Acid and Base Balance Lecture 17 PDF

Acid and base balance Lecture 17 Unit 3 Table of contents 1. Acids and bases in the body 2. Regulatory mechanisms 3. Laboratory tests 4. Compensation mechanisms 5. Practice 1. Acids and bases in the body Acids and bases - acids are compounds that release H+ ions. low ph = high H+...

Acid and base balance Lecture 17 Unit 3 Table of contents 1. Acids and bases in the body 2. Regulatory mechanisms 3. Laboratory tests 4. Compensation mechanisms 5. Practice 1. Acids and bases in the body Acids and bases - acids are compounds that release H+ ions. low ph = high H+ - bases are compounds that accept H+ ions. high pH = low H+ - the body uses weak acids as chemical buffers to prevent major swings in body fluid pH. - an acid (carbonic acid) and its conjugate base (bicarbonate) associate and dissociate freely depending on the availability of H+ ions. 3 1. Acids and bases in the body Metabolism produces acidic compounds - relevant metabolic acids can be classified into two categories: - volatile acids are those in equilibrium with CO2, like carbonic acid; they are volatile as CO2 leaves the body via the lungs (this is the only volatile acid). - nonvolatile (or fixed) acids are not eliminated by the lungs; they are buffered chemically by bicarbonate and proteins. 4 1. Acids and bases in the body What are common nonvolatile acids? - metabolism of our nutrient pool will produce these acids. amino acids in proteins - oxidation of sulfur-containing amino acids (like cysteine and methionine) produce sulfuric acid , while others produce hydrochloric acid. - oxidation of nucleic acids produce phosphoric acid. - anaerobic oxidation of glucose produces lactic acid. ketones: sweet odor, alcohol - oxidation of fatty acids and amino acids can produce keto acids. aerobic state: create CO2 5 2. Regulatory mechanisms Major maintenance mechanisms - there are three major ways the body maintains body fluid pH: - chemical buffers (including carbonic acid) inH+RBC and in Plasma + HCO3- = H2CO3 = H2O + CO2 - lungs (exhalation of CO2) - kidneys (excretion of H+ ions and absorption of bicarbonate) 6 2. Regulatory mechanisms Chemical buffer system - along with carbonic acid , there are two other mechanisms included in this category: - proteins and amino acids can buffer our body fluids, as the amino terminals , carboxyl terminals , and radical groups in proteins can accept and release H+ ions. - this protein buffer system occurs basic acidic largely inside cells, as with hemoglobin in RBCs but may occur in the plasma, too amino acids function as buffers (albumin and globulins ). 7 2. Regulatory mechanisms antiporter: against each other Chemical buffer system you want to mess up cells before ECF - the third mechanism is the transcellular H +/K + ECF exchange system mediated by an antiporter on the cells of the body. - this antiporter moves H+ and K+ in opposite ICF directions between the ICF and ECF. k+ out of cell in exhange of excess H+ - excess H+ in the ECF (acidosis) causes it to move into the ICF in exchange for K+ (can cause hyperkalemia ). - insufficiency of H+ in the ECF (alkalosis) causes it to move from the ICF into the ECF in exchange for K+ (can cause hypokalemia ). 8 2. Regulatory mechanisms Respiratory control mechanisms acidic -> normal -> alkaline -> normal = over compensation surrounding respiratory control so affected for longer - these respond if the chemical buffer system is overwhelmed (within minutes); does so by removing CO2 from the blood. - glossopharyngeal nerve senses changes in pH and pCO2, this can result in inc. ventilation to exhale more CO2. - adjustment of bicarbonate levels (by exhaling CO2) occur more quickly in the blood than in the cerebrospinal fluid; inc. ventilation may continue despite normal pH levels in the blood. 9 2. Regulatory mechanisms Renal control mechanisms kicks in after days and weeks making more acid therefore holding onto more buffers into the blood more bicarb in body - these mechanisms provide more permanent changes in acid-base balance , but occur more slowly than the resp. mechanisms and chemical buffers. kidney takes 1 hydrogen ion from cell : takes it mixes with bicarb : make carbonic enzyme - these changes occur as a result of: 1) reabsorbing bicarbonate (HCO 3-) and 2) secreting H + ions. we want to trap or reabsorb all the bicarbs that we can: we reabsorb carbon dioxide and xx 10 2. Regulatory mechanisms Renal control mechanisms - this begins with a sodium-hydrogen exchange system in the proximal convoluted tubule. to donate an H+ we need to reabsorb a sodium high BP + - H enters the tubular fluid and hyponatremia combines with HCO 3- filtered antiporter via the glomeruli to form H 2CO 3. - carbonic anhydrase breaks it down into CO2 and H2O, whereby CO 2 enters the cell. 11 2. Regulatory mechanisms Renal control mechanisms - inside the cell, carbonic anhydrase reforms H2CO3, which dissociates into H + and HCO 3-. - HCO 3- is reabsorbed with sodium back into the blood. - H + ions continue to be secreted in exchange for sodium along the nephron. - when HCO3- levels in the tubular fluid drop, H + ions remain in the fluid to be excreted. 