WEEK+4+Endocrine+and+Vascular

__//**4. Compare and contrast how the endocrine and nervous systems function together to maintain homeostasis. (Heuther, 424,429-431)(Lewis, 1238)**//__

Hormones convey special regulatory info among cells and organs and are integrated with the nervous system to maintain communication and control. Mechanisms to regulate hormonal release • Endocrine factors (blood sugar or calcium levels) • Neural control (From the hypothalamus receiving input from brainstem and limbic system) The **hypothalamic-pituitary unit** forms the structural and functional basis of central integration of the neurological and endocrine systems. Neurosecretory cells in the hypothalamus secrete releasing/inhibiting hormones that regulate secretion by other glands. The hypothalamus also makes the hormones that are stored in the posterior pituitary (ADH, Oxytocin). Pain, emotion, sexual excitement and stress can stimulate the nervous system to initiate hormone secretion. Secretion is initiated by the CNS and implemented by the SNS: i.e. Stress is sensed by CNS and the SNS secretes catecholamine that increases heart rate and BP

__//**5. Discuss the effects of thyroid hormone (T3, T4) and the mechanisms of thyroid hormone regulation. (Heuther 432-434) (Lewis, 1240-1241)**//__

Thyroid hormone (TH) is either T3 or T4 and needs iodine for it to be synthesized. TH affect: Metabolic rate, caloric requirements, oxygen consumption, carb and lipid metabolism, growth and development, brain function, and other nervous system activities.
 * T4** (thyroxine)-__//most abundant//__ (90% produced by thyroid gland) gets converted into T3
 * T3** (Triiodothronine)- __//much more potent//__ (20% produced by thyroid the rest is from T4 conversion)

Thyrotropin-releasing hormone (TRH) from the hypothalamus leads to Thyroid stimulating hormone (TSH) from the anterior pituitary leads Thyroid hormone (TH) from thyroid released.

All controlled by a negative feedback system. When circulating TH is low the hypothalamus releases TReleasingH which stimulates the pit to release TStimulatingH which goes to the thyroid to release more ThyroidH. High TH inhibits secretion of both TRH and TSH

TSH also increases the uptake of iodine, which is used to make TH

Islets of Langerhans innervated by both Para and sympathetic divisions of the ANS
 * //__6. Identify the hormones secreted by the alpha, beta, and delta cells of the pancreas and discuss their major functions. (heuther, 435-436) (Lewis, 1241-1242)__//**


 * Alpha- Glucagon**

• **increases blood glucose** by stimulating glycogenolysis (break down of glycogen to glucose) and gluconeogenesis (making glucose) in muscle • increases blood glucose by stimulating lipolysis(ketogenosis) in adipose tissue • Antagonist to insulin, stimulated by sympathetic division • Amino acids (alanine, glysine, and asparagines) stimlate glucagons secretion

**Beta-insulin**
• Is an anabolic (storage) hormone that **promotes glucose uptake** **and metabolism of proteins, carbs, fats, and nucleic acids** • regulated by chemical, hoemaonal, and nueral control • secreted when blood levels of glucose, amino acids(arginine, lysine) and GI hormones (glucagons, gastrin, cck, secretin) are increased • secreted when beta cells are stimulated by parasympathetic system • diminishes in response to low blood sugar(hypoglycemia), high insulin levels(through negative feedback), and sympathetic stimulation of alpha cell • combines with receptors which sends out signals to activate glucose transporters for entry of glucose into cells to keep range at **70-120 mg/dl** • Functions mainly in the liver, muscle, and adipose tissue (heuther 17-7 438)

**Beta- Amylin**
• Co-secreted with insulin in response to nutrient stimulus • Regulated blood glucose by delaying uptake and **suppressing glucagon** secreation after meals • Has a satiety effect • Has a antihyperglycemic effect

**Delta- somatostatin**
• Regulates alpha & Beta cell function w/in the islets by **inhibiting secretion of insulin and glucagon**

__//**7. Differentiate in the onset, etiology, pathophysiology, clinical manifestations of type 1 and type 2 diabetes mellitus.(Huether, 462-465) (Lewis, 1255-1257)**//__

**Type 1**
• Peaks at 12 years of age but occurs in people under 30 • Has a long pre-clinical period while b-cells are destroyed (months to years) • Once 80-90% reduction of b-cell funtion happens signs of hyperglycemia are usually rapid with end result being ketoacidosis • A genetic predisposition with certain HLA (human leukocyte antigens) • These people may also be exposed to a virus which causes b-cell destruction • This is called type 1A being caused by an immune mechanism • Autoantobodies to the islet cells cause destruction of b-cells • Severe, absolute lack of insulin • Glucose get not get into cells which causes hyperglycemia and ketonemia • Amylin (produced by b-cells) also is destroyed. Amylin suppresses glucagon release from A-cells • Lack of insulin and excess of glucagon cause the full metabolic syndrome
 * Onset:**
 * Etiology**
 * Patho**

