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Acid –Base Balance Adedapo K.S.FWACP( Lab. Med.) BASIC CONCEPTS OF HYDROGEN ION HOMOEOSTASIS Metabolic processes in the body lead to the production of hydrogen ions which, if left to accumulate, would be injurious to the body The body, therefore, has a number of ways to remove the hydrogen ions produced to provide a conducive environment for cellular processes to continue. Sources of Hydrogen ions Conversion of amino acid nitrogen to urea releasing equimolar amounts of hydrogen ions.(H+) Anaerobic carbohydrate metabolism yields lactate and H+ Anaerobic metabolism of fatty acids and ketogenic amino acids yield acetoactate and also equimolar amounts of H+. Definitions Acid: An acid is a compound which dissociates in an aqueous solution to produce hydrogen ions. e.g. HCl H+ + CLBase: A base is a substance that is capable of accepting hydrogen ion. e.g. HCO3- + H+ H2CO3 Buffering: Buffering is the process by which a strong acid (or base) is replaced by a weaker one with a consequent reduction in the number of free hydrogen ion(H+). The essence of a buffer is to mop up H+ and produce a minimal change in pH. H+ Cl- + NaHCO3 H2CO3 + NaCl strong acid Buffer weak acid neutral salt Buffer Buffer. A buffer is the salt of a weak acid which, when exposed to high H+ concentration of a strong acid, forms a weak acid. pH. is a measure of hydrogen ion activity. It is log10 of the reciprocal of the hydrogen ion. The log10 of a number is the power to which 10 must be raised to produce that number. pH of the blood is 7.35-7.45 Henderson-Hasselbalch Equation It expresses the relationship between pH and a buffer pair. In aqueous solution, the pH is determined by the concentration ratio of the acid to its conjugate base. pH = pK + log (HCO3-) (H2CO3) pK is the log of dissociation constant K Henderson’s equation H2CO3 is in equilibrium with dissolved CO2 and so can be inserted into the equation in place of H2CO3 which cannot be measured directly. Substituting (Co2) in place of H2CO3 in the previous equation; pH= pK + log(HCO3-) (CO2) Henderson’s equation pK for HCO3/H2CO3 buffer pair is 6.1 pCO2 in kilopascals is 0.23, and 0.03 in mmHg. Putting this back in the equation pH = 6.1 + log (HCO3-) PCO2x 0.23 Control of Carbon dioxide (CO2) Control of CO2 is by the lungs The lungs participates in the maintenance of H+ ion when: Inspired oxygen is carried from the lungs to tissue by haemoglobin. The tissue (cells) use the oxygen for aerobic metabolism and release CO2. CO2 diffuses along a concentration gradient from the cells into the extracellular fluid and is returned by the blood to the lungs where it is eliminated in the expired air. Buffer Pairs in body system Central to maintenance of the steady state of pH is the HCO3-/H2CO3 buffer pair. Other buffer pairs / systems are: ·Protein- /protein · Hb-/HHb · NH3-/NH4 pk=9.8 · NaHPO4-/NaH2PO4 pK=6.8 A buffer pair functions best at pH nearest its pK HCO3-/H2CO3 buffer pair Workhorse of the buffering Process Accounts for most of the buffering in the steady state 2 main mechanisms Bicarbonate resorption and Bicarbonate regeneration Regeneration in the Kidney and erythrocytes Bicarbonate Resorption Result: No net gain of HCO3, Most useful in steady state HCO3 Generation There is net gain of HCO3 Bicarbonate Generation by Erythrocytes Here Hb serves as the blood buffer Hb-/HHb Red Cell Urinary buffers These do not operate separately from the above mechanism, but are, however, brought into play when bicarbonate concentration becomes reduced in acidotic states. The two most important ones are phosphate and ammonia. Urinary buffers Ammonia is produced during the deamination of glutamine in the renal tubular cells, The enzyme glutaminase catalyses the reaction which is itself triggered off by the state of acidosis, thereby allowing the