Pathophysiology Test 2 Objectives

State the goals for dietary management of persons with chronic kidney disease.

to provide optimum nutrition while maintaining tolerable levels of metabolic wastes; severe restrictions on food/fluid intake = meals are unappetizing and complicated

Define biotherapy and list the three mechanisms whereby biotherapy exerts its effects

*Biotherapy* involves use of immunotherapy and biologic response modifiers to change a person's immune response and modify tumor cell biology · uses monoclonal antibodies, cytokines, and adjuvants

Explain the significance of casts in the urine

*Casts:* molds of the distal lumen of the nephron • develop due to the high protein concentration of the urine • devoid of cells = hylaine cast • mold + granules + cells = other types of casts

Describe the elimination functions of the kidney

Focuses on elimination of: • water, excess electrolytes, metabolic acids, and waste products from the blood As renal function declines: • increase in serum level of electrolytes and metabolic end products (e.g. urea, creatinine, phosphate, and potassium)

State at least four ways that benign and malignant neoplasms differ in regard to their characteristics

(1) the characteristics of the tumor cells, (2) the rate of growth (3) local invasion (4) the ability to metastasize.

List the common problems associated with chronic kidney disease, including alterations in fluid and electrolyte balance and disorders of skeletal, hematologic, cardiovascular, immune, neurological, skin, and sexual function, and explain their physiologic significance

*** LOOK AT THE CHART ON CHRONIC KIDNEY DISEASE ***

Cite the two most common causes of acute tubular necrosis and describe the course of the disease in terms of the initiation, maintenance, and recovery phases.

*ATN is the most common cause of intrarenal renal failure.* 1) Ischemia 2) Nephrotoxic drugs: risk/benefit factor to assist with the cure • first/second/third generation • Gram positive or gram negative • Different classification of drugs is nephrotoxicity and ototoxicity (deaden the nerves into and out of the ear) *Initiation/Oliguria Phase:* lasts hours or days, is the time from the onset of the precipitating event (ischemic phase of renal failure or toxin exposure) until tubular injury occurs • oliguria means decreased amount produced • 50-400 mL/day is for an oliguric patient - more than likely a catheter in place - close I&O - coca-cola urine because of the concentrations of the contaminants and hematuria (blood) - anticipate a rising BUN/creatinine level *hyperkalemia:* increased potassium in the blood *hyperphosphatemia:* increased phosphate *hypocalcemia:* decreased calcium level baseline is 125 ml/min to compare to *Maintenance/Diuretic Phase:* can either involve the oliguric or nonoliguric phase; characterized by marked decrease in the GFR, accompanied by retention of metabolic wastes such a creatinine, urea, and sulfate • increased urine output 2-4 L/day • unable to concentrate urine in response to massive amounts of output • increased GFR *Recovery:* period during which repair of renal tissue takes place; onset usually is heralded by a gradual increase in urine output and a fall in serum creatinine, indicating the nephrons have fully recovered to the point where urine excretion is possible • could take several months to a year • slowly the edema could go down • GFR is slowly returning to 70-80% of normal • BUN/serum creatinine may never return to normal • highly unlikely to go back to normal, including very much residual damage

Differentiate the pathology and manifestations of the nephrotic syndrome from those of the nephritic syndrome

*Acute nephritic syndrome* is an acute inflammatory process that occludes the glomerular capillary lumen and damages the capillary wall. It may occur as: • renal-limited primary disorder (acute postinfectious glomerulonephritis) • a secondary complicating disorder in systemic diseases Characterized by: - sudden onset of hematuria (either microscopic or grossly visible, with red cell casts) - proteinuria - diminished glomerular filtration rate (GFR) - oliguria - signs of impaired renal function. • extracellular fluid accumulation, edema, and hypertension develop because of the decreased GFR and enhanced tubular reabsorption of salt and water *Nephrotic syndrome* is not a specific glomerular disease, but a constellation of clinical findings that result from an increase in glomerular permeability and loss of plasma proteins in the urine Manifestations: - massive proteinuria (≥3.5 g/day in adults) - lipiduria (e.g., free fat, oval bodies, fatty casts) - hypoalbuminemia (<3 g/dL) - generalized edema - hyperlipidemia

Cite the method used for naming benign and malignant neoplasms

*Benign neoplasms* are differentiated cells have lost the ability to control cell proliferation • Benign tumors: tissue name + "-oma" *Malignant neoplasms* are less differentiated and have lost the ability to control both cell differentiation and proliferation. • Epithelial tissue: tissue name + "carcinoma" • Mesenchymal tissue: tissue name + "sarcoma"

Distinguish between cell proliferation and differentiation.

*Cell proliferation:* the reproduction or multiplication of similar forms, where tissues acquire new or replacement cells through mitotic cell division *Cell differentiation:* the cells take on other characteristics and change the specializations; the act or process in development in which unspecialized cells or tissues acquire more specialized characteristics; the orderly process in which new cells acquire new structure/ function of the cells they replace

Relate the effects of environmental factors such as chemical carcinogens, radiation, and oncogenic viruses to the risk for cancer development

*Chemical carcinogens:* alters gene expression, increasing DNA synthesis, enhancing gene amplification and altering intercellular communication *Radiation:* determines type of cancer development • sex of person and age of exposure, length of time exposed, and onset is related to age *Oncogenic viruses:* multifactorial, immunologically mediated chronic inflammation leading to persistent liver damage, regeneration, and genomic damages

State the basis for adverse drug reactions in patients with chronic kidney disease

