Acid-Base Balance (Dr. Ekoriko) PDF

ACID-BASE BALANCE(2) Dr. HENRY EKORIKO DEPT. OF MEDICAL BIOCHEMISTRY UNIUYO DISTURBANCES IN ACID-BASE BALANCE The body cells can tolerate only a narrow pH change Acidosis is the clinical state, where acids accumulate or bases are lost. A loss of acid or accumulati...

ACID-BASE BALANCE(2) Dr. HENRY EKORIKO DEPT. OF MEDICAL BIOCHEMISTRY UNIUYO DISTURBANCES IN ACID-BASE BALANCE The body cells can tolerate only a narrow pH change Acidosis is the clinical state, where acids accumulate or bases are lost. A loss of acid or accumulation of base leads to alkalosis Respiratory acidosis: Primary excess of carbonic acid. Metabolic acidosis: Primary deficit of bicarbonate Respiratory alkalosis: Primary deficit of carbonic acid. Metabolic alkalosis: Primary excess of bicarbonate Metabolic Acidosis(primary alkali deficit) It is caused when there is a reduction in the plasma HCO 3 – ↓ (B. HCO ) 3 ↓ with either no or little change in the H CO fraction. 2 3 pH is decreased, (primary bicarbonate deficit). In uncompensated phase Disproportionate decrease in [HCO ] - ↓ ↓ ↓ ↓ 3 [H CO ] pCO Ratio 2 3 2 compensatory mechanism: Primary: Respiratory-low pH stimulates respiratory centre producing hyperventilation( Kausmaul breathing) and decrease in [H CO ] 2 3 ↓ Metabolic Acidosis Secondary: Renal H+ -Na exchange ↑ increased HCO3- reabsorption ↑ increased NH3 formation ↑ increased Urinary findings pH: Acidic Increase excretion of NH4Cl and NaH2PO4 Increase in titratable acidity CAUSES OF Metabolic Acidosis Abnormal increase in anions other than HCO3- (acid gain acidosis) Endogenous production of acid ions when excessive Diabetic acidosis Starvation Lactic acidosis Ingestion of acidifying salts Renal insufficiency: Retention of acids normally produced Ingestion of acidifying salts Abnormal loss of HCO3–, e.g. in severe diarrhoea, fistulas  Respiratory acidosis (carbonic acid excess). ↑ The underlying abnormality here is increase in H2CO3 in the ↑ blood, which follows decreased elimination of CO2 (pCO2 ) in the pulmonary alveoli ↓ [HCO3-]/[H2CO3] is low, resulting lowering in pH In uncompensated phase; Disproportionate increase in [H2CO3] ↑, Ratio ↓ ↑ increase in [HCO3-] pCO2 ↑, Total CO2↑ increased Respiratory acidosis contd In fully compensated phase: Total CO2 content is high but the increase in [H2CO3] is proportionate and ratio 20:1 and pH maintained. Compensatory mechanism Primary: Renal: Most important Increase in H+: Na exchange, More HCO3- reabsorption, Increase NH3 formation Secondary: Respiratory—partial as the pathogenesis involves Lung disorders/or depression of respiratory centre Urinary findings- same as metabolic acidosis CAUSES OF RESPIRATORY ACIDOSIS 1.Conditions in which there is depression/or suppression of respiration  Damage to CNS Brain damage (trauma, inflammation, compression), convulsions Drug poisoning like morphine or barbiturates Excessive anaesthesia Bulbar polio  Effects of pain like pleurisy CAUSES OF RESPIRATORY ACIDOSIS CONTD 2 Reduction of respiratory surface: Emphysema, pneumonia, Pulmonary fibrosis, pulmonary oedema, etc. 3. Condition in which there is ‘obstruction’ to escape of CO2 from the alveoli: Obstruction to respiratory tract, Rebreathing from a closed space 4. Conditions in which pulmonary blood flow is insufficient, e.g. certain congenital heart diseases ALKALOSIS Metabolic Alkalosis (primary alkali excess). This condition results from an absolute or relative increase in [HCO3-]. The respiratory centre (RC) is inhibited by alkalosis causing shallow, irregular breathing In uncompensated phase: Disproportionate increase[HCO3-] ↑,[H2CO3] ↑ ↑ or N, pCO2 or N, Total CO2 ↑, ↑ pH In fully compensated phase: Total CO2 is high ↑ but increase in [HCO3-] and [H2CO3] are proportionate and ratio 20:1 and pH is maintained  Compensatory mechanisms Primary: Respiratory-Depression of RC and hypoventilation leading to retention in CO2 ↓, Secondary: Renal--H+ —Na exchange NH3 formation ↓, bicarbonate (HCO–3) reabsorption ↓, ↑, K+ excretion Cl– retention Urinary findings--pH of urine: Alkaline, Decrease NH3 ↓, ↓ Decrease titratable acidity Causes Excessive loss of HCl: Protracted gastric lavage, Pyloric obstruction, High intestinal obstruction Alkali ingestion and alkali administration Excessive loss of K+ leading to K+ deficiency Respiratory alkalosis Primary H CO deficit ↓, 2 3 In uncompensated phase: Disproportionate decrease[H CO ] [HCO -] ↓ or N, pCO ↓ or N, Ratio ↑, Total CO pH ↓, ↑ 2 3 3 ↓ 2 2 In fully compensated phase: Total CO content is low. decrease in 2 [HCO -] and [H CO ] are proportionate and ratio 20:1 and pH maintained 3 2 3 Compensatory mechanisms Primary: Renal--Decreased H+ –Na+ exchange Decreased ↓, ↓, excretion of acid Increased excretion of HCO - Decreased ↑, excretion of NH ↓, ↑, K+ excretion Cl retention 3 – 3 Secondary: Respiratory-High pH and low pCO produces 2 hypoventilation and increase in H CO 2 3 Causes Stimulation of respiratory centre (RC) CNS disease: Meningitis, encephalitis Salicylate poisoning Hyperpyrexia Others e.g High altitude ascending, Injudicious use of respirator, Some cases of hepatic coma Acid-base disturbances pCO2 > 45 mm Hg = Respiratory acidosis pCO2 < 35 mm Hg = Respiratory alkalosis HCO3 > 33 mmol/L = Metabolic alkalosis HCO3 < 22 mmol/L = Metabolic acidosis H+ > 45 nmol/L = Acidosis H+ < 35 nmol/L = Alkalosis pH (normal 7.4); pH 7.45 is alkalemia Anion Gap The “anion gap” is a mathematical approximation of the difference between the anions and cations routinely measured in serum. Routine electrolyte measurements include Na+, K+, Cl– and HCO3– The unmeasured anions constitute the anion gap. This is due to the presence of protein anions, sulphate, phosphate and organic acids The anion gap is calculated as the difference between (Na+ + K+) and (HCO3– + Cl–). Normally this is about 12 mmol/L. Assessment of Acid-Base Parameters Arterial blood is used to measure the acid-base parameters. Arterial blood gas (ABG) analyzer is used in assessing acid- base status and it measures pH, pCO2 and pO2 directly, by means of electrodes Bicarbonate is estimated by titration to pH 7.4. From the values of Na+, K+, Cl– and HCO3–, the anion gap is calculated. In the absence of a blood gas analyzer, venous blood may be collected under paraffin (to eliminate contact with air). Arterial Oxygen Saturation (SaO2) is measured by pulse oximeter  Normal serum electrolyte and arterial blood gas values pH = 7.35 – 7.45 Bicarbonate = 22–26 mmol/L Chloride = 96–106 mmol/L Potassium = 3.5–5 mmol/L Sodium = 136–145 mmol/L PO2 = 95 (85–100) mm Hg PCO2 = 40 (35–45) mm Hg  ROLE OF RESPIRATION IN ACID-BASE REGULATION An increase in blood pCO2 and of only 1.5 mmHg (0.2 per cent increase in CO2) results in 100 per cent increase in pulmonary ventilation, which increases also with slight increases in H+ ion concentration of the blood (acidosis). The excess CO2 is thereby promptly removed from the ECF in the expired air ↓ A decrease in blood pCO2 or H+ ion concentration(alkalosis), causes depression of respiratory centre, with consequent slow and hypoventilation resulting to retention of CO2 in the blood until the normal pCO2 and pH are restored.  This respiratory mechanism, therefore, tends to maintain the normal B-H CO3/H2CO3 ratio in the EC fluids  RENAL MECHANISMS FOR REGULATION OF ACID-BASE BALANCE(1) Normal urine has a pH around 6; this pH is lower than that of extracellular fluid (pH = 7.4). This is called acidification of urine. non-volatile acids viz. Lactic acid, H2SO4, ketone bodies, etc are buffered with cations (principally Na+) are removed by glomerular filtration. The pH of the urine may vary from as low as 4.5 to as high as 9.8, depending on the amount of acid excreted.  Na+ is recovered in the renal tubules by reabsorption in exchange of H+ ions which are secreted. It is recovered as NaHCO3 (“alkali reserve”). Kidneys use three mechanisms to achieve acid base balance viz; A. Bicarbonate mechanism B. Phosphate mechanism C. Ammonia mechanism  RENAL MECHANISMS FOR REGULATION OF ACID-BASE BALANCE(2) Bicarbonate Mechanism Excretion of H+; Generation of Bicarbonate Occurs in the proximal convoluted tubules The CO2 combines with water to form carbonic acid, with the help of carbonic anhydrase The H2CO3 then ionizes to H+ and bicarbonate. The hydrogen ions are secreted into the tubular lumen; in exchange for Na+ reabsorbed. These Na+ ions along with HCO3- will be reabsorbed into the blood. Excretion of hydrogen ions in the proximal tubules; CA = Carbonic anhydrase Reabsorption of bicarbonate from the tubular fluid; CA = Carbonic anhydrase  Above mechanism provides: For complete reabsorption of all of NaHCO3, Reduction of H+ ion load of plasma with little change in pH of urine Phosphate Mechanisms The pH of the urine is determined by the ratio both disodium hydrogen phosphate (Na HPO , alkaline PO4) and monosodium dihydrogen phosphate 2 4 (NaH PO ) 2 4  In plasma, concentration of Na HPO exceeds that of NaH2PO4 and the ratio 2 4 is maintained to 4:1. But in urine, the concentration of NaH PO exceeds that of Na HPO and the 2 4 2 4 ratio becomes 9:1. Due to the Na+ to H+ exchange occurring at the renal tubular cell boarder, the Na2HPO4 (basic phosphate) is converted to NaH2PO4 (acid phosphate) The acid and basic phosphate pair is considered as the urinary buffer. The maximum limit of acidification of urine is pH 4.5. Phosphate mechanisms operates in “distal tubule” and can be inhibited by carbonic anhydrase inhibitors like acetazolamide Phosphate Mechanisms C. Ammonia Mechanism This predominantly occurs at the distal convoluted tubules H+ is excreted and HCO3– is reabsorbed The Glutaminase present in the tubular cells hydrolyze glutamine to ammonia and glutamic acid. The NH3 (ammonia) diffuses into the luminal fluid and combines with H+ to form NH4+(ammonium ion). The glutaminase activity is increased in acidosis.  large quantity of H+ ions are excreted as NH4+ in acidosis Ammonia Mechanism