hydrogen ion homeostasis

H+ homeostasis

The mechanisms by which the body keeps the plasma [H+]

constant

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The Body and pH

Homeostasis of pH is tightly controlled

Extracellular fluid = 7.4 Blood = 7.35 – 7.45 < 6.8 or > 8.0 death occurs Acidosis (acidemia) below 7.35 Alkalosis (alkalemia) above 7.45

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Three Major Mechanisms

Buffering Expulsion or retention of CO2

Generation / reclamation of HCO3

–/excretion of H+

Body buffers (I)

Extracellular HCO3

-/H2CO3

HPO42-/H2PO4

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Plasma proteins

Body buffers (II)

Intracellular HCO3

-/H2CO3

HPO42-/H2PO4

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Proteins & Amino-acids

Buffering H++ HCO3

-⇄H2CO3 ⇄CO2+H2O H+ is buffered Bicarbonate is consumed To stop the backward reaction which

will lead to production of H+ ions, CO2

must be expelled To generate base from the backward

reaction H+ must be excreted

Respiratory mechanisms Hyperventilation

H2CO3 ⇌ H2O + CO2

Carbon dioxide diffuses through the CNS to the respiratory centre and stimulates hyperventilation

Hypoventilationless than normal PCO2 results in hypoventilation

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Metabolic/Renal mechanisms

Excretion of H+

Bicarbonate generation

Bicarbonate reabsorption / reclamation

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The proton pump

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The proton pump

The proton pump excretes H+ and generates bicarbonate

Parameters used in assessing acid-base balance

Plasma pH

Arterial PCO2

Plasma [bicarbonate]

Anion gap (AG)

Parameters used in assessing acid-base balance: Reference ranges

Plasma pH: 7.35-7.45 corresponding to [H+] of 43-36 nmol/L (7.4) av

Arterial PCO2 : 4.8-5.8 kPa (5.3) av

Plasma [bicarbonate]: 21-28 mmol/L (25) av

Anion gap: 13-18 mmol/L (15.5) av

What is an ABG? The Components

pH / PaCO2 / PaO2 / HCO3 / O2sat / BE Desired Ranges

pH - 7.35 - 7.45 PaCO2 - 35-45 mmHg (4.8-5.8 Kpa) PaO2 - 80-100 mmHg (> 11 mmol/L) HCO3 - 21-27 O2sat - 95-100% Base Excess - +/-2 mEq/L

Why Order an ABG? Aids in establishing a diagnosis Helps guide treatment plan Aids in ventilator management Improvement in acid/base management

allows for optimal function of medications

Acid/base status may alter electrolyte levels critical to patient status/care

Parameters used in assessing acid-base balance

Others: Actual bicarbonate Standard bicarbonate Base excess PO2

Definitions

Standard bicarbonate: The concentration of bicarbonate

in plasma of a blood specimen that has, following collection, been equilibrated with O2 and CO2 mixtures at 37C. Conditions: fully oxygenated and PCO2 5.3 kPa or 40 mm Hg

Definitions

Base excess: The amount of strong acid that

would be required to titrate one litre of fully oxygenated blood to a pH of 7.4 ([H+]= 40 nm/L) at 37C under conditions where PCO2 is 5.3 kPa or 40 mm Hg

pH / Henderson-Hasselbalch Equation using the dynamics of the bicarbonate buffer

pH = pK + 1ogl0 [HCO3-]

[H2CO3]

pH = 6.10 + 1ogl0 [HCO3 -]

S.PCO2

pH = ~ [base] [acid ]

S=solubility coefficient of CO2= 0.23 mmol/J if PCO2 is expressed in kPa and 0.03 mmol/J if PCO2 is expressed in mmHg

Anion gap Based on the electroneutrality of

plasma [total cations] = [total anions]

([Na+] + [K+] +[Ca+]) = ([Cl-]+[HCO3-]+

[pyruvate]+[acetoacetate]+[lactate]+[urate] +[citrate] )

([Na+] + [K+]) -([Cl-]+[HCO3-]) = Anion

Gap (AG).

Causes of metabolic acidosis and increased anion gap (increased production of fixed or organic acids)

Lactic acid (shock, infection, hypoxia)

Urate (renal failure) Ketones (diabetes mellitus, alcohol) Drugs and toxins (salicylates,

biguanides, ethylene glycol, methanol)

Causes of metabolic acidosis and normal anion gap (loss of HCO-

3 or ingestion of H+ ions)

Proximal renal tubular acidosis

Diarrhoea Drugs

(acetazolamide) Addison’s disease

Pancreatic fistulae

Ammonium chloride ingestion

Key to solving acid-base problems:

Look at the plasma pH Is there acidaemia or alkalaemia?