*Chronic kidney disease and its treatment can interfere with the absorption, distribution, and elimination of drugs* • Many drugs are bound to plasma proteins (ex: albumin for transport in the blood) with the unbound portion of the drug being free to act at receptor sites and metabolize. A decrease in plasma proteins (albumin) that occurs in many persons with CKD results in less protein-bound drug and greater amounts of free drug. • Some drugs form intermediate metabolites during metabolism that are toxic, if not eliminated. Some pathways of drug metabolism (ex: hydrolysis) are slowed with uremia. • In persons with diabetes, insulin requirements may be reduced as renal function deteriorates. Decreased elimination by the kidneys allows drugs or their metabolites to accumulate in the body, which requires drug dosages be adjusted accordingly. • Some drugs contain unwanted nitrogen, sodium, potassium, and magnesium and must be avoided in patients with CKD. Examples: Penicillin contains potassium / Nitrofurantoin and ammonium chloride add to the body's nitrogen pool. • Administration of large quantities of phosphate-binding antacids to control hyperphosphatemia and hypocalcemia in patients with CKD interferes with the absorption of some drugs. • Persons with CKD should be cautioned against the use of over-the-counter remedies because of problems with drug dosing and elimination,

Describe the mechanisms of endocrine hypofunction and hyperfunction

*Endocrine hypofunction:* absence or impaired development of an endocrine gland or the absence of an enzyme needed for hormone synthesis. • gland may be destroyed by a disruption in blood flow, infection, inflammation, autoimmune responses, or neoplastic growth • Some endocrine-deficient states are associated with receptor defects: hormone receptors may be absent, binding of hormones may be defective, or the cellular responsiveness to the hormone may be impaired. *Endocrine hyperfunction* can result from excessive stimulation and hyperplasia of an endocrine gland from a hormone-producing tumor.

Compare methods used in grading and staging cancers

*Grading* -- I: well differentiated II: moderate dysplasia(dysfunctional formation of cell)/ moderate differentiation III: poorly differentiated, very abnormal, severe dysplasia IV: diff to determine cells of origin, Anaplasia *Staging* -- · Stage O: cancer in situ (self contained entity) · Stage I: tumor is spreading but is limited to tissue of origin, i.e. localized to the point of origin) · Stage II and III: limited spread, still in vicinity of origin · Stage IV: metastasis

Use the concept of growth fraction and doubling time to explain the growth of cancerous tissue

*Growth fraction* is the number of cells that are actively dividing over the number of cells that are resting • dividing cells/resting cells = *growth fraction* • as growth fraction increases, the doubling time decreases • Cancer cells continue to divide until limitations in blood supply and nutrients inhibit their growth ○ Indicator of cancerous cells to healthy cells *Doubling time:* like half-life; time it takes for total mass of cells in tumor to double *Metastasis:* establishing a presence somewhere away from that original tumor

Explain how host factors such as heredity, levels of endogenous hormones, obesity, and immune system function increase the risk for development of selected cancers

*Heredity:* several cancers exhibit an autosomal dominant inheritance that greatly increases the risk of developing a tumor (ex: breast cancer genes) *Hormones:* can fuel tumor, can be bad for development of tumor • cancer grows faster if it arose from that cell • if tested positive for hormone receptor site, it is hormone positive *Obesity:* multi-factorial and contains network of metabolic and immunologic mechanisms; increases estrogen level and growth factor *Immunological function:* antigens are weaker which gives the opportunity to change ○ The antigens change constantly as they divide - leads to constant battle/escape ○ It grows so rapidly that the immune system say it gives up (overwhelming antigen exposure) *Blocking factors:* some tumors conceal their antigens with chemicals, so the immune system can't double check and try to kill it

State the function of a hormone receptor and state the difference between cell surface hormone receptors and intracellular hormone receptors

*Hormone receptor* recognizes a specific hormone and translates the hormonal signal into a cellular response. • Cell-surface receptors exert their actions through cytoplasmic second messenger systems • Intercellular nuclear receptors modulate gene expression by binding to DNA or promoters of target genes.

Describe mechanisms of hormone transport and inactivation

*Hormone transport:* Hormones are released into the bloodstream from which they will diffuse into the interstitial tissue surrounding the target cells and into the blood stream to travel to target sites. The target cell has receptors specific to a given hormone and will be activated by either a lipid-soluble (permeable to plasma membrane) or water soluble hormone (binds cell-surface receptor). *Hormone inactivation:* hormone secretion by endocrine cells must be inactivated continuously to prevent their accumulation

Define the term hormone

*Hormone*: chemical messenger secreted by cell into blood that binds to receptor on DISTANT cell in another tissue

Relate the functions of thyroid hormone to hypothyroidism and hyperthyroidism

*Hypothyroidism* involves not having enough thyroid hormone (congenital or required). *Hyperthyroidism* involves having too much thyroid hormone (Grave's disease, thyroid tumors).

Characterize the manifestations and treatment of myxedematous coma and thyroid storm

*Myxedematous coma* is a life-threatening, end-stage expression of hypothyroidism characterized by coma, hypothermia, cardiovascular collapse, hypoventilation, and severe metabolic disorders including hyponatremia, hypoglycemia, and lactic acidosis. - Treatment includes aggressive management of precipitating factors, supportive therapy, and thyroid replacement therapy. *Thyroid storm* is manifested by a very high fever, extreme cardiovascular effects (i.e., tachycardia, congestive failure, and angina), and severe CNS effects. - requires rapid diagnosis and implementation of treatment - Peripheral cooling is initiated with cold packs and a cooling mattress.

Define neoplasm and explain how neoplastic growth differs from the normal adaptive changes seen in atrophy, hypertrophy, and hyperplasia.

