Acid-base balance Flashcards
What is the normal serum pH of the body?
7.35-7.45
How does pH relate to [H+]?
pH = -log10 [H+]
What are the main sources of acid in the body?
OXPHOS (CO2)
Metabolism of dietary proteins (non-volatile acids, H2SO4 and HCl)
What are the main mechanisms governing serum pH?
ICF and ECF buffering systems
Respiratory system
Kidney
What is a buffer?
A solution that minimises changes in [H+] ie. pH
Which buffer systems are present in the ICF and ECF?
bicarbonate system
phosphate system
protein buffers (e.g. Hb)
What is the relationship between pK and pH?
when pH=pK
[acid] = [base]
What is pK?
equilibrium constant
When is a buffer most successful?
1 pH either side of its pK
What is the Henderson-Hasselbach equation?
CO2 + H2O-> H2CO3
-> H(+) + HCO3(-)
What is the relative molar ratio between HCO3- and CO2?
20 HCO3- : 1 CO2
Which buffer is the more suited (in terms of pK) to the blood pH?
phosphate buffer
Why is bicarbonate buffer system more readily used in the body?
CO2 and HCO3- the two critical components of the buffer are independently regulated and replenished
What is the pK of the bicarbonate buffer system?
pK = 6.1
How do the kidneys work in acid-base control?
excretion of H+ in tubular fluid
Reabsorption/secretion of HCO3-
ammonia, phosphate and bicarbonate buffer systems at play within tubular fluid
How is bicarbonate handled by the kidney?
HCO3- cons reabsorbed from the PCT
AND kidney generates new bicarb. which is released at a controlled rate
How do thiazide diuretics work?
Inhibition of carbonic anhydrase (dependent on h+ influx from Na+H+ ATPase pump)
Where does de novo synthesis of HCO3- occur?
in the PCT
For every 1xbicarb reabsorbed from the tubular fluid, one is returned to the blood
How much bicarbonate is reabsorbed at the PCT?
85-90%
Where does acid-balance occur in the nephron?
In the intercalated cells of the late DCT and collecting duct
What is the composition of the fluid in the DCT?
[HCO3-] is low
H+ reacts with other buffers
What is the role of the H+-ATPase pump in the DCT?
It pumps H+ against its concentration gradient into the tubule (secretion)
Which cells is the Cl - HCO3- exchanger predominantly found in?
intercalated cells
How does the phosphate buffer system work in the kidney?
H+ ions are mopped up by HPO4(2-) to make H2PO4(-)
H2PO4(-) is then excreted in urine
This occurs in the tubular lumen (extracellular to the intercalated cells)
The H+-ATPase pump which pumps out H+ ions from intercalated cells into the tubular lumen is sensitive to which RAAS hormone?
Aldosterone
What is the pK of the phosphate buffer system?
6.8
What is the breakdown reaction of glutamine in the kidney?
glutamine -> a-ketoglutarate + NH3
Which enzyme catalyses the breakdown of glutamine?
Glutaminase
How is ammonia excreted from the body?
urinary excretion
As ammonium salts
e.g. NH4+
What are the main ways by which acid-base balance is achieved by the kidney?
- reabsorption of bicarbonate
- acidification of phosphate
- Ammonia secretion
What are the 3 mechanisms by which plasma pH is corrected?
- intra- and extra-cellular buffering
- Respiratory compensation of pCO2 (in ECF)
- Renal adjustment of [bicarbonate] (in ECF)
What are pH changes in plasma called? What types are there?
Acidosis: pH<7.4
Alkalosis: pH>7.4
Respiratory or Metabolic
Defined depending on the causative event, initiating disturbance
What is the caveat with compensation for acid-balance disturbance?
Perfect compensation is not possible
UNLESS you are actively correcting the underlying cause as well
How does the kidney detect changes in pH balance?
