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Acid-Base Biochemistry Dr. Catherine Street Consultant Clinical Biochemist Colchester Hospital university NHS Foundation Trust.

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Presentation on theme: "Acid-Base Biochemistry Dr. Catherine Street Consultant Clinical Biochemist Colchester Hospital university NHS Foundation Trust."— Presentation transcript:

1 Acid-Base Biochemistry Dr. Catherine Street Consultant Clinical Biochemist Colchester Hospital university NHS Foundation Trust

2 Acid-Base Biochemistry ► Definitions ► Methods ► Physiology ► Pathology

3 Acid-Base Biochemistry Definitions What is an acid? What is a base?

4 Acid-Base Biochemistry Definitions ► Definitions of an acid 1.Taste 2.Boyle 3.Arrhenius 4.Bronsted-Lowry 5.Lewis

5 Acid-Base Biochemistry Definitions ► Taste Acere – tasting sour Lemon juice Vinegar Definition - Thousands of years old

6 Acid-Base Biochemistry Definitions ► Robert Boyle 17 th century ► Acids taste sour, are corrosive to metals, change litmus (a dye extracted from lichens) red, and become less acidic when mixed with bases (Alkali). bases ► Bases (Alkali) feel slippery, change litmus blue, and become less basic (alkaline) when mixed with acids. acids

7 Acid-Base Biochemistry Definitions Arrhenius ► Arrhenius suggested that acids are compounds that contain hydrogen and can dissolve in water to release hydrogen ions into solution. For example, hydrochloric acid (HCl) dissolves in water as follows: solutionacidsolutionacid H 2 O H 2 O HCl (g) → H + (aq) + Cl - (aq)

8 Acid-Base Biochemistry Definitions ► Arrhenius defined bases as substances that dissolve in water to release hydroxide ions (OH - ) into solution. For example, a typical base according to the Arrhenius definition is sodium hydroxide (NaOH): basesionssolutionbasesionssolution H 2 O H 2 O NaOH (s) → Na + (aq) + OH - (aq)

9 Acid-Base Biochemistry Definitions ► The Arrhenius definition of acids and bases explains a number of things. Arrhenius's theory explains why all acids have similar properties to each other (and, conversely, why all bases are similar): because all acids release H + into solution (and all bases release OH - ). acidsbases theorysolutionacidsbases theorysolution

10 Acid-Base Biochemistry Definitions ► The Arrhenius definition also explains Boyle's observation that acids and bases counteract each other. This idea, that a base can make an acid weaker, and vice versa, is called neutralization. neutralization

11 Acid-Base Biochemistry Definitions ► Neutralization: As you can see from the equations, acids release H + into solution and bases release OH -. If we were to mix an acid and base together, the H + ion would combine with the OH - ion to make the molecule H 2 O, or plain water: acidssolutionbasesion moleculeacidssolutionbasesion molecule ► H + (aq) + OH - (aq) → H 2 O

12 Acid-Base Biochemistry Definitions ► The neutralization reaction of an acid with a base will always produce water and a salt, as shown below: neutralizationacid basesaltneutralizationacid basesalt ► Acid Base Water Salt ► HCl + NaOH → H 2 O + NaCl ► HBr + KOH → H 2 O + KBr

13 Acid-Base Biochemistry Definitions ► Limitations of Arrhenius ► The Arrhenius definition does not explain why some substances, such as common baking soda (NaHCO 3 ), can act like a base even though they do not contain hydroxide ions. base ionsbase ions

14 Acid-Base Biochemistry Definitions Brǿnsted-Lowry 1923 An acid is any chemical species that donates a proton to another chemical species (proton donor) A base is any chemical species that accepts a proton from another chemical species (Proton acceptor)

15 Acid-Base Biochemistry Definitions ► The Brønsted-Lowry definition of acids is very similar to the Arrhenius definition, any substance that can donate a hydrogen ion is an acid (under the Brønsted definition, acids are often referred to as proton donors because an H + ion, hydrogen minus its electron, is simply a proton). acidsion electronacidsion electron

16 Acid-Base Biochemistry Definitions ► The Brønsted definition of bases is, however, quite different from the Arrhenius definition. Arrhenius base releases hydroxyl ions whereas the Brønsted base is defined as any substance that can accept a hydrogen ion. ► The Brønsted definition of bases is, however, quite different from the Arrhenius definition. Arrhenius base releases hydroxyl ions whereas the Brønsted base is defined as any substance that can accept a hydrogen ion. baseionbaseion

