51.5 Acid-Base Balance Flashcards
What does acid-base balance refer to?
The processes that maintain the hydrogen ion concentration of body fluids within its normal limits
What are the three main factors that determine pH?
- Difference between total conc of strong cations (e.g. Na+) and total conc of strong anions (e.g. Cl-)
- Quantity and pKa of weak acids present (e.g. phosphate ions or ionisable groups on proteins)
- Partial pressure of CO2
What are the 3 pH maintenance mechanisms?
1: Ventilatory mechanisms
2: Buffers
3: Renal mechanisms
What is the main EC buffer?
Bicarbonate
What is the Henderson-Hasselbach equation?
Are buffers short or long term? Why?
Temporary measure
*Limited
*Act in a timescale of seconds
What are the IC buffers?
Haemoglobin, other proteins, phosphate.
What is the ventilatory maintenance mechanism?
Acidotic –> hyperventilation (increase CO2 removal -> decrease blood pH)
Alkalotic –> hypoventilation
Generally greater response to acidosis (don’t want to stop breathing)
How is the pH of blood sensed?
By chemoreceptors in the carotid body in the aortic arch and by central chemoreceptors in the medulla. Send signal via glossopharyngeal nerve to respiratory centres in medulla –> in/decreased firing down phrenic nerve to diaphragm/ intercostal nerve to intercostal muscles depending.
less firing if less acidic.
What are the chemoreceptors sensitive to?
CO2 and directly to pH (increased non-volatile acids)
What is the timescale of the ventilatory mechanism?
Minutes (5-15)
What is the renal mechanism? What is the timescale?
Hours to weeks
Adjust resorption/ secretion/ regeneration of bicarbonate and H+
What are the 3 steps of pH maintenance that happen in the kidney?
- Reabsorbing filtered load of bicarbonate
- Excretion of non-volatile acids into tubule
- Helps regenerate bicarbonate that has been buffering non-volatile acids in blood.
Where and how is the filtered load of bicarbonate reabsorbed?
What do type A intercalated cells facilitate?
Type a intercalated cells facilitate the elimination of acids and regeneration of bicarbonate.
What happens in type A intercalated cells?
*CO2 hydrated by CA: CO2 + H20 –> HCO3- + H+
* HCO3- exits via basolateral membrane into blood (recovered)
* H+ secreted by ATPase into lumen where it is buffered by urinary buffers (phosphate + ammonia) trapping it in the urine where it can be excreted.
By what 2 processes is bicarbonate regenrated?
*Regeneration of bicarbonate in type A intercalated cells when CO2 is hydrated by CA.
*During production of ammonia in the proximal tubule
What is the role of Type B intercalated cells?
*Bicarbonate secretion (apical membrane has bicarbonate/Cl exchangers)
What happens to type B intercalated cells in alkalosis?
*Can increase the number of transporters
What are the two types of pH disturbances?
Respiratory and metabolic
What causes metabolic acidosis? (1)
Increased amounts of non-volatile acids
What causes metabolic alkalosis? (1)
Increased amounts of non-volatile bases
What causes respiratory acidosis? (1)
Failure to remove CO2 from the blood (alveolar hypoventilation)
What causes respiratory alkalosis? (1)
Fall in plasma pCO2 (alveolar hyperventilation)
What is the list of causes for metabolic acidosis?
- Endogenous acid loading (diabetic ketoacidosis)
- Exogenous acid loading (methanol ingestion)
- Loss of base from gut (diarrhoea)
- Impaired renal acid secretion (renal tubular acidosis)
What is the list of causes for metabolic alkalosis?
- Loss of gastric juice (vomiting)
- Excessive base ingestion
- Aldosterone excess (increased salt retention, so increased bicarbonate reabsorption and acid excretion)
- Alkaline diuresis therapy (for drug poisoning)
What is the list of causes for respiratory acidosis?
- Impaired ventilation, due to obstruction (asthma, COPD)
- Impaired gas exchange (V/Q mismatch)
- Decreased respiratory drive (drugs)
- Inhalation of CO2
- Neuromuscular problems (difficult to breathe)
What is the list of causes for respiratory alkalosis?
- Hypoxia
- Increased respiratory drive (cerebrovascular disease)
- Hepatic failure (stimulates respiration)
- Drugs, poisons
What is the summary for two single values each causing respiratory or metabolic pH disturbances?
Respiratory: pCO2
Metabolic: HCO3-
What are volatile acids? Give examples.
Acids that can be lost to the air so are removed by the lungs
- CO2, acetone
What is the anion gap? What can it tell us?
Whether metabolic acidosis is due to increased acid or decreased bicarbonate.
Na+ = K+ - Cl- - HCO3-
Acidosis with a high anion gap indicates more acid in blood than normal (>12)
If the anion gap is normal, indicates metabolic acidosis is due to bicarbonate loss.
What can cause a large anion gap? (>20mmol/L)
- Lactate
- Ketones
- Toxins
- Renal failure
What can cause a small anion gap? (<7mmol/L)
Low albumin
What are non-volatile bases? Give examples.
Bases produced from sources other than CO2 and not excreted by the lungs
- such as glutamate, aspartate, citrate, acetate
What are non-volatile acids? Give examples.
Acids produced from sources other than CO2 and not excreted by the lungs
- such as lactic acid, acetoacetic acid, β-hydroxybutyrate
(think metabolism)
What are some pathological consequences of pH becoming too high/alkaline?
7.5 - Tetany (low Ca2+), fainting (low cerebral blood flow)
7.6 - Hypokalaemia, cardiac dysrhythmias
7.7 - Haemoloysis
7.8 - Death
What are some pathological consequences of pH becoming too low/acidic?
