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year 2 renal > Acid Base Balance 1 & 2 > Flashcards

Acid Base Balance 1 & 2 Flashcards

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1
Q

why are acid/base balance important and what happens if it is disturbed?

A

Metabolic reactions are exquisitely sensitive to the pH of the fluid in which they occur. Relates to the high reactivity of H+ ions with Pr- = changes in configuration and function, especially enzymes

Acid/Base disturbances = all sorts of metabolic disturbances

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2
Q

pH of ECF is very closely regulated

Normal pH of arterialized blood is 7.4 = free [H+] of 40 x 10-9 moles/l or 40 x 10-6 mmoles/l

what is the important of free H+?

A

Only free H+ ions contribute to pH

Other plasma constituents are present in mmoles eg Na+, K+, Cl-, glucose etc. So [H+] is one millioneth that of other plasma constituents

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3
Q

does hte body produce H+?

A

yes

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4
Q

what ar ethe 2 main sources of H+?

A

respiratory acid

metabolic acid (non-respiratory acid)

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5
Q

how is respiratory acid a source of H+?

A

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

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

Problems occur if lung function is impaired

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6
Q

hwo is metabolic acid a source of H+?

A

via metabolism

a) inorganic acids: eg S-containing amino acids = H2SO4 and phosphoric acid is produced from phospholipids
b) organic acids: fatty acids, lactic acid. On a normal diet, there is a net gain to the body of 50-100 mmoles H+ per day

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7
Q

Major source of alkali is oxidation of what?

A

organic anions such as citrate

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8
Q

what do buffers do?

A

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

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9
Q

what equation is this:

pH = pK + log⁡[A-]/[HA]

A

Henderson-Hasselbalch equation

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10
Q

what is the Henderson-Hasselbalch equation?

A

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

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11
Q

what is the most important extracellular buffer? and what is the equation?

A

The most important is the bicarbonate buffer system

H2CO3 <=> H+ + HCO3-

pH = pK + log⁡ [HC03-]/[H2CO3]

pK = 6.1 so in plasma at pH 7.4, 7.4 = 6.1 + log⁡ [HC03-]/[H2CO3]

1.3 = log 20, so the ratio of [HCO3-]/[H2CO3] in blood at 7.4 is 20:1, Need 20 times more bicarbonate

The quantity of H2CO3 depends on the amount of CO2 dissolved in plasma, depends on solubility of CO2 and Pco2

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12
Q

how do you calculate the standard biocarbonate?

A

The quantity of H2CO3 depends on the amount of CO2 dissolved in plasma, depends on solubility of CO2 and Pco2

Solubility of CO2 in blood at 37°C = 0.03 mmoles/l/mmHg, PCO2 = 0.225 mmoles/l/kPa PCO2

So, at a normal Pco2 of 40mmHg, 5.3kPa, [H2CO3]= 40 x 0.03 mmoles/l or 5.3 x 0.225mmoles/l =1.2mmoles/l

Since the ratio of [HCO3-]/[H2CO3] in blood at 7.4 is 20:1, [HCO3-] = 24mmoles/l = “Standard bicarbonate”

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13
Q

what is the normal value and ranges for pH?

A

pH =7.4 Range 7.37-7.43

Range of pH compatible with life: 6.8-7.8 (US), 7.0-7.6(UK)

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14
Q

what is the normal value and rages for pCO2?

A

pCO2 = 5.3kPa Range 4.8- 5.9

= 40mmHg 36-44

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15
Q

what si the normal value and range of [HCO3-]?

A

[HCO3-] = 24mmoles/l Range 22-26

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16
Q

The Henderson-Hasselbalch equation can be more simply written as what?

A

pH = [HCO3-]/PCO2

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17
Q

The unique importance of the bicarbonate buffer system is crucial:

increased ­H+ + HCO3- <=> H2CO3 <=> H2O + CO2

describe what is happening?