*Neoplasm:* new and abnormal growth of a disorder of altered cell differentiation and growth, with uncontrolled proliferation of cells = not coordinated with normal cells • do not depend on negative feedback mechanisms to control their functions • uncoordinated and autonomous, lacking normal regulatory controls over cell growth and division/do not follow the normal "rules" of cell behavior

Describe methods used in detection and diagnosis of cancer, including the Papanicolaou smear, tissue biopsy, and tumor markers

*Pap smear:* is a cytologic method that consists of a microscopic exam of a properly prepared slide fro the purpose of detecting the presence of abnormal cells *Tissue biopsy:* the removal of a tissue specimen for microscopic study • obtained by needle biopsy; endoscopic methods, and laparoscopic methods *Tumor markers* are antigens expressed on the surface of tumor cells or substances released from normal cells in response to the presence of tumor • used for screening, establishing prognosis, monitoring treatment, and detecting recurrent disease

Describe alterations in physiologic function that accompany diabetic peripheral neuropathy, retinopathy, and nephropathy

*Peripheral neuropathy* is nerve damage caused by chronically high blood sugar and diabetes. It leads to numbness, loss of sensation, and sometimes pain in your feet, legs, or hands. It is the most common complication of diabetes. *Diabetic nephropathy* is the combination of lesions that occur concurrently in the diabetic kidney - the leading cause of chronic kidney disease (CKD) in persons starting renal replacement therapy - Not all people with diabetes develop clinically significant nephropathy; for this reason, attention is focused on risk factors for the development of this complication *Diabetic retinopathy* is characterized by abnormal retinal vascular permeability, microaneurysm formation, neovascularization and associated hemorrhage, scarring, diabetic macular edema, and retinal detachment

Differentiate the prerenal, intrinsic, and postrenal forms of acute renal failure in terms of the mechanisms of development and manifestations.

*Prerenal:* • causes include profound depletion of vascular volume, impaired perfusion due to heart failure and cardiogenic shock, and decreased vascular filling because of increased vascular capacity • medications inducing injury = endotoxins, radiocontrast agents for catheterization, cyclosporine (immunosuppressant used to prevent transplant rejection), amphotericin B (antifungal agent), epinephrine, and high doses of dopamine *Classes of drugs can impair renal adaptive mechanisms and convert compensated hyperfusion into injury (angiotensin II, NSAIDs)* • manifested by sharp decrease in urine output and disproportionate elevation of blood urea nitrogen compared to serum creatinine levels • impairment of blood entering the kidney to the point where it could not provide enough blood to the vessel -- What could affect? • atherosclerosis - narrowing of the arteries • blood clot • disease that could destroy the vessel and make it less elastic / blood pressure fluctuates moment by moment, you could tear the lining of the vessel because it's not flexible = diabetes • hypovolemic shock due to a severed left leg due to shock of massive amounts of blood *Intrinsic:* results from conditions that damage the structures within the kidneys major causes include ischemia associated with prerenal injury, injury to tubular structures of nephron (**acute tubular necrosis is most common), intratubular obstruction, acute glomerulonephritis, acute pyelonephritis • tumors are a possible obstruction *Postrenal:* obstruction of urinary outflow can occur in the ureter, bladder, or urethra • prostatic hyperplasia is common underlying problem • rarely causes injury unless one of the kidneys already is damaged or person only has one kidney • treatment consists of treating the underlying cause of obstruction so the urine flow can be reestablished before permanent nephron damage can occur • slow outlet obstruction of prostate in men/nephrotoxicity drugs also affects • if you have damage for one kidney, the other one can pick it up • prostatic hypertrophy

Describe the role of proto-oncogenes, tumor suppressor genes, apoptosis genes, and genes that control signal pathways in the development of a cancer cell line

*Proto-oncogenes:* normal genes that become cancer-causing genes if mutated *Tumor suppressor:* the category of cancer-associated under-activity genes that create an environment in which cancer is promoted *Apoptosis genes:* programmed cell death

Explain the value of urine specific gravity in evaluating renal function

*Specific gravity of urine* is a measure of the concentration of its solutes. • provides a valuable index of the hydration status and functional ability of the kidneys. Normal range = 1.010 - 1.025 with normal fluid intake. • during dehydration = 1.030 - 1.040 • during over-hydration < 1.000 Diminished renal function/kidney kailure = loss of renal concentrating ability = concentrations may fall as low as 1.006 to 1.010 • low levels are significant if they occur during periods that follow a decrease in water intake (e.g., during the first urine specimen on arising in the morning)

Describe the location and gross structure of the kidney

- Lies outside the peritoneal cavity in the back of the upper abdomen, one on each side of the vertebral column at the level of the 12th thoracic to 3rd lumbar vertebrae

Cite three theories that are used to explain the formation of kidney stones

1) Saturation Theory: urine is supersaturated with stone components 2) Matrix Theory: organic materials acts as nidus for stone formation 3) Inhibitor Theory: deficiency of substances that inhibit stone formation

Relate the functions of the adrenal cortical hormones to Addison disease (i.e., adrenal insufficiency) and Cushing's syndrome (i.e., cortisol excess).

Addison's is adrenal cortex insufficiency. Cushing's syndrome is glucocorticoid hormone excess.

Describe the function of the adrenal cortical hormones and their feedback regulation.

Adrenal cortex produces steroids, which are synthesized and released. Tissues exposure to high levels of steroids for prolonged periods of time = organ damage.

Explain the diagnostic tests that are used to diagnose and monitor diabetes mellitus

Blood and urine tests -- *Fasting plasma glucose:* food withheld for at least 8 hrs *Casual blood glucose test:* without regard of time or food eaten *Oral glucose tolerance test:* the test measures the body's ability to store glucose by removing it from the blood. *Capillary blood glucose monitoring:* methods use a drop of capillary blood obtained by pricking the finger or forearm with a special needle or small lancet. - Small trigger devices make use of the lancet virtually painless. - drop of capillary blood is placed on or absorbed by a reagent strip - glucose levels are determined electronically using a glucose meter. *Glycosylated hemoglobin:* is a widely used marker for chronic hyperglycemia, reflecting average blood glucose levels over a 2- to 3-month period of time - A1C plays a critical role in the management of persons with diabetes, is now recommended for use in the diagnosis of diabetes, with a threshold of greater than 6.5% - the test can also be used to identify persons at higher risk for developing diabetes

State the effects of a deficiency in growth hormone

Children with diabetes often fail to grow normally, even though GH levels are normal. When levels of thyroid hormone are lower than normal, bone growth and epiphyseal closure are delayed. • diabetes, diet, thyroid hormone

Explain the concept of GFR and how creatinine reflects its efficiency

GFR = how fast the blood is filtered • affected most by pressures in the blood that goes into the glomerulus and the integrity of the basement membrane *Creatinine* is a waste product of muscle function and breakdown. • should be cleared by the kidneys • GFR goes decreases = creatinine clearance goes down (blood levels of creatinine get higher)

Use the terms proliferation, sclerosis, membranous, diffuse, focal, segmental, and mesangial to explain changes in glomerular structure that occur with glomerulonephritis.

