ENDOCRINE & METABOLIC DISORDERS Presentation

ENDOCRINE & METABOLIC DISORDERS

1. Rab i a Abbasi 1

2. By the end of this lecture the learners will be able to:- Review of Anatomy & Physiology of endocrine pancreas Discuss the classification of diabetes mellitus (DM) Discuss etiology, pathophysiology, and clinical manifestations of Type-1 DM & Type-2 DM. Differentiate the main differences between Type-1 DM & Type-2 DM Understand pathogenesis, manifestations of acute and chronic complications of diabetes mellitus 2

3. The pancreas is a long, slender organ, most of which is located posterior to the bottom half of the stomach Although it is primarily an exocrine gland, secreting a variety of digestive enzymes, the pancreas has an endocrine function. Its pancreatic islets—clusters of cells formerly known as the islets of Langerhans— secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide (PP). 3

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5. ⚫ ⚫ The alpha cell produces the hormone glucagon and makes up approximately 20 percent of each islet. Glucagon plays an important role in blood glucose regulation; low blood glucose levels stimulate its release. The beta cell produces the hormone insulin and makes up approximately 75 percent of each islet. Elevated blood glucose levels stimulate the release of insulin. 6

6. ⚫ The delta cell accounts for four percent of the islet cells and secretes the peptide hormone somatostatin. Recall that somatostatin is also released by the hypothalamus (as GHIH), and the stomach and intestines also secrete it. An inhibiting hormone, pancreatic somatostatin inhibits the release of both glucagon and insulin . 7

7. ⚫ The PP cell accounts for about one percent of islet cells and secretes the pancreatic polypeptide hormone. It is thought to play a role in appetite, as well as in the regulation of pancreatic exocrine and endocrine secretions. Pancreatic polypeptide released following a meal may reduce further food consumption; however, it is also released in response to fasting . 8

8. The term diabetes is derived from a Greek word meaning “going through,” and mellitus from the Latin word for “honey” or “sweet. It was the discovery of INSULIN by Banting and Best in 1922 that transformed the once- fatal disease into a manageable chronic health problem. 9

9. Diabetes is a disorder of carbohydrate, protein, and fat metabolism resulting from an imbalance between insulin avail ability and insulin need. It can represent an absolute insulin deficiency, impaired release of insulin by the pancreatic beta cells, inadequate or defective insulin receptor, or the production of inactive insulin or insulin that is destroyed before it can carry out its action. 10

10. Definition Diabetes is a group of metabolic diseases characterized by increased levels of glucose in the blood (hyperglycemia) resulting from defects in insulin secretion, insulin action, or both (American Diabetes Association [ADA], 2016a). 11

11. It is estimated that more than 29.1 million people in the United States have diabetes, although almost one third of these cases are undiagnosed. The number of people older than 20 years newly diagnosed with diabetes increases by 1.7 million per year (Centers for Disease Control and Prevention [CDC], 2014). If this trend continues, one in every three adults in the United States could have diabetes by 2050. In 2014, the worldwide estimate of the prevalence of diabetes was 422 million people, and by 2040, this is expected to increase to more than 642 million (World Health Organization [WHO], 2015a). 12

12. Although diabetes mellitus clearly is a disorder of insulin avail ability, it is not a single disease. A revised system for the classification of diabetes was developed in 1997 by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . 15

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14. ⚫ ⚫ ⚫ Type 1 diabetes affects approximately 5% of adults with the disease (CDC, 2014). Type 1 diabetes is a catabolic disorder characterized by an absolute lack of insulin, an elevation in blood glucose, and a breakdown of body fats and proteins. It is characterized by the destruction of the pancreatic beta cells (Grossman & Porth, 2014). Combined genetic, immunologic, and possibly environmental (e.g., viral) factors are thought to contribute to beta cell destruction. 17

15. If the concentration of glucose in the blood exceeds the renal threshold for glucose, usually 180 to 200 mg/dL (9.9 to 11.1 mmol/L) , the kidneys may not reabsorb all of the filtered glucose; the glucose then appears in the urine (glycosuria). When excess glucose is excreted in the urine, it is accompanied by excessive loss of fluids and electrolytes. This is called osmotic diuresis. 18

16. Idiopathic Autoimmune destruction of pancreatic Islets . Exposure to viruses and other environmental factors Genetics 19

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18. Excessive thirst. Frequent urination, including frequent full diapers in infants and bedwetting in children. Excessive hunger. Unexplained weight loss Fatigue Blurred vision. Slow healing of cuts and sores. Vaginal yeast infections 21

19. ⚫ ⚫ RELATIVE 22 Type 2 diabetes affects approximately 95% of adults with the disease (CDC, 2014). It occurs more commonly among people who are older than 30 years and obese, although its incidence is rapidly increasing in younger people because of the growing epidemic of obesity in children, adolescents, and young adults (CDC, 2014). Type 2 DM describes the presence of hyperglycemia in association with insulin deficiency.

