Acid Base Balance 1 Flashcards

1
Q

What are metabolic reactions sensitive to in relation to the fluid they occur in?

A

pH of the fluid:

  • Relates to high reactivity of H+ ions with Protons causing changes in configuration and function, especially of enzymes
  • Acid/base disturbances lead to all sorts of metabolic disturbances
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2
Q

What is the normal pH of arterialised blood?

A
  • Normal pH of arterialised blood is 7.4, which is a free [H+] of 40 x 10-9moles/L or 40 x 10-6mmoles/L
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3
Q

What is the free hydrogen concentration of normal arterial blood>

A
  • 40 x 10-9moles/L or 40 x 10-6mmoles/L
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4
Q

Does all hydrogen contribute to pH?

A

No, only free H+ ions

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5
Q

What are some sources of the H+ that the body produces?

A
  • Respiratory acid
    • CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-
    • Formation of carbonic acid is not normally a net contributor to increased acid because any increase in production causes an increase in ventilation
    • Problems occur if lung function is impaired
  • Metabolic acid (non-respiratory acid)
    • Inorganic acids
      • Such as S-containing amino acids, H2SO4 and phosphoric acid is produced from phospholipids
    • Organic acids
      • Fatty acids, lactic acid
      • On a normal diet, there is a net gain to the body of 50-100mmols H+ per day
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6
Q

What is the formula that explains how the body produces H+ from respiratory acid?

A

CO2 + H20 H2C03 HCO3- + H+

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7
Q

Is formation of carbonic acid usually a net contributor to increased acid?

A

No because any increased in production causes an increase in ventilaiton

Problems occur if lung function is impaired

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8
Q

What are the 2 different kinds of metabolic acid?

A
  • Inorganic acids
    • Such as S-containing amino acids, H2SO4 and phosphoric acid is produced from phospholipids
  • Organic acids
    • Fatty acids, lactic acid
    • On a normal diet, there is a net gain to the body of 50-100mmols H+ per day
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9
Q

What are some examples of inorganic acids that contributes to the body producing H?

A
  • Such as S-containing amino acids, H2SO4 and phosphoric acid is produced from phospholipids
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10
Q

What are examples of organic acids that contributes to the bodies production of H?

A
  • Fatty acids, lactic acid
  • On a normal diet, there is a net gain to the body of 50-100mmols H+ per day
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11
Q

What is the net gain of organic acids in terms of H by the body due to a normal diet?

A

50-100mmoles/L of H+

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12
Q

What is a mjor source of alkalis to the body?

A

Oxidation of organic anions such as citrate

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13
Q

What minimised changes in pH when H ions are added or removed?

A

Buffers

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14
Q

What is the Henderson-Hasselbalch equation?

A
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15
Q

What is the most important extracellular buffer?

A

Bicarbonate buffer system

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16
Q

What is the ratio of bicarbonate to carbonic acid in the body in blood with a pH of 7.4?

A

20:1

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17
Q

What does the quantity of carbonic acid depend on?

A

Amount of CO2 dissolved in plasma, which depends on solubility of CO2 and PCO2

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18
Q

What is the chemical formula for carbonic acid?

A

H2CO3

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19
Q

What is the chemical formula for bicarbonate?

A

HCO3-

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20
Q

What does the amount of CO2 dissolved in plasma depend on?

A

Solubility of CO2 and PCO2

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21
Q

What is the solubility of CO2 in blood at 37oC?

A

0.03mmoles/L/mmHg

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22
Q

What is PCO2 in blood at 37oC?

A

0.0225mmoles/L/kPa

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23
Q

What is the normal PCO2?

A

40mmHg, 5.3kPa

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24
Q

What is [carbonic acid] at normal PCO2?

A

1.2mmol/L

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25
Q

What is the normal [bicarbonate] at normal PCO2?

A

24mmoles/L

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26
Q

What is normal [bicarbonate] known as?

A

“Stnadard bicarbonate”

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27
Q

What is the normal range of pH?

A

7.37-7.43

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28
Q

What range of pH is compatible with life?

A

7-7.6

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29
Q

What is the normal range of PCO2?

A

4.8-5.9kPa, 36-44mmHg

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30
Q

What is the normal range of [bicarbonate]?

A

22-26mmoles/L

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31
Q

What can the Henderson-Hasselbatch equation be more simply written as in terms of the bicarbonate system?

