Kidney Function & Tests (PDF)

Functions of kidney The function include : - Regulation water and electrolytes - Acid base balance - Excretion of the products of protein and nucleic acid metabolism (e.g. urea, creatinine and uric acid) - Producing number of hormones Kidney can be controlled by...

Functions of kidney The function include : - Regulation water and electrolytes - Acid base balance - Excretion of the products of protein and nucleic acid metabolism (e.g. urea, creatinine and uric acid) - Producing number of hormones Kidney can be controlled by AVP From posterior - Arginine vasopressin (AVP) = ADH ——> influence water balance pituitary gland - Aldosterone ——> sodium reabsorption in the nephron Aldoste Adrenal cortex rone - Parathyroid hormone. ——> promotes tubular reabsorption of calcium , phosphate excretion and synthesis of 1,25-dihydrocholecalciferol ( active form of VitD) Parathy Parathyroid gland roid H *Renin is made by the juxtaglomerular cells and catalyses the formation of angiotensin I and ultimately aldosterone synthesis. 1 Renal Function Tests Note : substance that contains nitrogens are classi ed into two group 1-protein nitrogen:Nitrogen found in the structure of proteins Some test used to assessment the Renal function Include 2- Non Protein Nitrogens (NPN) : urea form 75% of NPN and the other is 1- Blood Urea and Blood urea nitrogen (BUN) amino acid creatinine uric acid And ammonia 2- Serum creatinine ‫ هـذا الـنيتروجـني يـكون بـالـجسم عـلى شـكلني‬، ‫ جـزء مـن تـركـيبه هـو الـنيتروجـني‬amino acids ‫الـبروتـني هـو‬ 3- Glomerular ltration rate (GFR) ‫ ام ــا م ــوج ــود داخ ــل ال ــبروت ــينات او يتح ــلل ه ــذا ال ــبروت ــني ويخ ــرج م ــنها ال ــنيتروج ــني ب ــهاي ال ــحال ــه ي ــسمى‬، NPN Urea (CO{NH2}2 ) is the major nitrogen containing metabolic product of protein catabolism in human.The biosynthesis of urea is from ammonia (NH3) which derived amino nitrogen which is carried out exclusively by hepatic enzymes of the urea cycle. Proteolysis Transamination and oxidative deamination In liver Urea cycle Protein--------------→ amino acid-------------------------→ NH3 ---------------------→urea Note : more than 90% of urea is excreted through the kidneys. Losses of urea through the gastrointestinal tract and skin account for most of the remaining fraction. 2 fi fi Renal Function Tests Uremia : it is abnormal high urea nitrogen in blood. Aazotemia: it is significant increase in the plasma concentration of urea and creatinine in kidney insufficiency Causes of uremia 1- prerenal uremia : is caused by extra-renal factor like ‫ﺔ‬u‫ﻠ‬w‫ﻠﺔ ﺧﺎرج اﻟ‬z‫اﻟﻤﺸ‬ ‫„ﻌﻨﻲ ﻗ ﻞ ﻻ ﻳﻮﺻﻞ‬ -High protein diet prerenal.