Glomerular diseases have traditionally been named according to tissue appearance • *proliferative:* is used to describe a hypercellular inflammatory process with proliferation of glomerular cell • *membranous:* an abnormal thickening of the glomerular basement membrane • *sclerotic:* an increase in the amount of extracellular material in the mesangial, subendothelial, or subepithelial tissue of the glomerulus *Glomerulonephritis:* inflammation of the glumeruli • inflammation/changes can diffuse to all parts of the glomeruli • only some glomeruli are affected and others are essentially normal •segmental = involving only a certain segment of each glomerulus; • mesangial = affecting only mesangial cells

Describe the role of the hypothalamus in regulating pituitary control of endocrine function

Hypothalamus cues the pituitary gland to tell other organs/glands to produce and secrete/ inhibit the appropriate hormones. · Command center of the body: control temperature, blood osmolality, blood nutrients, blood hormone levels, inflammatory mediators, emotion, pain

State the major difference between positive and negative feedback control mechanisms

Negative feedback = maintain homeostasis (thermostat) = output reduces original affect of the stimulus Positive feedback = output enhances original stimulus

Explain why children with precocious puberty are tall-statured children but short-statured adults

Persons with precocious puberty usually are tall for their age as children, but short as adults because of the early closure of the epiphyses.

Explain the mechanisms of pain and infection that occur with kidney stones

Prevention: • investigate cause, blood chemistries, a stone analysis, adequate fluid reduces concentration Removal: • Nonsurgical - ureteroscopic, percutaneous, extracorporeal • Surgical - large stones that can't be passed

Characterize the actions of oral hypoglycemic agents in terms of the lowering of blood glucose

Primary Action of DM Drugs -- • secretagogues: bind to sulfonylurea receptors causing influx of CA that causes release of insulin • Biguanides: primary action is to inhibit liver glucose production and increase tissue sensitivity to insulin; secondary action is weight loss and improved lipid panel • aglucosidase inhibitor: Act like amylin so that they slow carbohydrate absorption • thiazolidinediones: only one that attacks insulin resistance; does so by increasing insulin sensitivity in tissues • incretins: amplify the release of insulin

Explain how diseases such as SLE, diabetes mellitus, and hypertension result in glomerular injury

SLE = antibody and antigen complexes DM = vascular damage from sclerosis of blood vessels Hypertension = sustained high hydrostatic pressure causes damage to the basement membrane

Explain the mechanism by which radiation exerts its beneficial effects in the treatment of cancer

Therapeutic effects of radiation are more likely to be injure the more slowly proliferating cells and poorly differentiated tissue.

Characterize the function of the juxtaglomerular complex

They originate deeper in the cortex and have longer and thinner loops of Henle that penetrate the entire length of the medulla. The juxtamedullary nephrons are largely concerned with urine concentration.

Describe two types of immune mechanism involved in glomerular disorders

Two types of immune mechanisms have been implicated in the development of glomerular disease: (1) injury resulting from antibodies reacting with fixed glomerular antigens or antigens planted within the glomerulus (2) injury resulting from circulating antigen-antibody complexes that become trapped in the glomerular membrane

Describe the characteristics of normal urine

Urine: - clear, amber-colored fluid - approximately 95% water and 5% dissolved solids (solutes) • kidneys normally produce approximately 1.5 L of urine each day • Normal urine contains metabolic wastes, few/no plasma proteins, blood cells, or glucose molecules.

State the underlying cause of the virilization syndrome in congenital adrenal hyperplasia

Virilization in the female is a condition characterized by: premature pubarche, hirsutism, acne, male-pattern baldness, or menstrual irregularities. - requires postnatal androgen exposure. Masculinization occurs in some patients, but not all. • High androgen levels are most commonly caused by hyperplasia of the adrenal gland

Relate the process of cell differentiation to the development of a cancer cell line and the behavior of the tumor.

better the differentiation of a neoplasm = the slower its rate of growth = the more completely it retains the functional capabilities of normal cells

List common causes of urinary tract obstruction.

https://jigsaw.vitalsource.com/books/9781469898087/epub/OEBPS/images/ff25-13.jpg *Level of Obstruction:* Cause *Renal pelvis:* • Renal calculi • Papillary necrosis *Ureter:* • Renal calculi • Pregnancy • Tumors that compress the ureter • Ureteral stricture • Congenital disorders of the uretero-vesical junction and ureteropelvic junction strictures *Bladder and urethra:* • Bladder cancer • Neurogenic bladder • Bladder stones • Prostatic hyperplasia or cancer • Urethral strictures • Congenital urethral defects

Describe methods used in diagnosis of endocrine function

· *blood tests* provide info about a hormone at a specific time · *urine tests:* measurement of urine hormone or hormone metabolite done on a 24 hour urine sample · *stimulation and suppression test:* used when hypofunction of an endocrine organ is expected; recognizes when endocrine organs are not doing their job correctly • *genetic tests:* uses DNA analysis · *imagining techniques:* important in diagnosis and follow up of endocrine disorders Diagnostic tests: • PET SCAN = brightest area are cells with fastest metabolism (not usually the healthy cells • DEXA SCAN: looking for density of the bones

Characterize the actions of insulin with reference to glucose, fat, and protein metabolism

· Insulin inhibits · Glycogen breakdown (glycogenolysis) · Fat breakdown (lipolysis) can be stored · Protein breakdown à glucose (gluconeogenesis) and proteins can be made

Explain the relation between diabetes mellitus and infection.

