Kidney Diseases & Kidney Function Tests PDF

KIDNEY DISEASES & KIDNEY FUNCTION TESTS 22.10.2024 Tuesday Groups 23.10.2024 Wednesday Groups Dr. Halil Resmi  Anatomy of Kidney Kidneys are a pair of organ located posterior part of abdomen on both side of vertebral column....

KIDNEY DISEASES & KIDNEY FUNCTION TESTS 22.10.2024 Tuesday Groups 23.10.2024 Wednesday Groups Dr. Halil Resmi  Anatomy of Kidney Kidneys are a pair of organ located posterior part of abdomen on both side of vertebral column. 2  Section of kidney The outer part is cortex which contains glomeruli and renal tubules, Inner part is medulla contains tubules and collecting ducts. 3  The renal pelvis rapidly diminish and merges into ureter, Each ureter decends in the abdomen to join bladder, Bladder is the storage organ for urine, which is voided to urethra and then to the exterior. 4  Microscopic anatomy Each kidney is made up approx. 1 million functional unit; NEPHRON, The nephron begins with glomerulus, its a tuft of capillaries, This tuft is made by afferent arteriols (incoming) and smaller efferent arteriols (outgoing). 5 6 7 8  The glomerulus is surrounded by Bowman’s capsule, The proximal convulated tubule runs through the cortex entering the medulla and forming first the descending limb of the loop of Henle and then the ascending limb of the loop of Henle, The thick section of the ascending limb of the loop of Henle returns to cortex and forms the distal convulated tubule. 9  Distal convulated tubule merges with collecting duct, Collecting duct descendens through the cortex and medulla, It’s size increases as it passes down the medulla, At the end collecting duct drains to pelvis. 10  Renal Physiology The kidney is the chief regulator of all body fluid end electrolytes. It has six main functions; – Urine formation, – Regulation of fluid and electrolyte balance, – Regulation of acid-base balance, – Excretion of end products of protein metabolism, – Hormonal function, – Protein conservation. 11  Urine formation The removal of waste product is accomplished with the formation of urine. The urine formation covers three major processes; – Filtration, – Reabsorption, – Secretion. 12 13  Glomerular Filtration 1000-1200 mL of blood passes through the kidneys per minutes, Glomerulus has a semipermeable membrane allows free passage of water and electrolyte, but is relatively impermeable to large molecules, In filtration process, fluid transfer from capillary lumen to Bowman’s space (urinary space). 14  The hydrostatic pressure in glomerular capillaries is approx. 3 times greater than the pressure in other capillaries, This pressure pushes the fluid to semipermeable membrane and the filtration occurs, The rate of this process is 130 mL/min and called Glomerular Filtration Rate (GFR). GFR is very important parameter in clinical assessment of renal glomerular function. 15  Proximal Tubule Approx. 80% of water and salts are reabsorbed from glomerular filtrate in the proximal tubule, All filtered glucose and most of filtered amino acids are reabsorbed in this part of tubule, Low molecular weight proteins, urea, uric acid, bicarbonate, phosphate, chloride potassium, magnesium and calcium are reabsorbed to varying degrees. 17  A variety of organic acids and bases, H+ ions, ammonia are secreted into tubular fluid by tubular cells. 18  Loop of Henle Loop of Henle, long U-shaped portion of the tubule within each nephron of the kidney. The loop of Henle has segments: thick descending limb, a thin descending limb and a thick ascending limb. Its main function is to reabsorb water and sodium chloride from the filtrate. This conserves water for the body, producing highly concentrated urine. 20 Countercurrent mechanism 23  Distal Convulated Tubule A small amount of filtered sodium, chloride and water is reabsorbed in the distal convulated tubule. Distal tubule respons to antidiuretic hormone (ADH), its water permeability is high in the presence of the hormone. 