A
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32
Q

Explain the mechanism by which the bicarbonate buffer system acts?

A
  • Increase in ECF H+ drives the reaction right, so some of the additional H ions are removed from solution and therefore a change in pH is reduced
  • If this was an ordinary buffer system then as increasing H drives the reaction right, the increase in products would begin to push the reaction back to reach a new equilibrium position, where only some additional H ions are buffered
  • But its not an ordinary buffer system due to ventilation, increasing the buffer capacity of bicarbonate
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33
Q

Does an increase in H lead to increased or decreased ventilation?

A

Increased ventilation

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34
Q

Does a decrease in H lead to increased or decreased ventilation?

A

Decreased ventilation

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35
Q

What is the aim of the bicarbonate buffering system and acid/base balance?

A

Protect arterial pH

36
Q

What is elimination of H from the body done by?

A

Kidneys and is coupled to the regulation of plasma bicarbonate

37
Q

Is the regulation of bicarbonate done by the renal or respiratory system?

A

Renal system

38
Q

Is the regulation of PCO2 done by the renal or respiratory system?

A

Respiratory system

39
Q

Is pH directly or inversely proportional to [bicarbonate]?

A

Directly proportionate

40
Q

Is pH directly or inversely proportionate to PCO2?

A

Inversely proportionate

41
Q

Other than bicarbonate, what are some other buffers in the ECF?

A
  • Plasma proteins
    • Pr- + H+ « HPr
  • Dibasic phosphate
    • HPO42- + H+ « H2PO4- monobasic phosphate
42
Q

What are the primary intracellular buffers?

A

Proteins, organic and inorganic phosphate and in erythrocytes, haemoglobin

43
Q

What does buffering of H ions by ICF buffers cause changes in?

A
  • In plasma electrolytes, since to maintain electrochemical neutrality movement of H ions must be accompanied by Cl as in red cells or exchanged for a cation, K
44
Q

What must be done to counter the changes in plasma electrolytes caused by buffering of H ions by ICF buffers?

A
  • Movement of H ions must be accompanied by Cl as in red cells or exchanged for a cation, K
45
Q

The exchange of H for K in acidosis can cause what?

A

In acidosis, movement of K out of cells into plasma can cause hyperkalaemia, causing depolarisation of excitable tissues then ventricular fibrillation and death

46
Q

Why do increases in H in acidosis lead to hyperhalaemia?

A

Because of the need to maintian electrochemical neutrality

47
Q

Why does renal failure lead to wasting of bones?

A

Bone carbonate provides additional store of buffer, important in chronic acid loads as in chronic renal failure leads to wasting of bones

48
Q

Explain why buffers are so important?

A
  • 10-100mmoles H per day is from the diet
  • If present as free H in total body water, brings the pH to 1.2-2.4
  • But arterial pH remains constant at 7.4 as long as the lungs and kidneys are working normally
  • So H is successfully buffered until the kidney excretes it
49
Q

How much H comes from the diet per day?

A

10-100mmoles

50
Q

What percentage of metabolic acid is buffered in plasma?

A

43% buffered in plasma, primarily with HCO3-

51
Q

What percentage of metabolic acid is buffered in the cells?

A

57%

52
Q

For respiratory acid, what percentage of buffering occurs within cells?

A

97%

53
Q

By what ways does do the kidneys regulate [bicarbonate]?

A
  • Reabsorbing filtered HCO3-
  • By generating new HCO3-
54
Q

What do both the processes of the kidneys regulated [bicarbonate] depend on?

A

Active H ion secretion from the tubule cells into the lumen

55
Q

Explain the mechanism for the reabsorption of bicarbonate?

A
  1. Active H secretion from tubule cells
  2. Coupled to passive Na reabsorption
  3. Filtered HCO3- reacts with secreted H+ to form H2CO3, in presence of carbonic anhydrate on the luminal membrane forms CO2 and water
  4. CO2 if freely permeable and enters cells
  5. Within the cell CO2 is converted to H2CO3 in the presence of carbonic anhydrase (present in all tubule cells) which then dissociates to form H+ and HCO3-
  6. H ions are the source of the secreted H
  7. The HCO3- ions pass into the peritubular capillaries with Na
  8. Bulk of HCO3­- reabsorption occurs in the proximal tubule, >90%
56
Q

What is active H secretion from tubule cell to the lumen coupled with?

