Renal Physiology Lectures PDF

RENAL PHYSIOLOGY LECTURES By Dr OLUFUNKE ONAADEPO. MD, PHD slides by Dr Onaadepo  RENAL ACID BASE BALANCE  OUTLINE  INTRODUCTION  REABSORPTION OF BICARBONATE IONS  SECRETION OF HYDROGEN IONS  REMOVAL OF HYDROGEN IONS AND ACIDIFICATION OF U...

RENAL PHYSIOLOGY LECTURES By Dr OLUFUNKE ONAADEPO. MD, PHD slides by Dr Onaadepo  RENAL ACID BASE BALANCE  OUTLINE  INTRODUCTION  REABSORPTION OF BICARBONATE IONS  SECRETION OF HYDROGEN IONS  REMOVAL OF HYDROGEN IONS AND ACIDIFICATION OF URINE -BICARBONATE MECHANISM -PHOSPHATE MECHANISM -AMMONIA MECHANISM  APPLIED PHYSIOLOGY  Introduction Acid–base homeostasis is the homeostatic regulation of the pH of the body's extracellular fluid (ECF). The proper balance between the acids and bases (i.e. the pH) in the ECF is crucial for the normal physiology of the body— and for cellular metabolism Improper balance can lead to acidosis (excess acids ) or alkalosis( excess bicarbonate ) in the body  COMPENSATORY MECHANISMS  The body has three different mechanisms to regulate acid- base balance ( H+ concentration to prevent acidosis or alkalosis) 1. Acid-base buffer system, which binds free H+ 2. Respiratory mechanism, which eliminates CO2 3. Renal mechanism, which excretes H+ and conserves the bases (HCO3–)  Buffer system is the fastest one and it readjusts the pH within seconds.  The respiratory mechanism does it in minutes.  Whereas, the renal mechanism is slower and it takes few hours to few days to bring the pH back to normal. RENAL MECHANISM FOR REGULATION OF PH  Exerts a Long term acid-base control mechanism.  Kidney plays an important role in maintenance of acid base balance by excreting hydrogen ions and retaining bicarbonate ions.  Normally, urine is acidic in nature with a pH of 4.5 to 6.  Metabolic activities in the body produce large quantity of acids which can push the body towards acidosis. However, kidneys prevent this by two ways: 1. Reabsorption of bicarbonate ions (HCO3–) 2. Secretion of hydrogen ions (H+).  1. REABSORPTION OF BICARBONATE IONS  About 4,320 mEq of HCO3– is filtered by the glomeruli everyday.  Excretion of this much HCO3– in urine will affect the acid-base balance of body fluids.  So, HCO3– must be taken back from the renal tubule by reabsorption.  Almost all the HCO3 filtered at the glomerulus is reabsorbed back by the proximal convoluted tubule  1. REABSORPTION OF BICARBONATE IONS Except in cases of alkalosis , where there is excess of bicarbonate production or accumulation in the body HCO3 is secreted into urine to reduce the amount of bicarbonate in the body This helps to restore the body to normal pH  2. SECRETION OF HYDROGEN IONS  Metabolic activities in the body produce large quantity of acids  About 4,380 mEq of H+ appear every day in the renal tubule by means of filtration and secretion.  Not all the H+ are excreted in urine.  Out of 4,380 mEq, about 4,280 to 4,330 mEq of H+ is utilized for the reabsorption of filtered HCO3  Only the remaining 50 to 100 mEq is excreted. It results in the acidification of urine.  SECRETION OF HYDROGEN IONS Cont’...  Carbon dioxide formed in the tubular cells or derived from tubular fluid combines with water to form carbonic acid in the presence of carbonic anhydrase.  The carbonic acid immediately dissociates into H+ and HCO3–.  H+ is secreted into lumen of proximal convoluted tubule, distal convoluted tubule & collecting duct.  SECRETION OF HYDROGEN IONS Cont’...  Distal convoluted tubule and collecting duct have a special type of cells called intercalated cells (I cells) that are involved in handling hydrogen and bicarbonate ions.  Secretion of H+ occurs by two pumps: 1. Sodium-hydrogen antiport pump (exchange protons from inside the cell with sodium ions from outside) 2. ATP-driven proton pump.  REMOVAL / SECRETION OF HYDROGEN IONS AND ACIDIFICATION OF URINE  Role of Kidney in Preventing Metabolic Acidosis: Kidney plays an important role in preventing metabolic acidosis by excreting H+.  Excretion of H+ occurs by three mechanisms: 1. Bicarbonate mechanism 2. Phosphate mechanism 3. Ammonia mechanism. 