NURS 7053 Endocrine Function PDF

NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Physiology Review Insulin Produced by beta cells in the Islets of Langerhans Influences carbohydrate and lipid (and to some degree prote...

NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Physiology Review Insulin Produced by beta cells in the Islets of Langerhans Influences carbohydrate and lipid (and to some degree protein) metabolism Peptide hormone – Short half-life; any insulin secreted will be cleared in 15 minutes Synthesis Preproinsulin Proinsulin – A, B and C peptides (insulin precursor) Insulin – bonded A and B peptides C-peptide Used as an index for insulin level measurement May play a role in slowing complications diabetes mellitus Secretion Stimulated by increased plasma levels of glucose (and amino acids, free fatty acids) Inhibited by low plasma glucose levels and high levels of insulin FYI - Other stimuli include GI hormones (gastrin, CCK, secretin) and parasympathetic stimulation 1  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Action on cells See Figure 21-15 on page 676 (9th Ed) Receptors for insulin are on plasma membrane of almost all cells Insulin receptors have two alpha sub units (bind to insulin) and 2 beta subunits (tyrosine kinase component) Insulin binds to its receptor, which activates tyrosine kinase which in turn activates a number of intracellular enzymes (e.g., protein kinase B and MAP kinase) to stimulate the range of physiological effects (see below) Binding of insulin to its receptor also directly stimulates glucose uptake via the tyrosine kinase pathway Glucose transporter proteins (GLUT4) are required for facilitated diffusion of glucose into cells General physiological effects Control of postprandial plasma glucose levels Promotes glucose storage as glycogen 2  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes General physiological effects (continued) Fatty acid synthesis and triglyceride formation Transport of amino acids into cells and stimulates protein synthesis Stimulates cell growth and differentiation Facilitates K+ transport into cells Glucagon Insulin antagonist secreted by the alpha cells in the islets Secretion Glucagon release is primarily stimulated in response to decreased plasma glucose levels Physiological effects Note: Little circulation beyond liver Promotes glycogenolysis and gluconeogenesis to raise blood sugars as well as lipolysis and ketogenesis 3  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Diabetes Mellitus A group of disorders associated with alterations in insulin activity resulting in chronic glucose intolerance, as well as alterations in protein and lipid metabolism. Diagnostic Criteria American Diabetes Association HbA1c > 6.5% FPG > 126 mg/dl (7.0 mmol/L); fasting is defined as no caloric intake for at least 8 hours) OR 2-hr plasma glucose > 200 mg/dl (11.1 mmol/L) during an OGTT OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose > 200 mg/dl (11.1 mmol/l) Type 1 Diabetes Mellitus (DM) Previously known as insulin-dependent diabetes mellitus or juvenile onset diabetes Types Autoimmune-mediated Type 1A DM Βeta-cell destruction usually leading to absolute insulin deficiency Appearance of autoantibodies and cytotoxic T cells that target beta cells and insulin Causes Genetics Environmental factors – viral infection, diet (low vitamin D, nitrates, early introduction of gluten) 4  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Nonimmune-mediated Type 1B DM Βeta-cell destruction usually leading to absolute insulin deficiency No evidence of autoimmune disease Causes: other diseases such as chronic pancreatitis, cystic fibrosis... Pathophysiology Destruction of pancreatic beta cells leads to insulin deficiency Alpha cells are uninjured leading to relative glucagon excess Decreased glucose uptake into cells Hyperglycemia (need destruction of 80-90% of beta cells to see hyperglycemia) Cell starvation 5  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Osmotic diuresis: renal tubules reach their transport maximum for glucose reabsorption Decreased potassium uptake into cells leads to hyperkalemia Fat breakdown in adipose tissue Liberation of fatty acids for fuel Release of ketones Lowers pH of blood, potentially leading to ketoacidosis 6  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Type 2 Diabetes Mellitus Previously known as non-insulin-dependent diabetes or adult onset diabetes Risk Factors Genetics: Multiple types of mutations have been identified (e.g., genes that code for insulin synthesis, insulin receptors, cell responsiveness to insulin, etc… see p. 702, 9th Ed) Obesity (increases risk 10 fold) (see figure 23.1, page 726, 9th Ed) Age > 40 years Ethnicity: increased incidence among Native American, Hispanic/Latino, Pacific Islander, and African American populations Polycystic ovarian syndrome (7-fold increase in risk) Metabolic syndrome: central obesity, dyslipidemia, elevated blood pressure, and elevated fasting blood glucose level 7  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Pathophysiology Development of insulin resistance (decreased cellular responsiveness to insulin) Genetics