24  Distal Convulated Tubule Potassium can be reabsorbed or secretes in this segment, Aldosterone stimulates sodium reabsorption and potassium secretion in distal tubule, Hydrogen, ammonia and ammonium ions, and uric acid secretion, but bicarbonate reabsorption occurs, This segment has a low permeability to urea. 25  Collecting duct ADH controls the water permeability of the collecting duct throughout its length. In the presence of ADH, the hypotonic tubular fluid entering the duct loses water. Aldosterone stimulates sodium reabsoption, chloride reabsorption follows sodium 26 The Roles of Kidneys in Regulation of Fluid and Electrolyte Balance 27  WATER Water is the most abudant component of the body; 60% of the body Kidneys regulate body water to maintenance serum osmolality [OSMOLALITY: The measurement of the number of the moles of particles per kilogram of water. A normal result is typically 275 to 295 mOsm/kg] 28  WATER Serum osmolality remains constant from day to day (but daily water and salt intake are variable), Kidneys can form more concentrated/diluted urine, When body need to conserve water, kidneys forms a concentrated urine (about 1200 mOsm/kg), Conversely, when body water is excess, diluting mechanisms can reduce the osmolality (as low as 50 mOsm/kg). 29  SODIUM Sodium is the main cation of extracellulary fluid Sodium is freely filtered by glomerulus and actively reabsorbed by tubules When sodium ions actively reabsorbed by proximal tubule cells, this reabsorption causes passive reabsorption of bicarbonate and chloride (as counter ions), and water. 31  SODIUM In normal persons, sodium content is constant In a normal person, the kidneys reabsorb more than 99% of the filtered sodium Sodium reabsorption is controlled by renin- angiotensine-aldosterone system. 32  CHLORIDE The concentration of chloride in extracellulary fluids is similar to sodium concentration and is influenced by same factors. 33  POTASSIUM Potassium is main cation of intracellulary fluid Maintenance of potassium concentration is essential for cells The ingested daily potassium amount is equal to the potassium excreted by kidneys (a small amount of potassium is eliminated by feces and sweat) 34  POTASSIUM Kidney is the major regulator of potassium in the body, Potassium is filtered freely at glomerulus, and reabsorption occurs throughout tubules (except descending loop of Henle), Distal tubule and collecting ducts are able to both reabsorb and secrete potassium, Aldosterone enhances potassium secretion in the distal tubule. 35 The Roles of Kidney in Acid-Base Balance 39  Acid-Base Balance The body produces acidic ions/compounds, In a person with normal diet about 50 to 100 mmole of hydrogen ions are generated each day, They must be effectively disposed from body otherwise cause cellular damage. 40  Acid regulation systems The body’s acid-base (pH) balance is regulated by three systems; ❖Buffer systems (acid-base buffers) ❖The lung ❖The kidneys 41 The kidney has four mechanism to control acid-base balance: 1. Excretion of hydrojen ions: Hydrogen ions (H+) are produced in proximal and distal tubule cells and the cells of collecting duct. 42 The Roles of Kidneys in Nitrogenous Waste Excretion One of the major functions of kidney is the elimination of nitrogenous products of cellular metabolism. 50  UREA Ammonia is removed from amino acid by deamination reaction. 51  UREA The toxic levels of ammonia is prevented by urea production in liver, The urea is generally reported as Blood Urea Nitrogen (BUN) in lab results, [BUN test measures the amount of urea nitrogen in patient’s blood. BUN (mg/dL) = Urea (mg/dL)/2.14] 52  High BUN levels indicates; ❖Protein-rich diet ❖Tissue breakdown (cancer?) ❖Decreased protein synthesis Low BUN levels indicates; ❖Protein-poor diet ❖Severe liver disease 53  Urea is readily filtered , Approx. 40-50% of filtered urea is normally reabsorbed by the proximal tubule, BUN levels are variable due to several reasons, BUN is a less specific indicator of a renal disease. 54  CREATININE Serum creatinine levels and urinary creatinine excretion are depend on muscle mass in a normal person, Dietary changes has only small effect on serum levels. 55  CREATININE Creatinine is filtered freely at the glomerulus and is not absorbed by tubules, Only a small amount of creatinine is secreted into urine from tubular secretion, Due to these properties of creatinine, the creatinine clearence can be used to estimate the GFR-Glomerular Filtration Rate. 56  URIC ACID Uric acid is derived from the oxidation of purine bases, Plasma uric acid levels are variable, It is completely filtered and both proximal tubule reabsorption and distal tubular secretion may occur, Advanced chronic renal failure is associated with progressive increase in the uric acid levels. 