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
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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)
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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
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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)
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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

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6
Q

How do we measure pH?

A
  • Using Arterial Blood Gases (ABG)
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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
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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
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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
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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
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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+
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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
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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
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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+

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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
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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