How do the lungs and kidneys control acid base balance

Question 1

What’s the normal range for plasma PH? What are the terms for when it is outside this range?

Answer 1

7.35- 7.45

> alkalaemia/ alkalosis

< acidaemia/ acidosis

Question 2

What effects does alkalaemia have on Ca2+ and what does this do? What effect does it have on K+?

Answer 2

Causes Ca2+ to come out of solution and bind to things like albumin and so lowers the free [Ca2+]

Ca2+ is a divalent cation (has 2+ charge) so acts as a charge shielded to protect excitable cells form getting too excitable

So lowering free Ca2+ means increased neuronal excitability -> paraesthesia (sensory neurones) + tetany (motor neurones) - muscular spasms if this occurs respiratory muscles dyspnoea

V serious: if Ph rises to 7.55 45% mortality, if it rises to 7.65 80% mortality

Also decreases plasma K+ bc K+ ions move into call as H+ comes out antiport & then enhanced excretion of K+ in distal nephron

Question 3

What effects does acidaemia have on plasma K+ and what effects does this have?

Answer 3

Increases plasma K+ by more K+ leaving cells antiport with H+ & then decreased K+ excretion in distal nephron, effects excitability

(Particularly for cardiac muscles: hyperkalaemia-> membrane potential depolarises -> inactivates Some voltage-gated Na+ channels-> slows upstoke -> arrthymias and potentially Asytole)

Increased H+ affects many enzymes and denatures proteins -> effects muscle contractility, glycolysis, hepatic function

Severe below 7.1
Life threatening below 7

Question 4

What controls the PCO2 and what disturbs it?

Answer 4

Determined by respiration

Controlled by chemoreceptors

Disturbed by respiratory disease

Question 5

What controls the [HCO3-] and what disturbs it?

Answer 5

Controlled by the kidney

Disturbed by metabolic and renal disease

Question 6

What’s the normal concentration of HCO3- in arterial blood?

Answer 6

22-26mmol.l-1

But can be changed to maintain Ph

Question 7

Explain how the kidneys filter HCO3- and produce it?

Answer 7

• Kidneys recover all filtered HCO3- (80% recovered PCt)
• Proximal tubule makes HCO3- from AA, putting NH4+ into urine

Gluatime makes alpha- ketoglutarate -> HCO3- (enters ECF via Na+ symporter) and NH4+ (enters lumen)

• Distal tubule makes HCO3- from CO2 and H2O, H+ is actively secreted (also at collecting ducts) buffered by phosphate and ammonia in the urine

HCO3- exported out of tubular cell with Na+ symporter basolateral membrane

(Na+ and H+ antiport to let Na+ into tubular cell apical membrane)

Slide 10

Question 8

What’s the major adaptive response to an increased acid load in healthy individuals? What acts as buffer for the urine and why is it important to have one?

Answer 8

Excretion of ammonia

Ammonium generation
from glutamine in proximal tubule can be increased in response to low PH

NH4+ -> NH3 + H+

• NH3 moves freely into lumen and throughout interstitium
• H+ actively pumped into lumen in DCT & CT
• H+ combined with NH3 -> NH4+ (trapped in lumen)

Phosphate and NH3 act as buffer for H+ in lumen -> H2PO4- ( keep minimum PH urine 4.5 so doesn’t damage urinary tract)

Question 9

How do acidosis, alkalosis and K+ serum concentration all link?

Answer 9

Acidosis hyperkalaemia
One can cause the other

Alkalosis hypokalaemia

Question 10

How does hyperkalaemia lead to metabolic acidosis?

Answer 10

Lots of K+ in blood so K+ moves into cells e.g. tubular cells become more alkaline as H+ ions move out of the cells -> increases HCO3- excretion -> metabolic acidosis

Question 11

How does hypokalaemia lead to metabolic alkalosis?

Answer 11

Low [K+] of blood so K+ moves out of cells down conc grad, H+ at antiport therefore moves into cells making them acidic, this favours HCO3- recovery -> metabolic alkalosis

Question 12

Why does hyperventilation lead to a respiratory alkalosis? what effect does it have on PO2?

Answer 12

Hyperventilation-> hypocapnia (pCO2 fall)
-> increase in PH -> respiratory alkalosis

(CO2 + H2O H+ + HCO3-)

Normal HCO3- as less excreted by kidney takes 2-3days

Higher PO2 as more fresh air is brought in

Question 13

Why does hypoventilation lead to respiratory acidosis? What effect does it have on PO2?

Answer 13

Hypoventilation-> hypercapnia (PCo2 rise) -> decreases plasma PH -> respiratory acidosis

(CO2 + H2O H+ + HCO3-)

Normal HCO3- (as kidney excretes more 2-3days)

Decreases PO2 less fresh air brought in

Question 14

What happens to PCO2, [HCO3-] and PH In compensated respiratory acidosis?

