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
* Just recovery of HCO3- wont be enough-which amino acid is used to make more HCO3-?
glutamine --\> alpha ketoglutate + NH4=
NH4--\> NH3+ (excreted) + H+
alpha-ketoglutarate --\> 2HCO3- (reabsorbed)
26
H+ excretion
* 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
* Excretion of .......... is the major adaptive response to an increased acid load in healthy individuals
* 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
minimum pH of urine is
4.5
29
ions in urine
* 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
acidosis leads to
hyperkalaemia
31
how does acidosis lead to hypokalaemia
* Hydrogen ions move into the cell
* Potassium ions moves out of cells
* Decreased potassium excretion in distal nephron
32
alkalosis can lead to
hypokalamaeia
* H+ moves out of cell
* Potassium ions move into cell
* Enhanced excretion of potassium in distal nephrons
33
**Acid base disturbances and potassium- hyperkalamia**
* **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
Acid base disturbances and potassium- hypokalamia
* **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
effect of respiratory acidosis on the ABG
* Hypoventilation --\> hypercapnia (pCO2 rises)
* Hypercapnia --\> fall in plasma pH
* Respiratory acidosis
* Characterised by
* High pCO2
* Normal HCO3-
* Low pH
36
**Respiratory alkalosis and the ABG**
* Hyperventilation hypocapnia (fall in pCO2- blowing off CO2)
* Hypocapnia rise in pH
* Resp alkalosis
* Characterised by
* Low pCO2
* Normal HCO3-
37
1. **Compensated respiratory acidosis**
* High pCO2 (due to hypoventilation)
* Raised [HCO3-]--\> kidneys help kicked in
* Relatively normal pH (fully (if slightly compensated= partial compensation)
38
1. **Compensated respiratory alkalosis**
* Low pCO2 (hyperventilating)
* Lowered [HCO3-]
* Relatively normal pH
* Raised pH
39
40
**Compensation**
* 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
the anion gap
* 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
Renal causes of acidosis and the anion gap
will be unchanged
Not making enough HCO3- but this is replaced by Cl-
Renal problem when Cl- replaces the HCO3-
43
Metabolic problem and anion gap
44
**Metabolic acidosis and ABG**
* 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
**3. Compensated metabolic acidosis**
* Peripheral chemoreceptors (carotid bodies) detect pH drop
* Stimulate ventilation
* Leading to decrease pCO2
* Characterised by:
* Low HCO3-
* Lowered pCO2
* Nearer normal pH
46
**Metabolic alkalosis**
* 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
**Conditions leading to respiratory acidosis**
* **Type 2 respiratory failure**
48
* **Type 2 respiratory failure**
* * Low pO2 and High pCO2
* The alveoli cannot be properly ventilated
* Severe COPD, severe asthma, drug overdose, neuromuscular disease (myasthenia gravis)
* Can be compensated for by increase in [HCO3-]
* Chronic conditions can be well compensated such that pH near normal
49
**Conditions leading to respiratory alkalosis**
* *
* Hyperventilation
* Anxiety / panic attacks – acute setting – Low pCO2, rise in pH
* Hyperventilation in response to long-term hypoxia – **Type 1 respiratory failure**
50
Type 1 respiratory failure
* 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
**Conditions leading to metabolic acidosis**
* **If anion gap is INCREASED**
*
* – 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
52
metabolic acidosis
* **If anion gap is NORMAL**
*
* 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
53
**Metabolic acidosis and potassium**
*
* 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
**Conditions leading to metabolic alkalosis**
* 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
conditions leading to **Metabolic alkalosis**
* *
* [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
**Metabolic alkalosis and potassium**
* Less H+ excretion in nephron leads to more K+ excreted
* Alkalosis also causes movement of K+ ions into cells
* This leads to hypokalaemia
57
* If pCO2 is not normal, [HCO3-] is normal and pH has changed in opp direction to pCO2
Respiratory acidosis/alkalosis
58
* If [HCO3-] is not normal, pCO2 is normal and pH has changed in the same direction as [HCO3-]
*
Metabolic acidosis/alkalosis
59
* If pCO2 is high, [HCO3-] is raised and pH is relatively normal
*
* Compensated resp acidosis
* This is only scenario as we cant compensate metabolic alkalosis
60
61
* If [HCO3-] is low, pCO2 is low, pH is normal
*
* 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
