L04. Ch11 - Nonprotein Nitrogen & Renal Function PDF

Nonprotein Nitrogen and Renal Function C h a p t e r 11 Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK...

Nonprotein Nitrogen and Renal Function C h a p t e r 11 Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES Unit Objectives are your study guide (not this PowerPoint) Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! Introduction The kidneys play a vital role in maintaining levels of many substances in the human body, retaining critical components and eliminating what is not essential. Renal function tests are included in chemistry screening profiles to test for renal disease, water balance, and acid-base disorders. The urinary system consists of: – Two kidneys – Two ureters – Bladder – Urethra Renal Anatomy (2 of 3) The kidneys are divided into two distinct areas: – The outer layer, or cortex – The inner layer, or medulla Each kidney contains approximately one to 1.5 million nephrons, the functional unit of the kidney. Renal Anatomy (3 of 3) Renal blood flow is vital to renal function. – Supplied by renal artery – Enters the nephron through afferent arteriole – Flows through glomerulus into efferent arteriole – Glomerulus ▪ Coil of approximately 40 capillary loops referred to as the capillary tuft located within the Bowman’s capsule. – Blood is filtered in the glomerulus – Filtrate flows through the proximal convoluted tubule (PCT). Box 11-1 Urinary Filtrate Flow (1 of 2) 1. Bowman’s capsule 2. Proximal convoluted tubule (PCT) 3. Descending loop of Henle 4. Ascending loop of Henle 5. Distal convoluted tubule (DCT) 6. Collecting duct 7. Renal calyces 8. Ureter 9. Bladder 10. Urethra Box 11-2 Renal Blood Flow 1. Renal artery 2. Afferent arteriole 3. Glomerulus 4. Efferent arteriole 5. Peritubular capillaries 6. Vasa recta 7. Renal vein Renal Physiology (1 of 5) The three major renal functions: 1. Glomerular filtration 2. Tubular reabsorption 3. Tubular secretion 1. Glomerular Filtration ▪ Enhanced by a number of factors ▪ Pressure in the glomerular capillaries is high because of the difference in size between the afferent and efferent arterioles. ▪ Gasement membrane is negatively charged and large, negatively charged molecules (e.g., proteins) are repelled. Renal Physiology (3 of 5) 2. Tubular Reabsorption ▪ Active transport – Substance to be reabsorbed must be combined with a carrier protein contained in the membranes of the renal tubular cells – Requires the expenditure of energy from adenosine triphosphate (ATP) ▪ Renal threshold – Concentration above which the substance cannot be totally reabsorbed and is excreted in the urine ▪ Passive transport – Requires no energy – Characterized by movement of a substance from an area of high concentration to one of lower concentration – Water and urea are always reabsorbed through passive transport. Renal Physiology (5 of 5) 3. Tubular Secretion – Passage of substances from the peritubular capillaries into the tubular filtrate – The two major functions are: ▪ Elimination of waste products not filtered by the glomerulus ▪ Regulation of acid-base balance in the body through secretion of 90% of the hydrogen ions excreted by the kidney Analytes Associated with Renal Function (1) Nonprotein Nitrogen (NPN) – Comprises the products of catabolism of proteins and nucleic acids, which contain nitrogen but are not part of a protein molecule Blood urea nitrogen (BUN) 45% Amino acids 20% Uric acid 20% Creatinine 5% Creatine 1%-2% Ammonia 0.2% Table 11-1 Nonprotein Nitrogen Compounds and Relative Concentration (%) Analytes Associated with Renal Function (2) Urea or Blood Urea Nitrogen – BUN ▪ Major nitrogen-containing metabolic product of protein catabolism in humans – BUN is formed from: ▪ Exogenous protein – Protein in the diet ▪ Endogenous protein – Protein from the breakdown of cells in the body The chemical structure of urea  Analytes Associated with Renal Function (3) Urea or Blood Urea Nitrogen – Direct relationship between urea and the glomerular filtration rate (GFR) ▪ In a