Acid-Base Balance and Disorders I Flashcards
(97 cards)
1
Q
Define pH?
A
pH = -log10 (H+)
where (H+) is in mol/L
(H+) = 10-pH mol/L
2
Q
What is normal pH for extracellular fluid (plasma)?
A
pH 7.4 (7.35-7.45)
3
Q
What do the terms alkalaemia and acideamia describe?
A
State of blood pH
4
Q
Acidaemia is a pathological process where pH is?
A
pH <7.35
5
Q
Alkalaemia is a pathological process where pH is?
A
pH >7.45
6
Q
What does a buffer do?
A
Addition or removal of H+ - to minimise pH changes.
A buffer only removes H+ temporarily, does not eliminate it from the body).
7
Q
What are the two buffers in blood?
A
- Bicarbonate (most important)
2. Proteins (albumin, haemoglobin)
8
Q
The Henderson-Hasselbach equation is pH = 6.74 + log (HCO3-/pCO2) - what does this demonstrate?
A
pH reflects the ratio of base/acid (HCO3/pCO2) - you never actually measure H+.
9
Q
Respiratory control of pCO2 - how does increased and decreased pCO2 affect pH levels?
A
Increased pCO2 > low pH > acidosis
Decreased pCO2 > high pH > alkolosis
10
Q
CO2 is the byproduct of metabolism - how is pH related to control of pCO2?
A
Low pH stimulates ventilation and CO2 is expired, so ventilation rate controls pCO2 and thereby pH.
Increased pCO2 > low pH > increased ventilation
Decreased pCO2 > high pH > decreased ventilated
11
Q
A patient with severe acute asthma is admitted to hospital - what is likely to be happening?
A
Bronchiolar restriction > reduced ability to ventilate > retaining pCO2 > respiratory acidosis
12
Q
A patient is light-headed and has pins and needles (parasthesiae) in his feet and hands and was having cramps in his hand muscles (tetany) - what is likely to be happening?
A
Decreased pCO2 (as a result of increased ventilation - hyperventilation) > high pH > respiratory alkolosis
13
Q
How can respiratory alkolosis as a result of hyperventilation be resolved?
A
Breathe in to a paper bag > rebreathe CO2 > increase CO2 > normalise pH
14
Q
What are the two main features of metabolic acidosis?
A
- Low pH
2. Low bicarbonate
15
Q
What is diabetic ketoacidosis?
A
- Absolute deficiency of insulin
- Cannot get glucose in to muscle cells
- Ketogenic metabolism produce ketone bodies which are acidic
- High H+, low pH and low HCO3
16
Q
What are the urinary buffers used by the kidney to get rid of the acid?
A
Phosphate and ammonia
H+ + PO43- <> H3PO4 (phosphoric acid)
H+ + NH3 <> NH4+ (ammonium ions)
17
Q
What are the main causes of metabolic acidosis?
A
- Increased acid production
(lactic acidosis, diabetic ketoacidosis) - Decreased acid excretion
(renal failure, renal tubular acidosis) - Bicarbonate loss
(severe diarrhoea, ileostomy - removing large bowel and putting part of small bowel on to surface of abdomen wall)
18
Q
What are some rare causes of metabolic acidosis?
A
- Methanol and ethylene glycol poisoning.
- Glue and paint sniffing
- Alcoholic ketoacidosis
- Genetic metabolic disorders (organic acidemias)
- Bladder diversion operations
19
Q
What are the two main features of metabolic alkolosis?
A
- High pH
2. High bicarbonate
20
Q
What are the normal measurements for pH, bicarbonate, and pCO2?
A
pH 7.4 (7.35 - 7.45)
Bicarbonate mmol/L 24 (22-26)
pCO2 5.3 (4.6-6.0)
21
Q
What is the type of acid-base disturbance if pH is high and bicarbonate levels are high?
A
Metabolic alkolosis
22
Q
What is the type of acid-base disturbance if pH is low and pCO2 levels are high?
A
Respiratory acidosis (acute)
23
Q
What is the type of acid-base disturbance if pH is high and pCO2 levels are low?
