Acid-Base Balance 1 Flashcards
What is the normal pH of the arterialised blood?
7.4 = free [H+] of 40x10^-1 mole/L
What type of ions contribute to pH?
Only free H+ ions
What are the two categories of sources of H+ ions?
Respiratory acid and metabolic acid
Describe the formation of H+ ions via respiratory acid
Due to aerobic respiration formation of CO2:
Formation of carbonic acid is not normally a net contributor to ↑ acid because any ↑ in production → ↑ in ventilation.
• Problems occur if lung function is impaired.
Describe the formation of H+ ions via metabolic acid (non-respiratory acid
Via metabolism
a) Inorganic acids: eg S-containing amino acids → H2SO4 and phosphoric acid is produced from phospholipids
b) Organic acids: fatty acids, lactic acid
Name three coping mechanism for increase in [H+]
- Buffers
- Ventilation
- Renal regulation
Define respiratory acidosis
State of respiratory acidosis occurs when alveolar hypoventilation results in CO2 retention and elevated plasma PCO2.
Define metabolic acidosis
Disturbance of mass balance that occurs when dietary and metabolic input of H+ exceeds H+ excretion.
What is the most important extracellular buffer?
Bicarbonate buffer system
H2CO3 → H+ + HCO3- ,
What is the Henderson-Hasselbalch Equation?
pH=pK+log〖([A-])/([HA])〗
(HA → H+ + A-)
OR
pH = [HCO3]/PCO2
What does the quantity of H2CO3 in the bicarbonate buffer system depend on?
Amount of CO2 in plasma and therefore the solubility of CO2 and Pco2 (as it is originally a gas)
At pH of 7.4 (normal) what is the ratio of bicarbonate to carbonic acid?
20:1
State the normal value and range for pH
pH = 7.4 Range = 7.37-7.43
State the normal value and range for pCO2
pCO2 = 5.3kPa or 40mmHg Range = 4.8-5.9 kPa or 36-44mmHg
State the normal value and range for [HCO3]
24mmoles and range 22-26
At normal PCO2 of 40mmHg, what is the concentration of bicarbonate?
24mmoles/l (as carbonic acid is 1.2 and ratio is 20:1)
What is the action of the bicarbonate mechanisms if there is an increase in H+ ions in ECF?
Drives the reaction to the right, so that some of the additional ↑ H+ ions are removed from solution via ventilation and therefore a change in pH is reduced.
What is the action of the bicarbonate mechanisms if there is a decrease in H+ ions in ECF?
↑CO2 as ↓ ventilation which pushes equation to the left to produce more H+ ions and bicarbonate
How are H+ ions eliminated from the body?
By the kidneys, which is coupled to the regulation of plasma [HCO3-]
pH = [HCO3] (renal regulated)/Pco2 (resp. regulated)
Changes is these levels are compensated by the changes in other levels
Name two other buffer systems in the ECF other than bicarbonate buffer
Plasma proteins: Pr- + H+ → HPr
Dibasic phosphate HPO4^2- + H+ → H2PO4- monobasic phosphate.
What are the primary intracellular buffers?
Proteins, organic and inorganic phosphates and, in the erythrocytes, haemoglobin
Also bone carbonate
How is an increase in intracellular H+ ions buffered?
Changes plasma electrolytes, so in order to maintain electrochemical neutrality, movement of H+ must be accompanied by Cl or exchanged for another cation, K+.
What is the clinical aspect of acidosis of the ICF?
The movement of K+ out of cells into plasma can cause hyperkalaemia → depolarization of excitable tissues → ventricular fibrillation and death.
In chronic renal failure → bone carbonate is used to buffer causing wasting of bones
How much buffer is received via the diet?
50-100 moles H+ per day
What is the effect of buffering metabolic acid?
[H+] increases because of the H+ contributed by the metabolic acids. This increase shifts the equilibrium to the LEFT, increasing CO2 levels and using up HCO3
43% buffered in plasma and 57% buffered within the cells
Where is most of respiratory acid buffered in the cells?
97% in the cells (as that’s where CO2 is mostly produced)
Hb particularly important and the rest occurs with plasma proteins.
How does the kidney regulate [HCO3]?
- Reabsorbing filtered HCO3
- Generating new HCO3 for increased H+ ions
These processes depend on active H+ ion secretion form the tubule cells into the lumen
Describe the mechanism of reabsorption of bicarbonate
Bulk HCO3 reabsorption occurs in prox. tubule:
- Active H+ secretion from the tubule cells
- Coupled to passive Na+ reabsorption
- Filtered HCO3- reacts with the secreted H+ to form H2CO3. In the presence of carbonic anhydrase on the luminal membrane CO2 and H2O
- CO2 is freely permeable and enters the cell
- Within the cell, CO2 H2CO3 in the presence of carbonic anhydrase (present in all tubule cells) which then dissociates to form H+ and HCO3-
- The H+ ions are the source of the secreted H+
- The HCO3- ions pass into the peritubular capillaries with Na+
What is the importance of the HCO3 reabsorption?
GFR = 180l/day [HCO3- ] = 24mmoles/l = 4320 mmoles HCO3- filtered per day. Must be reabsorbed, since failure to do so = to adding H+ to the ECF (causing acidosis)
There is no excretion of H+ ions during HCO3- reabsorption.
Why is the pH of urine not 1?
If H+ were present as free ions in the urine it would be, but as it is buffered by weak acids and bases, pH = 4.5-5
What weak acids and bases buffer H+ ions in the urine?
Dibasic phosphate, H2SO4, mainly as well as uric acid and creatinine
Why is dibasic phosphate called a titratable acid?
In the urine, is it able to titrate pH of urine back up to plasma pH of 7.4 by measuring the amount of NaOH needed to titrate the urine
What is the importance of titratable acidity?
Generated new HCO3 and excretes H+
Describe the steps in buffering pH of the urine
- Na2HPO4 in the lumen. One Na+ is reabsorbed in exchange for secreted H+. This monobasic phosphate removes H+ from the body.
- Within the distal tubule cell, CO2 (which has come form the blood) combines with H2O to form carbonic acid, in the presence of carbonic anhydrase, which then dissociates to yield H+, used for secretion, and new HCO3- , which passes with Na+ into the peritubular capillaries.
This process is dependent on PCO2 of the blood to allow CO2 to diffuse into the lumen of the tubule
What is the adaptive response to an increase in acid load?
Generate new HCO3 AND excrete H+
(whereas to reabsorb HCO3 it is converted to CO2 in lumen and then back into HCO3 in cell, which then diffuses out, there is NO excretion of H+)
Why is the distal tubule the site of tittle acidity?
Unreabsorbed dibasic phosphate becomes highly concentrated by the reabsorption of fluid in the loop of henle
What is another process which is used during chronic acidosis to excrete more protons and produce more bicarbonate?
Elimination of ammonium
How does ammonia help in acid loading?
- Ammonia (NH3) produces by deamination of AA by renal glutaminase within renal tubule cells and is LIPID SOLUBLE so diffuses into renal tubule
- CO2 from blood enters tubule cells → H+ and HCO3 (bicarbonate moves into blood)
- H+ ions move into renal tubule and join NH3 → ammonium (NH4)
- NH4 join Cl- (from NaCl) → NH4Cl which is excreted
Ammonium can also enter tubule via NH4/Na exchanger in the prox. tubule
Where does ammonia secretion occur?
Distal tubule
What regulates renal glutaminase activity (used to form NH3)
When intracellular pH falls → increase renal glutaminase activity and therefore more NH4+ produced and excreted (decrease pH as it uses up H+).
