Acid Base Balance I Flashcards Preview

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Flashcards in Acid Base Balance I Deck (49):
1

Why is pH important?

Metabolic reactions are exquisitely sensitive to the pH of the fluid in which they occur.

Relates to the high reactivity of H+ ions with negatively charges proteins -> changes in configuration and function, especially enzymes.

Therefore Acid/Base disturbances -> all sorts of metabolic disturbances

pH of ECF is very closely regulated

2

What does pH mean?

The free [H+] in that fluid

Only free H+ ins contribute to pH

3

What is the [H+] like compared to concentration of other plasma constituents?

Other plasma constituents are present in mmoles
(e.g. Na+, K+, Cl-, glucose etc)

So [H+] is 1 millionth that of other plasma constituents
(40x10-6mmoles/l for pH 7.4)

4

What produces H+?

The body

5

What are the sources of H+?

Respiratory acid

Metabolic acid

6

How is respiratory acid a source of H+?

CO2 + H2O H2CO3
H+ + HCO3-

Formation of carbonic acid is not normally a net contributor to increased acid because any increase in production -> increase in ventilation

7

How is metabolic acid (non-respiratory acid) a source of H+?

via metabolism

1. Inorganic acids: e.g. S-containing amino acids -> H2SO4 and phosphoric acid is produced from phospholipids

2. Organic acids: fatty acids, lactic acid
-On a normal diet there is a net gain to the body of 50-100 moles H+ per day.

8

Wht is the major source of alkali in the body?

Oxidation of organic anions such as citrate

9

What do buffers do?

Why are they so important?

Minimize changes in pH when H+ ions are added or removed

Way too many H+ per day from diet. If present as free H+ in total body water -> pH of 1.2-2.4

As long as kidneys and lungs are working this can be dealt with.

H+ is successfully buffered until it can be excreted by the kidneys

10

What is the Henderson-Hasselbalch equation?

Defines the pH in terms of the ratio of [A-]/[HA] NOT the absolute amounts

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

11

What is the most important extracellular buffer?

Bicarbonate buffer system

H2CO3 H+ +HCO3-

12

What is the ratio of
[HCO3-]/[H2CO3] in the blood?

pK of bicarbonate buffer system = 6.1

So in plasma at pH 7.4...

7.4 = 6.1 + log [HCO3-]/
[H2CO3]

1.3 = log 20, so the ratio at pH 7.4 is 20:1

13

What does the quantity of H2CO3 in plasma depend on?

The amount of CO2 dissolved in plasma

Which depends on the solubility of CO2 and Pco2

14

What is the normal pCO2?

pCO2
=5.3kPa = 40mmHg

Range
4.8-5.9kPa = 36-44mmHg

15

What is the normal pH?

7.4

Range = 7.37-7.43

16

What is the normal
[HCO3-]?

24mmoles

Range = 22-26mmoles

17

What is the basic mechanism of the bicarbonate buffer system (assuming its a closed system)?

H+ + HCO3- H2CO3
H2O +CO2

Increase in ECF [H+] drives the reaction to the right, so that some of the additional increase H+ ions are removed from solution and therefore a change in pH is reduced.

However if this is a closed system when equilibrium is established the [H+] will not return to the original level as everything in the system will be slightly raised

Therefore only some of the additional H+ ions are buffered

18

How does the respiratory system work with the bicarbonate buffer system to return an increased ECF [H+] to its original level?

Once the bicarbonate buffer system equilibriates CO2 will be raised

This causes an increase in ventilation to burn off this excess CO2.

Since CO2 lowers, the bicarbonate buffer system shifts even further to the right alowing H+ to return to its original level

19

What should be remember about the how the respiratory system controls pH?

H+ has NOT been eliminated from the body.

Instead the HCO3- has buffered the H+ and the respiratory compensation has greatly increased the buffering capacity so that free H+ ions are prevented from contricuting to the pH

20

What eliminates H+ from the body?

Kidneys

21

How do the kidneys control the Acid/base balance of the body?

Elimination of H+ from the body is by the kidneys and this excretion is coupled to the regulation of plasma [HCO3-]

22

How do the kidneys and respiratory system work together to control pH?

Demonstrate this through the Henderson-Hasselbach equation

pH = pK + log [HCO3-]
/Pco2

[HCO3-] = renal regulation
Pco2 = respiratory regulation

This "independent" regulation of these factors determining pH is the basis of compensatory mechanisms

23

Appart from the bicarbonate buffer system what other buffers in the EFC exist?

Plasma proteins
Pr- + H+ HPr

Dibasic phosphate
HPO4(2-) + H+ H2PO4-
(monobasic phosphate)

24

What are the primary intracellular buffers?

Proteins, organic and inorganic phosphates and, in the erythrocytes, haemoglobin.

25

How does buffering of H+ ions by ICF buffers cause changes in plasma erythrocytes?

To maintain electrochemical neutrality, movement of H+ must be accompanied by Cl- as in red blood cells or exchanged for a cation, K+.

26

How does acidosis effect K+?