Find the primary cause (parameters with a change consistent with or supporting the change in pH)

Find the secondary or compensatory changes (parameters with a change not consistent with or opposing the change in pH)

Simple acid-base disturbances

pH< 7.35 PCO2 AG HCO3

pH >7.45 PCO2 AG HCO3

Simple acid-base disturbances

pH< 7.35 PCO2 AG HCO3

Acute respiratory acidosis

Chronic respiratory acidosis

Metabolic acidosis Mixed acidosis pH >7.45 PCO2 AG HCO3

Acute respiratory alkalosis

Chronic respiratory alkalosis

Metabolic alkalosis Mixed alkalosis

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Metabolic Acidosis

Processes: Increased acids (endogenous/

exogenous) Increased H+

Decreased excretion of H+

Bicarbonate depletion / loss

Mechanisms of acid-base disturbances:Metabolic acidosis

Addition of hydrogen ions to body fluids in excess of the excretory capacity

(Processes that add hydrogen ions to body fluids faster than the body can excrete)

Starvation ketosis Diabetic ketoacidosis Lactic acidosis Ingestion of substances that are acidic or

yield acidic metabolites e.g. NH4Cl, methanol, paraldehyde, salicylates

(here , there is nothing

wrong with the kidneys)

Mechanisms of acid-base disturbances:Metabolic acidosis

Failure to excrete hydrogen ions at the normal rate (here , there is something wrong with the kidneys)

Inadequate production of ammonia by the kidney e.g. chronic renal failure

Inability to maintain the blood-urine H+ concentration gradient (pH 7.4 : 6) DRTA, Oliguria /Anuria: e.g. acute renal failure

Mechanisms of acid-base disturbances:Metabolic acidosis

Loss of bicarbonate from the body From the GIT e.g. severe diarrhoea,

fistulous drainage, uretero-sigmoidostomy

Proximal renal tubular acidosis (PRTA; failure to generate or reclaim bicarbonate) e.g. Fanconi syndrome, carbonate dehydratase inhibitors; e.g. acetazolamide)

Respiratory acidosis

Processes involved: Mechanical blockage of airway Respiratory depression.Structures involved: Brain, meninges, nerves,

respiratory muscles, lung tissue

Mechanisms of acid-base disturbances:Respiratory acidosis

Increased alveolar PCO2 leading to increased arterial PCO2

Lung disease e.g. chronic airways obstruction, respiratory distress syndrome

Weakness of respiratory muscles e.g. poliomyelitis

CNS disease e.g. encephalitis, meningitis Drug overdose e.g. hypnotics,

anaesthetics

Metabolic alkalosis

Processes involved: Loss of H+

Gain of base

Mechanisms of acid-base disturbances:Metabolic alkalosis

Metabolic Alkalosis Loss of hydrogen ions from the body Loss of H+ in vomit Diuretics (potassium non-sparing diuretics) Na+

, K + increased excretion of H+ ([H+])

Mineralocorticoid excess Na+ , K + increased excretion of H+ [H+]

Glucocorticoid excess Na+ , K + increased excretion of H+ [H+]

K+ depletion if severe increased excretion of H+

[H+]

Mechanisms of acid-base disturbances:Metabolic alkalosis

Addition of base to body fluids in excess of the excretory capacity

NaHCO3 infusions Ingestion of alkali e.g. NaHCO3,

MgO, CaCO3

Milk-alkali syndrome (treatment of peptic ulcer).

Respiratory alkalosis

Loss of carbon dioxide

Mechanisms of acid-base disturbances:Respiratory alkalosis

Respiratory alkalosis Lowered alveolar PCO2

Voluntary overbreathing, hysteria Artificial ventilation Drug overdose e.g. salicylate

poisoning sometimes

Salicylate toxicity: blood [salicylate]> 30mg dL

Usually: Accidental in children Deliberate in young adultsIn the treatment of: Rheumatoid arthritis Dermatosis

Salicylate toxicity

Initially there is stimulation of the respiratory centre ⇒ low PCO2, low HCO-

3, and respiratory alkalosis Salicylates alter peripheral

metabolism ⇒ production of various organic acids e.g. lactic acid ⇒metabolic acidosis with anion gap

Salicylate toxicity

Adults: Mixed respiratory alkalosis and

metabolic acidosisChildren: Metabolic acidosis

Salicylate toxicity: other features

Sweating Vomiting Dehydration A metabolic alkalosis can occur as

a result of vomiting

Salicylate toxicity: useful laboratory measurements

Total body K+ : () Plasma total CO2 : () Plasma [urea]: ()

Salicylate toxicity: Management

Initially and in case of spasm of pyloric

sphincter: Gastric lavageAfter significant absorption of

salicylate: Forced alkaline diuresis