NR283 EXAM 3 STUDYGUIDE (LATEST 2023/2024) 100% CORRECT

NR283 EXAM 3 STUDYGUIDE (LATEST 2023/2024) 100% CORRECT  NR283 EXAM 3 STUDYGUIDE (LATEST 2023/2024) 100% CORRECT CHAPTER 18 ENDOCRINE All right guys here is endocrine! Overview- functions of the endocrine system provide growth & reproductive capabilities. Dysfunction of the endocrine system includes excessive or insufficient function of the endocrine gland with alterations in hormone levels caused by either hypersecretion or hyposecretion of hormone abnormal hormone levels. Dysfunction of an endocrine gland can also be due to: 1) feedback systems failure to function or respond to inappropriate signals, 2) decreased hormone delivery caused by inadequate blood supply to the gland or target tissues, or an insufficient amount of the appropriate carrier proteins in the serum. Ectopic sources of hormones (hormones produced by nonendocrine tissues) may cause abnormally elevated hormone levels w/o the benefit of normal feedback system for hormone controls---ectopic production is autonomous. Look at (Table 18-1) Diseases of the Posterior Pituitary: Related to abnormal secretion of ADH. An excess of this hormone results in water retention and a hypoosmolar state, whereas deficiencies in the amount or response to ADH result in serum hyperosmolarity. 1) Syndrome of inappropriate ADH secretion (SIADH), also known as vasopressin dysregulation, occurs with high levels of ADH without normal physiologic stimuli for release. Most common cause is the ectopic production of ADH by tumors such as small cell carcinoma of the duodenum, stomach, and pancreas, bladder, prostate and endometrium CA, lymphomas, and sarcomas. Pulmonary disorders: bronchogenic carcinoma, pneumonia, asthma, cystic fibrosis, and respiratory failure requiring mechanical vent. CNS disorders: encephalitis, meningitis, intracranial hemorrhage, tumors and trauma. Surgery can result in increased ADH secretion. This is related to fluid and volume changes, the amount and type of IV fluids given and narcotic analgesics. Examples of medication causes include: hypoglycemic meds, narcotics, general anesthetics, chemo agents, NSAIDs, synthetic ADH analogs. PATHO: Enhanced water retention. ADH increases renal collecting duct permeability to water by inducing the insertion of (aquaporin-2), a water channel protein, into the tubular luminal membrane---increasing water reabsorption by the kidneys. Resulting in expansion of extracellular fluid volume----dilutional hyponatremia, hypoosmolarity, and urine is inappropriately concentrated with respect to serum osmaolarity. CLINICAL MANIFESTATION: * Thirst, ● impaired taste, ● anorexia, ● dyspnea on exertion (DOE), ● fatigue and dulled sensorium all due to hyponatremia. ● Vomiting, abd cramping (130-120 NA level). ● Levels below 110=confusion, lethargy, muscle twitching, convulsions, irreversible neurologic damage. 2) Diabetes Insipidus: Insufficient activity of ADH leading to polyuria and polydipsia. 2 Forms include: 1) Neurogenic or central DI- insufficient secretion of ADH occurring when any organic lesion of the hypothalamus, pituitary stalk, or posterior pituitary interferes with ADH synthesis, transport or release. Lesions include primary brain tumors, hypophysectomy, aneurysms, thrombosis, infections, and immunologic disorders, closed head injury. Also caused by hereditary disorders affecting ADH genes or structural changes in the pituitary gland. 2) Nephrogenic DI: inadequate response of the renal tubules to ADH, usually acquired or genetic. Acquired: disorders and drugs that damage the renal tubules or inhibit the generation of cAMO in the tubules. Disorders include, pyelonephritis, amyloidosis, destructive uropathies, polycystic kidney disease---all leading to irreversible diabetes insipidus. Drugs: lithium carbonate, colchicines, amphotericin B, loop diuretics, general anesthetics and demeclocycline. Genetic: mutation in the gene that codes for aquaporin-2. PATHO: Partial/total inability to concentrate urine. Insufficient ADH activity causes excretion of large volumes of dilute urine----increased plasma osmolality. CLINICAL MANIFESTATIONS: * Polyuria, Nocturia, Continued thirst, polydipsia, hydronephrosis. DIABETES MELITUS: Metabolic disease, defect in insulin secretion. ● Diagnosis based on HbA1C levels: Glycosylated hemoglobin is a form of hemoglobin that is measured primarily to identify three-month average plasma glucose concentration. DIABETES TYPE I: Most common among pediatrics. PATHO: Autoimmune T-cell mediated disease that destroys beta cells of the pancreas. Destruction of beta cells is related to genetic susceptibility and environmental factors. Strongest genetic association is with histocompatibility leukocyte antigen (HLA). Environmental factors=exposure to certain drugs, foods and viruses. Cellular immunity and humoral immunity are stimulated, resulting in beta-cell destruction and apoptosis. Insulin synthesis declines=hyperglycemia. Insulin-secreting beta cells of the islet of Langerhans must be destroyed. Glucagon, a hormone produced by the alpha cells of the islets, acts in the liver to increase blood glucose level by stimulating glycogenolysis and glucogenesis. In addition to decline in insulin secretion---decreased secretion of amylin (beta-cell hormone). Amylin suppresses glucagon release from the alpha cells. Thus both alpha-call and beta-cell functions are abnormal and both a lack of insulin and a relative excess of glucagon contribute to hyperglycemia. CLINICAL MANIFESTATIONS: Affects fat, protein and carb metabolism. (TABLE 18-5)! ● polyuria ● polydipsia 3P’s ● polyphagia ● Thirst ● Weight loss ● DKA ● Fatigue ● Visual changes DIABETES TYPE II: (non-insulin dependent) Risk factors: age, obesity, hypertension, physical activity and family history. Individuals with metabolic syndrome (obesity, dyslipidemia, prehypertension, and hyperglycemia). PATHO: Insulin resistance and decreased insulin secretion by beta cells. Insulin resistance- suboptimal response of insulin-sensitive tissues to insulin and assoc with obesity. Mechanisms of obesity: 1) obesity results in increased serum levels of leptin and decreased levels of adiponectin. These changes associated with inflammation and decreased insulin sensitivity. 2) elevated levels of serum free fatty acids and intracellular deposits of triglycerides and cholesterol interfering with intracellular insulin signaling and decreases tissue responses to insulin and contribute to beta-cell apoptosis. 3) inflammatory cytokines and interleukin-6 are released and induce insulin resistance and are cytotoxic to beta cells. 4) obesity is correlated with hyperinsulinemia and decreased insulin receptor density. LOOK AT FIG 18-12! ● Beta-cell dysfunction develops and leads to a relative deficiency of insulin activity. The islet dysfunction is caused by a combination of a decrease in beta-cell mass and reduction in normal beta-cell function. ● Glucagon concentration is increased due to pancreatic alpha cells becoming less responsive to glucose inhibition >>increase in glucagon secretion. These high levels of glucagon increase blood glucose level by stimulating glycogenolysis and gluconeogenesis. ● Hormones released from GI tract play a role in insulin resistance, beta-cell function. (Gherlin) CLINICAL MANIFESTATIONS: * overweight * dyslipidemic ● hyperinsulinemic ● hypertensive ● polyuria ● polydipsia ● fatigue ● pruritus ● recurrent infections ● visual changes ● neuropathy symptoms ACUTE COMPLICATIONS OF DIABETES MELLITUS 3 Major Acute complications: 1) Hypoglycemia: (insulin shock or insulin reaction) more common in type 1 DM. Symptoms: pallor, tremor, anxiety, tachycardia, palpitations, diaphoresis, headache, dizziness, irritability, fatigue, poor judgement, confusion, visual disturbances, hunger, seizures, and coma. 2) Diabetic Ketoacidosis (DKA): SERIOUS complication related to a deficiency of insulin and an increase in the levels of insulin counterregulatory hormones (catecholamines, cortisol, glucagon, growth hormone). More common in type I because insulin is more deficient. DX criteria: 1) serum glucose level >250, 2) serum bicarb level <18, 3) serum Ph <7.30, 4) presence of anion gap, and 5) presence of urine and serum Insulin deficiency enhances lipolysis therefore; increasing amount of nonesterfied fatty acids delivered to the liver. This results in increased glyconeogenesis which contributes to hyperglycemia and production of ketones bodies by mitochondria of the liver at a rate that exceeds peripheral use. Accumulation of ketone bodies causes drop in pH>>metabolic acidosis. 3) Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS): Sig complication of type II, occurring more often in elderly with infections or cardiovascular or renal disease. **differs from DKA in the degree of insulin deficiency and the degree of fluid deficiency*** Clinical Features: 1) serum glucose level >600, 2) serum Ph >7.30, 3) serum bicarb level >15, 4) serum osmolarity >320, 5) either absent or small numbers of ketones in the urine and serum. Somogyi effect: combination of hypoglycemia followed by rebound hyperglycemia. Dawn phenomenon: early morning rise in blood glucose with no hypoglycemia during the night. Nocturnal elevations of GH, which decrease metabolism of glucose by muscle and fat. CHRONIC COMPLICATIONS OF DM: Microvascular Disease: Diabetic retinopathy- leading cause of blindness. Results from relative hypoxemia, damage to retinal blood vessels and RBC aggregation. Diabetic nephropathy- end-stage kidney disease. Microalbuminuria is the first manifestation of kidney dysfunction. Diabetic neuropathy- metabolic and vascular factors related to chronic hyperglycemia with ischemia and demyelination contributing to neural changes. Sensory deficits are more common than motor involvement and often involve the extremities first. Macrovascular Disease: A) Coronary Artery disease: hyperglycemia and insulin resistance, high levels of LDL and triglycerides, low levels of HDL, platelet abnormalities and endothelial cell dysfunction. B) Stroke: Hypertension, hyperglycemia, hyperlipidemia and thrombosis. C) Peripheral vascular disease: Usually involves arteries below the knees. Occlusions of small arteries and arterioles cause most of the gangrenous changes of the lower extermities. Lesions begin as ulcers and progress to osteomyelitis or gangrene---amputation. Infections: Due to impaired senses which lead to loss of protection to injury. Hypoxia-compromised skin integrity, tissue’s susceptibility to infection increases as a result of hypoxia. Pathogens-proliferate rapidly due to increased glucose in body fluids, providing excellent source of energy. Blood supply-decrease WBC to affected area due to decreased blood supply from vascular changes. Suppressed immune response-chronic hyperglycemia impairs both innate and adaptive immune responses. DISEASES OF THE ANTERIOR PITUITARY Hypopituitarism: results from either an inadequate supply of hypothalamic-releasing hormones, because of damage to the pituitary stalk, or an inability of the gland to produce hormones. The most common causes lie within the pituitary gland itself and result from pituitary infarction or space-occupying lesions, such as pituitary adenomas or aneurysms. Other causes include: removal or destruction of the gland, head trauma, infections (meningitis, syphilis, tb), autoimmune hypophysitis, certain drugs, or mutation of the prophet of pituitary transcription factor gene involved in early embryonic pituitary development. PATHO: The pituitary gland is highly vascular and relies heavily upon portal blood flow from the hypothalamus, therefore; vulnerable to ischemia and infarction. Infarction may be seen with Sheehan syndrome (postpartum pituitary necrosis), pituitary apoplexy, traumatic brain injury, shock, sickle cell disease, and DM. Infarction results in tissue necrosis and edema with swelling of the gland. Expansion of the pituitary within the fixed compartment of the sella turcica further impedes blood supply. Over time there is shrinkage and fibrosis of tissue and symptoms develop. Adenomas and aneurysms compress otherwise normal secreting pituitary cells and lead to compromised hormonal output. CLINICAL MANIFESTATIONS: Panhypopituitarism-all hormones are deficient and ind. Suffers multiple complications including: cortisol deficiency from lack of ACTH, thyroid deficiency from lack of TSH, and loss of secondary sex characteristics bc lack of FSH and LH. Low levels of GH and IGF-1 affect growth in children and cause physiologic and psychologic symptoms in adults. Hyperpituitarism: Primary adenomas are usually benign, slow-growing that arise from cells of the anterior pituitary. PATHO: Expansion of the adenoma may impinge on the optic chiasma-causing visual disturbances. Locally aggressive tumor causes invasion of the cavernous sinuses compromising oculomotor, trochlear, abducens and trigeminal nerves. Extension to the hypothalamus disturbs control of wakefulness, thirst, appetite and temperature. Hormonal effects include: hypersecretion from the adenoma itself and hyposecretion from surrounding cells. The adenomatous tissue secretes the hormone of the cell type from which it arose, without regard to the needs of the body and w/o benefit of CLINICAL MANIFESTIONS: Increase in size causes headache, fatigue, neck pain or stiffness, and seizures. ● Visual changes ● Neuromuscular function ● Increase secretion of GH and prolactin ● Menstrual irregularity ● Decreased libido ● Receding secondary sex characteristics in both male and female. ● Thyroid and adrenal hypofunction bc of lack of TSH and ACTH=hypothyroidism and hypocortisolism. Hypersecretion of GH: Acromegaly results from high levels of GH and IGF- atherosclerosis, diabetes mellitus, or malignancy. PATHO: In children and adolescents whose epiphyseal plates have not yet closed, the effect of increased GH levels is termed Giatism. In the adult, increase amounts of GH and IGF-1 cause connective tissue proliferation and increased cytoplasmic matrix as well as bony proliferation that results in the characteristic appearance of acromegaly. Hyperglycemia results from GH’s inhibition of peripheral glucose uptake and increased hepatic glucose production, followed by compensatory hyperinsulinism and finally, insulin resistance. Diabetes occurs when the pancreas can’t secrete enough insulin to offset the effects of GH. Hypertension and left ventricular heart failure are seen. CLINICAL MANIFESTATIONS: Enlarged tongue ● Interstitial edema ● Overactive sebaceous and sweat glands ● Coarse skin and body hair ● Enlargement of the bones of the face, hands and feet. ● Barrel-chested (increased IGF-1) ● Weakness ● Muscular atrophy ● Foot drop, sensory changes in hands ● Diabetes symptoms Prolactinoma: most common hormonally active pituitary tumors. PATHO: Sustained increases in levels of serum prolactin. Elevated levels in women lead to amenorrhea, nonpuerperal mil production, hirsutism and osteopenia. Men=hypogonadism and erectile dysfunction. CLINICAL MANIFESTATIONS: ● Amenorrhea ● Hirsutism ● Osteoporosis ● Headache and visual impairment (men) ALTERATIONS OF THYROID FUNCTION: Develop as a result of primary dysfunction or disease of the thyroid gland or secondarily as a result of pituitary or hypothalamic alterations. Primary thyroid disorders- alterations of TH levels with secondary feedback effects on pituitary TSH. Primary elevations in TH level, TSH level will secondarily decrease bc of negative feedback. When TH level is decreased bc of condition affecting the thyroid gland, TSH level will be elevated. 