57 Hormonal Functions of Kidneys 58  VITAMIN D Kidney is the production site of active vitamin D (1,25-dihydroxycholecalciferol), The enzyme that responsible for the production this hormone is present almost exclusively in renal cortex. Patients with Chronic Kidney Disease have an exceptionally high rate of severe vitamin D deficiency. 59  RENIN Kidney release renin in response to a decreased in afferent arteriolar pressure or an increase sympathetic nervous system activity. Renin is a member of renin-angiotensin- aldosterone hormonal axis, that stimulation of this axis results in sodium conservation. 60  ERYTHROPIETIN This hormon stimulates red blood cell production, The kidney’s role in the EPO production explains the anemia associated with chronic renal disease. 61 The Roles of Kidneys in Protein Conservation 62 Protein Conservation Under physiological conditions the kidney maintain blood proteins, 180 L of plasma (each liter contains 70 g of protein) is filtered each day by glomerulus, A normal urine contains less than 200 mg of protein per day. 63  Most of plasma proteins (except those of very high MW) can be found in the urine, Albumin excretion is less than 20-30 mg/day. …………………………………………………………………………. Many proteins of nonserum origin are also found in urine, One of these, uromucoid (Tamm-Horsfall protein-THP) is the predominant (40 mg/day) protein of urine, THP (a high-MW mucoprotein) is secreted by distal tubules and collecting ducts. 64  Commercially available dipsticks are used to accurate and rapid assessment of urinary protein concentrations. 65 PATHOLOGICAL CONDITIONS OF KIDNEY 66  Acute Glomerulonephritis AG is an acute inflammation of the glomeruli that result in; – Oliguria – Hematuria – Increased BUN – Increased creatinine – Decreased GFR – Edema – Hypertension 67 68 [INFLAMMATION:Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells, toxic compounds, and physical damage. There are five symptoms that may be signs of an acute inflammation: Redness, heat, swelling, pain, and loss of function.] 69 [HEMATURIA: The presence blood (erythrocytes) in urine. Normal; less than 5 RBC/ high-power-field (hpf). Hematuria may not be of renal origin.] [OLIGURIA: Oliguria is defined a reduced urine volume. It is a clinical characteristic of acute renal injury.] 70  Hematuria alone is not sufficient evidence of acute glomerulonephritis, The presence of red blood cell casts in urine indicates glomerular inflammation. Other abnormalities indicates AGN includes proteinuria and anemia. 71  Nephrotic Syndrome Nephrotic syndrome is characterized the presence of; – Massive proteinuria (mostly albumin), – Hypoalbuninemia, – Hyperlipidemia, – Lipiduria. 72  Protein excretion rates greater than 2-3 g/day (in the absence of low GFR), Hematuria and oliguria may present, Massive protein loss causes low plasma protein levels and concomitant reduction of plasma oncotic pressure, This result in fluid movement from vascular to interstitial space with consequent edema formation. 73  Tubular Disease Defects of tubular function may result in – Depressed secretion or reabsorption of spesific biochemicals, or – Impairment of urine concentration and diluting mechanisms. 74  Renal tubular acidosis (RTA) is the most important clinical disorder of tubular functions, occurs in main two types; 1. Proximal RTA results from reduced tubular bicarbonate reabsorption and causes hyperchloremic acidosis, Reabsorptive disorders of proximal tubule may result in hypouricemia, hypophosphatemia, aminoaciduria and renal glucosuria, The Fanconi syndrome is a group of tubular defects that result in glucosuria, aminoaciduria and hypophosphatemia. 75 2. Distal RTA , in which there is an inability to maintain pH difference between tubular fluid and blood, Defects in potassium and uric acid secretion may result in elevation of serum potassium and uric acid levels, In tubular proteinuria, protein exceretion is less than 2 g/day. 76  Acute Renal Failure Acute renal failure (ARF) is characterized by an abrupt impairment in renal function and decreased GFR and/or urine output. ARF can be classified as follows; 1. Prerenal becuse of hypovolemia, poor perfusion that result from cardiovascular failure, 2. Renal because of acute tubular necrosis, arteriolar and venous obstruction, 3. Postrenal because of an obstruction. 