patient with a normal to increased G F R, approximately 40% of the B U N is reabsorbed and 60% is excreted. ▪ In a well-hydrated patient, more B U N is excreted, resulting in a lower serum B U N. ▪ In a dehydrated patient, 70% of the B U N is reabsorbed and 30% is excreted. – As a result, the patient’s serum B U N is increased and urine B U N is decreased. – BUN is dependent on three variables: ▪ Urea concentration ▪ Glomerular filtration rate (G F R) ▪ Level of hydration Analytes Associated with Renal Function (4) B U N Clinical Significance Azotemia An increased blood urea and other N P N compounds Uremia An increased urea/B U N Urea or Azotemia is classified into three categories Prerenal Blood Urea Renal Postrenal Nitrogen Box 11-3 Prerenal, Renal, and Postrenal Azotemia (1) Prerenal azotemia Prerenal azotemia Increased protein catabolism Decreased renal blood flow Muscle wasting (starvation) Congestive heart failure Gastrointestinal hemorrhage Dehydration Stress Shock (from blood loss) Steroids Advanced cirrhosis Uncontrolled diabetes mellitus Septic states High fever Increased protein catabolism Muscle wasting (starvation) Gastrointestinal hemorrhage Stress Steroids Uncontrolled diabetes mellitus High fever Box 11-3 Prerenal, Renal, and Postrenal Azotemia (3) Renal Azotemia Uremia Acute kidney injury Glomerulonephritis Nephrotic syndrome Acute renal failure Postrenal Azotemia Tumors of the bladder or prostate gland Prostatic hypertrophy Gynecologic tumors Nephrolithiasis Severe infections Analytes Associated with Renal Function (6 of 12) Urea or Blood Urea Nitrogen – B U N Clinical Significance ▪ B U N: Creatinine (B U N:C R) Ratio – The normal ratio is between 12:0 to 20:1. – In renal disease, B U N and C R are both elevated proportionally. – The ratio will fall within the normal range. – A high ratio >20:1 to 30:1 with a high B U N and a normal or only slightly elevated C R is associated with prerenal azotemia. – High ratios with an elevated C R suggest postrenal obstruction (azotemia) or prerenal azotemia in addition to renal disease. AnalytesAssociated with Renal Function (7 of 12) BUN Methodologies – Urease Urea + 2H2O ¾Urease ¾¾¾ ® 2NH4+ + CO3 -2 – In Berthelot’s reaction, the ammonium ion is reacted with phenol and hypochlorite in an alkaline medium to form indophenol blue, the chromagen which is measured. NH+4 + 5NaOCl + Phenol ¾Na ¾¾¾¾¾NaOH nitroprusside ® Indophenol blue + 5NaCl + 5H2O AnalytesAssociated with Renal Function (8 of 12) B U N Methodologies – In Nessler’s reaction, the addition of a double iodide compound (2Hgl2 + 2KI) results in the formation of a yellow to orange brown compound with NH4+. 2Hgl2 + 2Kl + NH4+ ® NH2Hg2I3 + 4KI + NH4I – The glutamate dehydrogenase (GLDH) procedure is the most commonly used. The disappearance of NADPH is measured as a decrease in absorbance as NADPH is oxidized to NAD+. NH4+ + 2-oxoglutarate + NADH ¾Glutamate ¾¾¾¾¾¾¾ dehydrogenase ® NAD+ + Glutamate + H2O Analytes Associated with Renal Function (9 of 12) BUN Methodologies – Diacetyl or Fearon Reaction ▪ Colorimetric reaction based on the condensation of diacetyl with urea to form the chromogen diazine H+ Urea + Diacetyl + H2O ¾¾¾¾® Diazine + 2H2O Strong acid Analytes Associated with Renal Function (10 of 12) BUN Reference Range – Reference range for BUN is 7-18 mg/dL. – Reference range for BUN on a 24-hour urine is 12 to 20 grams/24h. – A high protein diet increases BUN. – BUN 7.0 mg/dL Causes of hyperuricemia: Increased dietary intake Overproduction of uric acid Underexcretion of uric acid Specific enzyme defects Box 11-4 Hyperuricemia Primary Hyperuricemia Gout Idiopathic Secondary Hyperuricemia Cytotoxic chemotherapy Radiation therapy (leukemia, lymphoma) Malignancy (cancer) Acute or chronic renal disease, renal failure Increased tissue catabolism/starvation Glycogen storage disease High purine diet Ethanol abuse Toxemia of pregnancy Severe exercise Poisons (lead) Drug therapy (diuretics,barbiturates) Lesch-Nyhan syndrome Uric Acid (3) Uric Acid Clinical Significance – Primary gout ▪ Inborn error of metabolism ▪ Predominantly in men 30 to 50 years of age ▪ 7 times more common in men than women ▪ Symptoms – Arthritis (pain, inflammation of the joints) – Nephropathy – Nephrolithiasis ▪ Attacks can be precipitated by: – Alcohol – High-protein diets – Stress – Acute infection – Surgery – Certain medications Uric Acid (4) Uric Acid Methodologies – Phosphotungstic acid measures the development of a blue color (tungsten blue) as phosphotungstic acid (PTA) is reduced by uric acid in an alkaline medium. – Sodium carbonate is added to maintain the alkaline pH. Uric acid + Phosphotungstic acid ¾¾¾¾ ® Allantoin + Na CO 2 3 CO2 + Tungsten blue – Uricase catalyzes the oxidation of uric acid to allantoin. ▪ The decrease in absorbance at 293 nm, which is a peak absorbance for uric acid and one at which allantoin does not absorb. ▪ Peroxidase and a dye (4-aminoantipyrene) is a second modification and the most common automated method. Analytical Procedures for Assessment of Glomerular Filtration (1) Clearance Tests – Renal clearance ▪ The rate at which the kidneys remove a substance from the plasma or blood. ▪ A quantitative expression of the rate at which a substance is excreted by the kidneys in relation to the concentration of the same substance in the plasma usually expressed as mL cleared per minute. – Creatinine Clearance ▪ Creatinine is a very good indicator of glomerular filtration rate for three reasons: – Freely filtered by the glomeruli. – Not reabsorbed by the tubules to any significant extent. – Released into the plasma at a constant rate, resulting in constant plasma levels over 24 hours. Analytical Procedures for Assessment of Glomerular Filtration (3 of 11) Clearance Tests – Creatinine Clearance ▪ CrCl is calculated using the serum and urine creatinine levels and the urine volume. U V Clearance(X) = P U = urine concentration in mg/dL 24h volume (mL/day) P = plasma concentration in mg/dL ® V = urine flow in mL/minute (1440 min/24h) 1440 min/day Analytical Procedures for Assessment of Glomerular Filtration (4 of 11) Clearance Tests – Creatinine Clearance ▪ Creatinine clearance has to be corrected to an adult body surface area (BSA) of 1.73 m2 – Especially important for small or pediatric patients and obese patients – Dubois formula SA (surface area in m2 ) = W(kg)0.425 ´ H(cm)0.725 ´ 0.007184 Analytical Procedures for Assessment of Glomerular Filtration (5 of 11) Clearance Tests – Creatinine Clearance ▪ The correction or normalization factor for BSA is added to the CrCl equation. U´ V 1.73 m2 ´ 2 = CrCl (mL/minute/1.73 m2 ) P BSA m (normalization factor) – Patient’s instructions should stress the importance of complete collection because the largest source of error is incomplete urine collection. – Reference range ▪ For males is 97-137 mL/minute ▪ For females, 88-128 mL/minute. Analytical Procedures for Assessment of Glomerular Filtration (7 of 11) Clearance Tests – eGFR ▪ Use of an estimating or prediction equation to estimate glomerular filtration rate from the serum creatinine level in patients with chronic renal disease and those at risk for CKD ▪ Original Modification of Diet in Renal Disease (MDRD) Study Equation – In patients 18 years of age and older, the MDRD equation is the best means currently available to use creatinine values as a measure of renal function. Analytical Procedures for Assessment of Glomerular Filtration (8 of 11) Clearance Tests – eGFR ▪ When Scr is in mg/dL (conventional units) eGRF (mL/min/1.73 m2 ) = 175 ´ (Scr )-1.154 ´ (Age)-0.203 ´ 0.742 [if female] ´ 1.212 [if African American] Copyright © 2018, 2011 Pearson Education, Inc. All Rights Reserved Analytical Procedures for Assessment of Glomerular Filtration (9 of 11) Clearance Tests – Protein: Creatinine Ratio ▪ Normal protein excretion is 90 normal or increased ▪ Urinary tract and systemic GFR infections 2 Kidney damage with 60-89 mild reduction of G F R ▪ Nephrolithiasis ▪ Some medications 3 Moderate reduction of 30-59 GFR 4 Severe reduction of 15-29 GFR 5 Kidney failure