A
Respiratory alkolosis (acute)
24
Q
What is the type of acid-base disturbance if pH is low, bicarbonate levels are very low, and pCO2 is also low?
A
Metabolic acidosis
25
What is the type of acid-base disturbance if pH is low, bicarbonate levels are low, and pCO2 levels are high?
Mixed respiratory acidosis and metabolic acidosis.
26
What is acidotic breathing?
When low pH stimulates ventilation, lowering pCO2.
27
How does uncompensated metabolic acidosis differ from compensated metabolic acidosis?
Uncompensated metabolic acidosis has lower pH and lower bicarbonate levels, when pCO2 decreases to try and balance this than that is compensated.
28
What is the role of the kidney in acid-base balance?
Where does each of these processes occur?
1. Reabsorb bicarbonate HCO3(with carbonic anhydrase).
- proximal tubule
2. Production of new HCO3 – glutamine metabolism of NH4+ + HCO3-
- late distal convoluted tubule, connecting tubule and collecting duct
2. Using urinary buffers to get rid of the acid. By metabolising glutamine in to ammonia (NH3) and phosphate (PO43-) of which both are permeable to the apical surface of cell membrane - these then traps H+ ions in lumen and NH4+ (ammonium ion) and H3PO4 phosphoric acid can not permeate back in to cell so is passed in the urine.
- late distal convoluted tubule, connecting tubule and collecting duct.
29
What does titratable acid/base refer to?
The amount of acid/base required to counteract the current imbalance and return pH level back to 7.4.
30
What is the net acid excretion (NAE) equation?
```
NAE = (U NH4 + U TA - UHCO3) x V
NH4 - ammonium
TA - titratable acid
HCO3 - bicarbonate
U - urine concentration
V - Volume
```
31
What are the three main renal processes?
1. Bicarbonate reabsorption
2. Bicarbonate generation
3. H+ secretion in distal nephron (distal tubule and collecting duct) - mainly ammonia and phosphate.
32
What is glomerular filtration of HCO3 per day?
4000 mmol/day
33
Where in the kidney is HCO3 reabsorbed?
Mostly in the proximal tubule with a little more in thick ascending limb of Loop of Henle.
34
Explain the process, 7 part, of bicarbonate reabsorption by the proximal tubule.
1. NHE (Na+/H+ exchanger) antiporter located on the apical surface of the proximal tubule cell uptakes Na+ which drives H+ extrusion into lumen - lowering pH.
2. Together with the HCO3 (bicarbonate) the H+ in the lumen forms H2CO3 (carbonic acid).
3. In the presence of carbonic anhydrase the H2CO3 is converted to H2O and CO2.
4. CO2 is reabsorbed into the cytosol.
5. CO2 together with H2O and in the presence of carbonic anhydrase forms H2CO3
6. H2CO3 separates into H+ and HCO3
7. H+ cycles back out to lumen via NHE and HCO3 returns to plasma via basolateral membrane transporters.
35
Acetazolamide is a carbonic anhydrase inhibitor - what does is cause and why is it used?
Causes metabolic acidosis, so is used in mountaineering to counteract alkalosis due to hyperventilation.
36
What two types of cells are present in the collecting duct?
1. Principal cells
| 2. Intercalated cells
37
Intercalated cells have cellular mechanisms for H+ and HCO3- secretion - what are these?
H+ secretion = alpha IC cells (acid)
Secretes acid to tubular fluid
Secretes base to blood
HCO3- secretion = beta IC cells (base)
Secretes base to the tubular fluid
Secretes acid to the blood
38
The principal cells are involved in H+ excretion in the distal tubule/collecting duct, how is this achieved?
1. Aldosterone sensitive ENaC (epithelial Na channel) drive the movement of Na from lumen in to the blood.
2. Na/K ATPase channels on basal membrane pushes Na from the cell into ECF and K in to cell.
3. Transepithelial potential drives K+ and H+ secretion into the lumen.
4. Paracellular absorption of chlorine occurs.
5. More negative charge in the lumen so more drive for H+ (and K+) excretion (acid excretion).
39
What is the cellular mechanism for the generation of new HCO3?