• Recent history of weight loss, polydipsia (thirst), polyuria (pee), polyphagia(eat) • Glucose in urine • Proteins and fats break down due to lack of insulin cause weight loss • Ketoacidosis caused by increase metabolism of fats & proteins • Metabolic acidosis with respiratory compensation resulting in blowing off ketones with fruity smelling breath
 * Clinical manifestations (Huether,18-5 464) READ THIS TABLE**

**Type 2**
• Ususally gradual, may go for years undetected with few symptoms
 * Onset:**

• Primarily peple over 40 risk increases with age • Obesity, especiall abdominal and visceral adiposity • Family history is gaining significance • Metabolic syndrome
 * Etiology:**

Four major metabolic abnormalities lead to type 2 • **Insulin resistance-** body tissues dont respond to the action of insulin due to receptors that are insuffient in numbers or ineffectivness (insulin receptors are located on skeletal muscle, liver and fat cells. Early stages of insulin resistance the b-cells respond to high circulating glucose by producing more insulin (while they still can) leading to hyperinsulinemia • **Decreased ability for production of insulin**- B-cells become fatiqued from overproduction of insulin or when b-cell mass is lost (may be caused by hyperglycemia or free fatty acids that are toxic to B-cells) • **Inappropriate glucose production by the liver**- Liver is haphazardly regulating the release of glucose (**not a primary factor**) • **Alteration in the production of hormones and cytokines by adipose tissue (adipokines)-** A variety of cytokines (IL-1b, TNF) are toxic to b-cells. Abdominal fat produces these cytokines
 * Patho:**

• Recurrent infections, prolonged wound healing • Genital pruritus • Visual changes • Parethesia • fatigue
 * Clinical manifestations (Heuther, 18-6 465) READ TABLE**

__//**8. Examine in detail the pathophysiology of diabetic ketoacidosis (DKA) in relation to the following processes:**//__


 * -insulin deficiency**: Insulin not available, therefore cells cannot use glucose, liver responds b/c it perceives deficiency in muscle cells. Glycogenolysis leads to glycogen which leads to glucose production
 * -gluconeogenesis:** it is initiated by the increase in glucose in the cells. Sensed by anteriour pituitary which sends out corticotropins, stimulates adrenal cortex to release glucocorticoids, Cortisol is released which increases gluconeogenesis and formation of glycogen from non-CBH sources in the liver. Stres hormones (Epi & glucagon) are released & stimulate glycogenolysis. Lipolysis occurs which is stimulated by a lack of insulin. Adipose tissue breakdown leads to FFA, liver converts to glucose (gluconeogenesis). Fats are broken down faster than utilized leads to ketones. These break apart & form H+ ions. This alters pH which leads to metabolic acidosis.
 * -hyperglycemia & osmotic dieresis**: Glycosuria occurs b/c renal threshold exceeded. This leads to osmotic diuresis b/c glucose goes w/fluid (increase glucose = increase osmotic pull), thus H2O pulled from vascular space leading to hypovolemia and dehydration. Increased blood viscosity and platelet aggregation lead to thromboembolism, decreased tissue perfusion. Anaerobic metabolism causes increased lactic acid & exacerbates the acidosis.

__//**9. Relate the clinical manifestations to the underlying pathophysiology of DKA.**//__
 * Hyperglycemia-** BS>250-300 mg/dL (this could be seen higher). **Glycosuria** occurs which increases serum osmolality. The 3 P’s take place; Kussmal respirations, dizziness, CNS depression, also seen are anorexia, nausea, and abdominal pain. Hemoconcentration and dehydration are observed. Electrolyte imbalances related to the degree of patient’s dehydration. A decrease in HCO3, Na, Mg, Ca, PO4, pH. An increase in K is seen w/mild dehydration, a decrease in K is seen with severe dehydration. Azotemia occurs which is the build up of nitrogenous wastes b/c the kidneys can’t keep up (albumin & creatinine tests used). The anion gap will be HIGH w/DKA.

(HHNS) and relate the clinical manifestations to the underlying pathophysiology. Common in the elderly and fatal w/out Rx. It is basically DKA w/out ketosis, therefore **no ketones involved.** High mortality-40-70%, seen w/Type II DM, onset of days**. Patho**: a decreased amount of insulin & counterregulatory hormones. Minimal lipolysis, therefore minimal ketosis. Glycogenolysis & protein breakdown decreased and a decreased use of glucose is observed. Some FFA go to the liver but still very few ketones. Hyperglycemia present w/osmotic diuresis that is more profound (as much as 8-12 L could be lost, leading to extreme dehydration & electrolyte imbalance!). Clinical **Manifestations:** The 3 P’s, progressive dehydration followed by HOTN observed w/dry mm, sunken eye, decreased skin turgor, decreased central venous pressure. Lethary is the common chief complaint, accompanied by confusion, seizure activity. Also seen are fatigue, wt loss, weakness, aphasia & hallucinations. S/S related to ACS are renal failure & brain attack b/c decreased circulation. Serum glucose of >800mg/dL & serum osmolality >350 mOsm/L (b/c of fluid loss!). A decreased GFR, an increased Hgb & Hct also due to fluid loss. HHNS can mimic other diseases/conditions and lead to misDx. Client may tolerate fatigue or vague symptoms for weeks before intervention occurs.
 * //__10. Examine in detail the pathophysiology of hyperglycemia hyperosmolar nonketotic syndrome__//**
 * //__11. Describe the function, uses, and mechanisms of the polyol pathway.__//**( Heuther 467)

