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1

What is the normal range of plasma pH?

7.38 - 7.42

2

What are the major clinical effects of Alkalaemia?

Lowers free Ca2+ in serum:

Increases excitability of nerves

If greater than 7.45:

Parasthesia (tingling)

Tetany (Involuntary muscle contraction, danger to breathing)

 

3

What are the mortality rates of Alkalaemia at pH 7.55 and 7.65?

45% at 7.55

80% at 7.65

4

What are the major clinical effects of Acidaemia?

Increase plasma potassium

Affects enzymes:

Reduced cardiac and skeletal muscle contractility

Reduced glycolysis in many tissues

Reduced hepatic function

Effects sever below 7.1 and life threatening below 7.0

5

How is plasma pH determined? What systems are involved?

Dependent on pCO2 to [HCO3-] ratio

pCO2 determined by respiration

[HCO3-] determined by kidney

6

What causes respiratory acidaemia and alkalaemia?

Resipiratory Acidaemia:

Hypoventilation leads to hypercapnia, causing plasma pH to fall

Repiratory Akalaemia:

Hyperventilation leads to hypocapnia causing plasma pH to rise

7

Explain briefly the role of chemoreceptors in pH balance

Central:

Keeps pCO2 within tight limits

Corrects disturbances in pH with respiratory changes

Peripheral:

Enable changes in respiaration driven by changes in plasma pH

8

Explain the role of the kidneys in correcting respiratory driven pH changes

Kindey control [HCO3-] and hence can conpensate for change in pCO2 with change in [HCO3-]

Respiratory acidaemia can be compensated by increase in [HCO3-] (Compensated respiratory acidaemia)

Respiratory alkalaemia can be compensated by decrease in [HCO3-] (Compensated respiratory alkalaemia)

9

Describe metabolic acidaemia and it's compensation

Metabolic acidaemia:

Tissues produce acid (E.g. H+) that reacts with HCO3-

This leads to a fall in plasma pH

Also produces an anion which can replace HCO3-

Compensation via change in ventilation:

Peripheral chemoreceptors

Increased ventilation lowers pCO2

Restores normal pH (ideally)

10

Describe metabolic alkalaemia and its compensation

Metabolic alkalaemia:

Plasma [HCO3-] rises (E.g. post-vomiting)

Leads to rise in plasma pH

Compensation via ventilation change:

Decrease in ventilation can only partially compensate

11

Briefly describe renal control of [HCO3-]

Large quantities filtered per day (4500mmol)

Should be able to lose HCO3- very easily

To increase [HCO3-] must both recover all filtered and make new

12

How does the kidney produce HCO3-?

Normal metabolic activity:

CO2 + H2O = HCO3- + H+

HCO3- enters plasma

H+ excreted in urine

Additionally:

HCO3- can be produced from amino acids, this produces NH4- to enter urine

13

From where in the kidney tubule is HCO3- recovered?

80-90% in PCT

Rest in Tal of LoH

14

Describe the reabsorption of HCO3- from the kindey lumen

Basolateral Na+/K+ ATPase produces Na+ gradient across luminal membrane

Gradient allows Na+/H+ exchanger to pump H+ out of cell and Na+ in

H+ reacts with HCO3- in the lumen

HCO3- + H+ = H2O + CO2

H20 and CO2 are reabsorbed and react

H20 + CO2 = HCO3- + H+

HCO3- is reabsorped through basolateral membrane

H+ is recycled

15

How is HCO3- produced via the mechanism specific to the proximal tubule?

Glutamine is broken down to produce Alpha-Ketoglutarate and NH4-

Alpha-Ketoglutarate makes 2 HCO3-

HCO3- into ECF

NH4- into lumen

16

How does the kidney produce HCO3- via a mechanism specific to the DCT?

Intercalated cells:

Metabolic CO2 reacts with H20 to produce HCO3- and H+

HCO3- secreted into ECF

Na+ gradient insufficient to drive H+ secretion into lumen

Active secretion of H+ used instead

H+ in lumen buffered by filtered phosphate and excreted ammonia

 

17

What is the total acid excretion per day in the kidneys?

In what form is H+ found in the urine?

50-100mmol of H+

Some H+ buffered by phosphate, the rest attached to ammonia

18

How is H+ excretion controlled?

Probably by changes in tubular cell's intracellular pH

This pH change is the concequence of changing rates of [HCO3-] export

Therefore control of H+ is acheived through control of [HCO3-]

 

19

How might respiratory function lead to a change in H+ excretion?

Respiratory acidaemia/alkalaemia will affect intercellular pH in the renal tubule due to changes in CO2 diffusing in as pCO2 is altered

This will produce an increase/decrease in HCO3- export to plasma and hence increase/decrease H+ excretion

 

20

How does [K+] affect pH of plasma?

[K+] affects HCO3- reabsorption and ammonia excretion

E.g. [K+] rise leads to decreased capacity of the kidney to reabsorb and create HCO3-

Hypokalaemia can therefore lead to metabolic alkalosis

Hyperkalaemia can lead to metabolic acidosis

21

Outline the renal cellular responses to acidosis

Enhanced H+/Na+ exchange (Fully recover filtered HCO3-)

Increase NH4- production in PCT

Increased H+ ATPase in DCT

All lead to an increased capacity for the renal cells to produce and export HCO3- and correct acidosis

22

Explain the Anion Gap

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

Indicates whether HCO3- has been replaced with something other than Cl- (ie. unaccounted ions) 

Normally 10-15mmol.l-1

Increased if anions from metabolic acids have replaced plasma HCO3-

Sometimes renal problems can reduce [HCO3-] and not increase the anion gap as the HCO3- has been replaced with Cl-

23

Describe the kidney response to metabolic alkalosis

When might problems arise with correction?

[HCO3-] increases after persistent vomitting

HCO3- infusions can be corrected extremely rapidly as rise in intracellula pH in the renal tubule leads to decreased H+ secretion and hence HCO3- recovery

But:

If there is also volume depletion, Na+ conservation is prioritised

High rates of Na+ reabsorption raise H+ excretion, favouring HCO3- recovery

This limits our ability to excrete HCO3-

24

Describe the kidney's response to respiratory alkalosis

Rise in tubular pH due to lower pCO2 induce less HCO3- export by reducing H+ secretion into lumen (hence reduing HCO3- recovery from lumen)

HCO3- is therefore excreted and [HCO3-] falls to correct the [HCO3-]/pCO2 ratio

25

Give the reference ranges for:

pH

pCO2

[HCO3-]

pO2

pH = 7.38 - 7.42/7.46

pCO2 = 4.2 - 6.0 kPa

[HCO3-] = 22 - 29 mmol.l-1

pO2 = 9.8 - 14.0 kPa

26

What are the would you expect an increase or decrease in the values given below in uncompensated metabolic acidosis?

pH

pCO2

[HCO3-]

pO2

Decrease

Normal

Decrease

Normal

27

What are the would you expect an increase or decrease in the values given below in compensated metabolic acidosis?

pH

pCO2

[HCO3-]

pO2

Normal or Low

Low

Low

Normal

28

What are the would you expect the values given below to be low, high or normal in uncompensated metabolic alkalosis?

pH

pCO2

[HCO3-]

pO2

High

Normal

High

Normal

29

What are the would you expect the values given below to be low, high or normal in compensated metabolic alkalosis?

pH

pCO2

[HCO3-]

pO2

High/Normal

High

High

Low

30

What are the would you expect the values given below to be low, high or normal in uncompensated respiratory acidosis?

pH

pCO2

[HCO3-]

pO2

Low

High

Normal

Low