Acid and Balance Flashcards
Why is the pH of the ECF very closely monitored
As metabolic reactions are exquisitely sensitive to the pH of the fluid which they occur in
ie high reactivity of H+ ions can cause a change in configuration and functions of proteins - especially in enzymes
What is the normal pH and its range of the ECG
ph 7.4
Range 7.3-7.43
What defines the pH
Henderson-Hasselbalch equation defines the pH in terms of ratio acid to base
𝑝𝐻=𝑝𝐾+ log [𝐴−]/[𝐻𝐴]
What only contributes to the pH
Free H+ ions
What is the sources of H+ ions in the body
Respiratory Acid - Via respiration
Metabolic acid via metabolism
Diet
Why is carbonic acid (H2CO3) not a normally a contributor to increased acid
H2CO3 depends on the amount of CO2 dissolved in the plasma so an increase H2CO3 production causes an increase in ventilation,
(not an increase in acid production)
What is the purpose of buffers in the body
minimise changes in pH when H+ ions are added or removed
What kind of buffers are there in the body
Extracellular buffer
Intracellular buffer
What is the extracellular buffers in the body
Bicarbonate Buffer system
(most important buffer)
Plasma protein buffer
Dibasic phosphate buffer
What is the bicarbonate buffer the most important buffer
As pH is proportional to (HCO3)/PCO2
So the independent regulation of the (HCO3) and PCO2 is the basis of the compensatory mechanism to determine and maintain pH
What is the affect on pH and PCO2 if (HCO3-) decreased
The pH and the partial pressure of CO2 also decreases
What is the Normal value and range of PCO2
5.3KPa
(Range - 4.8-5.9KPa)
OR
40mmHg
(Range 36- 44mmHg)
What is the normal value and range of (HCO3-)
24mmoles
range 22-26mmoles
What is intracellular buffers
Primary intracellular buffers are proteins, organic and inorganic phosphates and in the erythrocytes haemoglobin
What is the occurs when ICF buffers buffer H+
causes changes in plasma electrolytes,
so to maintain electrochemical neutrality, movement of H+ must be accompanied by a Cl- in red cells or exchanged for a cation, K+
What is the clinical implications, of ICF buffer, in acidosis
So in acidosis (increase H+) the movement of K+ out of the cells into the plasma can cause hyperkalemeia
which can cause depolarisation of excitable tissues resulting in ventricular fibrillation and death
Why are buffers so important in the body
We receive 50-100moles H+ per day from diet, as present as free H+ in total body water causing a pH of 1.2-2.4
But due to the buffers the pH remains remarkebly constant at 7.4
What affect does metabolism have on respiratory acid
Metabolism produces CO2, which produces a respiratory acid loading
Why is the bicarbonate buffer, not an ordinary buffer system
If this was an ordinary buffer system then as increases H+ initially drives the reaction to the right, then over time an equilibrium would form
In bicarbonate buffer the reaction is pulled to the righr, greatly increasing the buffering capacity of the bicarbonate
the production of CO2 by the equilibrium shifting to the right stimulates ventilation, the ventilation then causes the elimination of the CO2, preventing the mechanism going backward
this is called acute respiratory regulation
What occurs to the H+ in acute respiratory regulation
The H+ is not being eliminated from the body, as the HCO3 has buffered the H+ and the respiratory compensation has greatly increased the buffering capacity so that free H+ ions are prevented from contributing to the pH
How does metabolism affect respiratory acid
Metabolism produces CO2 which causes respiratory acid loading
What is the ratio of HCO3 to H2CO3 at pH 7.4
HCO3 : H2CO3
20:1
Basically you need 20 HCO3 for 1 H2CO3
What occurs in respiratory regulation
An increase in PCO2, tiggers an increase in ventilation,
Reducing the PCO2
What occurs in renal regulation
The kidney regulates the (HCO3) in an acid load
How does the kidney regulate HCO3
By generating new HCO3
Reabsorbing filtred HCO3
What does kidney regulation depend upon
the active H+ ion secretion from the tubule into the lumen
What occurs in the mechanism of reabsorbing filtered HCO3, in kidney regulation
Active H+ secretion from tubule cells coupled to passive Na+ reabsorption
The filtered HCO3- reacts with secreted H+ to form H2CO3
H2CO3 is broke down into CO2 and H2O by carbonic anyhydrase on the luminal membrane
CO2 is freely permeable and enters the tubule cell, then