7.3 - Hyperkalaemia
7.2 - Reduced cardiac contractility
7.1 - Bone resorption
7.0 - Cerebral palsy in newborn
6.9 - Death
What are the four steps of physiological changes when pH decreases from 7.4 to 7.35?
- Hyperventilation
- Systemic vasodilation
- Pulmonary vasoconstriction
- Renal ammoniagenesis
What are the four steps of physiological changes when pH increases from 7.4 to 7.45?
- Hypoventilation
- Systemic vasoconstriction
- Pulmonary vasodilation
- Renal bicarbonate secretion
What is the normal range of arterial blood pH?
7.35-7.45
When faced with alkaline challenge (such as vomiting), how does the kidney respond?
- Decreases net acid excretion - reduces excretion rates of titratable acid and NH4+
- So less new HCO3- formed
What are Davenport diagrams?
- Plots of [HCO3-] against pH at different PCO2 values
- They allow us to see the effects of different metabolic disturbances
How do each type of acidosis and alkalosis appear on a Davenport diagram?
Show on a Davenport diagram how each type of acidosis and alkalosis is corrected. How fast does this happen?
- Metabolic disturbances are corrected by respiratory changes -> This is FAST
- Respiratory disturbances are corrected by metabolic changes -> This is SLOW
Describe how you can interpret blood gases to identify the various types of alkalosis and acidosis.
- Check the pH to see if it is acidosis or alkalosis
- Check to see if this can be explained by the pCO2 level
- If yes, then it is respiratory acidosis/alkalosis
- If not, then it is metabolic acidosis/alkalosis
Give the normal values for arterial and venous blood for these:
- pH
- PCO2
- PO2
- HCO3-
- Base excess
What is base excess and why is it important?
[IMPORTANT]
- There may be situations where there is both a respiratory acidosis AND metabolic acidosis simultaneously
- In these situations, the metabolic acidosis will only be revealed once the respiratory acidosis is corrected
- In these situations, the base excess is a way of identifying this right at the start
- How it is done:
- “Ventilate” a sample of blood
- Titrate to assess the acidity
- Base excess is a measure of this
What are the consequences of chronic acidosis and alkalosis?
[IMPORTANT]
Chronic acidosis:
- Loss of bone density -> Due to acid buffering
- Muscle wastage -> Due to increased protein catabolism Acid buffering leads to loss of bone density, resulting in an increased risk of bone fractures
Chronic alkalosis:
- Neuromuscular irritability + Tetany
- Abnormal heart rhythms (usually due to accompanying electrolyte abnormalities such as low levels of potassium in the blood)
What is the total amount of H+ that must be secreted into the tubular fluid per day by the kidneys?
- 4320mEq/day is needed to recovered filtered HCO3-
- 70mEq/day is needed to regenerate HCO3- that was used in buffering NVAs
So the total is 4390mEq/day (equal to 4390mmol/day).
Where does H+ secretion into the tubular fluid occur? [IMPORTANT]
All along the renal tubule.
What are the roles of the different segments of the nephron in acid-base homeostasis?
- Glomerulus
- Involved in filtering out almost all HCO3- from the blood
- Proximal tubule
- Involved in 80% of HCO3- reabsorption into the blood
- Not really involved in HCO3- regeneration
- Ammoniagenesis (ammonia is used as a urinary buffer)
- Loop of Henle
- Involved in 15% of HCO3- reabsorption into the blood
- Distal tubule and collecting duct
- Residual HCO3- recovery
- Involved in HCO3- regeneration
What determines the fate of H+ when it is secreted into the renal tubule?
- If the H+ reacts with filtered HCO3-, the bicarbonate is reabsorbed (4.3mol day-1)
- If the H+ reacts with a urinary buffer, it is excreted. This is used in regenerating bicarbonate. (70mmol day-1)
What can mutations in transport proteins involved in the reabsorption and regeneration of HCO3- in the tubule, as well as in carbonic anhydrase, result in?
Renal tubular acidosis -> This is acidosis of the plasma, NOT the tubular fluid
How much H+ is generated in the regeneration of HCO3- in type A intercalated cells of the collecting duct and distal tubule?
Equivalent to the amount of NVA buffered by HCO3- in the plasma.
Describe the location and mechanism for ammoniagenesis. [IMPORTANT]
Occurs in the cells of the proximal tubule:
- Glutamine is converted to glutamic acid by glutaminase
- Glutamic acid is converted to α-ketoglutaric acid by glutamate dehydrogenase
- Both of these steps yield: 1 NH3 and 1 HCO3-
What are urinary buffers?
- Buffers other than HCO3- that are found in the renal tubule
- They react with the H+ that is secreted into the renal tubule lumen at the collecting duct and distal tubule
- They are used to allow large amounts of free H+ secretion into the tubular fluid without unsustainable drops in urinary pH
Describe how ammoniagenesis is involved in acid-base balance. Where does it occur? [IMPORTANT]
- Ammoniagenesis is upregulated when plasma pH is acidic
- It occurs in proximal tubule cells
How does the renal tubule respond to acidosis?
- Acidosis leads to insertion of H+-ATPase into the apical membrane of the renal tubule cells, leading to increased H+secretion into the tubule.
- This is done by cytoskeletal-driven fusion of subapical vesicles.
What is the difference between respiratory and renal regulation of acid-base balance?
Respiratory - quick.
* induced by action of chemoreceptor on medullary respiratory centres
*acidosis - accelerated breathing
Renal - long-term
*altering bicarbonate flux.