Tissues that don’t require insulin for glucose transport, such as kidney, RBCs, blood vessels, eye lens, and nerves, use an alternate metabolic pathway for glucose metabolism known as the polypol pathway. W/hyperglycemia, glucose is shunted to this pathway and is converted to sorbitol (a polyol) by the enzyme aldose reductase. Sorbitol is then only very slowly converted to fructose by sorbitol dehydrogenase. The resulting accumulation of sorbitol increases intracellular osmotic pressure & attracts H2O, leading to cell injury. This is particularly evident in the lens of the eye & leads to swelling w/visual changes & cataracts. In nerves, sorbitol interferes w/ion pumps, damages Schwann cells, & disrupts nerve conduction. RBCs become swollen & stiff & interfere w/perfusion. Aldose reductase inhibitors have been studied in humans, but their clinical utility has been severely hampered by serious side effects. 1**//__2. Analyze both the microvascular and macrovascular complications associated with diabetes mellitus and discuss how good control of blood glucose limits the cellular degeneration in each instance.__//** 13. Analyze the pathophysiology, etiology, clinical manifestations, and collaborative management and incidence of a client with hypothyroidism. __** (M/S p1305, patho p 456, Mod 9 #4b,k-p) In primary hypothyroidism, loss of thyroid tissue leads to decreased production of TH, increased secretion of TSH, and goiter. Secondary hypothyroidism is usually caused by the pituitary's failure to synthesize adequate amounts of TSH. Pituitary tumors or the results of their treatment are the most common causes of secondary hypothyroidism.
 * Both are longterm complications!!!
 * Microvascular Complications** are related to small vessels & correlate w/retinopathy (eye problems) & nephropathy (kidney problems leading to a loss of protein in urine b/c the basement membrane is damaged in the kidney). Patho: Glycosylation occurs w/as excess glucose binds to collagen & proteins. The rate of glycosylation is proportionate to hyperglycemia. Walls of the blood vessels are permanently altered & hardening & thickening of the capillary basement membrane is seen leading to obstruction or rupture of caps. Necrosis & loss of fxn of those tissues involved is observed. Accumulation of sorbitol leads to intarcellular osmotic pressure increase thus setting patient up for glaucoma & cataracts. The accumulation of sorbitol is derived from metabolism of excess glucose by enzyme aldose reductase. Microalbuminuria is the first manifestation of renal dysfuction. Diabetes, HTN, & elderly status increases the risk for renal, CV morbidity & mortality. Nml albuminuria <30 mg and Microalbuninuria is 30-300mg, however it should be <10mg/day b/c of more preventative measures. Treatment w/ACE inhibitors to prevent vasoconstriction & promote vasodilation to the kidneys. Shown to decrease progression of neuropathy. Death from renal failure is much more common in individuals w/type I DM than in those w/type II DM b/c the appearance of proteinuria in these individuals is strongly correlated w/death from cardiovascular disease.
 * Macrovascular Complications** involved w/large vessels. The risk of coronary artery disease for those w/diabetes is higher than for the general population even when HTN & hyperlipidemia are taken into account. CAD is the most common cause of death in individs w/type 2 DM b/c of insulin resistance, high levels of LDLs and triglycerides, low levels of HDLs, platelet abnormalities, and endothelial cell dysfxn. Mortality high for men and women. Cerebrovascular Disease (stroke) is twice as common in those w/diabetes as in the nondiabetic population. Survival rate for diabetics after a stroke is lower than that of nondiabetic population. Peripheral Vascular disease has increased incidence in individuals w/diabetes along w/gangrene & amputation. Many diabetics are more likely to have atherosclerosis that appears at a younger age & advances more rapidly than vascular changes in nondiabetic persons. Age, duration of diabetes, genetics, and additional risk factors influence the development of PVD. B/c of occlusions of the small arteries & arterioles, most of the gangrenous changes of the lower extremities occur in patchy areas of the feet & toes. The lesions begin as ulcers & progress to osteomyelitis or gangrene requiring amputation. Significant morbidity & mortality are associated w/major amputation.
 * Good control of blood glucose can decrease cellular damage and decrease microvascular & macrovascular deterioration.
 * __
 * __ Pathophysiology __** (see algorithm on #4k, MOD 9)
 * __ Etiology __**
 * Hypothyroidism ** is a condition that results from inadequate levels of thyroid hormone. It can be caused by primary diseases of the thyroid gland or secondary to pituitary failure.