77  Manifestations of ARF ARF usually is accompanied by oliguria or anuria, ARF is associated with varying degree of proteinuria and hematuria, RBC casts and other casts can be seen in urine, Serum urea nitrogen and creatinine levels increases rapidly, ARF is associated with a great elevation in mortality risk. 78  Chronic Kidney Disease Chronic kidney disease (CKD) is a clinical syndrome that results from progressive loss of renal function. CKD is not only a excretory failure, but also; – A regulatory failure (water, sodium, etc.), – Biosynthetic failure (EPO, etc). 79  CKD consist of five stages Stage 1; GFR is greater than 90, but lab results indicate kidney damage such as hematuria and proteinuria, Stage 2; Lab. signs of kidney damage are evident, and GFR is between 60-90, Stage 3; GFR is between 30-60, Stage 4; GFR is between 15-30, Stage 5; GFR is less than 15, renal replacement therapy (dialysis or transplant) is required. 80  Determining the GFR and CKD is important because many drugs are cleared by the kidney and dosing may be modified according to GFR. 81  RENAL FUNCTION TESTS RFT can be evaluated as glomerular and tubular function tests. 82  Tests of Glomerular Function What is the optimal substance for measurement GFR? The optimal substance could be; – Nonmetabolized, – Exceted only by kidney, – Freely filtered by glomerulus, – Neither reapsorbed nor secreted by renal tubules. 83  Creatinine Clearance Creatinine is the most convenient compound to measure glomerular function, Creatinine clearance is the most convenient method to measure glomerular filtration rate, Clearance is a measure of the kidney's ability to remove a substance by excretion. 87  Advantage of Creatinine Clearance Creatinine is an endogenous substance, Amount of creatinine in urine depends on renal excretion, Filtered freely by glomerulus, Not resbsorbed by tubules, It is produced relatively constant rate and directly proportional to the body surface area, For these reasons; creatinine clearance can be used to estimate GFR. 88  Generally a 24-h urine is collected for the measurement. A blood sample is also drawn for creatinine measurement, Creatinine clearance is calculated from the following formula; Creatinine clearance=UxV/P U; urinary creatinine P; plasma creatinine V; volume of 24-h urine 89  Disadvantage of Creatinine Creatinine clearance generally parallels to GFR but overestimates it because of the tubular secretion of creatinine, Moreover; CrC is lower in women, elderly and small persons, For these reasons alternative (and more complicated) formulas can be used. 90  Estimated creatinine clearance (eCcr) The creatinine clearance test is not used very often any more. It has largely been replaced by the estimated GFR (eGFR), A 24-hour urine collection is not needed. 91  Tests for Tubular Function Assesment of concentrating and diluting abilities can provide early and most sensitive evidence of tubular impairments, Urinary specific gravity and osmolality are used to evaluate concentrating and diluting abilities of tubules. 92  Measurement of Osmolality Osmolality is measured by using freezing- point depression method, Dissolved salts increases osmolality thereby lowering the freezing-point of solution compared with that of pure solvent. The temperature at freezing-point of the solution is inversly related to osmolality. 93  Measurement of osmolality Osmolality (mOsm/kg)= FPD/1.86 °C x mOsm/kg Note: 1 osmole of solute lowers the freezing point by 1.86 °C 94  URINALYSIS Urinanlysis is one of the most important tool for assessing renal disease Standart urinanalysis includes, – Appearance – Color – pH – Specific gravity – Leukocyte – Erythrocyte – Protein – Glucose – Ketons – Nitrite – Bilirubin – Urobilinogen – Microscopic examination of sediment 95 96 97  Microscopic evaluation of urinary sediment for cells, crystals and casts should be done on a fresh specimen. Casts are protein clusters that take their shapes from renal tubules, Hyalin casts are composed of almost exclusively protein, Cellular elements may be trapped by hyalin casts, resulting in the formation of granular casts. 