Respiratory_Acid-Base_Balance.pdf

Respiratory Acid-Base Balance Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Respiratory Acid-Base Balance 1 Learning Outcomes • • • • • • • • Describe how PCO2 affects blood pH Calculate blood pH from given values D...

Respiratory Acid-Base Balance Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Respiratory Acid-Base Balance 1 Learning Outcomes • • • • • • • • Describe how PCO2 affects blood pH Calculate blood pH from given values Draw a Davenport diagram to indicate how pH and [HCO3-] alter with changes to PCO2 and changes to non-volatile acid or base List the primary causes of acid-base disturbances Describe, with the use of a Davenport diagram, respiratory acidosis and its compensation Describe, with the use of a Davenport diagram, respiratory alkalosis and its compensation Describe, with the use of a Davenport diagram, metabolic acidosis and its compensation Describe, with the use of a Davenport diagram, metabolic alkalosis and its compensation pH and Buffers • An acid is defined as any chemical substance that can donate a proton, H+ • A base (alkali) is defined as any chemical substance that can accept a proton, H+ • Because H+ concentration can vary over a large range in solutions, the pH scale was created pH = -log10 [H+] So a [H+] of 10-7M = pH 7.0 3 Calculation of Plasma pH • Defined by Henderson-Hasselbalch equation, so pH = pKa + log [HCO3-] [CO2] where, bicarbonate is in mmol/L (mM) and [CO2] is calculated as PCO2 x solubility constant 4 pKa (Dissociation Constant) • pKa is defined as the pH at which 50% is ionised and 50% is unionised in the reaction • For bicarbonate this would be: H2CO3 50% ↔ HCO3- + H+ 50% 5 How This Reaction Shifts H2CO3 ↔ HCO3- + H+ If H+ rises, the equation is driven to the left If H+ falls, the equation is driven to the right 6 Plasma pH • The pKa for carbonic acid/bicarbonate is 6.1 • Normal pH is 7.4 • At pH = 7.4 is there more H2CO3 or more HCO3- ? 7 The reaction we are considering is below: H2CO3 ↔ HCO3- + H+ pKa is defined as the pH at which 50% of your components are ionised (in this case HCO3- and H+) and 50% is unionised (in this case carbonic acid - H2CO3) in the reaction. So a pKa of 6.1 means that at a pH of 6.1 50% is ionised and 50% is unionised. I used the figure below to illustrate this during the lecture. This figure is for acetic acid (whose pKa value is 4.8 rather than 6.1 as for HCO3-) but the principle is the same. As the pH of the solution becomes more basic i.e. moves from 4.8 to 6.8 the acetic acid dissociates to produce acetate and a H+. As the pH of the solution becomes more acidic i.e. moves form 4.8 to 2.8 the acetic acid remains as acetic acid and does not dissociate. As the pH of blood is 7.4, which is higher (i.e. more basic) than the pKa of the bicarbonate reaction (at 6.1), the hydrogen ion concentration is reduced and this shifts the reaction to the right. So there will be more dissociated ions i.e. more bicarbonate. This is because more carbonic acid would dissociated to try to balance the increased bicarbonate (basic) by increasing H+. If the pH of blood was 5.0, which is lower (i.e. more acidic) than the pKa of the bicarbonate reaction, the hydrogen ion concentration would be increased and this shifts the reaction to the left. So there would be less dissociated ions i.e. more carbonic acid. This is because less carbonic acid would dissociated and the increased H+ concentration would combine with HCO3- to form carbonic acid. 8 The Effect of Respiratory System • The absolute levels of bicarbonate can be changed by changes to breathing H2O + CO2 → H2CO3 • Increased CO2 leads to more H2CO3 and vice versa 9 Acid-Base Disturbances Respiratory acid-base disturbances CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3Metabolic acid-base disturbances 10 Acid-Base Balance: Respiratory • pH < 7.35 acidosis • pH >7.45 alkalosis • A and B shows plasma pH change as CO2 changes • C and D shows plasma pH change when non-volatile acid is added/removed (static PCO2) D C 11 Causes of Acid-Base Disturbances – – – – Increased CO2 Decreased CO2 Increased non-volatile acid/decreased base Increased base/decreased non-volatile acid • • Where primary change is to the CO2 levels - respiratory disorders Where primary change is to bicarbonate levels - metabolic disorders • An acidosis can be caused by: – – • Rise in PCO2 Fall in HCO3- An alkalosis can be caused by: – – Fall in PCO2 Rise in HCO3- 12 Acid Base Disorders 13 Respiratory Acidosis • Results from an increase in PCO2 caused by: – – – • • Hypoventilation (less CO2 being blown off) Ventilation-perfusion mismatch Reduced lung diffusing capacity From Henderson-Hasselbalch equation, an increase in PCO2 causes an increase in H+, so a lowering of pH Thus, plasma HCO3- levels increase to compensate for increased H+ concentration • Renal compensation – increased HCO3- reabsorption and increased HCO3production – raises pH towards normal • Causes – – – – – COPD Blocked airway – foreign body or tumour Lung collapse Injury to chest wall Drugs reducing respiratory drive, eg morphine, barbiturates, general anaesthetics 14 Davenport Diagram is a Graphical Tool to Interpret Acid-Base Issues 15 Respiratory Alkalosis • Results from a decrease in PCO2 generally caused by – alveolar hyperventilation (more CO2 being blown off) • This causes a decrease in H+ concentration and thus a rise in pH • Renal compensation – reduced HCO3- reabsorption, and reduced HCO3- production – Thus plasma HCO3- levels fall, compensating for lower H+, moving pH back towards normal • Causes – – Increased ventilation, from hypoxic drive in pneumonia, diffuse interstitial lung diseases, high altitude, mechanical ventilation Hyperventilation – brainstem damage, infection driving fever 16 Davenport Diagram is a Graphical Tool to Interpret Acid-Base Issues 17 Metabolic Acidosis • Results from an excess of H+ in the body, • • This reduces HCO3 levels (shifts equation to the left) Addition of acid decreases pH, ventilation unaffected so PCO2 initially normal • Respiratory compensation – – – – • the lower pH is detected by peripheral chemoreceptors, causes an increase in ventilation which lowers PCO2 the bicarbonate equation is driven further to the left, lowering H+ and HCO3- concentration further The decrease in H+ concentration moves pH towards normal Respiratory compensation cannot fully correct the pH, HCO3 and H+, so excess H+ needs to be removed or HCO3- restored (by slow renal comp) Causes – – – – Loss of HCO3-, eg from gut in diarrhoea exogenous acid overloading (aspirin overdose) endogenous acid production (ketogenesis) Failure to secrete H+, eg in renal failure 18 Davenport Diagram is a Graphical Tool to Interpret Acid-Base Issues 19 Metabolic Alkalosis • Results from an increase in HCO3- concentration or a fall in H+ • • Removing H+ from equation drives reaction to right, increases HCO3Lowering of H+ raises pH, with PCO2 initially normal • Respiratory compensation – – – – – • increase in pH detected by peripheral chemoreceptors – decreases ventilation which raises PCO2 the equation is driven further to right, increasing H+ and HCO3Increase in H+ moves pH towards normal Respiratory compensation is often small (or even absent) – ventilation cannot reduce enough to correct imbalance Renal response is to secrete less H+ Causes – – – Vomiting - loss of HCl from stomach Ingestion of alkali substances Potassium depletion (eg diuretics) 20 Davenport Diagram is a Graphical Tool to Interpret Acid-Base Issues 21 The Acid-Base Nomogram • ABGs can be analysed using the acid–base nomogram • By plotting the PaCO2 and H+/pH values on the ABG nomogram, most ABGs can be analysed • If the plotted point lies outside the designated areas, this implies a mixed disturbance 22 Summary • Have looked at how to calculate pH of blood • Have discussed the Davenport diagram to indicate how pH and [HCO3-] alter with changes to PCO2 and changes to non-volatile acid or base • Have looked at the primary causes of acid-base disturbances • Have discussed in detail the various acid-base disturbances and their compensation 23 References • Boron, WF & Boulpaep, EL (2017) Medical Physiology (3rd Edition) – Chapter 28 Acid-Base Physiology p628-646 • Guyton & Hall (2016) Textbook of Medical Physiology (13th Edition) – • Hennessey, IAM (2016) Arterial Blood Gases Made Easy (2nd Edition) – • Chapter 31 Acid-Base Regulation p409-426 Chapter 1.4 Acid–Base Balance: The Basics p26-35 Preston RR & Wilson TE (2013) Lippincott’s Illustrated Reviews: Physiology (1st Edition) – Chapter 23 Gas Exchange p280-297 • Naish, J & Syndercombe Court, D. (2019). 3rd Edition. Medical Sciences – Chapter 13 The Respiratory System p603-642