My Clinical Notes

• If a molecule differs from another by only a proton the 2 are called a conjugate acid base pair
• pH of normal blood pH 7.35 to 7.45
• Physiological buffers that are important;
  • Haemoglobin
  • Bicarbonate
  • Phosphate
  • Proteins
• Haemoglobin and serum proteins have high concentrations of histidine residues – these accept protons
• Oxygenated Hb is a stronger acid than deoxygenates Hb therefore in the lungs Hb releases H+ as it becomes oxygenated

 

Bicarbonate buffer system

 

H⁺  +  HCO₃^-  «  H₂CO₃  «  CO₂  +  H₂O

 

• Accounts for over 60% of the bloods buffering capacity
• PCO₂ is the respiratory component
• Bicarbonate is the metabolic component
• It is necessary for efficient buffering by haemoglobin which provides most of the rest of the bloods buffering capacity
• H+ secretion by the kidney is dependant upon it
• The normal respiratory centre and the lungs can control the concentration of CO₂ within narrow limits by responding to changes in [H+] and can therefore compensate for changes in acid-base disturbances
• The renal tubular cells and erythrocytes generate bicarbonate, the buffer base in the bicarbonate system from CO₂;
• The erythrocyte mechanism makes fine adjustments to the plasma bicarbonate concentration in response to changes in PCO₂ in the lungs and tissues
• The kidneys play the major role in maintaining the circulating bicarbonate concentration and eliminating H+ from the body
• Carbonic anhydrase catalyses the production of carbonic acid from CO₂ and H₂O, which then dissociates to form bicarbonate and H+ ions
• Carbonic anhydrase is present in erythrocytes and renal tubular cells
• In a normal subject at a plasma PCO₂ of 5.3kPa (a CO2 of about 1.2mmol/L erythrocytes and renal tubular cells keep the extracellular bicarbonate concentration to 25mmol/L. The ratio of [HCO3-] to [CO2] is just over 20:1. according to the Henderson-Hasselbalch equation with a pK of 6.1, the pH is near 7.4
• The diffusion of HCO₃- out of RBC is balances by the influx of Cl- in the opposite direction. This is know as the ‘chloride shift’
• Only when bicarbonate levels are >25mEq/L is it secreted in the urine
• Phosphate buffering is more important in the urine and blood as urine contains less protein, haemoglobin or bicarbonate

 

Base excess

 

• Calculated parameter used to assess the metabolic component of the patients acid base disturbance
• Dose of acid required to return plasma to normal pH at standard temperature and PCO₂
• Used to describe excess or deficit of bicarbonate
• Used to estimate the number of mEq of sodium bicarbonate or ammonium chloride required to correct pH

 

Anion Gap

 

• Total measured anions are subtracted from anions
• Anion gap = [Na] + [K] – [Cl] – [HCO₃]
• Normally around 12mEq/L
• Due to phosphates, ketones, lactic acid, proteins, sulphates
• Increased anions increases the anion gap
• Normal anion gap acidosis;
  • Bicarbonate loss
  • H+ ingestion as ammonium chloride
• Increased anion gap acidosis;
  • Uraemia
  • Ketoacidosis
  • Lactate acidosis
  • Salicylate poisoning

 

Parameter	Â
pH	7.35-7.45
PCO2	4.5-6 kPa
PO2	11- 15 kPa
HCO3	22-30 mmol/L
O2 saturation	94-100%
Venous anion gap	5-14 mmol/L
Base excess	-2 - +2 mEq/L

 

 

The kidneys

 

• Two renal mechanisms control [HCO₃-] in the extracellular fluid;
• Bicarbonate reabsorption – carbonic anhydrase is present on the luminal surface and intracellularly within tubular cells. Converts H₂CO₃ to CO₂ which can cross the cell membrane. H₂CO₃ is generated by combining H+ which is secreted by the tubular cells (in exchange for Na) to HCO₃-. This occurs predominantly in the proximal tubules and in the first past of the distal tubule. As there is no net change in H+ ion balance and no net gain of bicarbonate this mechanism cannot correct an acidosis but can maintain a steady state
• Bicarbonate generation – important for correcting acidosis. Carbonic anhydrase can be stimulated by;
  • A rise in PCO₂
  • A fall in [HCO₃]

 

Urinary buffers

 

• The two most important urinary buffers other than bicarbonate are phosphate and ammonia. They are also involved in bicarbonate generation.