17 Acid-Base Biochemistry Definitions ► The Brønsted-Lowry definition includes the Arrhenius bases so ► NaOH and KOH, as we saw above, would still be considered bases because they can accept an H + from an acid to form water. ► But it extends the concept of a base and introduces the concept of conjugate acid-base pairs ► But it extends the concept of a base and introduces the concept of conjugate acid-base pairs

18 Acid-Base Biochemistry Definitions The removal of a proton (hydrogen ion) from an acid produces its conjugate base, which is the acid with a hydrogen ion removed, and the reception of a proton by a base produces its conjugate acid, which is the base with a hydrogen ion added

19 Acid-Base Biochemistry Definitions ► The Brønsted-Lowry definition also explains why substances that do not contain OH - ions can act like bases. ► The Brønsted-Lowry definition also explains why substances that do not contain OH - ions can act like bases. ► Baking soda (NaHCO 3 ), for example, acts like a base by accepting a hydrogen ion from an acid as illustrated below: ► Acid Base Salt ► HCl + NaHCO 3 → H 2 CO 3 + NaCl

20 Acid-Base Biochemistry Definitions ► Lewis definition 1923 ► A substance that can accept an electron pair from a base; thus, AlCl3, BF3, and SO3 are acids. ► The Lewis theory defines an acid as a species that can accept an electron pair from another atom, and a base as a species that can donate an electron pair to complete the valence shell of another atom

21 Acid-Base Biochemistry Definitions pH Under the Brønsted-Lowry definition, both acids and bases are related to the concentration of hydrogen ions present. Acids increase the concentration of hydrogen ions, while bases decrease the concentration of hydrogen ions (by accepting them). The acidity or basicity of something therefore can be measured by its hydrogen ion concentration. acidsbasesions acidsbasesions

22 Acid-Base Biochemistry Definitions ► In 1909, the Danish biochemist Sören Sörensen invented the pH scale for measuring acidity. The pH scale is described by the formula: pH ► pH = -log [H + ] ► Note: concentration is commonly abbreviated by using square brackets, thus [H + ] = hydrogen ion concentration. When measuring pH, [H+] is in units of moles of H+ per litre of solution. ionpH unitsmolessolutionionpH unitsmolessolution

23 Acid-Base Biochemistry Methods pH electrode

24 Acid-Base Biochemistry Methods ► pH electrode

25 Acid-Base Biochemistry Methods How the pH Electrode works ► As the pH Glass comes into contact with an aqueous substance to measure, a gel layer forms on the membrane. This also happens on the inside of the glass layer..

26 Acid-Base Biochemistry Methods How the pH Electrode works ► The pH value of the aqueous solution will either force Hydrogen Ions out of the gel layer or into this layer. The Internal buffer in the glass electrode has a constant pH value and this keeps the potential at the inner surface of the membrane constant.

27 Acid-Base Biochemistry Methods How the pH Electrode works ► The membrane potential is therefore the difference between the inner and outer charge. If you then factor in the stable potential of reference electrode, you have a voltage proportional to the pH value of the solution being measured, this being approximately 58mV/pH 20ºC

28 Acid-Base Biochemistry Methods Other methods you need to know and understand ► Carbon dioxide electrode ► Oxygen electrode ► Laboratory measurement of bicarbonate ► Ion selective electrodes for K + Na + Cl -

29 Acid-Base Biochemistry Physiology ► What is Physiological pH range?

30 Acid-Base Biochemistry Physiology ► Extracellular fluid pH 7.35 – 7.46 (35-45 nmol/L) Does this apply to whole body ?any different pH ranges elsewhere

31 Acid-Base Biochemistry Physiology More extreme/variable pH range Digestive tract Gastric Juice Pancreatic Juice Intercellular organelles Lysosomal pH 4-5 Digestive and lysosomal enzymes function optimally at these pH ranges

32 Acid-Base Biochemistry Physiology Traditionally use pH to measure acidity Problem 1. direction of pH change is opposite to increase/decrease of Hydrogen ion concentration 2. Use of log scale ‘masks’ the extent of the change -change of 0.3 in pH represents doubling/halving of hydrogen ion concentration

