RENAL: Functions of the Renal Tubule

Question 1

Describe glucose reabsorption in the proximal convoluted tubule

How can flozins and diabetes affect this?

Answer 1

Glucose reabsorption occurs mainly in proximal convoluted tubule

• Glucose moves across apical membrane (renal tubule lumen) into brush border cells (SGLT)
  
  • Glucose concentration inside cells typically higher than outside → sodium- glucose linked transporters use energy from existing sodium concentration gradient to move glucose against concentration gradient
• Glucose diffuses across basolateral membrane into peritubular capillaries outside the basolateral membrane (facilitated diffusion with GLUT1/GLUT2)

Glucose is able to bind to GLUT, which carries glucose across the membrane into the interstitial space into the peritubular capillaries, therefore moving glucose into concentration
- Normal plasma glucose levels (< 200mg/ dL): glucose reabsorption matches filtration
- High plasma glucose levels (> 200mg/ dL): limited number of glucose transporter proteins prevents reabsorption from keeping up with filtration
- Higher glucose levels (> 350mg/dL):
- glucose transporter proteins fully saturated, reabsorption cannot go faster; transport maximum (Im)

SGLT:
This is present on the apical membrane, moves in sodium (2Na+) and glucose (1) at same time

The concentration gradient is maintained the Na+/K+ ATPase pump, where sodium is being removed and potassium uptake, meaning there’s a constant need for sodium in the cell

• Site of action of flozins (used for type II diabetes)
• Inhibit SGLT
• Increase excretion of GLU
• Used in type II diabetes to lower blood plasma GLU levels

SGLT and GLUT:

• Can become saturated e.g. in diabetes large levels of GLU is filtered into renal tubules
• Not all GLU reabsorbed, glucose in urine

Question 2

Describe Na+ handling by the renal tubules

Answer 2

1. Proximal convoluted tubule (65% total Na rebasorbed)
   
   • Na exchanged via Na/H exchanger (NHE) across apical membrane
   • Na exchanged via Glu and SGLT across apical membrane
   • Na then exchanged via Na+/K+ ATPase exchanger across basolateral membrane, brings Na into interstitial space and therefore circulation
2. Thick ascending loop of Henle (25% total Na reabsorbed)
   
   • Na/K/Cl symporter, moves Na K and Cl into cell, then Na/K+ ATPase pump used to move Na into interstitial space and therefore circulation (NKCC)
3. Early distal convoluted tubule (5% total Na reabsorbed)
   
   1. Na/Cl symporter NaCC, moves both Na and Cl into cells, then use Na/K+ ATPase pump to move Na into interstitial space, and therefore into circulation
4. Principal cells of the collecting duct (<5% total Na reabsorbed)
   
   1. Epithelial sodium channel, moves sodium into cell, then uses Na+/K+ ATPase pump to move Na into interstitial space, therefore into circulation

Cl- rebasorbed with Na+ using NKCC and NCC

Cl- then moves passively across tubules (b/w intracellular gaps) following +ve charge

Question 3

Describe how H2O is handled by the renal tubules

Answer 3

Counter-current multiplication

PCT:

• Na+/H2O reabsorption
• Normo-osmotic (Osmotic gradient

Thin loop of Henle:

• Permeable to H2O, NOT Na+
• Renal tubule becomes hyperosmotic as it enters medulla due to greater concentration of Na

Drive of water out, sodium follows, more sodium follows, more water moves out (multiplication system)

Thick loop of Henle:

• Permeable to Na+ (NKCC symporter) NOT H2O
• Renal tubule reduces osmolality, as more Na moves out

Collecting duct:

• Urea reabsorption (urea transporter)
• Rise in NaCl and Urea in medulla both contribute to producing hyperosmotic interstitial fluid in medulla
• Aids H2O reabsorption by thin loop of Henle

Question 4

How is the hyperosmotic gradient between the cortex and medulla maintained?

Answer 4

Counter-current exchange:

• Vasa recta capillaries creates a counter-current of NaCl and H2O movement by flowing opposite to loop of Henle
• Vasa recta enters and goes down into medulla absorbing NaCL from thick loop
• Vasa recta moves up and exits medulla, releasing NaCl back into medulla and reabsorbing H2O

Vasa recta absorbs NaCL released by thick loop and release NaCl as it exits medulla ∴ gradients maintained

Question 5

Describe tubulo-glomerular feedback

Answer 5

Feedback mechanism controlling GFR

Carried out by interactions b/w NaCl load of the renal tubule sensed by macula densa

⬇️GFR e.g. hypovolemia:

• ⬇️NaCl load at macula densa
• Leads to increase in renin release from granular cells
• Activation of RAAS system
• ⬆️Ang II - efferent arteriole constriction
• ⬆️GFR

⬆️GFR e.g. hypertension:

• ⬆️NaCl load at macula densa
• Leads to increase in adenosine
• Afferent arteriole constriction
• ⬇️GFR

Question 6

Describe how sodium and water reabsorption is controlled by ADH

Answer 6

ADH released posterior pituitary gland

Release due to reduction in blood volume and/or increased osmolality

• Increases permeability of collecting duct to H2O through insertion of aquaporin (water channels)
• Also increases urea transported to increase urea reabsorption and increase osmolality of medulla, driving more H2O reabsorbption

Increases blood volume, reduces osmolality

Question 7

Describe how sodium and water reabsorption is controlled by RAAS

Answer 7

RAAS stimulated by hypovolemia, increase sympathetic nervous system, reduced GFR

Ang II (PCT)

Aldosterone (principal cells)

• Increased Na reabsorption
• Increased NHE (Na/H exchanger) and ENaC activities
• Increased H2O reabsorption

Increased blood volume