1. THE BICARBONATE MECHANISM  H+ secreted from tubular cell into the tubular fluid will combine with HCO3- in the lumen to form carbonic acid (H2CO+) under influence carbonic anhydrase enzyme  The H2CO3(carbonic acid) dissociates into CO2 and H2O  When the concentration of CO2 in the tubular fluid increases, CO2 diffuses into renal tubular cell where it combines with water to form carbonic acid. The cycle continues  BICARBONATE MECHANISM cont’ Now, the H+ is secreted into the tubular lumen from the cell in exchange for Na+ Thus, for every hydrogen ion secreted into lumen of tubule, one bicarbonate ion is reabsorbed from the tubule. In this way, kidneys conserve the HCO3 The reabsorption of filtered HCO3 is an important factor in maintaining pH of the body fluids.  PHOSPHATE MECHANISM  H+, which is secreted into renal tubules, reacts with phosphate buffer system.  It combines with sodium hydrogen phosphate to form sodium dihydrogen phosphate which is excreted in urine. 3. AMMONIA MECHANISM  Ammonia (NH3) formed in tubular cells is secreted into tubular lumen in exchange for sodium ion. Here, it combines with H+ to form ammonium (NH4).  The tubular cell membrane is not permeable to ammonium. Therefore, it remains in the lumen and then excreted into urine.  AMMONIA MECHANISM Cont’...  Most important mechanism by which kidneys excrete H+ and make the urine acidic.  In the tubular epithelial cells, ammonia is formed when the amino acid glutamine is converted into glutamic acid influenced by enzyme glutaminase.  Ammonia is also formed by the deamination of some of the amino acids such as glycine and alanine.  Ammonia (NH3) formed in tubular cells is secreted into tubular lumen in exchange for sodium ion. Here, it combines with H+ to form ammonium (NH4).  The tubular cell membrane is not permeable to ammonium. Therefore, it remains in the lumen and then excreted into urine.  APPLIED PHYSIOLOGY  Metabolic acidosis occurs when kidneys fail to excrete metabolic acids.  Metabolic alkalosis occurs when kidneys excrete large quantity of hydrogen. Biochemical changes in arterial blood during acid-base disturbance Causes of acidosis Causes of alkalosis  WATER –SALT BALANCE The kidneys also regulate body water by controlling the amount of urine lost per day, if the water intake is low, then the kidneys will excrete reduced volume of urine which will be concentrated conserving water On the other hand , if there is excess water in the body, the kidneys increase the volume of urine excreted and this continues until excess water is removed from the body  WATER –SALT BALANCE Regulation of body electrolyte A lot of Na+, K+, Cl -, HCO3- and other electrolytes are filtered into the kidneys Most of them are reabsorbed in the kidneys back into the body If there is excess of any particular electrolyte, the kidneys reabsorbs just the quantity required for normal body function and allow the excess to be excreted in urine  WATER –SALT BALANCE Conversely, if there is inadequate quantity of any electrolyte, the kidney ensures that none or little of that particular electrolyte is allowed to be excreted into urine It preserves most of this electrolyte and continues until the normal level of that electrolyte is restored Various hormones are responsible for regulation of electrolytes by the kidneys e.g aldosterone regulates the amount of Na absorbed in the kidneys CONCENTRATING AND DILUTING MECHANISM OF URINE OUTLINE MEDULLARY GRADIENT COUNTER CURRENT MECHANISM Role of ADH  CONCENTRATING AND DILUTING MECHANISM OF URINE When fluid intake is high, normal kidneys produce large volume of dilute urine When fluid intake is low or fluid loss is large small volume of urine is formed by the kidneys The kidney functions to maintain the normal osmotic concentration of the body at 300mOsm slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Therefore, when the urine is concentrated, water is retained in excess of solute; and when it is dilute, water is lost from the body in excess of solute. Both facts have great importance in the body economy and the regulation of the osmolality of the body fluids..  