Kidney Lab 1 PDF

Prof. Sahar El-Haggar Professor of Clinical Pharmacy  ANATOMY AND PHYSIOLOGY OF KIDNEY - Location : Retroperitoneal area Structure :- Cortex Medulla Nephron – Receives 20% to 25% of cardiac output. – Performs numerous functions. Overview:  The kidneys are two bean-shaped organs Loca...

Prof. Sahar El-Haggar Professor of Clinical Pharmacy  ANATOMY AND PHYSIOLOGY OF KIDNEY - Location : Retroperitoneal area Structure :- Cortex Medulla Nephron – Receives 20% to 25% of cardiac output. – Performs numerous functions. Overview:  The kidneys are two bean-shaped organs Location:  The kidneys are located on either side of the spine, in the retroperitoneal space.  The left kidney is situated a little higher than the right one, because of the liver on the right side of the abdominal cavity, above the right kidney. Functioning unit:  The functioning unit of kidney is the nephron , about 1.3 million per kidney Nephron is composed of: 1- Glomerulus responsible for filtration process 2- Proximal convoluted tubules responsible for secretion & reabsorption 3- Distal convoluted tubules responsible for secretion & reabsorption 4- Collecting duct responsible for urine collection  Kidney function: 1- Excretory function 2- Endocrine Function 3- Metabolic Function 1- Excretory function:  Filtration: leads to increase excretion of the drug  Secretion: leads to increase excretion of the drug  Reabsorption: decreases drug excretion  Rate of urinary excretion = Filtration rate + Secretion rate – Reabsorption rate Filtration:-  Passive diffusion of the low molecular weight molecules across the glomerular membrane.  Large molecules (Proteins > 60 kDa) and also protein bound drugs are not filtered through the glomerular membrane  So proteinuria indicates damage of glomerular membrane or Nephrotic syndrome Secretion:-  Secretion occurs mainly in the proximal tubules (from plasma to Tubular lumen) via active transport Reabsorption:-  It occurs mainly by passive diffusion. It depends on:  The urine flow rate  The physicochemical of substance (lipid & water solubility)  Changes in the urinary pH  Ionization of compounds All of these help in: ✓ Use of bicarbonate in treatment of salysilism ✓ Use of ascorbate or ammonium chloride to manage amphetamine & quindine toxicity 2- Endocrine Function:  Secretion of: Rennin, angiotensin, aldosterone , Prostaglandins, kinins and erythropoietin  Erythropoietin, which stimulates the bone marrow to produce red blood cells.  Renin, which controls the production of angiotensin and aldosterone. These cause, respectively, systemic vasoconstriction and renal salt and water retention to maintain effective circulating volume. This contributes to the regulation of blood pressure and fluid balance. 3- Metabolic Function:  Activation of Vit D3  Gluconeogenesis  Insulin metabolism  Drug metabolism LABORATORY ASSESSMENT OF KIDNEY DISEASES Urinary Ph: - Normal range: 4.5-8. - In general, acidic urine deters bacterial colonization. - Alkaline urine may be seen with Urinary tract infection. -Persistent pH greater than 7 are associated with calcium carbonate, calcium phosphate, and magnesium-ammonium phosphate stones. - pH below 5.5 are associated with uric acid stones. -Elevation may suggests urea-splitting bacterial infection. Specific Gravity:  Normal value 1015 -1020 It Dependent on:  Water intake  Urine concentrating ability which is estimated by osmolarity  Osmolality (measure of the of solute particles) is a better estimation for the urine concentrating ability Urine odor: - Urine does not have a strong smell if you are healthy and drinking plenty of fluids. Causes that result in changes in urine odor: Foul-smelling urine (offensively malodorous) may be due to bacteria as bladder infection or UTRI Sweet-smelling urine may be a sign of uncontrolled diabetes Musty-smelling (extremely bad) urine may be due to liver disease Ammonia like odor may be due to infection by urea splitting bacteria or due to low fluids in the body or concentrated urine Musty-apple odor may be due to Ketonuria Urine color: - The color of normal urine varies greatly from totally clear to dark yellow or amber depending on the conc of solutes. - Fresh normal urine is not cloudy, but urine may become cloudy if urates or phosphates crystallize. - Turbidity may also occur when large numbers of RBCs or WBCs are present. - An unusual amount of foam may be from protein or bile acids. - Drug induced changes in urine are rare (e.g., rifampin, doxorubicin, senna (red to orange)). Glucose:  Glucose is normally absent in urine  The filtered glucose is usually reabsorbed completely  When glucose plasma concentration exceeds the threshold for reabsorption (180 mg/dl) glucosuria will be present. Ketones: Acetoacetate and acetone are excreted in cases of:  Diabetic ketoacidosis  Fasting  Starvation Nitrite:  It is formed by conversion from nitrate by the action of bacteria.  