A

Basic mechanism by which it acts as a buffer is evident, an ­increased ECF H+ drives the reaction to the right, so that some of the additional increased ­H+ ions are removed from solution and therefore a change in pH is reduced

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18
Q

increased ­H+ + HCO3- <=> H2CO3 <=> H2O + CO2

If this was an ordinary buffer system then increased­H+ drives the reaction to the right and what would happen?

A

the ­increased products would begin to push the reaction back to reach a new equilibrium position, where only some of the additional H+ ions are buffered

In any normal buffer system the products would stop the reaction happening and make it go slower and make it reverse back the other way

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19
Q

is the bicarbonate an ordinary buffer system?

A

no

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20
Q

how is the bicarbnate buffering system not an ordinary buffering system?

A

the reaction is pulled to the right, greatly increasing the buffering capacity of the bicarbonate

Ventilation removes the product of CO2 and cant participate in the backwards reaction any more and increases capacity of this buffer system dramatically

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21
Q

does the bicarbonate buffering system eliminate the H+?

A

Important to note that 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 contributing to the pH

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22
Q

Elimination of H+ from the body is by the _______ and this excretion is coupled to the regulation of plasma _______

A

kidneys

[HCO3-]

pH = [HCO3-] = renal regulation

Pco2 = respiratory regulation

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23
Q

what are other buffers in the ECF?

A

Plasma proteins Pr- + H+ <=> HPr

Dibasic phosphate HPO42- + H+ <=> H2PO4- monobasic phosphate

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24
Q

what are intracellular buffers?

A

Primary intracellular buffers are proteins, organic and inorganic phosphates and, in the erythrocytes, haemoglobin

Buffering of H+ ions by ICF buffers cause changes in plasma electrolytes, since to maintain electrochemical neutrality, movement of H+ must be accompanied by Cl- as in red cells or exchanged for a cation, K+

