Acid-base balance Flashcards
What is normal plasma pH?
7.35-7.45
How are acids produced?
In the course of metabolism
- e.g. oxidation of carbohydrates, most amino acids produces CO2
- lactic acids during anaerobic glycolysis
- metabolism of AAs (sulfur-containing cysteine = H2SO4)
- alkali lost in faese
What different levels is acid-base balance regulated at?
- buffering systems within extracellular (and to a certain extent intracellular) fluids
- lungs
- kidneys
Which is the first level of acid-base regulation to respond to a change in pH?
Chemical buffer systems - act within seconds
What do buffers do?
Bind H+
Why are intracellular buffers important? Give examples
Since changes in extracellular pH cause changes in intracellular pH (largely because CO2 can rapidly diffuse across cell membranes), intracellular buffers are needed – important examples are haemoglobin, other proteins, and phosphates
What is the most powerful extracellular buffer?
Bicarbonate buffer system
Describe bicarb buffer system using an equation
H2O + CO2 → H2CO3 → H+ + HCO3-
Give the equation for the equilibrium coefficient for the bicarb buffer equation
K = [H+][HCO3-]/[CO2]
What can we derive from K = [H+][HCO3-]/[CO2]?
Henderson Hasselbalch equation, where 6.1 = the pK and 0.03 = the solubility of CO2 in the blood
pH = 6.1 + log{[HCO3-]/(0.03 x pCO2)}
What does the Henderson Hasselbalch equation show us?
the ratio between [HCO3-] and pCO2 determines the plasma pH
Describe the mechanism underlying the bicarbonate buffer system
When acid is added to the blood (i.e. the H+ concentration increases), the HCO3- accepts H+, forming carbonic acid, which is then converted into H2O and CO2 (catalysed by carbonic anhydrase). The CO2 is eliminated through the lungs, and so the [HCO3-]/pCO2 ratio has been brought back towards normal
Conversely, when the H+ concentration decreases, the carbonic acid dissociates to supply H+. The ventilation rate will then decrease, retaining CO2 and attempting to normalise the [HCO3-]/pCO2 ratio.
What is the second line of defence for changes in plasma pH?
Lungs
How can the lungs affect ph?
alter ventilation rate to increase/decrease. CO2 removal in acidosis/alkalosis respectively
What detects changes pCO2 and pH? What do these do?
Peripheral and central chemoreceptors
Input to the respiratory centre (response in 3-12 minutes)
Describe peripheral chemoreceptors
carotid bodies (changes in blood oxygen and CO2, pH) and aortic bodies (CO2 and O2), stimulate respiratory centre in medulla which sends nervous impulses to the external intercostals and the diaphragm via the intercostal nerve and the phrenic nerve to incease breathing rate and the volume of lungs durng inhalation
Describe central chemoreceptors
located on the ventrolateral surface of the medulla and detect changes of pH of the CSF - pH and CO2
On what time frame do the kidneys act to respond to a change in pH?
Hours - days
How much acid must be secreted to reabsorb HCO3-?
4390mEq
to recover 4320mEq passively filtered and 70mEq to buffer net acid production
How much HCO3- reabsorbed in the PCT?
~80%
Describe HCO3- reabsorption in PCT
See OneNote for diagram
- mainly driven by Na gradient → Na/H anti porter and H+/ATPase
- Can leave via NBCe1
Where does regeneration of HCO3- to replace the 70mEq that neutralises the daily non-volatile acid load occur?
Mainly in the CD
Draw a diagram of HCO3- reabsorption in the collecting duct
OneNote
- type A intercalated cells
- H+ secreted across the membrane via V-type H+-ATPases and HKA (H+/K+echange)
Draw a diagram of HCO3- secretion in the CD
OneNote
What happens when H+ is secreted into the tubular fluid?
Combines with urinary buffers:
phosphate or ammonia
When is HCO3- secretion possible? What is this mediated by?
Alkalosis
Type B intercalated cells
What is an additional important mechanism by which the kidney contribute to the maintenance of acid-base balance?
Through synthesis and excretion of ammonium ions
Ammoniagenesis occurs mainly in the PCT - generated ammonium secreted and HCO3- allow to re-enter the bloodstream
Produced through metabolism of glutamine
Glutamine → glutamic acid (glutaminase)
Glutamic acid → α-ketoglutarate (glutamate dehydrogenase)
Each step yields a molecule of NH4+ and HCO3-
HCO3- leaves basolaterally
NH4+ leaves cell, substituting for H+ in the Na+/H+ antiporter
Much of the secreted NH4+ from the PCT is reabsorbed in the TALH, substituting for K+ in NKCC2 (as well as the +ve transepithelial voltage means that there is paracellular absorption of NH4+)
The NH4+ reabsorbed by the TALH accumulates in the medullary interstitium. From there it is secrered into the tubular fluid by the collecting duct
NH3 which diffuses into the collecting duct through Rh glycoproteins from medullary interstitium becomes trapped as it is protonated in the acidic tubular fluid (increased diffusion trapping as pH falls luminally). This leads to the excretion of the NH4+.