1) Hyperthyroidism: Excess amounts of TH are secreted from the thyroid gland. It is a form of thyrotoxicosis-results from increased levels of TH. CLINICAL MANIFESTATIONS: FIG 18-6 Primary hyperthyroidism-caused by common diseases such as: Graves’ disease, toxic multinodular goiter, and solitary toxic adenoma. A. Graves’ disease: Autoimmune, type II hypersensitivity in which there is stimulation of the thyroid by autoantibodies (TSIs) directed against the TSH receptor, which override the normal regulatory mechanisms. Clinical Manifestations: Exophthalmos (orbital fat accumulation, inflammation, and edema of the orbital contents. Periorbital edema, extraocular muscle weakness leads to diplopia. ● Irritation ● Pain ● Lacrimation ● Photophobia ● Blurred vision/visual field impairment ● Decreased visual acuity ● Papilledema ● Exposure keratosis ● Corneal ulceration Graves dermopathy: very high levels of TSH. ● Subcutaneous swelling on anterior portions of legs and by indurated and erythematous skin. B. Toxic multinodular goiter: occurs when there are several hyperfunctioning nodules leading to hyperthyroidism. One nodule hyperfunctioning=toxic adenoma. C. Thyrotoxic crisis: usually occurs in those with undiagnosed or partially treated Graves’ disease and subjected to excessive stress, (ie) infection, pulmonary or cardio disorders, trauma, seizures, emotional stress, dialysis, plasmapheresis, or inadequate preparation for thyroid sx. S/S: hyperthermia, tachycardia, high-output heart failure, agitation, delirium, N/ V/D contributing to fluid volume depletion. 2) HYPOTHYROIDISM: Deficient production of TH by the thyroid gland. Most common. FIG 18-9! PATHO: Primary vs. Secondary Primary: loss of thyroid function leads to decreased production of TH and increased secretion of TSH and TRH. Common causes: autoimmune thyroiditis (Hashimoto disease), iatrogenic loss of thyroid tissue after surgical or radioactive treatment for hyperthyroidism or after head and neck radiation therapy, medications, endemic iodine deficiency. Secondary (central): caused by the pituitary’s failure to synthesize adequate amounts of TSH or a lack of TRH. Common causes: pituitary tumors compressing surrounding pituitary cells or the consequences of their treatment, traumatic brain injury, subarachnoid hemorrhage, or pituitary infarction. CLINICAL MANIFESTATIONS: Lowers energy metabolism ● Low basal metabolic rate ● Cold intolerance ● Lethargy ● Slightly lowered basal body temp ● Goiter- caused by decrease TH>>excessive TSH production stimulating thyroid tissue ● Myxedema-severe or long-standing hypothyroidism. ALTERATIONS OF PARATHYROID FUNCTION Hyperparathyroidism- Greater than normal secretion of PTH and hypercalcemia. PATHO: Primary: inappropriate excess secretion of PTH by one or more of the parathyroid glands. Majority cases caused by parathyroid adenomas. Other causes include parathyroid hyperplasia and parathyroid carcinoma and genetics. Secondary: compensatory response of the parathyroid glands to chronic hypocalcemia, which can be associated with decreased renal activation of Vit D. PTH can’t achieve normal calcium levels bc of insufficient levels of activated Vit D. Other causes include: dietary deficiency in Vit D or calcium, decreased intestinal absorption of Vit D or calcium, ingestion of drugs such as phenytoin, phenobarbital, and laxatives. CLINCIAL MANIFESTATIONS: Tetany presentation ● Fatigue ● Headache ● Depression ● Anorexia ● N/V ● Hypocalcemia (metabolic acidosis and production of an abnormally alkaline urine) and hypophosphatemia (PTH hypersecretion enhances renal phosphate excretion) ● Pathologic fx’s kyphosis of the dorsal spine and compression fx’s due to excessive osteoclast and osteocytic activity. Hypoparathyroidism: Abnormally low PTH levels most commonly caused by damage to the parathyroid glands, during thyroid sx. Also associated with genetic syndromes, including familial hypoparathyroidism and DiGeorge syndrome. PATHO: A lack of circulating PTH causes depressed serum calcium levels and increased serum phosphate levels. In the absence of PTH, reabsorption of calcium from bone and regulation of calcium reabsorption form the renal tubules are impaired. Phosphate reabsorption by the renal tubules is increased causing hyperphosphatemia. CLINICAL MANIFESTATIONS: Tetany ● Chvostek sign- tapping the cheek, resulting in twitching in upper lip. ● Trousseau sign-elicited by sustained inflammation of a bp machine placed on the upper arm to a level above the systolic bp with resultant painful carpal spasm. ● Dry skin ● Hair loss ● Hypoplasia of developing teeth ● Horizontal ridges on nails ● Bones deformity ● Cataracts ALTERATIONS OF ADRENAL FUNCTION Cushing syndrome: Excess cortisol (hypercortisolism). PATHO: 1) Normal diurnal or circadian secretion patterns of ACTH and cortisol are lost. 2) There is no increase in ACTH and cortisol secretions in response to a stressor. ACTH-dependent hypercortisolism, the excess ACTH stimulates excess production of cortisol and there is loss of feedback control of ACTH secretion. ACTH-independent hypercortisolism is caused by cortisol secretion from a rare benign or malignant tumor of one or both adrenal glands. CLINICAL MANIFESTIONS: ● Wheight gain ● Moon face ● Buffalo hump ● Supraclavicular fat pad ● Purple striae ● Pendulous abdomen Hyperaldosteronism: Excessive aldosterone secretion by the adrenal glands. Primary: Caused by excessive secretion of aldosterone from an abnormality of the adrenal cortex. PATHO: Increased renal sodium and water reabsorption with corresponding hypovolemia and hypertension, 2) renal excretion of potassium. Secondary: Extra-adrenal stimulus of aldosterone secretion, most often angiotensin II through a renin-dependent mechanism. Occurs in decreased circulating blood volume and decreased delivery of blood to kidney. Other causes: Bartter syndrome (renal tubular defect leading to hypokalemia and renin-secreting tumors of the kidney. PATHO: Potassium secretion is promoted by aldosterone, therefore; with excessive aldosterone, hypokalemia occurs. Hypokalemic alkalosis, changes in myocardial conduction, and skeletal muscle alterations may be seen. Renal tubules may become insensitive to ADH, promoting excessive water loss and in this situation hypernatremia also may occur because water is not able to follow the sodium that is reabsorbed. CLINICAL MANIFESTIONS: ● Hypertension (left ventricular dilation and hypertrophy and progressive arteriosclerosis) ● Hypokalemia ADRENOCORTICAL HYPOFUNCTION Hypocortisolism develops because of either inadequate simulation of the adrenal glands by ACTH or a primary inability of the adrenals to produce and secrete the adrenocortical hormones. Addison’s Disease: Autoimmune mechanisms that destroy adrenal cortical cells and more common in women. PATHO: Inadequate corticosteroid and mineralocorticoid synthesis and elevated levels of ACTH. CLINICAL MANIFESTIONS: ● Weakness ● Easy fatigability ● Hyperpigmentation ● Anorexia ● N/V/D ● Hypotension which can progress to complete vascular shock and collapse. TUMOR OF ADRENAL MEDULLA: Pheochromocytomas cause excessive production of catecholamines because of autonomous secretion of the tumor. CLINICAL MANIFESTATIONS: ● Persistent hypertension ● Headache ● Pallor ● Diaphoresis ● Tachycardia ● Palpitations CHAPTER 29 ALTERATION OF RENAL AND URINARY TRACT FUNCTION 1. Terms: - Hydroureter: accumulation of urine in the ureter - Hydronephrosis: enlargement of the renal pelvis and calyces 2. Renal Calculi (urinary stones) - Risk factors: age (before 50); gender (female); decreased fluid intake, diet, geographic location, race, occupation, immobility, ^ uric acid, ^ urinary oxalate - Patho process: Formation of the stones because of: 1. super saturation of salts 2. Precipitation of salt from liquid to solid (T, urine pH) 3. Crystallization 4. Absence of stone inhibitors Calcium stones (calcium oxalate or calcium phosphate) 70-80%. Intestinal hyperabsorption of dietary calcium; hyperparathyroidism and bone demineralization. Struvite stones (magnesium-ammonium-phosphate + matrix). Urinary tract infections and alkaline urine. Uric acid stones- gouty arthritis. Acidic urine increases risk of stone formation and genetic