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Lom acid base_lecture2013-1
- 1. Language of Medicine Chemical Pathology David Haarburger ACID-BASE
- 2. BASIC CHEMISTRY Acid Base HA ↔ H+ + A- B + H+ ↔ BH+ HCl ↔ H+ + Cl- NH3 + H+ ↔ NH4+
- 3. HOW MANY ACIDS? HOW MANY BASES? 1. H2SO4 2. H2PO4- 3. CH3COOH 4. H2CO3 5. KOH 6. H20
- 4. HOW MANY ACIDS? HOW MANY BASES? 1. H2SO4 ↔ H+ + HSO4- 2. H3PO4 ↔ H2PO4- + H+ ↔ HPO42 + 2H+ 3. CH3COOH ↔ CH3COO- + H+ 4. H2CO3 ↔ H+ + HCO3- 5. KOH + H+ ↔ K+ + H20 6. H20 + H20 ↔ H3O+ + OH-
- 5. ACID DISSOCIATION CONSTANTS HA ↔ H+ + A- [ H ][ A ] [ H ][Cl ] ka ka [ HA] [ HCl ] Acid Ka Hydrochloric Acid 108 Sulphuric Acid 103 Acetic Acid 1,8·10-5 Carbonic Acid 2,5∙10-4 Ammonium 5,6∙10-10
- 6. P FUNCTIONS pH = - log [H+] pKa = - log Ka pH of 1mM HCl = - log (0,001M) = 3 Ka of HCl = 108 → pKa of HCl = - log 108 = -8
- 7. BUFFERS Buffer solutions are solutions consisting of a weak acid and its conjugate base which resist changes in pH upon addition of small amounts of acid or base. Solution of Sodium Acetate and Acetic Acid CH3COO- + H+ ↔ CH3COOH
- 8. GAS SOLUBILITY Henry’s Law C=kxP C : Concentration of a gas k : Henry’s constant P : Partial pressure of a gas Examples of k (0ºC) O2 13μmol/l/kPa N2 6,0μmol/l/kPa CO2 340μmol/l/kPa
- 9. EXAMPLE A open beaker of water at atmospheric pressure Gas P k C (kPa) (μmol/l/kPa) (μmol/l) O2 21 13 273 N2 80 6 480 CO2 0,3 340 102
- 10. ACID-BASE BALANCE [H+] is tightly controlled between 35 and 45 nmol/ℓ (pH 7,35 – 7,45) [H+] too high Lethargy, neuromuscular irritability, seizures Cardiac arrhythmias [H+] too low Tetany, seizures Cardiac arrhythmias
- 11. ACID PRODUCTION Where does acid come from? Metabolism (40 – 80 mmol/l H+ per day) Metabolism of cysteine and methionine in proteins generates sulphuric acid : H2SO4 Metabolism of DNA and RNA and phospholipids yields phosphoric acid : H3PO4 Incomplete metabolism of fatty acids yields ketones : β- hydroxybutyric acid and acetoacetic acid Incomplete metabolism of glucose yields lactic acid Too many of these acids cause a metabolic acidosis Oxidative respiration (15 mol per day) Oxidative respiration generates CO2 Carbon dioxide combines with water to yield carbonic acid: H2CO3 Too much CO2 (decreased clearance) causes a respiratory acidosis
- 12. PHYSIOLOGICAL BUFFERS Buffers are only a temporary solution for too much or too little H+, but they work really well in the short term! Blood pH 7,35-7,45 (35-45 nM) Buffer pKa Conc Buffering (mmol/l) Capacity (mmol/l) Bicarbonate 6,33 25 1 Haemoglobin 7,2 53 40 Phosphate 6,8 1,2 0,3 Protein - - 8
- 13. HENDERSON-HASSELBACH EQUATION H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3- [ H ][ HCO3 ] ka [ H 2CO3 ] [ HCO3 ] pH pka log [ H 2CO3 ] [ HCO3 ] pH 6,1 log 0,225PCO2
- 14. HENDERSON-HASSELBACH EQUATION [ H ][ HCO3 ] [ H 2CO3 ] [ H ][ HCO3 ] ka kh ka ka kh [ H 2CO3 ] [CO2 ] [CO2 ] [ HCO3 ] log k a log[H ] [CO2 ] [ HCO3 ] log k a log[H ] log [CO2 ] [ HCO3 ] log[H ] log k a log [CO2 ] [ HCO3 ] pH pka log [CO2 ] [ HCO3 ] pH pka log PCO2 [ HCO3 ] pH 6,1 log 0,225PCO2
- 15. RESPIRATORY CONTROL Alveolus Cell CO2 CO2 HbH+ → H2O+CO2 → Hb + H+ H++HCO3- HCO3- Hb + H+→ HCO3- + H+→ HbH+ H2O+CO2
