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glomerulus The proximal and distal convoluted tubule long loop of Henle collecting duct glomerulus steep pressure and semipermeable glomerular basement membrane glomerular filtration rate (GFR) proximal tubule tubular reabsorption renal threshold tubular secretion tubular secretion loop of Henle ADH Aldosterone Collecting Duct Urea urea, creatinine, and uric acid urea creatinine uric acid purines, adenine and guanine water balance sodium potassium chloride phosphate ion calcium pth magesium nonvolatile-acid respiratory system and the acid-base buffering system renin

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a capillary tuft surrounded by the expanded end of a renal tubule known as Bowmans capsule. located in the cortex composed of the thin descending limb, which spans the medulla, and the ascending limb, which is located in both the medulla and the cortex, composed of a region that is thin and then thick. formed by two or more distal convoluted tubules as they pass back down through the cortex and the medulla to collect the urine that drains from each nephron. is the first part of the nephron and functions to filter incoming blood. factors facilitate filtration. The volume of blood filtered per minute ______ is the and its determination is essential in evaluating renal function, as discussed in the section on Analytic Procedures. is the next part of the nephron to receive the now cell-free and essentially proteinfree blood. When the substances move from the tubular lumen to the peritubular capillary plasma The plasma concentration above which the substance appears in urine and its determination is useful in assessing both tubular function and nonrenal disease states. Secrete products of kidney tubular cell metabolism, such as hydrogen ions, and drugs, such as penicillin. describes the movement of substances from peritubular capillary plasma to the tubular lumen, and tubular secretion also describes when tubule cells secrete products of their own cellular metabolism into the filtrate in the tubular lumen. a hairpin-like lo op between the proximal tubule and the distal convoluted tubule. is a peptide hormone secreted by the posterior pituitary, mainly in response to increased blood osmolality, stimulates water reabsorption. is produced by the adrenal cortex under the influence of the reninangiotensin mechanism. Its secretion is triggered by decreased blood flow or blood pressure in the afferent renal arteriole and by decreased plasma sodium stimulates sodium reabsorption in the distal tubules and potassium and hydrogen ion secretion. are the final site for either concentrating or diluting urine plays an important role in maintaining the hyperosmolality of the renal medulla. three principal compounds NPNs makes up the majority (more than 75%) of the NPN waste excreted daily as a result of the oxidative catabolism of protein. Urea synthesis occurs in the liver. Muscle contains creatine phosphate, a high-energy compound for the rapid formation of adenosine triphosphate This reaction is catalyzed by creatine kinase (CK) and is the first source of metabolic fuel used in muscle contraction. is the primary waste product of purine metabolism are precursors of nucleic acids ATP and guanosine triphosphate (GTP), respectively. the body is through water loss or water conservation, which is regulated by the hormone ADH is the primary extracellular cation in the human body and is excreted principally through the kidneys. is the main intracellular cation in the body. is the principal extracellular anion and is involved in the maintenance of extracellular fluid balance. occurs in higher concentrations in the intracellular than in the extracellular fluid environments It exists as either a protein-bound or a nonprotein-bound form; homeostatic balance is chiefly determined by proximal tubular reabsorption under the control of parathyroid hormone (PTH). the second-most predominant intracellular cation, is the most important inorganic messenger in the cell. The ionized form 28 is freely filtered by the glomerulus and reabsorbed in the tubules under the control of a major intracellular cation, is important as an enzymatic cofactor must be continually transported in the plasma and excreted from the body, causing only minor alterations in physiologic pH. The other two strategies involved in this regulation Acid-Base Balance initial component of the renin-angiotensinaldosterone system. is produced by the juxtaglomerular cells of the renal medulla when extracellular fluid volume or blood pressure decreases.

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Erythropoietin Hypoxia Erythropoietin Vit D prostaglandins urea and creatinine creatinine creatinine clearance serum creatinine cystatin C Biologic Variation urine electrophoresis _2-M Myoglobin Rhabdomyolysis Urine microalbumin Glomerular Diseases Acute Glomerulonephritis Chronic kidney disease (CKD) Renal Hypertension hemodialysis urea Uric acid creatinine Plasma creatinine ammonia

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urea Uric acid creatinine Plasma creatinine Creatinine clearance, ammonia Reyes syndrome

is a single-chain polypeptide produced by cells close to the proximal tubules, and its production is regulated by blood oxygen levels. 2. Produces increased serum concentrations within 2 hours. 3. acts on the erythroid progenitor cells in the bone marrow, increasing the number of red blood cells (RBCs). 4. is one of three major hormones that determine phosphate and calcium balance and bone calcification in the human body 5. are a group of potent cyclic fatty acids formed from essential (dietary) fatty acids, primarily arachidonic acid. Produced by the kidneys increase renal blood flow, sodium and water excretion, and renin release analytical procedures 1. which accumulate when the kidneys begin to fail 2. It is an endogenous metabolic product synthesized at a constant rate for a given individual and cleared essentially only by glomerular filtration. 3. has become the standard laboratory method to determine GFR 4. estimated GFR (EGFR) be calculated each time 5. is a low-molecular-weight protein produced by nucleated cells. to be at least as useful as #4 and #3 detecting early changes in kidney function. 6. is defined as the random fluctuation around a homeostatic setting point. 7. is used primarily to distinguish between acute glomerular nephropathy and tubular proteinuria. used to screen for abnormal monoclonal or polyclonal globulins 8. is used clinically to assess renal tubular function in renal transplant patients, with elevated levels indicating organ rejection. 9. is a low-molecular-weight protein associated with acute skeletal and cardiac muscle in jury, functions to bind and transport oxygen from the plasma membrane to the mitochondria in muscle cells. 10. myoglobin release from skeletal muscle is sufficient to overload the proximal tubules and cause acute renal failure. 11. important in the management of patients with diabetes mellitus, who are at serious risk of developing nephropathy over their lifetimes PATHOPHYSIOLOGY 1. Disorders or diseases that directly damage the renal glomeruli may, at least initially, exhibit normal tubular function. 2. Pathologic lesions in acute glomerulonephritis primarily involve the glomerulus 3. is a clinical syndrome that occurs when there is a gradual decline in renal function over time 4. can be caused by either decreased perfusion to all or part of the kidney (ischemia) 5. (removal of waste from blood), the membrane is synthetic and outside the body. 1. 2. 3. 4. 5. is the major excretory product of protein metabolism is the product of catabolism of the purine nucleic acids is formed from creatine and creatine phosphate in muscle and is excreted into the plasma at a constant rate related to muscle mass inversely related to glomerular filtration rate (GFR), it is commonly used to assess renal filtration function is formed in the deamination of amino acids during protein metabolism

