Acid Base Balance Flashcards
Acid-base balance in the body
- Body [H+] is tightly regulated for normal function of enzyes, blood clotting, muscle contraction
- Normal pH - 7.4 arterial blood
- Extreme ranges are compatible with life - pH 6.8 to 8.0
Where does acid input come from
VOLATILE - CO2
NON-VOLATILE - Metabolism and our diets
Where does base input come from
Few natural sources
When we measure blood pH, what are we making an assessment of
ICF pH
All the H+ ions and CO2 are produced inside cells and these then get dumped into ECF to be transported away to be disposed of
Difference in pH between IC and EC
Inside cells is a naturally slightly more acidic environment at 6.8 than the ECF of 7.4
EC pH is higher by 0.5 - 0.6 pH units and this represents about a fourfold gradient favouring the exit of H+ from cells
What effect does pH have on the charge state of biomolecules
The pH affects the change state of biomolecules thus at 6.8 most metabolites are charged and thus get trapped inside cells
3 lines of defence to maintain a stable IC pH
- Buffering - molecules that can accept or donate a H+ (instantaneous)
- pCO2 - keeping it low (removal of CO2 is fast)
- Acid removal - Pump H+ out of the cell into ECF (excrete an acidic or alkaline urine - slow)
** Aim to excrete H+ and SAVE any base
What are buffers
Solutions which can resist changes in pH when acid or alkali is added
Distribution of buffering capacity
- 52% of the buffering capacity is in cells
- 5% is in RBCs
- 43% is in EC space
Buffering capacity of phosphate
HPO4- + H+ <-> H2PO4
Renal tubule buffer
Buffering capacity of ammonia
NH3 + H+ <-> NH4+
Important renal tubule buffer
Buffering capacity of proteins
H+ + Hb <-> HHb
All proteins have some buffering capacity, as proteins have a carboxyl end and amino ends
Why are phosphate and ammonia particularly important in the renal system
They act as urinary buffers
Where is there a high conc of the bicarbonate buffering system
Most important system
High conc in ECF
Physiologically regulated by the lungs (PCO2) and kidneys (HCO3-)
Bicarbonate buffer system rxn
- CO2 is produced by actively respiring cells and in the presence of water and the ubiquitously expressed enzyme carbonic anyhdrase
- Active muscle - lots of CO2 produced
- Some of that CO2 will be transported as CO2, more as H+ bound to a buffer and in the form of HCO3-
- When it gets to the lungs the rxn is reversed and the CO2 is blown off by the lungs - gotten rid of acid
Henderson-Hasselbalch equation bicarbonate buffering system
- Can be used to help estimate the pH of a solution based on CO2 and HCO3- levels and identify disturbances and their causes
- Changes in [HCO3-] or pCO2 alter ECF pH
What does the Henderson-Hasselbalch equation tell us
- pH = the pK which is the dissociation constant for bicarbonate which is 6.1
- We have the log of HCO3- conc divided by the pCO2
- Because pCO2 is a gas pressure we take its solubility into A/C by multiplying the pCO2 by 0.03. So 0.03 is the SOLUBILITY constant for CO2
- The HCO3- component is controlled by the lungs
- Overall the bicarbonate system accomplishes 92% of plasma buffering. Most importantly is the ability of bicarbonate to convert protons to a readily excretable form (CO2)
2 main functions of the kidney
- Reabsorption of HCO3- (save base)
- Excretion of H+ (get rid of acid)
Why is HCO3- reabsorption vital
Due to a large filtered load
Mechanism of HCO3- reabsorption is linked to H+ secretion and the continued secretion of H+ is facilitated by the fact that there is a H+ acceptor in filtrate in the form of a urinary bladder
Distribution of reabsorption of HCO3-
- PCT - 80%
- TAL of LOH - 15%
- Distal tubule - 5%
How much of the filtered HCO3- is saved back to the plasma
Close to 100%
Mechanism of absorption of HCO3-
