 20 mmol/ L.

Treatment1. Mild cases: fluid restriction to 0.8- 1L/ d.2. Severe cases: 200- 300 ml 5% NaCl solution IN over several hours to increase Na level.3. Demecloycline: interfere with renal action of ADH and may be

useful when fluid restriction is impractical, but it has delayed onset of action.

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