· Soft tissue infections of the extremities, osteomyelitis, urinary tract infections and pyelonephritis, candidal infections of the skin and mucous surfaces, dental caries and periodontal disease, and tuberculosis. • neuropathy (can't feel and develop foot infections)

Explain what is meant by counterregulatory hormones and describe the actions of glucagon, amylin, somatostatin, gut-derived hormones, epinephrine, growth hormone, and the adrenal cortical hormones in regulation of blood glucose levels

· They counteract the storage functions of insulin in regulating blood glucose levels during periods of fasting, exercise, and other situations that either limit glucose intake or deplete glucose stores. *Glucagon:* a decrease in blood glucose concentration produces an immediate increase in glucagon secretion, and an increase produces a decrease in glucagon secretion. *Amylin:* slow down absorption of carbs in GI tract to give feeling of fullness *Somatostatin:* decreases GI activity; suppresses glucagon and insulin secretion *Gut-derived hormones:* increase insulin release after an oral nutrient load; suggests that gut-derived factors can stimulate insulin secretion after a predominantly carbohydrate meal. *Epinephrine*, a catecholamine, helps to maintain blood glucose levels during periods of stress. *Growth hormone:* decreases cellular uptake and use of glucose = increasing the level of blood glucose. Increased blood glucose level stimulates further insulin secretion by the beta cells. - Secretion of growth hormone normally inhibited by insulin and increased levels of blood glucose. - During fasting (when blood glucose levels & insulin secretion fall) growth hormone levels increase. - Exercise, such as running and cycling, and various stresses, including anesthesia, fever, and trauma, also increase growth hormone levels. *Adrenal cortical hormones:* critical to survival during periods of fasting and starvation. - Stimulate gluconeogenesis by the liver, sometimes producing a 6- to 10-fold increase in hepatic glucose production. - moderately decrease tissue use of glucose.

Describe the causes of foot ulcers in people with diabetes mellitus

· They represent the effects of neuropathy and vascular insufficiency · Neuropathy may prevent people from detecting pain; they are unable to adjust their gait to avoid walking on an area of the foot where pressure is causing trauma and necrosis.

Compare the distinguishing features of type 1 and type 2 diabetes mellitus, list causes of other specific types of diabetes, and cite the criteria for gestational diabetes

· Type 1A: autoimmune destruction of pancreatic beta cells · Type 1B: idiopathic diabetes : we don't know · Type 2: beta cell dysfunction and insulin resistance · Genetic defects in beta cell function: · Deformed pancreas · Diabetes secondary to other diseases, drugs, or transplant · Imposed on you, not your choices that happened but your body situation (Ex: rheumatoid arthritis and on medication, shut down beta cells) · Gestational diabetes mellitus: pregnant women can get this

Define the metabolic syndrome and describe its associations

· constellation of symptoms that typically occur together · associated with Hyperglycemia, Intra-abdominal obesity, Increased blood triglyceride level, Decreased HDL levels, Increased blood pressure, Systemic inflammation Parameters for girth: • waist circumference: females greater 35'' and males greater than 40'' • triglycerides greater or equal to 150 mg • HDL staying < 50 for females and < 40 for males • BP hypertension > 130/85 fasting glucose > 100mg/dl

Define prediabetes

· likely to have diabetes, but don't have it yet

Describe the clinical manifestations of diabetic ketoacidosis and their physiologic significance

· may be an initial manifestation of previously undiagnosed type 1 diabetes or may result from increased insulin requirements in type 1 diabetes during stress situations (Ex: infection or trauma, that increase the release of stress hormones)

Discuss possible concerns of adult survivors of childhood cancer

·Growth hormone deficiency in adults is associated with increased prevalence of dyslipidemia, insulin resistance, and cardiovascular mortality.

Explain the structure and function of the glomerulus and tubular components of the nephrons

• *glomerulus:* the filter for the blood, bringing everything smaller than a protein into Bowman's Capsule • *tubules:* bringing back across to the blood those components that the body needs; allowing the "trash" and extra fluid to be pulled out and form urine

Relate the physiologic functions of insulin to the manifestations of diabetes mellitus.

• Insulin attaches to sites on the cell wall to open the passageway for glucose to enter the cells. • When this doesn't occur , or does not occur adequately, the cells are low on fuel and as that happens in the brain, hunger is stimulated POLYPHAGIA. • High levels of glucose in the blood stream raises the oncotic pressure of the blood and decreases the plasma volume which stimulates the thirst drive POLYDIPSIIA. • Large quantites of fluids result in increased urination POLYURIA

Cite the early warning signs of cancer in children

• No early warning signs because children are less likely to recognize their symptoms than adults • younger children do not possess the verbal ability to describe them • often not diagnosed early

Distinguish between acute renal failure and chronic kidney disease in terms of causes, treatment, and outcome

• Acute Renal Failure: kidneys fail to remove metabolic end products from the blood and regulate the fluid, electrolyte, and pH balance of the extracellular fluids - abrupt in onset and often reversible, if recognized early and treated appropriately. - Common threat to those seriously ill • Causes: renal disease, systemic disease, or urologic defects of nonrenal origin. *prerenal:* marked decrease in renal blood flow *intrarenal:* damage to structures within the kidney account for 80% to 95% of cases *postrenal:* obstruction of urine outflow from the kidney • Treatment: treating the underlying cause of your kidney failure; treating complications until your kidneys recover (balance the amount of fluids in your blood, meds to control blood potassium, meds to restore blood calcium levels, dialysis to remove toxins from your blood) • Outcome: 25-80% mortality rate depending on cause and clinical status of patient (reflects on occurrence in elderly patients and frequently superimposed on other life-threatening conditions such as shock, trauma, and sepsis. *Chronic Kidney Disease:* the end result of irreparable damage to the kidneys • Causes: develops slowly • Treatment: often requires dialysis therapy or transplantation • Outcome: kidneys suddenly stop functioning = acute kidney failure