generation of the required ammonia which readily diffuses across the renal tubular cell. NH3 + H+ -- NH4 The ammonium ion (NH4) so formed is passed out in the urine, thus promoting the loss of excess H+ ions and reducing acidosis. Anion Gap This is the difference between the measured cations (Na+& K+) and the measured anions (Chloride and Bicarbonate) Normally between 15-20Mmol/L Increases when unmeasured anions such as phosphates and sulphates increase in the blood and HCO3 falls in acidosis The converse occurs in metabolic alkalosis METABOLIC DERANGEMENTS Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory alkalosis Mixed picture (largely compensational) Metabolic acidosis This occurs when the primary abnormality in the bicarbonate buffer system is the reduction of (HCO3-). Changes in pCO2 are secondary. When (HCO3-) is reduced in the equation; pH = pK + log HCO3PCO2 The pH will fall. Causes of Metabolic Acidosis Increased or excess H+ production: Ketoacidosis, e.g., uncontrolled diabetes mellitus, starvation, lactic acidosis, shock. Poisoning, e.g., salicylate over-dosage, Failure to excrete H+: Acute and chronic renal failure , distal renal tubular acidosis. Loss of HCO3- from GIT : Severe diarrhoea, pancreatic fistula Loss of HCO3- in urine: Ureteroenterostomy, proximal renal tubular acidosis, carbonic anhydrase inhibitors. Compensation Compensation for metabolic acidosis occurs through the respiratory centre. There is stimulation of the respiratory centre resulting in hyperventilation to ’wash out’ CO2, and avoid a change in pH. pH =6.1 + log (HCO3-) PCO2x 0.23 Renal Tubular Acidosis( RTA) Usually an acquired disorder Could be inherited No 10 glomerular lesion, urea & creatinine are normal Usually a tubular defect-2types Classical or Type 1,Distal RTA-abnormal permeability of distal tubular cells to H+ Proximal or type 2 -defect of Carbonic anhydrase Both result in metabolic acidosis Respiratory Acidosis This is characterized by an increase in pCO2 due to CO2 retention. If pCO2 is increased in the equation: pH = (HCO3-) PCO2 pH will fall. Causes of Respiratory Acidosis Pulmonary disease :Chronic obstructive airway disease(COAD), e.g, chronic bronchitis, emphysema, severe asthma, pulmonary oedema. Chest infection: Bronchopneumonia CNS depression :Anaesthetics, opiates. CNS disease: Stroke, trauma. Compensation Compensation occurs by the acceleration of the carbonic anhydrase mechanism in the erythrocytes and renal tubular cells, resulting in high HCO3 which could also lead to normal or no change in pH. Metabolic Alkalosis This disorder is characterised primarily by an increase in the concentration of bicarbonate in the ECF, resulting in the reduction of hydrogen ion concentration. When this occurs, bicarbonate reabsorption is reduced, resulting in bicarbonate excretion in urine. Causes of Metabolic Alkalosis · Ingestion of large amount of bicarbonate to treat indigestion. · Loss of unbuffered H+, e.g., Conn’s and Cushing’s syndrome · Loss of H+ from GI tract vomiting, e. g., nasogastric tube drainage pyloric stenosis. · Loss of H+ in urine thiazide diuretics Compenstion Largely by induction of respiratory acidosis by CO2 retention to avoid a shift in pH from the equation: Respiratory Alkalosis This occurs when there is a fall in PCO2 which reduces the ratio of pCO2 to bicarbonate concentration in the pH equation. Causes are: · Hysterical over breathing: Voluntary hyperventilation, excessive artificial respiration · Stimulation of Respiratory centre: Pain, fever, hypoxia, Lobar pneumonia , Hypoxia, pulmonary oedema · Raised intracranial pressure or brain stem lesions Compensation There is a compensatory fall in the drive of carbonic anhydrase system to reclaim bicarbonate in both the kidneys and the erythrocytes leading to a fall in HCO3- to minimise the change in pH. Thank you for Listening