Term 2 Lecture 12: Acid-Base regulation

Question 1

pH balance

Answer 1

Maintaining pH homeostasis - pH balance of the blood, varying within very narrow limits.
Outside of the ideal pH enzymes will be denatured and the organism will die.
H+ ions are regulated in the blood indirectly using bicarbonate as a buffer
Change of 1pH unit = 10x change in H+ concentration

Question 2

Blood plasma should be between 7.38 and 7.42 pH

Answer 2

If pH is disturbed:

Acidosis ( due to excess H+) is rebalanced by excreting H+ and reabsorbing K+

Alkalosis (not enough H+) is rebalanced by reabsorbing H+ and excreting K+

Acid disturbances (stress/ poor diet) are more common than alkali ones ( usually due to excess fruit/ veg intake)

Question 3

H+ input

Answer 3

Diet: fatty acids and amino acids
Metabolism: carbon dioxide (+water), lactic acid and ketoacids

Question 4

Buffers

Answer 4

-HCO3- in extracellular fluid ( from fruit/veg in diet)
-Proteins, Hb and phosphates in cells
-Phosphates and ammonia in urine

Question 5

H+ output

Answer 5

Ventilation: carbon dioxide (+ water) out
Renal: H+ out

Question 6

pH homeostasis depends on buffers: the lungs and kidneys

Answer 6

increased plasma H+ causes a reduction in pH and by law of mass action it also increases plasma carbon dioxide.

Plasma H+ is detected by carotid and aortic receptors that feed into the sensory neuron. Plasma carbon dioxide is detected by central chemoreceptors. Both receptors feed into the respiratory control centres in the medulla.

The medulla causes increased action potential in the somatic motor neurons. This is passed to the muscles of ventilation causing an increase in rate of breathing leading to a decrease in plasma carbon dioxide causing by law of mass action a decrease in plasma H+

Buffers: proteins, phosphate ions and HCO3-
Ventilation: (see resp physiology)
Kidneys: ammonia and phosphate buffers

Question 7

Chemoreceptors are more sensitive to H+ concentration than carbon dioxide level and very insensitive to a drop in oxygen level

Answer 7

Plasma carbon dioxide is detected by central chemoreceptors on the ventral surface (bottom) of brain stem near the cerebrospinal fluid - the carbon dioxide dissolved in the cerebrospinal fluid stimulates the receptors.

Receptors feed into the medullary control centre which sends out various motor signals.

Acidosis:
triggers an increase in rate/ depth of breathing to blow of carbon dioxide to reduce plasma H+ by the law of mass action. This negative feedback switches off the stimulus until there is a disturbance again.

Alkalosis:
causes the excretion of HCO3- and reabsorption of H+
(in acidosis HCO3- reabsorbed and H+ excreted)

Question 8

Renal compensation

Answer 8

is slower than respiratory, once active these mechanisms can handle all but the most severe disturbances.

Question 9

Proximal tubule secretes H+ and reabsorbs HCO3-

Answer 9

Na+K+ exchanger (NHE) moves Na+ into the cell and H+ out against the concentration gradient
Na+NH4+ antiport moves NH4+ from the cell to the lumen in exchange for Na+

Question 10

Steps in the proximal tubule

Answer 10

1) Na+H+ antiport secretes H+ out of the cell into the lumen
2) H+ in the filtrate (in lumen) combines with filtered HCO3- to form carbon dioxide
3) carbon dioxide diffuses into cells and combines with water to form H+ and HCO3-
4) H+ is secreted again (to lumen) and excreted
5) HCO3- is reabsorbed
6) glutamine is metabolised to ammonium ion and HCO3-
7) NH4+ is secreted and excreted
8) HCO3- is reabsorbed

Question 11

3 different types of Na+ channel

Answer 11

1) Na+H+ channel moves Na+ into cell and H+ out to lumen
2) Na+ NH4+ channel moves Na+ into cell and H+ out to lumen
3) Na+HCO3- channel moves Na+ and HCO3- out to the interstitial fluid where from they are reabsorbed by the peritubular capillary (blood vessel)

Question 12

H+ combinations

Answer 12

H+ + HPO4^2 <-> H2PO4- (dihydrogen phosphate)

H+ + HCO3- <-> H2CO3 ( carbonic acid)

H+ + NH4+ <-> NH4+ (ammonia)

Question 13

The distal nephron controls acid excretion

Answer 13

Intercalated cells (I cells) are interspersed among the principal cells and are responsible for acid-base regulation.

Type a I cells are for acid correction
Type b I cells are for alkali correction

I cells have ATPase pumps

Type a
Have a pump that moves H+ into the lumen in exchange for K+ ions moved into the cell. K+ is reabsorbed into the blood. Another channel allows Cl- into the cell and HCO3- out to the interstitial fluid where it is combined with H+:
HCO3- + H+ -> H2O + CO2
The carbon dioxide is reabsorbed into the type a I cell to be combined with water in the cell.
H2O + CO2 -> HCO3- + H+
H+ is moved to the lumen and excreted whilst the HCO3- is returned to the interstitial space.

Type b
have a channel that allows HCO3- to pass into the lumen in exchange for Cl- into the cell. ATP pump moves H+ ions produced from water and carbon dioxide into the interstitial space.
K+ ions leave through a channel into the lumen and are excreted.

So for acidosis Type a I cells secrete H+ and absorb HCO3- to combine with H+ and form water + carbon dioxide.
For alkalosis Type b I cells secrete HCO3- and reabsorb H+ so that it builds up to increase acidity in the interstitial space.

secrete = to lumen
absorb = to interstitial fluid
excrete = to external environment

Question 14

Acid-base disturbance may be respiratory or metabolic

Answer 14

Respiratory acidosis ( high PCO2 and H+ low pH and HCO3-)
caused by hypoventilation
- CO2 retention leads to elevated CO2 level in blood plasma
- elevated H+ and acidic pH
Respiratory depression (hypoventilation) causes:
- drugs including alcohol
-asthma ( increased airway resistance)
- impaired gas exchange due to: fibrosis, severe pneumonia or muscular dystrophy ( muscle weakness)
- chronic obstructive pulmonary disease (COPD): emphysema, inadequate alveolar ventilation compounded by loss of alveolar surface area.
Response: renal compensation (excrete H+ and reabsorb HCO3-)

Metabolic acidosis (uncommon) (normal/high PCO2 and H+ low pH and HCO3-)
causes:
- dietary and metabolic input of H+ exceeding H+ excretion
- lactic acidosis ( due to anaerobic metabolism e.g. in exercise)
- keto acidosis - excessive breakdown of fats or certain aas
- type 1 diabetes or atkins diet
Response:
respiratory compensation (almost immediate) and renal compensation to excrete H+ and reabsorb HCO3-

Respiratory alkalosis ( Low PCO2 and H+, high pH and HCO3-)
causes:
-hyperventilation- plasma PCO2, H+ and HCO3- decrease
- Low plasma HCO3- indicates a respiratory disorder
Response:
renal compensation to excrete HCO3- and reabsorb H+

cause of hyperventilation:
clinical - excessive artificial ventilation
anxiety - hysterical hyperventilation
can be treated by breathing into a paper bag as the patient rebreathes exhaled CO2 and this raises their PCO2.

Metabolic alkalosis ( Low/normal PCO2 and H+, high pH and HCO3-)
causes:
-excess vomiting
- excessive ingestion of bicarbonate antacids
Response:
respiratory compensation - hypoventilation.
renal compensation - excrete HCO3- and reabsorb H+