12 2. Regulatory mechanisms Renal control mechanisms - an active K +/H + antiporter is expressed on the surface of cells in the distal convoluted tubule (DCT). - it uses ATP to exchange potassium and hydrogen ions. - acidosis causes excess H+ ions to be secreted into the urine in exchange for potassium; inc. plasma K+ concentrations. - alkalosis causes fewer H+ ions to be secreted into the urine and less potassium reabsorbed; dec. plasma K+ concentrations. 13 2. Regulatory mechanisms Phosphate buffer system in the urine - urine cannot be too acidic, as it could damage the urinary passageways; the phosphate buffer system regulates urine pH. acidic we want to get rid of H+ theerefore goes in cell: we take in the potassium result in hyperkalemia - as the urine is concentrated along the nephron, H + ions continue to be exchanged with sodium , further - acidifying urinecombine excess H+ ions. with phosphate and sodium to form NaH 2PO 4 (monosodium phosphate), which is eliminated in the urine. acid too acid: damages urinary tubules 14 3. Laboratory tests Diagnosing acid-base imbalances - arterial blood gas test measures blood pH, partial pressure of CO 2 (pCO 2), and HCO 3- levels. - these will tell you if acidosis or alkalosis is present but not their cause. - arterial blood is measured since components of venous blood will vary according to the metabolic activities of the various tissues. 15 3. Laboratory tests CO2 and HCO3- levels - recall that CO2 occurs dissolved in plasma , attached to Hb - (carbaminohemoglobin), and converted to carbonic acid/HCO 3. - pCO2 should measure 35-45 mmHg, while arterial HCO3- content should measure 22-26 mmol/L. - we may not pay attention to pO2 unless we are assessing lung function. 16 3. Laboratory tests Base excesses and deficits - also called whole blood buffer base. - measures all of the blood’s buffer systems: Hb, plasma protein content, phosphate, and HCO3- (most important). - it specifically describes the amount of fixed acids and bases that must be added to a blood sample to achieve a pH of 7.40. - base excesses cause alkalosis , while base deficits cause acidosis. 17 3. Laboratory tests Anion gap - difference between sodium conc. (body’s major cation) and sum of the major anions (HCO 3- and Cl -). - the anion gap is the difference between these amounts [Na+ - (Cl- + HCO3-)] and represents the unmeasured anions , including the phosphates, sulfates, organic acids, and proteins (mainly albumin). - anion gap commonly measures 8-16 mmol/L. 18 3. Laboratory tests Anion gap bicarb decreases d/t buffering -> H2CO3 = increase in anion gap - the anion gap increases during lactic acidosis and ketoacidosis (lactic acid and ketones being - organic acidosis acids) caused by hyperchloremia maintains the anion gap within its reference range. - hyperchloremia causes acidosis as less HCO3- enters the plasma to buffer the blood. (more on this in the next lecture) 19 4. Compensation mechanisms Metabolic versus respiratory disorders - these describe conditions resulting from changes in dissolved CO2 and HCO3-. - metabolic disorders involve alterations in plasma HCO3- conc. as a result of nonvolatile acids in the ECF (acidosis) or an inc. in HCO3- (alkalosis). - respiratory disorders involve alterations in blood pH due to changes in ventilation and pCO2: inc pCO2 by rebreathing -> inc H+ -> dec pH to normal range hyperventilating: dec pCO2 -> dec H+ -> pH inc -> deep breaths - inc. ventilation causes a dec. in pCO2 resulting in alkalosis. - dec. ventilation causes an inc. in pCO2 resulting in acidosis. 20 4. Compensation mechanisms Acidosis and alkalosis - acidosis and alkalosis are caused by an initiating event or a compensatory event. - compensation mechanisms are interim measures while the body tries to reestablish homeostasis; respiratory measures occurs first. - for example, metabolic acidosis can be initiated by ketosis, and to compensate , ventilation inc.; prolonged ketosis and respiratory compensation can result in respiratory alkalosis. - compensation mechanisms are more effective with time, as the kidneys contribute greatly to reestablishing acid-base homeostasis. 21 4. Compensation mechanisms Examples of compensation - for example, metabolic acidosis initiated by ketosis can be compensated for quickly by increasing our respiratory rate. Normal ratio between Ketosis causes Resp. syst. can HCO3- and H2CO3 is 20:1 metabolic acidosis compensate 22 4. Compensation mechanisms pregnant women: co2 retainer: organs all pushed up: respiratory alkalosis Examples of compensation - for example, pregnancy can initiate respiratory alkalosis, while the kidneys can compensate by reabsorbing less HCO3-. Normal ratio between Pregnancy causes Renal compensation HCO3- and H2CO3 is 20:1 resp. alkalosis 23 5. Review Questions - How can a weak acid-base pair act as a buffer? - How is carbon dioxide transported in the blood? - Why must the pH of urine be regulated? How is it done? - How can protein act as a buffer? - How does respiration and kidneys regulate pH? - What is the anion gap? - What is the difference between the primary and compensatory mechanism of pH regulation? 24