Explain how the acid-base balance of blood is maintained. Discuss respiratory vs.

metabolic
pH disturbance, ABG interp.

Acid-Base Balance
Principles
1. Metabolism = acidosis. This acid needs to be secreted, to maintain optimum pH for
enzyme activity.
2. A weak acid/base is one in which there is a delicate equilibrium between the weak
acid/base and its constituents:
a. A weak acid is one which does not fully ionise from its acid form to a H + ion.
b. A weak base is one which does not fully ionise from its base form to a OH - ion.
[ base ]
3. pH (i.e. pH is directly proportional to concentration of base divided by
[acid]
concentration of acid (Henderson-Hasselbalch equation). If acid concentration rises, pH
drops, and vice versa.
4. Buffer = an aqueous substance which can resist changes in pH despite the addition of
acidic/basic solution.

Maintaining a balance
MECHANISMS

Lungs Kidneys
Circulation
Reacts over Reacts over Reacts
hours to
instantly
days
minutes
Buffers
The three main buffer systems to remember when it comes to regulating blood pH are:
(1) bicarbonate system; (2) phosphate system; and (3) plasma
protein system.

Bicarbonatei
Although this buffer system controls blood pH, its main
constituents are synthesised in the liver and kidney.
Carbonic acid (H2CO3) is formed when CO2 and H2O
combine, in a reaction catalysed by carbonic anhydrase.
Le Chteliers system dictates that if there is any stress (e.g. increased CO 2) to an
equilibrium, the equilibrium shifts in the opposite direction to rectify it. Increased CO 2
would push the equilibrium towards the right, favouring more production of carbonic
acid and its constituent H+ and carbonate ion.
o In response to an increase in CO2 concentration, chemoreceptors in the medulla
would excite the respiratory centre, thus increasing the respiratory rate and
eliminating more CO2.

Kidney: bicarbonate reabsorption

85-90% of bicarbonate resorption occurs in the cells of the proximal convoluted tubule.
Explain how the acid-base balance of blood is maintained. Discuss respiratory vs. metabolic
pH disturbance, ABG interp.
It is vital for reabsorption to occur, as plasma HCO 3- (and
by extension blood pH) is maintained through this
process.
Circulating in the blood, H+ and bicarbonate form
carbonic acid. This unstable acid dissociates into H 2O and
CO2 (thanks to carbonic anhydrase on the luminal brush
border).
CO2 moves into the tubular cell, where it recombines with
H2O into carbonic acid (under the action of carbonic anhydrase enzyme). The acid
dissociates back into H+ and bicarbonate.
H+ is pumped into the PCT lumen, due to the Na +-H+ transporter. This restarts the cycle.
The carbonate ions, however, are diverted out of the tubular cell into the circulation, via
a transporter on the basolateral membrane.
All the while, Na+ travels from lumen to cell to capillary, allowing H + to be pumped into
the lumen, and K+ into the cell.

Kidney: H+ excretion
Intracellular K+ is exchanged for Na+ in the principal cell.
Aldosterone enters the cell, stimulating H+ secretion (into lumen)
and opening Na+ channels in the apical membrane. There is an
increase in Na+-K+-ATPase activity.
As such, Na+ moves from lumen, to cell, to interstitium/blood. The
end result is a negative charge in the lumen. K + goes down the
electrochemical gradient, into the lumen. In doing so, it does the
reverse of Na+.
Aldosterone also activates H+-ATPase in the alpha-intercalated
cell, increasing H+ movement out of the lumen. Once urinary pH
+
drops to 4.0-4.5, H secretion ceases in the intercalated cell. However, filtering of
titratable acids* (e.g. phosphoric acid) out of lumen helps raise the pH, which allows
the intercalated cells activity to continue. The acid picks up an H + ion, and is secreted
in the urine. The H+ ion in question arises from the re-association of H 2O and CO2.

Production of new HCO3

This is thanks to phosphate and ammonia buffer systems.
Ammonia system: in the PCT, glutamine in the cell is metabolised into NH 3 and H+, with
NH3 binding with luminal H + (secreted by the collecting duct) to form ammonium (NH 4+).
Ammonia synthesis is triggered by systemic acidosis, and hypokalaemia.
Phosphate system: see below.

Phosphateii
This operates in the internal fluid of all cells. On one side is H 2PO4- (dihydrogen phosphate); on
the other are H+ ions and H2PO42- (hydrogen phosphate).
H2PO4-(aq) H+(aq) + HPO42-(aq)
The phosphate buffers role in acid-base balance in the blood is minimal, due to the relatively
small quantities of the various players in the equilibrium.

Plasma proteiniii
Most proteins have the capacity to act as buffers. This is due to having two tails a
positively charged amino group (R-NH 3+) and a negatively charged carboxyl group (R-COO -).
As these can bind to both OH- and H+ respectively, they act as potent buffers. It is estimated
plasma proteins account for 2/3 of the buffering power of the blood.
Explain how the acid-base balance of blood is maintained. Discuss respiratory vs. metabolic
pH disturbance, ABG interp.
Balance disturbance
Respiratory alkalosis
Causes
Central causes
o Head injury, stroke, anxiety
Hypoxaemia
o Respiratory stimulation via peripheral chemoreceptors
Pulmonary causes
o Pulmonary embolism, pneumonia, asthma, pulmonary oedema
Iatrogenic
o Excessive controlled ventilation

Compensation
Rapid cell buffering
Decrease in net renal secretion of: hydrogen, titratable acids, ammonia production, and
ammonium excretion.

Correction
If cause is over-ventilation due mechanical ventilation, reduce settings.
If due to anxiety, provide reassurance and potential treatment.