In **primary hypothyroidism**, the inability of the gland to produce thyroid hormone means that the negative feedback loop to the pituitary is insufficient, and TSH levels rise. Increased TSH cannot stimulate adequate hormone production but does stimulate gland hyperplasia and goiter formation. Inadequate hormone levels have many systemic effects including: Common causes of acquired hypothyroidism include: Most primary hypothyroidism is the result of thyroid inflammation (thyroiditis): clinical manifestations __** (MS p 1300, patho p 457) 10% of women and 3% of men over 65 years old in the US 14. Explain the serious event of myxedema coma related to hypothyroidism. ( __** M/S p1306, patho p458, mod 9 #4m) Unknown, but precipitating factors such as insufficient iodine supply, infection, and stressful life events may interact with genetic factors to cause Graves’ disease. Other causes include toxic nodular goiter, thyroiditis, exogenous iodine excess, pituitary tumors, and thyroid cancer. Occurs in women more than men with the highest frequency in persons 20-40 y/o. 16. Explain the following terms: ( __** patho p 588-593)
 * Slow metabolic rate and weight gain
 * Bradycardia and decreased cardiac output
 * Hoarseness, cold intolerance
 * Dry skin and brittle hair
 * Lethargy and decreased mental acuity
 * Autoimmune thyroiditis
 * Iodine deficiency
 * Iatrogenic hypothyroidism
 * Acute thyroiditis is a rare bacterial infection of the gland, and subacute thyroiditis can occur after viral infection.
 * Far more common is **autoimmune thyroiditis** (Hashimoto disease) that is an idiopathic disorder caused by autoimmune thyroid antibodies that destroy the gland.
 * __
 * ** Endocrine ** || Goiter, increased TSH ||
 * ** Reproductive ** || Galactorrhea, anovulation ||
 * ** Neurologic ** || Lethargy, confusion, slow movements, ataxia, decreased reflexes, coma ||
 * ** Cardiovascular ** || Decreased cardiac output, bradycardia, cardiomyopathy ||
 * ** Pulmonary ** || Dyspnea, hypoventilation and hypercapnia, laryngeal edema with hoarseness ||
 * ** Gastrointestinal ** || Weight gain, constipation, hyperlipidemia ||
 * ** Integumentary ** || Coarse dry skin and hair; cold intolerance ||
 * ** Special ** || Myxedema ||
 * __ incidence __**
 * __
 * Myxedema coma, ** a medical emergency, is a diminished level of consciousness associated with severe hypothyroidism. Symptoms include hypothermia without shivering, hypoventilation, hypotension, hypoglycemia, and lactic acidosis. Older patients with severe vascular disease and with moderate or untreated hypothyroidism are particularly at risk. The overuse of narcotics or sedatives or an acute illness in hypothyroid individuals also can be causative.
 * __ 15. Analyze the pathophysiology, etiology, clinical manifestations, collaborative management, and incidence of a client with hyperthyroidism and the related life-threatening event of thyrotoxic crisis. __** (M/S p1299, patho p 454, Mod 9, #4 b, d-j)
 * __ Pathophysiology __**
 * Graves **** disease ** is the most common cause of hyperthyroidism and is prevalent in women in their 30s and 40s. Although it is idiopathic in its primary cause, increased thyroid production is known to be the result of a type II autoimmune hypersensitivity disorder that is characterized by the production of antibodies to the TSH receptor called **thyroid-stimulating immunoglobulins (TSI)**.
 * These antibodies do not damage the gland but rather stimulate hyperplasia with goiter formation and production of high levels of thyroid hormone.
 * These increased levels of thyroid hormone feed back on the pituitary to turn off TSH production, but thyroid hormone synthesis and release continues because of the presence of the TSI.
 * __ Etiology __**
 * __ clinical manifestations __** (MS Table 50-5 p 1300, patho 455)
 * ** Endocrine ** || Goiter, decreased TSH ||
 * ** Reproductive ** || Amenorrhea, impotence ||
 * ** Neurologic ** || Restlessness, tremor, fatigue, insomnia, hyperreflexia ||
 * ** Cardiovascular ** || Increased cardiac output, tachycardia, dysrhythmias ||
 * ** Pulmonary ** || Dyspnea, decreased vital capacity ||
 * ** Gastrointestinal ** || Weight loss, diarrhea, hypolipidemia ||
 * ** Integumentary ** || Sweating, flushing, warm skin, soft fine hair, heat intolerance ||
 * ** Special ** || Exophthalmus with Graves disease, pretibial myxedema ||
 * __ incidence __**
 * __ thyrotoxic crisis __**
 * Thyrotoxic crisis ** (also called //thyroid storm//) is an acute, rare condition in which all hyperthyroid manifestations are heightened. Although it is considered a life-threatening emergency, death is rare when treatment is vigorous and initiated early. The physiologic factor or factors that initiate thyrotoxic crisis are unknown. The cause is thought to be stressors (e.g., infection, trauma, surgery) in a patient with preexisting hyperthyroidism, either diagnosed or undiagnosed. Heart and nerve tissues become more sensitive to catecholamines due to more binding sites for epinephrine and norepinephrine. Manifestations include severe tachycardia, heart failure, shock, hyperthermia (up to 105.3° F [40.7° C]), restlessness, agitation, seizures, abdominal pain, nausea, vomiting, diarrhea, delirium, and coma. Treatment is aimed at reducing circulating thyroid hormone levels and the clinical manifestations of this disorder by appropriate drug therapy. Supportive therapy is directed at managing respiratory distress, fever reduction, fluid replacement, and elimination or management of the initiating stressor(s).
 * __


