1. H+ Homeostasis

2. H+ homeostasis Why is it so important? Why is it so important? Organ functionOrgan function Cellular functionCellular function Enzyme and protein functionEnzyme and protein function

3. Acid production Respiratory acid Respiratory acid CO2 as carbonic acid Metabolic acids Metabolic acids Organic acids Lactate Pyruvate Keto-acids Lungs Lungs Kidneys Kidneys

4. Traditional pH control Respiratory control of CO2 Respiratory control of CO2 Ventilation rate and depthVentilation rate and depth Rapid and very sensitiveRapid and very sensitive Kidney control of H+ and HCO3- (maybe..) Kidney control of H+ and HCO3- (maybe..) NH4+NH4+ PhosphatesPhosphates Organic acidsOrganic acids Slower and less efficientSlower and less efficient

6. Henderson equation: [ H+ ] x [ HCO3- ] = k x [ CO2 ] x [ H2O ]

7. The trouble with Henderson.. [H+] ≈ CO2/HCO3- [H+] ≈ CO2/HCO3- But if CO 2 rises so will HCO3- But if CO 2 rises so will HCO3- Danish polio epidemic Danish polio epidemic So how can you distinguish between respiratory and metabolic problems? So how can you distinguish between respiratory and metabolic problems? Standard bicarbonate (1957)Standard bicarbonate (1957) BE or SBE (1958)BE or SBE (1958) Boston rulesBoston rules

8. History

9. bicarbonate at normal temp. and PCO2 terminology

12. An alternative explanation.. All H+ comes from the dissociation of water All H+ comes from the dissociation of water Anything that controls or effects water dissociation controls pH Anything that controls or effects water dissociation controls pH

13. The Six Simultaneous Equations used by Stewart 1. Water Dissociation Equilibrium [H+] x [OH-] = K’w 2. Electrical Neutrality Equation [SID] + [H+] = [HCO3-] + [A-] + [CO3-2] + [OH-] 3. Weak Acid Dissociation Equilibrium [H+] x [A-] = KA x [HA] 4. Conservation of Mass for "A“ [ATot] = [HA] + [A-] 5. Bicarbonate Ion Formation Equilibrium [H+] x [HCO3] = KC x pCO2 6. Carbonate Ion Formation Equilibrium [H+] x [CO3-2] = K3 x [HCO3-]

14. 3 factors independently control water dissociation or [H+] 1. CO2 (pCO2) 2. Strong ion difference (SID) 3. Total weak acid concentration (AH) Neither pH nor HCO3- can be regulated directly. Their concentrations are determined by other independent variables. The ratio of CO2/HCO3- describes pH but does not determine it…Henderson is only 1/6 th of the story!

16. Strong Ion Difference (SID) SIDa is always positive SIDa is always positive Should equal sum of HCO3 and A- (SIDe) Should equal sum of HCO3 and A- (SIDe) SIG = unmeasured anions and should be zero SIG = unmeasured anions and should be zero Unmeasured anions are Unmeasured anions are Ketoacids,organic acids Exogenous acids Gelatins, citrate

17. Where does Anion gap fit in? Anion gap = (Na + K) – (Cl + HCO3) Anion gap = (Na + K) – (Cl + HCO3) Clever AG = AG – [0.25 x albumin] – lactate Clever AG = AG – [0.25 x albumin] – lactate Easier than SIG and well correlated Easier than SIG and well correlated Note that a low albumin will augment an anion gap Note that a low albumin will augment an anion gap

18. If SID falls, pH falls. If SID falls, pH falls. SIG is a clever Anion gap (corrects for albumin, phosphate, lactate, Mg and Ca)

20. Total concentration of weak acids (Atot) 3. Weak Acid Dissociation Equilibrium [H+] x [A-] = KA x [HA] 4. Conservation of Mass for "A“ [ATot] = [HA] + [A-] Low albumin is alkalinizing…Low albumin is alkalinizing… Less HA means less H+Less HA means less H+ Low albumin may mask an acidosisLow albumin may mask an acidosis