‫اﻟﺪم‬ -Increase protein catabolism as in stress ,fever, sever burn -Reabsorption of of blood protein after gastrointestinal hemorrhage. -Treatment with cortisol. ( cortisol active the proteolysis enzymes ) -Dehydration. (‫ﺐ ﻧﻘﺼﺎن ﺗﺮﻛﻴﺰ اﻟﻤﺎء‬l‫ﺴ‬n ‫ﺎ‬o‫) ﻳﺰداد ﺗﺮﻛﻴﺰ اﻟﻴﻮر‬ -Heart Failure (decrease renal perfusion ) 2-Renal uremia: it is caused by diminished glomerular filtration as in acute or chronic renal disease ex. Acute and chronic glomerulonephritis ,polycystic kidney disease. in which the urea and creatinine may be increased ‫ﺔ‬u‫ﻠ‬w‫ﻠﺔ داﺧﻞ اﻟ‬z‫اﻟﻤﺸ‬ 3 Renal Function Tests 3-Postrenal uremia :it is usually result from - obstruction in pathway of urine , in which the urea is reabsorbed into the circulation ex. malignancy , stones, prostate gland enlargement. ‫ﻌﺪ ﻣﺎ ﺗﺼﻔﻰ اﻟﺪم‬Š ‫ﻠﺔ‬z‫اﻟﻤﺸ‬ ‫ﺎ اﻟﻰ‬o‫ح اﻟﻴﻮر‬Œ‫ﻌﺪ ﻣﺎ ﻧﻄ‬Š ‫ﻣﺜﺎل ﻣﻦ‬ in this condition there is often greater increase in plasma urea than creatinine. ‫ح‬Œ‫ﻤﺴﺎر ﻃ‬Š ‫اﻟﻨ–ﻴ ﺎت اذا ا“ﻮ ا’ﺴﺪاد‬ ‫ﺎﻟﻨ–ﻴ ﺎت ﻟﻔﺘﺮة‬Š ‫ﺎ‬o‫اﻟﻴﻮرن راح ﺗ ﻘﻰ اﻟﻴﻮر‬ ‫ﺚ راح „ﺼﻴﺮﻟﻬﺎ اﻋﺎدة‬u‫ﺤ‬Š ‫اﻃﻮل‬ ‫اﻣﺘﺼﺎص ﻣﻦ اﻟﻨ–ﻴ ﺎت اﻟﻰ اﻟﺪم‬ Urea is the major end product of protein catabolism (urea cycle in liver). More than 90% is excreted by the kidneys. BUN is calculated by: Uremia: Abnormally high BUN in blood. Azotemia: Significant increase in both urea and creatinine, often indicating renal insufficiency. 4 Serum Creatinine Creatinine is the cyclic anhydride of creatine that is produced as a the final product of decomposition of phosphocreatine.It is excreated in urine. Creatine is synthesis in the kidneys ,liver and pancreas ,then creatine is transported by blood to other organs such as muscle and brain where it is phosphorylated to phosphocreatine ,it is a high energy compound.The stored creatine phosphate in the muscle serves as an immediate store of energy in the muscle which is used in muscle contraction. * The amount of creatinine is related to the muscle mass. ‫ﻻزم ﻧﻤﻴﺰ ﺑﻴﻦ‬ Creatine ——> compound produced by liver,Kidney and pancreas Creatinine ——> waste products of phosphocreatine Keratin ——-> protein found in hair and Nails 5 Serum Creatinine Clinical Significance 1-Creatinine is freely filtered by glomeruli + small percentage 7-10% secreted by renal tubule ‫( ﯾﺘﻢ ﺗﺮﺷﯿﺤﮫ ﻣﺒﺎﺷﺮةً ﻋﺒﺮ اﻟﻜﺒﯿﺒﺎت اﻟﻜﻠﻮﯾﺔ‬%93-90 ‫ﻣﻌﻈﻢ اﻟﻜﺮﯾﺎﺗﯿﻨﯿﻦ )ﺣﻮاﻟﻲ‬ * not reabsorbed under normal circumstances. ‫( ﺗُﻔﺮز ﺑﺸﻜﻞ ﻣﺒﺎﺷﺮ ﻣﻦ ﺧﻼﯾﺎ اﻷﻧﺎﺑﯿﺐ اﻟﻜﻠﻮﯾﺔ‬%10-7) ‫اﻟﻨﺴﺒﺔ اﻟﻤﺘﺒﻘﯿﺔ‬ 2-There is relatively constant excretion of creatinine in the urine. 3-In renal disease the creatinine excretion is impaired and reflected by increased creatinine in the blood. 4-Serum Creatinine higher in males than in females. 5-Sustained high protein diets and catabolic states probably affect the plasma creatinine concentration less than that of urea. 6 Serum Creatinine 6-Plasma urea concentration tend to rise faster than creatinine in case of reduction of GFR in renal dysfunction. 