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25
In acidosis, the movement of K+ out of cells into plasma cause?
can cause hyperkalaemia = depolarization of excitable tissues = ventricular fibrillation and death
26
Bone carbonate provides what?
an additional store of buffer, very important in chronic acid loads as in chronic renal failure = wasting of bones
27
Are buffers important?
Buffers are incredibly important: 50-100 mmoles H+ per day from diet. If present as free H+ in total body water = pH of 1.2-2.4!! In fact arterial pH remains remarkably constant at 7.4, as long as the lungs and kidneys are working normally. So H+ is successfully buffered until the kidney excretes it
28
where is metabolic acid buffered?
43% buffered in plasma, primarily with HCO3- 57% in cells
29
where is repsiratory acid buffered?
97% of buffering occurs within cells, Hb particularly important, rest with plasma proteins
30
[HCO3-] = ____ regulation Pco2 = ___________ regulation
renal respiratory
31
The kidney regulates [HCO3-] by mechanism?
1. Reabsorbing filtered HCO3- 2. By generating new HCO3- Both of these processes depend on active H+ ion secretion from the tubule cells into the lumen
32
What is the mechanism for the reabsorption of HCO3-?
a) Active H+secretion from the tubule cells b) coupled to passive Na+ reabsorption c) filtered HCO3- reacts with the secreted H+ to form H2CO3. In the presence of carbonic anhydrase on the luminal membrane = CO2 and H2O d) CO2 is freely permeable and enters the cell e) Within the cell, CO2 = H2CO3 in the presence of carbonic anhydrase (present in all tubule cells) which then dissociates to form H+ and HCO3- f) The H+ ions are the source of the secreted H+ g) The HCO3- ions pass into the peritubular capillaries with Na+ h) Bulk of HCO3- reabsorption occurs in the proximal tubule \>90% Although the HCO3- reabsorbed is not the same ion as was filtered, the net effect is the same. HCO3- is a large charged molecule, by converting it to CO2 it is much easier to save this valuable buffer
33
what is the importance of HCO3- reabsorption?
GFR =180l/day [HCO3-] = 24mmoles/l = 4320 mmoles HCO3- filtered per day. Must be reabsorbed, since failure to do so = to adding H+ to the ECF There is no excretion of H+ ions during HCO3- reabsorption
34
in humans what is the iminmum and maximum urine pH?
In humans, minimum urine pH = 4.5.-5.0, maximum » 8.0 Usually, net production of 50 -100 mmoles H+ per day If present as free H+ ions in urine volume of 1litre = pH = 1. Stinging!! Fortunately, buffered in urine
35
What acts as buffers?
Several weak acids and bases act as buffers. Most is done by dibasic phosphate, HPO42-, also uric acid and creatinine
36
Importance of the formation of titratable acidity is what?
it generates new HCO3- AND excretes H+ Only used for acid loads 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 24hour urine sample
37
how are H+ removed?
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
38
Distal tubule is site of formation of titratable acidity because......
Distal tubule is site of formation of titratable acidity because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate
39
ammonium excretion does what?
Major adaptive response to an acid load, generates new HCO3- AND excretes H
40
ammonium excretion is only done for acid loads, describe how this removes H+ (in the distal tubule)
NH3 is lipid soluble, NH4+ is not. This differential solubility is basis for mechanism NH3 is produced by deamination of amino acids, primarily glutamine, by the action of renal glutaminase within the renal tubule cells 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) The new HCO3- passes with Na+ ions into the peritubular capillaries
41
where is the source of secreted H+ form in ammonium secretion?
The source of the secreted H+ is again CO2 from the blood
42
describe the process of ammonium excretion in the proximal tubule
In the proximal tubule, there is an NH4+/Na+ exchanger so NH4+ ions formed within the cells pass out into the lumen Net effect is the same Ammonium formation happens in the cells in the proximal tubule and uses a sodium transfer to get into the lumen to be excreted
43
can NH4 cross the cell membrane?
NH4 cant cross membrane as large charged molecule, but NH3 can as it is lipid soluble
44
what si the activity of renal glutaminase depedent on?
exquisitely pH dependent When intracellular pH falls =­increased renal glutaminase activity and therefore more NH4+ produced and excreted
45
what is the main adaptive response of the kidney to acid loads? and how long does it take?
