Kidney Function: Producing Urine Flashcards

1
Q

What is renal clearance?

A

The volume of plasma that is cleared of a substance in a given time.

Renal clearance = (UxV)/P
U= urine concentration
V= volume of urine/min
P= concentration in plasma

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2
Q

What is the clearance value of inulin? Why is this significant?

A

Inulin clearance = 126ml/min

Used experimentally to accurately determine the glomerular filtration rate (GFR).

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3
Q

What is used clinically to estimate the glomerular filtration rate?

A

Creatinine.

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4
Q

What does it mean if a substance has a clearance value less than inulin?

A

Assume the substance has undergone reabsorption.

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5
Q

What does it mean if a substance has a clearance value more than inulin?

A

Assumes the substance has been secreted (not reabsorbed)

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6
Q

What is para-aminohippuric acid(PAH)? How is it significant?

A

Diagnostic agent.
It is filtered and completely secreted. It is not reabsorbed.
Hence all the blood plasma that enters the kidney is cleared of PAH.
PAH clearance = renal plasma flow.

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7
Q

What is an estimate of the renal plasma flow?

A

PAH clearance = renal plasma flow

=600ml/min (slight underestimate)

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8
Q

How do you use renal plasma flow to calculate renal blood flow?

A

Whole bell is 45% cells
Plasma occupies 55% of blood volume.

Renal blood flow =600/0.55 = 110ml/min

Renal plasma flow = 600ml/min
% blood which is plasma = 0.55

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9
Q

What is osmolality?

A

Measured in mosm/kg
Osmolality is a measure of water concentration.
Higher the solution osmolality, the lower the water concentration.

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10
Q

What is the osmolality of plasma?

A

285-295mosm/kg

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11
Q

What is the osmolality of urine?

A

50-1400 mosmol/kg

urine concentration can vary greatly

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12
Q

What is the main osmotically active solute in plasma?

A

Sodium (Na+)

Plasma [Na+] = 140mM

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13
Q

How do you calculate the rate of Na+ filtration in the kidney?

A

[Na+] x GFR = Rate of Na+ filtration

140 x 0.125 = 17.5mmoles/min

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14
Q

Where in the nephron does Na+ reabsorption occur? Active/passive?

A
Active process via transporter proteins
-proximal tubule
-thick ascending limb
-distal tubule
- collecting duct
Passive absorption:
- in the thin ascending limb of the Loop of Henle
NO absorption in the descending limb
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15
Q

How does Na+ reabsorption occur in the proximal tubule?

A

Na+/H+ exchanger transports Na+ from tubule lumen into epithelial cell.
Na+ nutrient symporter transports Na+ from tubule lumen into epithelial cell along with X-(glucose, amino acids, organic molecules).
Na+ K+ ATPase pumps 3Na+ out of epithelial cells into capillary and 2K+ into epithelial cell.

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16
Q

How does Na+ reabsorption occur in the thick ascending limb?

A

Na+:K+:2Cl- co-transporter transports ions from tubule into epithelial cell.
Na+K+ATPase pump Na+ out of the epithelial cell into capillary.

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17
Q

How does Na+ reabsorption occur in the distal tubule?

A

Na+:Cl- co-transporter transports Na+ from the tubule into epithelial cell.
Na+K+ATPase pumps Na+ out of the epithelial cell into capillary.

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18
Q

How does Na+ reabsorption occur in the collecting duct?

A

Na+ channel in luminal membrane - Na+ pumped into principal cell.
Na+ transported into capillary from principal cell by Na+K+ transporter.

19
Q

What 3 factors does water reabsortion depend on?

A

Osmosis
Sodium reabsorption
Tubule permeability

20
Q

How does tubule permeability vary?

A

Aquaporin-1-channels.

Permeability at tight junctions between cells in the tubule wall varies.

21
Q

What defines whether dilute or concentrated urine is produced?

A

The osmolarity of the renal medulla interstitial fluid.
Osmolarity less than plasma = Dilute urine
Osmolarity greater than plasma = concentrated urine.
Water moves from low osmolarity to high osmolarity.

22
Q

How is sodium and water reabsorption separated?

A

Water - occurs in the descending limb.

Sodium - occurs in the ascending loop via Na+K+2Cl- transporters.(impermeable to water).

23
Q

What is the counter current multiplier?

A

Active transport of sodium out of the ascending limb creates osmotic gradient so water moves by osmosis out of the descending limb.
Counter current flow increases the osmotic gradient between the tubular fluid and the interstitial space.

24
Q

What is urea?

A

Waste breakdown product of protein.

Freely filtered at the renal corpuscle

25
Q

How does urea recylcing occur in the kidney?