disorders of amino acid metabolism. - Clinical Manifestation: Flank Pain radiating to the groin Renal colic (intermittent pain) Urgency Frequent voiding Urge incontinence Nausea and vomiting with severe pain Gross or microscopic hematuria 3. Bladder Cancer - Risk factors: men over 60 years old, smoking, exposed to aniline dyes or other aromatic amines. - Patho process: Transitional cell carcinoma is the most common Secondary bladder cancer develops from bordering organs (cervical and prostate cancer) - Clinical Manifestations: Gross painless hematuria Daytime voiding frequency Nocturia Urgency Urge urinary incontinence Flank pain may occur 4. Acute Cystitis Inflammation of the bladder - Hemorrhagic cystitis (mucosa is red) - Suppurative cystitis (puss formation or suppurative exudates) - Ulcerative cystitis (prolonged infection leads to ulcer formation) - Gangrenous cystitis (necrosis of the bladder wall) - Patho process: E. coli and staphylococcus saprophyticus are most common bacterial infections. Less common: Klebsiella, Proteus, Psudomonas fungi, viruses, parasite (Schistomiasis) Retrograde movement of gram negative bacilli into the urethra and bladder and then to ureter and kidneys. The inflammatory edema in the bladder wall stimulates discharge of stretch receptors initiating symptoms of bladder fullness with small volumes of urine and producing the urgency and frequency of urination associated with cystitis. - Clinical Manifestations: Elderly have highest risk of being asymptomatic. Urgency Frequency Dysuria (painful urination) Suprapubic or low back pain With more serious infection: Flank pain Hematuria Cloudy urine 5. Acute Pyelonephritis Infection of one of both upper urinary tracts (ureter, renal pelvis, and interstitium) - Risk Factors: Kidney stones; Vesicoureteral reflux; Pregnancy; Neurogenic bladder; Instrumentation; Female sexual trauma - Patho process: E. coli, Proteus, Pseudomonas (last two associated with instrumentation and urinary tract surgery) The infection cases medullary infiltration of WBC with renal inflammation, renal edema, and purulent urine. In severe infections localized abscesses may form in the medulla and extend to the cortex. Tubulus are affected. After the acute phase, healing occurs with fibrosis and atrophy of affected tubules. - Clinical Manifestation: Fever (low grade) Chills Flank or groin pain Frequency Dysuria Costovertebral tenderness Bacteriuria Hematuria 6. Glomerulonephritis Inflammation of the glomerulus. Caused by: 1. Primary glomerular injury (immunologic responses, ischemia, free radicals, drugs, toxins, vascular disorders) 2. Secondary glomerular injury (diabetes, lupus, cognitive heart failure, HIV) - Patho process: The most common mechanism is immune injury (hypersensitivity type II and III) Nonimmune glomerular injury is related to ischemia, drugs and toxins Activation of biochemical mediators of inflammation occurs. These mediators injure the glomerular membrane surface membrane. GFR decreases. Deposition of substances in Bowman space, making it larger. Decrease in glomerular blood flow. Decrease in riving hydrostatic pressure; hypoxic injury. Movement of proteins into urine. Proteinuria or hematuria develop or both. - Clinical Manifestation: Oliguria (urine output less than 30 ml/hour) Facial/ periorbital edema Pulmonary edema Hypertension --→ hypertensive encephalopathy Hematuria with red blood cell casts-→ smoky brown tinged urine Proteinuria exceeding 3-5 g/day with albumin Metabolic acidosis Nephritic sediment or nephrotic sediment Types of glomerulonephritis: 1. Diabetic nephropathy- metabolic and vascular complication. Thickening and fibrosis of the glomerular basement membrane. Most common cause of chronic kidney disease and end-stage renal failure. 2. Lupus nephritis- caused by the formation of autoantibodies against double strained DNA with glomerular deposition of the immune complex. 3. IgA nephropathy (Berger disease)- most common in developing countries like Asia. Affects people 20-30. Cause is unknown. It manifests with microscopic hematuria 24-48 hours after upper respiratory tract or GI mucosal viral infection. 7. Acute Kidney Injury Acute kidney injury (AKI) is a sudden decline in kidney function with a decrease in glomerular filtration and accumulation of nitrogenous waste products in the blood as demonstrated by an elevation in plasma creatinine and blood urea nitrogen levels. Renal injury and are described by the acronym RIFLE (R = risk, I = injury, F = failure, L = loss, and E = end-stage kidney disease [ESKD]) Renal insufficiency generally refers to a decline in renal function to about 25% of normal or a GFR of 25 to 30 ml/min. Levels of serum creatinine and urea are mildly elevated. Renal failure refers to significant loss of renal function requiring dialysis. End-stage renal failure (ESRF) refers to a renal function of less than 10% requiring dialysis or transplant. Patho Process: 1. Prerenal acute kidney injury is the most common reason for AKI and is caused by renal hypoperfusion. The GFR declines because of the decrease in filtration pressure. Poor perfusion can result from renal vasoconstriction, hypotension, hypovolemia, hemorrhage, or inadequate cardiac output. AKI may occur during chronic renal failure if a sudden stress is imposed on already marginally functioning kidneys. Failure to restore blood volume or blood pressure and oxygen delivery can cause cell injury and acute tubular necrosis or acute interstitial necrosis, a more severe form of AKI. 2. Intrarenal (intrinsic) acute kidney injury usually results from ischemic acute tubular necrosis (ATN) related to prerenal AKI, nephrotoxic ATN (i.e., exposure to radiocontrast media), acute glomerulonephritis, vascular disease (malignant hypertension, disseminated intravascular coagulation, and renal vasculitis), allograft rejection, or interstitial disease (drug allergy, infection, tumor growth). ATN caused by ischemia occurs most often after surgery (40% to 50% of cases) but also is associated with sepsis, obstetric complications, and severe trauma, including severe burns. Hypotension associated with hypovolemia produces ischemia, generating toxic oxygen free radicals that cause cellular swelling, injury, and necrosis. Ischemic necrosis tends to be patchy and may be distributed along any part of the nephron. Nephrotoxic ATN can be produced by radiocontrast media and numerous antibiotics, particularly the aminoglycosides (neomycin, gentamicin, tobramycin) because these drugs accumulate in the renal cortex. Other substances, such as excessive myoglobin (oxygen-transporting substance from muscles), carbon tetrachloride, heavy metals (mercury, arsenic), or methoxyflurane anesthetic, and bacterial toxins may promote renal failure. Dehydration, advanced age, concurrent renal insufficiency, and diabetes mellitus tend to enhance nephrotoxicity. Necrosis caused by nephrotoxins is usually uniform and limited to the proximal tubules. 3. Postrenal acute kidney injury is rare and usually occurs with urinary tract obstruction that affects the kidneys bilaterally (e.g., bladder outlet obstruction, prostatic hypertrophy, bilateral ureteral obstruction), tumors, or neurogenic bladder. A pattern of several hours of anuria with flank pain followed by polyuria is a characteristic finding. The obstruction causes an increase in intraluminal pressure upstream from the site of obstruction with a gradual decrease in GFR. This type of renal failure can occur after diagnostic catheterization of the ureters, a procedure that may cause edema of the tubular lumen. Stages: - The initiation phase is the phase of reduced perfusion or toxicity in which kidney injury is evolving. Prevention of injury is possible during this phase. - The maintenance phase is the period of established kidney injury and dysfunction after the initiating event has been resolved and may last from weeks to months. Urine output is lowest during this phase and serum creatinine and blood urea nitrogen (BUN) levels both increase. - The recovery phase is the interval when kidney injury is repaired and normal renal function is reestablished. Diuresis is common during this phase with a decline in serum creatinine and urea concentrations and an increase in creatinine clearance. 