21. Stewart’s bottom line(s).. It is not the direct control of HCO3- and H+ that determines pH. It is not the direct control of HCO3- and H+ that determines pH. It is the direct effect of CO2, SID and ATot that regulates the dissociation of water. It is the direct effect of CO2, SID and ATot that regulates the dissociation of water. CO2 is controlled by ventilation (lungs)CO2 is controlled by ventilation (lungs) SID is controlled by strong ion handling esp. Chloride/sodium (kidneys)SID is controlled by strong ion handling esp. Chloride/sodium (kidneys) ATot is chiefly determined by albumin and phosphate concentration (kidneys and liver)ATot is chiefly determined by albumin and phosphate concentration (kidneys and liver) It is the degree of water dissociation that determines pH It is the degree of water dissociation that determines pH

24. Back to the traditional.. …..With some unification

25. Blood gas analysis 1. Assess Oxygenation Is the patient hypoxicIs the patient hypoxic Is there a significant A-a GradientIs there a significant A-a Gradient 2. What is the pH pH>7.45 (H + 7.45 (H + < 35) alkalosis pH 45) acidosispH 45) acidosis 3. Is it a ventilation problem? PaCO 2 :>6.0 kPa - respiratory acidosisPaCO 2 :>6.0 kPa - respiratory acidosis PaCO2: <4.7kPa - respiratory alkalosisPaCO2: <4.7kPa - respiratory alkalosis Both methods agree Both methods agree

26. 4. Is there a metabolic problem? What is the HCO3- or SBE? (..or SID) SBE -2=metabolic acidosis SBE +2=metabolic acidosis 5. Is it both? 6. Investigate Metabolic acidosis (hunt the kipper)

27. Gem 3000 Measured variables Ph Ph pCO2 pCO2 P02 P02 Na Na K Ca total Ca total Glucose Glucose Lactate Lactate Hct Hct Derived variables Ca ionised Ca ionised HCO3- HCO3- BE/SBE BE/SBE O2 %Sats O2 %Sats Hb Hb

28. Respiratory Acidosis Any cause of hypoventilation (high CO2) CNS depressionCNS depression Neuromuscular diseaseNeuromuscular disease Acute or chronic lung diseaseAcute or chronic lung disease Cardiac arrestCardiac arrest Ventilator malfunctionVentilator malfunction

29. Respiratory Alkalosis Any cause of hyperventilation (low CO2) HypoxiaHypoxia Acute lung conditionsAcute lung conditions AnxietyAnxiety FeverFever PregnancyPregnancy Hepatic failureHepatic failure Some central CNS lesionsSome central CNS lesions

30. Metabolic Acidosis (low SID) Increased anion gap or SIG (unmeasured anions) Endogenous acids Endogenous acids Renal failure..organic acidsRenal failure..organic acids Ketoacidosis/starvationKetoacidosis/starvation Lactic acidosisLactic acidosis Exogenous acids Exogenous acids Salicylate/Tricyclic/methanol overdoseSalicylate/Tricyclic/methanol overdose CitrateCitrate gelatinsgelatins

31. Metabolic Acidosis Decreased or normal anion gap or SIG Diarrhoea (loss Na>Cl)Diarrhoea (loss Na>Cl) Carbonic anhydrase inhibitorsCarbonic anhydrase inhibitors Ureteral diversionUreteral diversion Chloride administrationChloride administration Renal tubular acidosis ?Cl retentionRenal tubular acidosis ?Cl retention

32. Metabolic Alkalosis (increased SID or low albumin) Loss of acid or gaining alkali or loss Chloride gaining Na VomitingVomiting DiarrhoeaDiarrhoea Diuretics (and hypokalaemia generally)Diuretics (and hypokalaemia generally) Cushings/steroids/mineralocorticoidsCushings/steroids/mineralocorticoids Ingestion/administration of alkali or is it Na?Ingestion/administration of alkali or is it Na?

