4. Basic tubular function Flashcards

1
Q

What components of urine do we not have a method of transporting on their own?

A

Urea and Water: so these move in by passive transport

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2
Q

What percentage of the ultrafiltrate is reabsorbed?

A

99%

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3
Q

2 pathways once entering renal artery

A

Glomerular filtration

Directly into efferent arteriole

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4
Q

Define osmolarity.

A

A measure of osmotic pressure exerted by a solution across a perfect semi-permeable membrane.
Dependent on the number of particles not the nature.

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5
Q

How do you calculate osmolarity?

A

Add all the concentrations of the different solutes together (mmol/l)
Each ion is counted separately

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6
Q

Describe the range for normal plasma osmolarity. What makes up the majority of this?

A

Tight range: 285-295 mosmol/L

Mainly consists of Na+ (140 mmol/L)

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7
Q

What is the range for normal urine osmolarity?

A

50-1200 mosmol/L

Can vary massively

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8
Q

What effect will a solute present at equal concentrations either side of a semi-permeable membrane have on water movement?

A

No net effect on water movement

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9
Q

What are the 2 pathways for absorption and secretion through the urinary epithelium?

A

Transcellular

Paracellular (depending on how tight tight junctions are)

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10
Q

What is the difference between lipophilic passive transport and hydrophilic passive transport?

A

Lipophilic passive transport rate has a linear relationship with solute concentration
Hydrophilic passive transport rateis saturable because it is dependent on the availability of channel proteins.

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11
Q

What are the 2 routes for water to pass through the renal tubular wall?

A

Transcellular (through aquaporins)

Paracellular

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12
Q

What are primary active transport mechanisms rate limited by?

A

Availability of ATP

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13
Q

What are secondary active transport mechanisms rate limited by?

A

Concentration gradient (of Na+ going in) across membrane

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14
Q

How can hydrophilic passive transport be upregulated or downregulated?

A

By changing the number of transporters available
Decrease: Store channels inside cell
Increase: Move channels to cell membrane

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15
Q

How does protein reabsorption normally happen?

A

Receptor mediated endocytosis:
Protein binds to a receptor and is endocytosed
Acidity of the endosome allows the complex to dissociate and the receptors are recycled

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16
Q

Specificity and capacity of protein receptors on the membrane for binding proteins

A

Low specificity

High capacity

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17
Q

What happens if the concentration of a solute in the urine exceeds the transport maxima?

A

It is excreted in the urine

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18
Q

Above which plasma glucose concentration do we see glucose in the urine?

A

15 mmol/l

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19
Q

Where are the majority of Na+ transporters found?

A

Proximal tubule

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20
Q

Describe secretion

A

Moves substances from peritubular capillaries into tubular lumen
Can occur by diffusion or by transcellular mediated transport

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21
Q

What are the most important substances that are secreted?

A

H+

K+

22
Q

Describe the differences in sodium reabsorption throughout the nephron.

A

PCT: 65%
Ascending loop of Henle: 25%
DCT: 8%

23
Q

Where is most bicarbonate reabsorbed?

A

90% is reabsorbed in the PCT

24
Q

Where and how much glucose is reabsorbed?

A

PCT

100%

25
Q

Where, along the nephron, do you find cells that don’t have that many mitochondria?

A

Descending loop of Henle and collecting duct

These areas are mainly involved in the passive transport of water

26
Q

Describe the features of a cell in the PCT

A

Numerous mitochondria
Brush border to increase SA
Designed for lots of reabsorption

27
Q

What is the most important protein of the cells lining the tubules throughout the nephron?

A

Na+/K+ ATPase:

responsible for the sodium gradient that drives the movement of most substances

28
Q

Which substances move in or out with Na+ in the early proximal tubule?

A

H+ moves out into tubule (Na+/H+ countertransport)
Glucose moves into cell (Na+/glucose cotransport)
Amino acids move into cell (Na+/amino acid cotransport)

29
Q

How is proton excretion linked to bicarbonate reabsorption?

A

H+ are pumped into the tubule via (Na+/H+ exchanger)
H+ react with HCO3- to form H2CO3
H2CO3 is converted by carbonic anhydrase to CO2 + H2O
CO2 + H2O moves into the cell and carbonic anhydrase converts it back to H2CO3, which dissociates to form H+ and HCO3-.
HCO3- is passes into the blood, H+ moves out again via the Na+/H+ exchanger

30
Q

Why is reabsorption of all solutes/ water sensitive to metabolic poisons?