20. ⚫ ⚫ Lifestyle factors, including obesity and a lack of exercise. Genetics, or abnormal genes, that prevent cells from working as they should. 23

21. ⚫ ⚫ he two main problems related to insulin in type 2 diabetes are insulin resistance and impaired insulin secretion. Insulin resistance refers to a decreased tissue sensitivity to insulin. In type 2 DM insulin is less effective at stimulating glucose uptake by the tissues and at regulating glucose release by the liver. 24

22. To overcome insulin resistance and to prevent the build up of glucose in the blood, increased amount of insulin must be secreted to maintain the glucose level at a normal or slightly elevated level . If the beta cells cannot keep up with the increased demand for insulin, the glucose level rises and type 2 diabetes develops. 25

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24. ⚫ ⚫ Clinical manifestations of diabetes include the “ three Ps” : polyuria, polydipsia, and polyphagia. 27 Polyuria (increased urination) and polydipsia (increased thirst) occur as a result of the excess loss of fluid associated with osmotic diuresis. ⚫ Patients also experience polyphagia (increased appetite) that results from the catabolic state induced by insulin deficiency and the breakdown of proteins and fats.

25. Fatigue and weakness Sudden vision changes, Tingling or numbness in hands or feet, Dry skin, Skin lesions or wounds that are slow to heal, and recurrent infections. 28

26. DIABETIC KETOACIDOSIS, HYPEROSMOLAR HYPERGLYCEMIC STATE, AND HYPOGLYCEMIA . . All are life-threatening conditions that demand immediate recognition and treatment . 29

27. ⚫ Hypoglycemia means low (hypo) sugar in the blood (glycaemia) and occurs when the blood glucose falls to less than 70 mg/ dL (3.7 mmol /L). Severe hypoglycemia is when glucose levels are less the 40 mg/ dL (2.5 mmol /L). It can occur when there is too much insulin or oral hypoglycemic agents, too little food, or excessive physical activity 30 ⚫ Hypoglycemia (Insulin Reactions):

28. Diabetic Ketoacidosis : Diabetic ketoacidosis (DKA) most commonly occurs in a person with type 1 diabetes, but it can also effect person with Type 2 DM. DKA is caused by an absence or markedly inadequate amount of insulin. 31

29. ⚫ ⚫ Pathophysiology of DKA: Without insulin, the amount of glucose entering the cells is reduced, and the production and release of glucose by the liver (gluconeogenesis) are increased, leading to hyperglycemia. In an attempt to rid the body of the excess glucose, the kidneys excrete the glucose along with water and electrolytes (e.g., sodium, potassium). This osmotic diuresis, which is characterized by excessive urination (polyuria), leads to dehydration and marked electrolyte loss 32

30. Patients with severe DKA may lose up to 6.5 L of water and up to 400 to 500 mEq each of sodium, potassium, and chloride over a 24-hour period. Another effect of insulin deficiency or deficit is the breakdown of fat (lipolysis) into free fatty acids and glycerol. The free fatty acids are converted into ketone bodies by the liver. Ketone bodies are acids; their accumulation in the circulation due to lack of insulin leads to metabolic acidosis 33

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33. Hyperosmolar Hyperglycemic State: The hyperosmolar hyperglycemic state (HHS) is characterized by hyperglycemia (blood glucose >600 mg/ dL [33.3 mmol /L]), hyperosmolarity (plasma osmolarity >320 mOsm /L) and dehydration, the absence of ketoacidosis. 36

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35. Long-term complications are becoming more common as more people live longer with diabetes; these complications can affect almost every organ system of the body and are a major cause of disability. The general categories of long-term diabetic complications are MACROVASCULAR DISEASEs (i.e., coronary artery, cerebral vascular, and peripheral vascular disease), MICROVASCULAR DISEASE(i.e ., neuropathies, nephropathies, and retinopathies), DIABETIC FOOT. 38

36. Macrovascular Complications Coronary artery disease, cerebrovascular disease, and peripheral vascular disease are the three main types of macrovascular complications that occur frequently in patients with diabetes. MI is twice as common in men with diabetes and three times as common in women with diabetes, compared with people without diabetes. Coronary artery disease accounts for an increased incidence of death among patients with diabetes 39

37. Cerebral blood vessels are similarly affected by accelerated atherosclerosis. People with diabetes have twice the risk of developing cerebrovascular disease and an increased risk of death from stroke Atherosclerotic changes in the large blood vessels of the lower extremities are responsible for the increased incidence (two to three times higher than in nondiabetic people) of occlusive peripheral arterial disease in patients with diabetes (ADA, 2016b). 40

38. ⚫ ⚫ Microvascular Complications Diabetic Retinophy Diabetic retinopathy is the leading cause of blindness among people between 20 and 74 years of age in the United States; it occurs in both type 1 and type 2 diabetes (ADA, 2016b). People with diabetes are subject to many visual complications 41

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40. ⚫ ⚫ Nephropathy, or kidney disease secondary to diabetic microvascular changes in the kidney, is a common complication of diabetes (ADA, 2016b). In the United States each year, people with diabetes account for almost 50% of new cases of ESKD, and about 25% of those require dialysis or transplantation. Nephropathy 44

41. Diabetic neuropathy refers to a group of diseases that affect all types of nerves, including peripheral (sensorimotor), autonomic, and spinal nerves. Diabetic neuropathy 45

42. ⚫ ⚫ . Between 50% and 75% of lower extremity amputations are performed on people with diabetes. Complications of diabetes that contribute to the increased risk of foot problems and infections include the following: Neuropathy: Peripheral vascular disease Immunocompromised Foot and Leg Problems: 46

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44. Pathophysiology concepts of altered health states eighth- edition Brunner Medical and surgical Nursing(14 th Edition) openstax.org/books/anatomy- and- physiology 52