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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?

A

pKa = 6.1

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?

A
32
Q

What is the equation for the bicarbonate buffering system?

A
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?

A
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

61
Q
A

Y2 MECHANISMS OF DISEASE (36 decks)

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