98  Red blood cell casts are important markers of glomerular inflammation, Presence of crystals may be an evidence of diagnosis of a specific type of renal calculus, Microscopic examination of urine sediment is required a skilled person, Nowaday,urinalysis device one of the important elements of a well-equipped lab, 99 CHANGE OF ANALYTE IN DISEASE 100  Serum Electrolytes Sodium Normal serum concentration is 136-145 mmol/L, Sodium and its attendant ions are the major contributors of serum osmolality. 101 Hyponatremia; Hyponatremia can occurs in renal disease because of increased extracellular fluid volume resulting from the kidney’s inability to excrete water. Hyponatremia occurs in; – Chronic renal insufficiency, – Adrenal insuffinciency, – States that cause increased level of ADH (such as nephrotic syndrome, cirrhosis, syndrome of inappropriate ADH secretion-SIADH). 102 Hypernatremia; Hypernatremia is defined a relative water deficit, Most frequently occurs in hospitalized patient (who can not take enough electrolyte-free water), It occurs in diabetes insipidus. 103  Chloride Chloride imbalances occur concurently with sodium imbalances, Hyperchloremia occurs in association with renal tubular acidosis. 104  Potassium Hypokalemia; Hypokalemia is associated with excess losses of potassium-rich fluid. Potassium loss may be renal or extrarenal, Increased renal excretion of potassium occurs with; – Diuretic agents, – Prolonged use of corticosteroids, – Primary or secondary aldosteronism, – Cushing’s syndrome, Extrarenal reasons include; – Prolonged vomiting, – Diarrhea. 105 Hyperkalemia; Hyperkalemia is an acute medical emergency, Usually results from increased cellular breakdown that exceed the renal excetory capacity or the presence of impaired excretion. Hyperkalemia may occur in; – Increased intake, – Intravenous potassium administration, – Cellular breakdown (excessive burns, acute muscle necrosis), – Decreased potassium excretion (acute and chronic renal failure), – Hypoaldosteronism. 106  Creatinine, Urea and Uric Acid Progressive renal insufficiency is characterized by retantion of urea, creatinine and uric acid in the blood. Normal BUN to creatinine ratio is between 10:1 and 20:1, In a renal failure caused by intrinsic kidney disease the ratio is similar. 107  BUN/creatinine ratio Ratios higher than 20:1 resulting from; – Decreased renal perfusion (such as volume depletion), – GIS bleeding, – Excessive protein intake, – Excessive protein catabolism. In contrast, urea production is reduced in the presence of; – Low protein intake, – Sever liver disease. 108  Ratios can be elevated because of reduced creatinine resulting from significant muscle loss, such as muscle wasting and amputation. Uric acid concentrations in the blood raise in advanced chronic renal failure, but this rearly result in classical gout. 109  Calcium and Phosphorus Chronic renal failure results in impaired excretion of phosphorus and progressive hyperphosphatemia. This failure results in a fall in plasma calcium levels (hypocalcemia), Hypocalcemia may be restored by calcium resorption from bone. 110  Hypocalcemia is more prevalent in uremia because of reduced calcium absorption in the gut that result from impaired production of Vitamin D3 (1,25-dihydroxycholecalciferol). 111  PROTEINURIA There are two major types of renal proteinuria. Glomerular proteinuria; large amount of relatively high-molecular weight proteins enter the glomerular filtrate and then appear in the urine. Heavy proteinuria (more than 2 g/day) results from incresed glomerular permeability, A greater protein loss (more than 3.5 g/day) results from nephrotic syndrome. 112  In tubular proteinuria (with normal glomerular function) relatively low-molecular weight proteins which normally filtered, appear in large amount in urine. Impaired tubular reabsorption of filtered proteins result in modest increases (1 to 3 g/day) in the urine excretion of low-molecular weight proteins and albumin. Physiological increases can be seen after a sternous excercise and in normal pregnancy. 113 Type of proteinuria 114 115  Microalbuminuria The first sign of renal glomerular disease is microalbumiuria, only a small amount of albumin is found in urine. The rate of urine albumin excretion (UAE) in microalbuminuria is 30 to 300 mg/d. It can not be detected with a dipstick. Screening patient with a predisposition to renal disease (especially diabetes and hypertension) for microalbuminemia is recommended. 117