Lecture 18 CH22 Pancreas and Diabetes PDF

The Pancreas and Diabetes Mellitus Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives 2. Describe the pathogenesis, manifestations, complications, and prognosis of pancreatic cystic fibrosis. 3. Differentiate between the two pri...

The Pancreas and Diabetes Mellitus Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives 2. Describe the pathogenesis, manifestations, complications, and prognosis of pancreatic cystic fibrosis. 3. Differentiate between the two principal types of diabetes mellitus with respect to pathogenesis, incidence, manifestations, complications, and treatment. 4. Compare and contrast diabetes with metabolic syndrome. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 1. Describe the pathogenesis and treatment of acute pancreatitis. Pancreas Two glands in one Exocrine function: Exocrine tissue of the pancreas, concerned solely with digestion ▪ Secretes alkaline pancreatic juice rich in digestive enzymes into the duodenum through the pancreatic duct to aid digestion of: ▪ proteins (trypsin and chymotrypsin) ▪ carbohydrates (amylase) ▪ and fats (lipase) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Exocrine glands (98-99%) - digestion ▪ Endocrine gland (1-2%) – glucose metabolism Pancreas Consists of multiple small clusters of cells scattered throughout the gland as pancreatic islets, or islets of Langerhans – regulation of blood glucose ▪ Discharge secretions directly into the bloodstream ▪ Each islet is composed of different types of cells ▪ Alpha cells: Secrete glucagon; raise blood glucose ▪ Beta cells: Secrete insulin; lower blood glucose ▪ Delta cells: Secrete somatostatin; inhibit secretion of glucagon and insulin Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Endocrine function: Endocrine tissue of the pancreas Pancreas Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 22-1 (A) Duct system of pancreas. The main pancreatic duct usually joins the common bile duct to form a common channel that enters the duodenum by a single opening at the apex of a nipplelike projection called the duodenal papilla (ampulla of Vater). A much smaller accessory pancreatic duct is frequently present and opens into the duodenum by a separate opening proximal to the duodenal papilla. Pancreas (B) Courtesy of Leonard V. Crowley, MD, Century College. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 22-1 (B) A photomicrograph of pancreatic islet surrounded by exocrine pancreatic tissue. Acute Pancreatitis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pathogenesis -Blockage ▪ Active production of pancreatic juice despite obstruction ▪ Resulting buildup of pancreatic juice increases pressure within the duct system, causing ducts to rupture and enzymes spread into tissues ▪ Escape of pancreatic juice from the ducts into pancreatic tissue ▪ Pancreatic digestive enzymes cause destruction of tissue and blood vessels in pancreas (possibility of severe hemorrhage) ▪ Leakage of enzymes (amylase/lipase) into blood can be detected ▪ Can manifest as mild/transient disease or lead to severe abdominal pain, multiple organ failure, shock and high mortality. Acute Pancreatitis Gallbladder disease or gallbladder stones ▪ Common bile duct and common pancreatic duct enter the duodenum via the ampulla of Vater ▪ Impacted stone in ampulla obstructs pancreatic duct Alcoholism excessive alcohol consumption ▪ Potent stimulus for pancreatic secretions ▪ Induces edema and spasm of pancreatic sphincter in ampulla of Vater ▪ Results in high intraductal pressure, duct necrosis, and escape of pancreatic juice Can also be due to trauma, infectious, surgery, CF, (endoscopy-ERCP) or idiopathic causes Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Upper abdominal pain ULQ (severe -radiating to back), nausea, vomiting Diagnosis – elevated amylase/lipase, ultrasound/CT Tx –fluids, pain management, antibiotics Chronic Pancreatitis Repeated inflammatory episodes – common in chronic alcoholism ▪ Inflammation subsides and damaged pancreatic tissue is replaced by scar tissue, leading to progressive destruction of pancreatic tissue Manifestations (In addition to) acute attack symptoms ▪ Difficulty digesting and absorbing nutrients (nutrient deficiency) ▪ Not