This ability to augment NH4+ production is the main adaptive response of the kidney to acid loads It takes 4-5 days to reach maximal effect because of the requirements of ­increased protein synthesis Normally only 30-50 mmoles H+ per day are lost as NH4+, but this can ­increase to 250 mmoles/l in the presence of severe acidosis It also takes time to switch off the ability to make NH4+ when there is excess of alkali
46
If renal or respiratory function is abnormal, or any acid or base load overwhelms the body, a change in pH occurs decreased pH = increased pH =
acidosis alkalosis
47
respiratory disorders affect what?
Pco2
48
what does renal disorders affect?
[HCO3-]
49
what is Respiratory Acidosis?
pH has fallen and it is due to a respiratory change, so Pco2 must have increased. Respiratory acidosis results from reduced ventilation and therefore retention of CO2 retention of carbon dioxide
50
what are acute causes of respiratory acidosis?
drugs which depress the medullary respiratory centres, such as barbiturates and opiates Or Obstructions of major airways
51
what are chronic causes of repsiratory acidosis?
lung disease eg bronchitis, emphysema, asthma
52
what is the response to respiratory acidosis?
Need to protect pH so need to increase­ [HCO3-] The increased­ Pco2 will = increased­ secretion of H+ and ­increased HCO3-. Acid conditions stimulate renal glutaminase so get more NH3 produced, BUT, it takes time So there is ­increased generation of new HCO3- as well as ­increased reabsorption, because having generated more HCO3- , the increased­ Pco2 will also ­increase the ability to reabsorb it
53
However, although the renal compensation to ­ increase HCO3- protects the pH in respiratory acidsosis, it does not correct the original disturbance, what does?
Only restoration of normal ventilation can remove the primary disturbance
54
what are the valvues like in chronic respiratory acidosis?
in chronic respiratory acidosis eg in bronchitis, blood gas values are never normalised They may be eg pH 7.32, Pco2 65mmHg (8.67 kPa), [HCO3-] 38 mmoles/l The underlying disease process prevents the correction of ventilation, but because the kidney maintains high [HCO3-], the pH is protected
55
Patients with lung disease will always have aberrant Pco2 and [HCO3-], but as long as ____ function is not impaired, __ can be maintained at a level compatible with life Problems arise when patients with lung disease develop ____ dysfunction
kidney pH renal
56
what is respiratory alkalosis?
Alkalosis of respiratory origin so must be due to a fall in Pco2 and this can only occur through increased ventilation and CO2 blow-off
57
what are the acute causes of respiratory alkalosis?
voluntary hyperventilation, aspirin, first ascent to altitude
58
what are the chronic cause of respiratory alkalosis?
long term residence at altitude, decreased Po2 to \<60mmHg (8kPa) stimulates peripheral chemoreceptors to increase ventilation
59
what is done to protect pH in repsiratory alkalosis?
To protect pH, [HCO3-] should decrease Alkaline conditions are dealt with by the HCO3- reabsorptive mechanism If decreased Pco2, less H+ is available for secretion, therefore less of the filtered load of HCO3- is reabsorbed so HCO3- is lost in the urine Again, ventilation must be normalized to correct the disturbance
60
what is metabolic acidosis?
An acidosis of metabolic origin must be due to a decreased [HCO3-] So, decreased [HCO3-], either due to ­increased buffering of H+ or direct loss of HCO3-
61
How do you protect pH in metabolic acidosis?
To protect the pH, Pco2 must be decreased
62
what are the causes of metabolic acidosis?
1. increased­ H+ production, as in ketoacidosis of a diabetic (acetoacetic acid, b- hydroxybutyric acid) or in lactic acidosis 2. Failure to excrete the normal dietary load of H+ as in renal failure 3. Loss of HCO3- as in diarrhoea ie failure to reabsorb intestinal HCO3- can be an excess of protons or a lack of bases
63
what happens to breathing in metabolic acidosis?
The resulting acidosis stimulates ventilation so that Pco2 falls The ­increase in ventilation is in depth rather than rate, may be very striking, reaching a maximum of 30 l/min cf normal 5-6 l/min when the arterial pH falls to 7.0 This degree of hyperventilation = Kussmaul breathing = an established clinical sign of renal failure or diabetic ketoacidosis. Very serious
64
metabolic acidosis: Normally the kidneys correct the disturbance by restoring _______ and getting rid of __ ions
[HCO3-] H+
65
Normally the kidneys correct the disturbance by restoring [HCO3-] and getting rid of H+ ions Problem: Source of H+ ions is the carbonic acid from CO2, but the respiratory compensation lowers the Pco2 to protect the pH!!!!!!!! what is the explanation?
