48) Acid-Base balance Flashcards
1
Q
What are the three main buffering systems of the body?
A
- Bicarbonate: H+ + HCO3- <=> H2CO3 <=> CO2 + H2O
- Phosphate: H+ + HPO42- <=> H2PO4-
- Proteins (including haemoglobin): H+ + Pr- <=> HPr
2
Q
How is blood pH maintained?
A
- The blood pH is maintained via 3 main buffering systems
- The 3 systems work together to coordinate blood pH and they each contribute to the [H+] via the ratio of different forms of the substance (i.e. the Ka equations)
3
Q
What is the pK?
A
- The pH at which half the substance exists in the protonated form and the other half in the deprotonated form
4
Q
What is the effective range of a buffer?
A
- A range of pH in which a substance can effectively buffer
- The effective range of a buffer is 1 pH above and below its pK (for example if the pK for phosphate is 6.8 then its effective range is at a pH of 5.8-7.8)
5
Q
What is the Henderson Hasslebach equation for the bicarbonate buffer system?
A
- pH = pK + log10( [HCO3-]/[CO2])
- Plasma [CO2] is proportional to pCO2 as plasma [CO2] can be converted to pCO2 by multiplying the [CO2] by 0.03
6
Q
How do we measure pH?
A
- Using Arterial Blood Gases (ABG)
7
Q
What are the cons of the bicarbonate buffer system?
A
- The pK of CO2/HCO3- buffer is 6.1 which is not close to the desired plasma pH of 7.4
- Hence from a chemist point of view it is not the ideal choice
8
Q
What are the pros of the bicarbonate buffer system?
A
- We have an abundant source of CO2 as lots of CO2 is made as a result of metabolism in cells
- Furthermore pCO2 can be controlled through alveolar ventilation and breathing
- Kidneys can also control the [HCO3-] within the ECF through excretion
- The pCO2 and [HCO3-] are regulated independently
9
Q
How does the kidney aid acid-base levels?
A
- The kidney controls acid-base balance through the excretion of acid and basic urine
10
Q
How does the kidneys maintain acid-base balance?
A
- The reabsorption and secretion of HCO3-
- Formation of new HCO3-
- Secretion of H+ into tubular fluid
11
Q
How does the secretion of H+ into the tubules aid acid-base balance?
A
- There are buffering systems within the tubules that react with secreted H+
- These systems are: HCO3-/H2CO3, HPO42-/H2PO4- and NH3/NH4+
12
Q
Describe the overall movement of substances within the kidneys that contribute to the acid-base balance?
A
- First the three main buffers (HCO3-, HPO42- and Pr-) travel in the the renal capillaries to the kidneys
- The proteins (Pr-) are unable to cross the glomerulus so remains in the plasma (and in circulation)
- The HPO42- cross the glomerulus however some of them are reabsorbed from the tubule into the peritubular capillaries
- The HCO3- are “reabsorbed” from the tubule.
- The kidney is also able to produce its own HCO3- which is released into the plasma at a controlled rate
- The kidney also produces NH3 which contributes to buffering within the tubule
- Ultimately this produces acidic urine
13
Q
Explain the renal control of H+ and HCO3-
A
- In the tubular epithelium we have the reaction of H2O and CO2 forming H2CO3 which is catalysed by carbonic anhydrase
- The activity of carbonic anhydrase is governed by the [H+] /pH of the ECF
- Thiazide anhydrase can inhibit carbonic anhydrase preventing H+ and HCO3- being released from the kidneys and less uptake of Na+
- H2CO3 disassociates into HCO3- and H+
- The H+ is transported into the lumen either via the Na+/H+ antiporter or through ATP dependent proton pumps
- These H+ are excreted in the urine causing it to be more acidic
- The HCO3- are excreted into the ECF via Na+/HCO3- symporters
14
Q
What happens to the H2CO3 buffer in the proximal tubule?
A
- Most of the HCO3- is reabsorbed
- It has a greater capacity to excrete H+
15
Q
How is HCO3- “reabsorbed” from the lumen?
A
- HCO3- in the lumen reacts with H+ that enter the lumen via the H+/Na+ transporter
- This forms H2CO3 which can then react with carbonic anhydrase to form CO2 and H20
- The CO2 can diffuse transcellularly into the renal cells where it can react with H20 to form a molecule of H2CO3 which can then dissociate to form HCO3-
- The CO2 can diffuse into the ECF rather than reacting in the renal cells
16
Q
What happens in the intercalated cells of the late DCT and collecting duct in the HCO3- buffer?
