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LR Renal > Physiology: Acid-Base Balance > Flashcards

Physiology: Acid-Base Balance Flashcards

1
Q

What is…

  • pH?
  • Acid-base balance?
A

pH = a measure of the acidity of a substance based on H+ concentration

Acid-base balance = the regulation of free (unbound) H+ ions in the body fluids

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2
Q

Give an equation for calculating pH

What does this tell us about the relationship between pH and H+ conc.?

A

pH = log (1/ [H+])

This tells us that a low pH = high [H+] and a high pH = low [H+]

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3
Q 
What is the...
- Average
- Venous
- Arterial 
... pH?
A

Average pH = 7.4 (slightly alkaline)
Venous pH = 7.35
Arterial pH = 7.45

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4
Q

Why is venous blood more acidic than arterial blood?

A

H+ ions are generated from the dissociation of carbonic acid which is formed by CO2 and H2O (which are more abundant in deoxygenated blood)

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5
Q

What pH defines an…
- Acidosis
- Alkalosis
…?

A
  • Acidosis: pH < 7.35

- Alkalosis: pH > 7.45

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6
Q

Why must pH of the ECF be tightly controlled close to 7.4?

A

Because small changes in pH reflect large changes in [H+] e.g.,

  • pH 7 = H+ 100 nmol/L
  • pH 7.4 = H+ 40 nmol/L
  • pH 7.7 = H+ 16 nmol/L
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7
Q

What 3 effects can fluctuations in ECF [H+] have?

A
  • Altered nerve activity
  • Altered enzyme activity
  • Altered K+ levels
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8
Q

How does an…
- Acidosis
- Alkalosis
… affect nerve activity?

A
  • Acidosis: can lead to depression of the CNS e.g., disorientation, loss of consciousness
  • Alkalosis: can lead to overexitability of the PNS e.g., pins and needles, muscle spasms
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9
Q

Why is enzyme activity altered by changes in [H+]?

A

Enzymes are proteins and so changes in [H+] changes their secondary and tertiary structures, resulting in altered function

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10
Q

Why are K+ levels altered by changes in [H+]?

A

Increased H+ increases renal tubular secretion of H+ in the distal segments of the nephron

Increased H+ secretion is coupled to decreased K+ secretion, leading to K+ retention

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11
Q

What pH values result in death?

A

pH <6.8 or pH >8

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12
Q

In order to maintain homeostasis, H+ input and output must be balanced.

What are the 3 ways that H+ is added to the body fluids?

A
  1. Carbonic acid formation from CO2 + H2O
  2. Inorganic acids produced during the breakdown of nutrients e.g., meat
  3. Organic acids resulting from metabolism e.g., fatty acids, lactic acid
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13
Q

What is the difference between a strong acid and a weak acid? Give an example of each

A

Strong acids (e.g., HCl) dissociate completely in solution

Weak acids (e.g., carbonic acid) dissociate partially in solution

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14
Q

What is a buffer/buffering system?

A

A solution that can resist pH change upon the addition of an acid or a base to the solution

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15
Q

What does a buffering system consist of?

A

A pair of substances:

  • One that can give up free H+ when [H+] decreases and
  • One that can bind to free H+ when [H+] increases
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16
Q

Write out the equilibrium for a buffering system

A

HA (undissociated acid) < – > H+ (proton) + A- (base)

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17
Q

In what way does the buffering equilibrium shift when an acid is added? Why?

A

Equilibrium shifts to the left:

HA (undissociated acid) < – H+ (proton) + A- (base)

This is because extra H+ is bound by the A-, leading to formation of more HA

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18
Q

In what way does the buffering equilibrium shift when a base is added? Why?

A

Equilibrium shifts to the right:

HA (undissociated acid) – > H+ (proton) + A- (base)

This is because the extra base removes H+ from the equation. This causes more HA to dissociate to replace the lost H+. A- rises too as more of it is also being produced

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19
Q

Write an equation for the dissociation constant, K, of a buffering system at equilibrium

A

K = [H+] [A-] / [HA]

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20
Q

If K is known for a buffering system, then pK can be worked out using pK = -log K

What is the definition of pK?

A

The pH of the undissociated acid which is required for the buffering system to be in equilibrium i.e., a measure of the strength of an acid

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21
Q

A lower pK = a stronger/weaker acid?

A

Stronger

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22
Q

What is the Henderson-Hasselbach equation?

A

An equation used to work out the pH of a buffering system if you know the pK, base conc., and undissociated acid conc.

23
Q

Write the Henderson-Hasselbach equation

A

pH = pK + log ( [A-] / [HA] )

24
Q

What is the most important physiological buffer system in the body?

A

The carbon dioxide - bicarbonate ion buffer system

CO2-HCO3- buffer

25
Q

Why is carbonic anhydrase important in the CO2 - HCO3- buffering system?

A

It catalyses the formation of carbonic acid from CO2 and H2O

Carbonic acid then dissociates to form H+ and HCO3-

CO2 + H2O < – > H2CO3 < – > H+ + HCO3-

26
Q

How is the CO2 - HCO3- buffering system written in the Henderson-Hasselbach equation?

A

pH = 6.1 + log ( [HCO3-] / (PCO2 x 0.03) )

as [H2CO3] can be written as a function of the partial pressure of CO2 in the ECF

27
Q

Why is the CO2 - HCO3 buffering system so important?

A

Because [HCO3-] in the ECF is controlled by the kidneys and PCO2 is controlled by the lungs

It is the lungs and the kidneys which interact to regulate ECF pH

28
Q

How can we try to remember the Henderson-Hasselbach equation for the CO2-HCO3- buffering system:
pH = 6.1 + log ( [HCO3-] / (PCO2 x 0.03) )
?