33. Reminder of normal values pH = 7.35 – 7.45[H + = 35 -45nmol/l] pH = 7.35 – 7.45[H + = 35 -45nmol/l] pO 2 = 10 -13 kPa on air pO 2 = 10 -13 kPa on air pCO 2 = 4.6 – 6.0 kPa pCO 2 = 4.6 – 6.0 kPa HCO 3 = 25 – 35 mmols/l HCO 3 = 25 – 35 mmols/l Base excess ± 2.0 Base excess ± 2.0 Lactate < 1.0 mmols/l Lactate < 1.0 mmols/l Chloride = 100 Chloride = 100 Albumin 35 Albumin 35 Anion gap 10-12 but less if albumin low Anion gap 10-12 but less if albumin low SIG = 0 SIG = 0

34. Bed 1 Middle aged man admitted with cough sputum and haemoptysis. Life-long smoker pO 2 4 on air H + 65 pH7.19 PaCO 2 9.7 HCO 3 28

35. Bed 2 Middle aged man admitted with cough sputum and haemoptysis. Life-long smoker pO 2 6 on airSpO2 92% H + 46 pH7.32 PaCO 2 10.0 HCO 3 39

36. Bed 9 50 yr-old man admitted with exacerbation of long-standing bronchial asthma. Respiratory rate of 18 pO 2 5.1 on 60% oxygen H + 41 pH7.39 PaCO 2 5.8 HCO 3 26

37. or corrected Anion Gap (AGc)

38. Bed 3 Young female admitted with overdose of unknown tablets and smelling of alcohol pO 2 12 kPa on air H + 58 pH7.24 PaCO 2 2.5 HCO 3 8

39. I need to know… SBE SBE Lactate Lactate Corrected Anion gap or Strong ion gap (chloride) Corrected Anion gap or Strong ion gap (chloride) SBE -12 SBE -12 Lactate 4 Lactate 4 Corrected Anion gap high (>12) Corrected Anion gap high (>12)

40. Bed 4 Elderly male admitted from nursing home with one week history of fever and vomiting pO 2 12 kPa on 4L/min by mask H + 32 pH7.49 PaCO 2 6.3 HCO 3 35 SBE +8 Lactate 3

41. Bed 5 Middle aged man post cardiac arrest. Breathing spontaneously on endotracheal tube pO 2 35 on 15l via resus bag (with reservoir) H + 126 pH6.9 PaCO 2 8.9 HCO 3 13 SBE -20 Lactate 12 Cl 111

42. Bed 6 Elderly lady with congestive cardiac failure pO 2 9 on 40% oxygen H + 23 pH7.64 PaCO 2 3.5 HCO 3 29 SBE +2

43. Bed 7 Young diabetic male admitted with chest infection, vomiting and drowsiness pO 2 12 on air H + 49 pH7.31 PaCO 2 1.6 HCO 3 6.0 SBE -18 Lactate 6 Cl 111

44. Bed 8 54 yr-old lady post MI. Acutely unwell, cold, clammy, hypotensive and oliguric pO 2 10 on 60% oxygen H + 102 pH6.99 PaCO 2 7.8 HCO 3 14 SBE -17 Lactate 6 Cl 101

45. Bed 10 40 year old woman with pancreatitis and sepsis has been resuscitated aggressively with IV fluids on the ward for 24 hours pH 7.30 Na138 pO2 8.21 FiO2 0.7 K3.5 pCO 2 3.5 Ca 2+ 1.15 HCO 3 - 14.6 Cl - 116 Anion gap =10.9 albumin 15

46. Apparently “normal anion gap” acidosis, points to chloride…but Apparently “normal anion gap” acidosis, points to chloride…but Albumin is very low Albumin is very low SIG is high…because SIDe (A- + HCO3-) is low SIG is high…because SIDe (A- + HCO3-) is low Lactate was 4 Lactate was 4 Still underesuscitated. Still underesuscitated.