33 Acid-Base Biochemistry Physiology ► More recently – use Hydrogen ion concentration [H + ] ► Traditionalists and older equipment use pH ► For large pH changes may not register change in units eg nmole/L to  moles/L ► Most practical - give both

34 Acid-Base Biochemistry Physiology ► WHAT THE SOURCES OF ACID IN THE BODY?

35 Acid-Base Biochemistry Physiology ► Sources of acid  Metabolism of food  Metabolism of drugs  Inborn errors of metabolism

36 Acid-Base Biochemistry Physiology ► Acid production from metabolism of food  Sulphuric acid from metabolism of sulphur- containing amino acids of proteins  Lactic acid from sugars  Ketoacids from fats

37 Acid-Base Biochemistry Physiology ► Acid production from metabolism of drugs  Direct metabolism of drug to more acidic compound eg salicylates urates etc  Induction of enzymes which metabolise other compounds (endogenous or exogenous) to acids

38 Acid-Base Biochemistry Physiology ► Inborn errors of metabolism  Organic acid disorders  Lactic acidosis

39 Acid-Base Biochemistry Physiology Greatest potential source of acid Carbon dioxide (1)CO 2 + H 2 O H 2 CO 3 (2) H 2 CO 3 H + + HCO 3 - Potentially 15,000 mmol/24 hours

40 Acid-Base Biochemistry Physiology ► Hydrogen ion homeostasis ► 1. buffering ► 2. excretion

41 Acid-Base Biochemistry Physiology Buffering of hydrogen ions In health as hydrogen ions are produced they are buffered – limiting the rise in [H + ]

42 Acid-Base Biochemistry Physiology Buffer solutions consist of a weak acid and its conjugate base As hydrogen ions are added some will combine with the conjugate base and convert it to undissociated acid

43 Acid-Base Biochemistry Physiology Bicarbonate – carbonic acid buffer system H + + HCO 3 - H 2 CO 3 ► Addition of H + drives reaction to the right Conversely ► Fall in H + drives reaction to the left as carbonic acid dissociates producing more H +

44 Acid-Base Biochemistry Physiology ► Buffering systems in blood  Bicarbonate ions-most important  Proteins including intracellular proteins  Haemoglobin

45 Acid-Base Biochemistry Physiology ► Buffer solutions operate most efficiently at [H + ] that result in approximately equal concentration of undissociated acid and conjugate base ► But at normal extracellular fluid pH [H 2 CO 3 ]  1.2 mmol whereas [HCO 3 - ] is twenty times greater

46 Acid-Base Biochemistry Physiology ► The bicarbonate system is enhanced by the fact that carbonic acid can be formed from CO 2 or disposed of by conversion to CO 2 CO 2 + H 2 O H 2 CO 3

47 Acid-Base Biochemistry Physiology ► For every hydrogen ion buffered by bicarbonate – a bicarbonate ion is consumed. ► To maintain the capacity of the buffer system, the bicarbonate must be regenerated ► However, when bicarbonate is formed from carbonic acid (CO 2 and H 2 O) equimolar amounts of [H + ] are formed

48 Acid-Base Biochemistry Physiology ► Bicarbonate formation can only continue if these hydrogen ions are removed ► This process occurs in the cells of the renal tubules where hydrogen ions are secreted into the urine and where bicarbonate is generated and retained in the body

49 Acid-Base Biochemistry Physiology ► 2 different processes ► Bicarbonate regeneration (incorrectly reabsorption) ► Hydrogen ion excretion

50 Acid-Base Biochemistry Physiology Importance of Renal Bicarbonate Regeneration ► Bicarbonate is freely filtered through the glomerulus so plasma and glomerular filtrate have the same bicarbonate concentration ► At normal GFR approx 4300 mmol of bicarbonate would be filtered in 24 hr ► Without re-generation of bicarbonate the buffering capacity of the body would be depleted causing acidotic state ► In health virtually all the filtered bicarbonate is recovered

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52 Acid-Base Biochemistry Physiology ► Renal Bicarbonate Regeneration involves the enzyme carbonate dehydratase (carbonic anhydrase) ► Luminal side of the renal tubular cells impermeable to bicarbonate ions ► Carbonate dehydratase catalyses the formation of CO 2 and H 2 O from carbonic acid (H 2 CO 3 ) in the renal tubular lumen ► CO 2 diffuses across the luminal membrane into the tubular cells

