S2: Acid Base Balance Flashcards
Where is acid in body coming from?
Acid is from the metabolism of carbohydrates and fats, which produces CO2 which reacts with water to produce carbonic acid.
CO2+H2O H2CO3 H+ + HCO3-
Another source of acid is the metabolism of proteins and this generates non volatile (fixed) acids. Proteins containing sulphor in AA will produce H2SO4.
Other will produce HCl
What type of acid is more dangerous?
Non volatile acids need to be removed or there will be a build up of H+
What type of acid is carbonic anhydrase?
It is a volatile acid so it isn’t usually a problem. Removing CO2 will remove the amount of carbonic acid which shifts some protons to the left of the equation.
How do living organisms control PH?
Presence of buffers in ICF and ECF, the respiratory system and the kidney
What is the first line of defence against PH changes?
Intracellular and Extracellular buffer systems. All buffer systems participate according to their pK and their quantity.
eg. bicarbonate buffer system which is the major EC buffer
What is the second line of defence against PH changes?
The respiratory system which regulates plasma PCO2, by controlling excretion or retention of metabolically produced CO2 which is the acid component of the bicarbonate buffer system
What is the third line of defence against PH changes?
The kidney plays a dual role, it regulates excretion or retention of HCO3- and also regulates the regeneration of HCO3-.
What are the 3 blood buffering systems?
- Bicarbonate buffer system
H+ + HCO3- H2CO3 CO2 + H2O
- The Phosphate System
H+ + HPO42- H2PO4-
- The Protein Buffers (including Hb)
H+ + Pr- HPr
How do you measure the effectiveness of a buffer?
- Look at pK
- When pH is equal to the pK it means that the concentration of acid equals the concentration of the base
- A buffer is effective 1pH above and under its pK
- Buffer solutions resist changes in pH when [base]=[acid]
What is the range of pH needed for survival?
6.8-7.8
Compare the amount of pH the phosphate and bicarbonate system can buffer
On the graph, with the range of pH we’re looking at (compatible with life) the phosphate buffer is much better than the bicarbonate buffer as it can cope with a larger amount of H+ while keeping pH in range 6.8-7.8. This is from the biochemical perspective
What is the Henderson-Hasselbalch Equation?
It describes the derivation of pH as a measure of acidity (using pKa, the neagitive log of acid dissociation constant)
The equation is useful for estimating the pH of a buffer solution and finding the equilibrium pH in acid-base reactions.
How would you calculate the pH of the bicarbonate system using the henderson-hasselbalch equation?
[H+] = K1 [CO2] /[HCO3-]
Doing inverse log gives us..
pH= pK + log [HCO3-]/[CO2]
pH = 6.1 + log 24/1.3
where pK is the equilibrium constant
The equation allows us to focus on the [HCO3-]:[CO2] ratio, this is the most important thing in determining pH.
Plasma [CO2] is proportional to partial pressure of CO2 (pCO2) in plasma.
So to convert PCO2 (mmHg) to [CO2] mmol/L we multiply PCO2 by 0.03.
This gives us a ratio of 24:1.2. Commonly measured and spoken about clinically is 20:1.
The pK of CO2-HCO3- is not close to the desired plasma pH of 7.4
How is this still a good buffer?
The unique thing about this buffer is that alveolar ventilation controls pCO2 (acid form) and the kidneys control [HCO3-] in ECF.
Each do this independently and this can be controlled very quickly so CO2/HCO3- can be added/replenished quickly
Why does excess acid/base need to be eliminated if we have buffers?
Buffers are in limited supply.
So the excess acid/base must eventually be eliminated otherwise it will start to cause a change in pH, this is the role of the renal and respiratory systems.
How do kidneys control acid-base levels?
Excretion of acidic or basic urine
What are the primary renal mechanisms involved in renal control of acid-base levels?
- HCO3- can be reabsorbed and secreted to alter the ECF levels of bicarbonate
- Kidneys can also form new HCO3-
- Kidneys can secrete [H+] into tubular fluid
- There are buffer systems in tubular fluid that react with secreted [H+] e.g. NH3 – NH4+, HPO42- - H2PO4-, HCO3- - H2CO3
Explain Kidney and Buffering System
The main buffers: Bicarbonate, phosphate and proteins
- Phosphate can be reabsorbed from tubule back into blood if needed. They are also present in the tubular fluid to bind to any [H+] present in the tubule
- Bicarbonate can be reabsorbed in order to replenish its levels in the blood. Kidney also produces bicarbonate - this is released into plasma at a controlled rate.
- Proteins are not filtered into tubule and remain in plasma.
- Kidney also produces Ammonia which also contributes to buffering
What type of urine do we produce overall?
Acidic Urine
Explain renal control of [H+] and {HCO3-}
Carbonic acid dissociates to from H+ and HCO3-
Depending on the part of the kidney:
- H+ will be exchanged out into the lumen (tubular fluid) via and antiport that brings Na+ in at the same time
- In another part e.g. intercalated cells, there is an H+ ATPase that kicks H+ out into tubular fluid
The bicarbonate goes back into the blood along with Na+ in an symport
What can inhibit carbonic anhydrase?
What is the consequence of this?
- Acetazolamide and other thiazide diuretics can inhibit CA
The consequence of this is that there will not be formation of H+ or bicarbonate hence there will not be acidification of urine and there is an risk of becoming acidotic.
Where in the tubule is most of the bicarbonate reabsorbed and H+ secreted?
PCT
Is H+ ATPase found in the PCT?
No
Explain what happens to bicarbonate and H+ at PCT
- Filtered bicarbonate combines with secreted carbonic acid in the tubular lumen.
- Carbonic acid then dissociates into carbon dioxide and water- this is catalysed by carbonic anhydrase present on the luminal brush border (epithelium) of the PCT cells only
- CO2 readily crosses the tubular cell down its concentration gradient. Once inside the cell, it recombines with H2O forming carbonic acid. This then dissociates into H+ and bicarbonate.
- Bicarbonate passes back into plasma with Na+ symporter
- H+ passes back into tubular fluid with Na+ antiporter
H+ appear in urine as water. Net result is re absorption of bicarbonate and a slight fall in tubular pH and no change of pCO2 of tubular fluid