Lec 17 - Renal Structure + Micturation

Requirements for concentrated urine

High ADH + high medullary osmolarity

Medullary interstitium

Hyperosmotic region of kidney medulla

Main goal of concentration

Reabsorb water to conserve body fluids

Mechanisms creating medullary osmolarity

NaCl transport, urea diffusion, limited water diffusion

NaCl role in medulla

Actively transported into interstitium

Urea role in medulla

Diffuses into medulla, increases osmolarity

Water movement in medulla

Limited compared to solute reabsorption

Segment with greatest effect

Thick ascending limb

Thick ascending limb function

Active Na+, K+, Cl- transport

Descending limb function

Water reabsorption

Ascending limb permeability

Impermeable to water

Tubule permeability (PCT)

High water permeability

Thin descending limb

Permeable to water

Thin ascending limb

Not permeable to water

Thick ascending limb

Active solute transport only

Distal tubule permeability

Variable, ADH dependent

Collecting duct permeability

ADH dependent

Countercurrent multiplication

Mechanism to create medullary gradient

Single effect

~200 mOsm gradient between limbs

Limitation of single effect

Diffusion opposes gradient

Initial condition of loop

Isosmotic (~300 mOsm)

Step 1 of countercurrent

NaCl pumped out of ascending limb

Step 2 of countercurrent

Water leaves descending limb

Step 3 of countercurrent

Flow brings new fluid

Gradient formation

Repeated cycles increase osmolarity with depth

Final medullary gradient

~300 → 1200–1400 mOsm

Direction of gradient

Increases deeper into medulla

Importance of flow

Allows gradient buildup

Why gradient matters

Drives water reabsorption

Distal tubule fluid

Dilute coming from loop

Early distal tubule

Reabsorbs NaCl

Late distal tubule

ADH-dependent water reabsorption

Collecting tubule function

Major site of water reabsorption

Collecting duct function

Final urine concentration

Medullary collecting duct

Highest concentration capability

Maximum urine concentration

Limited by medullary osmolarity

Role of ADH

Increases water permeability

Effect of ADH

More water reabsorbed → concentrated urine

Urea contribution to medulla

~40–50% of osmolarity

Urea transporters

Activated by ADH

Urea recycling

Returns urea to loop of Henle

Urea recirculation path

Collecting duct → loop → back to medulla

Purpose of urea recycling

Maintains medullary gradient

Effect of antidiuresis

Increases urea recycling

Vasa recta

Blood vessels parallel to loop of Henle

Vasa recta function

Maintains gradient via countercurrent exchange

Countercurrent exchange

Passive exchange of solutes and water

Vasa recta role

Prevents washout of medullary gradient

Vasa recta removes

Excess water

Vasa recta maintains

NaCl concentration

Osmolarity in proximal tubule

~300 mOsm

Osmolarity in descending limb

Increases with depth

Osmolarity in ascending limb

Decreases (diluting segment)

Osmolarity in distal tubule

Low (~100 mOsm)

Osmolarity in collecting duct

Variable depending on ADH

Effect of ADH on osmolarity

Increases urine concentration

Without ADH

Dilute urine produced

With ADH

Concentrated urine produced

Why mammals are good concentrators

Long loops + strong gradient

Human max urine concentration

~4.2x plasma

Small animals (shrew)

~12x plasma

Large animals (whale)

~2.5x plasma

Scaling of urine concentration

Smaller animals concentrate better

Reason for scaling

Differences in loop length and metabolism

Sodium concentration in plasma

140–145 mEq/L

Primary determinant of ECF osmolarity

Sodium

Sodium regulation systems

Osmoreceptor-ADH + thirst

Osmoreceptors

Sense ECF osmolarity

ADH response to high osmolarity

Increases

ADH response to low osmolarity

Decreases

Hypo-osmotic plasma

Low ADH → more water excretion

Hyperosmotic plasma

High ADH → water retention

Thirst mechanism

Drives water intake

Trigger for thirst

Hyperosmotic CSF

Thirst + ADH

Work together to regulate osmolarity

Effect of low blood pressure

Increases ADH

Effect of low blood volume

Increases ADH

Threshold for volume response

10% decrease

Angiotensin II role

Increases Na+ and HCO3- reabsorption

Angiotensin II effect

Increases H+ secretion

Aldosterone role

Increases Na+ reabsorption and K+ secretion

Why aldosterone doesn’t change osmolarity

Water follows Na+

Why angiotensin II doesn’t change osmolarity

Water follows Na+

Potassium regulation

Linked to aldosterone activity

Aldosterone effect on K+

Increases secretion

Concept: What happens if ADH increases?

More water reabsorbed → concentrated urine

Concept: What happens if ADH decreases?

Large volume dilute urine

Concept: What happens if medullary gradient lost?

Cannot concentrate urine

Concept: What happens if thick ascending limb fails?

No gradient formation

Concept: What happens if descending limb impermeable to water?

No concentration gradient

Concept: What happens if urea recycling stops?

Reduced medullary osmolarity

Concept: What happens if vasa recta flow too high?

Gradient washed out

Concept: What happens if vasa recta blocked?

Gradient disrupted

Concept: Why is countercurrent multiplication important?

Creates osmotic gradient

Concept: Why is countercurrent exchange important?

Preserves gradient

Concept: Why is ADH essential?

Controls final water reabsorption

Concept: Why is sodium key regulator?

Determines ECF osmolarity

Concept: Why does thirst matter?

Controls water intake

Concept: What happens in dehydration?

ADH ↑, urine concentrated

Concept: What happens in overhydration?

ADH ↓, urine dilute