Renal physiology Flashcards

1
Q

What is the plasma clearance?

A

The volume of plasma completely cleared of a particular substance per minute

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2
Q

How can the plasma clearance of a substance be calculated?

A

Clearance of substance X = rate of excretion of X/plasma concentration of X

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3
Q

What is the clearance of inulin and what implications does this have clinically?

A

Inulin clearance = GFR

Therefore, inulin clearance can be used to calculate GFR

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4
Q

What is the plasma clearance of glucose and why?

A

Clearance = 0

It is filtered in the glomerulus, completely reabsorped and not secreted from plasma or excreted in urine

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5
Q

What will the clearance of a substance that is filtered, partly reabsorped and not secreted be and give an example?

A

Clearance < GFR

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6
Q

What will the clearance of a substance that is filtered, secreted and not reabsorped be, and give an example?

A

Clearance > GFR

H+

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7
Q

What is para-amino hippuric acid?

A

An exogenous organic anion used clinically to calculate renal plasma flow

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8
Q

What is the clearance of para-amino hippuric acid?

A

Complete - it is filterd, secreted, but not reabsorped

All the PAH in the plasma that escapes filtration is secreted from the peritubular capillaries

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9
Q

What is the filtration fraction?

A

The fraction of plasma flowing through the glomeruli that is filtered into the tubules

i.e. ~20% of the plasma that enters the glomeruli is filtered - the remaining 80% moves on to the peritubular capillaries

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10
Q

Which substances are reabsorped in the proximal tubule?

A

Sugars

Amino acids

Phosphate

Sulphate

Lactate

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11
Q

Which substances are secreted in the proximal tubule?

A

H+

Hippurates

Neurotransmitters

Bile pigments

Uric acid

Drugs

Toxins

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12
Q

What are the five steps in tubular reabsorption?

A
  1. Absorption into epithelial cell
  2. Movement across epithelial cell
  3. Transport out of epithelial cell
  4. Diffusion across interstitial fluid
  5. Diffusion across capillary wall
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13
Q

What does paracellular transport in the proximal tubule depend on?

A

Tightness of junction between tubular epithelial cells

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14
Q

Which kind of transport mechanism is essential at th basolateral membrane for sodium reabsorption, and how does this occur?

A

The energy-dependent Na+-K+ ATPase transport mechanism at the basolateral membrane pumps sodium out of the epithelial cell, creating a concentration gradiant that draws sodium out of the proximal tubule by diffusion

Sodium pumped into interstitial fluid is then taken into blood by diffusion

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15
Q

How can the concentration gradient of sodium from proximal tubule to epithelial cell, created by the active transport pump at the basolateral membrane, be used for reabsorption of other substances?

A

The sodium gradient can be used to drive glucose and amino acid uptake, using secondary active transport and co-transporters
It can also be used to secrete H+ into the filtrate

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16
Q

What percentage of the filtered glucose is reabsorbed in the proximal tubule?

A

Normally 100%

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17
Q

What is the definition of the transport maximum e.g. of glucose?

A

The greatest quantity of glucose filtered from the plasma that can successfully be reabsorped in the proximal tubule

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18
Q

Explain why the blue line for ‘excreted’ only occurs later in the graph?

A

Glucose only begins to be excreted once the transport maximum has been reached

Excretion is the difference between filtration and reabsorption

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19
Q

What percentage of salt and water is reabsorbed in the proximal tubule?

A

~67%

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20
Q

How is Cl- reabsorption in the proximal tubule driven?

A

Driven by the paracellular pathway to Na+ reabsorption

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21
Q

What is the function of the loop of henle?

A

To create a cortico-medullary solute concentration gradient

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22
Q

What is reabsorped in the ascending limb of the loop of henle?

A

Na+

Cl-

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23
Q

Is the ascending limb of the loop of henle permeable or impermeable to water?

A

Relatively impermeable

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24
Q

Is the reabsorption of salt active or passive in the ascending limb of the loop of henle?

A

Active in the upper/thick part

Passive in the lower/narrow part

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25
Q

What is reabsorped in the descending limb of the loop of henle?

A

Water

It does not reabsorb salt

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26
Q

Through which transport mechanism is salt reabsorped in the thick ascending limb of the loop of henle?

A

Na+ K+ Cl- triple co-transporter

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27
Q

How is potassium from the triple co-transporter in the thick ascending limb of the loop of henle used in salt reabsorption?

A

It is recycled: a cotransporter uses potassium to pump Cl- into the interstitial fluid and then the K+ is used in a countertransporter to pump Na+ from the cell

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28
Q

What is the purpose of countercurrent multiplication?

A

To concentrate the medullary interstitial fluid, enabling the kidney to respond to ADH to produce urine of different volume and concentration

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29
Q

What effect does ADH have on the collecting duct?

A

ADH changes the permeability of the collecting duct from water impermeable to water permeable, to allow reabsorption

30
Q

What is vasa recta?

A

A group of straight capillaries in the medulla that lie alongside the loop of henle and act as a countercurrent exchanger

31
Q

How does the vasa recta ensure NaCl and urea aren’t washed away by essential medullary blood flow, as illustrated in this diagram?

A

Vasa recta capillaries follow hairpin loops and are freely permeable to NaCl and water

Blood flow to vasa recta is low

32
Q

Which two receptors control ADH release?

A

Hypothalamic osmoreceptors

Atrial stretch receptors

33
Q

What is ADH release stimulated by?

A

Increased osmolarity (detected by hypothalamic osmoreceptors)

Decreased blood pressure/fluid volume (detected by atrial stretch receptors)

34
Q

Does nicotine inhibit or stimulate ADH release?

A

Stimulates

35
Q

Does alcohol inhibit or stimulate ADH release?

