Lecture 18 Flashcards
Pancreas Glands
Exocrine glands (98-99%) - digestion
Endocrine gland (1-2%) – glucose metabolism
Exocrine function
Secretes alkaline pancreatic juice rich in digestive enzymes into the duodenum through the pancreatic duct to aid the digestion of proteins (trypsin and chymotrypsin), carbohydrates (amylase), and fats (lipase)
Endocrine function
Endocrine tissue of the pancreas which consists of multiple small clusters of cells scattered throughout the gland as pancreatic islets, or islets of Langerhans – regulation of blood glucose
Alpha cells
Secrete glucagon; raise blood glucose
Beta cells
Secrete insulin; lower blood glucose
Delta cells
Secrete somatostatin; inhibit secretion of glucagon and insulin
Acute Pancreatitis
Pathogenesis - Blockage (gallstones or alcoholism) but there is an active production of pancreatic juice which results in a buildup and increases pressure in the ducts. Juices will leak into pancreatic tissue which cause destruction of tissue and blood vessels in pancreas. Can manifest as mild/transient disease or lead to severe abdominal pain, multiple organ failure, shock and high mortality.
Acute Pancreatitis Diagnosis and Treatment
Diagnosis – elevated amylase/lipase, ultrasound/CT
Tx –fluids, pain management, antibiotics
Chronic Pancreatitis
Repeated inflammatory episodes (gets worse and worse) which are replaced by scar tissue – are common in chronic alcoholism
Chronic Pancreatitis manifestations
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 and treatment of Chronic Pancreatitis
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
Cystic Fibrosis
Pancreatic fibrosis and cysts present in pancreas; Serious hereditary disease, autosomal recessive trait caused by mutation of CFTR on long arm of chromosome 7 (regulates chloride regulation in cells) - manifests in infancy and childhood ; average lifespan is 40 years (could be more or less depending on the severity of the disease)
Cystic Fibrosis pathogenesis
Defective transport of chloride (decreased secretion), sodium (increased reabsorption), and increased H2O across the 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 very thick and causes obstruction
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
Treatments for Cystic fibrosis
Gene therapy (Future), drugs, bronchodilators, prophylactic treatment with antibiotics, lung transplant
Insulin
Made by pancreas - influences carbohydrate, protein, and fat metabolism on liver cells, muscle, and adipose tissues (main stimulus is high glucose); promotes the entry, use, conversion, and storage of glucose
Type 1 diabetes (8%)
Insulin deficiency and occurs primarily in children and young adults
Type 2 diabetes (90%)
Inadequate response to insulin, Typically, adult-onset, More common than Type 1, Becoming more common in children
Pancreatogenesis diabetes (3% -2%) causes
Pancreatitis (Chronic – Alcohol, CF, obstructive), Pancreatic cancer, Autoimmunity, Trauma/ resection
Prediabetes and treatment
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)
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
Mild hyperglycemia symptoms
Asymptomatic or mild symptoms like fatigue, frequent urination/thirst
Diabetes Mellitus
Very common and important metabolic disease (9% of Canadian population, 25% of over 65yo); 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); glucose leaves body through urine causing chronic dehydration and electrolyte imbalance
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)
Type 1 Diabetes Mellitus
An autoimmune disease (80% non-hereditary) which results from damage to pancreatic islets leading to reduction or absence of insulin secretion. CD8+ T-cells infiltrate and destroy the pancreatic islets, often following a viral infection
Factors that can increase likelihood of developing diabetes
Obesity
Insulin resistance
Blood lipid abnormalities
Hypertension
Type 2 Diabetes Mellitus
Complex metabolic disease – much more common than type 1 (hereditary and population factors included - obesity, etc.); Occurs in older, overweight, or obese adults – spectrum of severity. Reduced response of tissues to insulin (insulin resistance).
Severe hyperglycemia
Blood glucose increases 10 to 20 times normal value
Hyperosmolar Hyperglycemic Nonketotic Coma
Type 2 diabetes complication; Results in coma due to extreme hyperosmolarity of blood (Cells become dehydrated)
Hyperglycemia
Insufficient insulin, blood glucose levels increase
Hypoglycemia
Too much insulin, glucose levels decrease
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), Insulin shock (Excess insulin causes a precipitous drop in blood glucose, leading to insulin reaction), Oral hypoglycemic drugs in type 2 diabetics, Islet cell tumor
Treatment of Diabetes
Diet – control glucose intake (glycemic control), insulin, constantly checking blood glucose and glycosylated hemoglobin measurements, weight management, and oral hypoglycemic drugs
Complications of Diabetes
High blood glucose which can lead to increased susceptibility to infection, Diabetic coma (T1D) – hyper glycemia or ketoacidosis, Hyperosmolar coma (T2D) – hyperglycemia without acidosis, arteriosclerosis, blindness, renal failure, and peripheral neuritis
Pregnancy-Associated Diabetes (Gestational Diabetes) + treatment
High levels of placental hormones raise blood glucose and cause the pregnant woman to be less responsive to insulin (higher risk for obese patients). Higher risk of developing TD2 after delivery. Treat with supplementary insulin if necessary
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 side effects (some diuretics, beta-blockers, corticosteroids (most common), antipsychotics), Hereditary diseases (rare, characterized by disturbed carbohydrate metabolism), Autoimmunity - pancreatic
Carcinoma of the pancreas
Usually develops in the head of the pancreas, Blocks common bile duct Causes obstructive jaundice
90% of pancreatic cancers are adenocarcinoma, and poor prognosis (1 yr survival 25%, 5y survival 5%) since they are usually found in later stages