Some candidate molecular pH sensors: GRP4, ErbB1/2 kinases, bicarbonate-stimulated adenylate cyclase (sAC)
But no one master pH sensor
What is the role of the respiratory system in acid-base balance?
chemosensitive centre in medulla of brainstem - regulates respiration
monitors CO2 levels as indirect measure of pH in CSF and therefore plasma
(Indirect because H+ cannot cross BBB)
Where are the peripheral chemoreceptors located?
Aortic arch
Carotid bodies
What happens when medullary chemoreceptors detect a reduction in CSF pH?
Increased respiration rate
(compensatory hyperventilation)
-> hypocapnia (as more CO2 is breathed off)
-> normal plasma pH is restored
What are common causes of metabolic acidosis?
severe sepsis: lactate
DKA: ketone bodies such as 3-hydroxybutyrate
Diarrhoea: loss of bicarbonate from GI tract
What is the chemical pathology underlying metabolic acidosis?
increased [H+]
OR
reduced [HCO3-]
in ECF
What equations connects [H=], [HCO3-] and pH?
pH = pK + log([HCO3-]/[H+])
What is the main function of compensation in acid-base balance?
returns dysregulated ECF pH to within normal range
What are the main mechanisms that are employed to correct acid-base imbalance?
kidney: increased H+ and NH4+ secretion, increased neobicarbonate synthesis and reabsorption
Lung: change in respiratory rate to modulate pCO2
ICF+ECF buffering: HCO3- used up to mop up excess H+
H+ may remain high after this
What are the main causes of metabolic alkalosis?
excessive diuretic use:
chronic loss of electrolytes (e.g. Cl-, Na+, K+) -> causes increased H+ secretion
Vomiting: loss of H+ from GI tract
Ingestion of alkaline antacids
Hypokalaemia
What are common causes of respiratory acidosis? What are the compensatory mechanisms?
causes:
emphysema, asthma, COPD
compensation:
increased plasma HCO3-
acidic urine -> increased H+ excretion
What are common causes of respiratory alkalosis? What are the compensatory mechanisms?
causes:
hyperventilation
compensation:
reduced plasma HCO3-
alkaline urine -> increased HCO3- excretion and reduced H+ secretion
reduced pCO2 loss mediated by reduced respiratory drive
How are pH, [H+] and [HCO3-] affected in the different types of acid-base imbalance?
respiratory acidosis:
reduced pH
increased pCO2
increased HCO3-
respiratory alkalosis:
increased pH
reduced pCO2
normal or reduced HCO3-
metabolic acidosis:
reduced pH
normal pCO2
reduced HCO3-
Metabolic alkalosis:
increased pH
normal CO2
increased HCO3-
What is simple acid-base disorder?
results from a single primary disturbance
WITH normal physiological compensation
What is mixed acid-base disorder?
Occurs in seriously unwell patients
2 or more primary disorders of pH imbalance occurs simultaneously
Net affect may be additive = extreme alteration to pH
e.g. metabolic acidosis + resp. acidosis
or may have opposing effects causing no net difference in pH
e.g. metabolic acidosis + respiratory alkalosis
What is the Siggaard-Andersen in vivo nomogram?
Diagram which predicts behaviour of whole body during pH imbalance and acid-base disturbance
PLUS body’s response to therapeutic intervention
What is an anion gap in acidosis?
High anion gap metabolic acidosis is a form of mixed acid-base balance disorder
high anion gap is when > 12mEq/L
(measure of serum ion concentrations)
Typically caused by excess acid production in body. Can also be caused by MeOH ingestion or aspirin OD
What are the causes of high anion-gap metabolic acidosis?
Carbon monoxide, cyanide, congenital HF Aminoglycosides Theophylline, toluene (glue) Methanol Uraemia DKA, alcoholic KA, Starvation KA Paracetamol OD, phenformin, paraldehyde Iron, Isoniazid, inborn errors of metabolism Lactic acidosis EtOH, ethylene glycol Salicyclates/Aspirin
What is Isoniazid?
Antibiotic
used in Tx of TB
Often used in combo with rifampicin, pyrazinamide and streptomycin or ethambutol for active TB