enough surviving pancreatic tissue to produce adequate enzymes ▪ Destruction of pancreatic islets may lead to diabetes ▪ Can form blockage of bile duct and associated symptoms of cholestasis Diagnosis: Elevated amylase/lipase in blood (often not seen in chronic pancreatitis), Xray – calcification, CT scan – calcification, inflammation, necrosis or cancer (risk for adenocarcinoma) Treatment: Pain management, IV hydration, pancreatic enzyme supplements - Removal Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Each episode destroys some pancreatic tissue Cystic Fibrosis Terminology refers to pancreatic fibrosis and cysts present in pancreas CFTR highly expresses in Pancreatic duct epithelia – organ is affected earliest and with most severity by CF compared to other affected organs. Spectrum of disease severity, depending on extent and locations of gene mutations (360 identified as disease causing) – average 40y Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Serious hereditary disease, autosomal recessive trait caused by mutation of CFTR (CF transmembrane conductance regulator), on long arm of chromosome 7 (regulates chloride regulation in cells) - manifests in infancy and childhood Cystic Fibrosis Pathogenesis (affects mucous secreting cells throughout the body) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Defective transport of chloride (decreased secretion), sodium (increased reabsorption), and increased H2O across cell membrane ▪ Results in deficient electrolyte concentrations and H2O in the mucus secreted by the pancreas, bile ducts, respiratory tract, and other secretory cells ▪ Mucus becomes abnormally thick; precipitates; and forms dense plugs that obstruct the pancreatic ducts, bronchi, bronchioles, and bile ducts ▪ Obstruction causes damage/inflammation leading to progressive fibrosis of glandular tissues in the pancreas ▪ Obstruction of pancreatic ducts: Causes atrophy and fibrosis (85% exhibit chronic pancreatitis) – leads to maldigestion/malnutrition – also destruction of exocrine tissues ▪ Obstruction of bronchi: Causes lung injury, susceptibility to infection ▪ Obstruction of biliary ducts: Causes liver scarring ▪ Abnormal function of sweat glands: Unable to conserve sodium and chloride with excessively high salt concentration in sweat; basis of diagnostic test for CF Cystic Fibrosis Treatments: future gene therapy? ▪ drug combinations used to assist airway clearance therapy(physical therapy to assist the removal of mucous collection in lungs) ▪ Prophylactic treatment with antibiotics – prevent chronic/repeated lung infections ▪ Lung transplant may eventually be required if lungs are severely damaged over time Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Drugs - improve CFTR gene function and thin mucous, bronchodilators Insulin Main stimulus for release is high glucose in blood (after a meal) Promotes ▪ Entry of glucose into cells (carrier that is required for cellular uptake) ▪ Utilization of glucose as source of energy ▪ Storage of glucose as glycogen ▪ Conversion of glucose into triglycerides ▪ Storage of newly formed triglyceride in fat cells ▪ Entry of amino acids into cells and stimulates protein synthesis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Made by pancreas - influences carbohydrate, protein, and fat metabolism on liver cells, muscle, and adipose tissues Type 2 diabetes (90%) ▪ Inadequate response to insulin ▪ Typically, adult-onset ▪ More common than Type 1 ▪ Becoming more common in children Pancreatogenesis diabetes (3c -2%) ▪ Pancreatitis (Chronic – Alcohol, CF, obstructive) ▪ Pancreatic cancer ▪ Autoimmunity ▪ Trauma/ resection Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Two major groups, depending on cause Type 1 diabetes (8%) ▪ Insulin deficiency ▪ Occurs primarily in children and young adults Prediabetes ▪ Mild hyperglycemia: asymptomatic or mild symptoms like fatigue, frequent urination/thirst ▪ Indication that weight loss, exercise, healthy eating habits are needed to improve or diabetes can occur ▪ Pharmacologic treatment (metformin) ▪ Glucose tolerance can be improved with alpha-glucosidase inhibitors (oral pill) ▪ Reduces sugar mobilization from liver and improves insulin resistance ▪ Decreases glucose absorption