Lecture 9 - Respiratory and Urinary Unit Acid-Base Balance Flashcards
1
Q
- Kidneys and resp system work together to
A
maintain pH homeostasis
2
Q
- Lungs …………. responders
- Kidneys ……….. ……….. homeostasis- takes days for full compensation
- Both essential
A
- Lungs rapid responders
- Kidneys longer term homeostasis- takes days for full compensation
- Both essential
3
Q
- pH homeostasis primarily determined by
A
CO2- bicarbonate system
4
Q
- ratio of[bicarbonate]: [CO2] must remail equal to
A
20/21/:1 – pH will remain 7.4
5
Q
- [CO2] determined by
A
lungs
6
Q
- [HCO3-] determined by
A
kidneys
7
Q
how do the kdimeys control [HCO3-]
A
- Absorption
- Secretion
- Synthesis
8
Q
pH equation and how it relates to CO2 and bicarbonate
A
pH= 6.1 + log([HCO3-]/ 0.03x [pCO2])
if HCO3- conc gets smaller= pH will be lower
if pCO2 gets smaller= pH will be higher
9
Q
- Plasma pH must be maintained within a tight range
A
- pH 7.35-7.45
10
Q
- Plasma pH greater than 7.45-
A
- alkalosis
11
Q
Plasma pH less than 7.35-
A
acidosis
12
Q
which is most dangerpis alkalosis or acidosis
A
alkalosis
13
Q
why is alkalosis more dangerous
A
- Alkalaemia lowers free calcium by causing Ca2+ to come out of solution increases neuronal excitability
- pH>7.45 leads to paraesthesia and tetany
- Issue when affects lung muscles
- 45% mortality if higher than 7.55
- 80% if higher than 7.65
14
Q
acidodis increases which plasma ion
A
potassium
- Effected excitability
- Due to increase in potassium conc
- Particularly affects heart- arrhythmia
- Increasing [H+] affects enzymes and proteins
- Effects muscles contractility, glycolysis, hepatic function
- Effects severe below pH 7.1
- Life threatening below pH 7
15
Q
plasma pH depends on
A
- pH depends on ratio of [HCO3-] to pCO2
16
Q
- pCO2 determined by respiration but controlled by
A
- controlled by chemoreceptors
- disturbed by resp disease
17
Q
- [HCO3-] determined by the kidneys
- Disturbed by
A
metabolic and renal disease
18
Q
Henderson Hasselbach equation for plasma pH
A
19
Q
how do the kidneys control plasma pH
A
- Control pH- variable recovery of HCO3- and active secretion of hydrogen ions
20
Q
how do the lungs control plasma pH
A
- Alveolar ventilation allows diffusion of O2 into blood and CO2 out of blood- control pO2 and pCO2
- Rate of ventilation controlled by chemoreceptors
21
Q
pH of arterial blood
A
- Determined by ratio of pCO2 and [HCO3-]
- HCO3- made in RBC
- But conc controlled by kidneys
- Normal conc in arterial blood is around 25 mmol.-1
- Range 22-26
- Can be changed to maintain pH
22
Q
why do we produe acid
A
due to metabolism
23
Q
why does acid production due to metabolism not deplete HCO3-
A
- We produce acid due to metabolism
- This does not deplete HCO3- because
- Kidneys recover all filtered HCO3-
- Proximal tubule makes HCO3- from amino acids (glutamine), putting NH3 into urine
- DCT make HCO3- from co2 and h2o
- h+ is buffered by phosphate and ammonia in the urine
24
Q
Renal control of HCO3-
A
- HCO3- filtered at the glomerulus
- Mostly recovered in PCT
- H+ excretion linked to Na+ entry in PCT
- H2CO3 carbonic anhydrase HCO3- + H+)
- H+ reacts with HCO3- in the lumen to form CO2 which enters cells
- Converted back to HCO3- which enter ECF
25
Q
- Just recovery of HCO3- wont be enough-which amino acid is used to make more HCO3-?