CONCENTRATING AND DILUTING MECHANISM OF URINE Formation of concentrated urine is not as simple as that of dilute urine. However, the following factors are concerned with mechanism of concentrating and diluting urine 1. Development and maintenance of medullary gradient (hyperosmotic gradient) 2. Secretion of ADH  CONCENTRATING AND DILUTING MECHANISM OF URINE 1. Development and maintenance of medullary gradient in renal medulla From the corticomedullary junction to the renal papillae there exists a gradient in the renal interstitium osmolality This gradient is necessary for the production of concentrated urine If the gradient is not present, water from the collecting duct is not reabsorbed and dilute urine is formed This gradient is developed and maintained by a countercurrent mechanism slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Counter current mechanism It is a system in which fluid flow in parallel arranged tubes but in opposite direction in the kidneys LH,CD and Vasa recta form the system The system consist of two parts ,the counter current multiplier and the countercurrent exchanger slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Development of medullary gradient This gradient is developed by two mechanisms a counter current multiplication by the loop of henle ( mainly) Recycling of urea Maintenance of Medullary gradient By the vasa recta that act as the counter current exchanger CONCENTRATING AND DILUTING MECHANISM OF URINE slides by Dr Onaadepo CONCENTRATING AND DILUTING MECHANISM OF URINE slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Development of medullary gradient 1.Counter current multiplier This is mainly formed by the LH but CD also participate Sodium reabsorption is mainly responsible for this The wall of the ascending limb of Henle is impermeable to water The fluid that enters the descending limb is isotonic, as it moves up the ascending limb of Henle, chloride ions are actively reabsorbed and deposited in the renal medulla slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE This is followed by passive reabsorption of sodium due to electrochemical gradient created by active reabsorption of chloride The wall of this segment of nephron is impermeable to water, no water is reabsorbed Since GFR is a continuous process, each time the isotonic fluid enters the U-shaped portion it becomes hypotonic because of NaCl reabsorption The continuous deposition of NaCl in the interstitium is called a multiplier effect slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE It leads to accumulation of NaCl in the renal interstitium and a build up of increasing osmotic concentration tissues It has been shown that as one moves from cortex to the medulla, the osmotic concentration of the interstitial fluid increases progressively until it reaches a maximum of 1200 milliosmoles at the level of the papillae slides by Dr Onaadepo slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Development of medullary gradient 2. UREA recycling also contributes to this build up of osmotic concentration in the renal interstitium Urea contributes about 40-50% of the osmolality Urea is passively reabsorbed from the PCT and the CD The rest of the nephron is impermeable to urea Therefore, as the tubular lumen moves towards the CD, urea load increases because of reabsorption of water slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE However ,when the tubular fluid reaches the inner medullary portion of the collecting fluid urea diffuses out passively into the interstitium adding to the hyperosmolality The movement of urea in this portion is facilitated by ADH Simultaneous movement of water and urea in the inner medullary CD maintains a high concentration of urea in the tubular fluid and eventually in urine , even though urea is being reabsorbed slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Some of the urea that moves into the medullary interstitium eventually diffuse into the thin loop of Henle From there, it passes upward through the ascending loop of Henle, DCT through to the medullary CD again From there it diffuses back into the medullary interstitium In this way, urea can re-circulate through the terminal part of the nephron several times before it is excreted slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Each time it moves around the circuit leads to a higher concentration of urea in the interstitium Thus, this urea recirculation provides an additional mechanism for forming an hyperosmotic renal medulla slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Maintenance of osmotic gradient Counter current exchanger Vasa recta also has a U shape like the loop of Henle Blood flow in the vasa recta is also