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Acid-Base Balance Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acid-Base 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 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. pH Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Buffer Systems Provide or remove H+ and stabilize the pH. Include weak acids that can donate H+ and weak bases that can absorb H+. Change in pH, after addition of acid, is less than it would be in the absence of buffer. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical Buffers Act within fraction of a second HCO3-. Protein. Phosphate. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. HCO3 pk= 6.1. Present in large quantities. Open system. Respiratory and renal systems act on this buffer system. Most important ECF buffer. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bicarbonate buffer Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bicarbonate buffer Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Quantitative Dynamics of the Bicarbonate Buffer System Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bicarbonate buffer Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) Maintain a 20:1 ratio : HCO3- : H2CO3 HCl + NaHCO3 ↔ H2CO3 + NaCl NaOH + H2CO3 ↔ NaHCO3 + H2O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Henderson-Hassalbalch Equation pH = pK + log [base] [acid] Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. APPLICATIONS OF HH EQUATION Use to calculate how pH of a physiologic solution responds to changes in the concentration of a week acid and/or it’s corresponding salt form. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proteins COOH or NH2. Largest pool of buffers in the body. pk close to plasma. Albumin, globulins such as Hb. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Protein Buffers Includes hemoglobin, work in blood Carboxyl group gives up H+ Amino Group accepts H+ Side chains that can buffer H+ are present on 27 amino acids. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phosphates pk. = 6.8. Low [ ] in ECF, better buffer in ICF, kidneys, and bone. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phosphate buffer Major intracellular buffer H+ + HPO42- ↔ H2PO4- OH- + H2PO4- ↔ H2O + HPO42- Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urinary Buffers Nephron cannot produce a urine pH < 4.5. IN order to excrete more H+, the acid must be buffered. H+ secreted into the urine tubule and combines with HPO4-2 or NH3. HPO4-2 + H+ H2PO4-2 NH3 + H+ NH4+ Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Acid-Base Regulation Kidneys help regulate blood pH by excreting H+ and reabsorbing HC03-. Most of the H+ secretion occurs across the walls of the PCT in exchange for Na+. Antiport mechanism. Moves Na+ and H+ in opposite directions. Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03- and excrete H+. Returns blood pH back to normal range. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reabsorption of HCO3 Apical membranes of tubule cells are impermeable to HCO3-. When urine is acidic, HCO3- combines with H+ to form H2C03-, which is catalyzed by CA located in the apical cell membrane of PCT. Reabsorption is indirect. As [C02] increases in the filtrate, C02 diffuses into tubule cell and forms H2C03. H2C03 dissociates to HCO3- and H+. HCO3- generated within tubule cell diffuses into peritubular capillary. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urinary Buffers Nephron cannot produce a urine pH < 4.5. In order to excrete more H+, the acid must be buffered. H+ secreted into the urine tubule and combines with HPO4-2 or NH3. HPO4-2 + H+ H2PO4NH3 + H+ NH4+ Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Acidosis Gain of fixed acid or loss of HCO3-. Plasma HCO3- decreases. pH decreases. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Alkalosis Loss of fixed acid or gain of HCO3-. Plasma HCO3- increases. pH increases. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Acidosis Bicarbonate deficit - Blood concentrations of Bicarbonate drop below 22mEq/L Causes: Loss of bicarbonate through diarrhea or renal dysfunction Accumulation of acids (lactic acid or ketones) Failure of kidneys to excrete H+ Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Compensation for Metabolic Acidosis Increased ventilation Renal excretion of hydrogen ions if possible K+ exchanges with excess H+ in ECF ( H+ into cells, K+ out of cells) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Alkalosis Bicarbonate excess - concentration in blood is greater than 26 mEq/L Causes: Excess vomiting = loss of stomach acid Excessive use of alkaline drugs Certain diuretics Endocrine disorders Heavy ingestion of antacids Severe dehydration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Compensation for Metabolic Alkalosis Alkalosis most commonly occurs with renal dysfunction, so can’t count on kidneys Respiratory compensation difficult – hypoventilation limited by hypoxia Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diagnosis of Acid-Base Imbalances 1. 2. Note whether the pH is low (acidosis) or high (alkalosis) Decide which value, pCO2 or HCO3- , is outside the normal range and could be the cause of the problem. If the cause is a change in pCO2, the problem is respiratory. If the cause is HCO3- the problem is metabolic. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3. Look at the value that doesn’t correspond to the observed pH change. If it is inside the normal range, there is no compensation occurring. If it is outside the normal range, the body is partially compensating for the problem. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anion Gap The difference between [Na+] and the sum of [HC03-] and [Cl-]. + [Na ] – ([HC03 ] - [Cl ]) = 144 - 24 - 108 = 12mEq/L Normal = 8-16mE/l Clinicians use the anion gap to identify the cause of metabolic acidosis. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anion Gap Law of electroneutrality: Blood plasma contains an = number of + and – charges. The major cation is Na+. Minor cations are K+, Ca2+ , Mg2+. The major anions are HC03- and Cl (Routinely measured.) Minor anions include albumin, phosphate, sulfate (called unmeasured anions). Organic acid anions include lactate and acetoacetate,. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anion Gap In metabolic acidosis, the strong acid releases protons that are buffered primarily by [HC03]. This causes plasma [HC03-] to decrease, shrinking the [HC03-] on the ionogram. Anions that remain from the strong acid, are added to the plasma. If lactic acid is added, the [lactate] rises. Increasing the total [unmeasured anions]. If HCL is added, the [Cl-] rises. Decreasing the [HC03 ]. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anion Gap in Metabolic Acidosis Salicylates raise the gap to 20. Renal failure raises gap to 25. Diabetic ketoacidosis raises the gap to 35-40. Lactic acidosis raises the gap to > 35. Largest gaps are caused by ketoacidosis and lactic acidosis. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. THANKS