CO2 —> H2CO3 in the presence of carbonic anyhyrase
H2CO3 then dissociates to from H+ and HCO3-
The HCO3- passes into the peritubular capillaries with Na+
What occurs to the H+ ion formed in the tubule cell
Is the source of secreted H+ ion into the lumen
No H+ ions are excreted
Where does the bulk of HCO3 reabsorption occur
90% at the proximal tubule
Why is HCO3 converted to CO2 in the reabsorbtion of HCO3 mechanisms
HCO3- is a large charged molecule by converting it to Co2 its much easier to save this valuable buffer
What is the importance of renal regulation allows the reabsorption of HCO3
as need to buffer H+ from diet, metabolic acid and respiratory acid, so must be reabsorbed as failure to do so cases H+ adding to the ECF
What are the two methods in kidney regulation of generating new HCO3
By titratable Acidity
Ammonia excretion
What is the purpose of titratable acidity
used for acid loads
Measures the amount of NaOH needed to titrate urine pH back to 7.4
What is the overall affect and importance of Titratable acid
Generates new HCO3- and excretes H+
What is the importance of titrating and buffering urine
As in human the minimum urine pH = 4.5-5 and maximum is 8
But with a net production of 50-100mmoles H+ per day, if present as free H+ ions in urine of volume 1litre then pH =1 (which would be stingy)
What is the mechanism of titratable acid to cause the excretion of H+
from the Na + HPO42- (mono basic phosphate) in the lumen, only Na+ is reabsorbed in exchange for secreted H+
The HPO42- combines with H+ and forms H2PO4- (dibasic phosphate)
What is the purpose of how the H+ is excreted in tithable acidity
Phosphate takes our the H+ and gets rid of it, this prevents the H+ lowering the pH of the urine
What is the mechanism of generating new HCO3 in triturable acidity
CO2 enters from the tubule from the blood, and combined with H2O to form H2CO3
This then dissociates to yield H+ and a new HCO3
The HCO3 then passes with Na+ into the peritubular capillaries
What links the two processes in titratable acidity
The H+ produced in the distal cells, by the diffusion of CO2, is used as the Secretion into the lumen to form Dibasic phosphate to excrete the H+
Where does tithable acidity occur, and why there
Occurs in the distal tubule
because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate
What is the purpose of ammonia excretion in kidney regulation
Used for acid loads
as the increased NH4+ is the main adaptive response to the kidney for acid loads
What is the overall affect of ammonia excretion in kidney regulation
Generate new HCO3- and excrete H+
Why is titratable acid initially used in acid loads rather than ammonia excretion
NH3 production takes 4-5 days Because renal glutaminase takes 4-5 days to reach maximum level,
then NH3 has considerable capacity to raise (HCO3)
(also takes time to switch off the ability to make NH4+ when there is excess alkali )
What is the mechanism for ammonia excretion
NH3 is produced by the deamination of glutamate by renal glutaminase in the tubule cells
NH3 then moves out into the tubule lumen, where it combines with secreted H+ ions to form NH4+ and then Cl- (from NaCl) to from NH4Cl which is excreted
AT THE SAME TIME
CO2, moves from the blood and combines with water in the tubule to from H2CO3 which then dissociates
to form
H+ - which is the secreted H+
and HCO3-
The new HCO3- passes with Na+ into the peritubular capillaries
What is the Process of ammonia excretion dependant on
PCO2 of the blood
What is the activity of renal glutaminase dependant on
pH dependant
When intracellualr pH falls it increase renal glutaminase activity and therefore more NH4+ produced and excreted
Where does ammonia excretion occur
Distal tubule and proximal tubule
What is the difference between distal tubule and proximal tubule ammonia excretion
In the proximal tubules there is an NH4+/Na+ exchnager so NH4+ ions formed within the cell pass out the lumen
Where in the distal tubule, NH3 has to moves across the tubule into the lumen then become NH4
What is the basic principle of ammonia excretion
basically requires you to waste amino acids to buffer pH and decrease acidosis
What is another name for tithable acidity buffer
Dibasic phosphate, mono basic phosphate extracellular buffer
What is the anion Gap
= Difference between the sum of principle cations (Na+ and K+) and the principal anions in the plasma (Cl- and HCO3-
Normally 14-18mmoles/L