A
glutamine –> alpha ketoglutate + NH4=
NH4–> NH3+ (excreted) + H+
alpha-ketoglutarate –> 2HCO3- (reabsorbed)
26
Q
H+ excretion
A
- DCT and CD ducts also secrete H+ produced from reaction of CO2 with water
- H+ ions are actively secreted
- H+ buffered by ammonia and phosphate (titratable)
- Produce NH4+ and H2PO4- which are excreted
- No CO2 is formed to re-enter the cell
- Allows HCO3- to enter the plasma
27
Q
- Excretion of ………. is the major adaptive response to an increased acid load in healthy individuals
A
- Ammonium generation from glutamine in PCT can be increased in response to low pH
- NH4+ –> NH3 + H+ (PCT – major adaptive response to increase in H+)
- NH3 freely moves into lumen and throughout interstitium
- H+ actively pumped into lumen in the DCT and CT
- H+ combines with NH3–> NH4+ (trapped in lumen forever)
- NH4+ can also be taken up in the TAL and transported to interstitium and dissociated to H+ and NH3 –> lumen of collecting ducts
28
Q
minimum pH of urine is
A
4.5
29
Q
ions in urine
A
- No HCO3- (all has been recovered)
- Some H+ is buffered by phosphate (titratable)
- Some has reacted with ammonia to form ammonium
- Total acid excretion = 50-10-0 mmol H+ per day
- This is needed to keep [HCO3-] normal
30
Q
acidosis leads to
A
hyperkalaemia
31
Q
how does acidosis lead to hypokalaemia
A
- Hydrogen ions move into the cell
- Potassium ions moves out of cells
- Decreased potassium excretion in distal nephron
32
Q
alkalosis can lead to
A
hypokalamaeia
- H+ moves out of cell
- Potassium ions move into cell
- Enhanced excretion of potassium in distal nephrons
33
Q
Acid base disturbances and potassium- hyperkalamia
A
-
Hyperkalaemia makes intracellular pH of tubular cells more alkaline (intracellular alkalosis)
- H+ ions move out of the cells
- This favours HCO3- excretion
- Metabolic acidosis (in the plasma)
34
Q
Acid base disturbances and potassium- hypokalamia
A
-
Hypokalaemia makes the intracellular pH of tubular cells more acidic (intracellular alkalosis)
- H+ ions move into the cells
- This favour H+ excretion and hCO3- recovery
- Metabolic alkalosis (in the plasma)
35
Q
effect of respiratory acidosis on the ABG
A
- Hypoventilation –> hypercapnia (pCO2 rises)
- Hypercapnia –> fall in plasma pH
- Respiratory acidosis
- Characterised by
- High pCO2
- Normal HCO3-
- Low pH
36
Q
Respiratory alkalosis and the ABG
A
- Hyperventilation hypocapnia (fall in pCO2- blowing off CO2)
- Hypocapnia rise in pH
- Resp alkalosis
- Characterised by
- Low pCO2
- Normal HCO3-
37
Q
- Compensated respiratory acidosis
A
- High pCO2 (due to hypoventilation)
- Raised [HCO3-]–> kidneys help kicked in
- Relatively normal pH (fully (if slightly compensated= partial compensation)
38
Q
- Compensated respiratory alkalosis
A
- Low pCO2 (hyperventilating)
- Lowered [HCO3-]
- Relatively normal pH
- Raised pH
39
Q
A
40
Q
Compensation
A
- Plasma pH depends on ratio of [HCO3-] to pCO2 not on their absolute values
- Changes in pCO2 can be compensated by changes in [HCO3-]
- Kidneys increase [HCO3-] to compensate for resp acidosis
- Kidneys decrease [HCO3-] to compensate for resp alkalosis
- Takes time…. 2-3 days
41
Q
the anion gap
A
- Difference between measured cations and anions
- ([Na+] + [K+]) – ([Cl-] + [HCO3-])
- Normally 10-18 mmol-1
- Due to other anions that are not measured
- This gap is increased if HCO3- is replaced by other anions
- If metabolic acid (such as lactic acid) reacts with HCO3- the anion of the acid replaced HCO3-
42
Q
Renal causes of acidosis and the anion gap
A
will be unchanged
Not making enough HCO3- but this is replaced by Cl-
Renal problem when Cl- replaces the HCO3-
43
Q
Metabolic problem and anion gap
A
44
Q
Metabolic acidosis and ABG
A
- Normal CO2 (no breathing problem)
- Low HCO3- (problem with kidneys)
- Low pH
- Increased anion gap if HCO3- is replaced by another organic anion from an acid
- BUT HCO3- normal anion gap if replaced by Cl-
45
Q
3. Compensated metabolic acidosis
A
- Peripheral chemoreceptors (carotid bodies) detect pH drop
- Stimulate ventilation
- Leading to decrease pCO2