8. Chronic Kidney Disease Irreversible loss of renal function that affect all organ systems. Associated with systemic diseases, such as hypertension and diabetes mellitus, or with intrinsic kidney diseases, such as chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies, or vascular disorders Loss of nephron mass. GFR <60 over three months Patho process: Glomerular hyperfiltration and increased glomerular capillary permeability lead to proteinuria. Proteinuria contributes to tubulointerstitial injury by accumulating in the interstitial space and activating complement proteins and other mediators and cells, such as macrophages, that promote inflammation and progressive fibrosis. Angiotensin II activity is elevated with progressive nephron injury. Angiotensin II promotes glomerular hypertension and hyperfiltration caused by efferent arteriolar vasoconstriction and also promotes systemic hypertension. The chronically high intraglomerular pressure increases glomerular capillary permeability, contributing to proteinuria. Angiotensin II also may promote the activity of inflammatory cells and growth factors that participate in tubulointerstitial fibrosis and scarring. Clinical Manifestations: Azotemia- increased level of serum urea and other nitrogenous compounds Uremia- systemic symptoms associated with the accumulation of nitrogenous wastes and accumulation of toxins in the plasma caused by decline in renal function. Bone demineralization: decreased vitamin D. hypocalcemia, increased phosphorus Metabolic Acidosis Hypertension Stroke Pulmonary edema Bleeding Infection Pruritus Palor because of anemia Diarrhea Nausea Vomiting Anorexia Neurologic symptoms Proteinuria Decreased GFR Increase in BUN, creatinine Potassium levels increase Dyslipidemia 9. Kidney Cancer Renal adenomas (benign)- cortex Renal cell carcinoma Renal transitional cell carcinoma (renal parenchyma, renal pelvis; occurs in men 50-60 years old) Risk factors: smoking, obesity, uncontrolled hypertension Clinical Manifestation: Hematuria Dull flank pain Palpable flank mass Weight loss (UNKNOWN CHAPTER) GI SYSTEM • Bulimia nervosa is characterized by bingeing—the consumption of normal to large amounts of food, often several thousand calories at a time—followed by self-induced vomiting or purging of the intestines with laxatives. • Anorexia o Anorexia is lack of a desire to eat despite physiologic stimuli that would normally produce hunger. This nonspecific symptom is often associated with nausea, abdominal pain, diarrhea, and psychologic stress. Malnutrition is lack of nourishment from inadequate amounts of calories, protein, vitamins, or minerals and is caused by improper diet, alterations in digestion or absorption, chronic disease, or a combination of these factors. Starvation is a state of extreme malnutrition and hunger from lack of nutrients. Vomiting Vomiting (emesis) is the forceful emptying of stomach and intestinal contents (chyme) through the mouth. Stimuli initiating the vomiting reflex include severe pain; distention of the stomach or duodenum; • Nausea o Nausea is a subjective experience associated with various conditions, including abnormal pain and labyrinthine stimulation (i.e., spinning movement). • Retching • Retching begins with deep inspiration. The glottis closes, the intrathoracic pressure falls, and the esophagus becomes distended. • Projectile Vomiting o Spontaneous vomiting not preceded by nausea or retching is called projectile vomiting. • Constipation  Constipation is difficult or infrequent defecation. • Diarrhea  An increase in the frequency of defecation and in the fluid content and volume of feces.  Osmotic diarrhea. A nonabsorbable substance in the intestine draws excess water into the intestine and increases stool weight and volume, producing large-volume diarrhea. Causes include lactase and pancreatic enzyme deficiency; excessive ingestion of synthetic, nonabsorbable sugars; full-strength tube-feeding formulas; or dumping syndrome associated with gastric resection  Secretory diarrhea. Excessive mucosal secretion of fluid and electrolytes produces large-volume diarrhea. Infectious causes include viruses (e.g., rotavirus), bacterial enterotoxins (e.g., Escherichia coli andVibrio cholerae), or exotoxins from overgrowth of Clostridium difficile following antibiotic therapy.  Motility diarrhea. Food is not mixed properly, digestion and absorption are impaired, and motility is increased. Causes include resection of the small intestine (short bowel syndrome), surgical bypass of an area of the intestine or fistula formation between loops of intestine, irritable bowel syndrome–diarrhea predominant, excessive motility of the intestine caused by diabetic neuropathy and hyperthyroidism, and laxative abuse.  Steatorrhea (fat in the stools), bloating, and diarrhea are common signs of malabsorption syndromes. Anal and perineal skin irritation can occur. • Melena  Dark, tarry stools • Hematemesis  Vomiting blood • Hematochezia  Frank bleeding from the rectum • Alcoholic fatty liver (steatosis) is the mildest form of alcoholic liver disease. It can be caused by relatively small amounts of alcohol, may be asymptomatic, and is reversible with cessation of drinking. • Alcoholic steatohepatitis is a precursor of cirrhosis characterized by inflammation, degeneration, and necrosis of hepatocytes and infiltration of neutrophils and lymphocytes. • Alcoholic cirrhosis is caused by the toxic effects of alcohol metabolism on the liver, immunologic alterations, inflammatory cytokines, and oxidative stress from lipid peroxidation, and malnutrition.  Fatty infiltration causes no specific symptoms or abnormal liver function test results. The liver is usually enlarged, however, and the individual has a history of continuous alcohol intake during the previous weeks or months. Anorexia, nausea, jaundice, and edema develop with advanced fatty infiltration or the onset of alcoholic steatohepatitis.  Nonalcoholic fatty liver disease (NAFLD) is infiltration of hepatocytes with fat, primarily in the form of triglycerides, but it occurs in the absence of alcohol intake.  NAFLD will develop nonalcoholic steatohepatitis (NASH) with hepatocellular injury, inflammation, and fibrosis; NASH is difficult to distinguish from alcohol-induced liver fibrosis. NAFLD is usually asymptomatic and may remain undetected for years. • Parietal pain- localized, intense, most severe, arises from the organs themselves • Visceral pain- arises from a stimulus (distention, inflammation, ischemia) acting on an abdominal organ, diffuse and vague • Referred pain- is visceral pain felt at some distance from a diseased or affected organ. • Achalasia- rare form of dysphagia, loss of esophageal peristalsis and failure of the lower esophageal sphincter to relax (functional obstruction) • Upper gastrointestinal bleeding is bleeding in the esophagus, stomach, or duodenum, and is characterized by frank, bright red bleeding or dark, grainy digested blood (“coffee ground”) that has been affected by stomach acids. • Lower gastrointestinal bleeding, or bleeding from the jejunum, ileum, colon, or rectum, can be caused by polyps, diverticulitis, inflammatory disease, cancer, or hemorrhoids. • Occult bleeding is usually caused by slow, chronic blood loss that is not obvious and results in iron deficiency anemia as iron stores in the bone marrow are slowly depleted. • Dysphagia is difficulty swallowing. o Mechanical obstruction of the esophagus or a functional disorder that impairs esophageal motility. o Functional dysphagia is caused by neural or muscular disorders that interfere with voluntary swallowing or