A
- In the distal part of the nephron [HCO3-] is low and H+ reacts with other buffers
- H+ ATPase pump is the most important and most active
17
Q
How does the Phosphate buffer achieve its function?
A
- H2O and CO2 react to form H2CO3 via carbonic anhydrase in the renal cells
- H2CO3 dissasociates into H+ and HCO3-.
- The H+ is secreted into the lumen via aldosterone sensitive H+ ATPase where they react with HPO42- in the lumen
- This forms H2PO4- which is excreted in the urine
- The HCO3- formed in the renal cells are excreted into the ECF via HCO3-/Cl- antiporters
- The Cl- that diffuses into the renal cells can diffuse back into the ECF via a channel
18
Q
How does the NH3 buffer achieve its function?
A
- Glutamine is converted to α-ketoglutarate and 2 NH3 molecules via the enzyme gultaminase
- Through the Krebs cycle α-ketoglutarate is converted to 2 H2CO3 molecules which dissociates into 2 H+ and 2 HCO3-
- These 2 H+ ions can combine with the 2 NH3 molecules to form 2 NH4+ ions which are secreted into the lumen via a NH4+/Na+ antiporter
- These NH4+ are then excreted in the urine
- The 2 HCO3- is excreted into the ECF via HCO3-/Na+ symporters
- Hence for one glutamine molecule we get 2 HCO3- ions
19
Q
Why does NH4+ secretion differ at different times?
A
- NH4+ secretion can increase vastly to combat metabolic acidosis
20
Q
What detects disturbances in the acid-base balance?
A
- They are detected by chemosensitive are in the medulla oblangata as it sensors altered pH
- It monitors [H+] of plasma indirectly through the cerebrospinal fluid (CSF)
- This is because charged ions are unable to cross the blood-brain barrier
- However CO2 can diffuse across the blood-brain barrier and reacts with water to form H2CO3
- This H2CO3 disassociates into H+ and HCO3- via carbonic anhydrase
- The [H+] is detected by the chemoreceptors
21
Q
Explain how a change in pH is detected and opposed?
A
- An increase in plasma pCO2 causes a decrease in pH in the plasma and in the CSF
- The decrease in CSF pH is detected by the medulla oblangata which signals the lungs (via nerves) to increase respiratory ventilation (i.e. you breathe more)
- The decrease in plasma pH is detected by peripheral chemoreceptors in the aortic arch and carotid bodies which also signals the lungs (via nerves) to also increase respiratory ventilation
- This increased respiratory ventilation decreases plasma pCO2 which returns ECF back to normal pH
22
Q
What is metabolic acidosis?
A
- It is characterised by a low pH caused by an increase in [H+] or a decrease in [HCO3-] in the ECF.
23
Q
What are the causes of metabolic acidosis?
A
- Severe sepsis or shock that can cause a build up of lactic acid
- Uncontrolled diabetes which causes a build up of ketoacids
- Diarrhoea which causes loss of HCO3- from the GI tract
24
Q
How does the body deal with metabolic acidosis?
A
- When there is an increase in [H+] there will be buffering in the ICF and ECF
- However during metabolic acidosis HCO3- will continue to be used by the body while [H+] will remain high
- In this case the medulla oblangata detects the high [H+] and will increase respiratory ventilation
- This will decrease the pCO2 in the plasma and so increases the pH of the ECF
- Furthermore the kidney will increase H+ secretion through increase NH4+ secretion
- The kidneys will also produce more HCO3- and will increase the reabsorption of HCO3- which will further increase the pH of the ECF
25
Q
What is metabolic alkalosis?
A
- It is characterised by a high pH caused by a decrease in [H+] or an increase in [HCO3-] in the ECF.
26
Q
What are the causes of metabolic alkalosis?
A
- Excessive diuretic usage (e.g. thiazide) as they cause a chronic loss of Cl-, Na+ and K+ which ultimately leads to an increase in H+ secretion
- Vomiting causes loss of H+ through the GI tract
- Ingestion of alkaline antacids
- Hypokalaemia
27
Q
How does the body deal with metabolic alkalosis?
A
- When there is an increase in [HCO3-] buffering in the ECF and ICF take place
- However during metabolic alkalosis H+ will still be used up and [HCO3-] remains high
- In this case the medulla oblangata detects the low [H+] and will decrease respiratory ventilation
- This causes an increase in pCO2 within the plasma which in turn decreases the pH in the ECF
- The kidney will also decrease H+ secretion by decrease NH4+ secretion.
- Furthermore it will also decrease HCO3- formation and reabsorption while also increasing excretion of HCO3- in the urine
- This will further decrease the pH in the ECF
