Physiology 6 - Acid Base Flashcards
Why is Acid/Base Balance crucial?
- Metabolic reactions are exquisitely sensitive to the pH of the fluid in which they occur
- Relates to the high reactivity of H+ ions with Pr- ⇒ changes in configuration and function, especially enzymes
- Acid/Base disturbances ⇒ all sorts of metabolic disturbances
What is the normal arterialized blood pH?
7.4 = free [H+] of 40 x10-9moles/l or 40 x10-2mmoles/l
What are the major sources of H+?
- Respiratory Acid (CO2 + H2O ⇔ H2CO4 ⇔ H+ + HCO3-)
- Formation of carbonic acid not normaly a net contributor to increased acid because any increase in production ⇒ increase in ventilation
- Problem if lung function impaired
- Formation of carbonic acid not normaly a net contributor to increased acid because any increase in production ⇒ increase in ventilation
- Metabolic Acid (Non-respiratory acid)
- Inorganic
- Sulphuric acid from Amino acids
- Phosphoric acid from Phospholipids
- Organic e.g. fatty acids/lactic acid
- Normal diet = no net gain to body of 50-100 mmoles H+/day
- Inorganic
What do buffers do?
Minimise changes in pH when H+ ions are added or removed
What does the quantity of H2CO3 depend on?
The quantity of H2CO3 depends on the amount of CO2 dissolved in plasma
- This depends on solubility of CO2 and Pco2
What does the Henderson-Hasselbalch equation define pH in terms of?
In terms of the ration of [A-]/[HA] NOT the absolute amounts
pH = pK + log[A-]/[HA]
What is the most important extracellular buffer?
Bicarbonate buffer system
H2CO3 ⇔ H+ + HCO3-
pH = pK + log[HCO3-]/[H2CO3]
- 4 = 6.1 + log[HCO3-]/[H2CO3]
- 3 = log 20
So ratio of [HCO3-]/[H2CO3] at pH 7.4 = 20:1
What is the normal concentration of bicarbonate?
Solubility of CO2 in blood at 37oc
= 0.03 mmoles/l/mmHg Pco2
= 0.225 mmoles/l/kPa Pco2
So at a normal Pco2 of 40mmHg, 5.3kPA, [H2CO3] = 40 x 0.03mmoles/l or 5.3 x 0.225 mmoles/l
= 1.2 mmoles/l
Since ration of [HCO3-]/[H2CO3] in blood at pH 7.4 is 20:1
[HCO3-] = 24mmoles/l = “Standard bicarbonate”
What are the normal values are ranges?
- pH = 7.4
- Range 7.37 - 7.43
- (Range compatible with life = 6.8-7.8 (US) 7.0-7.6(UK)
- pCO2 = 5.3kPa = 40mmHg
- Range 4.8 - 5.9 = 36 - 44
What are the major H+ buffer systems of the body?
- Bicarbonate
- Plasma proteins
- Dibasic ⇒ Monobasic phosphate
- HPO4 {2-} + H{+} ⇒ H2PO4{-}
- Intracellular buffers
- Bone carbonate
Whats the consequence of using intracellular buffers?
H+ ions moved into the cells must either come with Cl- or be exchanged with K+ to maintain electrical equilibrium. In acidosis this can cause Hyperkalemia –> Vfib & death
Whats the consequence of using bone carbonate as a buffer?
Occurs mainly in chronic renal failure when H+ can’t be excreted. Causes bone wasting due to the chronic acid load
How much H+ do you take in a day?
50-100mmoles/day
BY what mechanisms do the kidneys regulate acid/base balance?
1) Reabsorption of Bicarbonate 2) Excretion of H+ as titratable acids 3) Excretion of H+ with ammonium
Explain the process of HCO3- reabsorption?
1) H+ ions actively secreted into proximal tubule (coupled to passive Na+ Reabsorption) 2) H+ & filtered bicarbonate form carbonic acid 3) dissociates to CO2/H2O which are then reabsorped 4) forms carbonic acid again in proximal tubule cell 5) dissociates to H+ & bicarbonate 6) bicarbonate is reabsorped and H+ secreted again for the same purpose
How is H+ excreted as a titrable acid?
Excess (Exceeding Tm) dibasic PO4{2-} ions reach distal tubule. H+ secreted into distal tubule (coupled to passive Na+ reabsorption) and binds to dibasic phosphate Making monobasic phosphate (HPO4{-}) Which is then excreted This process is dependant on blood PaCO2 Also works with uric acid and creatinine
What else is produced when H+ ions are excreted as titratable acids?
New bicarbonate. Blood CO2 is absorbed into distal tubule cells +water –> Carbonic acid Then dissociates to H+ (for secretion) and HCO3- (absorped into blood)
Whats different about ammonium excretion compared to other methods of regulating Acidity?
It is variably active. Normally it excretes 30-50mmoles H+/day but during a chronic acid load the kidneys can synthesize new proteins over 4–5 days and up that to 250mmoles/day
How does ammonium excretion work in the distal tubule?
