Urine Formation: Tubular Reabsorption and Secretion

How much glomerular filtrate is reabsorbed by the PCT?

• 65%

Tubular Reabsorption 

• reclaiming water and solutes from the tubular fluid and returning it BACK to the blood 

What reabsorbs the greatest variety of chemicals compared to any section in the nephron?

• the PCT

What are the two different routes of reabsorption?

• transcellular

• paracellular

Transcellular route

• substances pass through the cytoplasm and out of the base of epithelial cells 

Paracellular route

• substances pass through gaps between cells

• specifically “tight junctions” 

Solvent Drag

• tight junctions between cells are very leaky

• this allows water to pass through and take a variety of solutes along with it

Why is sodium chloride so important in tubular reabsorption in the PCT?

• it creates an osmotic and electrical gradient 

• drives reabsorption of water and other solutes

• most abundant cation in glomerular filtrate

What methods are used to transport sodium into the apical cell surface?

• symports

• antiports

How do symports work for transporting sodium?

• bind Na+ to anther solute (glucose, amino acids, lactate)

• these will go into epithelial cell

• considered secondary active transport

How do Na+ -H+ antiporter work for transporting sodium? 

• Na+ is pulled into cell from tubular fluid

• H+ is pumped out of cell into tubular fluid

  • eliminates acid from body fluids

what hormone has a strong influence on sodium reabsorption?

• angiotensin II

  • activates the Na+ -H+ pump 

What helps prevent sodium from accumulating inside epithelial cells?

• Na+ -K+ pump (active ATP consuming transport)

  • located in basal domain 

  • pumps Na+ into extracellular fluid 

    • this is picked up and brought to capilaries 

what substances can enter via the paracellular route?

• H2O, urea, uric acid, Na+, K+, Cl-, Mg2+, Ca2+, Pi

How is Cl- brought into the epithelial cells?

• antiports in apical cell membrane

  • absorb Cl- and exchange for other anions that are ejected into tubular fluid 

• follows Na+ due to electrical attraction 

How is Cl driven out of the basal cell surface?

• K+ -Cl- symport 

  • drives potassium and chloride out 

how do potassium, magnesium, and phosphate ions travel?

• via paracellular route along with water

• phosphate can be transported into epithelial cell with Na+ 

How much calcium is reabsorbed in the PCT?

• 52% via paracellular route

• 14% via trancellular route 

How is glucose transported into the cell? 

• cotransported with Na+ symporter 

  • called sodium-glucose transporters (SGLTs) 

How is glucose removed from the basolateral end of cells 

• facilitated diffusion 

How much glucose is reabsorbed? 

• should be all, with none left in urine 

How does urea get reabsorbed by the capilaries?

• passes through epithelium with water 

The nephron as a whole reabsorbs how much of the urea in the tubular fluid? 

• 40-60%

The nephron as a whole reabsorbs how much water?

• 99%

How does the urea concentration compare when blood enters the kidney vs when it leaves?

• concentration is around 20 mg/dL when it enters

• when it leaves it is down to 10.4 mg/dL

• this means urine has a much higher urea concentration than blood or glomerular filtrate

How does uric acid reabsorption work in the PCT?

• nearly all of it is reabsorbed 

• later, it is secreted back into tubular fluid

• creatine is not reabsorbed at all 

  • stays in tubule and is all passed in urine

How much water is reduced by the kidneys per day

• 180 L glomerular filtrate to 1-2 L of urine per day 

How much water is reabsorbed by the PCT?

• approx. 2/3

How come water can travel by osmosis?

• reabsorption of salt and solutes makes the tubule cells and extracellular tissue fluid hypertonic

• water will move that way to balance that

what method is used for transcellular reabsorption of water?

• aquaporins

  • water chanels in the apical and basolateral domains

  • allow water to enter cells and leave (return to blood)

How does the osmolarity of the PCT vary compared to other parts of the nephron?

• osmolarity remains unchanged

  • water and solutes are reabsorbed proportionately 

Obligatory water reabsorption

• water reabsorption kept at a constant rate in the PCT

what happens after solutes and water leave the basal surface of tubule epithelium? 

• they are reabsorbed by the peritubular capilaries 

What factors promote osmosis into capilaries

• High interstitial fluid pressure due to
  accumulation of reabsorbed fluid in
  extracellular space.

•  Low blood hydrostatic pressure in
  peritubular capillaries due to
  narrowness of efferent arterioles.

• High colloid osmotic pressure in blood due to presence of proteins that were not filtered.

What are the mechanisms of absorption used by the peritubular capilaries? 

• osmosis

• solvent drag 

What hormone aids in the reabsorption by the peritubular capilaries? 