peristalsis. • Hiatal hernia is a type of diaphragmatic hernia with protrusion (herniation) of the upper part of the stomach through the diaphragm and into the thorax. • Sliding hiatal hernia (the most common). The stomach slides or moves into the thoracic cavity through the esophageal hiatus; a congenitally short esophagus, trauma, or weakening of the diaphragmatic muscles at the gastroesophageal junction is contributory. Coughing, bending, tight clothing, ascites, obesity, and pregnancy accentuate the hernia. • Paraesophageal hiatal hernia. The greater curvature of the stomach herniates through a secondary opening in the diaphragm and lies alongside the esophagus. Symptoms include congestion of mucosal blood flow leading to gastritis and ulcer formation. Strangulation of the hernia is a major complication. • CM: Hiatal hernias are often asymptomatic. Generally, a wide variety of symptoms develop later in life and are associated with other gastrointestinal disorders as well. Manifestations include gastroesophageal reflux, dysphagia, heartburn, vomiting, and epigastric pain. Regurgitation and substernal discomfort after eating are common. • Gastroparesis, or delayed gastric emptying in the absence of mechanical gastric outlet obstruction, is estimated to occur in 20%-40% of individuals with diabetes mellitus and may also be present in 25%-40% of individuals with functional (non-ulcer) dyspepsia, a condition affecting approximately 20% of the U.S. general population. • Pyloric obstruction (gastric outlet obstruction) is the narrowing or blocking of the opening between the stomach and the duodenum. This condition can be congenital. o CM: Early in the course of pyloric obstruction, the individual experiences vague epigastric fullness, which becomes more distressing after eating and later in the day. Nausea and epigastric pain may occur as the muscles of the stomach contract in attempts to force chyme past the obstruction. These symptoms disappear when the chyme finally moves into the duodenum. o Rolling or jarring of the abdomen produces a sloshing sound called the succussion splash. • Intestinal obstruction can be caused by any condition that prevents the normal flow of chyme through the intestinal lumen. • Simple obstruction is mechanical blockage of the lumen by a lesion and it is the most common type of intestinal obstruction. • Paralytic ileus, or functional obstruction, is a failure of intestinal motility often occurring after abdominal surgery. Acute obstructions usually have mechanical causes, such as adhesions or hernias. Chronic or partial obstructions are more often associated with tumors or inflammatory disorders, particularly of the large intestine. o PATHO: Postoperative paralytic ileus results from inhibitory neural reflexes associated with inflammatory mediators, and the influence of exogenous (meperidine) and endogenous opioids (endorphins). o CM: Crampy/colicky pains followed by vomiting and distention are the cardinal symptoms of small bowel obstruction. Colonic obstruction usually presents as hypogastric pain and abdominal distention. Typically, the pain occurs intermittently and intensifies for seconds or minutes as a peristaltic wave of muscle contraction meets the obstruction. • GERD- reflux of chyme acid and pepsin from the stomach through the lower esophageal sphincter to the esophagus • nonerosive reflux disease (NERD), individuals have symptoms of reflux disease but no visible esophageal mucosal injury. • In some individuals, however, a combination of factors causes an inflammatory response to reflux called reflux esophagitis • Pathophysiology- Normally the resting tone of the LES maintains a zone of high pressure that prevents reflux. In individuals who develop reflux esophagitis, this pressure tends to be lower than normal. The severity of the esophagitis depends on the composition of the gastric contents and the length of time they are in contact with the esophageal mucosa. If the chyme is highly acidic or contains bile salts and pancreatic enzymes, reflux esophagitis can be severe. In individuals with weak esophageal peristalsis, refluxed chyme remains in the esophagus longer than usual. H. pylori may be protective by decreasing the potency of the gastric refluxate (gastritis leading to achlorhydria). • Clinical Manifestations-heartburn, acid regurgitation, dysphagia, chronic cough, asthma attacks, laryngitis, upper abd pain within 1 hr. of eating. Symptoms worsen if pt lays down-cough, vomiting. Edema, strictures, esophageal spasms, • Gastritis- is an inflammatory disorder of the gastric mucosa. It can be acute or chronic and affect the fundus or antrum, or both.  Acute Gastritis-erodes the epithelium in a defuse or localized patter, superficial, result of injury to the mucosal barrier caused by drugs of chemicals  Clinical Manifestations- vague abd discomfort, epigastric tenderness and bleeding  Chronic Gastritis-tends to occur in elderly individuals and causes thinning and degeneration (atrophy) of the gastric mucosa.  Chronic fundal gastritis, also called atrophic or autoimmune gastritis, is the most severe type. The gastric mucosa degenerates extensively in the body and fundus of the stomach, leading to gastric atrophy. Loss of chief cells and parietal cells diminishes acid secretion, so the feedback mechanism that normally inhibits gastrin secretion is impaired, causing elevated plasma levels of gastrin. • C.M.-associated with autoimmune diseases (rheumatoid arthritis, thyroid, type 1 DM), increased risk of gastric carcinoma, pernicious anemia.  Chronic antral gastritis- involves the antrum only and occurs more often than fundal gastritis. Caused by H. pylori and etoh, smoking and NSAIDS • C.M- anorexia, fullness, nausea, vomiting and epigastric pain, bloody stools • Peptic Ulcer-is a break, or ulceration, in the protective mucosal lining of the lower esophagus, stomach, or duodenum. Ulcers develop when mucosal protective factors are overcome by erosion Superficial ulcerations are called erosions because they erode the mucosa but do not penetrate the muscularis mucosae factors. PEPTIC ULCER RISK FACTORS ● Infection of the gastric and duodenal mucosa with Helicobacter pylori ● Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) ● Alcohol ● Smoking ● Advanced age ● Chronic diseases, such as emphysema, rheumatoid arthritis, cirrhosis, and obesity and diabetes o Zollinger-Ellison syndrome is a rare syndrome that is also associated with peptic ulcers caused by a gastrin-secreting neuroendocrine tumor or multiple tumors (gastrinoma) of the pancreas or duodenum. Increased secretion of gastrin causes excess secretion of gastric acid, resulting in gastric and duodenal ulcers, gastroesophageal reflux with abdominal pain, and diarrhea.  Risk Factors- infection (H. pylori), NSAIDs, etoh, smoking, advanced age, chronic diseases (emphysema, RA, cirrhosis, obesity) • Duodenal ulcers- 0ccur with greater frequency than other types of peptic ulcers and tend to develop in younger persons and perhaps in individuals with type O blood. ● 1. Serum gastrin levels remain high longer than normal after eating and continue to stimulate secretion of hydrochloric acid and pepsin (may be caused by H. pylori). ● 2. There is failure of the feedback mechanism in which acid in the gastric antrum inhibits gastrin release. ● 3. Rapid gastric emptying overwhelms the buffering capacity of the bicarbonate-rich pancreatic secretions. ● 4. H. pylori is associated with death of mucosal epithelial cells and elevated levels of gastrin and pepsinogen. ● 5. H. pylori releases toxins and enzymes that promote inflammation and ulceration. ● 6. Use of NSAIDs inhibits the action of cyclooxygenase-1 (COX-1), resulting in inhibition of prostaglandins and consequent reduced maintenance of the mucosal barrier as well as decreased bicarbonate secretion. ● 7. Cigarette smoking stimulates acid production. ● 8. The mass of gastric parietal (acid-secreting) cells increases. o C.M  The characteristic manifestation of a duodenal ulcer is chronic intermittent pain in the epigastric area. The pain begins 2 or 3 hours after eating, when the stomach is empty. It is not unusual for pain to occur in the middle of the night and disappear by morning. Pain is relieved rapidly by ingestion of food or antacids, creating a typical pain-food-relief pattern. • Gastric ulcers- ulcers of the stomach and occur equally in males and females between 55-65 yrs. 4th common duodenal ulcers  PATHO: Use of NSAIDs and H. pylori infection are major causes of gastric ulcer. Generally, gastric ulcers develop in the antral region, adjacent to the acid-secreting mucosa of the body. The primary defect is an abnormality that increases the mucosal barrier's permeability to hydrogen ions. Gastric secretion may be normal or less than normal and there may be a decreased mass of parietal cells.  