Renal Function Chapter 4 PDF

Renal Function Chapter 4 1 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 re...

Renal Function Chapter 4 1 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! 2 1  Renal Physiology Nephron: functional unit of the kidney 1 to 1.5 million per kidney Two types of nephrons Cortical 85% Situated within the cortex of the kidney Removal of waste products & Reabsorption of nutrients Juxtamedullary Longer loops of Henle Extend deep into the medulla of the kidney Urine concentration 3 Renal Anatomy and Physiology 4 2  Renal Physiology Four Renal functions 1.Blood flow 2.Glomerular filtration 3.Tubular reabsorption 4.Tubular secretion 5 2 1 Renal Blood Flow 4 3 1. Renal artery 2. Afferent arteriole Supplies blood to the kidney 3. Glomerulus Receives blood from the arteriole 4. Efferent arteriole Blood leaves the glomerulus These vessels assist in maintaining hydrostatic pressure differential 6 3  Renal Blood Flow (continued_1) 7 4. Peritubular capillaries/proximal 6 convoluted tubule 4 5. Vasa recta/loops of Henle 6. Peritubular capillaries/distal convoluted 4 tubule 7. Renal vein 5 5 7 Renal Plasma Flow Average body size 1.73 m2 surface Renal blood flow ~1200 mL/min Renal plasma flow = 600 to 700 mL/min Correction for variance in body surface area must be calculated 8 4  Glomerular Filtration Glomerulus Coil of eight capillary lobes Glomerular filtration barrier Located in Bowman’s capsule Nonselective filtration Filtration factors 1. Cellular structure 2. Hydrostatic and oncotic pressure 3. Renin-angiotensin-aldosterone system 9 Cellular Structure of the Glomerulus Three cellular layers Capillary wall Endothelial cells have pores (fenestrated) Large molecules and cells are blocked Basement membrane Further restriction of large molecules Bowman’s capsule inner layer Intertwining podocytes Membrane covered filtration slits 10 5  Cellular Structure of the Glomerulus (continued) Shield of negativity Repels molecules with a negative charge Small enough to pass through three layers of the barrier Albumin has a negative charge and is repelled 11 Glomerular Pressure Juxtaglomerular apparatus: regulation of arteriole size Maintains consistent glomerular blood pressure Low systemic blood pressure Larger afferent and smaller efferent Prevents decreased glomerular blood flow High systemic blood pressure Smaller afferent arteriole Prevents overfiltration and glomerular damage 12 6  Renin-Angiotensin-Aldosterone System (RAAS) Regulates blood flow to and within the glomerulus Responds to blood pressure and plasma sodium changes Juxtaglomerular apparatus Juxtaglomerular cells: afferent arteriole Macula densa: efferent arteriole Macula densa initiates RAAS in response to blood pressure changes 13 Renin-Angiotensin-Aldosterone System RAAS (continued_1) Renin secreted by juxtaglomerular cells Angiotensinogen: blood substance Angiotensin 1: passes through lungs Angiotensin-converting enzyme (ACE) Angiotensin II Aldosterone 14 7  Renin-Angiotensin-Aldosterone System RAAS (continued_3) Dilates afferent arteriole Constricts efferent arteriole Stimulates sodium and water in proximal convoluted tubules Triggers release of aldosterone Triggers release of antidiuretic hormone 15 Renin-Angiotensin-Aldosterone System RAAS (continued_4) Normal 120 mL/min of filtrate Composition Ultrafiltrate of plasma Same composition minus plasma proteins, protein-bound substances, and cells Filtrate specific gravity = 1.010 16 8  RAAS System Animation 17 17 3. Tubular Reabsorption Reabsorption starts when the plasma ultrafiltrate enters the proximal convoluted tubule Active transport Carrier proteins and cellular energy needed for transport back to blood Glucose, salts (Na is highest), amino acids in proximal convoluted tubule Chloride in ascending loop of Henle Sodium in distal convoluted tubule 18 9  3. Tubular Reabsorption (continued) Passive transport Controlled by the differences in substance concentration gradients on sides of a membrane Water