in intestine Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Number of insulin-producing beta cells is beginning to decline – not enough to cause disease, may develop in the future (50% of people over 65) Diabetes Mellitus Very common and important metabolic disease (9% of Canadian population, 25% of over 65yo) Excess glucose (normal range 60-100 mg/dl) is eliminated in urine and pulls water and electrolytes along with it leading to chronic dehydration and electrolyte imbalance Hyperglycemia also impacts carbohydrate, fat and protein metabolism that can cause acute life-threatening disease and serious chronic disease of multiple organ systems (cardiovascular, kidney, eyes and nervous system) Ketoacidosis: Metabolism relies on adipose (fat) stores exclusively and can lead to metabolic acidosis (diabetic ketosis), a serious condition that can cause cardiac (abnormal rhythm -VT), respiratory (Kussmaul – starts rapid and shallow and becomes deep/labored as acidosis worsens) and neurological symptoms (lethargy, coma, seizures) Also contributes progression of CKD, cardiovascular disease, bone and muscle wasting Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Glucose is absorbed by intestines normally but is not used properly for energy due to insulin deficiency or insensitivity – glucose is unable to enter cells and accumulates in blood (hyperglycemia) Type 1 Diabetes Mellitus Results from damage to pancreatic islets leading to reduction or absence of insulin secretion ▪ Abnormal humoral immune response may play a part: Production of autoantibodies directed against islet cells ▪ Variable progression – once 80% of islet tissue is destroyed – disease onset ▪ Hereditary predisposition though certain polymorphisms in HLA –DQ and DR types (common in 40-50% of hereditaryT1D) ▪ 80% of cases are not hereditary Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Autoimmune disease where CD8+ T cells infiltrate and destroy the pancreatic islets, often follows a viral infection Diabetes and Metabolic Syndrome ▪ Obesity ▪ Insulin resistance ▪ Blood lipid abnormalities ▪ Hypertension Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Group of conditions identified in person with impaired glucose tolerance that can progress to diabetes–associated complications and cardiovascular disease Type 2 Diabetes Mellitus Complex metabolic disease – much more common than type 1 ▪ Increasingly seen among younger people who are overweight or obese ▪ Insulin secretion can be normal or increased ▪ Reduced response of tissues to insulin (insulin resistance) ▪ Islet function is not completely normal because pancreas is not able to increase insulin output to compensate for the insulin resistance ▪ Resistance not well understood – seem tied to adipose tissue quantity as weight reduction restores insulin sensitivity ▪ Hereditary factors (spectrum – multiple (over 200 most associated with obesity risk) play greater role than T1D, children of parents with diabetes are at a significant risk (70%) ▪ Incidence in some populations as high as 40% (in some first nations communities) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Occurs in older, overweight, or obese adults – spectrum of severity Hyperosmolar Hyperglycemic Nonketotic Coma Severe hyperglycemia ▪ Blood glucose increases 10 to 20 times normal value Absence of ketosis ▪ Less insulin is required to inhibit fat mobilization than is needed to promote entry of glucose into cells ▪ Patients have enough insulin to prevent ketosis, not enough to prevent hyperglycemia Results in coma due to extreme hyperosmolarity of blood ▪ H2O moves out of the cells into the extracellular fluid ▪ Cells become dehydrated, disturbing functions of neurons and leading to coma Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Type 2 diabetes complication Hypoglycemia in Diabetes Diabetic patients must adjust dose of insulin to match the amount of ingested carbohydrate ▪ Insufficient insulin, blood glucose levels increase (hyperglycemia) ▪ Too much insulin, glucose levels decrease (hypoglycemia) Conditions predisposing to hypoglycemia in a diabetic patient taking insulin ▪ Skipping a meal: Carbohydrate intake is insufficient in relation to amount insulin and blood glucose falls ▪ Vigorous