Answer 14

High PCO2
Raised [HCO3-]
Relatively normal PH

Question 15

What happens to PCO2, [HCO3-] and PH in compensated respiratory alkalosis?

Answer 15

PCo2 low
[HCO3-] low
PH relatively normal (on higher side)

Question 16

How does metabolic acidosis occur, what would the changes in [HcO3-], PCO2, LH and the anion gap be?

Answer 16

If tissues produce acid it reacts with and removes HCO3- (H+ + HCO3- CO2 + H20)

So fall in HCO3- (attempts to react with all H+)

Extra CO2 is breathed off so PCo2 stays normal

Lowered PH

If increased metabolic acids the anion of the acid replaces HCO3- and anion gap increases but if renal cause of acidosis anion gap stays the same (less HCO3- but replaced by Cl-)
Bc calculated by:
([Na+] + [K+]) - ([Cl-] + [HCO3-])

Question 17

What is the anion gap? When does it change?

Answer 17

Difference between measure cations and anions
([Na+] + [K+]) - ([Cl-] + [HCO3-])

normally 10-18 mmol.l-1 due to other non-measured anions

Increased if HCO3- is replaced
E.g. if a metabolic acid reacts with HCO3- the anion of the acid replaces HCO3- but in renal causes of acidosis anion gap will be unchanged (less HCO3- but replaced by Cl-)

Question 18

How does the body compensate for metabolic acidosis? What happens to the levels of [HcO3-], PcO2 and Ph?

Answer 18

Peripheral chemoreceptors (carotid bodies) detect drop in Ph -> stimulate ventilation -> decreased PCO2

Compensated:
Low HCO3-
Lowered PCO2
Nearer normal PH (lower side)

Question 19

What occurs in metabolic alkalosis? What would PCO2, [HcO3-] and PH be like?

Answer 19

[HCO3-] increases so

[HcO3] high
Normal PCO2 (extra is breathed off)
Increased Ph

Question 20

What conditions can lead to respiratory acidosis?

Answer 20

Type 2 respiratory failure
- low PO2
- high PCO2
Alveoli can’t be properly ventilated

Question 21

What conditions can lead to respiratory alkalosis?

Answer 21

• hyperventilation e.g. panic attacks
• low PCO2, rise in PH
• hyperventilation in response to long term hypoxia (type 1 respiratory failure) low PcO2 will initially raise Ph but can be compensated for chronically by fall in HCO3-

Question 22

What’s the difference between type one and two respiratory failure?

Answer 22

Type 1 involves low O2 with normal/ low CO2 -> respiratory alkalosis

Type 2 involves low O2 with high CO2 -> respiratory acidosis

Question 23

What conditions may lead to metabolic acidosis?

Answer 23

If anion gap is increased indicates a metabolic production of acid e.g.
- keto-acidosis, diabetes

• lactic acidosis, exercising to exhaustion/ poor tissue perfusion
• uraemia acidosis, advanced Renal failure (reduced acid secretion, build up of phosphate, sulphate and urate in blood)

If anion gap is normal indicates renal problem:

• renal tubular acidosis (rare) type 1 inability to pump out H+ or type 2 problems with HCO3- reabsorption
• severe persistent diarrhoea loss of HCO3-
  Replaced by Cl-

Question 24

Acidosis normally leads to hyperkalaemia, when is this not the case?

Answer 24

Non-renal causes of metabolic acidosis cause increased reabsorption of K+ by kidneys and movement of K+ out of cells

However in diabetic ketoacidosis may be a totals body depletion of K+
(Although K+ moves out of cells due to acidosis and lack of insulin, os optic diuretics means lots K+ lost in urine)

Question 25

What conditions lead to metabolic alkalosis?

Answer 25

HCO3- is retained in place of Cl-

Stomach major site of HCO3- production (by-product of H+ secretion)

• Severe prolonged vomiting -> loss H+
• mechanical drainage of stomach (drug overdose)
• K+ depletion/ mineralocorticoid XS
• certain diuretics (loop and thiazides)

Question 26

How does the body correct metabolic alkalosis e.g. increased [HCO3-]?

Answer 26

Rise in PH of tubular cells -> fall in H+ excretion and reduction in HCO3- recovery but problem if there is also volume depletion bc need Na+ recovery which favours H+ excretion and HCO3- recovery
(Na+ and H+ exchanger recovers Na+)

Question 27

What happens to the serum K+ concentration during metabolic alkalosis?

Answer 27

Less H+ excretion in nephron leads to more K+ excreted (antiport)

and more K+ moves into cells
-> hypokalaemia

Question 28

If PCO2 is high, [HCO3] is high and PH is normal what could the condition be?

Answer 28

Only compensated respiratory acidosis

Can’t be metabolic alkalosis bc can’t be compensated