reabsorption occurs throughout the nephron Exception is ascending loop of Henle Accompanies high amount of sodium reabsorption in PCT Urea in PCT and ascending loop of Henle Sodium in the ascending loop of Henle 19 Maximal Reabsorptive Capacity (T m) Plasma concentration of a substance that is normally completely reabsorbed reaches an abnormally high level Renal threshold: plasma level causing active transport to cease Glucose threshold: 160 to 180 mg/dL Threshold distinguishes excess filtration from tubular damage 20 10  4. Tubular Concentration Descending loop of Henle Passive reabsorption of water into the high osmotic gradient of the renal medulla Ascending loop of Henle Chloride actively reabsorbed Sodium passively reabsorbed Walls are impermeable to water 21 Tubular Concentration (continued) Countercurrent mechanism Maintain the osmotic gradient in the medulla Medulla is diluted by the water from the descending loop Reconcentrated by sodium and chloride from the filtrate in the ascending loop Aldosterone-controlled Na reabsorption if needed by body 22 11  Collecting Duct Concentration Final filtrate concentration Water reabsorption controlled by ADH in response to body hydration Osmotic gradient in the medulla Vasopressin (ADH) ADH Controls permeability of DCT and CT walls to water Amount of ADH produced by hypothalamus determines permeability The chemical balance in the body is actually the final determinant of urine volume and concentration 23 Diagram of ADH Regulation ↑Body Hydration = ↓ADH = ↑Urine Volume ↓Body Hydration = ↑ADH = ↓Urine Volume 24 12  4. Tubular Secretion Secretion = blood peritubular capillaries to filtrate Contrast to reabsorption = filtrate to blood Eliminate nonfiltered wastes Protein-bound substances Regulate acid-base balance Secrete H+ ions to return filtered buffers to the blood Excrete excess H+ ions 25 Acid-Base Balance Normal blood pH 7.4 Buffering and elimination of excess acid Dietary intake Body metabolism Bicarbonate (HCO3) returned to blood Secretion of hydrogen ions (H+) into filtrate 100% of bicarbonate reabsorption 26 13  Acid-Base Balance (continued_2) 27 Acid-Base Balance (continued_3) Rates determined by the acid-base balance in the body Disruption causes Metabolic acidosis Renal tubular acidosis 28 14  Renal Function Tests 29 Glomerular Filtration Tests Clearance tests Measure rate at which the kidneys can remove a filterable substance from the blood Substance analyzed cannot be reabsorbed or secreted by the tubules Stability of substance during a long urine collection period Consistency of plasma level Availability to the body Availability of tests to measure the substance 30 15  Substances Measuring GFR Creatinine Beta2 microglobulin Cystatin C Radioisotopes Exogenous procedure Requires an infused substance Endogenous procedure Substance already present in the body Method of choice 31 Urea Clearance Tests Urea is present in all urine specimens Approximately 40% is reabsorbed Normal values were adjusted Patients were hydrated to produce a urine flow of 2mL/min 32 16  Inulin Clearance Polymer of fructose Stable substance neither reabsorbed nor secreted by the tubules Not a normal body constituent Must be infused by IV during the testing period 33 Creatinine Clearance Creatinine is a waste product of muscle metabolism Links with adenosine triphosphate to produce adenosine diphosphate and energy Found at a constant level in the blood Endogenous procedure Newer methods of testing have been developed that use the serum creatinine, cystatin C, or B2M values Results of these tests are reported as estimated glomerular filtration (eGFR) 34 17  Creatinine Clearance Disadvantages Tubular secretion increases with high blood creatinine levels Chromogens present in human plasma react in the chemical analysis Gentamicin, cephalosporins, and cimetidine inhibit tubular secretion Bacteria break down creatinine if urine is stored at room temperature Diet heavy in meat during timed collection increases urine creatinine