ࡱ> #` bjbj (&d U U U8DUdU jV6W"XXX ZZL-[($hXr98\Y@ Z8\8\XX@```8\hXX`8\``nIAXV  U^Q -V0qʏ@_fʏ@AʏAU["w[`[[U[U[U[`XU[U[U[8\8\8\8\)B$Bd<@| The Normal Kidney  INCLUDEPICTURE "http://galileo.phys.virginia.edu/classes/304/kidney.gif" \* MERGEFORMATINET Kidney Size by Age0-1 wk 1-4 mo 8-12 mo 1-2 yrs 2-3 yrs 3-4 yrs 4-5 yrs 5-6 yrs 6-7 yrs 7-8 yrs 8-9 yrs 9-10 yrs 10-11 yrs 11-12 yrs 12-13 yrs 13-14 yrs 14-15 yrs 15-16 yrs 16-17 yrs 17-18 yrs 18-19 yrs4.48 cm 5.28 6.15 6.65 7.36 7.36 7.87 8.09 7.83 8.33 8.90 9.20 9.17 9.60 10.42 9.29 10.05 10.93 10.04 10.53 10.81 Weight: 150 gram each Structure: The cut surface is made of Cortex, Medulla, Renal Pyramids (papillae), Major/Minor Calyces, and Pelvis that empties into the Ureter. The kidney is divided into 12 lobes, each consisting of a pyramid, of Medullary and Cortical Tissue. The Basic Unit of Kidney Structure is the NEPHRON made up of Glomerulus surrounded by Bowmans Capsule, and the renal tubules. Functions: Regulates total body water Regulates blood pressure (renin-angiotensin-aldosterone) Regulates acid-base status Regulates electrolytes, calcium and phosphorus Hydroxylates Vitamin D Produces Erythropoietin Removes nitrogenous wastes Drug metabolism and removal Laboratory Values: Urine Analysis Specific gravity: 1.001 1.035 pH : 4.6 8.0 Creatinine: 0.6 1.3 mg/dl Normal Creatinine clearance is 75 125 ml/min, decreases with age. Negative for bilirubin, blood, acetone, glucose, protein, nitrite (bacteria), and Leukocyte esterase. RBCs count 0-5/HPF WBCs count 0-4/HPF. Epithelial Cells: Occasional Hyaline Casts: Occasional. Crystals: Disease, Medications. BUN: 7- 18 mg/dl. When elevated called AZOTEMIA Structure of the Kidney and Urinary System A. Gross Outer cortex glomeruli and convoluted tubules Inner medulla collecting ducts, Henles loops, osmotic gradient Collecting system: calices, pelvis, ureter Bladder and urethra  B. Microscopic Nephron: glomerulus and its tubule. Each nephron is an independent unit of function. Approx. 1 million nephrons in each kidney. Glomerulus: compact tuft of capillary loops surrounded by Bowmans capsule. Ultrafiltration apparatus: cells and protein are held within blood while small solutes/water pass into tubules Tubule: divided into segments proximal, distal, Loop of Henle. Absorption (water, sodium, glucose, etc), secretion (K+, H+), formation of osmotic gradient (Loop of Henle, distal tubule). Collecting ducts: concentration of urine under control of ADH   C. Blood supply Renal artery: 25% of cardiac output to glomerulus Interlobar arteries ( arcuate arteries ( interlobular arteries ( afferent arterioles ( glomerulus ( efferent artery ( peritubular plexus (superficial and middle cortex)( vasa recta (juxtamedullary cortex) INCLUDEPICTURE "http://www.umm.edu/images/ency/fullsize/8817.jpg" \* MERGEFORMATINET Glomerular Filtration Rate and Creatinine Clearance Glomerular Filtration Rate The GFR is equal to the sum of the filtration rates in all of the functioning nephrons, so estimation of the GFR gives a rough measure of the number of functioning nephrons. Thus a reduction in GFR implies worsening renal function. A glomerular substance is one which is: (1) freely filtered at the glomerulus, (2) neither reabsorbed nor secreted. Creatinine clearance Creatinine clearance overestimates GFR in a variety of circumstances, because of tubular secretion Nonetheless Creatinine is very close to being a glomerular substance The basic formula for clearance of a substance is CrCl (ml/min) = UV/P Ux: urine concentration of X V: urine volume/time Plasma concentration of X Fortunately we have easy formulas to calculate the GFR: Children: Use the Schwartz Equation Schwartz Equation (Ped Clinics of America, 1987: 34:571) CLcr = k x H/Scr Where: H = height (cm); Scr = serum creatinine (mg/dL); k = constant Age k value Low birth weight babies, <1 yr old 0.33 Term (average gestational age) babies, <1 yr old 0.45 Children (1 - 12) and adolescent girls 0.55 Adolescent boys (13 - 17 yrs) 0.70 . Adults and Children > 12 yo: Use the Cockroft-Gault Equation The Cockroft-Gault Equation (Nephron 1976; 16:31) CLcr (male) = IBW (140 - Age) / (72 x Scr) CLcr (female)= 0.85 x IBW (140 - Age)/(72 x Scr) Where: A = age in yrs;  HYPERLINK "http://www.thedrugmonitor.com/clcreqs.html" \l "IBW#IBW" IBW = Ideal Body Weight in Kg Ideal Body Weight(kg): Non-Metric IBW (male) = 50 + 2.3 (H - 60) IBW (female) = 45.5 + 2.3 (H - 60) H = height in inches Ideal Body Weight (kg) : Metric IBW (male) = 0.9 H - 88 IBW (female) = 0.9 H - 92 H = height in centimeters As a quick rule of thumb, Creatinine and GFR have a relatively reciprocal relationship: Creatinine (mg/dL) GFR (mL/min) 1 100 2 50 4 25 8 12.5 Also, note that normal GFR values vary with age and sex: Children achieve adult values for mean GFR at approximately two years of age .  