- 16. RENAL CONTROL
- 17. RENAL CONTROL BICARBONATE RE-ABSORBTION HCO3- Proximal renal tubular cell H2O+CO2 → Na+ HCO3-+H+ H+ Na+ ATP H++HCO3- → K+ CO2+H2O Tubular lumen
- 18. RENAL CONTROL PROTON SECRETION Tubular lumen Distal renal tubular cell H2O+CO2 → Na+ ATP HCO3-+H+ H+ H++ NH3 → NH4+ H+ + HPO32- → H2PO-
- 19. CLINICAL ACID-BASE Acidaemia A condition of decreased pH of the blood Alkalaemia A condition of increased pH of the blood Acidosis A pathological condition resulting from accumulation of acid in the body Alkalosis A pathological condition resulting from loss of acid from the body
- 20. BLOOD GAS MEASUREMENT Arterial or capillary blood to measure arterial pO2 and pCO2 values A heparinised sample Most O2 is carried in red cells Sealed syringe Prevents O2 diffusing in and CO2 diffusing out of the sample On ice Prevents ongoing red cell metabolism from generating a lactic acidosis What we measure pO2 11 – 15 kPa pCO2 4.5 – 6.0 kPa pH 7.36 – 7.44 HCO3- 22 – 30 mmol/L (calculated) [ HCO3 ] pH 6,1 log 0,225 pCO2
- 21. RESPIRATORY ACIDOSIS Disorder that interferes with the ability of the lungs to expel CO2. Examples Depression of respiratory centre Drugs - morphine, barbiturates, alcohol Head injury Physical inability to ventilate Crush injury to chest Muscle paralysis Airway obstruction Asthma Chronic obstructive airways disease Disease causing decreased CO2 and O2 exchange Severe pneumonia Severe lung collapse Laboratory results pH ↓ pCO2 ↑ HCO3- ↑ H2O + CO2 ↔ H+ + HCO3-
- 22. RESPIRATORY ALKALOSIS Disorder that results from an excessive loss of CO2 from the lungs. Examples Direct stimulation of respiratory centre Drugs – salicylates Anxiety Mechanical overventilation Hypoxia High altitude Anaemia Laboratory results pH ↑ pCO2 ↓ HCO3- ↓ H2O + CO2 ↔ H+ + HCO3-
- 23. METABOLIC ACIDOSIS Disorder that results from an excessive loss of HCO3-. Examples Hypoxia Diabetic ketoacidosis Renal failure Laboratory results pH ↓ pCO2 ↓ HCO3- ↓
- 24. METABOLIC ALKALOSIS Disorder that results from an excessive accumulation of HCO3-. Examples Vomiting Anti-acids Laboratory results pH ↑ pCO2 ↑ HCO3- ↑
- 25. COMPENSATION Metabolic compensation When lung function is compromised, the kidneys attempt to increase the excretion of hydrogen ions via the renal route Metabolic compensation is slow to take effect, coming into effect over 2 - 4 days Respiratory compensation When there are metabolic disorders, some compensation is possible by the lungs by altering the rate and depth of respiration, which is affected directly by the blood pH Respiratory compensation is quick to take effect, coming into effect within 15 - 30 minutes If compensation is complete, the pH returns to normal, although the bicarbonate and CO2 concentrations are abnormal Compensation is however often partial, in which case there is a change in both bicarbonate and CO2 concentrations, but the pH is still abnormal.
- 26. APPROACH TO ACID-BASE pH Example ↑ Alkalosis pH 7,32 (7,36-7,44) ↓ Acidosis pCO2 8kPa (4,5-6,0) pCO2 HCO3- 31mmol/l (22-30) ↑ Respiratory Acidosis ↓ Respiratory Alkalosis HCO3- ↑ Metabolic Alkalosis ↓ Metabolic Acidosis Primary / Compensation