1. In the presence of carbonic anhydrase within the cells CO2 and H20 forms H+ and HCO3.
2. H+ is secreted into the tubular fluid and joins a urinary buffer.
3. HCO3 is secreted towards to ECF and blood as a buffer.
40
What are the two urinary buffers?
1. Phosphate
| 2. Ammonia
41
Outline renal handling of ammonium ion (NH4+)?
1. Ammonium is generated from glutamine in proximal tubule cells and secreted into lumen
2. 2 x HCO3 is also produced which is reabsorbed in the TAL.
3. In the collection duct -
A) NH4 secreted into lumen via diffusion trapping of NH3 with the H+ (ammonium is not able to freely diffuse).
B) via direct secretion
42
What is the response of the kidney to acidosis?
1. Increased HCO3 and H+ transport along the nephron
2. Increased ammoniogenesis
3. Increased availability of urinary buffers
43
What are the main points of renal compensation in respiratory acidosis.
1. Renal compensation that deals with an acid/base disorder
2. Needs some time to adjust
3. Respiratory system is more instantaneous
Normal pH> respiratory acidosis which is rapid > bicarbonate generations that takes days to adjust > respiratory acidosis with renal compensation
44
What are the three main mechanisms for renal compensation?
1. Bicarbonate absorption
2. Bicarbonate regeneration
3. Increased ammonia secretion
45
A 60 year old man developed emphysema after smoking since age 20, how is renal compensation taking place?
CO2 retention > reduced pH > respirator acidosis > increased bicarbonate levels
By increasing bicarbonate the kidneys have restored the pH ratio towards norma (renal compensation).
Increased net acid excretion as a result of bicarbonate absorption, bicarbonate regeneration, and ammonia secretion.
46
What is the 3-step approach for simple interpretation of acid-base data?
1. Is it an acidosis (low pH) or alkalosis (high pH)
Look at the pH
2. Is the primary disturbance respiratory or metabolic?
Look at the pCO2, bicarbonate or base excess.
3. Is it compensated or not
Look at the non-primary component.
47
What is the detailed approach to interpreting acid-base data?
1. What is the primary diagnosis?
- Acidaemia/Alkalaemia first, then; Is it a primary acidosis or primary alkalosis (Look at the pH)
- Is the primary disturbance respiratory or metabolic? (Look at the pCO2, bicarbonate (and base excess))
2. Is the compensation appropriate?
- Use an acid base map or use a 'rule of thumb' (inappropriate compensation implies a mixed disorder)
3. Calculate the anion gap.
(A high anion gap implies metabolic acidosis is present, and can determine the diagnosis).
4. Calculate the delta anion gap/delta HCO3 ratio.
(This helps to identify the presence of a co-existing metabolic acidosis or alkalosis).
48
What is an acid-base map?
A graphical tool that allows a clinician or investigator to describe blood bicarbonate concentrations, blood pH, and pCO2 an acid-base disturbance - metabolic, respiratory, mixed, chronic, or acute.
49
With metabolic acidosis what is the primary change and the compensatory response?
Decrease in HCO3 (either loss of HCO3- or gain of H+)
| Decrease in pCO2 - respiratory compensation, acute
50
With metabolic alkalosis what is the primary change and the compensatory response?
Increase in HCO3 (either gain of HCO3- or loss of H+)
| Increase in pCO2 - respiratory compensation, acute
51
With respiratory acidosis the primary change is an increase in pCO2, what occurs with acute RA?
Change is over a period of <24 hours, and kidneys compensate by increasing HCO3 by 1mmol/L for every 1.3kPa increase in pCO2.
52
With respiratory acidosis the primary change is an increase in pCO2, what occurs with chronic RA?
Change is >24 hours, and kidneys compensate by increasing HCO3 by 3.5mmol/L for every 1.3kPa increase in pCO2.
53
Compensation never returns your pH to normal, with one exception, what is that exception?
Respiratory alkalosis that applies to people living in high altitudes. The Sherpa's have respiratory alkalosis but normal pH, so are able to fully compensat
54
```
Case one - what is the condition:
pH (7.4) - 7.30
pCO2 (kPa) (5.3) - 7.0
Bicarbonate (24) - 25
Base Excess (0) - -1
```
Respiratory acidosis (not compensated)
55
```
Case two - what is the condition:
pH (7.4) - 7.20
pCO2 (kPa) (5.3) - 3.5
Bicarbonate (24) - 9
Base Excess (0) - -18
```
Metabolic acidosis with respiratory compensation.
| Base excess of -18 where base is needed to balance.