53 Acid-Base Biochemistry Physiology ► within the renal tubular cells carbonate dehydratase catalyses the formation of carbonic acid (H 2 CO 3 ) from CO 2 and H 2 O ► Carbonic acid then dissociates into H + and HCO3 - ► The bicarbonate ions pass into the extracellular fluid and the hydrogen ions are secreted back into the lumen in exchange for sodium ions which pass into the extracellular fluid ► Exchange of sodium and hydrogen ions an active process involving Na + /K + /H + ATP pump ► K + important in electrolyte disturbances of acid-base

54 Acid-Base Biochemistry Physiology ► Regeneration of bicarbonate does not involve net excretion of hydrogen ions ► Hydrogen ion excretion requires the same reactions occurring in the renal tubular cells but also requires a suitable buffer in urine ► Principal buffer system in urine is phosphate ► 80% of phosphate in glomerular filtrate is in the form of the divalent anion HPO 4 2- ► This combines with hydrogen ions ► HPO H + ↔ H 2 PO 4 -

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56 Acid-Base Biochemistry Physiology ► Hydrogen ion excretion capacity ► The minimum urine pH that Can be generated is 4.6 ( 25µmol/L) ► Normal urine output is 1.5L ► Without the phosphate buffer system the free excretion of Hydrogen ions is less than 1/1000 of the acid produced by normal metabolism

57 Acid-Base Biochemistry Physiology ► The phosphate buffer system increases hydrogen ion excretion capacity to mmol/24 hours ► In times of chronic overproduction of acid another urine buffer system ► Ammonia

58 Acid-Base Biochemistry Physiology ► Ammonia produced by deamination of glutamine in renal tubular cells ► Catalysed by glutaminase which is induced by chronic acidosis ► Allows increased ammonia production and hence increased hydrogen ion excretion via ammonium ions ► NH 3 + H + ↔ NH 4 +

59 Acid-Base Biochemistry Physiology ► At normal intracellular pH most ammonia is present as ammonium ions which can’t diffuse out of the cell ► Diffusion of ammonia out of the cell disturbs the equilibrium between ammonia and ammonium ions causing more ammonia to be formed ► Hydrogen ions formed at the same time! ► These are used up by the deamination of glutamine to glutamate during gluconeogenesis

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61 Acid-Base Biochemistry Physiology ► Carbon dioxide transport ► Carbon dioxide produced by aerobic respiration diffuses out of cells and into the ECF ► A small amount combines with water to form carbonic acid decreasing the pH of ECF ► In red blood cells metabolism is anaerobic and very little CO 2 is produced hence it diffuses into red cells down a concentration gradient to form carbonic acid (carbonate dehydratase) buffered by haemoglobin.

62 Acid-Base Biochemistry Physiology ► Haemoglobin has greatest buffering capacity when it is dexoygenated hence the buffering capacity increases as oxygen is lost to the tissues ► Net effect is that carbon dioxide is converted to bicarbonate in red cells ► Bicarbonate diffuses out of red cells down concentration gradient and chloride ions diffuse in to maintain electrochemical neutrality (chloride shift)

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64 Acid-Base Biochemistry PhysiologyAcid-Base Biochemistry Physiology ► In the lungs this process is reversed ► Haemoglobin is oxygenated reducing its buffering capacity and generating hydrogen ions ► These combine with bicarbonate to form CO2 which diffuses into the alveoli ► Bicarbonate diffuses into the cells from the plasma

65 Acid-Base Biochemistry Physiology ► Most of the carbon dioxide in the blood is present as bicarbonate ► Carbon dioxide, carbonic acid and carbamino compounds less than 1/10 th of the total ► Bicarbonate /total CO 2 used interchangeably though not strictly the same ► Most analytical methods actually measure total CO 2 as bicarbonate difficult to measure

66 Acid-Base Biochemistry Physiology The hydrogen ion concentration of plasma is directly proportional to the PCO 2 and inversely proportional to bicarbonate [H + ] = k pCO 2 /[HCO 3 - ] [H + ] = k pCO 2 /[HCO 3 - ] [H + ] in nmoles/L, [HCO 3 - ] in mmoles/L pCO 2 in kPa k = 180 pCO 2 in mm Hg k= 24

67 Acid-Base Biochemistry Physiology ► Derived bicarbonate ► Possible to use the equation to calculate the bicarbonate concentration from the pCO 2 and pH (blood gas analysers) ► ?how valid in non-ideal solutions ► Auto analysers – measured bicarbonate