7-Creatinine is affected by age, sex, exercise, certain drugs ( cimetidine ,trimethoprim) , muscle mass.. ‫ﺎ‬o‫ﺎﺗ¯ﻨﻴﻦ ادق واﻓﻀﻞ ﻣﻦ ﻓﺤﺺ اﻟﻴﻮر‬oŒ°‫¶ﻞ ﻫﺬە اﻟﻨﻘﺎط ﺗﺠﻌﻞ ﻓﺤﺺ اﻟ‬ Creatinine clearance: It is milliliters of plasma that are cleared of creatinine by the kidneys per minute. Creatinine clearance is calculated as : Creatinine clearance(ml/min) = U/P X V X 1.73/A U: urine creatinine concentration (mg/dl) ( 24hrs collection) P: plasma creatinine concentration (mg/dl) V: is the volume in milliliter of urine excreted per minute. A: is the body surface area in sequare meters and 1.73 is the standard body surface area 7 ‫)‪Glomerular filtration rate (GFR‬‬ ‫)‪Glomerular filtration rate (GFR‬‬ ‫‪It is the quantity of glomerular filtrate formed per unit of time in all nephrons of both kidney. The substance was used‬‬ ‫‪to measure the GFR are Inulin , Cystatin C and creatinine.‬‬ ‫ﻫﻮ ﻣﻌﺪل ﺗﺼﻔ‪u‬ﺔ اﻟ‪w‬ﻠﻰ ﻟﻠﺪم ﻓﻲ اﻟﺪﻗ‪u‬ﻘﺔ اﻟﻮاﺣﺪة ‪GFR‬‬ ‫ﻣﻮؤﺷﺮ ﻟ‪°‬ﻔﺎءة اﻟ‪w‬ﻠﻰ‬ ‫‪The aim of measurement of GFR is to‬‬ ‫) ‪ Detect the onset of renal insufficieny ( help to diagnosis‬‬ ‫) ‪ Adjust drug dosage for drugs excreted by the kidney.( calculate the dose of drug according to the degree of failure‬‬ ‫)‪ - 140‬اﻟﻌﻤﺮ ﺑﺎﻟﺴﻨﻮات(‬ ‫‪.1‬‬ ‫ﯾﻌﻜﺲ ﺗﺄﺛﯿﺮ اﻟﻌﻤﺮ ﻋﻠﻰ وظﺎﺋﻒ اﻟﻜﻠﻰ‪ ،‬ﺣﯿﺚ أن ‪ GFR‬ﯾﻘﻞ ﻣﻊ اﻟﺘﻘﺪم ﻓﻲ اﻟﺴﻦ‪.‬‬ ‫)اﻟﻮزن ﺑﺎﻟﻜﯿﻠﻮﺟﺮام(‬ ‫‪.2‬‬ ‫ﻷن إﻧﺘﺎج اﻟﻜﺮﯾﺎﺗﯿﻨﯿﻦ ﯾﻌﺘﻤﺪ ﻋﻠﻰ ﻛﺘﻠﺔ اﻟﻌﻀﻼت‪ ،‬واﻟﻮزن ﯾﻌﻜﺲ ذﻟﻚ إﻟﻰ ﺣﺪ ﻣﺎ‪.‬‬ ‫ ‬ ‫)‪ 0.85‬إذا ﻛﺎن أﻧﺜﻰ(‬ ‫‪.3‬‬ ‫ﻷن اﻟﻨﺴﺎء ﻋﺎدةً ﻟﺪﯾﮭﻦ ﻛﺘﻠﺔ ﻋﻀﻠﯿﺔ أﻗﻞ ﻣﻦ اﻟﺮﺟﺎل‪ ،‬ﻓﯿﻜﻮن إﻧﺘﺎج اﻟﻜﺮﯾﺎﺗﯿﻨﯿﻦ أﻗﻞ‪ ،‬ﻟﺬﻟﻚ ﯾﺘﻢ ﺗﺼﺤﯿﺢ اﻟﻤﻌﺎدﻟﺔ ﺑﻀﺮﺑﮭﺎ ﻓﻲ ‪.0.85‬‬ ‫ ‬ ‫)‪ × 72‬ﻣﺴﺘﻮى اﻟﻜﺮﯾﺎﺗﯿﻨﯿﻦ ﻓﻲ اﻟﺪم(‬ ‫‪.4‬‬ ‫ﻣﺴﺘﻮى اﻟﻜﺮﯾﺎﺗﯿﻨﯿﻦ ﻓﻲ اﻟﺪم ﯾﻌﻜﺲ ﻛﻔﺎءة اﻟﻜﻠﻰ ﻓﻲ ﺗﺼﻔﯿﺔ اﻟﻔﻀﻼت‪ ،‬ﻟﺬا ﯾﻜﻮن ﻓﻲ اﻟﻤﻘﺎم‪.‬‬ ‫ ‬ ‫اﻟﺮﻗﻢ ‪ 72‬ھﻮ ﺛﺎﺑﺖ رﯾﺎﺿﻲ ﯾﺴﺘﺨﺪم ﻟﻤﻌﺎﯾﺮة اﻟﻮﺣﺪات‬ ‫ ‬ ‫‪8‬‬ Acute Renal Failure (ARF) Acute Kidney Injury abrupt decline in renal function, clinically manifesting as low GFR with a reversible acute increase blood urea nitrogen (BUN) and serum creatinine levels. Classification of ARF 1-Pre-renal ARF: this occur because the blood supply to kidney is reduced either due to vascular obstruction or reduced renal perfusion and decrease GFR. The most common cause , blood loss ,sever water loss like burn ,vomiting and diarrhea Body response : increase ADH and aldosterone secretion. Q: What are some of the biochemical finding in patients with pre –renal failure A: Biochemical finding The blood supply to kidney is reduced leading to reduced renal perfusion and decrease GFR causing 1-High urea and creatinine in serum but urea more than creatinine 2-Hyperkalemia due to decrease GFR and acidosis 3-Metabolic acidosis due to the inability of the kidney to excrete H+ 4-High urine osmolality 2-Renal : there is renal damage either due to disease or consequence of prolong pre-renal or post- renal proplems effecting kidney , the causes are: Prolonged renal circulatory insufficiency, acute glomerulonephritis , septicaemia and Poisons or drugs or myoglobulinuria 3-Post –renal :post renal obstruction causes