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Kidneys and Renal functions > Acid Base Balance > Flashcards

Acid Base Balance Flashcards

1
Q

What is the significance of acid base balance?

A

Very important for normal body functions that [H+]/pH of body fluids is kept relatively constant

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2
Q

Why is pH significant to enzyme function?

A

Enzymes function at particular pH within a narrow range

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3
Q

What are the consequences of pH disturbances on enzyme function?

A

Enzymes have lots of functions in body, so disturbances in pH may result in abnormal respiratory and cardiac function, derangements in blood clotting and drug metabolism etc.

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4
Q

What is the normal body pH?

A

Normal [H+]/pH of body fluids (7.35-7.45)

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5
Q

What is the normal plasma [H+] ?

A

(40nM)

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6
Q

What is the main source of acid in the body?

A

metabolism of carbs & fats produces CO2

    CO2 + H2O ↔ H2CO3 (volatile acid) ↔ H+ + HCO3-
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7
Q

Why does CO2 production not cause an increase in pH?

A

CO2 produced as a result of carb metabolism doesn’t usually result in increase in plasma H+ as it is excreted from body via lungs – hence the H2CO3 produced is known as a volatile acid

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8
Q

What is the product of protein metabolism?

A

Metabolism of proteins generates non-volatile (fixed) acids
S-containing amino acids (cysteine, methionine) ⇒ H2SO4
Lysine, arginine and histidine ⇒ HCl

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9
Q

What is the product of sulphur containing amino acids?

A

Sulphur containing aa produce sulphuric acid, which is non-volatile – these non-volatile acids need to be removed otherwise will get a net gain of H+

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10
Q

How is pH regulated in the body?

A

Presence of buffers are effective in controlling changes in pH in vivo

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11
Q

How does the body compensate for pH disturbances?

A

Disturbance in [H+]/pH compensated for:

  1. ICF & ECF buffering systems
  2. Respiratory system
  3. Kidney
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12
Q

What is the first line of defence against pH disturbance?

A

ECF and ICF

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13
Q

What is the major extracellular buffer system?

A

CO2-HCO3- buffer system

CO2 and HCO3- can be regulated independently via this system

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14
Q

How does the respiratory system compensate for pH alterations?

A

Regulates plasma PCo2 by controlling excretion / retention of metabolically produced CO2 (which is acid component of CO2 - HCO3- buffer system) in response to pH changes

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15
Q

What are the 2 ways the kidneys compensates for pH changes?

A

Regulates excretion or retention of HCO3- (the basic component of CO2-HCO3- buffer system)
Also regulates regeneration of HCO3-

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16
Q

What are the buffering systems of the blood?

A

the bicarbonate system
H+ + HCO3- ⮀ H2CO3 ⮀ CO2 + H2O

the phosphate system
H+ + HPO42- ⮀ H2PO4-

the protein buffers (inc haemoglobin)
H+ + Pr- ⮀ HPr

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17
Q

What are the advantages of CO2-HCO3 buffer system

A

CO2 and HCO3- can be regulated independently

Excretion / retention of CO2 is controlled by lung and reabsorption and regeneration of HCO3- is controlled by the kidney
There’s a readily available supply of CO2 from cellular metabolism

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18
Q

How many buffers are present in the body?

A

While buffering is the first, and immediate, defense against changes in H+ concentration, the buffers are present in limited quantities

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19
Q

How is the availability of buffer systems maintained?

A

As buffer capacity is used, less is available to control pH

Respiratory + renal systems eliminate excess H+ or base to restore buffer capacity to normal

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20
Q

Describe the bicarbonate buffer system

A

Most important is the [HCO3–]:[CO2] ratio
Plasma [CO2] proportional to partial pressure of CO2 (pCO2) in plasma
Constant to convert pCO2 (mmHg) to [CO2] mmol/L is 0.03, hence

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21
Q

How do we measure blood pH?

A

» measure pH with arterial blood gases (ABG)

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22
Q

What is the pK?

A

equilibrium constant of reaction

i.e. numerically existing to pH when the concentration of acid=base of that buffer

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23
Q

When are buffers most effective?

A

Buffer solutions resist change in pH when [base]=[acid]

Buffer is most effective 1pH on either side of pK

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24
Q

what controls PCO2?

A

Alveolar ventilation controls PCO2

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25
Q

What controls [HCO3-]?

A

Kidneys control [HCO3–]ECF

Independent regulation

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26
Q

How do kidneys control acid-base balance?

A

Kidneys control acid-base levels by excretion of acidic or basic urine

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27
Q

What are the primary renal mechanisms involved in acid-base control?

A

“Reabsorption” and secretion of HCO3-
Formation of “new” HCO3-
Secretion of [H+] into tubular fluid
Buffer systems within tubule that react with secreted [H+]
NH3: NH4+, HPO42-:H2PO4-, HCO3-:H2CO3

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28
Q

How do the kidneys buffering systems work?

