Acid-base Balance

Question 1

What is the normal pH of bodily fluids?

Answer 1

7.35-7.45

Question 2

What is the normal plasma concentration of [H+]?

Answer 2

0.00000004 mol/litre (40nM)

Question 3

What is the equation for pH?

Answer 3

-log10[H+]

Question 4

There are sources of acid in the body

How is the metabolism of carbs and fats involved with the production of acid

Answer 4

metabolism of carbs & fats produces CO2

CO2 + H2O ↔ H2CO3 (volatile acid) ↔ H+ + HCO3-

Question 5

What does metabolism of proteins generate?

Answer 5

metabolism of proteins generates non-volatile (fixed) acids
S-containing amino acids (cysteine, methionine) -> H2SO4
Lysine, arginine and histidine -> HCl

Question 6

How is pH regulated?

Answer 6

1. ICF & ECF buffering systems
2. Respiratory system - excretion or retention of CO2
3. Kidney - excretion, retention, synthesis or HC03-

Question 7

How does the bicarbonate system, phosphate system and protein buffers regulate pH

Answer 7

On image

Question 8

What do titrations curves illustrate?

where is the buffer region on the curve?

Which is a better buffer system: the phosphate or bicarbonate?

Answer 8

They illustrate the changes in these systems and how effective they are in resisting pH

Buffer is most effective 1pH on either side of pK

The linear part of the curve

The phosphate - pK is within the buffer range

Question 9

What is pK?

Answer 9

The amount of acid = the amount of base

the equilibrium constant of the reaction

Question 10

What are the Henderson-Hasslebach Equation?

How do we convert from pCO2 to [CO2]

Answer 10

Most important is the [HCO3–]:[CO2] ratio
Plasma [CO2] proportional to partial pressure of CO2 (pCO2) in plasma

Constant to convert pCO2 (mmHg) to [CO2] mmol/L is 0.03, hence

Question 11

What is the unique physiological advantage of this buffer system?

Answer 11

At 6.1 the pKA of the CO2-HCO3- buffer is not close to the desired plasma pH of 7.4. The unique physiological advantage of this buffer system is that the acid form (CO2) and salt form (HCO3-) can be regulated independently. Excretion or retention of CO2 is controlled by the lung and reabsorption and regeneration of HCO3- is controlled by the kidney.

Question 12

How do the kidney control acid-base levels?

Answer 12

By excretion of acidic or basic urine

Question 13

What primary mechanisms are involved with the excretion of acidic or basic urine?

Answer 13

Primary renal mechanisms involved in this are:
“Re-absorption” and secretion of HCO3-
Formation of “new” HCO3-
Secretion of [H+] into tubular fluid
Buffer systems within tubule that react with secreted [H+]
NH3: NH4+, HPO42-:H2PO4-, HCO3-:H2CO3

Question 14

Describe the transport of HCO3-, HP042- and Pr- through the BC

Answer 14

Bicarbonate ions “reabsorbed” from tubule AND kidney generates new HCO3-  released into plasma at a controlled rate

Phosphate ions reabsorbed from tubule

The kidney also produces NH3 which contributes to buffering

Leads to the production of acidic urine

Question 15

Describe the renal control of [H+] and [HCO3-]

What diuretics inhibit this process?

Answer 15

On slides

Acetazolamide & other thiazide diuretics

Question 16

Where does the renal control of [H+] and [HCO3-] occur?

Answer 16

Proximal tubule
85-90% of filtered HCO3- “reabsorbed”
Great capacity to secrete [H+]

Question 17

What also happens in the collecting tubule in terms of acidic production of urine?

Answer 17

Collecting duct

H+-ATPase pump more important in this part of the nephron

Question 18

In the DCT [HCO3-] is low so what buffers the [H+]?

Why is it an effective buffer?

Answer 18

Further H+ secreted into lumen buffered by HPO42-

Very effective buffer because pK=6.8 (close to pH of filtrate)

On image

Question 19

How does ammonia act as a buffer?

Answer 19

On slides

Question 20

How is changes in pH mechanisms corrected?

Answer 20

Change in pH corrected by 3 mechanisms:

1. Intra- and extra-cellular buffering
2. Respiratory adjustment of ECF PCO2
3. Renal adjustment of ECF [HCO3-]

Question 21

Describe the role of central respiratory chemoreceptors and where are they located?

Describe the pathway that occurs when there is an increase in plasma PCO2

Answer 21

Located in the medulla (part of the brainstem)

Indirectly monitor changes in PaCO2 by responding to change in pH in the cerebrospinal fluid (CSF).

An increase in PaCO2 decreases blood pH, H+ cannot pass across the blood-brain barrier as they are charged.

Therefore CRC do not respond to blood pH directly, however arterial CO2 can pass through the blood-brain barrier into the CSF, where it will then react to produce carbonic acid, and the resulting H+ activates CRCs. This CRC response to PaCO2 provides the predominant (physiological experiments estimate ≈ 70%) signal involved in regulating ventilation and initiating the urge to breathe.

Chemosenstive area in medulla regulates respiration
Monitors [H+] of plasma via CSF indirectly
Charged ions can not cross BBB but CO2 does

Question 22

What does metabolic acidosis involve?

What is it caused by?

Answer 22

An increase ECF [H+] or Decrease ECF [HCO3-]

severe sepsis or shock -> lactic acid
uncontrolled diabetes -> overproduction of 3-OH-butyric acid & other ketoacids
diarrhoea -> loss of HCO3- from GI tract

Question 23

Describe the integrated renal and pulmonary compensation in response to an increase in [H+]

(metabolic acidosis)

Answer 23

On image

Question 24

What does metabolic alkalosis involve?

What is it caused by?

Answer 24

Characterised by high pH caused by
Increase ECF [HCO3-] or Decrease ECF [H+]

Caused by:
Excessive diuretic (thiazide) use -> chronic loss of Cl-,Na+ & K+ -> increase H+ secretion
Vomiting -> loss of H+ from GI tract
Ingestion of alkaline antacids
Hypokalemia

Question 25

Describe the integrated renal and pulmonary compensation in response to a decrease in [H+]

Answer 25

On slides