Ammonium (NH3) is lipid soluble but ammonia (NH4+) is not. Distal Tubule: 1) Renal glutaminase deaminates amino acids producing NH3 2) NH3 moves into lumen, combines with H+ –> NH4+ and is excreted The H+ ions are secreted from the distal tubule cells after being produced from blood CO2 (So this process is also reliant on PaCO2)
How does ammonium excretion work in the proximal tubule?
Almost the same as in the distal. But H+ and NH3+ combine in the cell and are actively excreted using a NH4+/Na+ exchanger
What else is produced during ammonium excretion?
HCO3- is produced when you make H+ from blood CO2 to secrete. The bicarbonate is then reabsorped into the blood
Summary of renal regulation:
1) HCO3- reabsorption # No new HCO3- # No net excretion of H+ # Proximal tubule 2) H+ excretion as titrable acids # New HCO3- produced # Net loss of H+ as monobasic phosphate # Distal tubule 3) Ammonium excretion # New HCO3- # Net loss of H+ as NH4+ # Proximal and distal tubule
Describe the blood gasses of Respiratory Acidosis?
High PaCO2 = Directly High HCO3- = Kidney’s regulating pH Slightly acidic pH
What could cause respiratory alkalosis?
Acute- aspirin or high altitude Chronic - Low PaO2 or high altitude
Describe the bloods of respiratory alkalosis?
Low PaCO2 = directly Low HCO3- = because less H+ means less secretion which means less HCO3- reabsorption/production Slightly raised pH
What can cause metabolic acidosis?
Excess H+ or loss of HCO3-: 1) Increased H+ production e.g. DKA 2) Decreasd H+ excretion e.g. renal failure 3) Decreased intestinal HCO3- reabsorption e.g. Diarrhoea
Describe the bloods of metabolic acidosis?
Low PaCO2 = kussmauls respiration blows off CO2 to lower H+ Low HCO3- = Directly (either lost or used up buffering extra H+) pH slightly low
What can cause metabolic alkalosis?
H+ ion loss in vomit Excess aldosterone –> Na+ reabsorption in exchange for H+ –> More H+ excretion and also less H+ available for HCO3- reasborption. Excess HCO3- administration in the renally impaired Massive blood transfusions (contain citrate for anticoagulation)
Describe the bloods of metabolic alkalosis?
High PaCO2 = to raise acidity High HCO3- = Directly Slightly high pH
What is the anion gap?
A measure of the difference between the principle cations (Na+/K+) and anions (Cl-/HCO3-). Usually about 14-18mmoles/l more cations than anions.
When is the anion gap a useful measurment?
In acidosis It increases when bicarbonate is used up by lactic acidosis/DKA It stays the same when HCO3- is lost in the gut as its compensated by extra Cl-
Patient with pH = 7.32, [HCO-3]= 15 mM, PCO2 = 30mmHg (4kPa) What Acid/base disturbance is this?
Metabolic acidosis pH low = Acidosis HCO3- & PaCO2 are low = metabolic acidosis
Patient with pH = 7.32, [HCO-3]= 33 mM, PCO2 = 60mmHg (8kPa) What acid/base disturbance is this?
pH low = Acidosis PaCO2 high = Respiratory acidosis High HCO3- = Chronic Crhonic because more H+ means more HCO3- production and reabsorption. In the acute form HCO3- would not be elevated
Patient with pH = 7.45, [HCO-3] = 42 mM, PCO2 = 50mmHg (6.7kPa) What they got?
high pH = alkalosis High HCO3- & PaCO2 = metabolic
pH = 7.45, [HCO-3]= 21 mM, PCO2 = 30mmHg (4kPa) What they got?
high pH = alkalosis Low PaCO2 = Respiratory Normal HCO3- = acute (chronically it would adjust downward)
Patient with pH = 7.31, PCO2 = 7.7.kPa, (58mmHg), [HCO3-] =36mmoles/l. Which of the following is true: 1. It is likely that he has renal disease. 2. He may have an acute respiratory infection. 3. It is possible that he may have chronic bronchitis. 4. There will be a decrease in his excretion of ammonium ions. 5. His plasma potassium will be reduced.
3!! 1) He’s acidotic but his HCO3- is still raised so hes not losing to renal disease 2) Hes in respiratory acidosis, we know its not acute due to the high HCO3- so it not a resp infection 3) His High HCO3- indicates it a chronic respiratory acidosis as its compensating with more HCO3- 4) False it will increase 5) False it will go up as H+ is exchanged into cells for K+ in order to be buffered
The following acid/base values were obtained: pH = 7.25, [HCO3-] = 12mmoles/l, PCO2 = 3.3kPa (25mmHg) Which of the following are true? 1) They are indicative of a respiratory acidosis 2) The reduction in Pco2 is a result of under-breathing 3) The subject has probably been taking bicarbonate of soda 4) It could be related to impaired renal function 5) The subject may have been vomiting very badly
4!! They’re in metabolic acidosis 1) Low HCO3- and PaCO2 indicates its metabolic 2) False, you hyperventilate in response to acidosis 3) Why would their bicarbonate be so low 4) True, thats where the HCO3- might be going 5) that would cause alkalosis (So a high pH)