A

HCO3- reabsorbed from tubule
Kidney regenerates new HCO3-; released into plasma

Kidney produces NH3

Protein remains in plasma

Phosphate ions reabsorbed from tubule

29
Q

How are HCO3- filtered?

A

Like Na+ and other small solutes, bicarbonate ions are freely filtered by the glomeruli

30
Q

What is the significance of HCO3- conservation?

A

If even a small proportion of HCO3- was excreted in urine, normal stores of this important buffer would be quickly exhausted

31
Q

How is HCO3- excretion prevented?

A

Prevented by avid tubular reabsorption of HCO3- (>99.9%) sot only 2mmol of HCO3- are excreted in urine each day

32
Q

Explain renal control of [H+] and [HCO3-]?

A
  1. Kidney tubule cells - CO₂ + H₂O = H₂CO₃ via carbonic
    anhydrase
  2. Carbonic acid dissociates into H+ and HCO3-
  3. Na+ moving down it’s conc gradient from tubular fluid →
    cell provides energy for secondary active secretion of
    H+ into tubule lumen. ATP provides energy for primary
    active secretion of H+ from cell into lumen
  4. With each H+ that’s secreted, one HCO3- enters blood
    accompanied by Na+ which is swapped for H+ -
    buffering in ECF
33
Q

When is new HCO3- generated?

A

Only when H+ derived from intracellular H2CO3 is secreted into the tubule and buffered in the tubular fluid by a non-bicarbonate buffer

34
Q

What is the role of Acetazolamide?

A

Acetazolamide inhibits H+ formation so tubular fluid acidification doesn’t occur
Leads to inhibition of HCO3- reabsorption leading to acidosis, loss of Na+ which is obligated to the unreabsorbed HCO3- and diuresis

35
Q

Where does reabsorption of filtered HCO3 occur?

A

Occurs in the proximal tubule
85-90% of filtered HCO3- “reabsorbed”
Great capacity to secrete [H+]

36
Q

How is HCO3 reabsorbed?

A
  1. Filtered HCO3⁻ combines with secreted H+ =>
    H2CO3
  2. H2CO3 –> CO2 + H2O catalysed by carbonic
    anhydrase in luminal brush border of PCT cells
  3. CO2 diffuses into tubular cell down [ ] gradient
  4. Inside cell, CO2 + H2O due to carbonic anhydrase, to
    form H2CO3
  5. H2CO3 –> HCO3⁻ and H+
  6. HCO3⁻ passes back into bloodstream
  7. H+ passes back into tubular fluid in exchange for Na+.

In this way, virtually all the filtered HCO3⁻ is reabsorbed in the healthy individual

37
Q

Where is urine acidified?

A

Occurs in Intercalated cells of late Distal tubule and Collecting duct
H+-ATPase pump more important in this part of nephron

38
Q

Describe the [HCO3-] in the DCT

A

In distal part of nephron [HCO3-] is low and H+ react with other buffers

39
Q

What is the significance of the H+/ATPase pump in the distal nephron?

A

Allows H+ secretion against [H+] gradient acidifying the urine

40
Q

What is a buffer?

A

a solution that minimizes change in [H+], usually a base that can accept H+

41
Q

How can we determine the most effective pH of a buffer system?

A

Using titration curves

- linear portion = most effective pH (1 pH unit either side of the pK)

42
Q

How is acidity of the blood recorded clinically ?

A

as 20;1 ratio of [HCO3-]:[CO2}

43
Q

What is the activity of the enzyme Carbonic anydrase dpeendent upon?

A

Carbonic anhydrase activity depends on [H+] in ECF

44
Q

Where is carbinic anhydrase located in the body?

A

Only in the luminal epithelial membrane of the proximal tubule

45
Q

What is the role of the phosphate buffer?

A

During the acidification of urine, as majority of HCO3- has been used up other buffer systems are used to buffer the H+

46
Q

Why is the phosphate buffer so effective?

A

Very effective buffer because pK = 6.8 (close to pH of filtrate)

47
Q

Describe the sequence of events of the phosphate buffer system

A
  1. H2CO3 dissociates
  2. H+ pumped out via aldosterone sensitive ATPase pump
  3. H+ reacts with phosphate in lumen
    H+ + HPO₄²⁻ → H₂PO₄⁻ maintains a single -ve charge
    so is excreted in urine as polar molecules cannot cross
    membrane
  4. HCO3- exchanged for Cl- (HCO3-/Cl- exchanger in
    intercalated cells) into ECF
48
Q

Outline how the ammonia buffers work

A
  1. Tubular epithelium produces NH3 from glutamine via
    enzyme glutaminase
  2. Produces α-ketogluterate + 2NH₃
  3. α-ketogluterate → 2H₂CO₃ → 2H+ + 2HCO₃-
  4. H+ + NH₃ → NH₄ which is exchanged with Na via
    antiporter
  5. 2HCO₃- reabsorbed into blood via Na driven symporter
49
Q

Summarise the 3 buffer systems in the kidneys

A

Reabsorption of HCO3-
Formation of titratable acid phosphate
NH4 secretion creating new HCO3-

50
Q

How are disturbances in acid-base balance cayegorised?