Important as should the NH4+ instead be reabsorbed, it is neutralised to produce urea (consuming HCO3-) in the process, meaning it doesn’t result in the net excretion of acid
What does the Henderson-Hasselbalch model not account for?
the intake and output of all substances that can affect [H+]
What is an alternative to the Henderson-Hasselbalch model? Describe it.
Stewart model
based upon three ‘independent’ variables that determine pH: the strong ion difference (SID), the total weak acids ([ATot]) and pCO2
What are strong ions?
hose that fully dissociate in plasma, including sodium, potassium, and chloride, thus the SID can be calculated by subtracting the sum of all the strong anions from the sum of all the strong cations:
SID ≈ [Na+] + [K+] – [Cl-]
What is the SID approximately equal to?
Because SID is dependent on plasma electrolyte concentration, it is largely controlled by the kidneys, and under normal physiological conditions is approximately equal to 40mEq/L
Describe conc of weak acid from Stewart model
[ATot] is the concentration of weak acid, composed in the plasma mainly of albumin and phosphate
It can therefore be defined as the total protein in the blood and as such, the liver and haematopoietic system are crucial in its control
What is pCO2 controlled by?
Lungs
What can we model acid-base disturbances using?
Davenport diagrams
How may deviations from normal pH on a Davenport diagram be compensated for?
Respiratory deviations are compensated for by renal mechanisms, whereby plasma [HCO3-] is either increased or decreased (in acidosis or alkalosis respectively), which helps to return plasma pH to normal
Comparatively, the compensatory response for metabolic deviations is mediated by alterations in the rate of ventilation, thereby increasing or reducing pCO2 to bring about a change in plasma pH of the opposite nature
Draw a Davenport diagram
OneNote
Draw the table expected changes mediated by acid-base disturbances
OneNote
What us metabolic acidosis caused by?
Low [HCO3-]
What may cause metabolic acidosis?
1- Hyperkalaemia 2 - Intense exercise 3 - Diarrhoea → loss of HCO3- 4- Diabetic ketoacidosis 5 - Renal tubular acidosis → where the kidney fails to either reabsorb or regenerate HCO3-
How does the body compensate for metabolic acidosis? Give example of this
Respiratory compensation
Characteristic Kussmaul breathing n DKA -hyperventilation
What could be used to neutralise metabolic acidosis?
- sodium bicarbonate
What is respiratory acidosis characterised by?
Characterised by high pCO2 and a compensatory high [HCO3-]
What may cause respiratory acidosis?
- Reduced ventilation (e.g. kyphoscoliosis)
- Opoid analgesics or damage to respiratory centre
- COPD or asthma
Treatment of respiratory acidosis
mechanical ventilation, however it may be possible to treat the cause of the disturbance – for example the administration of salbutamol (a β2-agonist, hence bronchodilator) to asthmatics.
how may the body increase [HCO3-] to compensate for respiratory acidosis?
Upregulation of ammonia genesis (increasing formation of NH3 buffer)
Increased expression of apical H+/K+ ATPase in type A intercalated cels in order to increase H+ secretion and thus increase HCO3- reabsorption
What is metabolic alkalosis characterised by?
Elevated [HCO3-]
What may cause metabolic alkalosis?
- vomiting (loss of HCl)
- hyperaldosteroism or Conns (upregulation of Na+/K+ ATPase, ENac, increase Na+ reabsorption and K= excretion → hypokalaemia → H+ secreted in order to attempt to take up K+)
- diuretics
Describe the compensation that occurs with metabolic alkalosis?
Respiratory
Central chemoreceptors detect increased pH and cause a decreased ventilatory drive → hypoventilation
This raises levels of pCO2 in the body, which is used to form the carbonic acid intermediate, thus decreasing pH
This hypoventilation however may cause hypoxia, which would stimulate the peripheral chemoRs to increase ventilatory drive, nullifying any effects of the alkalaemia on ventilatory drive
This is thought to account for the variability in patients’ pCO2 levels in respiratory alkalosis
This is important clinically as patients presenting with hypoxaemia and hypercapnia may be incorrectly diagnosed with respiratory failure, with the underlying respiratory alkalosis going undetected
Treatment of metabolic alkalosis
oral ammonium chloride
What is respiratory alkalosis characterised by?
low pCO2
What is respiratory alkalosis caused by?
hyperventilation – can occur due to anxiety (in which there is increased respiratory drive) or ascent to high altitude, as hypoxia stimulates peripheral chemoRs which increase ventilatory drive as a result
This causes more CO2 to be “blown off”, decreasing [H+] of the plasma
How may compensation for respiratory alkalosis occur?
Long-term compensation can occur in the kidneys through the activation of B-type intercalated cells, which have the reverse orientation to type A intercalated cells, and so secrete HCO3- and retina H+, causing elevated levels of [HCO3-]
What may be used for the treatment of respiratory alkalosis
carbonic anhydrase inhibitors (e.g. acetazolamide), are often used in the treatment of altitude sickness. These inhibit the uptake of HCO3- in the kidney, thereby helping to correct alkalosis.