 * __ -capillary filtration and reabsorption( __** ppt. p 18)

~exchange occurs at the capillary membrane ~hydrostatic pressure and osmotic pressure affect the direction of the exchange ~filtered at the arteriole end ~reabsorbed at the venous end ~edema indicates dysfunction -peripheral vascular resistance( __** ppt. p 18)
 * __
 * Resistance ** is the opposition to force. In the cardiovascular system, most opposition to blood flow is provided by the diameter and length of the blood vessels themselves. Therefore, changes in blood flow through an organ result from changes in the vascular resistance within the organ. Resistance in a vessel is inversely related to blood flow—that is, increased resistance leads to decreased blood flow.

Factors affecting PVR ~blood viscosity ~length of vessel ~diamenter of vessel -peripheral vascular regulating mechanism __** (ppt p 19) ~sympathetic nervous system is one of the most important components. The release of norepinephrine leads to vasoconstriction ~Kidneys(RAAS) rennin, angiotensin II, aldosterone (see algorithm on ppt p.19) ~arterial chemoreceptors (concentrations of 02, CO2, pH) ~receptors are in the aortic and carotid arteries. Decreases in O2 or pH and increases in CO2 all lead to increases in BP ~natriuretic peptides ~atria and brain sense increase in volume and and send message to kidneys
 * __

__ ppt __ ~arterial pressure is greater than venous pressure ~Fluid flows from an area of greater pressure to an area of lower pressure
 * __ -dynamics of blood flow( __** ppt p 20)
 * Blood flow ** is the amount of fluid moved per unit of time and is usually expressed as liters or milliliters per minute (ml/min) or cubic centimeters per second (cm3/sec). Flow is regulated by the same physical properties that govern the movement of simple fluids in a closed, rigid system—that is, pressure, resistance, velocity, turbulent versus laminar flow, and compliance.

__//**17. Examine the mechanisms involved in the regulation of blood pressure. Huether p. 594-598, p.593 fig 22-28, p.595 fig 22-30, p. point p.19, Lewis 762-764**//__ Arterial BP**= cardiac output x systemic vascular resistance (force opposing mvmt of blood)** It’s constantly regulated to maintain tissue perfusion during wide range of physiologic conditions, including body position, muscular activity, and circ. blood volume Arterial BP is influenced and regulated by factors that affect, cardiac output (HR, SV), total resistance, and blood volume Vascular resistance & HR regulators; ANS; one of the most important components; regulates constriction / dilation, HR - **Sympathetic Nervous System**; Releases norepinephrine, epinephrine which is a vasodilator skel muscles, vasoconstrictor to peripheral vascular system, increases HR and cardiac contractility, promotes release of Renin in kidneys; Overalll outcome; Increases BP; -**Alpha receptors i**n SNS cause constriction (Lewis table 33-1, fig 33-1 p. 763) -**Beta receptors** in SNS cause dilation -Stimulated by barorecptors that sense changes in BP (below), stress, fight or flight, exercise (increases CO and BP in response to increased O2 demands of muscles), From lying position to standing (when getting up, there is a normal transient decrease in BP- SNS kicks in, causing peripheral vasoconstriction and increased venous return to heart)

-decreased heart rate by parasympathetic system -increased heart rate and stroke volume by sympathetic system -Sympathetic system can also constrict or dilate blood vessels The overall effect or goal reduces cardiac output and peripheral resistance to decrease BP –If hypertension is long standing, baroreceptors become adjusted to high BP and think it’s normal.
 * Arterial Baroreceptors**; Stretch receptors located in aorta and carotid sinus that detect change in blood pressure (respond to changes in sm. muscle fiber length). They tell cardioregulatory and vasomotor centers about the changes. Activates SNS

These are mostly in place to regulate respirations, but also; Regulates BP w/ANS -Decreased BP causes sympathetic response; increased Heart Rate, contractility, Vasoconstriction -Increased BP causes vagal response; decreased HR and vasodilation -Vasomotor center responds w/ vasoconstriction or dilation of blood vessels, increases in HR (sympathetic system); decreases in HR (parasympathetic/ vagal response).
 * Arterial Chemoreceptors**; (regulator of peripheral vascular system) located in the aortic and carotid bodies and Left Ventricle; sensitive to changes in concentrations of O2, CO2 and pH in blood; Send message to medulla oblongata.