A
  1. Proximal tubule - passive reabsorption of urea - 50% of intial ultrafiltrate concentration is reabsorbed
  2. Loop of Henle - apical secretion vai urea transporters. Urea is removed from medullary interstium and returned to filtrate.
  3. Inner medullary collecting duct - apical reabsorption via UT-A1. 70% is reabsorbed.

Overall: 40% of urea is excreted.

26
Q

What is the effect of ADH on water reabsorption?

A

ADH acts on V2 receptor in collecting duct.
Second messenger system - cAMP mediated.
Aquaporin-2 membrane insertion.
Increased number of water channels so more water is reabsorbed.
Urine becomes more concentrated.

27
Q

What is oligouria and polyuria?

A

Oligouria - urine output below 0.428l/day

Polyuria - excessive urine output

28
Q

What is normal and maximum urine output?

A
Normal = 1-2l/day
Maximum = ~23l/day
29
Q

What is osmolar clearance(Cosm) and how can it be calculated?

A

The clearance rate of all osmotically active particles. The volume of plasma cleaved of osmotically active particles per unit time.

Cosm = (Uosm x V)/Posm

V = urine flow rate
Uosm = urine osmolarity
Posm = plasma osmolarity
30
Q

What is fasting osmolar clearance?

A

2-3ml/min

31
Q

What is free water clearance (Ch2o) and how is it calculate?

A

The volume of blood plasma cleared of solute-free water per unit time.
Used to assess renal function.

Ch2o = V - Cosm
= urine flow - osmolar clearance

32
Q

What do the values of free water clearance indicate?

A

Ch2o >0 indicates hyposmotic urine (dilute)
Ch2o = 0 indicates iso-osmotic urine
Ch2o < 0 indicates hyperosmotic urine (concentrated)

33
Q

How is plasma osmolarity controlled?

A

Plasma osmolarity is detected by osmoreceptors in the hypothalamus. Neurosecretory cells in the paraventricular and supraoptic nuclei produce and secrete ADH into blood via the posterior pituitary gland.

34
Q

What is diabetes insipidus?

A

‘Water diabetes’
Characterised by polyuria and polydipsia.
ADH disfunction - too much urine produced

35
Q

What is osmotic diuresis?

A
  1. Increased blood glucose
  2. increased glomerular filtration of glucose
  3. Increased osmolarity in filtrate.
  4. Decreased water reabsorption from proximal tubule.
36
Q

Outline the K+ transport pathways in the thick ascending limb.

A

30% of K+ is reabsorbed at the thick ascending limb by Na+:K+:2Cl- co-transporters.
5% is reabsorbed in the distal tubule by K+/H+ exchanger protein.

37
Q

Outline the K+ transport pathways in the collecting duct.

A

K+ is reabsorbed by intercalated cells (in exchange for H+).

K+ is secreted by principal cells.

38
Q

Give 4 factors which affect K+ secretion by principal cells in the collecting duct.

A

1) Factors affecting Na+ entry through epithelial cells.
2) Aldosterone stimulates K+ channels
3) Tubular flow rate - high flow rates favour secretion.
4) Acid-base balance - acidosis inhibits secretion whilst alkalosis enhances secretion.

39
Q

What is hypokalemia and what is it caused by?

A

Hypokalaemia = Low plasma potassium concentration [K+]<3.5mM
Caused by:
- increased external losses e.g. diuretics, vomiting, diarrhoae
- Redistribution of K+ into cells during metabolic alkalosis and insulin excess.
- Inadequate K+ intake in starvation.

40
Q

How does an insulin excess cause low plasma [K+]?

A

Insulin in excess stimulates activity of Na+K+ATPase pump which pumps K+ out of interstitial space and into epithelium thus lowering the plasma [K+]

41
Q

What occurs as a result of hypokalemia?

A

Resting potential will become more negative.

Nerves need to be depolarised more to reach threshold for action potential - repolarisation occurs more slowly.

42
Q

What is hyperkalemia and how is it caused?

A

High plasma [K+]. [K+] > 5.5mM
Caused by:
- Decreased external losses. Renal failure, action of drugs.
- Redistribution out of cells. Acidosis, tissue destruction/cell lysis.

43
Q

What problems occur as a result of hyperkalemia?

A

Resting membrane potential shifts up closer to threshold - easier for action potentials to fire.
Causes problems with cardiac function, skeletal muscle, gastrointestinal problems and renal problems.

44
Q

What is the treatments for hypo and hyperkalemia?

A

Hypokalemia - Replace K+ via eating foods rich in K+.
Hyperkalemia:
- Short term: stabilise cardiac membrane and administer calcium intravenously to antagonise the effect of K+ on cardiac muscle.
- Long term: shifting potassium into cells. Insulin administered + glucose. Removing potassium from the body - increase K+ excretion with diuretics or treat for renal failure.