A

pH = kidneys/lungs = HCO3-/PCO2

29
Q

By what 2 mechanisms does the kidney control plasma [HCO3-]?

A
  • Varying the reabsorption of filtered HCO3-

- By generating ‘new’ HCO3- that can be added to the blood

30
Q

What action of the tubules drives both of the mechanisms used by the kidney that control [HCO3-]?

A

Both mechanisms depend on H+ secretion into the tubule

31
Q

Why is HCO3- reabsorption important?

A

HCO3- needs to be reabsorbed to prevent the body fluids from becoming too acidic

32
Q

HCO3- ions are freely filtered into the tubular fluid. Are they reabsorbed directly or indirectly by the epithelial cells in the tubular wall?
Why?

A

Indirectly

HCO3- ions are freely filtered into the tubular fluid but cannot cross the apical membrane of the epithelial cells in the tubular wall, as there are no transport mechanisms present to move it across

33
Q

Describe the steps of reabsorption of the filtered HCO3- in the tubule

A
  1. HCO3- is reabsorbed indirectly by combining with H+ ions (which enter the tubular fluid from the Na+/H+ exchanger in the apical membrane)
  2. Carbonic anhydrase combines HCO3- and H+ to form carbonic acid, which dissociates to form CO2 and H2O
  3. CO2 and H2O enter the apical membrane of the cell by diffusion
  4. Intracellular carbonic anhydrase combines CO2 and H2O to again form carbonic acid which dissociates to yield H+ and HCO3-
  5. The H+ is secreted back across the apical membrane by the Na+/H+ exchanger while the HCO3- leaves the basolateral membrane via the Na+/HCO3- cotransporter
34
Q

Why does H+ secretion cause basically all HCO3- to be reabsorbed?

A

Because more H+ is secreted than HCO3- is filtered

35
Q

When [HCO3-] in the tubular fluid is low (e.g., during acidosis), what is the next most plentiful buffer in the filtrate that secreted H+ will combine with?

A

Phosphate

36
Q

What is the result of H+ binding with phosphate?

A

This leads to the formation of an acidic form a phosphate which is excreted from the body

37
Q

In what 2 ways does generation of acid phosphate reduce the acidity of the body fluids?

A
  1. Acid has been secreted
  2. There is a net gain of HCO3- (‘new’ HCO3-), as the H+ originated from the breakdown of carbonic acid into H+ and HCO3-
38
Q

Acid phosphate is the main titratable acid in H+ excretion. What is meant by a ‘titratable acid’?

A

An excreted acid which allows the amount of H+ excreted to be calculated by adding a strong base to the urine sample

39
Q

How is the titration of a titratable acid carried out?

A

A strong base is added to the urine sample until the pH is brought back up to 7.4

40
Q

Why does the amount of titratable acid measured give you a value for the amount of ‘new’ HCO3- that has been added to the body?

A

Because one HCO3- is gained for every one H+ excreted

41
Q

What is the maximal amount of titratable acid that can be excreted per day?

A

40 mmol/day

42
Q

If acidosis persists and phosphate stores are used up, what is the next most plentiful buffer in the filtrate that secreted H+ will combine with?

A

Ammonia

43
Q

What is the result of H+ binding with ammonia?

A

This leads to the formation of an ammonium ion which is excreted from the body

44
Q

Can NH4+ be measured by measuring the amount of titratable acid in the urine?

A

No

A separate ammonium ion determination is necessary

45
Q

What is the normal rate of daily NH4+ excretion?

What may it rise to in acidosis?

A

Normal: ~20 mmol/day

Severe acidosis: 500-600 mmol/day

46
Q

So what 3 things does H+ secretion by the tubule do?

A
  • Drives reabsorption of HCO3-
  • Forms acid phosphate (a titratable acid)
  • Forms ammonium ion
47
Q

How much HCO3- is reabsorbed per day?

Therefore, how much H+ secretion must occur to achieve this?

A

HCO3- reabsorbed per day = 4300 mmol/day

Therefore, 4300 mmol/day H+ secretion is required to achieve this

48
Q

What 2 things does a titratable acid concentration of 20 mmol/day tell us?

A
  • 20 mmol of H+ has been secreted as acidic phosphate

- 20 mmol of ‘new’ HCO3- has been added to the blood

49
Q

If measuring ammonium ion concentration of the urine gives us 40 mmol/day, what 2 things does this tell us?

A
  • 40 mmol of H+ has been secreted as ammonium ions

- 40 mmol of ‘new’ HCO3- has been added to the blood

50
Q

How would you use HCO3-, TA, and NH4+ to work out the total H+ secretion rate for an individual?

A

Total H+ secretion rate

= HCO3- reabsorption + TA excretion + NH4+ excretion

51
Q

How would you use TA and NH4+ to work out the total H+ excretion rate for an individual?

A

Total H+ excretion

= TA excretion + NH4+ excretion

52
Q

Why might you want to work out the total H+ excretion rate for an individual?

A

As it is equal to the rate of addition of new HCO3- to the blood

53
Q

In summary, what is the vast majority of H+ used for?

A

To drive HCO3- reabsorption to prevent acidosis

54
Q

The minority of secreted H+ is used to generate titratable acid (acid phosphate) and ammonium ions. In what 2 ways do these functions also prevent acidosis?

A
  • Reduces the body’s acid load by excretion of H+

- Regenerates the blood buffer stores by adding ‘new’ HCO3-

LR Renal (16 decks)

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