exercise: With high physical activity there is high glucose utilization; excess insulin ▪ Excess insulin causes a precipitous drop in blood glucose, leading to insulin reaction (insulin shock) Neurologic manifestations appear if blood glucose continues to fall (lethargy, confusion, LOC, seizures) Other causes of hypoglycemia: Oral hypoglycemic drugs in type 2 diabetics, Islet cell tumor Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pancreas regulates the glucose in blood by adjusting its output of insulin to correspond with blood sugar levels ▪ Adrenal medulla can also respond by discharging epinephrine that raises blood glucose by converting glycogen (liver, muscles) to glucose Insulin Shock versus Hyperosmolar Coma Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Treatment of Diabetes Diet – control glucose intake (glycemic control), insulin Type 1 diabetes: Requires insulin; dosage adjusted to control level of blood glucose Type 2 diabetes ▪ Management: Weight reduction and diet ▪ Oral hypoglycemic drugs if patient does not respond adequately to diet and exercise regimen (metformin) ▪ May require insulin (as disease progresses) or other drugs to control hyperglycemia Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Goal: Achieve control of blood glucose as close as possible to normal ▪ Frequent periodic measurements of blood glucose (finger stick before/after meals, exercise) ▪ Use small sensor inserted under the skin coupled to a glucose pump or “artificial pancreas” ▪ Urine test: Detects glucose spilling into the urine when blood glucose is too high ▪ Measurement of glycosylated hemoglobin (RBC last 3-4 months: Serves as an index of long-term control of hyperglycemia (normal 6%, controlled 7%, poor is over 8%) Complications of Diabetes High blood glucose: -Diabetic coma (T1D) – hyper glycemia or ketoacidosis ▪ Ketoacidosis – from increased fat metabolism, metabolic acidosis Hyperosmolar coma (T2D) – hyperglycemia without acidosis ▪ Arteriosclerosis – from elevated blood lipids increased cardiovascular incidents ▪ Blindness –retinal blood vessel degeneration ▪ Renal failure – damage to vascular system from hyperglycemia, lipids ▪ Peripheral neuritis – damage to vascular system Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com -Increased susceptibility to infection Pregnancy-Associated Diabetes Gestational Diabetes: high level of placental hormones raise blood glucose and cause the pregnant woman to be less responsive to insulin ▪ Human placental lactogen (HPL), Human chorionic somatomammotropin (HCS) ▪ Most women secrete more insulin to compensate ▪ Those who cannot secrete more insulin develop pregnancy-related diabetes ▪ Treatment is diet with supplementary insulin if necessary ▪ Returns to normal after delivery – associated with increased T2D disk development Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Increased risk of development for obese patients Other causes of hyperglycemia ▪ Chronic pancreatic disease: Damage or destruction of pancreatic islets ▪ Endocrine diseases: Overproduction of pituitary or adrenal hormones that raise blood glucose ▪ Drugs that impair glucose utilization as a side effects (some diuretics, beta blockers, corticosteroids (most common), antipsychotics) ▪ Hereditary diseases (rare) characterized by disturbed carbohydrate metabolism ▪ Autoimmunity - pnacreatic Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Conditions that impair glucose utilization, but are less common than diabetes: Tumors of the Pancreas Islet cell tumors ▪ Benign – don’t tend to spread/metastasize (paraneoplastic disease) ▪ Disease not related to tumor growth, but characterized by factors synthesized from tumor cells ▪ Beta cell tumors produce hyperinsulinism (insulin secreting tumors) resulting in hypoglycemia Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Carcinoma of the pancreas, usually develops in the head of the pancreas ▪ Blocks common bile duct ▪ Causes obstructive jaundice ▪ 90% pancreatic cancers are adenocarcinoma ▪ poor prognosis (1 yr survival 25%, 5y survival 5%) Tumors elsewhere in pancreas: No specific symptoms, usually far advanced when first detected The Pancreas and Diabetes Mellitus Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com.