Physiology - Acid/Base Balance Flashcards

1
Q

What is normal ECF pH?

A

7.4

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2
Q

What are the sources of H ions within the body?

A

Respiratory acid - CO2 + H2O

Metabolic acid - inorganic and organic acids

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3
Q

What is the normal level of bicarbonate in the body? What is it used for?
What is normal PCO2?

A

~24mM bicarb, used to buffer metabolic acidosis

5.3kPa CO2 (4.8-5.9)

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4
Q

Apart from the bicarb/CO2 buffer system, what other buffers exist in the ECF and ICF?

A

ECF:

  • Plasma proteins (Pr- + H+ <> HPr) - minor
  • Phosphate (dibasic + H+ <> monobasic) - minimal
  • Ammonia buffering system

ICF:

  • Proteins (Pr- + H+ <> HPr)
  • Phosphates
  • Haemoglobin in erythrocytes

Bone
- Calcium carbonate - important in prolonged metabolic acidosis as causes bone wasting

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5
Q

What effect does H+ have across the membrane in acidotic/alkalotic conditions regarding electrolytes?

A

Buffering causes changes in plasma electrolytes
- H+ movement accompanied by Cl- or exchanged for K+

In acidosis - H+ moves into cells, K moves out > hyperkalaemia

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6
Q

How does the kidney regulate HCO3- balance?

A

Reabsorbing filtered bicarb
Generating new bicarb

Both processes depend on active H secretion from tubule cells into the lumen

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7
Q

What is the mechanism for reabsorption of bicarb? Where does it mostly occur?

A

Active H secretion from tubule cells
Coupled to passive Na reabsorption
Filtered HCO3- joins H to form H2CO3
- in the presence of carbonic anhydrase, this then goes to CO2 + H2O
CO2 is freely permeable, enters cell
Becomes H2CO3 via carbonic anhydrase again
- dissociates into H+ and HCO3-
H goes back into cycle, Bicarb moves into capillary with Na

Bulk of reabsorption occurs in proximal tubule (>90%)
- no net effect on H+

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8
Q

What buffers exist for the urine? Where does most urine buffering occur?

A

Mostly dibasic phosphate
Also uric acid and creatinine

Generates new bicarb and secretes H

Occurs mostly in distal tubule (as this is where phosphate most concentrated)

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9
Q

What is the mechanism of urine buffering?

A

Na + phosphate exist in lumen
Na+ reabsorbed, coupled with H+ secretion
H+ joins monobasic phospate, is excreted

New bicarb generated from CO2 from blood
- enters tubule cell, combines with H2O to form H2CO3, which then dissociates to H+ which is secreted, and bicarb which passes into the capillary with Na

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10
Q

What is the role of ammonium in acid/base balance?

A

Only used for acid loads
Works as NH3 is permeable, NH4+ is not (lipophobic)
NH3 produced by AA deamination (mainly glutamine by renal glutaminase) within tubule cells
NH3 moves into lumen, combines with H+ to form NH4+, which then combines with Cl (from NaCl) to form NH4Cl
- source of H is CO2, corresponding bicarb passes into capillary with Na
This is all mainly in distal tubule

In proximal tubule, there is NH4/Na exchanger on luminal membrane - net effect is same

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11
Q

How does the ammonium buffer system depend on renal glutaminase?

A

Renal glutaminase needed to produce the ammonia
Its activity is pH dependent
- when pH falls, activity increases > more NH4 excreted

This is the main adaptive response of kidney to adapt to acid load, but takes 4-5 days to reach maximum effect

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12
Q

What is the body’s response to respiratory acidosis?

A

Increases bicarb via retention and generation
Decrease H via secretion (and the buffers)
Renal glutaminase increased to increase NH3/4 buffering

Only restoration of normal breathing can correct disturbance
- in chronic, blood gases are never normalised

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13
Q

What is the body’s response to respiratory alkalosis?

A

Bicarb decreases

- less CO2 means less H available for secretion, therefore less bicarb reabsorption

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14
Q

What is the body’s response to metabolic acidosis?

A

Stimulate ventilation (inc depth) to decrease PCO2

Decreased bicarb available as it buffers the H+ (or increased loss led to acidosis in the first place)

Kidney restores bicarb and secretes H
- H+ secretion technically decreased as source would be CO2 (which has been decreased in compensation), but what matters is proportion to bicarb

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15
Q

What is the body’s response to metabolic alkalosis?

A

PCO2 will increase (so reduced respiration)

Increased bicarb excretion

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16
Q

What are some causes of respiratory acidosis?

A

Acute - Drugs that depress respiratory centre

Chronic - lung disease

17
Q

What are some causes of respiratory alkalosis?

A

Acute - voluntary hyperventilation, aspirin, first ascent to altitude
Chronic - long-term altitude (decreased PO2 <8kPa stimulates peripheral chemoreceptors to increase ventilation)

18
Q

What are some causes of metabolic acidosis?

A

Ketoacidosis, lactic acidosis
Renal failure
Diarrhoea - loss of bicarb (don’t have time to reabsorb from intestine)

19
Q

What are some causes of metabolic alkalosis?

A

Vomiting - loss of H+ ions from gastric secretion
Aldosterone excess (inc renal H+ loss)
Excess bicarb administration in renally impaired
Blood transfusions - citrate to prevent coagulation in storage, which gets converted to bicarb (8 units+)

20
Q

How does pH vary in acute vs chronic respiratory acidosis?

A

For a given increase in PCO2, the pH decrease will be smaller in chronic than acute
- time to adapt with ammonium

21
Q

What happens in severe vomiting with regards to pH control alongside volume control?

A

Loss of HCl > metabolic alkalosis
Loss of fluid/NaCl > hypovolaemia

Kidney wants to retain H
But increase aldosterone due to volume will increase Na reabsorption - mainly exchanged for H (loss of Cl with vomit)
Respiratory compensation for alkalosis (Inc PCO2) drives further H secretion and exacerbates metabolic alkalosis by adding the counterpart bicarb to the circulation

Restoration of volume takes precedence over pH

22
Q

What happens to pH in vomiting also with diarrhoea?

A

Lose acid and alkali, but overall become alkalotic as decreased ECF volume > increased aldosterone > ‘contraction alkalosis’

23
Q

What is the anion gap? What is it normally?

A

Difference between sum of principal cations (Na and K) and principal anions (Cl and HCO3) in the plasma
‘Gap’ refers to fewer anions
Normally 14-18mM

24
Q

When is the anion gap measured and useful?

A

Useful to measure in metabolic acidosis
Can be no change or change

If acidosis due to bicarb loss, compensated by Cl increase so no change
But in lactic/ketoacidosis, reduction in bicarb made up by other anions e.g. lactate, acetoacetate - so anion gap is increased