Homeostasis Normal water Balance: a)Intake of water , water is normally absorbed into the body from through the gastrointestinal tract. b)Output of water , water is lost via : 1-kidney as urine ( the minimum volume of urine to be excreted to eliminate waste products is 500ml /day) . 2-Skin as insensible perspiration 600 – 800ml in 24h. 3-Lungs in the expired air 400 -600ml in 24h> 4-Large intestines in feaces. Thus the obligatory losses of water is approximately 1600ml , so in order to maintain normal water balance the intake of water should not be less than the volume of obligatory water losses. Kidney Structure The kidney is a bean shaped organ that weighs 150g , it is made up mainly of two lopes or parts : 1-The cortex which is the outer part and includes the glomerulas , proximal and distal tubules and part of henles loop. 2-the medulla which is the inner part which is covered by the cortex and includes the parts of henles loop and the collecting tubules. Nephrone: It represents the anatomical and functional unit of the kidney , each kidney contains 1x106 nephrons. Each nephrone contains the following: 1-The Glomerulas , it is made up of a network of capillaries resembling the filtering unit of the kidney 2-Bowmans Capsule, which is a sac like structure that engulfs the glomerulas and has a double layered wall of epithelium cells. Kidney Structure 3- The convoluted proximal tubules followed by the straight proximal tubules. 4- The loop of henle . 5-The straight distal tubules followed by the convoluted distal tubules. 6- the collecting tubules. Formation of Urine: Urine is formed by the combined effort of the following three processes, 1-The filtration process where 1L/min of blood is filtered by the glomerulas in both kidneys. Helped by the increased pressure in the glomerular capillaries, a filtration process occurs in which some blood fluid is forced out of the glomerulus and into the capsular space of the Bowman's Capsule. Which will enter Bowman's capsule leading to the formation of 120ml of glomerular filterate which is a cellular free and partially protein free filtrate of the blood. 2-Tubular reabsorption, is the process by which solutes (such as glucose , amino acids , small MW proteins ) and water are reabsorbed from the glomerular filterate and transported back into the blood and this process is carried out by the proximal tubules. Formation of Urine: 3-tubular secretion, it is the transfer of materials from the blood capillaries to the renal tubular lumen. Tubular secretion is caused mainly by active transport, and usually involves the secretion of substances that are poisons or are present in great excess such as uric acid , organic anions , K+ , H+ ,which except for potassium and uric acid occurs in the proximal tubules. Thus by the selective reabsorption and secretion action of the renal tubules the glomerular filterate is modified leading eventually to the excretion of urine that has a composition different from that of the glomerular filterate . The change in osmolarity of the GF during urine formation: -The glomerular filtrate enters the proximal tubules in an isotonic state. -In the proximal tubules the reabsorption process begins, water and salt ( Nacl) is reabsorbed. -At the descending limp of Henle the water reabsorption continues but not to solute (75%of water reabsorption occurs here ) and the waterbecomes more and more concentrated as it descends. -At the hairpin of Henles loop the fluid reaches maximum concentration (becomes hypertonic) and the epithelium becomes water impermable so water reabsorption Formation of Urine: Ceases . -the fluid continues ascending entering the ascending limp , which is impermable to water ,and becomes progressively less concentrated due to Nacl reabsorption and will become isotonic then hypotonic at the end of the thick ascending limp of henles loop . -In the distal tubules active reabsorption of Nacl continues although to a less extent . _both the distal convoluted tubule and the collecting tubules are sensitive to stimulation by the ADH (anti diuretic hormone)thus their major function is to reabsorb water only to the extent required by the body. Glomerular Filtration Rate Glomerular filtration rate (GFR) : It is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman's capsule per unit time. The glomerular filterate rate in a normal individual is 120ml/min ,the rate is maintained constant despite changes in blood pressure. Abnormalities in the GFR : Low glomerular filtration rate can be caused by cardiovascular disease, or renal disease , which will lead to the inefficient elimination and accumulation of the body waste products and toxins . High glomerular filtration rate , can lead to insufficient time for proper reabsorption which can happen in cases of e.g pregnancy or hypoproteinemia. Renal function tests ; Estimation of the GFR is used to assess the kidney function. Glomerular filtration rate (GFR) can be calculated by measuring any chemical that has a steady level in the blood, and is freely filtered but neither reabsorbed nor secreted by the kidneys such as creatinine. Glomerular Filtration Rate Urine concentration of the analyte investigated (eg. Creatinine) . Urine flow rate ml/min. Plasma concentration of analyte investigated (eg. Creatinine) . Kidney function tests Examples of kidney function tests include : -Serum creatinine; Involves determining the level of creatinine in serum .Creatinine is a waste product blood that comes from muscle activity. It is normally removed from your blood by your kidneys, but when kidney function slows down, the creatinine level rises indicating kidney problems. Blood Urea Nitrogen (BUN): Involves determining the level of urea in serum .Urea is a normal waste product in blood that comes from the breakdown of protein from the food or body metabolism, it is excreted from blood by the kidneys ,if kidney function is abnormal it will accumulate in blood . BUN is not a very reliable test since the BUN level can rise if you eat more