 

Phosphate buffer pair

 

• At pH 7.4 most of the phosphate in plasma and glomerular filtrate is monohydrogen phosphate (HPO₄^2-) which can accept H+ to become dihydrogen phosphate (H₂PO₄^-)^. the pK of this buffer pair is around 6.8

 

Ammonia

 

• Produced by deamination of glutamine in renal tubular cells. The enzyme which catalyses this reaction, glutaminase is induced in states of chronic acidosis, allowing increased ammonia (NH₃) production and hence increased hydrogen ion excretion via ammonium (NH₄⁺) ions. Ammonia can readily diffuse across cell membranes but ammonium ions, formed when ammonia buffers hydrogen ions cannot.
• NH₃  +  H⁺  «  NH₄⁺

 

Metabolic acidosis

 

• Can be caused by;
• Increased H+ formation

o       Lactic acid (Type I lactic acidosis there is tissue hypoxia, Type II there is no tissue hypoxia)

o       b-hydroxybutyric acid – uncontrolled diabetes

o       acetoacetic acid – uncontrolled diabetes

o       can also be caused by ingestion of carbonic anhydrase inhibitors – acetazolamide and sulphonamides

o       digestion of other drugs such as, methanol, ethylene glycol and paraldehyde also cause metabolic acidosis

• Acid ingestion

• • acid poisoning
  • excessive parenteral administration of amino acids e.g. arginine, lysine and histidine

• Decreased H+ excretion

• • renal tubular acidosis there is decreased H+ secretion

• Loss of bicarbonate

• • diarrhoea
  • pancreatic, intestinal and biliary fistulae or drainage

• response – hyperventilation to cause a compensatory respiratory alkalosis
• if kidneys are not damaged renal tubules will exchange H+ for Na+ to make urine more acidic
• Lab findings;

­       HCO₃ (if compensated)

¯    pH

¯    CO₂

base deficit

 

Respiratory acidosis

 

• Caused by the inability to expel CO₂;
• Airway obstruction
  • COPD
  • Bronchospasm e.g. asthma
  • Aspiration
• Depression of respiratory centre
  • Anaesthetics
  • Sedatives
  • Cerebral trauma
  • Tumours
• Neuromuscular disease
  • Poliomyelitis
  • Guillia-Barre syndrome
  • Motor neurone disease
  • Tetanus/botulism
  • Neurotoxins, curare
• Pulmonary disease
  • Pulmonary fibrosis
  • Severe pneumonia
  • Respiratory distress syndrome

 

• Response;
  • Increased renal secretion of acids
  • Retention of Na and bicarbonate
  • Hyperventilation (if possible)
  • Metabolic alkalosis compensates for a respiratory acidosis

 

Metabolic alkalosis

 

• Due to;
• Loss of unbuffered H+ ion
  • Gastrointestinal;
    • Gastric aspiration
    • Vomiting with pyloric stenosis
    • Congenital chloride-losing diarrhoea
  • Renal;
    • Mineralocorticoid excess – Cushing’s syndrome, Conn’s syndrome
    • Non K+ sparing diuretics
• Administration of alkali
  • Chronic alkalis ingestion
• Response
  • Slowing of respiration
  • Increased renal excretion of excess bicarbonate unless the proximal tubule increases reabsorption of bicarbonate such as occurs in;
  • Hypokalaemia
  • Dehydration
  • hypochloreamia
• Biochemical features
  • Increased pH
  • Increased pCO₂
  • Increased bicarbonate

