Renal Acid - Base Balance

• Acid and Base • Acid • Any substance that can yield a hydrogen ion (H+) or hydronium ion when dissolved in water : • Release of proton or H+ • Base • Substance that can yield hydroxyl ions (OH-) • Accept protons or H+ 4 • PH/PK • PK= Negative log of the ionization constant of an acid • Strong acids would have a pK <3 • Strong base would have a pK >9 • • PH= Negative log of the hydrogen ion concentration • pH= pK + log([base]/[acid]) • Represents the hydrogen concentration 5 • Buffer: Combination of a weak acid and /or a weak base and its salt • What does it do? • Resists against any changes of physiologic pH • Buffer Effectiveness depends on: • pK of buffering system ( of Acid) • pH of environment in which it is placed 6 • Acidosis: Physiology pH is less than 7.35 • Alkalosis: physiology pH is greater than 7.45 • Note: Normal pH is 7.35-7.45 7 • Acid-Base Balance • Function: • Maintains the pH homeostasis • Maintenance of H+ concentration • Potential Problems of Acid-Base balance: • Increased H+ concentration yields decreased pH • Decreased H+ concentration yields increased pH 8 • Regulation of pH • Acid-Base Balance (Balance of the production and retention of acids and bases) are kept by systems of: • Respiratory Center and Lungs • Kidneys • Buffers • The whole acids and base are found in all body fluids ( extracellular and interacellular) • Weak acids are good buffers since they can tilt (reverse) a reaction in the other direction • AH H+ + A• Strong acids are poor buffers because they make the system more acid AH H+ + A9 • What is Buffer? • Buffer is a mixture of one weak acid and a salt of that acid from strong Alkali Example: • Mixture of carbonic acid and sodium carbonate • Mixture of acetic acid and sodium acetate • Function of a Buffer? It Prevents from remarkable change in physiologic PH 10 • Defense Lines against PH change? • There are three lines as follow: • First line of defense against PH shift is Chemical buffers ( Bicarbonate , phosphate , amino acids and proteins systems )in a few seconds • Second line of defense against PH shift is Respiratory mechanisem (CO2 excretion) in a few minutes • Last line of defense against PH shift is renal mechanism ( H+ excretion) in a few hours to day 11 • Buffering Capacity distribution in Body • 52% of the buffering capacity is in cells • 5% is in RBCs • The rest in extracellular space ( 43%) • Kinds of Buffering capacity extracellular space • 43% of the buffering capacity is in the extracellular space • of which 40% by bicarbonate buffer, 1% by proteins and 1% by phosphate buffer system 12 • Type of buffering systems : • The three different buffering systems are based on their location: 1) Respiratory buffering system :Uses bicarbonate 2) Blood buffering system: Uses bicarbonate, phosphate, and protein 3) Renal buffering system: Uses bicarbonate, phosphate, and ammonia 13 • Source of acids production in our body: • Acids are being created constantly through metabolism by: • Protein breakdown that produces phosphoric acid • Anaerobic respiration of glucose produces lactic acid • Fat metabolism yields organic acids and ketone bodies • Carbon dioxide is also an acid that is produced in metabolism. • Transporting CO2 as bicarbonate leads to a release of H+ (an acid) 14 • Acid Base Balance • There is a partial different between arterial blood pH(pH=7.4) and intracellular fluid pH(pH = 7.0). • The Most metabolic reactions liberate H+, and a buffer system is needed to maintain physiological pH and neutralize it. 15 • Kinds of Protein Buffer System • Originates from amino acids • 1-ALBUMIN- primary protein due to high concentration in plasma • 2- Hemoglobin Buffer System • Roles • Binds CO2 • Binds and transports hydrogen and oxygen • Participates in the chloride shift • Maintains the physiology blood pH as hemoglobin changes from oxyhemoglobin to deoxyhemoglobin 16 • Albumin and hemoglobin buffering capacity comparison • There are 16 histidine (amino acid) residues in albumin and 38 histidines residues in hemoglobin. • These amino acids can accept a H+ and act as a buffer in the RBCs and plasma 17 • Bicarbonate/carbonic acid buffer system • CO2 + H20 H+ + HCO3- • Function almost immediately • Cells that are utilizing O2 can convert it to CO2. • Thus, more CO2 is found in the tissue cells rather than in blood cells. • This results in a pressure (pCO2). • Diffusion of CO2 occurs, and CO2 leaves the tissue into the capillary blood 18 • Bicarbonate as a Buffer • It is the Most important buffer system in the plasma • Accounts for 65% of the buffering capacity in plasma • Accounts for 40% of the buffering capacity in the whole body 19 • How is the CO2 transported? • 5-8% of CO2 transported in dissolved form ( in water) • A small amount of the CO2 combines directly with the hemoglobin to form carbamino hemoglobin • 92-95% of CO2 will enter the RBC, and under the following reaction • CO2 + H20 H+ + HCO3• Once bicarbonate formed, exchanged for chloride 20 Normal ratio of bicarbonate/carbonic