56
```
Case three - what is the condition:
pH (7.4) - 7.50
pCO2 (kPa) (5.3) - 6.5
Bicarbonate (24) - 37
Base Excess (0) - +13
```
Metabolic alkalosis with respiratory compensation.
| Base excess of +13 where base is needed to balance.
57
```
Case four - what is the condition:
pH (7.4) - 7.20
pCO2 (kPa) (5.3) - 4.5
Bicarbonate (24) - 13
Base Excess (0) - -14
```
Metabolic acidosis with respiratory compensation.
| Base excess of -14 where base is needed to balance.
58
```
Case five - what is the condition:
pH (7.4) - 7.32
pCO2 (kPa) (5.3) - 8.5
Bicarbonate (24) - 32
Base Excess (0) - +6
```
Respiratory acidosis
??
59
```
Case six - what is the condition:
pH (7.4) - 7.42
pCO2 (kPa) (5.3) - 3.5
Bicarbonate (24) - 17
Base Excess (0) - -7
```
alkalosis
??
60
Does base excess relate to metabolic conditions, respiratory conditions, or both?
Metabolic conditions only.
61
What is the definition of base excess?
Amount of acid or base needed to restore pH to 7.4 (at a pCO2 of 5.3 kPa).
62
What is normal base excess?
0 (-2 to +2)
63
Base excess is a calculated parameter from what?
pH, pCO2 and haemoglobin
64
When is base excess positive and when is it negative?
Base excess is positive in metabolic alkalosis.
| Base excess is negative in metabolic acidosis.
65
What does base excess reflect?
ALL buffers in plasma (not only bicarbonate)
| It demonstrates how much base or acid is needed to get the level back to normal.
66
```
A patient with chronic lung disease on a ventilator in ICU.
pH (7.4) - 7.55
pCO2 (kPa) (5.3) - 5.2
Bicarbonate (24) - 33
Base Excess (0) - +10
```
What type of acid-base disturbance is this?
How did it arise?
Respiratory acidosis with renal/metabolic compensation
On the ventilator respiratory component is corrected, but the compensating metabolic alkalosis remains. Also known as post-hypercapnic alkalosis.
BE is positive because metabolic condition is chronic metabolic alkalosis.
67
When is the anion gap (AG) useful - metabolic conditions, respiratory conditions, or both?
Metabolic conditions only
68
What is the normal AG range?
14 - 18
69
How is the AG parameter defined?
AG = (Na+ + K+) - (Cl- + bicarb)
= (140 + 4) - (104 + 24)
= 16
Add all cations and add all anion
Cations - anions = anion gap.
70
What does normal AG reflect (mainly)?
Proteins and albumin
71
What does increased AG indicate?
The presence of unmeasured anions (extra proteins, lactate and other anions).
72
What is the three part approach to metabolic acidosis?
1. Confirm metabolic acidosis.
- low pH with a low HCO3
2. Check serum anion
- High = anion gap acidosis
- Normal = non-anion gap acidosis
3. If normal serum anion gap, check urine anion gap.
73
What are the most common causes of acidosis with increased anion gap?
1. Lactic acidosis
2. Diabetic ketoacidosis (beta-hydroxybutyrate is the main anion)
3. Alcoholic ketoacidosis
4. Starvation ketoacidosis
5. Renal failure (severe, i.e. due to uraemic toxins/failure of acid excretion
74
What are rare causes for high AG acidosis?
1. Methanol poisoning (formate anion)
2. Ethylene glycol - anti-freeze - poisoning (glycolate, glyoxylate and oxalate anions)
3. Salicytate (asprin) overdose
4. Organic acidurias (children (e.g. methylmalonic aciduria)
5. Pyroglutamic aciduria (critically ill adults administered paracetamol)
75
42 year old man admitted semi-comatose with seizures.