Antidiuretic Hormone; Overall ADH is released to increase blood volume and BP -Affects BP because it influences volume of blood in the circ. System. Released by posterior pituitary Stretch receptors in heart sense blood volume; if low, ADH released causing reabsorption of H20, which increases blood plasma, which increases BP
 * Regulators that Fluid Volume (plasma)**

Overall RAAS is activated with low volume or hypotension, it’s suppressed w/ volume is normal; increases BP starts w/ Renin; secreted by kidney. Releases (or doesn’t) for a number of reasons, including -A drop of BP (detected b/c of decreased blood flow to renal artery) -Decreased sodium chloride delivered to kidney -Low potassium in plasma -Angiotensin II (reduces renin release) -B-adrenergic stimuli (increase in renin) or inhibitors (decrease in renin) Once in circulation; Renin splits from angiotensinogen to make Angiotensin I, which is converted by ACE to Angiotensin II, which stimulates Aldosterone from adrenal gland Angiotensin II; alone causes a ton of stuff (huether 596) including vasoconstriction, increased BP, glomerular hypertension, activation of SNS, Na+ and fluid retention and has been implicated in the progression of heart failure. Aldosterone; causes Na+ absorption and H2O retention-causing increase in fluid volume and increase in BP
 * RAAS; see p.point p. 19, Huether 518-519**

-Help regulate sodium excretion (natriuresis), diuresis, vasodilation, and antagonism of renin-angiotensin system; decreases BP -Leads to large volumes of dilute urine to decrease blood volume and BP -There are a few different ones, but working towards same thing (above);
 * Natriuretic Peptides;**
 * Atrial natriuretic peptide (ANP); hormone secreted from cells in Rt atrium when BP increases; inhibits ADH by increasing sodium loss (H2O follows Na+): increases GFR
 * Brain natriuretic peptide (BNP); secreted from cardiac cell, increases Na+ loss from kidneys (H2O follows Na+); increases GFR
 * C-type natriuretic peptide; found throughout vascular endothelium, promotes vasodilation
 * Urodilation; made in kidneys, promotes natriuresis


 * Endothelium;** can have effect on BP too; mostly with production of vasoconstrictors and vasodilators, see below

__//**18. Describe the critical role of the endothelium for vascular function. Huether p. 585, p. 590, table 22-4, power point p. 17**//__

All tissues rely on blood supply and blood supply depends on endothelial cells, which form the endothelium (lining) of the blood vessel. Endothelial cells can adjust their # and arrangement to accommodate local requirements and enable tissue growth, motion, and repair. Dysfunction of endothelium is linked to most vascular disorders including HTN and Atherosclerosis Read Huether p.618-619 about injury of endothelium, and captions under fig 23-10 and 23-11- gives a better overall view of the regular functions. -Facilitates transport of large molecules via vesicular transport mvmt through intercellular junctions -Facilitates transport of small molecules via mvmt of vesicles through opening tight junctions, and across the cytoplasm -Stimulates vascular relaxation by producing nitric oxide, prostacyclin, and other vasodilators -Stimulates vascular constriction by producing endothelin (vasoconstrictor) and angiotensin II (endothelium converts angiotension I to angiotension II by the membrane-bound angiotensin-converting enzyme (ACE) -Stimulates clotting by inducing platelet adhesion via production of factors -Prevents clotting through production of endogenous anticoagulants ie; heparin sulfate -Promotes fibrinolysis (the breakdown of fibrin in blood clots and prevention of new clots) - Expresses adhesion molecules that allow monocyte, neutrophil margination (cells adhering to vessel wall, so they don’t float past injury site) and diapedesis (WBCs moving through blood vessels) -Expresses receptors for oxidized lipoproteins allowing them to enter vascular intima (innermost layer of bl. Vessel wall)
 * TABLE 22-4, look at p.point too**
 * Filtration and permeability**;
 * Vasomotion**;
 * Clotting**;
 * Inflammation**:


 * //__19. Differentiate among primary, secondary, complicated, and isolated systolic hypertension specific to etiology, and pathophysiology. Huether 609-612, p.point p. 21-22, Lewis 765__//**