acid is : 20/1 20 = Kidney = metabolic 1 Lungs respiratory • The ratio of HCO3- (salt) to H2CO3 ( acid) is normally 20:1 • This ratio allows the blood pH of 7.40 • The pH falls (acidosis) as bicarbonate decreases in relation to carbonic acid • The pH rises (alkalosis) as bicarbonate increases in relation to carbonic acid 21 • Phosphate Buffer System • It has a major role in the buffering and elimination of H+ via the kidney in urine • It helps to exchange of sodium for hydrogen • It participates in the following reaction: • HPO4-2 + H+ H2PO4 – • It is essential within the erythrocytes 22 • Lungs/respiratory • It is the quickest way to respond to pH change , takes minutes to hours to correct the pH • It Eliminates the volatile respiratory acids such as CO2 • It doesn’t affect other acids ( Fixed acid) like lactic acid • Body pH can be adjusted by changing the rate and depth of breathing “blowing off” via Lungs/respiratory system • It provides O2 for cells and remove CO2 from lung 23 • Kidney/Metabolic • Can eliminate large amounts of acid • Can excrete base ( Bicarbonate) as well • Can take several hours to days to correct pH • It is the most effective regulator of pH • If kidney fails, pH balance is failed 24 25 • Renal Buffering Systems • The renal buffer system uses bicarbonate, phosphate and ammonium. • In the kidneys, the bicarbonate buffer may increase plasma pH in three ways: • Secrete H+, • “Reabsorb" bicarbonate, • or produce new bicarbonate. • H+ secretion occurs mostly in the proximal tubule by the carbonic anhydrase reaction. 26 27 28 • What happen in In acidic conditions, • CO2 diffuses inside tubular cells • Then is converted to carbonic acid, • carbonic acid dissociates to yield a H+ • H+ is then secreted into the lumen by the Na+/H+ shuttle ( active secretion) 29 Compensation by kidneys : How can the kidneys control acids and bases? • In Acidosis • kidneys Secrete the excessive hydrogen • A little bite of secreted excessive hydrogen binds to ammonia and phosphate base in the lumen and be buffered and then exert from urine and prevent from decrease of urine pH NH4+ Production and exceretion by kidney in urine a: H+ + NH3 NH4+ excrete in urine excrete in b: H+ + HPO42- H2PO4- ( Titerable acid) urine The majority of excreted hydrogen leads to formation of Of bicarbonate and reabsorbed in blood and tissue fluid 30 NH4+ production and excretion 31 Compensation by kidneys : How can the kidneys control acids and bases? • In Alkalosis : If the blood is too alkaline, • Componsation: the cells(tubule cells) stop the secreting H+ • and subsequently stop the CO2 and HCO3- production • And stop the bicarbonate reabsorption • and blood stream PH returns to normal range 32 Respiratory Compensation • If the kidneys has problem, the respiratory system can compensate. metabolic alkalosis and compensation • If the kidneys are secreting too much H+(which makes too much bicarbonate, causing metabolic alkalosis), breathing will become slower so that less CO2 (an acid) is lost. Metabolic acidosis and compensation • If the kidneys are reabsorbing too much H+(metabolic acidosis), breathing will become faster to excrete more CO2. 33 34 Role of Bone Buffering • Bone consists of matrix • The matrix is composed of: 1- organic compounds [collagen and other proteins in ground substance] and 2- inorganic hydroxyapatite crystals with general formula Ca10(PO4)6(OH)2] components (hydroxyapatite crystals ). • The hydroxyapatite crystals make up two-thirds of the total bone volume • They are extremely small and consequently have a huge total surface area. • The crystals contain a large amount of carbonate (CO3-2) as this anion can be replaced for both phosphate and hydroxyl in the apatite crystals.) 35 • Bone is the major CO2 reservoir in the body and contains carbonate and bicarbonate 36 • Bone is an important source of buffer in chronic metabolic acidosis • Bone is probably involved in providing some buffering (mostly by ionic exchange) in most acute acid-base disorders • Release of calcium carbonate from bone is the most important buffering mechanism involved in chronic metabolic acidosis. 37 • CO2 in bone is in two forms: • bicarbonate (HCO3-) and carbonate (CO3-2). • The bicarbonate makes up a exchangeable pool because: • it is present in the bone water which makes up the ‘hydration shell’ around each of the hydroxyapatite crystals. • The carbonate is also present in the crystals and its release from crystals requires dissolution of the crystals, which is much slower process but the amounts of buffer involved are much larger. 38 • Mechanism and function of bone as a buffer in acid –base balance • In acidosis the pH is decreased : • What is the function of bones for compensation of acidosis? • Bones function as below: • The bicarbonate is released from bones and enters in blood stream( its main place) to neutralize the acidosis • Then phosphate base leaves the stream instead , and enters to bones • Finally, stop the decrease of blood pH and it returns to normal range 39