```
pO2 (10.6 - 13.3 kPa) - 12.0
pH (7.4) - 7.15
pCO2 (kPa) (5.3) - 3.0
Bicarbonate (24) - 8
Base Excess (0) - -19
```
Na (135-145) - 140
K (3.5 - 5.0) - 4.0
Cl (95-110) - 102
What type of acid-base disturbance is this?
How did it arise?
Metabolic acidosis, pCO2 is low to compensate.
AG = (Na+ + K+) - (Cl- + bicarb)
= (140 + 4) - (102 + 8)
= 144-110
=34
High anion gap
76
How is ethylene glycol (anti-freeze) poisonous?
Ethylene glycol in itself is not poisonous but:
| ethylene glycol + alcohol dehydrogenase (liver) > glycolic and oxalic acid (toxic metabolites)
77
How is ethylene glycol poisoning treated?
Ethanol (alcohol) or the drug fomepizole.
They compete for the enzyme alcohol dehydrogenase so that the toxic metabolites are not formed.
Could also use dialyses with the above treatment to get rid of the poison.
78
Non-renal causes are the main causes of normal anion gap acidosis (hyperchloremic acidosis) - what is this?
Normal renal acidification, loss of bicarbonate
Largely from bowel - i.e. diarrhoea, GI ureteral connections (ileostomy) or external loss of pancreatic or biliary secretions.
79
What are renal causes of normal anion gap acidosis?
Failure of renal acidification
Proximal renal tubular acidosis, hyperkalaemic distal renal tubular acidosis.
80
What is renal tubular acidosis (RTA)?
Defects in acid excretion; urine pH >5.5 and urine ammonium not increased (inappropriate for metabolic acidosis).
81
What is Type 4 RTA (with hyperkalaemia)?
Aldosterone deficiency or resistance i.e. Addisons Disease.
| Glue or pain sniffing (toluene metabolised to hippuric).
82
A 9 year old girl presented with growth delay - features of rickets were seen on x-rays.
pH (7.4) - 7.2
pCO2 (kPa) (5.3) - 4.0
Bicarbonate (24) - 11
Base Excess (0) - -17
Na (135-145) - 140
K (3.5 - 5.0) - 3.6
Cl (95-110) - 115
Albumin, calcium, phosphate, vit D: normal
Anion gap (Na + K) - (Cl + HCO3) = 17 (12-20)
What type of acid-base disturbance is this?
What further tests should be performed?
NOTE: Rickets is sometimes associated with renal tubule acidification.
Metabolic acidosis, with respiratory compensation.
Negative base excess confirms metabolic acidosis.
Normal anion gap acidosis - and thereby caused by loss of HCO3 (mostly from bowel), or kidney not acidifying the urine adequately.
Further tests:
Urine pH: 6.5
Urine ammonium: 45 mmol/L
Urine anion gap = Na + K -Cl (another means to estimate urinary ammonium) - A way to determine if it's a renal tubular acidosis.
Interpretation: In the presence of an acidosis urine pH should be <5.5 and ammonium should be >100mmol/L
Diagnosis: Renal tubular acidosis.
If the urine pH is inappropriate for the acidosis, then it must be an RTA.
In metabolic acidosis:
UAG positive = suggest low NH4+
UAG negative = suggest high NH4+
(appropriate acidification)
83
Why is a patient hyperchloremic (high chloride) with normal anion gap acidosis?
To maintain electroneutrality - so if a patient has normal anion gap acidosis it's because the kidney compensates for lack of ability to reabsorb negatively charged bicarbonate HCO3- by reabsorbing more Cl-.
84
What is the association between potassium and acid-base - "the rule"?
Acidosis <> hyperkalemia (high potassium)
| Alkalosis <> hypokalemia (low potassium)
85
What are the 2 mechanisms for the link between potassium and acid-base?
1. H+ and K+ are either driven in to the cell (acidosis/hyperkalemia) or out of the cell (alkalosis/hypokalemia).
Exceptions being diarrhoea and renal tubule acidosis.
2. H+ and K+ complete with each other for secretion into the lumen.
86
A 21 year old woman presented with muscle weakness.
A keen runner. She had no periods for a year, since starting marathon training.