68 Acid-Base Biochemistry Physiology ► The relationship between [H + ], pCO 2 and bicarbonate fundamental to understanding pathophysiology of hydrogen ion homeostasis

69 Acid-Base Biochemistry Pathology ► 4 Components to acid-base disorders  Generation  Buffering  Compensation  Correction Occurring concurrently

70 Acid-Base Biochemistry Pathology ► Classification of acid-base disorders ► Acidosis ► [H+] above normal, pH below normal ► Alkalosis ► [H+] below normal, pH above normal

71 Acid-Base Biochemistry Pathology ► Further classified as  Respiratory  Non-respiratory (metabolic)  Mixed – difficult to distinguish between primary mixed condition and compensated disorder

72 Acid-Base Biochemistry Pathology ► Respiratory disorders involve a change in pCO 2 ► Metabolic disorders involve change in production or excretion of hydrogen ions or both

73 Acid-Base Biochemistry Pathology ► Non-respiratory acidosis ► Increased production/reduced excretion of acid ► ?causes

74 Acid-Base Biochemistry Pathology ► Non-respiratory acidosis ► Overproduction of acid  Keto acidosis (diabetes, starvation, alcohol)  Lactic acidosis (inherited metabolic defect or drugs)  Inherited organic acidoses  Poisoning (salicylate, ethylene glycol, alcohol)  Excessive parenteral amino acids

75 Acid-Base Biochemistry Pathology ► Non-respiratory acidosis ► Reduced excretion of acid  Generalised renal failure  Renal tubular acidoses  Carbonate dehydratase inhibitors

76 Acid-Base Biochemistry Pathology ► Non-respiratory acidosis ► Loss of Bicarbonate  Diarrhoea  Pancreatic, intestinal, biliary fistula or drainage

77 Acid-Base Biochemistry Pathology ► Compensation of non-respiratory acidosis Excess hydrogen ions are buffered by bicarbonate forming carbonic acid which dissociates to carbon dioxide to be lost in expired air The buffering limits the rise in [H+] at the expense of reduction in bicarbonate

78 Acid-Base Biochemistry Pathology ► Compensation of non-respiratory acidosis ► Hyperventilation increases removal of CO 2 lowering pCO 2 ► PCO 2 / [HCO 3 - ] ratio falls reducing [H + ] ► Hyperventilation is the direct result of increased [H + ] stimulating the respiratory centre (Kussmaul respiration) Respiratory compensation of non-respiratory acidosis

79 Acid-Base Biochemistry Pathology ► Compensation of non-respiratory acidosis ► Limitations ► Respiratory compensation cannot completely normalise the [H + ] because the hyperventilation is stimulated by the increase in [H + ] and as this falls the drive on the respiratory centre is reduced ► Increased work of respiratory muscles during hyperventilation produces CO 2 limiting the degree to which PCO 2 can be lowered

80 Acid-Base Biochemistry Pathology ► The degree of compensation may be limited further if respiratory function is compromised ► If it is not possible to correct the cause of the acidosis may get a new steady state of chronic acidosis  [H + ]  [HCO 3 - ] and ↓ PCO2  [H + ]  [HCO 3 - ] and ↓ PCO2

81 Acid-Base Biochemistry Pathology ► In the absence of acidosis - hyperventilation would normally generate a respiratory alkalosis ► Compensatory mechanisms usually involve generation of a second opposing disturbance ► In non-respiratory acidosis the hyperventilation limits the severity of the acidosis but is not great enough to cause alkalosis in the patient

82 Acid-Base Biochemistry Pathology ► Non-respiratory compensation of non- respiratory acidosis ► If renal function is normal excess [H + ] can be excreted by the kidneys ► But renal function is often impaired even if not the primary cause of the acidosis

83 Acid-Base Biochemistry Pathology ► Correction of acidosis ► Complete correction requires reversal or removal of the underlying cause ► Ethylene glycol poisoning – slow the rate of metabolism with ethanol ► Diabetes – rehydration and insulin

84 Acid-Base Biochemistry Pathology ► Summary of non-respiratory acidosis ► pH  ► [H + ]  ► PCO 2  ► [HCO 3 - ]  

85 Acid-Base Biochemistry Pathology ► Management of non-respiratory acidosis ► 1. Removal of cause ► 2. Administration of Bicarbonate – only in severe cases pH <7.0 and where 1 is not possible ► Must be given in small quantities with constant monitoring of pH

