Acid-Base disturbances Physiological approach

Pieter Roel Tuinman, M.D., PhD, intensivist Department of Intensive Care, VU Medical Center, Amsterdam, The Netherlands [email protected] Content

• Introduction

• Regulation of acid-base balance

• Diagnosis of acid-base disturbances

• Examples Acid-Base balance

• definition: Bronsted-Lowry (1923)

• Homeostasis

• Physiologic effects of pH on protein function

• normal A:B ratio  1:20

– strength is defined in terms of the tendency to donate (or accept) the hydrogen ion to (from) the solvent (i.e. water in biological systems)

Relation pH and H+

pH H+ nanomol/L

7,80 16

7,60 26

7,40 40

7,20 63

7,00 100 Henderson-Hasselbalch equation

+ - 0.03 PCO2 H + HCO3 + • H = 800 x ------K d = ————— - CO HCO3 2 disolved

- HCO3 Metabolic by kidneys • pH = 6.1 + log ------

CO2 disolved Respiratory by lungs pH pH is and indirect measure of [H+] CAVE! Hydrogen ions (i.e. protons) do not exist free in solution but are linked to adjacent water molecules by + hydrogen bonds (H3O )  [H+] by a factor of 2 causes a  pH of 0.3

normal plasma pH  pH 7.4 (7.36-7.44)  normal  Acidosis <7.35 pH 7.45> alkalosis  Range compatible with life 6.80-7.80 (H+ 160-16 nM)

Acid-base disturbances Why of interest?

• Frequently encountered • Are (first) sign of illness • Can be used to diagnose the disease • Require early treatment Examples of diseases resulting in acid-base disturbance

• CZS: CVA, bleeding, trauma • Circulation: hypotension, myocardial infarction • Respiratory: COPD, asthma. • Renal: acute / chronic kidney injury • Tr dig: vomiting, chronic diarrhea. • Liver: acute / chronic liverfailure H+-regulation

• Chemical buffering

• Control of PCO₂

- • Control of plasma HCO3 Regulation of acid-base balance How ?

• Dilution (distribution)

• Chemical buffering (intra – and extracellular)

• Regulation of CO2 concentration (respiratory)

+ - • Regulation of H and HCO3 concentration (metabolic)

Acid excretion Lungs • 20 – 50 mol volatile acid/day – (2 – 4 liter concentrated HCL)

Kidneys • 80 mmol/l non-volatile, sulfate, phosphate, urineacid, citrate, ammoniumsalts.

 x 1000 times more acid trough lungs than kidneys Respiratory system - CO2 + differences in the stimulation of respiration by pCO2, H and pO2 alveolar ventilation disturbances  acidemia  respiratory centre of the brain  alveolar ventilation

 CO2  alkalemia  respiratory centre of the brain   alveolar ventilation

  CO2 Respiratory regulation Influence of pH on breathing

Daily CO2 production : 15.000 mmol/day

H+  chemoreceptors medulla oblongata

• pH ↑  alveolar ventilation /Minute volume  • pH   alveolar ventilation /Minute volume↑ Renal regulation

- • Serum pH ↑ pH↑ = netto HCO3 excretion

• Serum pH  Urine pH = netto H+ excretion

Regulation kidney in summary serum pH↑ - HCO3 resorption  H+ secretion  = Netto base loss Urine buffers  serum pH  - HCO3 resorption ↑

H+ secretion↑ = Netto acid loss

Urine buffers ↑  Quantative rules (see Berend et al. NEJM)

• Compensation of acid-base disturbance is bound by quantative rules • Are this rules disregarded, than there is a mixed-acid-base disturbance • Over - or undercompensation does not exist

- HCO3 ( nier ) Rules in general pH =pK + log ------CO2 ( long )