Explain the physiology of renal blood flow

• Afferent vessel brings blood into the glomerulus - relaxation leads to more blood into kidney, increase in GFR and pressure • Returns through Efferent - decrease resistance of outflow, decrease GFR *Hydrostatic pressure:* pressure within the capillaries = blood pressure • HPg (of glomerulus pushing fluid into Bowman's capsule) = 45 mmHg • HPc (of the capsule pushing back) = -10 mmHg *Capillary osmotic pressure:* force that pulls back into the capillaries as a result of large molecules • OPg (of glomerulus) = -28 mmHg *45 + (-10) + (-28) = *the optimal pressure of *7 mmHg* for filtration and the processes in place to adjust for shifts in blood pressure

Identify the age-related factors that predispose children and elderly persons to chronic kidney disease

• Causes of CKD in infants and children include congenital malformations (e.g., renal dysplasia and obstructive uropathy), inherited disorders (e.g., polycystic kidney disease), acquired diseases (e.g., glomerulonephritis), and metabolic syndromes (e.g., hyperoxaluria). • Problems associated with CKD in children include growth impairment, delay in sexual maturation, and more extensive bone abnormalities than in adults. Although all forms of renal replacement therapy can be safely and reliably used in children, CCPD, NIPD, and transplantation optimize growth and development. • Normal aging is associated with a decline in the GFR, which makes elderly persons more susceptible to the detrimental effects of nephrotoxic drugs and other conditions that compromise renal function.

List three causes of tall stature

• Causes of tall stature: are genetic or chromosomal disorders such as Marfan syndrome or XYY syndrome. • Endocrine causes of tall stature include sexual precocity because of early onset of estrogen and androgen secretion and excessive GH

Compare the action of cell cycle-specific and cell cycle-independent chemotherapeutic drugs

• Cell-cycle nonspecific have a linear dose-response curve (the greater the dose of the drug) = the greater is the fraction of cell kill • Cell-cycle-phase-specific drugs have a plateau; cell kill will not increase with further increases in drug dosage

Discuss the role of diet and exercise in the management of diabetes mellitus

• Diabetics must maintain steady blood glucose within acceptable ranges so protein and complex carbohydrates are desirable. • Insulin therapy is administered based upon the blood sugars before and after food intake. • Exercise is advised to help DMII patients to manage the disease by managing weight, however, a balance between increase exercise and the increased demand of sugars/insulin regulation requires careful monitoring and patient education

Describe the scientific principles underlying dialysis treatment and compare hemodialysis with peritoneal dialysis.

• Dialysis or renal replacement therapy is indicated when advanced uremia or serious electrolyte imbalances are present • transplantation is the preferred treatment, however dialysis plays a critical role as treatment method for kidney failure 1) hemodialysis (artificial kidney) • consists of a blood delivery system, a dialyzer, dialysis fluid system • dialyzer is a hollow cylinder composed of capillary tubes w/ semipermeable membrane for blood circulation allowing all molecules except blood cells/plasma proteins to flow freely • direction of flow is determined by concentration gradient • waste/excess electrolytes in the blood normally diffuse into dialyzing solution • tubing implanted into an artery and vein 2) peritoneal dialysis • same principles of diffusion/osmosis/ultrafiltration • a thin serous membrane of the peritoneal cavity serves as the dialyzing membrane • surgical implantation of a silastic catheter into the peritoneal cavity at a point below the umbilicus • catheter is tunneled through subcutaneous tissue and exits on the side of the abdomen

Describe the genetic basis for renal cystic disease, the pathology of the disorder, and its signs and symptoms

• Dominant disorders occur in adults • Recessive presents in children • causes more structural damage to the kidney and leads to CRF

Explain the function of sodium in terms of tubular transport mechanisms:

• Glomerular filtrate is changed considerably by the tubular transport of water and solutes • Tubular transport can result in reabsorption of substances from the tubular fluid into the peritubular capillaries or secretion of substances into the tubular fluid from the blood in the peritubular capillaries • The mechanisms of transport across the tubular cell membrane are similar to those of other cell membranes in the body and include active and passive transport mechanisms. • Water and urea (a byproduct of protein metabolism) are passively absorbed along concentration gradients. • Sodium (Na+), other electrolytes, as well as urate (a metabolic end-product of purine metabolism), glucose, and amino acids, are reabsorbed using primary or secondary active transport mechanisms to move across the tubular membrane.

Describe the adverse effects of radiation therapy

• Injurious to all rapidly proliferating cells Adverse effects of radiation therapy: infection, bleeding, anemia (due to loss of blood cells), nausea, and vomiting. • total number of rads that can be used in any body region due to cumulative effects on other organs in the region. • Palliative radiation is limited to just enough to get results and the rest saved for later treatments • Radiation for cure is best given in one long sequence of radiation; breaks decrease the therapeutic benefits.

Describe the effects of urinary tract obstruction on renal structure and function

• Obstruction causes retention of urine within the kidney. • Stones are most common cause, typically in the ureters, but they can get stuck in the pelvis of the kidney. • Urine made ~ about 125 ml per hour, so it backs up into the kidney. • More glomeruli that are damaged, the lower the GFR.