counter current As blood in the vasa recta flows from the corticomedullary junction into the deeper layers of the medulla, the blood traverses areas of increasing osmotic concentration slides by Dr Onaadepo  Maintenance of osmotic gradient Vasa recta functions as countercurrent exchanger. The osmotic gradient in the medullary pyramids would not last long if the Na+ and urea in the interstitial spaces were removed by the circulation. These solutes remain in the pyramids primarily because the vasa recta operate as countercurrent exchangers. Vasa recta acts like countercurrent exchanger because of its position. It is a ‘U’shaped tubule with a descending limb, hairpin bend and an ascending limb. Vasa recta runs parallel to loop of Henle. Its descending limb runs along the ascending limb of Henle loop and its ascending limb runs along with descending limb of Henle loop  CONCENTRATING AND DILUTING MECHANISM OF URINE Vasa recta as a capillary is freely permeable to water and electrolytes Thus as blood in the vasa recta moves into the medulla, its content equilibrate with the surrounding interstitium and becomes progressively concentrated By the time the blood in the vasa recta reaches the level of the papilla its osmotic concentratoin is 1200 milliosmoles slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Vasa recta then curves round the loop of Henle and blood flowing through it moves from the papillar region back to the corticomedullary junction through areas of decreasing osmotic concentration Most of the solute gained by the blood on entry into the medulla is lost into the interstitium on exit However all the solute gained by the vasa recta is not given up on exit from the medulla, a very small quantity is removed slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Vasa recta by giving up the electrolytes it gained on entry as it moves out of the medulla is said to act as countercurrent exchanger The process prevents the blood flow to this part of the kidney from carrying away the high solute concentration that the counter current multiplier have built up in the renal interstitial tissues, By giving up on exit the solute it gained on entry, the vasa recta helps to preserve the osmotic concentration gradient earlier established by the loop of Henle slides by Dr Onaadepo slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Vasa recta also removes on exit a very small quantity of the solutes deposited in the renal interstitium It prevents an indefinite accumulation of solutes in the interstitium, thereby preventing supersaturation slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE Role of Antidiuretic hormone Antidiuretic Hormone also called vasopressin which is an hormone from the posterior pituitary gland plays a role in the final concentration of urine. Osmoreceptors cells are present in the hypothalamus are are capable of detecting changes in the osmolarity of the plasma slides by Dr Onaadepo  ROLE OF ADH IN URINE CONCENTRATION The fluid from the thick ascending loop of henle to the DCT is hypotonic.sodium and chloride is further reabsorbed in the DCT which make the fluid more hypotonic Normally, the distal convoluted tubule and collecting duct are not permeable to water. But the presence of ADH makes them permeable, resulting in water reabsorption..  ROLE OF ADH IN URINE CONCENTRATION. A large quantity of water is removed from the fluid while passing through distal convoluted tubule and collecting duct. So, the urine becomes hypertonic with an osmolarity of 1,200 mOsm/L..  CONCENTRATING AND DILUTING MECHANISM OF URINE When the tonicity of the plasma increases(fluid loss, reduce fluid intake), it stimulates the osmoreceptors cells and cause them to fire nervous impulses to the posterior pituitary to release ADH When there is decrease tonicity, osmoreceptors are not stimulated and ADH is not released slides by Dr Onaadepo  CONCENTRATING AND DILUTING MECHANISM OF URINE When ADH is released in hypertonicity. it reaches the kidneys and act on the walls of the DCT and makes it permeable to water The degree of urinary concentration depends on the level of ADH in circulation If ADH is absent, urine concentration can not occur even when the countercurrent multiplier and exchanger aspects of the system are fully functional slides by Dr Onaadepo