back pressure leading to reduction of glomerular filtration , the causes are either renal calculi , Ca of prostate or cervix or bladder or prostate hypertrophy 9 Uric Acid Purine metabolism Nucleic acids contain two different bases , pyrimidines and purines. The catabolism of the purines ( adenine and guanine  AMP , GMP ) produces uric acid. uric acid is mostly ionized and present in plasma as sodium urate. Hyperuricaemia : Abnormal high level of uric acid concentration in blood. Uric acid and sodium urate are relatively insoluble molecules that readily precipitate in aqueous solutions such as urine or synovial fluid. The consequence of this is the medical condition known gout. Urate is formed in three ways 1- De novo synthesis 2- The metabolism of endogenous DNA, RNA 3- The breakdown of dietary nucleic acids. ‫ﻄﺔ دون‬u‫ﺴ‬n ‫ﻦ ﻣﻦ ﻣﻮاد‬o‫ﻴﻊ اﻟﺒﻴﻮر‬Â‫ﺔ ﺗﺼ‬u‫ﻋﻤﻠ‬ RNA ‫ او‬DNA ‫ﻚ ال‬u‫اﻟﺤﺎﺟﺔ اﻟﻰ ﻃﻌﺎم او ﺗﻔﻜ‬ DNA ,RNA ‫ﻢ‬u‫ﻦ ﻣﻦ ﺗﺤﻄ‬o‫„ﺼﻨﻊ اﻟﺒﻴﻮر‬ ‫ﻪ ﻣﻦ اﻟﻐﺬاء‬u‫اﻟﺤﺼﻮل ﻋﻠ‬ Urate is excreted in two ways: The kidney: the majority of urate (70%) is excreted via the kidney. The gut: Smaller amounts(30%) of urate are excreted into the gut where it is broken down by bacteria. 10 Uric Acid Gout : is a clinical syndrome occure due to accumulation of urate crystals in the synovial fluid resulting in inflammation leading to acute arthritis. uric acid is deposited in the joints to cause tophi like distal joints of foot. Increased excretion of uric acid may cause deposition of uric acid crystals in the urinary tract leading to stone formation with renal damage Type of gout : Primary Gout : About 10% of cases of primary gout are idiopathic and primary gout may be familial ,it can be enzyme deffect like abnormal PRPP Synthetase Secondary gout : a-Increased Production of Uric Acid : It may be due to increase turnover rate of nucleic acid as seen in rapid growing malignant tissues e.g. leukemias ,or in radiotherapy or chemotherapy or trauma or Increase intake of meat. b-Reduced Excretion Rate : e.g Renal failure , Treatment with thiazide diuretics , Lactic acidosis and keto-acidosis due to interference with tubular secretion. ) (‫ ﻣﻤﺎ ﯾﺆدي إﻟﻰ اﺣﺘﺒﺎس ﺣﻤﺾ اﻟﯿﻮرﯾﻚ ﻓﻲ اﻟﺪم‬،‫ ﻓﺈﻧﮭﺎ ﺗﻨﺎﻓﺲ ﺣﻤﺾ اﻟﯿﻮرﯾﻚ ﻋﻠﻰ اﻹﻓﺮاز ﻋﺒﺮ اﻷﻧﺎﺑﯿﺐ اﻟﻜﻠﻮﯾﺔ‬،‫ﻋﻨﺪ وﺟﻮد زﯾﺎدة ﻓﻲ ﺣﻤﺾ اﻟﻼﻛﺘﯿﻚ أو اﻟﻜﯿﺘﻮﻧﺎت ﻓﻲ اﻟﺪم‬ 11 Proteinuria Types of proteinuria 1. Glomerular proteinuria :increase infilteration load of protein due to glomerular damage and vascular permeability. 2. Overflow proteinuria : increased circulating concentration of low molecular weight proteins. 3. Tubular proteinuria : decrease in reabsorptive capacity of protein due to tubular damage. 