• angiotensin II

How does angiotensin II increase absorption into peritubular capilaries

• it constricts afferent/efferent arterioles 

• reduced BP in capilaries

• reduces resistance to fluid reabsorption 

Steps in the effects of angiotensin II release on tubular reabsorption 

1. angiotensin II secreted 

2. constriction of afferent/efferent arterioles

3. glomerular BP and filtration is maintained

4. BP is reduced in capilaries

5. this reduces resistance to reabsorption 

6. tubular reabsorption increases

7. urine volume is less, but highly concentrated 

Transport Maximum

• maximum rate of reabsorption

• reached when transporters are saturated

• each solute molecule has one 

What would happen if all transporters were occupied as a solute passed through? 

• some of that solute would escape

• it would appear in urine because it isn’t being reabsorbed

What happens if blood glucose levels ae above 220 mg/dL? 

• glucose is filtered faster than renal tubule can reabsorb it 

glycosuria

• excess glucose passed in urine

How is diabetes mellitus related to glycosuria

• plasma glucose concentration may exceed 400 mg/dL

• glycosuria is a classical sign of the disease

Tubular Secretion 

• renal tubule extracts chemicals from the capillary blood and secretes them INTO tubular fluid 

What is the purpose of tubular secretion in the PCT and nephron loop

• contributes to acid-base balance

• extracts wastes from blood

• clears drugs and contaminants from blood

what is the primary function of the nephron loop?

• generate an osmotic gradient that enables collecting duct to concentrate the urine and conserve water

What is reabsorbed by the nephron loop

• 25% 

  • Na+, K+, Cl-

• 15%

  • H2O

How are Na+, K+, Cl- reabsorbed in the thick segment of the ascending nephron loop?

• apical membrane proteins

  • bind 1 Na+, 1 K+, 2 Cl- from tubular fluid and cotransport them into cytoplasm 

How do Na+, K+, Cl- leave the basolateral cell surface

• active transport: Na+

• diffusion: K+ and Cl- 

  • K+ can re enter cell via Na+ -K pump 

Why does the tubular fluid become very dilute by the time it passes from the nephron loop to the DCT?

• thick segment of loop is impermeable to water

• cannot follow electrolytes out of tubules into capilaries

• water stays in tubule

What is the composition of fluid when it arrives to the DCT?

• 20% water

• 7% salts from glomerular filtrate

What is the function of the DCT and collecting duct?

• reabsorb variable amounts of water and salts

• regulated by hormones

What hormones regulate reabsorption by the DCT and collecting duct? 

• aldosterone

• natriuretic peptides

• antidiuretic hormone

• parathyroid hormone

What cell types are located in the DCT and collecting duct?

• Principal cells

• Intercalated cells

Principal cells

• most abundant 

• have receptors for foreign hormones 

• involved in salt and water balance 

Intercalated cells

• ferer in number

• reabsorb K+ and secrete H+ in tubule

• involved in acid base balance

Aldosterone

• salt retaining hormone

• secreted by adrenal cortex when blood Na+ concentration falls or K+ concentration increases

What does aldosterone stimulate? 

• reabsorption of Na+

  • water and Cl- follow 

• secretion of K+

what does water retension help with?

• maintaining blood volume and pressure

Aldosterone acts on what?

• thick segment of ascending limb of nephron loop

• DCT

• cortcal porton of collecting duct

How does a drop in BP induce aldosterone secretion?

• drop causes kidney to secrete renin which produces angiotensin II which then stimulates aldosterone secretion 

What is the overall effect of aldosterone?

• body retains NaCl and water

• urine volume is reduced 

• urine has elevated K+ 

Naturetic peptides

• released by the heart

• respond to high blood pressure

• result in excretion of more salt and water in the urine

Four main actions of natriuretic peptides?

• dilate afferent / constrict efferent arteriole

• inhibit renin and aldosterone secretion 

• inhibit secretion of ADH

• inhibit NaCl reabsorption

What is the overall effect of natriuretic peptides?

• reducing blood volume and pressure

Antidiuretic Hormone (ADH)

• dehydration, loss of blood volume, rising osmolarity stimulate arterial baroreceptors and hypothalamic osmoreceptors 

• secreted by pituitary gland

Effects of ADH

• makes collecting duct permeable to water 

• tubular fluid re enters tissue fluid and blood rather than being lost in urine

Parathyroid Hormone (PTH)

• released by parathyroid gland

• responds to calcium deficiency (hypocalcemia)

• has several methods of restoring calcium homeostasis

How does the PTH affect the kidney?

• PCT

  • inhibits phosphate reabsorption

• DCT and thick nephron loop 

  • increases calcium reabsorption 

Role of PHT

• increases phosphate content of urine and lowers calcium content 

  • minimizes further calcium loss 

  • helps calcium stay in circulation longer instead of precipitating into bone tissue as calcium phosphate

• also stimulates calcitriol synthesis by epithelial cells of PCT

what is the principal function of the collecting duct?

• to conserve water