In acidosis, the movement of K+ out of cells into the plasma can cause hyperkalaemia -> depolarisation of excitable tissues -> ventricular fibrillation and death.

27

How does bone carbonate effect Acid/Base balance?

What is the clinical significance?

Provides an additional store of buffer, very important in chronic acid loads as in chronic renal failure -> wasting of bones

28

How much metabolic acid is buffered in ICF compared with ECF?

43% buffered in plasma

57% in cells

29

Where is respiratory acid buffered?

97% of buffering within cells, Hb particularly important, rest with plasma proteins

30

How does the kidney regulate [bicarbonate]?

1. Reabsorbing filtered bicarbonate

2. By generating new bicarbonate

Both of these processes depend on active H+ ion secretion from the tubule cells into the lumen

31

What is the mechanism for reabsorption of HCO3-?

Active H+ secretion from tubule cells coupled to passive Na+ reabsorption

Filtered bicarbonate reacts with the secreted H+ to form H2CO3.
In the presence of carbonic anhydrase on the luminal membrane -> CO2 and H2O

CO2 is freely permeable and enters the cell.
Within the cell, CO2 -> H2CO3 (carbonic anhydrase in all tubule cells) which then dissociates to H+ and HCO3-

The H+ ions are the source of the secreted H+

The HCO3 ions pass into the peritubular capillaries with Na+

32

Where does the bulk of bicarbonate reabsorption occur?

Proximal tubule >90%

33

Why does bicarbonate have to go through so many reactions to be reabsorbed?

Although the HCO3- reabsorbed is not the same ion as was filtered, the NET effect is the same.

HCO3- is a lrage charged molecule, by converting it to CO2 it is much easier to save this valuable buffer

34

Why is reabsorption of bicarbonate important?

GFR = 4320mmoles HCO3- filtered per day.

Must be reabsorbed, since failure to do so would be the same as adding H+ to the ECF

35

What happens to H+ ions during HCO3- reabsorption?

There is no excretion of H+ ions during HCO3- reabsorption

36

What is the minimum and maximum pH of urine in humans?

Minimum = pH 4.5-5.0

Maximum = pH around 8.0

37

Why cant we have pH 1 urine?

How do we solve this?

This would cause stinging and be intensely painful -> damage

Several weak acids and bases act as buffers.
Most done by dibasic phosphate, HPO4(2-), also urine acid and creatinine.

The process is called "titratable acidity" because its extent is measured by the amount of NaOH needed to titrate urine pH back to 7.4 for a 24 hour urine same

38

What is the importance of the formation of titratable acidity?

Genrated new HCO3- AND excreted H+

Only used for acid loads

39

How does the secretion of H+ work?

1. Na2HPO4 in the lumen. One Na+ is reabsorbed for secreted H+. This mono basic phosphate removes H+ from the body

2. The source of the new HCO3- is indirectly CO2 from the blood. It enters the tubule cells, combining with water to form carbonic acid in the presence of carbonic anhydrase, which then dissociates to yield H+, used for secretion, and new HCO3-, which passes with Na+ into the peritubular capillaries.

3. Occurs principally in the distal tubule, This is where phosphate ions, not reabsorbed by the proximal tubule Tm mechanism, become greatly concentrated because of removal of up to 95% of the initial filtrate.

40

What does the production of new bicarbonate in the tubule cells depend on?

Pco2 of the blood.

41

Why is the distal tubule the site of formation of titratable acidity?

Because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate

42

Why do we excrete ammonium?

Major adaptive response to an acid load
Generates new HCO3- AND excretes H+

43

When is Ammonium excreted?

Only used for acid loads

44

What is the difference in solubility between NH3 and NH4+?

Why is this important?

NH3 is lipid soluble
NH4+ is not

Differential solubility is basis for mechanism of ammonium excretion.

45

How is NH3 produced by renal tubule cells?

Produced by deamination of amino acids, primarily glutamine, by the action of renal glutaminase within the renal tubule cells.

46

What happens to NH3 produced by renal tubule cells?

Moves out into the tubule lumen where it combines with secreted H+ ions to form NH4+ which combines with Cl- ions (from NaCl) to form NH4Cl which is excreted.

Secreted H+ from CO2 in blood

NEW HCO3- passes with Na+ ions into peritubular capillaries

Distal tubule mechanism

47

How is the ammonium excretion mechanism in the distal tubule different from the proximal tubule?

Distal Tubule Mechanism:
-NH3 moves into lumen
-Combines with H+
-NH4+ formed and excreted

Proximal tubule mechanism:
-NH3 combines with H+ from H2CO3 breakdown
-NH4+ exchanged for Na+ and pumped into lumen

48

How is renal glutaminase effected by pH?

Exquisitely pH dependent

When intracellular pH falls renal glutaminase activity increases and therefore more NH4+ produced and excreted.

This ability to augment NH4+ production is the main adaptive response of the kidney to acid loads.

49

How long does the kedney adaptive response through renal glutaminase take to kick in?

It takes 4-5 DAYS to reach maximal effect because of the requirement of increased protein synthesis.

Also takes time to switch off the ability to make NH4+, when there is excess alkali