A

Reabsorption is dependent on ATP production

31
Q

Why is net secretion in the PCT important?

A

Route of excretion for some substances

Some drugs enter the tubular fluid here and act further down the nephron

32
Q

Describe the differences between the ascending and descending loop of Henle.

A
Descending:
Squamous epithelium
Few mitochondria
Water passively reabsorbed
Draws in Na+ and K+
Ascending: 
Cuboidal epithelium
Few microvilli but many mitochondria
Cl- actively reabsorbed
Na+ passively reabsorbed with it
HCO3- reabsorbed
Impermeable to water (very tight TJs and no aquaporins)§
33
Q

Describe the tubular fluid leaving the loop of Henle with respect to plasma

A

Hypo-osmolar
(More salt than water has been reabsorbed)
Water: 85%
Na+: 90%

34
Q

What do Loop diuretics block?

A

Na+/K+/Cl- co-transporter in ascending loop of henle

35
Q

Which transporter is found on the apical membrane in cells in the DCT?

A

Na+/Cl- cotransporter

36
Q

Which 3 ions are reabsorbed on the apical membrane of cells in the DCT?

A

Na+
Cl-
Ca2+

37
Q

Describe how thiazide diuretics would lead to increase in plasma Ca2+

A

If Na+/Cl- channel is blocked, there is only 1 passive route of entry for Na+: so more is brought in by the Na+/Ca2+ transporter, and more Ca2+ is exchanged out into the blood
This decreases intracellular Ca2+, so more Ca2+ enters passively from the lumenal side of the membrane (thus more Ca2+ is reabsorbed)

38
Q

List 5 features of the epithelium of the distal convoluted tubule.

A
Cuboidal epithelium
Few microvilli
Complex lateral membrane
Interdigitations with Na+ pumps 
Numerous large mitochondria
39
Q

What do the macula densa cells do?

A

Detect Na+ concentration in the filtrate

Can stimulate release of renin

40
Q

What is the reabsorption of Na+ in the distal part of the DCT and the collecting duct dependent on?

A

Aldosterone

41
Q

What is needed for reabsorption of water in the collecting duct?

A

ADH

42
Q

What other ions are adjusted in the DCT and CT?

A

K+
H+
NH4+

43
Q

What are the two types of cells in the collecting duct and how do their functions differ?

A
Principal cells:
Have Na+ channel sensitive to aldosterone
Regulate movement of Na+/K+/water 
Intercalated cells: 
Regulate acid-base balance
44
Q

What are each of the cells pumps in the CT mediated by?

A

Principal: Na+/K+ ATP pump
Intercalated: ATP dependent H+ pump

45
Q

State 3 single gene defects that affect tubular function.

A
Renal tubule acidosis
Bartter syndrome 
Fanconi syndrome (Dent's disease)
46
Q

What is renal tubule acidosis? State 3 clinical features.

A

Metabolic acidosis caused by failure of the renal tubules.
Hyperchloremia
Hypokalemia
Impaired growth

47
Q

What is Bartter syndrome? State 6 clinical features.

A
Excessive electrolyte secretion
Hypokalemia 
Premature birth 
Polyhydramnios 
Renin and aldosterone hypersecretion 
Moderate metabolic alkalosis
Severe salt loss
48
Q

What causes Bartter syndrome?

A

Mutation in the Na+/K+/Cl- triple transporter

This point is responsible for 25% of Na+ reabsorbtion

49
Q

What is Fanconi syndrome? List 2 clinical features

A

Disease of the proximal tubules associated with renal tubular acidosis
Increased excretion of low molecular weight proteins
Increased excretion of uric acid, glucose, phosphate and bicarbonate

50
Q

Describe how Dents disease is a cause of fanconi syndrome

A

Mutation in endosomal compartment of Cl- transporter
The endosome never gets to the pH that allows dissociation of the protein from its carrier, so cant recirculate carrier, so excrete protein

51
Q

Describe how a normal endosomal compartment of Cl- transporter would work

A

To acidify endosome, you have to pump H+ into it
As you pump H+ in, pH decreases, +ve charge increases
Becomes increasingly harder to pump H+ in, so have a transporter that lets some H+ out in exchange for bringing Cl- in
(1 charge goes out, but neutralise 2 charges) net reduction in charge of -3 so more H+ can be pumped in