protein, and it can fall if you eat less protein. Creatinine clearence test : It is one of the common tests used to assess kidney function Since creatinine is readily filtered by the kidneys and it is not reabsorbed nor secreted by the kidneys ,thus its clearance is a measure of the GFR, which is the best test by which kidney function can be tested. Creatinine clearance = creatinine U x urin e flow rate creatinine S Physical Characteristics of urine Urine Physical characteristics; a) volume; the normal individual excretes 600-2500ml of urine per day . The volume of urine varies depending on water intake and water loss (sweating ,perspiration ,consumption of tea, coffee….) Abnormalities in urine volume; - Polyuria : when the volume of urine exceeds 2500ml , which could be due to physiological reasons such as increased fluid intake or consumption of diuretic drinks or drugs - Or due to diseases such as diabetis insidipus ,or nephritis. - Oliguria ; when the volume of urine is less than 400ml, which could occur be due to hemorrhage or loss of water by other routes such as vomiting or diarrhea ,or could be indicative of kidney disease and in terminal stages of kidney disease might lead to anuria . - anuria ; when the urine volume is less than 100ml , such as in cases of renal failiure. b) Colour; The normal colour of urine is clear pale yellow , the principle pigment being urochrome (a compound originating from uribilinogen). The colour of urine might be darker or lighter due to variations in water intake , or by the consumption of certain drugs or foods such as vitamine B complex. Urine colour can change in abnormal conditions such as ,; -a brown deep color in obstructive jaundice. Physical Characteristics of urine -Blood or hemoglobin gives urine a Smokey pink to red color. -It can also be dark in some metabolic disorders such as in alkaptinuria where homogentisic acid is excreted. c) pH; The urine is normally acidic with pH less than 6.0 ( 4.7-8.0) , the acidic urine is explained by the H2SO4 and the H3PO4 produced from metabolism of proteins and nucleic acids respectively , which explains why a vegetarian diet leads to excretion of an alkaline urine. abnormal pH of urine ; Increased acidity of urine can occur in fever ,in cases of acidosis. Alkaline pH can occur in excessive vomiting or increased secretion of H+ and in cases of bacterial infection of the urinary tract , due to production of ammonia by the bacteria . Physical Characteristics of urine d) Smell; Normal urine does not have a strong order ,but its smell can be affected by diet such as asparagus , or diseases such as in cases of ketosis an acetone smell dominates due acetone excretion and in urinary tract infection it has a strong ammonia smell , Density or specific gravity: (This is the ratio of the weight of a volume of a substance compared with the weight of the same volume of distilled water) Normal urine density or specific gravity values vary between 1.003–1.035 (g·cm−3) , and any deviations may be associated with variations in water intake or urinary disorders. Normal constituents of urine Urine is aprox. 95% water. The other components of normal urine are the solutes that are dissolved in the water component of the urine. These solutes can be divided into two categories; 1- ions . 2-organic molecules. 1- ions : Anions ; Chlorides ( Cl- ) is the chief anion of urine and the amount excreted is related to diet. Phosphates (H2PO4-, HPO42-, PO43-) amount in urine varies with diet and the amount of parathyroid hormone in the body - parathyroid hormone increases the quantity of phosphates in urine. Sulphates (SO42-) : Sulphates are derived mainly from amino acids. The quantity of sulphates excreted in urine varies according to the quantity and type of protein in the diet. Normal constituents of urine Cations; Na+ and K+ are the major cations in diet thus they are also the major cations in urine , the amount in urine varies with diet and the amount of aldosterone (aldosterone is a hormone that increases the reabsorption of sodium and water and the secretion of potassium in the kidneys) in the body . Magnesium (Mg2+) : Amount in urine varies with diet and the amount of parathyroid hormone (which increases the reabsorption of Mg2+ and Ca2+ in the body). Calcium (Ca2+) : Amount in urine varies with diet and the amount of parathyroid hormone in the body. Ammonium (NH4+) : The amount of ammonia produced by the kidneys may vary according to the pH of the blood and tissues in the body. 2-organic molecules: Urea ; It is the major end product of protein metabolism,thus its excretion is directly related to protein intake .Its excretion can increase in cases of increased protein catabolism such as in fever , while its excretion can decrease in cases of liver disease. Uric acid ; Is the most important end product of purine metabolism . Due to its weak solubility, uric acid has a tendency to crystallize, and is a common part of kidney stones .Its excretion is increased in cases of lukemia , Gout , . Normal constituents of urine Creatinine ; It is produced mainly as a result of the breakdown of creatine phosphate in muscle tissue, and is produced by the body at a fairly constant rate ,which depends on the muscle mass of the body regardless of diet and the amount excreted is affected by age and gender . Its excretion therefore is a reliable index of the efficiency of a 24 h urine collection . Creatinine excretion is decreased in renal diseases and excretion increases in muscle wasting diseases . Hippuric acid ;ingested benzoic acid is excreted in the form of hippuric acid (benzoic acid is present in fruits ,berries and used as a preservative ). Uribilinogen :Is the precursor of the urine pigment , its excretion can increase in hemolytic jaundice. Glucosiduronides ;glycosides or glucuronic acid is the excretion form of eg. methanol, phenol, aspirin . other substances that may be found in small amounts in normal urine include carbohydrates, , fatty acids, hormones, pigments, and others .