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1 ACID BASE BALANCE Dr. Eman El Eter pH Review 2 pH = - log [H+] H+ is really a proton Range is from 0 - 14 If [H+] is high, the solution is acidic; pH < 7 If [H+] is low, the solution is basic or alkaline ; pH > 7 pH Review, cont…………. 3 Acids are H+ donors. Bases are H+ acceptors, or give up OH- in solution. Acids and bases can be: Strong – dissociate completely in solution HCl, NaOH Weak – dissociate only partially in solution Lactic acid, carbonic acid The Body and pH 4 Homeostasis of pH is tightly controlled Extracellular fluid pH= 7.4 Arterial Blood pH= 7.35 – 7.45 Venous blood is more acidic than arterial? Because it contains more CO2 than arterial blood. < 6.8 or > 8.0 death occurs Acidosis (acidemia) below 7.35 Alkalosis (alkalemia) above 7.45 5 Why Small changes in pH is a serious condition? 6 It can produce major disturbances: Most enzymes function only with narrow pH ranges. Acid-base balance can also affect electrolytes (Na+, K+, Cl-). Can also affect hormones. The body produces more acids than bases 7 Sources of acids: Acids take in with foods Acids produced by metabolism of lipids and proteins Cellular metabolism produces CO2. CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3- 8 Body defense against changes in Hydrogen ion concentration 9 10 Rates of correction 11 Buffers function almost instantaneously Respiratory mechanisms take several minutes to hours Renal mechanisms may take several hours to days A- buffer systems of body fluids: 12 Take up H+ or release H+ as conditions change Buffer pairs – weak acid and a base Exchange a strong acid or base for a weak one Results in a much smaller pH change 1- Bicarbonate buffer 13 Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3). Most important extracellular buffer why? Because the components of the system are closely regulated by the lungs and kidneys. It acts both extracellular and intracellular. Its concentration in blood equals = 27mEq/L and is called alkali reserve. Maintain a 20:1 ratio : HCO3- : H2CO3 CO2 + H2O H2CO3 HCl + NaHCO3 ↔ H2CO3 (week acid)+ NaCl NaOH + H2CO3 ↔ NaHCO3 (weak base) + H2O. Bicarbonate buffer system, cont……. 14 The relationship of bicarbonate and carbon dioxide to pH is given by Handerson-Hasselbalch equation: pH = 6.1 + log HCO3- 0.03 X PCO2 CO2: is the acid element as it binds with water to form H2CO3. HCO3-: is the basic element. 2- Phosphate buffer 15 Important intracellular buffer& renal tubular fluid. It is an important buffer in renal tubules. H+ + HPO42- ↔ H2PO4- OH- + H2PO4- ↔ H2O + H2PO42- 3- Protein Buffers 16 Includes hemoglobin, work in red blood cells. Carboxyl group gives up H+ Amino Group accepts H+ Plasma proteins. Intracellular proteins. Most important buffer systems in the body are the proteins of the cells b. Respiratory mechanisms 17 Exhalation of carbon dioxide. Powerful, but only works with volatile acids Doesn’t affect fixed acids like lactic acid CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3Body pH can be adjusted by changing rate and depth of breathing. Works within seconds to minutes and acts as a second line of defense. Hyperventilation wash out excess CO2. Hypoventilation retain CO2. This process is controlled by chemoreceptor. C. Renal control of acid base balance 18 Can eliminate large amounts of acid Can also excrete base Can conserve and produce HCO3- ions Most effective regulator of pH Adjust H+ ion concentration to normal It is a slow mechanism that works over a period of hours to several days, but a powerful mechanism. If kidneys fail, pH balance fails. C. Renal control of acid base balance, cont…… 19 Renal regulation of acid base occurs through 3 basic mechanisms: 1- Secretion of H+ and urine acidification at pH 5.0 2- Reabsorption of filtered HCO33- Production of new HCO3- Secretion of H+ & Reabsorption of filtered HCO320 This mechanism of HCO3reabsorption occurs in: PCT Thick ascending loop of Henle DCT Where H+ is secreted into tubular fluid by Na+-H+ countertransport. Normally > 99% of filtered HCO-3 is reabsorbed by renal tubules Reabsorption of filtered HCO321 Secretion of H+ & Reabsorption of filtered HCO3-, 22 In distal and collecting tubules H+ is secreted by primary active transport. These segments can increase H+ secretion by 900fold pH of tubular fluid thus can be reduced to 4.5. This is the lower limit that can be achieved in normal kidneys. For the kidney to continue secretion of H+, it has to be buffered by two main urinary buffers: 1- phosphate buffer 2- Ammonia: most important urinary buffer in acidosis. Reabsorption of new of HCO3- by distal & collecting tubules 23 Cell metabolism As sodium salt Under normal condition H+ secretion= 4400 mEq/day, Rate of HCO3- Filtration = 4320 mEq/day H+ and HCO3- normally titrate each other in the tubules. For each H+ excreted with phosphate buffer, a new HCO3- is generated and reabsorbed. It represents a net gain of HCO3- by the blood 24 Under normal conditions , 75%of filtered phosphate is reabsorbed, only 30-40 mEq/day is available for buffering H+. That is why much of the buffering of excess H+ in the tubular fluid in severe acidosis occurs through ammonia buffer system. Ammonia buffers H+ and form Ammonium 25 new 2 2 How is ammonia formed? Where? 26 Ammonia buffer system: Ammonia (NH3)/ammonium (NH4+) Synthesized from glutamine which is actively transported into the cells of: PCT Thick ascending limb of Henle Distal tubules. Ammonia is a product of glutamine metabolism. Glutamine is actively transported into renal cells. Once inside, each molecule is metabolized to give two NH3 and two HCO3NH3 is secreted into tubular lumen. HCO3+ moves across the basolateral membrane. This is a new bicarbonate added to the blood. Ammonia formation 27