Chronic gastritis is often associated with development of gastric ulcers and may precipitate ulcer formation by limiting the mucosa's ability to secrete a protective layer of mucus. Other factors include the following:  1.Decreased mucosal synthesis of prostaglandins  2.Duodenal reflux of bile and pancreatic enzymes  3.Use of ulcer genic drugs (e.g., aspirin, ibuprofen, naproxen) • C.M.- Stress Ulcer-pain occurs immediately after eating, can cause anorexia, vomiting, weight loss, chronic, and alternate between periods of remission and exacerbation Stress Ulcer o Acuter for of peptic ulcer, seen in severe illness, systemic trauma or neural injury, emotional stress  Ischemic ulcer- develops within hours or hemorrhage, multi-system trauma, burns, heart failure or sepsis. Curling ulcers (burn injury)  Cushing ulcer- stress ulcer associated with head trauma or brain surgery, decreased blood mucosal blood flow and hypersecretion of acid • Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with no specific structural or biochemical alterations as a cause of disease. It is broadly characterized by recurrent abdominal pain and discomfort associated with altered bowel habits that present as diarrhea or constipation or both. o PATHO:  Visceral hypersensitivity or hyperalgesia particularly with distention of the rectum, but also other areas of the gut, may originate in either the peripheral or the central nervous system.  Abnormal gastrointestinal motility and secretion are associated with IBS. Individuals with diarrhea-type IBS have more rapid colonic transit times, whereas those with bloating and constipation have delayed transit times.  Intestinal infection (bacterial enteritis) has been associated with symptoms of IBS, and post infectious IBS appears to be related to ongoing low-grade inflammation, changes in intestinal permeability, and an abnormal immune response in gut tissues.  Overgrowth of small intestinal flora (normal gut bacteria) may precipitate IBS symptoms, and it is proposed that methane gas may slow intestinal transit time, resulting in constipation and bloating.  Food allergy or food intolerance is associated with IBS. Food antigens or food-borne pathogens may activate the mucosal immune system, alter intestinal flora, or mediate hypersensitivity reactions and IBS symptoms. Food elimination approaches are helpful in some cases.  Psychosocial factors, including emotional stress, influence brain-gut interactions and neuroendocrine, autonomic nervous system, and pain modulatory responses, contributing to the symptoms of IBS. o CM: IBS is characterized by lower abdominal pain or discomfort and can be diarrhea-predominant, constipation-predominant, or alternating diarrhea/constipation. Symptoms including gas, bloating, and nausea are usually relieved with defecation and do not interfere with sleep. • Ulcerative colitis (UC) and Crohn disease (CD) are complex, idiopathic chronic inflammatory bowel diseases (IBDs). o The lesions of UC are continuous and located in the colon, whereas the lesions of CD may involve the entire GI tract and occur in patches with normal areas in between— “skip lesions.” However, the combined effects of environmental changes, multiple genetic variations, mucosal immune dysregulation in response to gut microbes, epithelial barrier dysfunction, and alterations in microbial flora have some role for both in disease pathogenesis • Ulcerative colitis- chronic inflammatory disease that causes ulceration of the colonic mucosa (rectum and sigmoid colon), seen in people 20-40yers, Jewish, family history, Caucasian o Patho- The primary lesion of UC begins with inflammation at the base of the crypt of Lieberkühn in the large intestine. The disease begins in the rectum (proctitis) and may extend proximally to the entire colon (pancolitis). The mucosa is hyperemic and may appear dark red and velvety, and is involved in a continuous fashion. Small erosions form and coalesce into ulcers. Abscess formation, necrosis, and ragged ulceration of the mucosa ensue. Edema and thickening of the muscularis mucosae may narrow the lumen of the involved colon. Mucosal destruction and inflammation causes bleeding, cramping pain, and an urge to defecate. Frequent diarrhea, with passage of small amounts of blood and purulent mucus, is common. Loss of the absorptive mucosal surface and rapid colonic transit time cause large volumes of watery diarrhea. o C.M- intermittent periods of remission and exacerbation, bloody stools, fever, elevated HR, stools (10 to 20 a day), camping, anemia, fluid loss, • Crohns disease- inflammatory disorder that affects the large and small intestine, rectum seldomly involved, genetics and altered immunity, increases IgA and suppressor T cells. o Patho- Cell mediated, skip lesions (some areas affected and others aren’t), fistulae may occur o C.M.- vary based on location, diarrhea, bloody stools, weight loss, abd pain, malabsorption, hypoalbuminemia (low proteins) • Diverticula are herniations or saclike outpouchings of the mucosa and submucosa through the muscle layers, usually in the wall of the sigmoid colon. o Diverticulosis is asymptomatic diverticular disease. o Diverticulitis represents inflammation. Diverticular disease is most common among elderly women, but the incidence is increasing in younger individuals, particularly when much of the diet consists of refined foods.  Patho-Diverticula can occur anywhere in the gastrointestinal tract, and the most common sites are the left sigmoid colon in Western countries and the right colon in Asian countries. The exact etiology of diverticular disease remains unknown.50 The diverticula form from increases in intraluminal pressure, particularly at weak points in the colon wall, usually where arteries penetrate the tunica muscularis. A common associated finding is thickening of the circular muscles and shortening of the longitudinal (teniae coli) muscles surrounding the diverticula. Increased collagen and elastin deposition, not muscle hypertrophy, is associated with muscle thickening and this contributes to increased intraluminal pressure and herniation.  