Presence of nitrite indicate the presence of urinary tract infection. Heme:  The positive heme test indicates the presence of hemoglobin (blood) or myoglobin (skeletal muscles)  Positive test without the presence of RBC indicates red cell lysis (Hemolysis) or Rhabdomyolysis (sk muscle breakdown). MICROSCOPIC ANALYSIS OF URINE RBCS: ◦ RBCS More than 2 RBCs per high-power field (HPF) is indication of hematuria WBCS : ◦ WBCS indicate infection or inflammation (>1 cell per HPF) PUS cells: ◦ PUS cells indicate infection (>1 cell per HPF)  CONT. MICROSCOPIC ANALYSIS OF URINE Crystals: - The presence of crystals in the urine depends on: - urinary pH - and the presence of other substances in the urine that may promote crystallization. - There are numerous types of crystal that can be detected in the urine. - Calcium oxalate, calcium phosphate, magnesium ammonium phosphate, and uric acid crystals are suggestive of stones. Casts:  They are tiny tube-shaped particles or cylindrical proteins that can be found when urine is examined under the microscope  Casts are formed by epithelial cells of renal tubules SO it reflect damage to cells in the renal tubules.  Normal casts : Hyaline casts are usually caused by dehydration, exercise Abnormal casts include:  Fatty casts are seen in people who have lipids in urine or those with nephrotic syndrome  Granular casts are a sign of many types of kidney diseases  Red blood cell casts are a sign of bleeding into the kidney  Waxy casts can be found in persons with advanced kidney disease and CRF  White blood cell (WBC) casts are more common with acute kidney infections. - Hyaline casts: it is not indicative of disease. Hyaline cast can be seen in concentrated urine or with the use of diuretics. - Cellular casts: they are seen with intrinsic renal disease. They form when leukocytes, RBCs, or renal tubular epithelial cells become entrapped in the tubule. ◦ WBC casts suggest intrarenal inflammation or pyelonephritis. ◦ Epithhelial cell casts suggests tubular destruction. ◦ RBC casts are seen in glomerulonephritis. - Granular and waxy casts: granular cast can be seen in acute tubular necrosis and glomerulonephritis. ◦ Waxy cast do not offer much diagnostic information. Mucus threads:  Mucus threads in urine is quite natural phenomenon since urinary tract is basically filled with mucus that might appear as secretions, or threads.  But If the mucus threads in urine are associated with red blood cells (blood), bacteria or yeast then this indicates to some sort of infection, irritation or other problems. Epithelial cells:  The presence of columnar epithelial cells in the urine indicates the presence of a pathological condition associated with the kidneys or some other part of the urinary tract.  Bacteria, yeast cells, or parasites: ◦ There are no bacteria, yeast cells, or parasites in urine normally. ◦ If these are present, it can mean you have an infection. Protein or Albumin:  Persistent proteinuria is maker for kidney damage  Normally protein molecules are not filtered in the glomerulus  Healthy individuals excrete small amount of proteins in urine(< 10 mg/dl) Dipstick results (semi-quantitative):  < 10 mg/dl---------- negative  10-20 mg/dl--------- trace  30 mg/dl-------------- +1  100 mg/dl------------- +2  300 mg/dl------------- +3  >1000 mg/dl---------- +4 Albumin (mg): Creatinine (gm) Ratio:  It is used to determine progression of kidney disease  24-hour urine collection to measure albumin excreted is non-convenient So, albumin: creatinine ratio in urine samples can be used instead.  The normal ratio is < 30 mg albumin to 1 gm creatinine  Ratios of 30-300 mg alb/1gm Cr is in the range of micro- albuminuria.  Good correlation exists between Alb: Cr ratio and progression of kidney disease.  BLOOD ANALYSIS Blood Urea Nitrogen (BUN): ◦ Normal range: 8-20 mg/dL ◦ AA ---- Ammonia------- Urea ◦ BUN is actually the concentration of nitrogen (as urea) in the serum and not in RBCs (blood) as the name implies. ◦ Although the renal clearance of urea can be measured, it cannot be used by itself to assess kidney function. ◦ Its serum concentration depends on urea production (which occurs in the liver) and tubular reabsorption in addition to glomerular filtration. ◦ BUN can be used to assess or monitor hydration, renal function, protein tolerance, and catabolism. ◦ Also it is used to predict the risk of uremic syndrome in patients with severe renal failure.  ◦ Urea is freely filtered in the kidney, and its reabsorbed dependent on the re-absorption of water ◦ Serum BUN: SCr is 10:1 or 15:1 ◦ This ratio increases due to decreased effective circulating volume Elevated BUN: Urea production is increased by:  A high-protein diet(including amino acid infusions)  Upper GI bleeding  Administration of corticosteroids, tetracyclines, or any other drug with antianabolic effects Common causes of true BUN elevations (Azotemia) Prerenal causes  Decreased renal perfusion: dehydration, blood loss, shock, severe heart failure Intrarenal (intrinsic) causes  Acute kidney failure: nephrotoxic drugs, severe hypertension, glomerulonephritis, tubular necrosis  Chronic kidney dysfunction: pyelonephritis, diabetes, glomerulonephritis, polycystic kidney, chronic analgesic overuse, arteriosclerosis Postrenal causes  Obstruction of ureter, bladder neck, or urethra Decreased BUN:  BUN may be low in patients who are malnourished or have profound liver damage (due to inability to synthesis urea).  Intravascular fluid overload may initially dilute BUN causing low conc. - Many causes of extravascular volume overload (e.g., CHF, renal failure) result in increased BUN because effective circulating volume is decreased. Concomitant BUN and SCr:  In acute kidney injury due to volume debetion, both BUN and SCr are elevated. However, the BUN:SCr ratio is often > 20:1.  In acute changes in kidney function, BUN:SCr ratio greater than 20:1 suggest prerenal causes of acute renal impairment, whereas ratios from 10:1 to 20:1 suggest intrinsic kidney damage. Serum Creatinine: - The standard marker for kidney disease S.Cr. concentration is dependent on: Cr production and Cr elimination so it can be used to assess GFR or kidney function - Normal range 0.5 – 1.5 mg/dL - S.Cr. solely is not an accurate marker for measuring the kidney function Factors that affect S.Cr. Include: - Age, weight, race, gender, exercise , meals - Increased muscle mass can increase Cr production and S.Cr. - Exercise can increase Cr. Production - S.Cr. Increases after meat meal and may remain elevated for 6-8 hr. Measurement of creatinine clearance (CrCl):  A complete 24-hour urine collection to measure Cr Cl is difficult to obtain.  In addition measured Cr Cl are not better than the estimates of creatinine clearance provided through equations such as the Cockcroft Gault. Interpreting Cr Cl values with other renal parameters: The most common clinical uses for Cr Cl and SCr include:  Assessing kidney function in patients with acute or chronic kidney disease  Monitoring the effects of drug therapy on slowing the progression of kidney disease  Monitoring patients on nephrotoxic drugs  Determining dosage adjustments for renally eliminated drugs - Because the relationship between SCr and Cr Cl is inverse, significant declines in Cr Cl may occur before SCr rises above the normal range. - Therefore, SCr alone is not a sensitive indicator of early kidney dysfunction. - Relatively small changes in SCr at lower levels represent significant change in kidney function as assessed by Cr Cl. Calculating Cr Cl from a timed urine collection: Cr Cl (mL/min) = (UCr x V) / (SCr x T) x 1.73/ BSA  Where Cr Cl is creatinine clearance in mL/min/1.73 m2, UCr = urine creatinine concentration (mg/dL), V = volume of urine produced during the collection interval (mL), SCr = serum creatinine concentration (mg/dL), T = time of the collection interval (minutes), BSA = body surface area (m2). Cockcroft-Gault Equation:  This formula provides an estimation of creatinine clearance.  The patient's age, weight, and serum creatinine conc are necessary for the estimation. Cr Cl (mL/min)=(140 – age )x weight (Kg)x0.85(if female) 72 x SCr (mg/dL) Pediatric patients: - The Schwartz formula provides an estimation of Cr Cl  Cr Cl (mL/min) = k x ht in cm / SCr (mg/dL) K = 0.45 for infants < 1 year of age K = 0.55 for children and adolescent females K = 0.7 adolescent males - The Counahan-barratt formula provides an estimation of the GFR - GFR(mL/min/1.73 m2)= 0.43 x ht in cm / SCr (mg/dL) Measurement of the GFR:  The GRF is the volume of plasma filtered across the glomeruli/unit time  Normal range: 100-140 ml/min  One important factor to consider in measuring the GFR is that the oral protein intake or IV infusion of amino acids can significantly increase the GFR due to : - Renal vasodilatation - Increased renal blood flow GFR is determined by measuring renal clearance of certain markers: Markers should be: ◦ Freely filtered through the glomeruli ◦ Not reabsorbed from the renal tubules ◦ Not metabolized in the tubules ◦ Not affect kidney function ◦ Have no or minimal non renal clearance ◦ Minimally bound to plasma proteins Markers used for Measuring the GFR are:  Inulin which is a fructose polysaccharide  Radiolabeled markers such as: ◦ 1251-iothalamate and 99m Tc-diethylenetriamine  Serum creatinine  Creatinine clearance Urinary electrolytes ◦ Sodium  Hyponatremia is most often observed in volume depletion (GI loss and diuretics).  Urine sodium conc of