INCLUDEPICTURE "http://www.utdol.com/data/images/pedi_pix/normal12.gif" \* MERGEFORMATINET  Definition of Chronic Renal Failure Within the pediatric nephrology community, chronic renal failure typically has been characterized by an estimated GFR of less than 75 mL/min per 1.73 m2. In contrast, the K/DOQI workgroup defined CKD in adults and children older than 2 years of age as: Kidney damage for  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/ge.gif" \* MERGEFORMATINET 3 months, as defined by structural or functional abnormalities of the kidney, with or without a decreased GFR, manifested by either pathological abnormalities; or markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests OR GFR < 60 mL/min per 1.73 m2 for  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/ge.gif" \* MERGEFORMATINET 3 months, with or without kidney damage. Stages of chronic kidney disease Patients who experience a gradual decline in kidney function because of CKD are initially asymptomatic. Although the early symptoms of uremia are nonspecific in nature, their presence indicates that kidney function has decreased significantly. CKD has been classically staged as renal failure that is:  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Mild (GFR of 50 to 80 percent of normal)  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Moderate (GFR of 25 to 50 percent of normal)  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Severe (GFR of less than 25 percent of normal)  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET End-stage (ESRD) (GFR of less than 10 percent of normal). The observation that many of the complications of CKD can be prevented or delayed through early detection and treatment prompted the K/DOQI workgroup to develop a formal staging system for stratification of CKD based on the level of kidney function, independent of the primary renal diagnosis:  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Stage 1 disease is defined by a normal GFR ( INCLUDEPICTURE "http://www.utdol.com/application/images/characters/ge.gif" \* MERGEFORMATINET  90 mL/min per 1.73 m2)  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Stage 2 disease is a GFR between 60 to 89 mL/min per 1.73 m2  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Stage 3 disease is a GFR between 30 and 59 mL/min per 1.73 m2  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Stage 4 disease is a GFR between 15 and 29 mL/min per 1.73 m2  INCLUDEPICTURE "http://www.utdol.com/application/images/characters/bull.gif" \* MERGEFORMATINET Stage 5 disease is a GFR of less than 15 mL/min per 1.73 m2 or ESRD. UpToDate:  HYPERLINK "http://www.utdol.com/application/topic/topicText.asp?file=pedineph/11062&type=P&selectedTitle=1~173" \l "top" Overview of the management of chronic kidney disease in children Blood Urea Nitrogen and Serum Creatinine  Blood Urea NitrogenSerum Creatinine Source  Protein (exogenous or endogenous) derived from breakdown of proteins delivered to the liver  Nonenzymatic hydrolysis of creatine released from skeletal muscle Constancy  Variable More stable (unless !! skeletal muscle mass) Renal Handling " Small, uncharged molecule that is not protein bound  so completely filtered at glomerulus BUT " Significant tubular reabsorption which limits the value of BUN as marker for GFR  Completely filtered; some tubular secretion Value as GFR Marker  Modest Good in steady state Correlation with Uremic Symptoms  Good Poor BUN:Creatinine Ratio (Normal = 10:1) Increased Ratio > 10:1 Decreased Ratio < 10:1 Increased protein intake Starvation Catabolic state Advanced liver disease Fever Postdialysis state Sepsis Drugs that impair tubular secretion Trauma Cimetidine Corticosteroids Trimethoprim Tissue necrosis Rhabdomyolysis Tetracylines Diminished urine flow Hypocomplementemia in Glomerular Diseases Memorize this What are 5 classic renal diseases associated with hypocomplementemia? Post Strep GN MPGN SLE Cryoglobulinemia Shunt Nephritis  Hypocomplementemia Pathogenesis Due to increased consumption via complement activation by immune deposits Other factors may include: Hereditary complement deficiency Presence of circulating factors that promote complement activation. Importance of Complements Complement activation normally plays an important role in clearing immune complexes (in part via attachment to C3b receptors on erythrocytes) Differential Diagnosis Hypocomplementemia can also occur with some non-immune complex-mediated renal diseases, resulting in a clinical picture that may mimic a primary glomerulonephritis Atheroembolic renal disease - complement pathway activated by exposed atheromata. HUS and TTP -complement may be activated by endothelial damage or bacterial toxins. 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