Clinical application 1. is used to evaluate renal function, to assess hydration status, to determine nitrogen balance, to aid in the diagnosis of renal disease, and to verify adequacy of dialysis. 2. is measured to assess inherited disorders of purine metabolism, to confirm diagnosis and monitor treatment of gout, to assist in the diagnosis of renal calculi, to prevent uric acid nephropathy during chemotherapeutic treatment, and to detect kidney dysfunction 3. concentration is used to determine sufficiency of kidney function and the severity of kidney damage and to monitor the progression of kidney disease 4. is a function of relative muscle mass, the rate of creatine turnover, and renal function. 5. measure of the amount of creatinine eliminated from the blood by the kidneys, and GFR are used to gauge renal function 6. provides useful information are hepatic failure, Reyes syndrome, and inherited deficiencies of urea cycle enzymes. 7. occurring most commonly in children is a serious disease that can be fatal. is preceded by a viral infection and the administration of aspirin. metabolic disorder of the liver

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Enzymatic methods urease glutamate dehydrogenase GLDH coupled enzymatic Indicator dye Conductimetric Caraway method Uricase Jaffe reaction Picric acid Kinetic Jaffe method IDMS Plasma Ion-selective electrode Spectrophotometric GLDH glutamate dehydrogenase.

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plasma, serum, or urine citrate and fluoride heparinized plasma, serum or urine bilirubin concentration salicylates and thiazides plasma, serum, or urine.

Methods 1. are used most frequently in urea 2. hydrolyzes urea in the sample and the ammonium ion (NH4_) produced in the reaction is quantified 3. The most common method couples the urease reaction with 4. Used on many automated instruments; best as kinetic measurement 5. Used in automated systems, multilayer film reagents, and dry reagent strips 6. Specific and rapid 7. The most common method for uric acid ____ which is based on the oxidation of uric acid in a protein-free filtrate, with subsequent reduction of phosphotungstic acid in alkaline solution to tungsten blue This method lacks specificity. 8. the enzyme that catalyzes the oxidation of uric acid to allantoin, are more specific and are used almost exclusively in clinical laboratories 9. The methods most frequently used to measure creatinine are based on the 10. creatinine reacts with _____ in alkaline solution to form a red-orange chromogen. 11. serum is mixed with alkaline picrate and the rate of change in absorbance is measured 12. is now used as a reference method in creatinine 13. The accurate laboratory measurement of ammonia in 14. Diffusion of NH3 through selective membrane into NH4Cl causing pH change, which is measured potentiometrically 15. NH3 _ bromophenol blue blue dye 16. GLDH NH4 _ _ 2-oxoglutarate _ NADPH _ H_ glutamate _ NADP_ _ H2O, Most common on automated instruments; accurate and precise 17. Ammonia can be measured by an enzymatic method using Specimen Requirements 1. Urea concentration may be measured in 2. inhibit urease 3. Uric acid may be measured in 4. may falsely decrease results obtained by peroxidase methods 5. have been shown to increase values for uric acid 6. Creatinine may be measured in Pathophysiology 1. An elevated concentration of urea in the blood 2. Very high plasma urea concentration accompanied by renal failure 3. is caused by reduced renal blood flow 4. causes an increase in plasma urea concentration as a result of compromised urea excretion 5. can be due to obstruction of urine flow anywhere in the urinary tract by renal calculi, tumors of the bladder or prostate, or severe infection. 6. is an X-linked genetic disorder (seen only in males) caused by the complete deficiency of hypoxanthine guanine phosphoribosyltransferase an important enzyme in the biosynthesis of purines 7. enzyme in the purine synthesis pathwaycause elevated uric acid concentration 8. concentration is found in gout, increased catabolism of nucleic acids, and renal disease 9. overproduction of uric acid 10. is less common than hyperuricemia and is usually secondary to severe liver disease or defective tubular reabsorption, as in Fanconi syndrome 1. 2. Plasma concentration of creatinine is inversely proportional to are neurotoxic and often associated with encephalopathy. increased extracellular glutamate concentration and subsequent depletion of adenosine triphosphate (ATP) in the brain is associated with inherited deficiency of enzymes of the urea cycle

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azotemia uremia Prerenal azotemia Decreased renal function Postrenal azotemia Lesch-Nyhan syndrome Phosphoribosylpyrophosphate Elevated plasma uric acid concentration Hyperuricemia Hypouricemia clearance of creatinine High concentrations of ammonia Hyperammonemia

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