A 
Acidosis (plasma pH<7.4) or Alkalosis (plasma pH>7.4) 
Either respiratory (PaCO2) or metabolic (HCO3⁻)
> depends on the event which initiates the disturbance
51
Q

What 3 mechanisms are responsible for correcting changes in pH?

A

Intra- and extra-cellular buffering
Respiratory adjustment of ECF PCO2
Renal adjustment of ECF [HCO3-]

52
Q

What is respiration controlled by?

A

Chemosenstive area in medulla regulates respiration

Monitors [H+] of plasma via CSF indirectly

53
Q

Why is p not monitored directly by the brain?

A

Charged ions can not cross Blood Brain Barrier (spinal fluid and brain can’t adjust pH directly so do so indirectly via CO2 (indirectly responds)

54
Q

Whatcauses metabolic acidosis?

A

Characterised by low pH as a result of

🡩ECF [H+] or 🡫ECF [HCO3-]

55
Q

Explain how the regulation of respiration resolves acidosis

A
  1. inc. Plasma PCO2
  2. Detected as 🡫CSF pH and 🡫plamsa pH
  3. inc. respiratory ventilaton
  4. dec. Plasma PCO2
  5. Returning to normal ECF pH
56
Q

What detects change sin CSF pH?

A

The medulla

57
Q

What detects change sin CSF pH?

A

The medulla

58
Q

What causes metabolic acidosis?

A

severe sepsis or shock ⇒ lactic acid
uncontrolled diabetes ⇒ overproduction of 3-OH-butyric acid & other ketoacids
diarrhoea ⇒ loss of HCO3- from GI tract

59
Q

Explain how the lungs and renal circulation integrate to reduce acidosis

A
  1. ICF and ECF buffering
    • less [HCO3-] used up to buffer H+
    • [H+] remain high
  2. Lungs
    • increased Ventilation
    • decreased pCO2 (compensates 🡫ECF pH)
  3. kidneys
    • more H+ secretion into urine
    • more NH4- secretion
    • more New HCO3- formation
    • more HCO3- reabsorption
    • (compensates low ECF pH)
60
Q

What is metabolic alkalosis?

A

Characterised by high pH caused by

high ECF [HCO3-] or low ECF [H+]

61
Q

What is metabolic alkalosis caused by?

A

Excessive diuretic (thiazide) use ⇒ chronic loss of Cl-,Na+ & K+ ⇒ increase H+ secretion
Vomiting ⇒ loss of H+ from GI tract
Ingestion of alkaline antacids
Hypokalemia

62
Q

How does alkalosis effect urine?

A

During alkalosis urine = alkaline due to presence of HCO3-

Normally urine = acidic as HCO3- is destroyed

63
Q

How do diuretics lead to alkalosis of the urine?

A

Diuretics such as frusemide and thiazides interfere with reabsorption of Cl- and Na+ in renal tubules

64
Q

Outlin ehow renal and lund lung compensate in response to alkalosis

A
  1. ICF and ECF buffering
    • less [H+] as its used up
    • inc. [HCO3-] remains high
  2. Lung
    • dec. ventilation
    • high pCO2 (compensates for inc. ECF pH)
  3. Kidneys
    • less H+ secretion into urine
    • less NH4- secretion
    • less HCO3- formation and reabsorption
    • more HCO3- excretion
    • (compensates for increased ECF pH)
65
Q

What causes respiratory acidosis?

A

Hpoventilation due to actions of drugs (anaesthetics/barbiturates)
Chronic emphysema
Bronchitis

66
Q

Why do lung conditions cause acidosis?

A

These conditions impair CO2 removal from lungs, causing a build up in plasma
CO2 enters cells rapidly and they contain CA so get rapid rise in H+

67
Q

How is respiratory acidosis resolved?

A

↑[H+] buffered by proteins in plasma
(within hours) ⇒ ↑[HCO3-]
Within days kidney compensates by stimulating H+ secretion & increasing HCO3- reabsorption

68
Q

Explain why respiratory alkalosis occurs

A

Less CO2 enters cells and less HCO3 diffuses out into plasma so [HCO3] is reduced

69
Q

How is respiratory alkalosis resolved?

A

Within days kidney compensates by reducing H+ secretion & decreasing HCO3- reabsorption

Kidneys and Renal functions (14 decks)

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