4. Tubular Function Flashcards

1
Q

What is osmolarity?

A
  • A measure of solute concentration in a solution
  • A measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane
  • Dependent on the number of solute particles (not the nature)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the normal plasma and urine osmolarity?

A

• Plasma - 285-295mosmol/L
• Urine - 50-1200mosmol/L
- huge variation
- intake of different solutes from external environment varies considerably
- necessary to maintain a constant plasma osmolarity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Outline transport across the renal tubular wall

A
  • Single epithelial layer
  • Tight junctions at apical membrane
  • Lateral intercellular spaces between cells at basolateral membranes
  • Peritubular capillary in close association with basal membrane
  • Movement may be in either direction (reabsorption or secretion) and can be transcellular or paracellular
  • Active
  • Passive - osmosis, co-transport, counter transport (antiporters) etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How does the passive movement of lipophilic molecules compare to hydrophilic molecules?

A
  • Lipophilic - protein independent, directly proportional to solute concentration
  • Hydrophilic - protein dependent, rate has a maximum (due to transport maxima of protein carriers)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 2 types of active movement across a cell?

A

1) Directly coupled to ATP hydrolysis - substance moved into cell using energy from ATP hydrolysis (apical)
2) Indirectly coupled to ATP hydrolysis - substance moves out of the cell using the energy from ATP hydrolysis (basal), creating a concentration causing passive movement in at the apical membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is glycosuria related to transport across a cell?

A
  • Transport system for reabsorption of glucose is overloaded
  • Not all glucose is reabsorbed from tubular fluid
  • Some is excreted in the urine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What important substances are secreted from the peritubular capillaries into the tubular fluiid?

A
(passive or active)
• H+
• K+
• Choline
• Creatinine
• Penicillin and other drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What proportion of glucose, amino acids, bicarbonate and sodium is reabsorbed in the PCT?

A
  • 100% glucose, amino acids (+ nutrients)
  • 90% bicarbonate
  • 65% sodium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is secreted and what is not reabsorbed from the PCT?

A
  • H+ secreted

* Creatinine, sulphates, phosphates and nutrients are not reabsorbed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are proteins reabsorbed?

A
  • Protein binds to protein-receptors on the apical membrane
  • Formation of a put
  • Internalisation of protein-receptor complex into a vesicle
  • Receptor dissociates + recycled
  • Proteins broken down into amino acids and transported into the blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which component drives the majority of the reabsorption in the PCT and describe how different substances use this mechanism?

A
  • Na/K pump on basolateral membrane
  • Pumps Na+ out of cell into peritubular capillary
  • Concentration and electrochemical gradient favours Na+ movement into the cell (indirect absorption)
  • Couples the uphill movement of glucose and amino acids into the cell (symporter) and H+ out of the cell (antiporter)
  • Urea and water follows passively
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does the structure of the descending limb compare to the ascending limb?

A
  • Descending limb - thinner, highly permeable to water, fewer mitochondria
  • Ascending limb - thicker, impermeable to water, more mitochondria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the microstructure of the ascending limb

A

• Cuboidal epithelium with few microvilli
• Na/K pump on basal membrane creates gradient
- drives the symporter on apical membrane
- 1 Na+, 1 K+ and 2 Cl- ions into the cell
- inside of the cell becomes more negative (due to other movements of the ions)
• K+ channel on apical membrane allows it to leak back into the lumen
- this exaggerates the electrical gradient, driving the paracellular movement of Na+, K+, Ca2+ and Mg2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do loop diuretics do?

A

Block the Na/K/Cl co-transporter (lumen=>cell)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What proportion of water and Na & K is reabsorbed in the Loop of Henle?

A
  • 85% of water

* 90% of Na+ % K+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the movement of substances into the DCT cell

A
  • Cuboidal epithelium with few mitochondria
  • Na+ dependent uptake of Cl- occurs (co-transporter)
  • Ca2+ enters cell by gradient
17
Q

What do thiazides do?

A
  • Target Ca2+ channels in DCT cell

* Knock on effect on plasma calcium

18
Q

What is special about the part of the DCT where it meets the glomerulus?

A
  • Macula densa
  • Forms part of the juxtaglomerular apparatus
  • Detects changes in [Na+] of the tubular fluid filtrate
19
Q

Describe the distal DCT and cortical collecting duct

A

• Fine tuning of filtrate
• Principle cells:
- important in sodium, potassium and water balance
- in DCT, apical sodium channels are sensitive to aldosterone, and linked to K+ channel
- cortical collecting duct: controlled by vasopressin, tight epithelium - tightly regulate water
• Intercalated cells:
- exist between each principle cell
- important in acid-base balance
- mediated by a H+-ATP pump on the apical membrane

20
Q

What are the 3 single gene defects which affect tubular function?

A
  • Renal tubule acidosis
  • Bartter syndrome
  • Fanconi syndrome
21
Q

What is renal tubule acidosis?

A

• Inability to acidify urine below pH5.5
• Leads to hypercholermic metabolic acidosis of the blood
• Symptoms also include impaired growth and hypokalaemia
• Defect in the distal renal tubule => failure of H+ secretion (usually swapped in with HCO3-)
• Can be caused by:
- malfunction of bicarbonate transport out of tubular cell into blood, accumulation, limited carbonic anhydrase activity
- mutation in carbonic anhydrase enzyme

22
Q

What is Bartter Syndrome?

A
  • Excessive electrolyte secretion
  • Mutation in Na/Cl/K co-transporter on ascending limb or mutation in the K+ channel
  • Causes evere salt loss, moderate metabolic alkalosis, hypokalaemia, renin & aldosterone hypersecretion
  • Antenatal Bartter syndrome = more severe, premature birth, polyhydramnios
23
Q

What is Fanconi Syndrome?

A

• Failure of protein reabsorption
• Increased excretion of low molecular weight proteins
• Increased excretion of uric acid and glucose phosphate
• Caused by defect in Cl- channel involved in protein-receptor vesicle recycling
- reduction in protein receptors
• Consequences include excessive amount of cytokines flowing through tubular system => immune response