2007A11 Discuss how the body handles a metabolic acidosis.

 

List:

·         Intro

·         Dilution

·         Buffering: ICF and ECF

·         Compensation: respiratory, renal, ion exchange

 

Intro:

Definition

·  Excess production or addition of metabolic acid or excess loss of base

ABG features

·  ABG: pH <7.4, PaCO2 <40mmHg, HCO3- <24mmol/L

Classification

·  NAGMA: loss of HCO3- or base (e.g. diarrhoea, renal tubular acidosis)

·  HAGMA: addition of fixed acid (e.g. lactic acidosis, ketoacidosis)

Summary of response

1. Dilution

2. Buffering: ICF and ECF

3. Compensation: respiratory and renal

4. Correction of the underlying cause

 

Dilution (immediate)

Purpose

·  Minimise fall in local or plasma pH

Mechanism

·  Distribution of acid across body fluid compartments

 

Buffering – minutes:

Purpose

·  Resists the fall in pH when acid is added or base removed

Mechanism

·  System comprises a weak acid and its conjugate base

·  H+ readily exchanged

·  AH <-> A- + H+

Ideal properties

·  Abundant

·  Rapid

·  pKa = prevailing pH +/- 1

·  Open-ended

 

Intracellular buffering (60%)

Proteins

·  Imidazole groups of histidine residues

·  Abundant

·  pKa = pH ICF = 6.8

Phosphate

·  H2PO4- <-> H+ + HPO42-

·  High concentration (30-60mmol/L)

·  pKa = pH ICF = 6.8

 

Extracellular buffering (40%)

Bicarbonate

·  CO2 + H2O <-> H+ + HCO3-

·  ↑[H+] -> L shift -> ↑CO2 formation -> exhaled

·  Most important ECF buffer

·  High concentration 24mM

·  Rapid enzyme carbonic acid

·  pKa 6.8 is near pH 7.4

·  Open ended since can exhale CO2 and urinate H+

Haemoglobin

·  2nd most important ECF buffer

·  Imidazole groups on histidine residues

oHHb + K+ <-> KHb + H+

oAbundant (140g/L, 39 imidazole groups per molecule)

opKa 6.8

·  Carbamino compounds

oCO2 + Hb-NH2 <-> Hb-NHCOO- + H+

oCO2 binds terminal amino groups, and amino groups on side chains of arginine and lysine

oReleased H+ buffered by imidazole groups as above

Plasma proteins

·  Imidazole groups of histidine residues

·  AH <-> A- + H+

·  Abundant (70g/L, 13 imidazole groups per molecule), but 6x less than Hb

·  pKa 6.8

 

Respiratory compensation: (minutes)

Mechanism

·  Acidosis -> stimulation of peripheral chemoR -> ↑ MV -> ↓ PaCO2 -> ↓[H+]

Extent

·  Winter’s formula: PaCO2 = 8 + 1.5 x HCO3-

Effect on pH

·  As per HH equation: pH = 6.1 + [HCO3] / 0.03 x PaCO2

·  ECF pH approaches but does not reach or exceed 7.4

·  *Note resp compensation cannot remove fixed acid, because both H+ and HCO3- are being removed*

 

Renal compensation: (hours-days)

↑HCO3 reabsorption

·  ↑Activity of Na+/H+ antiporter in PCT (major)

·  ↑Activity of H+ ATPase in DT (minor, under aldosterone control)

↑Excretion of titratable acid

·  Includes phosphoric and sulfuric acid, very minimal free H+

·  (i.e. buffering of secreted H+ by filtered buffer)

·  Usual 30mmol/L, max 60mmol/L (small increaseO

↑NH3 production

·  Occurs when titratable acid exhausted

·  Glutamine -> 2 x NH4+ + HCO3-

·  NH4+ excreted -> 100% HCO3- reabsorbed, 50% NH4+ reabsorbed and recycled

·  Up to 300mmol/day, i.e. large ↑

 

Ion exchange:

Cells (minutes)

·  H+/K+ exchange

Bone
(days-weeks)

·  H+/Ca2+ exchange

 

 

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