and/or high caloric/carbohydrate diet causes hyperinsulinemia which leads to down-regulation of insulin receptors In obese individuals, release of adipokines by adipose cells also stimulates insulin resistance Decreased glucose uptake leads to hyperglycemia and associated complications (osmotic diuresis, hyperosmolarity, etc) Development of dyslipidemia (high LDL & triglycerides, low HDL) Insulin resistance in adipose cells results in lipolysis Release of fatty acids into the bloodstream eventually leads to hyperlipidemia By the time type 2 DM is diagnosed, dyslipidemia is usually present Eventually hyperglycemia, presence of adipokines and other factors cause beta cell destruction, which leads to decreased insulin secretion 8  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Chronic Complications of Diabetes Mellitus Chronic complications are related to chronic hyperglycemia regardless of type of diabetes Pathophysiology Hyperglycemia and nonenzymatic glycosylation Nonenzymatic glycosylation = binding of glucose to proteins, lipids and nucleic acids without presence of certain enzymes With chronic or persistent hyperglycemia, glucose becomes irreversibly bound to these molecules in the RBCs, endothelial cells lining the blood vessels, and other tissues. Hemoglobin glycosylation – The HgbA1c test measures the build up of glucose that has become irreversibly bound to hemoglobin in the circulating RBCs Hyperglycemia leads to the formation of advanced glycosylation end-products (AGE) that cause the following problems: § Capillary basement membrane thickening Leads to decreased gas exchange between the capillary and tissues § Increased capillary permeability Leads to edema which reduces oxygen delivery to the cells. § Arterial smooth muscle proliferation Leads to thickening of arterial walls and eventually hypertension. § Production of oxygen free radicals Cause endothelial cell injury and injury to cells in the tissues. § Inactivation of nitric oxide – a vasodilator Vasoconstriction of the arteries leads to hypertension. Vasoconstriction in the arterioles leads to ischemia. § Promotion of coagulation Clot formation in capillaries leads to ischemia. Clot formation in the veins leads to DVT. 9  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Shunting of Glucose to the Polyol Pathway Use of glucose via the polyol pathway occurs in tissues that do not use insulin for glucose transport (CNS neurons, lens of eye, RBCs) Hyperglycemia causes more glucose to be shunted through the polyol pathway Glucose is converted to sorbitol, which increases osmotic pressure in these cells Leads to cell swelling and injury Cataracts Disruption of nerve conduction RBCs become swollen & stiff Inappropriate Protein Kinase C (PKC) Activation Promotes insulin resistance Increases capillary permeability Increases basement membrane thickening Promotes vasoconstriction 10  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Microvascular Disease Severity related to age, duration of diabetes, and blood glucose control Pathophysiology involves AGE’s, polyol pathway use, PKC activation Retinopathy See Figure 22-15, page 712, 9th Ed Caused by retinal ischemia – vessel thickening and clotting Infarcts of nerve layer of the retina Sometimes see retinal detachment or hemorrhages Nephropathy See Figure 22-16, page 713, 9th Ed Mechanisms of renal glomerular & tubular destruction are unknown (probably patho described above) See intraglomerular hypertension, basement membrane thickening, and glomerulosclerosis Proteinuria/albuminuria (first clinical sign), then develops into chronic renal failure and eventually ESRD 11  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Macrovascular Disease - Atherosclerosis Premature onset related to hyperglycemia and dyslipidemia AGE’s cause endothelial injury Dyslipidemia: Low HDL, increased LDL as well as facilitated deposition of lipids Clinical Consequences Coronary artery disease Myocardial ischemia leading to heart failure Myocardial infarction Cerebral infarct (stroke) Renal arterial stenosis leading to chronic renal failure Intestinal vascular insufficiency Peripheral arterial disease leading to skin ulceration Peripheral arterial disease leading to gangrene and amputation Neuropathies Peripheral neuron dysfunction Pathophysiology involves polyol pathway use, AGE’s, PKC activation Results in: Ischemia of peripheral neurons Axonal degeneration Demyelination of neurons - conduction velocity of neuron is impaired 12  NURS 7053 – Advanced Pathophysiology for DNP Students Alterations of Endocrine Function I - Class Notes Clinical Consequences Sensory deficits – loss of sensation with tingling, burning and numbness Motor deficits – alterations in gait and strength Autonomic dysfunction Diarrhea (parasympathetic) Orthostatic hypotension (sympathetic) Increased Risk of Infection Micro- and macrovascular changes lead to decreased perfusion to tissues and skin breakdown Impaired vision and sensation - fail to notice wounds or infections Pathogens multiply rapidly because there is a lot of glucose Decreased perfusion decreases WBC supply to infected area WBC function is impaired 13