A

Passive Na reabsorption

57
Q

What enzyme is found in tubule that allows carbonic acid to form CO2 and water?

A

Carbonic anhydrate on luminal membrane

58
Q

Where does most of the bicarbonate reabsorption occur?

A

Proximal tubule, >90%

59
Q

Is the HCO3- reabsorbed by the kidneys the same ion as was filtered?

A

No, but the net effect is the same

60
Q

Why is bicarbonate converted to carbon dioxide to recycle?

A

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

61
Q

How much bicarbonate is filtered each day?

A
  • GFR is 180L/day and [HCO3-] is 24mmol/L
  • So 4320mmoles HCO3- is filtered each day
62
Q

Why is bicarbonate reabsorption so important?

A
  • GFR is 180L/day and [HCO3-] is 24mmol/L
  • So 4320mmoles HCO3- is filtered each day
  • It must all be absorbed, since failure to do so is the same as adding H to the ECF
  • Note there is no excretion of H ions during HCO3- reabsorption
63
Q

What is the minimum and maximum pH of urine?

A

Min - 4.5 to 5

Max - 8

64
Q

What is the usual net production of H per day that is excreted in urine?

A

50-100mmoles

65
Q

Due to the usual net production of H and the amount of urine produced per day, urine should have a pH of 1 and sting. Why is this not the case?

A
  • This is not the case because it is buffered in urine
    • Several weak acids and bases act as buffers
    • Most done by dibasic phosphate HPO42-, also uric acic and creatinine
  • This 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 sample
  • The importance of the formation of titratable acidity is that it generates new HCO3- and excreted H
    • Only used for acid loads
66
Q

What buffers act in the urine?

A
  • Most done by dibasic phosphate HPO42-, also uric acic and creatinine
67
Q

What is the process of buffers acting on H in the urine known as?

A

“Titratable acidity”

68
Q

What is the importance of the formation of titratable acidity?

A

It generates new bicarbonate and excretes H

69
Q

What is titratable acidity only used for?

A

Acid loads (not base loads)

70
Q

Explain the process of titratable acidity?

A
  1. Na2HPO4 in the lumen. One Na+ is reabsorbed in exchange for secreted H+. This monobasic 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 H2O 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.
  4. Process is dependent on Pco2 of the blood.
71
Q

What is the process of titratable acidity dependent on?

A

PCO2 of the blood

72
Q

Where does titratable acidity principally occur?

A

In the distal tubule

73
Q

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

A

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

74
Q

Is ammonium excretion used for acid or base loads?

A

Acid loads

75
Q

What is the net result of ammonium excretion?

A

Generates new bicarbonate and excretes H

76
Q

Is NH3 lipid soluble or insoluble?

A

Soluble

77
Q

Is NH4+ lipid soluble or insoluble?

A

Insoluble

78
Q

What is the basis for ammonium excretion?

A

NH3 is lipid soluble

NH4+ is lipid insoluble

79
Q

Explain the process of ammonium excretion as a response to an acid load?

A
  1. NH3 is produced by deamination of amino acids, primarily glutamine by the action of renal glutaminase within the renal tubule cells
  2. NH3 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 (distal tubule mechanism)
  3. The source of the secreted H is again CO2 from the blood
  4. The new HCO3- passes with Na ions into the peritubular capillaries
  5. In the proximal tubule, there is an NH4+/Na exchanger so NH4+ ions formed within the cell pass out into the lumen, net effect is the same
80
Q

What is NH3 produced by?

A

Deamination of amino acids, primarily glutamine by the action of glutaminase within the renal tubule cells

81
Q

What is the activity of renal glutaminase dependent on?

A

pH dependent, when intracellular pH falls there is an increase in renal glutaminase activity and therefore more NH4+ is produced and excreted

82
Q

When intracellular pH falls is there an increase or decrease in renal glutaminase activity?

A

Increase

83
Q

What enzyme is responsible for the deamination of glutamine?

A

Glutaminase

84
Q

What is the main adaptive response of the kidney to acid loads?

A

Ability to augment (make) NH4+

85
Q

How much H is excreted per day as NH4+?

A

Normally only 30-50mmoles/L, but this can increase to 250mmol/L in the presence of severe acidosis

86
Q

Is the ability to make NH4+ stopped immediately in the presence of excess alkali?

A

It takes time to switch off this ability