TRANSCELLULAR
Involves H+ secretion
HCO3- reabsorption in the proximal tubule
- What is central to the transport process
- MOA
- Net effect
- As always Na+ is central to this transport process like that for glucose and other important solutes in the filtrate we want to save
- IN RED - HCO3- that was filtered and is now in the nephron - want to save it
- Inside the H+ is produced and is pumped out through an antiport system with Na+ (apical)
- Filtered HCO3- and the and pumped H+ combine to give carbonic acid which dissociates to CO2 and water
- Water goes to LOH
- CO2 diffuses into cell
- CO2 inside cell combines with water to generate carbonic acid which dissociates to H+ and HCO3-
- HCO3- is then pumped out of the basolateral membrane to the plasma driven by Na+ cotransporter
- Net effect here in this example is sodium drives H+ secretion, which traps HCO3- and leads to HCO3- being reabsorbed to the plasma
HCO3- reabsorption in the distal tubule
- What is NOT powered by
- MOA
- Net effect
- Not powered by Na+ gradient
- In red is the HCO3- that was filtered (remember 80% already saved in the PCT) and is now in the nephron - want to save this
- Inside the H+ is produced and is pumped out through an antiport system with K+ or pumped out directly by a proton pump (found in intercalated cells
- Filtered HCO3- and the pumped H+ combine to give carbonic acid which dissociates to CO2 and water
- Water goes to LOH and CO2 diffuses into the cell
- CO2 inside cell combines with water to generate carbonic acid which dissociates to H+ and HCO3-
- HCO3- is then pumped out of the basolateral membrane to the plasma driven by Cl- antiport system
- Net effect is that H+ are secreted, trap HCO3- and lead to HCO3- being reabsorbed by the plasma
H+ secretion in the distal tubule
- Secreted H+ binds to phosphate, not filtered HCO3-
- BOund H+ is excreted in the urine
- H+ secretion results in HCO3- formation inside the tubular cell
- This new HCO3- is transported into the interstitium
This way, the H+ is trapped and the pH of what is filtered is not excessively low and we can get rid of H+ in the urine
H+ secretion with ammonium
- Ammonium (NH4+) is produced by H+ binding to ammonia (NH3)
- In this way the H+ is trapped, the pH of what is filtered is not excessively low and we can get rid of H+ in the urine
- Proximal tubule produces ammonia for this purpose only if it is needed
- The ammonia buffer is special as it is produced from glutamine inside the cell
- The enzyme that does this is said to be ACID INDUCIBLE - creates more NH3 as the pH drops
- In generating NH3 it also produces a free or new HCO3- it did not come from CO2 thus it is free to buffer H+ produced from any source and contributes to the base pool to manage H+ levels
- New HCO3- is transported into the interstitium
- NH3 diffused into tubular lumen and binds to a secreted H+
2 steps to characterise an acid/base disturbance
- Acid/base problem
- Is the problem due to pCO2 or due to HCO3-
What does excess pCO2 indicate
Acidosis because the lungs deal with pCO2
RESP ACIDOSIS
What does excess HCO3- indicate
Alkalosis because the kidneys deal with HCO3-
METABOLIC ALKALOSIS
Acidosis - pH < 7.4
METABOLIC
Decreased HCO3-
RESPIRATORY
Increased pCO2
Alkalosis - pH > 7.4
METABOLIC
Increased HCO3-
RESPIRATORY
Decreased pCO2
Kidneys role in compensation for ACIDOSIS (resp is suppressed so pCO2 rises)
If too much acid (low pH)—intercalated cells will secrete more acid into tubular lumen and make NEW bicarbonate (more base) and raise pH back to set point
Kidneys role in compensation for ALKALOSIS (hyperventilation, so pCO2 drops)
If too little acid/excessive base (high pH)- proximal convoluted cells will NOT reabsorb filtered bicarbonate (base) and will eliminate it from the body to lower pH back toward normal
