1. 1 FUNCTION/DYSFUNCTION OF ENDOCRINE PANCREAS Diabetes

2. 2 Anatomy of the pancreas: Both an exocrine and endocrine organ Cells with exocrine function release an alkaline fluid containing sodium bicarbonate and enzymes → pancreatic duct → small intestine Pancreatic “juice” aids in breakdown and digestion of food in the small intestine Pancreatic exocrine cells = acinar cells

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5. 5 Endocrine Function : Cells of the Islet of Langerhans synthesize and release hormones into the circulation. Hormones travel through the bloodstream to target tissues (especially liver and muscle) At the target cells, hormones bind specific receptors and cause cell changes that control metabolism

6. 6 Insulin secretion is controlled through several mechanisms: Chemically – high levels of glucose and amino acids in the blood Hormonally – beta cells are sensitive to several hormones that may inhibit or cause insulin secretion Neurally – stimulation of the parasympathetic nervous system causes insulin to be secreted.

7. 7 Insulin secretion is decreased by: Decreased blood glucose concentration Increased blood insulin concentration Sympathetic stimulation

8. 8 Insulin Transported through the blood to target tissues where it binds to specific receptors The binding of insulin to target cells: –Acts as a biochemical signal to the inside of the cell Overall, cell metabolism is stimulated There is increased glucose uptake into the cell Regulation of glucose breakdown within the cell Regulation of protein and lipid breakdown within the cell

9. 9 Blood glucose is decreased because insulin causes glucose to leave the bloodstream and enter the metabolizing cells. With the exception of brain, liver and erythrocytes, tissues require membrane glucose carriers.

10. 10 Diabetes mellitus Historically ‑ distinguished by weight loss, excessive urination, thirst, hunger Excessive urination = polyuria Excessive thirst = polydipsia Excessive hunger = polyphagia Modern characterization is by hyperglycemia and other metabolic disorders

11. 11 Modern classifications (Table17.7) Type 1 or IDDM ‑ Insulin Dependent Diabetes Mellitus Type 2 or NIDDM ‑ Non ‑ Insulin Dependent Diabetes Mellitus Other Types of Diabetes Mellitus GDM ‑ Gestational Diabetes Mellitus

12. 12 Accounts for 10% all DM in the Western world ~10-15% have parent or sibling with the disease Peak age of diagnosis = 12 years Genetic/environmental/autoimmune factors destroy beta cells Believed abrupt onset – now immunomarkers and preclinical symptoms have been discovered Type 1 or IDDM

13. 13 Clinical Manifestations: Weight loss - Patient eats, but nutrients are not taken up by the cells and/or are not metabolized properly Osmotic diuresis results in fluid loss Loss of body tissue by metabolism of fats and proteins

14. 14 Polyuria, polydipsia, pholyphagia Ketoacidosis Fats and proteins are metabolized excessively, and byproducts known as ketone bodies are produced. These are released to the bloodstream and cause: Decreased pH (so increased acidity) Compensations for metabolic acidosis Acetone given off in breath

15. 15 1. Administer insulin May be of animal or human origin Cannot be given orally Patient must monitor their blood glucose concentration and administer insulin with the correct timing Treatment

16. 16 2. Control diet Carbohydrates should make up about 55-60% of patient’s total calories Fats should make up <30% of patient’s total calories Proteins should make up about 15-20% of patient’s total calories

17. 17 3. Monitor exercise Remember: muscles are a target tissue of insulin, and metabolize much glucose for energy Sometimes exercise → irregular blood glucose levels So diabetic patients should be monitored when they are exercising

18. 18 Other: Pancreatic transplant – so far not successful Experimental therapies – not as successful as hoped

19. 19 Type 2 or NIDDM More common than IDDM, often undiagnosed It has a slow onset Most common in those > 40 years, though children are being diagnosed more regularly May be genetic Obesity is the greatest risk factor for this disease And is related to increased incidence in children

20. 20 NIDDM → insulin resistance in target cells See decreased β cell responsiveness → Decreased insulin secreted by β cells Also abnormal amount of glucagon secreted

21. 21 These effects may be due to: 1.Abnormally functioning β cells 2. Decreased β cell mass, or a combination of the two 3. Target cell resistance to insulin Due to: Decreased number of insulin receptors Postreceptor events may be responsible Cells “burn out” and become insensitive

22. 22 Overweight, hyperlipidemia common (but these are precursors, not symptoms) Recurrent infections Visual changes, paresthesias, fatigue Clinical manifestations

23. 23 1. Weight loss 2. Appropriate diet (see IDDM above) 3. Sulfonyl ureas stimulate β cells to increase insulin secretion Works only when β cells are still functioning → An enhancement of insulin’s effect at target cells 4. Exercise - promotes weight loss Treatment

24. 24 Due to increased hormone secretion during pregnancy Seen if patient has predisposition If previous or potential glucose intolerance has been noted Important ‑ increased mortality risk for mother, child Gestational Diabetes

25. 25 Complications of Diabetes Mellitus Acute: Hypoglycemia = rapid decrease in plasma glucose = insulin shock Neurogenic responses – probably due to decreased glucose to hypothalamus. Symptoms include: Tachycardia, palpitations, tremor, pallor Headache, dizziness, confusion Visual changes

26. 26 Treatment : provide glucose (I.V. or subcutaneous if unconscious) Observe for relapse

27. 27 Ketoacidosis – involves a precipitating event: Increased hormones released w/ trauma  increased glucose produced by the body’s cells This “antagonizes” the effects of any glucose present  Increased ketones in blood Acid/base imbalance Polyuria, dehydration Electrolyte disturbances Hyperventilation (Kussmaul – deep, gasping) CNS effects Acetone on breath

28. 28 Treatment: ‑ low dose insulin Also, administer fluids, electrolytes

29. 29 Chronic Complications of DM Neuropathies = nerve dysfunctions → slowing of nerve conduction. In these patients, see: Degeneration of neurons → Sensory, motor deficits → Muscle atrophy, paresthesias Depression G.I. problems, as muscle motility decreased Sexual dysfunction

30. 30 Microvascular disease – chronic diabetes w/ improper glucose metabolism → thickening of the basement membrane of capillaries, particularly in the eye and the kidney. As the capillary changes in this way, → Decreased tissue perfusion So ischemia → hypoxia

31. 31 In the eye – the retina is metabolically quite active, so hypoxia here is a big problem So see: Retinal ischemia → Formation of microaneurisms, hemorrhage, tissue infarct, formation of new vessels, retinal detachment

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34. 34 In the kidney – diabetes is the most common cause of end ‑ stage renal disease Injured glomeruli (glomerulosclerosis) In these patients, see: Proteinuria (protein is excreted into the urine) → Generalized body edema, hypertension

35. 35 Macrovascular disease – atherosclerosis Plaque formation increases → Increased risk of coronary artery disease, so increased risk of myocardial infarction Increased risk of congestive heart failure Stroke Peripheral vascular disease why diabetic patients face problems with their lower legs and feet Increased risk of infections