- Characterised by:
- Low HCO3-
- Lowered pCO2
- Nearer normal pH
- Characterised by:
46
Q
Metabolic alkalosis
A
- If [HCO3] increases
- Normal pCO2
- Raised HCO3-
- Increased pH
- Cannot normally be compensated to a great extent by reducing breathing – need to maintain pO2
- Should be easy for kidney to correct- see later
47
Q
Conditions leading to respiratory acidosis
A
- Type 2 respiratory failure
48
Q
- Type 2 respiratory failure
A
- Low pO2 and High pCO2
- The alveoli cannot be properly ventilated
- Severe COPD, severe asthma, drug overdose, neuromuscular disease (myasthenia gravis)
- Low pO2 and High pCO2
- Can be compensated for by increase in [HCO3-]
- Chronic conditions can be well compensated such that pH near normal
49
Q
Conditions leading to respiratory alkalosis
- *
A
- Hyperventilation
- Anxiety / panic attacks – acute setting – Low pCO2, rise in pH
- Hyperventilation in response to long-term hypoxia – Type 1 respiratory failure
50
Q
Type 1 respiratory failure
A
- cause of resp alkalosis
- Low pCO2 with initial rise in pH
- Chronic hyperventilation can be compensated for by fall in [HCO3-]
- Can restore pH to near normal
51
Q
Conditions leading to metabolic acidosis
-
If anion gap is INCREASED
*
A
- – indicates a metabolic production of an acid
- Keto-acidosis
- diabetes
- Lactic acidosis
- Exercising to exhaustion
- Poor tissue perfusion
- Uraemic acidosis
- Advanced renal failure – reduced acid secretion, build up of phosphate, sulphate, urate in blood
- Keto-acidosis
52
Q
metabolic acidosis
-
If anion gap is NORMAL
*
A
- HCO3- is replaced by Cl-
- Renal tubular acidosis (rare)
- Problem with transport mechanism in tubules
- Type 1 (distal) RTA- inability to pump out H+
- Type 2 (proximal) RTA (VERY RARE) – problems with HCO3- reabsorption
- Severe persistent diarrhoea can also lead to metabolic acidosis due to loss of HCO3-
- Replaced by Cl-
- Therefore anion gap unaltered
- Renal tubular acidosis (rare)
53
Q
Metabolic acidosis and potassium
*
A
- Non-renal causes of metabolic acidosis cause increase reabsorption of K+ by kidneys
- And movement of K+ by kidneys
- Hyperkalaemia
- However in diabetic ketoacidosis may be due to total body depletion of K+
- K+ moves out of cell (due to acidodis and lack of insulin)
- But osmotic diuresis means K+ lost in urine
- Give insulin and K+
54
Q
Conditions leading to metabolic alkalosis
A
- In metabolic alkalosis HCO3- is retained in place of Cl-
- Stomach major site of HCO3- production
- By product of H+ secretion
- Serve prolonged vomiting- loss of H+
- Or mechanical drainage of stomach
- Other causes
- Potassium depletion/ mineralocorticoid excess
- Certain diuretics (loop and thiazide)
55
Q
conditions leading to Metabolic alkalosis
- *
A
- [HCO3-] increase e.g. after persistent vomiting
- This should be easy to correct
- HCO3- can be excreted very rapidly following infusion of HCO3-
- Corrected by
- Rise in pH of tubular cells leads to fall in H+ excretion and reduction in HCO3- recovery
- BUT
- Problem if there is also volume depletion
- Capacity to lose HCO3- is reduced because of high rate of Na+ recovery
- Recovering Na+ favours H+ excretion and HCO3- recovery
56
Q
Metabolic alkalosis and potassium
A
- Less H+ excretion in nephron leads to more K+ excreted
- Alkalosis also causes movement of K+ ions into cells
- This leads to hypokalaemia
57
Q
- If pCO2 is not normal, [HCO3-] is normal and pH has changed in opp direction to pCO2
A
Respiratory acidosis/alkalosis
58
Q
- If [HCO3-] is not normal, pCO2 is normal and pH has changed in the same direction as [HCO3-]
*
A
Metabolic acidosis/alkalosis
59
Q
- If pCO2 is high, [HCO3-] is raised and pH is relatively normal
*
A
- Compensated resp acidosis
- This is only scenario as we cant compensate metabolic alkalosis
60
Q
A
61
Q
- If [HCO3-] is low, pCO2 is low, pH is normal
*
A
- Could either be compensated respiratory alkalosis or compensated metabolic acidosis
- Think history: if no resp disease or altitude, unlikely to be resp
- GO CHECK ANION GAP- if increase it is metabolic acidosis