86 Acid-Base Biochemistry Pathology ► Respiratory acidosis ► Primarily an increase in PCO 2 ► Number of different causes

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88 Acid-Base Biochemistry Pathology ► Retention of CO 2 ► Production of carbonic acid ► For every hydrogen ion produced a bicarbonate ion is generated ► Most of the [H + ] is buffered by intracellular buffers (haemoglobin) ► Development of renal compensation if renal function is normal

89 Acid-Base Biochemistry Pathology ► Acute respiratory acidosis For every KPa increase in PCO 2  increase in bicarbonate < 1 mmole  Increase in [H+] 5.5 nmol/L ► Chronic For every KPa increase in PCO 2  increase in bicarbonate 2-3 mmole  Increase in [H+] 2.5 nmol/L

90 Acid-Base Biochemistry Pathology ► Compensation of respiratory acidosis ► Increased renal excretion of hydrogen ions

91 Acid-Base Biochemistry Pathology ► Management of respiratory acidosis ► With reduced ventilation it is usually the hypoxaemia that is life threatening 4 mins if ventilation ceases ► Improve alveolar ventilation bronchodilators and antibiotics ► Artificial ventilation close monitoring required to avoid over correction esp in chronic acidosis

92 Acid-Base Biochemistry Pathology Summary of respiratory acidosis AcuteChronic pH Slight  or low normal [H + ]  Slight  or high normal PCO 2  [HCO 3 - ] Slight  

93 Acid-Base Biochemistry Pathology ► Non respiratory alkalosis ► Loss of un-buffered hydrogen ions Gastrointestinal - vomiting with pyloric stenosis - vomiting with pyloric stenosis - diarrhoea - diarrhoea - nasogastric aspiration - nasogastric aspiration

94 Acid-Base Biochemistry Pathology Causes of non respiratory alkalosis Renal Mineralo-corticoid excess Conn’s syndrome Cushings syndrome Drugs with mineralocorticoid activity Diuretic therapy (not K + sparing)

95 Acid-Base Biochemistry Pathology Causes of non respiratory alkalosis Causes of non respiratory alkalosis Administration of alkali  Over-treatment of acidosis  Chronic alkali ingestion (antacids)

96 Acid-Base Biochemistry Pathology ► Non respiratory alkalosis ► Characterised by primary increase in ECF bicarbonate ► Consequent reduction in [H + ] ► Normally increase in bicarbonate causes reduction in renal bicarbonate regeneration and increased urinary excretion of bicarbonate

97 Acid-Base Biochemistry Pathology ► non respiratory alkalosis ► Maintenance requires inappropriate renal bicarbonate reabsorption/regeneration - decrease in ECF volume (hypovolaemia) - mineralocorticoid excess - potassium depletion

98 Acid-Base Biochemistry Pathology ► non respiratory alkalosis ► Hypovolaemia  Increased stimulus to sodium reabsorption  Dependant on adequate anions  If chloride deficient (GI losses) electrochemical neutrality during Na + absorption maintained by increased bicarbonate absorption and by H + and K + excretion

99 Acid-Base Biochemistry Pathology ► non respiratory alkalosis ► Mineralocorticoid excess  Alkalosis perpetuated by increased hydrogen ion excretion secondary to increased sodium reabsorption Potassium depletion Potassium and hydrogen ion excretion compete for exchange with sodium so depletion of potassium causes increased H + excretion

100 Acid-Base Biochemistry Pathology ► non respiratory alkalosis ► Compensation ► Low H + inhibits the respiratory centre causing hypoventilation and increase in PCO 2 ► Self- limiting as increase in PCO 2 increases drive on respiratory centre ► In chronic state development of reduced sensitivity to PCO 2 – more significant compensation BUT ► Hypoventilation causing hypoxaemia will provide stimulation of RC and prevent further compensation

101 Acid-Base Biochemistry Pathology ► non respiratory alkalosis ► Management ► Dependent on severity and cause ► - severe hypovolaemia /hypochloraemia correct with saline infusion ► - potassium supplements/removal of diuretics

102 Acid-Base Biochemistry Pathology ► Summary of non respiratory alkalosis ► [H + ]  ► pH  ► PCO 2  ► [HCO 3 - ]  

103 Acid-Base Biochemistry Pathology ► Respiratory alkalosis ► Causes ► Hypoxia  High altitude  Severe anaemia  Pulmonary disease