Differentiate primary, secondary, and tertiary endocrine disorders

• Primary disorders: originate in the target gland responsible for producing the hormone. • Secondary disorders: the target gland is essentially normal, but its function is altered by defective levels of stimulating/releasing hormones from the pituitary gland • Tertiary disorders: hypothalamic dysfunction; both the pituitary and target glands are under-stimulated

State a difference between the synthesis of protein hormones and that of steroid hormones

• Protein and polypeptide (amino) hormones are synthesized and stored in cytoplasm until secreted. • Steroid hormones, lipid-soluble hormones, are released as synthesized.

Explain the vulnerability of the kidneys to injury caused by drugs and toxins

• Renal tubular cells, particularly proximal tubule cells, are vulnerable to the toxic effects of drugs because their role in concentrating and reabsorbing glomerular filtrate exposes them to high levels of circulating toxins. The tolerance to drugs varies with: • age • renal function • state of hydration • blood pressure • pH of the urine Elderly persons are particularly susceptible to kidney damage caused by drugs and toxins. The dangers of nephrotoxicity are increased when two or more drugs capable of producing kidney damage are given at the same time.

Differentiate short stature of endocrine causes from short stature of nonendocrine causes

• Short stature of endocrine causes: emotional (malnourished children) disturbances, which can lead to functional endocrine disorders - causing psycho-social dwarfism. • Short stature from non-endocrine causes: chromosomal abnormalities, protein calorie malnutrition, chronic kidney disease, poorly controlled diabetes

Characterize the synthesis, transport, and regulation of thyroid hormone

• Synthesis of the thyroid hormone includes the thyroid release of T3 and T4 that are carried by binding proteins - T3 stimulates metabolism - T4 is inactive until converted into T3 in tissues • Both exert negative feedback regulation of thyroid hormone

Describe the pathophysiology of the Somogyi effect and the dawn phenomenon

• The Somogyi effect describes a cycle of insulin-induced post hypoglycemic episodes. • These counterregulatory hormones cause blood glucose to become elevated and produce some degree of insulin resistance. - cycle begins when the increase in blood glucose and insulin resistance is treated with larger insulin doses. - hypoglycemic episode often occurs during the night or at a time when it is not recognized, rendering the diagnosis of the phenomenon more difficult. • The dawn phenomenon occurs alone, it may produce only mild hyperglycemia, but when it is combined with the Somogyi effect, it may produce profound hyperglycemia.

Describe the clinical condition resulting from the hyperosmolar hyperglycemic state including type 2 diabetes, acute pancreatitis, severe infection, myocardial infarction, and treatment with oral or parenteral nutrition solutions. It is seen most frequently in people with type 2 diabetes

• The condition may be complicated by thromboembolic events arising because of the high serum osmolality. • The most prominent manifestations are weakness, dehydration, polyuria, neurologic signs and symptoms, and excessive thirst.

Describe methods used in the diagnosis and treatment of kidney stones

• Ultrasounds, IVP to look at kidney are typically done. • Objective is to see the location of the obstruction. • Ultrasound waves are used to try to crush the stone. • Urine collected and filtered to gather the "gravel" • Purpose is to identify the composition of the stone. • Treatment then is to observe kidney function to measure the damage and then alter diet, hydration, and pH of urine to try to stop the formation of more stones

Describe how the kidney produces a concentrated or dilute urine

• ability of the kidney to respond to changes in the osmolality of the extracellular fluids by producing either a concentrated or dilute urine depends on the establishment of a high concentration of osmotically active particles in the interstitium of the kidney medulla and the action of the antidiuretic hormone (ADH) in regulating the water permeability of the surrounding medullary collecting tubules • osmolarity of body fluids relies heavily on the ability of the kidney to produce dilute or concentrated urine • Urine concentration depends on three factors: (1) the osmolarity of interstitial fluids in the urine-concentrating part of the kidney (2) the antidiuretic hormone (ADH) (3) the action of ADH on the cells in the collecting tubules of the kidney.

Define and describe cancer cachexia as a clinical manifestation of cancer

• common manifestation of most solid tumors with the exception of breast cancer • Muscle wasting and weakness as a symptom of the cancer. • more common in children and elderly persons • more pronounced as the disease progresses • responds less to chemotherapy and are more prone to toxic side effects

Describe the clinical features and causes of hypopituitarism

• decrease secretion of pituitary hormones • hypersecretion and hyposecretion of - pituitary adenoma (adults) - hypothalemic tumors (neoplasms arrive) -- short stature due to lack of endocrine gland -- headache, visual loss, expanding tumor

Relate the functions of growth hormone to the manifestations of acromegaly and adult-onset growth hormone deficiency

• excessive GH occurs in adulthood • represents an exaggerated growth of the ends of the extremities (fingers, hands, and toes)

Characterize Wilms tumor in terms of age of onset, possible oncogenic origin, manifestations, and treatment

• usually presents 3-5 years of age in one or both kidneys • composed of normal fetal tissue, congenital anomalies, usually solitary mass National Wilms Tutor Study Group Stage I: limited to kidney and excised with capsular surface intact Stage II: extend to renal capsule and can be excised Stage III: extends to abdomen Stage IV: hematogenous metastisis, usually in lung Treatment: surgery, chemo and radiation therapy

State the definition, classifications, and diagnostic criteria for chronic kidney disease

