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Y2 MECHANISMS OF DISEASE > Acid Base - Physiological Mechanisms > Flashcards

Acid Base - Physiological Mechanisms Flashcards

1
Q

What is the role of buffers in acid-base homeostasis?

A

they help maintain a normal [H+]

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2
Q

What are the components involved in the overview of acid-base homeostasis

A
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3
Q

Around how much acid is produced each day in the form of:

  1. total CO2
  2. unmetabolised acids
  3. plasma [H+]

?

A
  1. total CO2 - 25 mol/day
  2. unmetabolised acids - 50 mmol/day
  3. plasma [H+] - 40 nmol/day
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4
Q

What does the maintenance of plasma [H+] depend on?

A
  1. buffers
  2. excretion of CO2
  3. nitrogenous waste
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5
Q

Which 3 processes lead to H+ production?

A
  1. incomplete metabolism of glucose
  2. triglycerides (incomplete metabolism is ketogenesis)
  3. amino acid metabolism (ureagenesis)
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6
Q

What process in glucose metabolism leads to the production of H+?

Where does this usually take place?

A

in the intermediate anaerobic process:

glucose -> 2 lactate + 2 H+

this takes place in skeletal muscle and RBCs

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7
Q
A
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8
Q
A
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9
Q

What are the equations relating to fatty acid metabolism that produce H+?

A

triglycerides -> free fatty acids + H+

this occurs in adipose tissue

free fatty acids -> ketones + H+

this occurs in the liver

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10
Q

How can amino acid metabolism lead to the production of H+?

A

the metabolism of neutral amino acids leads to the generation of H+

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11
Q

Why must plasma [H+] be tightly controlled?

A

plasma [H+] is low and cannot be allowed to rise or fall appreciably as H+ ions bind avidly to proteins

this changes their conformation and their actions

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12
Q

What is the difference in the way H+ ions are produced and the concentration at which they must be maintained?

A

H+ ions are produced in mmol quantities but must be kept at nmol concentrations (40 nmol)

this is the role of buffers

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13
Q

What is the definition of a buffer?

A

a solution which resists changes in pH when an acid or base is added

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14
Q

Why are buffers important in the body?

A

they ensure that H+ ions are transported and excreted without causing damage to physiological processes

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15
Q

What are the 5 main buffers in the body?

A
  1. bicarbonate
  2. phosphate
  3. ammonia
  4. haemoglobin
  5. proteins
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16
Q

What is meant by acids and bases being H+ donors/acceptors?

A

Acids are H+ donors

HCl -> H+ + Cl-

Bases are H+ acceptors

OH- + H+ -> H2O

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17
Q

What is pH?

What is the equation for pH?

A

it is the negative logarithm of the hydrogen ion concentration (mol/L)

pH = -log10[H+]

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18
Q

What is meant by acidaemia?

When does a patient become acidaemic?

A

having a low blood pH

If [H+] is > 45 nmol/L or pH is < 7.35

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19
Q

When does a patient become alkalaemic?

A

If [H+] < 35 nmol/L or pH > 7.45

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20
Q

What is the difference between acidaemia and acidosis?

A

acidaemia is having a low blood pH

acidosis is an abnormal process or condition that lowers arterial pH

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21
Q

What is a normal pH and [H+]?

A

[H+] - 35 - 45 nmol/L

pH - 7.35 - 7.45

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22
Q

What is meant by Ka?

What is the equation for Ka?

A

it is the acid dissociation constant

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23
Q

What is pKa?

A

the negative logarithm of Ka

pKa = -log10Ka

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24
Q

What would the Ka and pKa values be like for a strong acid?

A

A strong acid would have a higher Ka value and a lower pKa value

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25
Q

What is the Henderson-Hasselbalch equation?

A

it explains how acids and bases contribute to pH

26
Q

How is CO2 acting as an acid in this equation?

A

when dissolved in plasma, CO2 becomes carbonic acid (H2CO3)

this readily dissociates to release H+

27
Q

In this equation, how is HCO3- acting as a base?

A

it accepts a proton from carbonic acid, which is converted to CO2 for excretion in the lungs

28
Q

How does the amount of CO2 and HCO3- influence the blood pH?

A

blood pH depends on the ratio of CO2 and HCO3-, not on the absolute amounts

29
Q

What is the pKa value of bicarbonate buffering in the blood?

30
Q

How can the Henderson Hasselbalch equation be applied to work out the pH of the blood?

A

pCO2 is the partial pressure of CO2

a is the solubility constant

31
Q

What important equation/assumption can be made from this equation?

32
Q

What is the equation for the bicarbonate buffering system?

33
Q

Why can bicarbonate not act as a buffer of CO2?

What is the consequence of this?

A

buffering by bicarbonate would result in the production of more CO2

equilibration of CO2 requires non-bicarbonate buffers

34
Q

What is involved in the phosphate buffering system?

Where is it found?

A

monohydrogen phosphate and dihydrogen phosphate form a buffer pair

concentrations of these anions are too low in plasma to make an appreciable difference, but they are important in urine

35
Q

What is involved in the ammonia buffering system?

