Acid-Base Disorders - Introduction and Physiology (PDF)

Acid - Base Disorders Introduction and physiology Dr Shaida Khan Pathologist Department of Chemical Pathology University of the Witwatersrand Chris Hani Baragwanath Hospital shaida.khan @nhls.a.c.za  Objectives 1. The role of buffers, the...

Acid - Base Disorders Introduction and physiology Dr Shaida Khan Pathologist Department of Chemical Pathology University of the Witwatersrand Chris Hani Baragwanath Hospital shaida.khan @nhls.a.c.za  Objectives 1. The role of buffers, the renal and respiratory systems in acid base balance 2. Henderson-Hasselbach equation 3. Assessing acid base balance: An approach and laboratory parameters (blood gas analysis, bicarbonate concentrations, anion gap) 4. Acid base disorders  Terminology Acid Substance that donates H+ ions Base Substance that accepts H+ ions Acidosis Excess acid Alkalosis Excess base Acidaemia pH < 7.35 Alkalaemia pH > 7,45 Buffer Mixture of a weak acid and its conjugate base which lessens a change in [H+] when a strong acid/base is added.  Definitions Acid is a substance that donates protons [H+] Base is a substance that accepts protons [H+] Base HCl + NH3 ⇌ NH4+ + Cl- Acid  The concept of pH [H+] in the blood is 35 – 45 nmol/L nmol/L to mol 10-9 = 40 x 10-9 = 0.000000040 mol Neutral pH = 7, 10-7 pH = - log [H+] Acidic Basic = - log (40) 0 14 = 7,4 Physiological pH = 7,35 – 7,45 [H+] 40 to 80 pH decreases by 0.3  The importance of physiological [H+] Enzymes 1. Intracellular environment Metabolic intermediates Acidosis – hyperkalaemia, 2. Electrolyte balance ionized hypercalcaemia Alkalosis - hypokalaemia 3. Cardiac contractility Acidosis – decreased CC Alkalosis – decreased O2 delivery because of Hb 4. Oxygen delivery affinity to oxygen increased 5. Fatal  Sources of [H+] Metabolic processes Aerobic metabolism Triglyceride breakdown Ketoacids CO2 ≈ H2CO3 Metabolism of phosphoric, sulphuric proteins and amino acids Anaerobic metabolism Lactic acid Phosphoric, sulphuric, hydrochloric acids Net 50 – 100 mmol H+  Maintaining [H+] Buffers Respiratory system Kidneys Seconds Minutes Hours to days  Buffers Buffer is a mixture of a weak acid and its conjugate base which lessens a change in [H+] when a strong acid/base is added Bicarbonate buffer ECF Phosphate buffer ICF and Urine Haemoglobin buffer ECF Other protein buffers ICF Bone buffer Chronic acidosis  Bicarbonate buffer H2CO3 ⇌ H+ + HCO3- Weak Acid Conjugate base Volatile acid  Bicarbonate buffer CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3- pKa = 6.1 Carbonic anhydrase pH = 7.4 Hyperventilation Hypoventilation Reclaim/ regenerate HCO3- Decrease CO2 Increase CO2 and excrete H+ Henderson Hessalbach Equation A-, Anion (mmol/L) − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 pKa Solubility coefficient HA, Weak acid (mmHg) Henderson Hessalbach Equation 24 7.4 = 6.1 + 𝑙𝑜𝑔 1.2 − 𝐻𝐶𝑂3 24 𝑅𝑎𝑡𝑖𝑜 = = 20: 1 𝑃𝑎𝐶𝑂2 1.2 The more stable this ratio, the more stable the pH  Phosphate buffer H2PO4- ⇌ H+ + HPO42- Weak acid Conjugate base Intracellular pKa = 6.8 Urine  Protein buffers Haemoglobin buffer Other protein buffers H2O + CO2 CO2 H+ + Protein ⇌ H.Protein HHb H2CO3 Hb- H+ + HCO3- HCO3- Cl- Cl- RBC Plasma Tissues Bone buffer HCO3- in bone water Exchange of protons on bone surface Carbonate and phosphate proton buffers released Reduced bone formation, increased bone resorption  Respiratory regulation pH of CSF CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3- Crosses BBB ↓pH ↑pH Medulla Central chemoreceptors Central chemoreceptors Brainstem Central chemoreceptors Increase ventilation Decrease ventilation ↓ CO2 ↑ CO2  Respiratory regulation PCO2, pH and PO2 ↑PaCO2, ↓pH, ↓PaO2 Peripheral chemoreceptors Peripheral chemoreceptors Increase ventilation  Renal regulation Metabolic component: HCO3- and H+ HCO3- Reabsorption, regeneration H+ Excretion ↑H+ ↓pH ↓H+ ↑pH ↑HCO3 ↑Reabsorption, regeneration ↓HCO3 ↓Reabsorption, regeneration ↓H+ ↑Excretion ↑H+ ↓Excretion  Bicarbonate reabsorption HCO3- reabsorption/ reclamation/ conservation 6% 80% 10% 4%  Bicarbonate reabsorption Filtered HCO3- Filtered Na+ Na+ ATP K+ Na+ Na+ HCO3- + H+ H+ + HCO3- HCO3- Na+ H2CO3 H2CO3 HCO3- CA CA Cl- Net HCO3- reabsorption H2O + CO2 CO2 + H2O No net H+ excretion Proximal renal Blood Tubular lumen tubular cell  Bicarbonate regeneration Linked to H+ excretion Titratable acidity Filtered HPO42- H+ K+ K+ ATP HPO42- + H+ H+ + HCO3- HCO3- ATP Cl- H2CO3 H2PO4 Titratable acid CA Excreted in urine H2O New HCO3- absorbed CO2 + Net acid excretion Tubular lumen Intercalated cell Blood  Bicarbonate regeneration Ammoniagenesis Na+ Na+ ATP K+ H+ + HCO3- HCO3- Cl- NH3+ NH3+ H+ α ketoglutarate NH4 Glutamate NH4 NH4 formed Reabsorbed in TAL Glutamine New HCO3- Tubular lumen Proximal tubular cell Blood  Bicarbonate regeneration Ammoniagenesis NH3 from medullary interstitium K+ K+ ATP NH3 + H+ H+ + HCO3- HCO3- ATP Cl- H2CO3 NH4 CA Excreted in urine CO2 + H2O Net H+ excreted as NH4 New HCO3- Tubular lumen Intercalated cell Blood  Approach Traditional approach Stewart’s approach Henderson-Hasselbach equation Physiochemical approach − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 PaCO2 ATOT Independent SID variables HCO3- Independent CO2 variables  Approach − 𝐻𝐶𝑂3 Acid base status 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Acidosis Alkalosis Respiratory Metabolic Interpreting pH, HCO3, PCO2 Primary disorder − Metabolic 𝐻𝐶𝑂3 Or 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Respiratory 7.45, Alkalaemia Metabolic or Respiratory Alkalosis  Interpreting pH, HCO3, PCO2 Compensation − Metabolic compensation 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Primary: Respiratory acidosis 7.45, Alkalaemia Metabolic alkalosis with respiratory compensation  Interpreting pH, HCO3, PCO2 Compensation Complete = pH is normal, HCO3- and CO2 abnormal Partial = pH is abnormal, HCO3- and CO2 abnormal  Interpreting pH, HCO3, PCO2 Correction Compensation: Response by non-primary system to bring pH back within range Correction: Response by the body to bring all parameters within range  Laboratory parameters Blood gas U&E Laboratory parameters Blood gas 1. Arterial/Capillary blood Electrodes 2. Anticoagulated 3. Sealed syringe 4. On ice 5. Minimal delays Actual bicarbonate using H-H equation: pH and PaCO2 Standard bicarbonate is better – Corrected for abnormal PaCO2 Standard base excess – Corrected for CO2, temperature, effect of Hb as a buffer Laboratory parameters U&E 1. Serum sample 2. Minimize significant delays Measured TCO2 Calculated using 4 parameters: Na+, K+, CL-, HCO3-  Laboratory parameters Overview − 𝐻𝐶𝑂3 Arterial blood gas 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 - Calculated base excess Arterial blood gas 0.03 𝑥 𝑃𝑎𝐶𝑂2 - Calculated standard - Measured pH bicarbonate U&E/C - Measured HCO3- (TCO2) Arterial blood gas - Measured PaCO2  Acid Base Disorders pH < 7.35 > 7.45 Acidosis Alkalosis Respiratory Metabolic Respiratory Metabolic  Respiratory acid base disorders Respiratory acidosis - Causes Inadequate mechanical ventilation CNS depression Hypoventilation Airway obstruction CO2 Lung defects Increased CO2 intake Nerve, muscle, chest wall disorders  Respiratory acid base disorders Respiratory acidosis – Primary