• fewer nephrons are functioning • decreased GFR greater than 3 months • remaining nephrons must filter more which lead to hypertrophy, increasing function to compensate for the few nephron left = working harder • MUST MONITOR how much protein the patient is intaking • the amount of BUN in a patient's blood = how much protein the patient should include in his diet *CKD* is a pathophysiological process that results in the loss of nephrons and a decline in renal function as determined by a measured or estimated decrease in the GFR that has persisted for more than 3 months. *Diagnostic Criteria:* • the GFR is considered the best overall measure of kidney function • normal GFR is 120-130 ml/min/1.73 m^2 • GFR below 60 ml/min/1.73m^2 represents a loss of one half or more of the level • GFR is usually estimated using the serum creatinine concentration • Modification of Diet in Renal Diseases (MDRD) equation takes the factors of age, sex, ethnicity, and body size into account and is often used for estimating GFR based on serum creatinine levels • proteinuria serves as a key adjunctive tool for measuring nephron injury and repair - urine normally contains a small amounts of protein - persistent increase in protein excretion is usually a sign of kidney damage • measurement of urinary albumin is preferred - urine dipstick testing are acceptable for detecting albuminuria - positive (+1 or greater), albuminuria is usually confirmed by quantitative measurement of the albumin-to-creatinine ratio in a spot (untimed) urine specimen - *microalbuminuria:* early sign of diabetic kidney disease, refers to albumin excretion that is above the normal range but below the range normally detected by tests of total protein excretion in the urine - populations at risk include those with diabetes mellitus, hypertension, or family history of kidney disease *CLASSIFICATION CHART* Stage 1) •kidney damage that is present but undetected • Kidney damage with normal or increased GFR; GFR ≥ 90 Stage 2) • decreased GFR without recognized markers of kidney damage can occur in infants/older adults - considered "normal for age"; characteristic loss of renal reserve • Other causes of chronically reduced GFR without kidney damage includes removal of one kidney, extracellular fluid depletion, and systemic illnesses associated with reduced kidney perfusion (heart failure and cirrhosis); • kidney damage with mild decrease in GFR; GFR = 60-89 Stage 3) •Moderate decrease in GFR; GFR = 30-59 Stage 4) •kidney damage noted; severe decrease in GFR; GFR = 15-29 Stage 5) •accompanied by most signs and symptoms of uremia or a need for dialysis or transplantation • kidney failure; GFR = <15 (or dialysis)

Describe tests in the diagnosis and management of thyroid disorders

• free T4 test measures the unbound portion of T4 that is free to enter cells to produce its effects • radioiodine (123I) uptake test measures the ability of the thyroid gland to remove and concentrate iodine from the blood • Thyroid scans (123I, 99mTc-pertechnetate) can be used to detect thyroid nodules and determine the functional activity of the thyroid gland • Ultrasonography can be used to differentiate cystic from solid thyroid lesions • CT and MRI scans are used to demonstrate tracheal compression or impingement on other neighboring structures • Fine needle aspiration biopsy of a thyroid nodule has proved to be the best method for differentiation of benign from malignant thyroid disease

*GFR (Glomerular Filtration Rate:* 125mL/min

• higher GFR = faster flow of blood through the kidney --> more you loose essential nutrients such as glucose, vitamins, minerals, amino acids, etc. • lower GFR = slower flow of blood through the kidneys --> waste (urea) is able to leak back into the blood, indicates a degree of renal failure [lower = worse off it is]

Cite a definition of tubulointerstitial kidney disease

• histologic and functional alterations that affect renal tubular structures (including the proximal and distal tubules) and may affect the interstitial tissue that surrounds the tubules These alterations may be due to: • primary disease that affect the glomerulus • secondary manifestation of other diseases such as DM (diabetes mellitus)

Describe the effects of congenital hypothyroidism

• leads to mental retardation and impaired physical growth, unless treatment is initiated during the first months of life • increase in weight, swollen thyroid = mass called goiter

Trace the pathway for hematologic spread of a metastatic cancer cell

• lungs and liver are the most frequent metastatic sites for hematologic spread • To metastasize: 1. a cancer cell must be able to break loose from the primary tumor which is facilitated by the loss of cell affinity in cancer cells (begins as a solid, then breaks off) 2. spread to thoracic duct and into blood stream in order to emerge in a favorable location 4. invade the surrounding tissue and begin to grow by establishing a blood supply (goes to surrounding tissue, then blood and lymph system)

Define the term paraneoplastic syndrome and explain its pathogenesis and manifestations

• manifestations in sites that are not directly affected by the disease • can caused by the elaboration of hormones by cancer cells, other result from the production of circulating factors that produce hematopoietic, neurologic, and dermatologic syndromes • most associated with lung, breast, and hematologic malignancies

Cite the risk factors and manifestations of renal cell carcinoma.

• peaks between 55-84 years of age • most are sporadic; 5% inherited *Inherited:* multifactorial and bilateral; appears earlier than sporadic • Epidemiologic evidence suggests heavy smoking and kidney disease. • obesity • mainly silent disorder in early stages, symptoms mean advanced disease

Characterize the role of insulin like growth factors (IGFs)

• produced mainly by the liver • Growth hormone cannot directly produce bone growth; instead, it acts indirectly by causing the liver to produce IGFs. • possess during normal child growth • primary mediator of GH • helps with protein synthesis of bone, muscle, and organ

Describe the clinical manifestations of insulin-induced hypoglycemia and state how these may differ in elderly people

• produces a compensatory increase in blood levels of catecholamines, glucagon, cortisol, and growth hormone • these counterregulatory hormones cause blood glucose to become elevated and produce some degree of insulin resistance

Explain the endocrine functions of the kidney

• renin-angiotensin-aldosterone mechanism = regulation of blood pressure • activating vitamin D = calcium metabolism/absorption • synthesis of erythropoietin = production of red blood cells in bone marrow

Discuss the effects of pituitary tumors

• the most common cause of pituitary dysfunction is hypothalamic tumors. • usually manifest with signs of pituitary hyposecretion prior to development of headache, visual loss, and other neurological symptoms due to the mass effect of the expanding tumor

State the importance of angiogenesis in cancer growth and metastasis

• tumors cannot enlarge unless angiogenesis occurs, also needed for metastisis *Lymphatic metastasis:* extracellular fluid is drained into the lymph system for filtering, cancer cells can and do get washed away (Ex: include breast cancer and axillary nodes, lung cancer and mediastinal nodes)