- • Definition acid-base distubance pH, PCO2 en HCO3

• Compensation is usually not complete pH < 7.35 acidosis pH > 7.45 alkalosis

• Inadequate compensation Mixed disturbance

- • Direction compensation the same HCO3 / CO2 ratio. Assessment of A-B balance

Arterial blood Mixed venous blood

range range

pH 7.40 7.35-7.45 pH 7.33-7.43

pCO 40 mmHg 35 – 45 pCO2 41 – 51

pO2 95 mmHg 80 – 95 pO2 35 – 49

Saturation 95 % 80 – 95 Saturation 70 – 75

BE 2 BE

- - HCO3 24 mEq/l 22 - 26 HCO3 24 - 28 Disorders of A-B balance  Acidosis: abnormal condition lowering arterial pH  Alkalosis: abnormal condition raising arterial pH

 Homeostatic response predictable  Simple A-B disorders: there is a single primary aetiological acid-base disorder  Mixed A-B disorders: more primary aetiological disorders are present simultaneously

Causes Respiratory  abnormal processes which tend to alter pH because of a

primary change in pCO2 levels acidosis alkalosis Metabolic  abnormal processes which tend to alter pH because of a - primary change in [HCO3 ] acidosis alkalosis Stepwise approach

1. History 2. Look at the pH 3. Look at PCO2 and HCO3- 4. In : what is ? 5. With high AG: delta-ratio? 6. Normal AG: calculate urine AG 7. Is compensation adequate? 8. In respiratory process: acute or chronic?

Metabolic acidosis (MA)

- • primary disorder is a pH due to HCO3 : –  fixed [H+] = high anion gap - – loss or  reabsorption of HCO3 = normal anion gap

• Anion Gap

Use and limitations of Anion Gap

• [Na+]- [Cl⁻]-[HCO³⁻] • Calculate the excess of unmeasured anions • Range 8-12 mM/L  Correction for albumin (alb ↓1 g/L->↑ 2.5 AG)

High Anion Gap Acidosis

Berend K, et al. NEJM 2014 (oct): 371:15 Normal Anion Gap Acidosis

Berend K, et al. NEJM 2014 (oct): 371:15 Primary acid-base disturbances Disturbance Compensation Classification

- pH  HCO3  PCO2  metabolic acidosis with

- PCO2 ↑  HCO3 ↑ with metabolic compensation

- pH ↑ HCO3 ↑ PCO2 ↑ with respiratory compensation

- PCO2  HCO3  respiratory alkalosis with metabolic compensation

Diagnosis mixed acid-base disturbances

There is a discrepancy between real and expected compensation

• compensation CO2 ↑↑ : extra acidosis

• CO2  : extra alkalosis

- • compensation HCO3 ↑↑ : extra alkalosis

- HCO3  : extra acidosis Berend K, et al. NEJM 2014 (oct): 371:15 Case 1

44 yr man dehydrated with sever diarrhea. pH 7.31/33/bic 16/93 Na 134/K 2.9/Cl 108/Cr 150/Ur 25 What is the acid base disorder? Answer

1.Based on history: normal AG because of diarrhea or elevated AG because of due to hypovolemia 2.Look at pH 3.Look at the process (HCO3 and PCO2) 4.Calculate the AG: =10 5.Compensation adequate PCO2= 1.5 x bic +8 (+/-2)= 30-34 C/ Normal AG acidosis with adequate compensation, most likely due to diarrhea

Case 2

22 yr female with DM1, N/V+, polyuria, abnormal breathing pH 7.27/23/bic 10 Na 132/K 6/Cl 93/gluc 36/Cr 200 What is acid-base disorder? Answer

1.History: elevated AG because of DKA or lactic acidosis secondary to hypovolemia due to vomiting and polyuria; metabolic alkalosis due to vomiting 2.Look at the pH 3.What is the primary process (bic/pCO2)? 4.Calculate AG=28 5.Is compensation adequate? = 1.5 ×11 + 8 ± 2 = 22.5 - 26.5. C/ High AG metabolic acidosis due to diabetic ketoacidosis Case 3

70 yr man, with history of CHF, increased dyspnoe and leg swelling pH 7.24/60/bic 27/ 52 What is acid-base disorder? Answer

1.History acute respiratory acidosis due to acute pulmonary edema 2.Look at pH 3.What is process? (PCO2/bic)? 4.Acute/chronic? 60-40=20/10=2 +24=26 (is almost bic 27) so acute respiratory acidosis C/ Acute respiratory acidosis secondary to pulmonary edema

Questions?

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