Diabetes MellitusDiabetes Mellitus Pathology and complicationsPathology and complications

ByByDr. Abdelaty ShawkyDr. Abdelaty Shawky

Assistant professor of pathology Assistant professor of pathology

Diabetes Mellitus Metabolic disease affecting CHO, protein and

fat metabolism due to insulin deficiency or

inefficiency.

Two types:

1.Type I (insulin dependent).

2.Type II (insulin independent).

  TYPE I Type II

1. Age Under 25 years. Above 40 years.

2. B. Cell mass. Reduced Not reduced.

3. Insulin

secretion

Reduced Not reduced

4. Etiology 1. Hereditary.

2. Autoimmune destruction of

the B.cells.

1. Decreased insulin

specific surface receptors

on most of the body cells.

2. Premature aging of body

cells including B.cells.

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* Pathological lesions:

1. Pancreas:

- In type I: the pancreas is atrophic. M/P:

degranulated and destroyed B.cells, lymphocytic

infiltration and fibrosis.

- In type II: the pancreas is normal. M/P: normal in

early stage, later on shows hyalinosis.

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2. Disturbance of metabolism:

A. Carbohydrate metabolism: Hyperglycemia due to

either decreased glucose utilization or due to

glycogenolysis, leads to:1. Glucose retention in the tissue (increase the liability to infection).2. Glycogen deposition in the tissues (heart, muscle, kidney and pancreas).3. Glucosuria: leads to osmotic diuresis and dehydration.

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B. Fat metabolism: Lipolysis: Leads to:1. Hperlipidaemia (atheroma formation and fatty infiltration in the parenchymatous organs).2. Formation of ketone bodies in the liver with keto-acidosis and coma.

C. Protein metabolism: Loss of weight.

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3. Vascular changes:1. Diabetic macroangiopathy: accelerated atherosclerosis in aorta, large and medium sized arteries. 2. Hyaline arterioloscelrosis: hyaline thickening of the arterioles due to deposition of hyaline material.3. Diabetic microangiopathy: diffuse thickening of the basement membranes due to deposition of hyaline material. Involves predominantly the capillaries of, retina, renal glomeruli, and peripheral nerves. Leads to diabetic nephropathy, retinopathy and neuropathy.

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* Complications of diabetes mellitus:

I. Acute complications:

1. Diabetic ketoacidosis2. Hypoglycemic coma

II. Chronic complications:a. Microvascular

Retinopathy Nephropathy Neuropathyb. MacrovascularI. Cerbrovascular.II. Cardiovascular.III. Peripheral vascular disease.

Diabetic ketoacidosis (DKA)

• May be the 1st presentation of type 1 DM.

• Result from absolute insulin deficiency or increase requirement.

• Mortality rate around 5%.

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* Predisposing factors for DKA• Infection • Trauma• Myocardial Infarction• Stroke• Surgery• Emotional stress

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* Clinical presentation of DKA:• Polyurea and polydepsia.• Nausea and vomiting.• Anorexia and abdominal pain.• Tachycardia.• Signs of dehydration.• Hypotonia.• Coma.

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* Diagnosis of DKA:

• Hyperglycemia• Ketonuria and ketonemia• Acidosis (PH< 7.3 )

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* Treatment of DKA:

• Fluid replacement. • Insulin therapy for hyperglycemia.• Electrolyte correction.• Acidosis correction.• Treatment of precipitating cause.

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* Complications of DKA:

• Cerebral edema• Vascular thrombosis• Infection• M I• Respiratory distress syndrome

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Hypoglycemic coma

• Hypoglycemia is the most frequent acute complication in type 1 diabetes.

• Hypoglycemia is the level of blood glucose at which autonomic and neurological dysfunction begins

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* Clinical manifestations of hypoglycemia:• Autonomic dysfunctions: 1. Hunger 2. Tremor 3. Palpitation 4. Anxiety 5. Pallor 6. Sweating

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• Neurologic dysfunctions: 1. Impaired thinking 2. Change of mood 3. Irritability 4. Headache 5. Convulsion 6. Coma

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* Predisposing factors:

• Missed meal• Change in physical activity• Alterations or errors in insulin dosage• Alcohol ingestion

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* Treatment of hypoglycemia

• In mild cases oral rapidly absorbed carbohydrate.

• In sever cases (comatose patient) I.V hypertonic glucose 25% or 50% concentration & glucagon injection.

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Chronic Complications of DM

A. Macrovascular Complications.

B. Microvascular Complications.

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A. Macro-vascular Complications:

• Accelerated atherosclerosis involving the aorta and

large- and medium-sized arteries.

• Myocardial infarction, caused by atherosclerosis of

the coronary arteries, is the most common cause of

death in diabetics.

• Gangrene of the lower extremities.• Hypertension due to Hyaline arteriolosclerosis.

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• Microvascular complications are specific to diabetes

and related to longstanding hyperglycaemia.

• In diabetes, the microvasculature shows both

functional and structural abnormalities.

• The structural hallmark of diabetic microangiopathy is

thickening of the capillary basement membrane.

B. Microvascular Complications

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• Many chemical changes in basement

membrane composition have been identified

in diabetes, including increased type IV

collagen and its glycosylation (i.e. binding of

glucose to wall of blood vessels).

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• The main functional abnormalities include increased

capillary permeability and disturbed platelet

function.

• Increased capillary permeability is manifested in the

retina by exudation and in the kidney by increased

urinary losses of albumin.

• Platelets from diabetic patients show an exaggerated

tendency to aggregate, perhaps mediated by altered

prostaglandin metabolism.24

Diabetic retinopathy

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* Pathological lesions:

•Thickening of the capillary basement membrane.

•Capillary dilatations (microaneurysms) which may give

rise to; haemorrhage or exudate (red dots and blots).

•Vascular occlusion leads to large ischaemic areas

(cotton-wool spots).

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Normal Retina

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Diabetic Retinopathy

Cotton wool spots

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Other Eye Complications

- Cataracts.- Glaucoma-Vitreous Bleeding.

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Vitreous Bleeding

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Diabetic Nephropathy (DN)

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- Diabetic nephropathy is defined by persistent

albuminuria (>300 mg/day), decrease glomerular

filtration rate and rising blood pressure.

- About 20 – 30% of patients with diabetes develop

diabetic nephropathy .

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Diabetic Neuropathy

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1. Sensorimotor neuropathy.2. Autonomic neuropathy.

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Sensorimotor Neuropathy

• Numbness, paresthesias.

• Feet are mostly affected, hands are seldom affected.

• Complicated by ulceration (painless), charcot

arthropathy, Callosities

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Complications of Sensorimotor neuropathy

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Autonomic Neuropathy

Postural hypotension.

Diabetic diarrhea.

Erectile dysfunction.

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The end

Mon 29 0ct 201339