1. Diabetes Mellitus Pathology and complications By Dr. Abdelaty Shawky Assistant professor of pathology

2. 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).

3. TYPE I Type II 1. AgeUnder 25 years.Above 40 years. 2. B. Cell mass.ReducedNot reduced. 3. Insulin secretion ReducedNot reduced 4. Etiology1.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. 3

4. * 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. 4

5. 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. 5

6. 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. 6

7. 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. 7

8. * Complications of diabetes mellitus: I.Acute complications: 1.Diabetic ketoacidosis 2.Hypoglycemic coma II. Chronic complications: a. Microvascular  Retinopathy  Nephropathy  Neuropathy b. Macrovascular  Cerbrovascular.  Cardiovascular.  Peripheral vascular disease.

9. Diabetic ketoacidosis (DKA) May be the 1 st presentation of type 1 DM. Result from absolute insulin deficiency or increase requirement. Mortality rate around 5%. 9

10. * Predisposing factors for DKA Infection Trauma Myocardial Infarction Stroke Surgery Emotional stress 10

11. * Clinical presentation of DKA: Polyurea and polydepsia. Nausea and vomiting. Anorexia and abdominal pain. Tachycardia. Signs of dehydration. Hypotonia. Coma. 11

12. * Diagnosis of DKA: Hyperglycemia Ketonuria and ketonemia Acidosis (PH< 7.3 ) 12

13. * Treatment of DKA: Fluid replacement. Insulin therapy for hyperglycemia. Electrolyte correction. Acidosis correction. Treatment of precipitating cause. 13

14. * Complications of DKA: Cerebral edema Vascular thrombosis Infection M I Respiratory distress syndrome 14

15. 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 15

16. * Clinical manifestations of hypoglycemia: Autonomic dysfunctions: 1. Hunger 2. Tremor 3. Palpitation 4. Anxiety 5. Pallor 6. Sweating 16

17. Neurologic dysfunctions: 1. Impaired thinking 2. Change of mood 3. Irritability 4. Headache 5. Convulsion 6. Coma 17

18. * Predisposing factors: Missed meal Change in physical activity Alterations or errors in insulin dosage Alcohol ingestion 18

19. * 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. 19

20. Chronic Complications of DM A. Macrovascular Complications. B. Microvascular Complications. 20

21. 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. 21

22. 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 22

23. 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). 23

24. 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

25. Diabetic retinopathy 25

26. * 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). 26

27. Normal Retina 27

28. 28

29. Diabetic Retinopathy Cotton wool spots 29

30. Other Eye Complications - Cataracts. - Glaucoma -Vitreous Bleeding. 30

31. Vitreous Bleeding 31

32. Diabetic Nephropathy (DN) 32

33. - 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. 33

34. Diabetic Neuropathy 34

35. 1. Sensorimotor neuropathy. 2. Autonomic neuropathy. 35

36. Sensorimotor Neuropathy Numbness, paresthesias. Feet are mostly affected, hands are seldom affected. Complicated by ulceration (painless), charcot arthropathy, Callosities 36

37. Complications of Sensorimotor neuropathy 37

38. Autonomic Neuropathy  Postural hypotension.  Diabetic diarrhea.  Erectile dysfunction. 38

39. The end Mon 29 0ct 201339