Diseases; -Renal disease -Dysfunction of adrenal medulla/ adrenal cortex -Coarctation or congenital narrowing of aorta -Brain tumors, head injuries, encephalitis, psychiatric disturbances Medications; -Estrogen -Glucocorticoids -Mineralcorticoids -Sympathomimetics, MOIs (causing hypertensive crisis), erythropoietin, cyclosporins -often caused by loss of elasticity in large arteries from atherosclerosis -vessels become rigid w/ calcification -ISH is most common form of HTN for people over 65
 * Primary;** Accounts for most cases (92%-95%); combined systolic and diastolic hypertension. Exact etiology is unknown, but known factors include genetic and environmental, increases in SNS activity, over-production of sodium-retaining hormones and vasoconstrictors, increased sodium intake, overweight, DM, excessive ETOH See #20
 * Secondary;** Account for 5%-10% cases in adults and 80% cases in children; caused by an underlying disease process or medication that raises peripheral vascular or cardiac output. Usually relieved if underlying cause is eliminated
 * Isolated Systolic Hypertension;(ISH)** defined as SBP greater than or equal to 140 mmHg with average DBP less than 90 mm Hg. (widened pulse pressure). More common in older adults and can be attributed to aging process
 * Complicated Hypertension;** Huether p. 611, 612 table 23-2 This is when sustained hypertension start leading to complications. See table 23-2 huether and #21


 * //__20. Examine the pathophysiology and clinical manifestations related to the client with primary hypertension: Huether 608-612, p.point, Lewis 765; Exact cause is unknown.__//**

Read middle P.Point p. 25 Basically there are Genetic and Environment Factors (below) that lead to; (Read # 17) -Insulin resistance; -Dysfunction of the SNS, RAA, Adducin, & naturiuretic hormones (controls of BP) -Inflammation ALL of these things lead to vasoconstriction (causing increased peripheral resistance) and renal salt & H2O retention (causing increased blood volume). Both of these lead to sustained hypertension.
 * Pathophysiology;**

Genetic (unmodifiable) and Environment (modifiable) risk factors in BP -Family History BIG ONE increases risk by two -1St generation relative; increased risk by 4 -Age; due to decreased vascular compliance -Vessel compliance - Gender (more common in men before age 55, more common in women after 55yrs) -Race- more common in African Americans -High dietary sodium intake -Na+, H2O retention -Obesity, especially Central obesity -Excess ETOH consumption -Glucose intolerance (DM), Insulin resistance -Low intake of minerals; potassium, calcium (to balance out Na+) and magnesium (has a role in regulating vascular resistance) -Smoking- Nicotine causes vasoconstriction -Increased plasma Catecholamines -Stress; which stimulates SNS, which stimulates catecholamines, increases HR, increases renin release all causing increased BP -SNS stimulation (above)

W/ Severe HTN; may have symptoms 2ndary to effects on blood vessels and tissues or increased workload on heart; fatigue, reduced activity intolerance, dizziness, palpitations, angina, and dyspnea. Called silent killer because it is often asymptomatic until a target organ disease has occurred. Symptoms of target organ failure; see #21
 * Clinical Manifestations; Lewis 766-767**

21. Analyze the relationship between hypertension and “silent killer”. Elaborate on the long term effects related to hypertension, specifically cardiovascular and renal changes. Hypertension is called the “silent killer” because it can progress in the body with out symptoms. Patho page 612 table 23-2 Pathologic effect of sustained complicated hypertension. Lewis page 767 Heart disease: hypertension is major risk factor for Coronary Heart Disease (CAD) reason not fully known. “Response to injury” hypothesis= atherogenesis disrupts cardiac endothelium; exposing the intamal layer to activated white blood cells and platelets. Arteriole changes result in stiffened arterial wall and narrowed lumen. Resulting in problems of angina and Myocardial infaraction. Left ventricular hypertrophy: sustained high BP increases the cardiac workload and the cardiac muscle grows to overcome peripheral resistance. Increased contractility and increases the work and 02 consumption. Heart failure develops when heart can no longer meet the demands for myocardial oxygen. Nephrosclerosis: renal dysfunction is the direct result of ischemia caused by narrowed lumen of the intrarenal blood vessels. Atrophy of the tubules destruction of the glomeruli and eventual nephron death.

22. Compare childhood systemic hypertension to adulthood primary hypertension. Hypertension in children is almost always associated with a secondary condition such as renal disease or coarctation of aorta. Compared to adults that can have primary (no-known origin) or secondary to another systemic condition. Patho page 690 Table 24-5 most common causes of chronic sustained hypertension. Relates age group to common causes.