104 Acid-Base Biochemistry Pathology ► Respiratory alkalosis ► Causes ► Increased respiratory drive  Stimulants eg salicylates  Cerebral – trauma, infection, tumours  Hepatic failure

105 Acid-Base Biochemistry Pathology ► Respiratory alkalosis ► Causes Pulmonary disease - Pulmonary oedema - Pulmonary embolism Mechanical over-ventilation

106 Acid-Base Biochemistry Pathology ► Respiratory alkalosis ► Characterised by reduction in PCO 2 ► Reduces the PCO 2 / [HCO 3 - ] ratio For every KPa decrease in PCO 2  decrease in [H+] 5.5 nmol/L  Small decrease in bicarbonate

107 Acid-Base Biochemistry Pathology ► Respiratory alkalosis ► Compensation -reduction in renal hydrogen ion excretion Develops slowly maximal in hours

108 Acid-Base Biochemistry Pathology ► Respiratory alkalosis management ► Mainly removal of underlying cause ► Increasing inspired PCO 2 by rebreathing of expired air for temporary measure - Prolonged – risk of hypoxia

109 Acid-Base Biochemistry Pathology ► Summary of respiratory alkalosis ► AcuteChronic ► pH  Slight  or low normal ► [H + ]  Slight  or high normal ► PCO 2   ► [HCO 3 - ] Slight  

110 Acid-Base Biochemistry Pathology ► Mixed acid base disorders respiratory alkalosis with metabolic acidosis respiratory alkalosis with metabolic acidosis e.g. salicylate poisoning causes respiratory alkalosis by directly stimulating the hypothalamic respiratory centre causing over-breathing and increased excretion of CO 2 Salicylate metabolised to acids

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112 Interpretation of results ► Reference ranges ► pH 7.35 – 7.46 ► [H + ] nmol/L ► pCO kPa (35-46 mm Hg) ► pO kPa ( mm Hg) ► Total Bicarbonate (CO 2 ) mmol/L

113 Further information A further algorithm for interpretation of acid-base data and a number of clinical cases were provided as hard-copy. These can be found in Marshall (see recommended reading)

114 Acid-Base Biochemistry Methods

115 ► The polarographic (Clark) oxygen electrode measures the oxygen partial pressure in a blood or gas sample. A platinum cathode and a silver/silver chloride anode are placed in a sodium chloride electrolyte solution, and a voltage of 700 mv is applied (Figure 1). The following reactions occur. ► At the cathode: O 2 + 2H 2 O + 4e – = 4OH –. ► In the electrolyte: NaCl + OH– = NaOH + Cl –. ► At the anode: Ag + Cl – = AgCl + e –. ► Electrons are taken up at the cathode and the current generated is proportional to oxygen tension. A membrane separates the electrode from blood, preventing deposition of protein but allowing the oxygen tension in the blood to equilibrate with the electrolyte solution. The electrode is kept at a constant temperature of 37°C and regular checks of the membrane are required to ensure it is not perforated or coated in proteins. Sampling two gas mixtures of known oxygen tension allows calibration.

116 Acid-Base Biochemistry Methods ► The Severinghaus or carbon dioxide electrode is a modified pH electrode in contact with sodium bicarbonate solution and separated from the blood specimen by a rubber or Teflon semipermeable membrane. Carbon dioxide, but not hydrogen ions, diffuses from the blood sample across the membrane into the sodium bicarbonate solution, producing hydrogen ions and a change in pH. ► Hydrogen ions are produced in proportion to the pCO2 and are measured by the pH-sensitive glass electrode. As with the pH electrode, the Severinghaus electrode must be maintained at 37°C, be calibrated with gases of known pCO2 and the integrity of the membrane is essential. Because diffusion of the CO2 into the electrolyte solution is required the response time is slow at 2–3 minutes.

117 Acid-Base Biochemistry Methods ION SELECTIVE ELECTRODE

118 Acid-Base Biochemistry RECOMMENDED READING ► Analytical/methods  Tietz Textbook of Clinical Chemistry by Carl A. Burtis (Author), Edward R. Ashwood (Author) Carl A. BurtisEdward R. Ashwood Carl A. BurtisEdward R. Ashwood ► Clinical  Clinical Biochemistry by William J. Marshall and Stephen Bangert


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