Professional Documents
Culture Documents
in
Internal
Medicine
By
Dr. Nabil Lymon
Professor of Internal Medicine
Mansoura University
ACUTE DIABETIC
COMPLICATIONS
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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.
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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)
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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.
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Differential diagnosis
Ketoacidosis Hopolycemia
Precipitating factors. See before See later
Onset Slow Rapid
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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.
III. Lactic acidosis
1. Occur with: biguanide therapy especially
phenformin.
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._________________________
__
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.
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.
CHRONIC DIABETIC
COMPLICATIONS
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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.
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.
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.
Cont._________________________
__
2. Cardiovascular dysfunction
a. Persistent tachycardia.
b. Postural hypotension.
c. Painless myocardial infarction.
3. 6ostrointestinal tract
a. 6astroparesis 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. Pupi/lacy 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. IVleuropathic 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.
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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.
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".
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 .
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.
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.
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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.
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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.
Preparations
1. Old generation Dose Duration
b. Protamine zinc 6 12 24
c. Ultralente 4-6 12-16 30
4. Biphasic Rapitard, 1/2 8-12 16-24
mixtard
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
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 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.
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.
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DIABETES WITH
PREGNANCY
Classification
Gestational diabetes:- Impaired glucose tolerance
(IGT) during pregnancy.
A:- I&T 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.
F: - The presence of diabetic nephropathy.
H:- The presence of coronary artery disease.
R:- The presence of prof iferative retinopathy.
T:- Prior renal transplantation.
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.
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.
HYPOGLYCEMIA
Causes
I. Fasting hypoglycemia
1. Increased Glucose utilization
1. With hyperinsulinemia:-
Insulin.
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.
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
4. Insulinoma.
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III. Artifactual causes of
hypoglycemia
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.
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
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.
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 INSIPIDUS
(DI)
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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.
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).
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.
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Causes
I. Tumors release ADH
1. Oat cell carcinoma of the lung.
2. Cancer pancreas.
3. Hodgkin's lymphoma.
4. Thymoma.
m
release from the pituitary
co
A. Chest disorders
s.
1.Tuberculosis.
an
2. Lung abscess.
sF
3. Pneumonia.
an
4. Empyema.
5. C.O.P.D. .M
w
6. +ve pressure respiration
w
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.
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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.
Thank
you
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