```
Na (135-145) - 140
K (3.5 - 5.0) - 2.5
Cl (95-110) - 88
pH (7.4) - 7.55
pCO2 (kPa) (4.6 - 6.0) - 5.8
Bicarbonate (24) - 37
Base Excess (0) - +14
```
Urine electrolytes:
Na+ 30mmol/L
K+ 7mmol/L
Cl+ <10mmol/L
She denied and history of vomiting.
What type of acid-base disturbance is this?
After much counselling, she admitted to inducing vomiting (bulimia) and to frequent use of laxatives.
Diagnosis: Metabolic alkalosis with hypokalemia and chloride depletion.
Answer - alkalosis with chloride depletion.
Pathogenesis:
1. Loss of HCl due to vomiting causes alkalosis
2. Hypokalemia is due to (a) alkalosis and (b) K+ loss due to excessive laxative use*
3. Hypokalemia causes muscle weakness (hyperpolarises excitable cells)
*In chronic diarrhoea K+ loss predominates, due to Na/K exchange in the colon. In acute diarrhoea Na+ loss predominates.
87
What are the two types of metabolic alkalosis?
1. Chloride responsive (chloride related)
| 2. Chloride resistant (not chloride related)
88
What are the two main causes of chloride-responsive metabolic alkalosis?
1. Vomiting or gastric drainage (loss of H+ and Cl-)
| 2. Diuretic-induced alkalosis (K+ and Cl loss)
89
What is the main cause of chloride-resistant metabolic alkalosis?
Mineralocorticoid excess (primary aldosteronism, apparent MC excess, fludrocortisone)
90
What can aldosterone lead to metabolic alkalosis?
ENaC channels are sensitive to aldosterone, so high aldosterone results in high Na+ reabsorption at the expense of H+/K+ excretion, leading to metabolic alkalosis.
91
How can chloride-depletion be recognised?
1. Low plasma Cl-
2. Urine Cl- <10 mmol/L
3. ECF volume depletion
92
What occurs in chloride-responsive metabolic alkalosis?
1. Kidneys attempt to increase HCO3 loss
2. if chloride-depletion is present, bicarbonate reabsorption becomes obligatory to preserve Na+ balancd (electroneutrality)
3. The kidney cannot correct the alkalosis unless chloride is replaced (it keeps reabsorbing HCO3- 'inappropriately').
93
What are causes of Cl depletion?
Gastric fluid loss and diuretics.
94
Arterial vs venous blood gas - what is the gold standard and what are the issues with having that undertaken?
Arterial puncture is gold standard however it can be painful, occasionally leads to severe complications (thrombosis, haemorrhage).
95
When is it OK to use venous blood for blood gases?
In patients with reasonable perfusion, pH, bicarbonate and base excess are almost identical in venous and arterial blood.
Venous blood gases are perfection OK when - pO2 is not needed AND severe circulatory failure is not present.
Examples include - diabetic ketoacidosis, renal acidosis, poisoning cases.
96
Name two causes of artefacts in blood gases and what the result is for each?
1. Air in blood-gas syringe (falsely low pCO2, apparent respiratory alkalosis).
2. Delayed separation of plasma from RBCs (RBCs produce lactic acid, leading to an apparent lactic acidosis (a metabolic acidosis with high AG).
97
Case quiz:
The following results were obtained on a baby with pyloric stenosis (which causes obstruction to stomach emptying) who had severe vomiting for a prolonged period.
Na+ 137 (N 135-145)
K+ 2.2 (N3.5 -5.1)
HCO3 44 (N 22-28)
Questions:
1. What is the predominant cation in gastric juice?
2. What is the predominant anion in gastric juice?
3. Explain why potassium is low.
4. What acid base disorder is likely to be present?
1. H+
2. Cl-
3. Because of the loss of H+ the patient is alkalotic (where H+ and K+ are driven out of the cell - alkalotic <>hypokalemia
4. chloride-responsive metabolic alkalosis - caused by vomiting or gastric drainage (loss of H+ and CL-)
chloride-responsive metabolic alkalosis?Vomiting or gastric drainage (loss of H+ and Cl-)