Not reliable with muscle-wasting diseases Accurate results depend on the accurate completing of a 24-hour collection It must be corrected for smaller/larger body surface area 35 Procedure Greatest error is improperly timed urine specimen; Report in milliliters per minute This is referred to as the glomerular filtration rate (GFR) Principle: to determine the amount of creatinine (mL) completely cleared from the plasma during 1 minute Required measurements Urine volume in milliliters per minute (V) Calculation of urine volume: Milliliters in specimen/minutes collected Example  2-hour specimen volume = 240 mL  2 × 60 = 120 min  240/120 = 2 mL/min Urine creatinine in mg/dL (U) Plasma creatinine in mg/dL (P) Standard Clearance Formula: CP = UV and C = UV P 36 18  Normal Values Creatinine is produced as a result of muscle destruction; therefore, normal values are based on size; the larger the person, the more creatinine is produced Men: 107 to 139 mL/min Women: 87 to 107 mL/min Normal reference range of plasma creatinine is 0.6 to 1.2 mg/dL Values are lower in older people Nomograms are available to adjust for size Nomogram Fig. 4-13 37 eGFR-Modification of Diet in Renal Disease (MDRD) Formula eGFR equations are superior to serum creatinine solely because they include variables for race, age, and gender Methods correspond most closely to the isotope dilution mass spectrophotmetry GFR = 175 × serum creatinine−1.154 × age−0.203 × 0.742 (if patient is female) × 1.202 (if patient is black) 38 19  eGFR-Modification of Diet in Renal Disease (MDRD) Formula (continued_1) Calculated on average body size Not accurate for pediatric patients Results with numerical values below 60 mL/min should be reported as 59 mL/min for example Results with higher values equal or greater than 60 mL/min should be reported as ≥60 mL/min for example 39 eGFR-Modification of Diet in Renal Disease (MDRD) Formula (continued_2) Stages of chronic kidney disease Stage1 FR ≥ 90 mL/min/1.73 m Stage 2 GFR between 60 and 89 mL/min/1.73 m Stage 3 GFR between 45 and 59 mL/min/1.73 m Stage 4 GFR between 15 and 29 mL/min/1.73 m Stage 5 GFR ≤ 15 mL/min/1.73 m (end-stage renal disease) 40 20  Cystatin C Good procedure for screening and monitoring GFR Small protein produced by all nucleated cells; filtered by the glomerulus Absorbed by the renal tubules and broken down; no cystatin C secreted Serum levels directly reflect GFR Recommended for pediatrics, diabetics, elderly, and critically ill 41 Beta2 Microglobulin Small protein that dissociates from human leukocyte antigens at a constant rate Rapidly removed from the plasma by the kidneys B2M used to identify end-stage renal disease and early rejection of kidney transplant Sensitive indicator of decrease in GFR Not reliable in patients with patients who have immunologic disorders or malignancy 42 21  Radionucleotides Exogenous procedure measuring plasma disappearance of an injected isotope Provides simultaneous visualization of the kidneys 125I iothalamate Valuable to measure the viability of a transplanted kidney Nonradioactive contrast used for children 43 Clinical Significance Results are based on functioning nephrons Plus functioning capacity Nephrons can double their workload if needed This is seen in persons with one kidney Monitor extent of known renal disease Determine feasibility of administering medications that may build up to toxic blood levels 44 22  Tubular Reabsorption Tests Good indicator of early renal disease Measure renal concentrating ability Salts and water Often termed concentration tests Baseline for determining concentration is the 1.010 specific gravity of the original ultrafiltrate Control of fluid intake is necessary for accurate results 45 Tubular Reabsorption Tests (continued) Controlled intake procedures can include after-dinner overnight deprivation of fluid for 12 hours followed by collection of a urine specimen Urine osmolality of 800 mOsm or higher is normal Urine-to-serum ration of 3:1 or greater or a urine