A

Inhibit

36
Q

How does salt imbalance manifest in the body?

A

As changes in extracellular volume

37
Q

When is aldosterone secreted?

A

In response to the RAAS

In response to rising K+ or falling Na+ in the blood

38
Q

What does aldosterone do?

A

Stimulates Na+ reabsorption and K+ secretion

39
Q

What effect does a change in body pH have on the nervous system?

A

Acidosis can lead to depression of the CNS

Alkalosis can lead to overexcitability of the peripheral NS and later the CNS

40
Q

From what three sources is H+ continually added to the body from?

A

Carbonic acid formation

Inorganic acids produced during breakdown of nutrients

Organic acids resulting from metabolism

41
Q

What is pKa?

A

The pH at which an acid is 50% dissociated

= -logK

42
Q

What is the normal plasma pH?

A

7.4

43
Q

What is the most important physiological buffer system?

A

The CO2-HCO3 buffer system

44
Q

How is bicarobonate reabsorbed in the proximal tubule?

A

CO2 and H2O are taken into the epithelial cell and carbonic anhydrase converts these into carbonic acid, H2CO3

This then dissociates into H+ and bicarbonate, HCO3

Bicarbonate is then taken into the extracellular fluid by co-transportation out of the epithelial cell with Na+

45
Q

What happens to H+ ions that have dissociated from carbonic acid in the epithelial cell?

A

It can be transported actively back into the tubule and can either combine with phosphate to be excreted or may be recycled and taken back into the epithelial cell

46
Q

How is ‘new’ bicarbonate generated in the kidney?

A

In the epithelial cell, carbonic acid dissociated into H+ and bicarbonate

The H+ is pumped actively into the tubule and binds with phosphate to form an acid, which is then excreted

It can also bind to NH3 in the filtrate to form ammonia which is then excreted

The corresponding bicarbonate is then reabsorped, and there is a net gain of bicarbonate

47
Q

What is titratable acid and how is it measured?

A

The amount of H+ excreted as (largely) H2PO4-

Measured as the amount of strong base needed to titrate the solution back to pH 7.4

48
Q

What is the maximum amount of titratable acid the kidneys can produce daily?

A

~40mmol/day

49
Q

What is the normal bicarbonate concentration in plasma?

A

Close to 25mmol

(23-27)

50
Q

What is the normal arterial pCO2?

A

40mmHg

(35-45)

51
Q

What is the difference between compensation and correction?

A

Compensation is the fixing of pH irrespective of what happens to pCO2 and [HCO3-]

Correction restores pH, pCO2 and [HCO3-] to normal

52
Q

How does CO2 retention generate acidosis?

A

Increased [CO2] increases [H+] as the equilibrium of the CO2-HCO3 buffer system is shifted to the right

This also increases [HCO3] but pH is only a measure of [H+] concentration so only this is reflected

53
Q

When is uncompensated respiratory acidosis indicated?

A

pH < 7.35 and PCO2 > 45 mmHg

54
Q

Where would respiratory acidosis lie on a Davenport diagram?

A

Low pH, high [HCO3-]

55
Q

How is respiratory acidosis compensated for?

A

Virtually no cellular buffering

High pCO2 stimulates H+ secretion into the filtrate

This generates ‘new’ HCO3 and plasma [HCO3] concentration rises

56
Q

How does compensated respiratory acidosis look on a Davenport diagram?

A
57
Q

What are some of the causes for respiratory alkalosis?

A

Low inspired PO2 at altitude (hypoxia stimulates peripheral chemoreceptors, hyperventilation lowers PCO2)

Hyperventilation (causes include fever, brainstem damage)

Hysterical overbreathing

58
Q

How does excessive removal of CO2 due to ventilation disorders cause alkalosis?

A
59
Q

When is uncompensated respiratory alkalosis indicated?

A

pH > 7.45 and PCO2 < 35 mmHg

60
Q

What does uncompensated respiratory alkalosis look like on a Davenport diagram?

A
61
Q

How is respiratory alkalosis compensated for?

A

Reduced pCO2 reduces secretion of H+ from the kidney

This reduces the reabsorption of HCO3- and it is excreted in the urine, making the urine slightly alkaline

Plasma [HCO3-] is lowered

62
Q

What does compensated respiratory alkalosis look like on a davenport diagram?

A
63
Q

What are [H+] and [HCO3-] in metabolic acidosis and why?

A

Raised [H+] = lowered pH

Depleted [HCO3] due to excess buffering of H+, or due to loss from the body e.g. diarrhoea

64
Q

How is metabolic acidosis indicated?

A

pH < 7.35 and [HCO3-]p is low

65
Q

What does uncompensated metabolic acidosis look like on a davenport diagram?

A
66
Q

How is metabolic acidosis compensated for?

A

Excess CO2 is blown off, shifting equilibrium to the right and decreasing [H+] and [HCO3-]

Because [HCO3-] is very low, filtered HCO3- is also low and very readily reabsorbed

This stimulates H+ secretion into the tubule to

1) allow more excretion of acid in the urine in the form of NH4 and titratable acid
2) generate ‘new’ bicarbonate

67
Q

What does compensated metabolic acidosis look like on a davenport diagram?

A
68
Q

How is metabolic alkalosis indicated?

A

pH > 7.45 and [HCO3-]p is high

69
Q

What does metabolic alkalosis look like on a davenport diagram?

A
70
Q

How is metabolic alkalosis compensated for?

A

Hypoventilation

Retention of CO2 shifts equilibrium to the right

[H+] and [HCO3-} increases

Filtered HCO3- load is so large compared to normal that not all of the filtered HCO3- is reabsorbed, so much of the HCO3- is excreted in the urine

71
Q

What does compensated metabolic alkalosis look like on a davenport diagram?

A