Metabolic alkalosis
Causes
1. Initiating process
a. Alkali gain in ECF: exogenous (IV NaHCO3), or endogenous (ketoanion
metabolism)
b. Loss of H+ from ECF: diuretics, vomiting, NG suction
2. Maintenance process
a. Chloride depletion: vomiting, diuretics
b. Potassium depletion: hyperaldosteronism
c. Reduced GFR
d. ECF volume depletion

Compensation
Hypoventilation

Correction
Treat cause of initiating process
Correct factors involved in maintenance, e.g. give chloride
Explain how the acid-base balance of blood is maintained. Discuss respiratory vs. metabolic
pH disturbance, ABG interp.
Respiratory acidosis
Causesiv
Inadequate alveolar ventilation MAIN CAUSE
o Central respiratory depression (CNS): opiates, infarct, tumour, trauma, polio
o Neuromuscular disorders: Guillain-Barr, myasthenia gravis, toxins, myopathy
o Lung/chest wall defects: chest trauma, pneumothorax, pulmonary oedema,
ARDS, restrictive lung disease, aspiration
o Airway disorders: obstruction, spasm, asthma
o External factors: inadequate ventilation
Overproduction of CO2
o Hypermetabolic disorders: malignant hyperthermia
Increased intake of CO2
o Rebreathing of CO2-containing expired gas
o Addition of CO2 to inspired gas
o Insufflation of CO2 into body cavity

Compensation
Protein buffer (more so in acute)
Renal loss of bicarbonate (more in chronic disease state)

Correction
Drop in pCO2 causes respiratory alkalosis. Also causes hypoxaemia (due to respiratory
drive). Hypoxaemia can damage tissue. Therefore, target hypoxaemia first, with
improved oxygen delivery.

Metabolic acidosis
Causes
Ketoacidosis diabetic, alcoholic, starvation
Lactic acidosis
Renal failure acidosis with acute renal failure
Toxins methanol, salicylates
Renal causes renal tubular acidosis, carbonic anhydrase inhibitors
GIT causes severe diarrhoea, drainage of pancreaticobiliary excretions, small bowel
fistula
Other causes recovery from ketoacidosis, addition of HCl/NH 4Cl

Compensation
Hyperventilation

Correction
Emergency ABCDE, treat cause, replace fluid/electrolyte loss
While kidney recovers, liver helps with accelerating bicarbonate synthesis needed to
correct acid-base balance.
Explain how the acid-base balance of blood is maintained. Discuss respiratory vs. metabolic
pH disturbance, ABG interp.

ABG interpretation: recap

Ste Value Normal Acidot Alkalot Significance
p range ic ic
1 pH 7.35-7.45 <7.35 >7.45 Based on this you can assess whether the
patient is overall acidotic/alkalotic. If the pH is
within normal range, this may mean there is
full compensation by respiratory and metabolic
centres. If pH is outside the normal limits, but
there is evidence of compensation, we consider
this partial compensation.
2 PaCO 35-45 >45 <35 This gives an indication of the respiratory state.
2 If it is aligned with the pH, this suggests there
is a respiratory cause for the pH change. If it
does not, this may indicate some form of
compensation.
3 [HCO 22-26 <22 >26 This is an indicator of metabolic state. Same as
-
3] PaCO2 in that, if it matches the pH, metabolic
acidosis/alkalosis is the primary mechanism.

Example
An 82-year old lady is brought into your clinic. She is hyperventilating, and muttering about
her cat at home. As part of your metabolic screen, you perform an ABG on her (successful on
first go!). The results are as follows. I have intentionally shrunk the size of the words in the
working out section, but feel free to enlarge them.

pH: 7.34 [7.35-7.45]

PaCO2: 32 [35-45]
[HCO3-]: 17 [22-26]

1. What is your interpretation of her ABGs?

2. What may be the cause of them?
3. What is your approach in treating this patient?
4. Have you registered to vote yet?

WORKING OUT
1. Ph is low, and so is HCO3-, suggesting the primary mechanism is a metabolic acidosis. There is a respiratory alkalosis (see PaCO 2), suggesting compensation. However, as Ph is not within normal limits, this compensation is only partially effective.
2. The main potential cause is a ketoacidosis, either diabetic, alcoholic, starvation related. It may also be due to renal tubular acidosis, or severe diarrhoea.
3. It is important to treat the underlying cause, while also replacing any loss of fluids/electrolytes. The liver will gradually help the kidney in producing more bicarbonates, and the blood Ph should recover. Important to monitor ABG and vitals regularly.
4. If you have, great! If not, heres the link: https://www.gov.uk/register-to-vote.

For more practice on ABG interpretation, try ABG ninja (https://abg.ninja/abg).

i Khan Academy. (2017). Khan Academy. [online] Available at:
https://www.khanacademy.org/test-prep/mcat/physical-sciences-practice/physical-
sciences-practice-tut/e/the-role-of-the-bicarbonate-buffer-system-in-regulating-blood-
ph [Accessed 12 May 2017].

ii Chemistry.wustl.edu. (2017). pH Buffers in the Blood. [online] Available at:

http://www.chemistry.wustl.edu/~edudev/LabTutorials/Buffer/Buffer.html [Accessed 12
May 2017].

iii Oerpub.github.io. (2017). Acid-Base Balance. [online] Available at:

http://oerpub.github.io/epubjs-demo-book/content/m46409.xhtml [Accessed 12 May
2017].

iv Anaesthesiamcq.com. (2017). 4.2 Respiratory Acidosis - Causes. [online] Available

at: http://www.anaesthesiamcq.com/AcidBaseBook/ab4_2.php [Accessed 12 May
2017].