1. Compensations for A/B disturbances are always in the same direction as the initial disturbance. Remember pH is defined as the ratio of [HCO3-]/ PCO2. However they are never quite to the same extent ie not complete, so pH not restored to 7.4 2. Complete compensation would remove the drive to correct the original disturbance. Survival value of this is that if there were no pressure to correct initial disturbance, a further perturbation may push the system so far that compensation can no longer be effective 3. Because of the decreased Pco2, the total amount of H+ secreted by the renal tubule will be less than normal BUT because the plasma [HCO3-] and therefore filtered load of HCO3- is reduced to an even greater extent , a smaller fraction of total H+ is needed for HCO3- reabsorption and therefore a greater proportion is available for excretion in the form of titratable acid and NH4+
66
increased metabolic H+ within the body causes what?
1. Immediate buffering in ECF and then ICF 2. Respiratory compensation within minutes 3. Renal correction of the disturbance takes longer to develop the full response to increase­ H+ excretion and generate new HCO3- because renal glutaminase takes 4-5 days to reach maximum. As HCO3- starts to increase­, repiratory compensation begins to wear off until eventually get rid of all excess H+
67
in metabolic acidosis, respiratory compensation ______ the ____ correction, but ______ the pH, much more important
dleays renal protects
68
what is metabolic alkalosis? and what is done to protect the pH?
[HCO3-] must have increase­ and Pco2 will ­increase to protect the pH
69
what are the causes of metabolic alkalosis?
1. increased H+ ion loss - vomiting loss of gastric secretions 2. ­ increased renal H+ loss - aldosterone excess, excess liquorice ingestion 3. Excess administration of HCO3- is unlikely to produce a metabolic alkalosis in subjects with normal renal function, but may do so if renal function impaired 4. Massive blood transfusions can lead to metabolic alkalosis because bank blood contains citrate to prevent coagulation, which is converted to HCO3-, but need at least 8 units to have this effect The greatly increased­ filtered load of HCO3- exceeds the level of H+ secretion to reabsorb it, even in the presence of ­ Pco2, so the excess is lost in the urine. Again, respiratory compensation delays renal correction, but protects the pH
70
name a, b, c and d
increase decrease increase increase
71
name e, f, g and h?
dcerease increase decrease decrease
72
name i, j, k and l
increase decrease decrease decrease
73
name M, N, O and P
decrease increase increase increase
74
A decrease in pH (acidosis) is CAUSED by either what?
75
An increase in pH (alkalosis) is CAUSED by either what?
76
how do you tell between chronic and acute respiratory acidosis?
Note that for a given increase in Pco2, there is a smaller decrease in pH in chronic respiratory acidosis than in acute respiratory acidosis
77
Note that for a given increase in Pco2, there is a smaller decrease in pH in chronic respiratory acidosis than in acute respiratory acidosis why is this?
Answer lies in mechanisms used to raise [HCO3-]. NH3 production takes 4-5 days to be fully turned on. So initially can only raise [HCO3-] by titratable acid, so limited. With time, can use NH3 production which has a considerable capacity to raise [HCO3-] A similar difference is seen between acute and chronic respiratory alkalosis because of the delay in turning off NH3 production. In contrast to renal compensations, which need time to reach completion, respiratory compensations occur in minutes so no differences
78
Important to realize that acid/base disorders don’t just occur in isolation and in otherwise healthy individuals Consider a badly controlled diabetic in ketoacidosis = (1) This patient, despite the best advice, has always smoked, = chronic bronchitis = (2) Patient has a haemorrhage = (3) ie combined metabolic and respiratory acidosis
1 - metabolic acidosis 2 - respiratory acidosis 3 - lactic acidosis
79
carrying on from previous flashcard: blood/gas values: pH = 6.99, Pco2 = 60mmHg (8kPa), [HCO3-] = 13mmoles/l What would you suggest to help him? And let us not forget Potassium. The high acidity will cause Hyperkalaemia as H+ ions are buffered intracellularly in exchange for K+ ions. Danger of Ventricular Fibrillation.
1. Insulin (+ glucose if non-diabetic), stimulates cellular uptake of K+ BUT????? 2. Also for hyperkalaemia, calcium resonium, either oral or pr (per rectum), exchanges Ca2+ ions for K+ ions (12-24 hours) 3. Ca gluconate (iv) = decreased excitability of heart, stabilizes cardiac muscle cell membranes
