2. ACUTE DIABETIC
COMPLICATIONS
By
Dr. Nabil Lymon
Professor of Internal Medicine
Mansoura University

3. 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, pheochromocytosis.
5. Drugs which decrease the insulin secretion such as:a. Steroids, Diuretics.
b. Azathioprine, Diazoxide, Phenytoin.

4. Pathogenesis and clinical picture
A. 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)

5. 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.

6. Differential diagnosis
Ketoacidosis
Hopolycemia
Precipitating factors.
Onset
See before
Slow
See later
Rapid
Skin
Tongue
Dry and cold
Dry
Wet
Moist
Temperature
Respiration
Breath
Subnormal
Kausmaull
Acetone odour
Normal
Normal
Normal
Blood pressure
Effect of oral sugar
Low
No effect
Systolic pressure
Rapid recover

7. Investigations
1. 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.

8. Treatment
A. 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).

9. B. Curative
1. 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%.

10. 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.

11. Complications
1. Acute fatty infiltration of the liver.
2. Infection
a. 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"

12. 
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 12 gm/kg over 20 min.

13. 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.

14. 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.

15. Treatment
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.

16. 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.

17. IV. Hypoglycemia
Cause:
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.

18. Cont.__________________________
_ Brain manifestations
2.
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:- βblockers tranqulizers.
4. Prolonged hypoglycemia leads to irreversible
brain damage.

19. Investigations
Low plasma glucose level < 50 mg% in male and < 45
mg% in female.
Differential diagnosis
1. From diabetic ketoacidosis:- see before.
2. From other causes of hypoglycemia:- see later.
Treatment
1. 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.

20. DIABETES WITH
PREGNANCY

21. Classification
Gestational 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.

22. The relation between diabetes and pregnancy
A. Effects of pregnancy on DM
1. 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 female
1. Abortion.
2. Premature labor.
3. Toxemia of pregnancy.
4. Postpartum hemorrhage.
5. Puerperal sepsis.
C. Effects of DM on the baby
1. High birth weight.
2. Congenital anomaly especially anencephaly.
3. Hyaline membrane disease.
4. Hypoglycemia after birth ( due to maternal hyperglycemia  over active
pancreas.

23. Treatment
I. 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 pregnancy
1. Diet. small frequent meals to prevent nocturnal and preprandial hypoglycemia.
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.

24. Thank
you

25. CHRONIC DIABETIC
COMPLICATIONS

26. Diabetic neuropathy
Pathogenesis
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.

27. Clinical picture
I. 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. Polyneuropathy
A. 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. Motor
1. 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.

28. IV. Autonomic neuropathy
1. 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.

29. Cont.__________________________
_
2. Cardiovascular dysfunction
a. Persistent tachycardia.
b. Postural hypotension.
c. Painless myocardial infarction.
3. Gostrointestinal tract
a. 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.

30. Cont.__________________________
_ Sweating disturbance "due to affection of the
4.
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.

31. 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.

32. Cardiovascular disorders
A. 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.

33. Retinopathy
1. 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".

34. Nephropathy
I. Glomerular injury (Diabetic glomerulosclerosis)
Pathogenesis
It 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 glomerulosclerosis
1. The commonest form, constitute about 75% of the cases.
2. Diffuse thickening of the basement membrane.
3. Hyalinization of the afferent and efferent arterioles .

35. 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.

36. Treatment
1. 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 CRF
a. 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.

37. 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

38. 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.

39. 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.

48. Treatment
Treatment 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.

49. Cont.__________________________
_ Distribution of calories: The patient is given 3
C.
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.

50. 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.

51. Preparations
1. Old generation
Dose
Duration
Acetohexamide
250-1500 mg twice
14 hours
Chloropropamide
100-500 mg once
up to 60 hours
Tolzamide
100-1000 mg once or twice
14 hours
Tolbutamide
500-3000 mg 2-3 times
6-12 hours
Glibenclamide
1.25-20 mg once or twice
up to 24 h
Glipizide
2.5-40 mg once or twice
up to 24 h
Gliclazide
80-480 mg
up to 12 h
Glimepiride (amaryl)
1-8 mg
up to 24 h
2. New generation

52. Metabolism
1. 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.

53. B. Biguanide group
Mechanism of action
1. 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 dosage
1. 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.

54. 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.

55. 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 effects
1. 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).

56. D. Troglitazone "insulin sensitizer":- it acts by
improving the insulin receptors.
III. Insulin therapy
Indications
1. All type I (IDDM) patients.
2. Patients with type II (NIDDM) in the following
conditions:
a. Not responding to diet and oral hypoglycemic agents.
b. During pregnancy and operations. c. During severe infection.
3. Patients with diabetic ketoacidosis

57. Preparations
A. Type of insulin
Type
Preparation
Onset
(hours)
Peak
Duration
1. Short acting
Neutral (regular)
Semilente
1/2
1
3
3
6-8
6-8
2.Intermediate acting
Isophane (NPH)
3
8
16-24
3. Long acting
a. Lente
2
8
24
b. Protamine zinc
6
12
24
c. Ultralente
4-6
12-16
30
Rapitard,
mixtard
1/2
8-12
16-24
4. Biphasic

58. B. Origin of insulin
1. 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 regimen
1. 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 1/3
regular insulin.
c. Begin by 20-30 U/day‘ and increase guided by
the' response

59. 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

60. Side effects
1. 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.

61. 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.

62. HYPOGLYCEMIA
Causes
I. Fasting hypoglycemia
1. Increased Glucose utilization
1. 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.

63. 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.

64. II. Postprandial hypoglycemia
1. Alimentary hypoglycemia: gastrectomy, gastrojejunostomy 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.

65. III. Artifactual causes of hypoglycemia
1.
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.

66. 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

67. Treatment
I. 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.

68. 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.

69. DIABETES INSIPIDUS
(DI)

70. Physiology
1. 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 secretion
a. 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.

71. Causes
I. 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. Familial
1. Dominant or recessive inheritance.
2. DIDMOAD "wolfram syndrome"
(DI., D.M., optic atrophy, nerve deafness).

72. B. Acquired
1. Trauma
2. Tumors: large pituitary tumors.
3. Infections: meningitis, encephalitis.
4. Infilteration: sarcoidosis
5. Infarction: sheehan syndrome.
6. Idiopathic: most common cause.
II. Nephroqenic D.I.
A. familial: X- linked
B. Acquired
1. Electrolyte disturbance: hypok or hyperca.
2. Chronic renal failure.
3. Drugs: demethylchlortetracycline, lithium.
4. Systemic: multiple myeloma, amyloidosis.

73. 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.

74. Investigations
I. 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.

75. 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.

76. Differential diagnosis
From other causes of polyuria :see later
Treatment
I. Central D.I.
A. Hormone replacement
1. 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.

77. SYNDROME OF
INAPPROPRIATE ADH
SECRETION

78. Causes
I. 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 disorders
1.Tuberculosis.
2. Lung abscess.
3. Pneumonia.
4. Empyema.
5. C.O.P.D.
6. +ve pressure respiration

79. 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.

80. Diagnosis
Symptoms 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.
Treatment
1. 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.

81. Thank
you