 

Respiratory alkalosis

 

• Due to;
• Hypoxia
  • High altitude
  • Severe anaemia
  • Pulmonary disease
• Increased respiratory drive
  • Respiratory stimulants e.g. salicylates
  • Cerebral disturbances e.g. trauma, infection, tumours
  • Hepatic failure
  • Gram-negative septicaemia
  • Primary hyperventilation syndrome
  • Voluntary hyperventilation
• Pulmonary disease
  • Pulmonary oedema
  • Pulmonary embolism
• Main feature is a fall in PCO₂
• Compensation occurs through a reduction in renal hydrogen ion excretion, which further decreases plasma bicarbonate concentration
• Patient often complains of tingling of fingers and around mouth, this is due to low free calcium. This is due to reduced binding of protons to proteins which enhances calcium binding. Low free calcium reduces threshold for firing action potentials

 

Taking a sample

 

• Radial, brachial and femoral arteries commonly used
• Allow syringe to fill with pressure of arterial blood. Apply pressure to artery for several mins once needle has been removed
• Record patients temperature if hypothermic because results measures at 37 degrees would overestimate the PCO₂ and the [H+]

• Specimen tube should be full to minimize in vitro loss of CO₂  into a large dead space of air during centrifugation – this will give a falsely low result
• Arterial samples are preferable to capillary samples
• Syringe should be well moistened with heparin and the specimen should be well mixed
• Excess heparin may dilute the sample and cause haemolysis
• If sodium heparin is used don’t measure sodium on the same sample – danger of diagnosing hypernatraemia
• Gas exchange with the atmosphere should be minimised by leaving the specimen in the syringe and expelling any air bubbles at once. The nozzle should then be stoppered
• The specimen should be kept cool to minimise the effect of anaerobic erythrocyte metabolism on the pH
• If the specimen is required to be taken from a capillary such as in a new born infant the following precautions are required;
  • Area the specimen should be taken from should be warm and pink (ensures that it is close to arterial supply)
  • The blood should flow freely, sqeezing the skin may dilute the sample with interstitial fluid
  • The capillary tubes must be heparinised and the blood must be completely mixed
  • Tubes must be completely filled with no air bubbles
  • The ends of the tubes should be sealed immediately
• If pH and PCO₂ are not required then the assay can be performed on venous blood and urea and bicarbonate can be measured
• Total CO₂ is effectively a measure of plasma [HCO₃]
• If plasma total CO₂ is too low;
  • Exclude artificial causes such as loss of CO₂ from a small sample or a sample that has been standing for some hours
  • Reassess clinical picture;
    • Any evidence of renal dysfunction
    • Hypotension or volume depletion which might suggest poor tissue perfusion
    • A history of ureteric transplantation in to the ileum or colon
    • A drug history with specific reference to biguanides such as phenformin and acetazolamide
  • Estimate plasma urea and glucose concentration and test urine for ketones
  • Possible diagnosis;
    • Respiratory alkalosis due to overbreathing
    • Renal tubular acidosis
  • Therefore test blood pH and pCO₂ to differentiate
  • The finding of a high plasma chloride concentration suggests renal tubular acidosis
• If the plasma total CO₂ concentration is too high
  • Reassess clinical picture;
    • Is there obstruction airway disease
    • Is there a cause for potassium depletion such as non potassium sparing diuretics
    • Has bicarbonate be ingested or infused
    • Has there been severe vomiting especially if there is a history of dyspepsia which might indicate pyloric stenosis
  • Estimate plasma potassium concentration

 

 

• Respiratory and metabolic disturbances can co-exist;
  • After cardiac arrest
  • In renal failure complicated by liver disease
  • Salicylate overdose

 

Indications for chloride estimation

 

