Lecture 47 - Urinary System: Regulation of Urine and the Creation and Role of the Medullary Osmotic Gradient

Question 1

Describe the anatomy of the Loop of Henle and the collecting duct

Answer 1

Loop of Henle:
- Thin limb: squamous and tight epithelia (no paracellular transport)
- Thick limb: cuboidal and tight epithelia

Collecting duct:
- 2 types of cells: intercalated cells (microvilli) and principal cells (no microvilli)
- cuboidal and tight epithelia

Question 2

Describe the location of the Loop of Henle. How does its location affect its osmolarity gradient?

Answer 2

It descends into the hyperosmotic renal medulla, then returns to the cortex via the ascending limb. The deeper in the medullar, the higher the osmolarity

Question 3

Describe the tubular flow from the PCT and through the Loop of Henle

Answer 3

Tubular fluid flows from the PCT to the thin descending limb and on into the thick ascending limb

Question 4

What is the counter-current multiplication of the Loop of Henle?

Answer 4

Counter-current - tubular flow in the limbs of the loop go in opposite directions

Multiplication - the 2 limbs have different permeabilities for water and solute movement, which enhances overall reabsorption

Question 5

What are the properties of the thin descending limb?

Answer 5

It is permeable to water, but impermeable to solutes

Thin limbs express aquaporin-1 (water channel) on their membranes that allow for water transport. Because the osmolarity of the ISF increases as the limb goes deeper, the direction of tubular flow enhances water reabsorption

Question 6

What are the properties of the thick ascending limb?

Answer 6

It can pump ions out of the tubular fluid, but it’s impermeable to water

NKCC transporters (Na+K+/2Cl-) are on the apical surface, allowing the thick limb to pump Na+ and Cl- out of the tubular lumen and into the ISF. Water cannot diffuse back into the lumen due to the impermeability despite the osmotic gradient

Question 7

How is the counter-current exchange further enhanced?

Answer 7

By the exchange across the parallel loops of the vasa recta

Exchange between the limbs and the vasa recta leads to counter-current multiplication and net reabsorption of both water and solutes

Question 8

What is the osmolarity gradient in the deep medulla partly maintained by?

Answer 8

Urea permeability in the papillary duct:

Urea becomes a larger component of tubular fluid as other solutes and water are removed. Urea transporters (and thus permeability) are only present in the papillary duct, which runs through the renal papilla. Therefore, urea diffusion into the papillary ISF maintains the high osmolarity in the deep medulla

Question 9

What is the purpose of the DCT (distal convoluted tubule) and collecting duct sites?

Answer 9

They are sites for facultative water and solute reabsorption, which means permeability/transport (ie. reabsorption) of solutes will only occur in these segments by hormonal signals (recall ADH and aldosterone from L44)

Question 10

How do the epithelia properties of the DCT and collecting duct affect solute and water transportation?

Answer 10

The epithelia in the DCT and collecting duct have little to no paracellular transport and are impermeable to water “at rest”. Without hormone signalling, water would be retained in the lumen of the DCT and CD even while passing through the high osmolarity in the deep medulla

This would lead to large volume of dilute urine

Question 11

What is the function of ADH (vasopressin)?

Answer 11

It binds to DCT and CD cells to promote the addition of aquaporins to their apical membranes

Question 12

Where is ADH secreted from and how does it lead to the addition of aquaporins?

Answer 12

Anti-diuretic hormone (ADH, also vasopressin) is secreted from the posterior pituitary. ADH acts through AVPR2 receptors (found on the basolateral membrane of DCT/CD cells). AVPR activation signals for insertion of aquaporin-2 (into the apical side of the DCT/CD cells)

Question 13

What is the purpose of aquaporins?

Answer 13

They create transmembrane permeability to water, allowing for osmotic reabsorption and the concentration of urine

Question 14

How does ADH affect urine volume, concentration, and osmolarity?

Answer 14

When ADH is present, water is reabsorbed by the DCT and CD cells, which eventually goes into the ISF and back to the bloodstream. This increased reabsorption decreases urine volume, increases concentration, thereby increasing osmolarity

Question 15

Why are ADH levels important?

Answer 15

They are the body’s key effector for homeostatic regulation of body fluid osmolarity

Question 16

What are the sensors and effectors of regulating body fluid osmolarity?

Answer 16

Sensor - ADH neurons in the hypothalamus are intrinsically osmosensitive. So when plasma osmolarity increases, they produce higher frequencies of APs

Effector - DCT and CD cells enhance facultative water reabsorption when stimulated by ADH, decreasing plasma osmolarity

ADH regulation of plasma osmolarity is a direct feedback loop

Question 17

What is diabetes insipidus (DI)? Name 2 causes

Answer 17

It is an endocrine disorder that is due to the loss of either ADH secretion or AVPR2. Some causes can be:

• Physical damage to the hypothalamus or infundibulum of the pituitary can prevent ADH secretion
• Inherited diabetes insipidus can be caused by mutations in the AVP gene or the AVPR2 gene

Question 18

How does the RAAS play a role in ion and urine regulation?

Answer 18

It regulates ion reabsorption and urine volume through aldosterone. Reductions in blood volume trigger the RAAS, resulting in aldosterone secretion, which stimulates Na+/K+-ATPase pump, enhancing K+ excretion and Na+ retention

Question 19

What does aldosterone trigger in the DCT and CD?

Answer 19

DCT: aldosterone stimulates the Na+/K+-ATPase in the basolateral membrane, amplifying the gradient for Na+ reabsorption at the apical membrane

CD: aldosterone causes addition of ENaC channels (Na+ leak channels) to the apical surface, enhancing Na+ reabsorption

Reabsorption of Na+ maintains ion gradients in the rest of the body and enhances the reabsorption/retention of water

Question 20

What are the sensors and effectors of the homeostasis of fluid in response to a loss of fluid?

Answer 20

Sensory - the JGA activates the RAAS, and angiotensin-II also stimulates ADH-secreting neurons, even if plasma osmolarity is normal

Effectors - cells of the DCT and CD increase both water and ion reabsorption

The combination of aldosterone and ADH will restore plasma volume without a change in osmolarity

Question 21

What is a diuretic?

Answer 21

Any drug that causes diuresis (increased production of urine). Most diuretics are inhibitors for specific renal transporter proteins and they are often prescribed to manage hypertension and oedema