Lec 18 - Urine Formation + Glomerular Filtration

Urine concentration scaling

Relationship between body size and urine concentration ability

Scaling exponent (b)

~ -0.097

Small animals (shrew)

~12x plasma concentration

Large animals (whale)

~2.5x plasma concentration

Humans urine concentration

~4.2x plasma

Why small animals concentrate urine better

Higher metabolic demand + relatively longer loops

Why large animals concentrate less

Less efficient medullary gradient

Primary extracellular ion

Sodium (Na+)

Normal plasma Na+

140–145 mEq/L

Main determinant of ECF osmolarity

Sodium concentration

Sodium regulation systems

Osmoreceptor-ADH system + thirst mechanism

Osmoreceptors

Sense osmolarity of ECF

Location of osmoreceptors

Hypothalamus region (implied)

ADH (vasopressin)

Controls water reabsorption

ADH release trigger

High ECF osmolarity

ADH effect

Increases water reabsorption → lowers osmolarity

Low osmolarity response

↓ ADH → ↑ water excretion

High osmolarity response

↑ ADH → water retention

Thirst mechanism

Controls water intake

Thirst definition

Conscious desire for water

ADH + thirst relationship

Work together to regulate osmolarity

Goal of sodium regulation

Maintain ECF osmolarity

Effect of water excess

ADH decreases

Effect of dehydration

ADH increases

Effect of decreased blood pressure

Increases ADH

Effect of decreased blood volume

Increases ADH

Threshold for volume effect

10% decrease

Osmotic mechanism

Primary driver of ADH release

Volume mechanism

Secondary unless severe loss

Angiotensin II function

Increases Na+ and HCO3- reabsorption

Angiotensin II effect

Increases H+ secretion

Aldosterone function

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+

Effect of aldosterone

Increases total Na+ reabsorption

Effect of angiotensin II

Enhances Na+ reabsorption

Key idea of sodium regulation

Controls volume more than osmolarity

Decoupling of water and solute excretion

ADH allows independent control

Potassium (K+) importance

Critical for cardiac function

Normal ECF K+

~4.2 mEq/L

Danger of high K+

Arrhythmias or cardiac arrest

Potassium balance

Maintained tightly

Immediate buffering of K+

Shift into cells (ICF)

Why intracellular storage important

Prevents dangerous spikes after meals

Factors affecting K+ movement

Between ECF and ICF

Example trigger for K+ shift

High K+ intake

Primary site of K+ regulation

Distal tubule + cortical collecting tubule

Main mechanism

K+ secretion

Principal cells

Cells responsible for K+ secretion

K+ secretion mechanism

Passive diffusion into tubular fluid

Source of K+ secretion

Peritubular fluid

Na+/K+ pump role

Moves K+ into cells

Driving force for K+ secretion

Concentration gradient

Factors increasing K+ secretion

Gradient, pumps, channel number

Concentration gradient role

More K+ in blood → more secretion

Na+/K+ pump stimulation

Increases K+ movement into cells

K+ channel number

More channels → more secretion

Aldosterone effect on K+

Increases secretion

Mechanism

Increases Na+/K+ pumps + K+ channels

High K+ effect on aldosterone

Increases aldosterone release

Feedback loop for K+

High K+ → ↑ aldosterone → ↑ K+ excretion

Low K+ effect

Decreases aldosterone

Effect of decreased aldosterone

↓ K+ secretion

Effect of increased aldosterone

↑ K+ secretion

Tubular flow rate effect

Increases K+ secretion

Why flow rate matters

Washes away K+ → maintains gradient

High flow effect

More K+ excretion

Integration of Na+ and K+ regulation

Linked via aldosterone

Low Na+ intake effect

↓ aldosterone → ↓ K+ secretion

High K+ intake effect

↑ aldosterone → ↑ K+ secretion

Balancing Na+ and K+

Kidneys maintain both simultaneously

Diet effect

Low Na+, high K+ beneficial for BP

Concept: What happens if ADH increases?

Water retention → lower osmolarity

Concept: What happens if ADH decreases?

Water loss → dilute urine

Concept: What happens if Na+ increases?

ADH increases → water retention

Concept: What happens if Na+ decreases?

ADH decreases → water loss

Concept: What happens if thirst is impaired?

Hyperosmolar dehydration

Concept: What happens if ADH is absent?

Large volume dilute urine

Concept: What happens if aldosterone increases?

↑ Na+ reabsorption, ↑ K+ secretion

Concept: What happens if aldosterone decreases?

Na+ loss, K+ retention

Concept: What happens if K+ increases in blood?

Aldosterone increases → excretion

Concept: What happens if K+ decreases?

Aldosterone decreases

Concept: What happens if Na+/K+ pump inhibited?

K+ secretion decreases

Concept: What happens if K+ channels blocked?

K+ secretion decreases

Concept: What happens if tubular flow increases?

K+ excretion increases

Concept: What happens if tubular flow decreases?

K+ excretion decreases

Concept: Why is potassium tightly regulated?

Small changes affect heart function

Concept: Why is sodium key to osmolarity?

Main extracellular solute

Concept: Why do ADH and thirst work together?

Control intake and output

Concept: Why doesn’t aldosterone affect osmolarity?

Water follows Na+

Concept: Why is K+ secretion passive?

Driven by gradient

Concept: Why is Na+ reabsorption active?

Requires ATP

Concept: Why is intracellular buffering of K+ important?

Prevents acute toxicity

Concept: Why does high K+ stimulate aldosterone?

Feedback regulation

Concept: Why is flow rate important for K+?

Prevents buildup in tubule

Concept: Why is K+ secretion in distal nephron?

Final regulation step

Concept: What happens in hyperkalemia?

Increased secretion + aldosterone

Concept: What happens in hypokalemia?

Decreased secretion

Concept: Why is sodium regulation linked to water?

Sodium determines osmolarity

Concept: Why is potassium regulation separate?

Primarily intracellular ion