C.M- vague or absent, cramping lower abd, constriction of thickened vessels, diarrhea constipation, distention or flatulence • Appendicitis- Inflammation of the vermiform, projection from the apex of the cecum] o Patho- unknown cause, could be obstruction of the lumen with stool, tumors, or foreign bodies with consequent bacterial infection is the most common theory. The obstructed lumen does not allow drainage of the appendix, and as mucosal secretion continues, intraluminal pressure increases. The increased pressure decreases mucosal blood flow, and the appendix becomes hypoxic. The mucosa ulcerates, promoting bacterial or other microbial invasion with further inflammation and edema. o C.M- gastric or periumbilical pain, vague at first, increasing over 3-4 hrs, nausea vomiting, low fever, diarrhea, constipation. Perforation, peritonitis most common complications. • Varices are distended, tortuous, collateral veins. Prolonged elevation of pressure in the portal vein cause collateral veins to open between the portal vein and systemic veins and their transformation into varices, particularly in the lower esophagus and stomach but also over the abdominal wall (known as the caput medusae [Medusa head]) and rectum (hemorrhoidal varices). Rupture of varices can cause life-threatening hemorrhage. o Hepatopulmonary syndrome (vasodilation, intrapulmonary shunting, and hypoxia) and portopulmonary hypertension (pulmonary vasoconstriction and vascular remodeling) are complications of liver disease and portal hypertension. o C.M: Vomiting of blood (hematemesis) from bleeding esophageal varices is the most common clinical manifestation of portal hypertension. Slow, chronic bleeding from varices causes anemia and the presence of digested blood in the stools. Usually the bleeding is from varices that have developed slowly over a period of years. Rupture of esophageal varices causes hemorrhage and voluminous vomiting of dark-colored blood. The ruptured varices are usually painless. • Ascites- accumulation of fluid in the peritoneal cavity, traps fluid into the third space, cirrhosis is the most common cause of ascites other than heart failure, constrictive pericarditis, abd malignancies o PATHO: Several factors contribute to the development of ascites, including decreased synthesis of albumin by the liver and fluid retention. Portal hypertension and reduced serum albumin levels cause capillary hydrostatic pressure to exceed capillary osmotic pressure. This imbalance pushes water into the peritoneal cavity. Portal hypertension also increases the production of hepatic lymph, which “weeps” into the peritoneal cavity. Bacteria may be translocated from the gut into the peritoneal cavity causing peritonitis. Bacterial peritonitis causes an inflammatory response that increases mesenteric capillary permeability and fluid movement into the peritoneal cavity that promote ascites. Peripheral vasodilation. o C.M: accumulation of ascetic fluid causes weight gain, abd distension, increased abd girth, displace diaphragm and causes dyspnea, can develop into bacterial peritonitis- causes fever, chills, abd pain, decreased bowel sounds • Hepatic encephalopathy- (portal-systemic encephalopathy is a complex neurologic syndrome characterized by impaired cerebral function, flapping tremor (asterixis) and EEG changes. o PATHO: Hepatic encephalopathy results from a combination of biochemical alterations that affect neurotransmission. Liver dysfunction and the development of collateral vessels that shunt blood around the liver to the systemic circulation permit toxins absorbed from the gastrointestinal tract to accumulate and circulate freely to the brain. The accumulated toxins alter cerebral energy metabolism, interfere with neurotransmission, and cause edema. The most hazardous substances are end products of intestinal protein digestion, particularly ammonia, which cannot be converted to urea by the diseased liver. o C.M:subtle changes in personality, memory loss, irritability, lethargy and sleep disturbances, tremor, convulsion, coma, death • Jaundice, or icterus, is a yellow or greenish pigmentation of the skin caused by hyperbilirubinemia (plasma bilirubin concentrations greater than 2.5 to 3.0 mg/dl). Hyperbilirubinemia and jaundice can result from (1) extrahepatic (post hepatic) obstruction to bile flow, (2) intrahepatic obstruction, or (3) prehepatic excessive production of unconjugated bilirubin (i.e., excessive hemolysis of red blood cells) Jaundice in newborns is caused by impaired bilirubin uptake and conjugation o PATHO: Obstructive jaundice can result from extrahepatic or intrahepatic obstruction.  Extrahepatic obstructive jaundice develops if the common bile duct is occluded (e.g., by a gallstone, tumor, or inflammation). Bilirubin conjugated by the hepatocytes cannot flow into the duodenum. Therefore, it accumulates in the liver and enters the bloodstream, causing hyperbilirubinemia and jaundice.  Intrahepatic obstructive jaundice involves disturbances in hepatocyte function and obstruction of bile canaliculi. The uptake, conjugation, or excretion of bilirubin can be affected with elevated levels of both conjugated and unconjugated bilirubin. o Hemolytic Jaundice: Excessive hemolysis (destruction) of red blood cells can cause hemolytic jaundice (prehepatic jaundice). Increased unconjugated bilirubin is formed through metabolism of the heme component of destroyed red blood cells and exceeds the conjugation ability of the liver, causing blood levels of unconjugated bilirubin to rise. Decreased bilirubin uptake or conjugation also causes unconjugated hyperbilirubinemia, as occurs with reaction to some drugs (e.g., rifampin) and in genetic disorders such as Gilbert syndrome. o CM: conjugated bilirubin is water soluble and appears in the urine, complete obstruction of the bile flow from the liver to duodenum causes light colored stools, partial obstruction causes normal color and bilirubin is apparent in urine, fever chills, pain, bacterial or viral inflammation, puritis • Obstruction and inflammation are the most common disorders of the gallbladder. Obstruction is caused by gallstones, which are aggregates of substances in the bile. The gallstones may remain in the gallbladder or be ejected, with bile, into the cystic duct. o Cholelithiasis (gallstones) is a prevalent disorder in developed countries, where the incidence is 10% to 15% in white adults and 60% to 70% in Native Americans. Risk factors include obesity, middle age, female gender, use of oral contraceptives, rapid weight loss, Native American ancestry, genetic predisposition, and gallbladder, pancreatic, or ileal disease.  PATHO: Cholesterol gallstones form in bile that is supersaturated with cholesterol produced by the liver. Supersaturation sets the stage for cholesterol crystal formation, or the formation of “microstones.” More crystals then aggregate on the microstones, which grow to form “macrostones.” • Pigmented stones form from increased levels of unconjugated bilirubin, which binds with calcium. They are associated with chronic liver disease.  CM: Cholelithiasis is often asymptomatic. Abdominal pain and jaundice are the cardinal manifestations of cholelithiasis. Vague symptoms include heartburn, flatulence, epigastric discomfort, and food intolerances, particularly to fats and cabbage. The pain (biliary colic) occurs 30 minutes to several hours after eating a fatty meal. It is caused by the lodging of one or more gallstones in the cystic or common duct. It can be intermittent or steady and usually occurs in the right upper quadrant, radiating to the mid-upper area of the back. Jaundice indicates that the stone is located in the common bile duct. • Cholecystitis- Cholecystitis can be acute or chronic, but both forms are almost always caused by a gallstone lodged in the cystic duct. Acute acalculous cholecystitis has been reported as a complication of surgery, multiple trauma, or burn injury and is treated with cholecystostomy. The gallbladder becomes distended and inflamed, with pain similar to that caused by gallstones. Pressure against the distended wall of the gallbladder decreases blood flow and may result in ischemia, necrosis, and perforation. Fever, leukocytosis, rebound tenderness, and abdominal muscle guarding are common findings. Serum bilirubin and alkaline phosphatase levels may be elevated. The acute abdominal pain of cholecystitis must be differentiated from that caused by pancreatitis, myocardial infarction, and acute pyelonephritis of the right kidney. • Acute pancreatitis is usually a mild disease (edematous pancreatitis) and resolves spontaneously. Pancreatitis develops because of obstruction to the outflow of pancreatic digestive enzymes caused by bile and pancreatic duct obstruction (e.g., gallstones). The obstructed ducts result in accumulation of pancreatic secretions and pathologic activa