• Hyperchloraemia occurs in metabolic acidosis associated with;
  • Ureteric transplantation
  • Renal tubular acidosis
  • Actazolamide administration
• Hypochoraemia occurs in metabolic alkalosis associated with;
  • Pyloric stenosis
• Chloride estimation may help in two situations;
  • If there is a low total plasma CO₂ of obscure origin the finding of a high [Cl-] and therefore a normal anion gap, strengthens the suspicion of a renal tubular acidosis. In most other causes of acidosis the [Cl-] is normal and the anion gap is increased
  • If a patient who has been vomiting has a high total CO₂ the finding of a low [Cl-] favours the diagnosis of pyloric stenosis
• The plasma [Cl-] must be interpreted in relation to plasma [Na+], the principle cation with which chloride is associated

 

Loss of a mixture of anions and cations

 

• In this case electrochemical neutrality is maintained by loss of equivalent amounts of cation (Na) and anion (bicarbonate). The anion gap is unaffected.
• Examples where this might occur;
• Loss of intestinal secretions
• Generalised renal tubular dysfunction

Chloride ion

 

• The combination of a low plasma [HCO₃] and high [Cl] is known as hyperchloraemic acidosis and is rare. The anion gap in such cases is normal;

o       HCO₃- loss in a one to one exchange for Cl-. This occurs if the ureters are transplanted into the ileum or colon. If chloride containing fluid such as urine enters the bowel, the cells exchange some of the chloride for HCO₃-. Bicarbonate depletion may occur and large doses of bicarbonate are needed to prevent hyperchloraemic acidosis

o       Impaired hydrogen ion secretion and therefore bicarbonate production due to renal tubular disease. If the tubular ability to handle H+ is an isolated lesion, and other functions are relatively unimpaired, hyperchloraemic acidosis results

• In normal tubules most sodium is reabsorbed with chloride, the rest is exchanges for secreted H+ or K+
• If H+ secretion is impaired and yet the same amount of sodium is absorbed, then it must be accompanied by Cl- or in exchange for K+
• Therefore hyperchloraemic acidosis is often accompanied by a hypokalaemia (acidosis is normally associated with a hyperkalaemia as H+ is exchanged for K+ within cells). Two types are;

o       Renal tubular acidosis

o       Administration of carbonate dehydratase inhibitors as in the treatment of glaucoma

 

Renal tubular acidosis (RTA)

 

• Because there is no primary glomerular lesion the plasma urea and creatine are often normal
• However renal failure can develop due to calcium precipitation – in acidosis free-ionised calcium is released from bone more rapidly than usual
• Two principle forms of renal tubular acidosis;
  • Classical renal tubular acidosis is due to a distal tubular defect. The urinary pH cannot fall much below the plasma even in severe acidosis. The distal tubular cells are abnormally permeable to H+
  • RTA II defect in carbonic anhydrase impairs bicarbonate reabsorption in the proximal tubule. Loss of bicarbonate may lead to acidosis. The ability to form acidic urine when acidosis becomes severe is retained

 

Interpretation

 

• Check pH, pCO₂, HCO₃, if they are not abnormal then quit
• If pH is > 7.4 alkalosis
• If pH is < 7.4 acidosis
• What is responsible?
• If HCO₃ is shifted in the direction of the pH then it is to blame
• If CO₂ is shifted opposite to the direction of the pH then it is to blame
• If one is guilty, check the other. If it is shifted then compensation is present

 

 

 

Treatment

 

• Treat underlying cause
• Dialysis may be required for uraemia or for overdoses such as ethylene glycol, methanol and salicylate
• Bicarbonate infusion can be given if pH is < 7 but there is a danger of the following complications;
  • hyperosmolarity
  • hypernatraemia
  • volume overload
  • overshoot alkalosis
  • hypokalaemia
• Once acidosis is corrected this can result in hypokalaemia requiring supplementation
• Rapid correction of a metabolic alkalosis may require administration of ammonium chloride
• Respiratory dysfunction which will impair compensatory CO₂ elimination should be treated

 

 

This entry was posted on Friday, October 19th, 2007 at 10:55 am and is filed under Chemical Pathology. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.