disorder − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 Hypoventilation 0.03 𝑥 𝑃𝑎𝐶𝑂2 CO2 CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-  Respiratory acid base disorders Respiratory acidosis – Compensation Metabolic Compensation Hypoventilation − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 CO2  Respiratory acid base disorders Respiratory acidosis – Compensation Ventilation Acute CO2 ECF/ Tissues Hypoventilation CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3- CO2 Buffering of H+ by Hb and proteins Small HCO3- H+ excretion H+ HCO3- Greater HCO3- reabsorption/ Chronic CO2 regeneration  Respiratory acid base disorders Respiratory alkalosis – Causes Excessive mechanical ventilation CNS Hyperventilation Hypoxaemia CO2 Lung defects  Respiratory acid base disorders Respiratory alkalosis – Primary disorder − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 Hyperventilation 0.03 𝑥 𝑃𝑎𝐶𝑂2 CO2 CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-  Respiratory acid base disorders Respiratory alkalosis – Compensation Metabolic Compensation Hyperventilation − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 CO2 0.03 𝑥 𝑃𝑎𝐶𝑂2  Respiratory acid base disorders Respiratory alkalosis – Compensation Equilibrium shifts Intracellular buffering Hyperventilation Acute CO2 Small HCO3- CO2 Chronic CO2 H+ H+ excretion HCO3- Greater HCO3- reabsorption/ regeneration  Metabolic acid base disorders Metabolic acidosis - Causes Gain of [H+] Anion gap [HCO3-] HAGMA NAGMA Loss of [HCO3-] Ketoacids GIT losses of Lactic acids HCO3- Renal failure Renal losses of Toxins HCO3-  Metabolic acid base disorders Metabolic acidosis – Anion gap Anion gap (Na+ + K+) – (Cl- + HCO3-) 9-16 mmol/L Cations Anions Unmeasured anions  Metabolic acid base disorders Metabolic acidosis – Anion gap High anion gap (Na+ + K+) – (Cl- + HCO3-) Cations Anions Cations Anions K+ AG K+ AG Ketoacids, lactic acids HCO3- HCO3- Buffering H+ Na+ Na+ CL- CL-  Metabolic acid base disorders Metabolic acidosis – Anion gap Normal anion gap (Na+ + K+) – (Cl- + HCO3-) Cations Anions Cations Anions K+ AG K+ AG HCO3- HCO3- Loss Na+ Na+ Reabsorbed CL- CL-  Metabolic acid base disorders Metabolic acidosis – Primary disorder [HCO3-] − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2  Metabolic acid base disorders Metabolic acidosis – Compensation − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Compensation [HCO3-] CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3- Compensation Blow off CO2 Metabolic acid base disorders Metabolic acidosis – Compensation − 𝐻𝐶𝑂3 Primary 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Compensation HCO3 reabsorption/ regeneration H+ excretion  Metabolic acid base disorders Metabolic alkalosis – Causes Maintenance Cause [HCO3-] Chloride responsive Chloride unresponsive Loss of [H+] Gain of [HCO3-] Loss of gastric Mineralocorticoid acid excess syndrome Bicarb infusion Diuretics Potassium loss Citrate in Cystic fibrosis (diuretics) transfused blood Low chloride HCO3- HCO3- reabsorbed reabsorption and to maintain regeneration electroneutrality enhanced  Metabolic acid base disorders Metabolic alkalosis – Primary disorder [HCO3-] − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2  Metabolic acid base disorders Metabolic alkalosis – Compensation − 𝐻𝐶𝑂3 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Compensation [HCO3-] CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3- Compensation Retain CO2 Metabolic acid base disorders Metabolic alkalosis – Compensation − 𝐻𝐶𝑂3 Primary 𝑝𝐻 = 6.1 + 𝑙𝑜𝑔 0.03 𝑥 𝑃𝑎𝐶𝑂2 Compensation HCO3 reabsorption/ regeneration H+ excretion