A

ammonia and ammonium ions form a buffer pair

36
Q

Whereabouts in the body does the ammonia buffer system play a key role?

A

the vast majority of ammonia in the body is already in the ammonium (NH4+) form

NH3 is an important buffer in urine

37
Q

What is the principal non-bicarbonate buffer?

A

haemoglobin

it is important for buffering CO2

38
Q

What are the 3 main stages in haemoglobin buffering?

A
  1. reduction of CO2
  2. production of HCO3-
  3. formation of HHb from Hb
39
Q

How do proteins act as buffers?

What is different in the way they act as buffers?

A

they contain weakly acidic and basic groups due to their amino acid composition

they can both accept and donate H+ ions to some extent

40
Q

What is the main plasma protein involved in buffering?

A

albumin

it has a net negative charge so can mop up H+ ions

41
Q

What conditions are shown in the diagram?

42
Q

What are the 4 sites of acid-base metabolism in the body?

A
  1. liver
  2. lungs
  3. GI tract
  4. kidneys
43
Q

How are the lungs involved in acid-base maintenance?

A

they are involved in excretion of CO2

respiratory control mechanisms are sensitive to pCO2

44
Q

In a healthy person, how are the lungs involved in maintenance of blood pCO2?

A

the rate of elimination of CO2 is equal to the rate of production

this means that blood pCO2 remains constant

45
Q

What is described by the oxyhaemoglobin dissociation curve?

What happens to O2 as pO2 rises and falls?

A

it describes the relationship between pO2 and %O2 saturation

as pO2 rises, O2 binds to Hb

as pO2 falls, O2 is released from oxyhaemoglobin

46
Q

What is meant by the Bohr effect?

A

an increase in [H+] causes the oxyhaemoglobin dissociation curve to shift to the right

the H+ ions alter amino acid residues on Hb and destabilise oxyhaemoglobin so that it has a lower affinity for oxygen

47
Q

What conditions cause the oxyhaemoglobin curve to shift to the right?

What does this mean?

A

Hb has a reduced affinity for O2, meaning a higher pO2 is required to maintain saturation

  1. increase in body temperature
  2. patient is hypoxic or anaemic
  3. [H+] increases
48
Q

What processes occur in the proximal and distal tubules of the nephron that are involved in acid-base balance?

A

proximal tubule:

  • reabsorption of bicarbonate

distal tubule:

  • excretion of H+ ions
  • regeneration of bicarbonate

This creates acidic urine that contains almost no bicarbonate

49
Q

In the tubular cell of the nephron, what happens to CO2?

A

H2CO3 is generated from CO2 and H2O under the action of carbonic anhydrase

This dissociates into H+ and HCO3-

50
Q

What happens in the kidneys once H2CO3 has dissociated into H+ and HCO3-?

A

H+ is actively secreted into the glomerular filtrate in exchange for Na+

H+ ions are excreted as dihydrogen phosphate (H2PO4-)

HCO3- and Na+ ions are pumped into the plasma

51
Q

How is regeneration of bicarbonate acheived in the kidney?

A

continued formation of H+ in renal tubular cells is accompanied by generation of bicarbonate

excretion of H+ results in regeneration of bicarbonate

this maintains the buffering capacity

52
Q

Why can bicarbonate not be directly reabsorbed in the kidney?

A

luminal membranes are impermeable to bicarbonate

53
Q

How is bicarbonate reabsorbed in the kidney?

A

Bicarbonate formed in tubular cells is pumped into the plasma with Na+ for charge balance

H+ ions are secreted into glomerular filtrate in exchange for Na+

Some CO2 formed from excreted H+ and HCO3- diffuses into the tubular cells and provides a substrate for continued formation of H2CO3

54
Q

What is meant by mineralocorticoid action in the kidney?

A

There is excretion of potassium and hydrogen ions in the distal tubule

There is reabsorption of sodium ions

This is under the control of aldosterone

55
Q

What is the effect of aldosterone on the distal tubule of the nephron?

A

increased aldosterone leads to:

  • increased sodium reabsorption
  • increased potassium/hydrogen ion excretion
56
Q

What is the role of bicarbonate in the GI tract?

A
  • H+ is secreted into the stomach as HCl
  • bicarbonate is secreted into the duodenum by the pancreas

The bicarbonate neutralises the acid from the stomach

57
Q

What are the 2 processes occurring in the liver that are involved in acid-base balance?

A
  1. it is the dominant site of lactate metabolism (cori cycle)
  2. it is the only site of urea synthesis
58
Q

What 2 processes can lead to lactic acidosis?

A
  1. increased production of lactic acid (e.g. anaerobic glycolysis)
  2. decreased consumption of lactic acid (e.g. liver disease)
59
Q

Why can liver failure lead to hyperammonaemia?

A

the liver is unable to perform the urea cycle

this normally converts toxic ammonia into urea for excretion in urine

60
Q

What condition can hyperammonaemia in liver failure lead to and why?

A

ammonia stimulates the respiratory centre, causing the patient to hyperventilate

there is loss of CO2, leading to an increase in blood pH

this is respiratory alkalosis

Y2 MECHANISMS OF DISEASE (36 decks)

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