80
The kidneys that are so important in Acid/Base balance are the same ones that are so important in regulating ECF volume and composition. Consider a bad case of vomiting: loss of NaCl and H2O = .......... loss of HCl = ............
hypovolaemia metabolic alkalosis
81
what happens in a case of bad vomiting?
loss of NaCl and H2O = hypovolaemia loss of HCl = metabolic alkalosis The hypovolaemia will stimulate aldosterone to ­ increased distal tubule Na+ reabsorption Under conditions of avid Na+ reabsorption, (and due to loss of Cl- ), the main ion exchanged for Na+ is H+ The respiratory compensation for the metabolic alkalosis ie increased ­Pco2 helps drive the H+ secretion and exacerbates the metabolic alkalosis by adding yet more HCO3- to the plasma
82
The hypovolaemia will stimulate __________ to ­ increase distal tubule ___ reabsorption
aldosterone Na+
83
Under conditions of avid Na+ reabsorption, (and due to loss of Cl- ), the main ion exchanged for Na+ is what?
H+
84
The respiratory compensation for the metabolic _______ ie increased ­Pco2 helps drive the H+ secretion and exacerbates the metabolic alkalosis by adding yet more HCO3- to the plasma
alkalosis
85
summary diagram
86
Shows that restoration of _____ takes precedence over correction of metabolic alkalosis
volume Give NaCl, restore volume, alkalosis will be corrected
87
In vomiting and diarrhoea, although lose acid and alkali, become alkalotic, why is this?
decreased ECF volume, increased aldosterone = contraciton alkalosis Liquorice contains glycyrrhizic acid, which is very similar to aldosterone, so that excess ingestion = metabolic alkalosis
88
what is the anion gap?
Anion Gap = The difference between the sum of the principal cations ( Na+ and K+) and the principal anions in the plasma (Cl- and HCO3- ) Normally 14-18mmoles/L ie (140 +4) – (104 +24) = 16mmoles/L, (due to plasma proteins)
89
when may it be useful to measure the anion gap?
It can be useful to measure the anion gap in metabolic acidosis
90
what are the patterns of metabolic acidosis in terms of anion gap? and how are they caused
There are 2 patterns of metabolic acidosis in terms of anion gap, in one there is no change from normal and in the other the anion gap increases If the acidosis is due for example to a loss of bicarbonate from the gut, then the reduction of bicarbonate is compensated by an increase in chloride and so there is no change in anion gap However in eg lactic or diabetic acidosis, the reduction in bicarbonate is made up by other anions such as lactate, acetoacetate, b-OH butyrate and so the anion gap is increased
91
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got? pH = 7.32, [HCO-3] = 15 mM, PCO2 = 30mmHg (4kPa) 1. Metabolic Acidosis 2. Metabolic Alkalosis 3. Respiratory Acidosis (acute) 4. Respiratory Acidosis (chronic) 5. Respiratory Alkalosis (acute) 6. Respiratory Alkalosis (chronic)
92
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got? pH = 7.32, [HCO-3] = 33 mM, PCO2 = 60mmHg (8kPa) 1. Metabolic Acidosis 2. Metabolic Alkalosis 3. Respiratory Acidosis (acute) 4. Respiratory Acidosis (chronic) 5. Respiratory Alkalosis (acute) 6. Respiratory Alkalosis (chronic)
93
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got? pH = 7.45, [HCO-3] = 42 mM, PCO2 = 50mmHg (6.7kPa) 1. Metabolic Acidosis 2. Metabolic Alkalosis 3. Respiratory Acidosis (acute) 4. Respiratory Acidosis (chronic) 5. Respiratory Alkalosis (acute) 6. Respiratory Alkalosis (chronic)
94
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got? pH = 7.45, [HCO-3] = 21 mM, PCO2 = 30mmHg (4kPa) 1. Metabolic Acidosis 2. Metabolic Alkalosis 3. Respiratory Acidosis (acute) 4. Respiratory Acidosis (chronic) 5. Respiratory Alkalosis (acute) 6. Respiratory Alkalosis (chronic)
95
A 75 year old man has the following blood gas values: pH = 7.31, PCO2 = 7.7.kPa, (58mmHg), [HCO3-] =36mmoles/l. 1. It is likely that he has renal disease. 2. He may have an acute respiratory infection. 3. It is possible that he may have chronic bronchitis. 4. There will be a decrease in his excretion of ammonium ions. 5. His plasma potassium will be reduced.
3
96
The following acid/base values were obtained: pH = 7.25, [HCO3-] = 12mmoles/l, PCO2 = 3.3kPa (25mmHg) a. They are indicative of a respiratory acidosis b. The reduction in Pco2 is a result of under-breathing c. The subject has probably been taking bicarbonate of soda d. It could be related to impaired renal function e. The subject may have been vomiting very badly
d

year 2 renal (26 decks)

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