osmolality of 800 mOsm or greater indicates normal tubular reabsorption 46 23  Osmolality Osmolarity has replaced specific gravity as the test to assess renal concentration Osmolality is performed for a more accurate evaluation of real concentrating ability 47 Freezing-Point Osmometers Freezing-point osmometers (primary urine method) Measured sample is supercooled and vibrated to form crystals; heat of fusion raises temperature to freezing point; probe measures freezing point Comparison: 1 mol (1000 mOsm) of nonionizing substance in 1 kg water lowers freezing point to 1.86°C; clinical reference standard is NaCl 48 24  Vapor Pressure Osmometers Actual measure is dew point (temperature at which water vapor condenses to a liquid) Microsamples on small filter-paper disks in sealed chamber; evaporating sample forms vapor Temperature lowered, vapor condenses, thermocoupler measures heat of condensation that raised temperature to dew point Requires careful technique because of microsamples, commonly used for serum samples 49 Technical Factors Lipemic serum Affects both instruments Insoluble lipids produces erroneous results Lactic acid Elevates readings in both instruments Separate or refrigerate within 20 minutes Volatile/ethanol Elevate results for freezing-point osmometers 50 25  Clinical Significance (continued_1) Evaluating renal concentrating ability Monitoring course of renal disease Monitoring fluid and electrolyte therapy Differential diagnosis of hyponatremia and hypernatremia Evaluating secretion of and response to ADH 51 Clinical Significance (continued_2) Serum osmolality reference values are 275-300 mOsm Fluid intake and exercise can influence the urine concentration Ratio of urine to serum osmolality should be 1:1; after controlled fluid intake it should be 3:1 Decreased ADH production Inability of tubules to respond to ADH After ADH injection 1:1 ratio = no ADH receptors in CD 3:1 ratio = inability to produce ADH 52 26  Free Water Clearance Expands serum:urine ratio Osmolar clearance performed first using water deprivation, timed urine and serum Cosm = Uosm × V ---------------- Posm Second: V(mL/min) – Cosm= CH2O Osmolar clearance indicates how much water must be cleared each minute to produce a urine with the same osmolality as the plasma Calculation of free water clearance determines the ability of the kidneys to respond to the body’s state of hydration 53 Tubular Secretion and Renal Blood Flow Tests Tests are related because secretion is dependent on renal blood flow Interpretation requires an understanding of the principles and limitations of the tests Test most commonly associated with both tests is the p-aminohippuric acid test 54 27  PAH Test Test for renal blood flow PAH is secreted in proximal convoluted tubule, not by glomerular filtration PAH is loosely bound to plasma proteins PAH is completely removed from the blood each time it comes in contact with functional renal tissue Exogenous procedure 55 PAH Test (continued) U (mg/dL PAH) × V (mL/min) CPAH = ------------------------- = mL/min P (mg/dL PAH) Normal values are based on normal Hct Average renal blood flow = 1200 mL/min PAH is only in the plasma, so a normal would be 600 to 700 mL/min effective renal plasma flow; about 8% does not come in contact with functional renal tissue 56 28  Titratable Acidity and Urine Ammonia Tests for tubular secretion of H+ and NH4+ Normal: 70 mEq/day of acid in form of H+, H2PO4−, NH4+ Alkaline tide = first morning, postprandial 2 to 8 p.m.; lowest pH at night Renal tubular acidosis is inability to produce an acid urine = metabolic acidosis PCT = secretion of H+ DCT = secretion NH3 57 Titratable Acidity and Urine Ammonia (continued) Measurement of pH, titratable acidity, and ammonia Prime patients with acid load of ammonium chloride 2-hr urine specimens, fresh or toluene Titrate free H+ (titratable acidity) and total acidity Total acidity − titratable acidity = ammonia 58 29  Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 59 30