23. Examine the complication of pregnancy induced hypertension that place a pregnant client and the fetus at risk. // (Pillitteri p. 431-433)  // · a condition in which vasospasm occurs during pregnancy in both small and large arteries · Signs of hypertension, proteinuria , and edema develop · It is unique to pregnancy and occurs in 5% to 7% of pregnancies in the United States · the cause of the disorder is still unknown o Originally it was called toxemia because researchers pictured a toxin of some kind being produced by a woman in response to the foreign protein of the growing fetus, the toxin leading to the typical symptoms. No such toxin has ever been identified. · A condition separate from chronic hypertension, PIH tends to occur most frequently in: o women of color or with a multiple pregnancy o primiparas younger than 20 years of age or older than 40 years o women from low socioeconomic backgrounds (perhaps because of poor nutrition) o those who have had five or more pregnancies o those who have hydramnio o those who have an underlying disease such as heart disease, diabetes with vessel or renal involvement, and essential hypertension. · The symptoms of PIH affect almost all organs ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> The vascular spasm may be caused by increased cardiac output that injures the endothelial cells of the arteries and the action of prostaglandins (notably decreased prostacyclin and increased thromboxane) ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Normally, blood vessels during pregnancy are resistant to the effects of pressor substances such as angiotensin and norepinephrine, so blood pressure remains normal during pregnancy ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> With PIH, this reduced responsiveness to <span class="yshortcuts" style="background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">blood pressure changes appears to be lost o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Vasoconstriction occurs and blood pressure increases dramatically ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> With <span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); cursor: pointer;">hypertension, the cardiac system can become overwhelmed because the heart is forced to pump against rising peripheral resistance ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> This reduces the blood supply to organs, most markedly the kidney, pancreas, liver, brain, __and placenta__ ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> __ Poor placental perfusion may reduce the fetal nutrient and oxygen supply __ ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Ischemia in the pancreas may result in epigastric pain and an elevated amylase–creatinine ratio ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Spasm of the arteries in the retina leads to vision changes ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> If retinal hemorrhages occur, blindness can result. ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Vasospasm in the kidney increases blood flow resistance ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Degenerative changes develop in kidney glomeruli because of back-pressure o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> This leads to increased permeability of the glomerular membrane, allowing the serum proteins albumin and globulin to escape into the urine (proteinuria) o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> The degenerative changes also result in decreased glomerular filtration, so there is lowered urine output and clearance of creatinine o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Increased kidney <span class="yshortcuts" style="background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">tubular reabsorption of sodium occurs o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Because sodium retains fluid, edema results o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Edema is further increased because as more protein is lost, the osmotic pressure of the circulating blood falls and fluid diffuses from the circulatory system into the denser <span class="yshortcuts" style="background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">interstitial spaces t o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Extreme edema can lead to cerebral and <span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">pulmonary edema and seizures (<span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); cursor: pointer;">eclampsia ). ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Arterial spasm causes the bulk of the blood volume in the maternal circulation to be pooled in the venous circulation, so a woman has a deceptively low arterial intravascular volume ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> In addition, thrombocytopenia or a lowered platelet count occurs as platelets cluster at the sites of endothelial damage ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Measuring hematocrit levels helps to assess the extent of plasma loss to the interstitial space or the extent of the edema (the higher the hematocrit, the more is being lost) ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;"> A hematocrit level above 40% suggests significant fluid loss into interstitial spaces
 * __ PIH __**
 * __ Pathophysiology of PIH __**

24. Examine the collaborative management of hypertension to illustrate the multi-step approach. the collaborative management of hypertension starts with lifestyle modifications which includes cessation of smoking, stress management, weight reduction and maintenance at a healthy weight, reduction of sodium intake, increasing physical exercise, limit alcohol consumption to moderate levels, regular monitoring of BP and taking BP medications as directed by doctor, Client teaching, and stress management.

25. Discuss gestational diabetes and it's effect on the fetus (Huether, pg. 466) (Pillitteri, pg 378) ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Develops when <span class="yshortcuts" style="background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">glucose intolerance appears during pregnancy, and pregnant women at risk should be screened. ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  <span class="yshortcuts" style="background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;"> Risk factors  : family history of diabetes, membership in a high risk ethnic group (Hispanic /native American, asian), advanced maternal age (> 25 years of age), prior history of <span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); cursor: pointer;">gestational diabetes or polycystic ovary syndrome, overweight (BMI > 25 kg/m2) , and history of obstetrical complications associated with gestational diabetes. ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Large weight babies, if it is managed well birth weight can be kept down. ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Increases risk to develop type 2 in 5-10 tears ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Causes by hormones released during pregnancy ·<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Assessment o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Because gestational diabetes is such a serious complication in pregnancy, all women should be screened. o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Usuall done at 24 weeks to <span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); background: transparent none repeat scroll 0% 0%; cursor: pointer; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial;">28 weeks of pregnancy. After 50 g glucose load is ingested, a vonous blood sample is taken for determination 60 minutes later. o<span style="font-family: 'Times New Roman'; font-style: normal; font-variant: normal; font-weight: normal; font-size: 7pt; line-height: normal; font-size-adjust: none; font-stretch: normal;">  Results over 140 mg/dl, the women is scheduled for a 100 g, 3 hour fasting <span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); cursor: pointer;">glucose tolerance test. If two of the four blood samples are abnormal or the fasting value is above 95 mg/dL, a <span class="yshortcuts" style="border-bottom: 1px dashed rgb(0, 102, 204); cursor: pointer;">diagnosis of diabetes is made.