1-glomerular proteinuria : The glomeruli of kidney are not permeable to substances with molecular weight more than 69,000 and so plasma proteins are absent in normal urine. When glomeruli are damaged or diseased, they become more permeable and plasma proteins may appear in urine. The smaller molecules of albumin pass through damaged glomeruli more readily than the heavier globulins. Albuminuria is always pathological. Protein /Creatinine ratio : is calculated to decide whether the patient has nephrotic range proteinuria or not. If proteinuria are 1000 mg/day = Glomerular proteinuria 12 Proteinuria Microalbuminuria : It is identified, when small quantity of albumin (30–300 mg/day) is seen in urine. Microalbuminuria is an early indication of nephropathy in patients with diabetes mellitus and hypertension. Hence, all patients who are known diabetics and hypertensive should be screened for microalbuminuria. It is an early indicator of onset of nephropathy. The test should be done at least once in an year. 2-Overflow Proteinuria When small molecular weight proteins are increased in blood, they overflow into urine. For example, Hb having a molecular weight of 67,000 can pass through normal glomeruli, and therefore, if it exists in free form (as in hemolytic conditions), hemoglobin can appear in urine (hemoglobinuria). Similarly, myoglobinuria is seen following muscle crush injury. another example is the Bence-Jones proteinuria in multiple myeloma. 3-Tubular Proteinuria This occurs when tubular damage or functional nephrons are reduced, so low molecular weight proteins appear in urine. e.g alpha-1 microglobulin are synthesized in liver and are readily filtered by the glomerulus. Tubular damage results in the release of intracellular components to the urinary tract and may be used as markers of tubular damage. Transient proteinuria: it associated with physical exertion ,trauma, cardiac failure, fever Orthostatic ( postural) proteinuria: It may be severe proteinuria in the upright than in prone position, it glomerular origin. ‫ﺔ اﻟﻮﻗﻮف‬u‫ﻓﻲ وﺿﻌ‬ ‫ﺔ اﻻﺳﺘﻠﻘﺎء‬u‫ا“ﺜﺮ ﻣﻦ وﺿﻌ‬ 13 Case Scenario Q2: Susan is a 42 yrs old female with heart failure history , a random blood sample was obtained and the following biochemical results Na+ 120 ( normal value 135 - 145) , K+ 5.9 (normal value 3.5 – 5) , HCO3- 15 ( normal value 24 -32) , urea 55 ( normal value 15 -42) , creatinine 4.3 ( normal value 0.7 -1.4) What do these biochemistry results indicate about patient s condition ? Comment on these biochemical findings ? Could the edema appear in this case ? why? the patient is a case of heart failure but increase level of blood urea and creatinine and potassium and blood acidosis (low bicarbonate ) all indicate renal failure which may be secondary to heart failure. Low cardiac output in heart failure stimulate ADH secretion which causes water retention leading to formation edema which causing fall in S.Na+. Renal failure also causes stimulation to secretion of ADH as a result to decrease of GFR this lead to retention of fluid causing edema and hyponatremia. 14