tubular reabsorption and secretion

tubular reabsorption

• reclaiming those important solutes that were lost during filtration

• virtually everything gets reabsorbed; glucose, amino acids, 99% water, etc.

transcellular route

molecules move through the apical surface into the cell and out through the basement membrane or lateral intercellular space to reach the interstitial fluid

• requires facilitated diffusion (transport proteins and active transport)

paracellular route

molecules move between cells into the interstitial fluid

• tight junctions become leaky in PCT but tight enough to prevent pathogens

• solvent drag moves solutes through the leaky junctions

peritubular capillaries

uptake the molecules

• low hydrostatic, high colloid osmotic

concepts of tubular reabsorption

1. Na+ is the most important ion in EC fluid. Reabsorption of Na+ closely linked to transport of many other ions and molecules. Na+ intake is equal to Na+ excreted

2. reabsorption of nutrients (glucose + AA) is directly linked to reabsorption of Na+

3. reabsorption of sodium sets up osmotic gradient in proximal convoluted tubule. Where Na+ goes, water flows

4. K+ intake is equal to K+ excreted and also influenced by Na+

5. water balance is regulated in distal convoluted tubule and collecting duct (under influence of ADH)

Na+ is the most important ion in EC fluid. Reabsorption of Na+ closely linked to transport of many other ions and molecules

1. equal concentration of Na+ in filtrate and tubular cell

2. Na/K ATPase moves Na+ out of basolateral surface of cell (primary active transport)

   1. makes Na+ low inside tubulate cell

3. active transport of Na+ out of basolateral surface sets up a concentration gradient for Na+ at apical surface. Na+ moves into cell via proteins (secondary active transport)

4. 2/3 of Na+ reabsorbed in PCT through Na+/H+ exchanger

   1. active transport of Na+ at basolateral surface allows exchange protein to function

   2. antiporter; H+ goes into lumen of tubule, Na+ goes into tubular cell

The reabsorption of nutrients (like glucose and AA) is directly linked to reabsorption of Na+

1. Sodium is pumped out at basolateral surface + concentration gradient developed

2. Na+ moves into cell through transport proteins

   1. symporters move Na+ down gradient and glucose against gradient (secondary active transport)

   2. 2Na+ for 1 glucose

• Tmax- max rate of reabsorption allowed

  • reached when molecules outnumber transporters

diabetes mellitus

• in normal kidney, there’s always enough transport proteins for glucose

• insulin not produced or not effective at stimulating glucose reabsorption

• too much glucose in blood → too much glucose in filtrate → overwhelms glucose transporters

• excreted in urine

Where are nutrients reabsorbed

• 67% in proximal convoluted tubule (phosphate, nutrients, Cl-)

• 25% in thick ascending limb of nephron loop (K+, Cl-, Na+) (reabsorption of Na+ is load dependent)

• 5% in distal convoluted tubule (Cl-, Na+)

• 3% in collecting duct (Na+ reabsorption is load dependent)

what happens when there’s an increase in Na+ intake

• ECF volume and blood volume increase

• sympathetic activity decreases

• ANP increases

• capillary osmotic pressure decrease

• renin decrease

• Na+ excretion increases

what happens when Na+ intake decreases

• ECF volume and blood volume decrease

• sympathetic activity increases

• ANP decreases

• capillary osmotic pressure increase

• renin increase

• Na+ excretion decrease

the reabsorption of sodium sets up an osmotic gradient in the proximal convoluted tubule. where Na+ goes, water flows: through transport proteins in apical membrane of the tubule cells

• concentration gradient for Na+ at apical surface

• water reabsorption in PCT is obligate water reabsorption

• water MUST follow sodium (isosmotic)

• 65% water reabsorption occurs in PCT

• passive transport of water

• water moves via aquaporins and solvent drag

aquaporins

integral protein that moves water

solvent drag

paracellular transport; brings other molecules and ions with the water

potassium balance is continually modified based on dietary intake. K+ intake is equal to K+ secreted/excreted

• most K+ in ICF, so if any changes occur where K+ leaves cell and enters ECF, small changes have large effects on K+ levels

• internal K+ balance modified by:

  • insulin- stimulates K+ uptake into cells via Na+/K+ ATPase after a meal or when K+ levels in ECF rise

  • epinephrine- exercise causes tremendous release of K+ ions into ECF

    • K+ is intrinsic vasodilator in skeletal muscle

    • exercises also results in epinephrine secretion which stimulates K+ uptake into cells

  • H+ ion concentration- decrease in H+ ion concentration in ECF results in K+ movement into cells (Na+/H+ pump)

how is K+ regulated in the nephron (K+ in = K+ out)

• most K+ reabsorbed in PCT and nephron loop (thick ascending limb)

  • K+ dragged by water in PCT

  • actively transported into cells in TAL (Na+K+2 Cl- pump)

• DCT and collecting duct fine tune K+

  • reabsorption by tubule cells or intercalated cells

  • secretion by principal cells

• levels of Na+ in filtrate

  • more Na+ to DCT + collecting duct, more Na+ that is reabsorbed

  • the more Na+ reabsorbed into tubular cells = more K+ secreted into tubular fluid

• aldosterone

  • stimulates Na+ uptake in principal cells

  • in response to increase in Na+ uptake, principal cells secrete K+

hyperkalemia

increase in blood K+ concentration; repolarization of ventricles impacted; can lead to v-fib

hypokalemia

decrease in blood K+ concentration; atrial and ventricular arrhythmias

water balance is regulated in the distal convoluted tubule and collecting duct

• deprived of H2O, increased plasma osmolarity

  • osmoreceptors stimulated, ADH secretion increased, thirst increased, increased aquaporins, increased H2O reabsorption, increased urine osmolarity and decreased urine volume, plasma osmolarity down

• increased H2O, decreased plasma osmolarity

  • inhibits osmoreceptors, ADH secretion decreased, thirst decreased, decreased aquaporins, decreased urine osmolarity and increased urine volume, increased plasma osmolarity

countercurrent multiplier

generates salt concentration gradient within interstitial fluid (nephron loop)

• more concentrated deeper into medulla

• occurs in descending and ascending limb

H2O balance in collecting duct is dependent on salt concentration

• descending limb permeable to water but not salt

• ascending limb permeable to salt but not water

• combination of two allows water to be reabsorbed into interstitial fluid

countercurrent exchange

maintains salt concentration gradient within interstitial fluid (vasa recta)

• blood vessels exchange water and salts as blood passes by nephron loop

water balance is regulated by several hormones in the collecting duct

• aldosterone: stimulates Na+ reabsorption and water follows (increases Na+ channels)

• ADH: stimulates aquaporin synthesis

reabsorption

the movement of molecules from the tubular filtrate through the cells of the tubule and into the peritubular capillaries

• proximal convoluted tubule- ions, all nutrients, lipid soluble solutes, water, wastes

• nephron loop

  • thin segment- water by osmosis

  • thick segment- Na+, Cl-, K+ ions by secondary active transport

• distal convoluted tubule- Na+, Cl- (primary active) via aldosterone, Ca+ via PTH

• collecting duct- Na+ (primary active) via aldosterone, water, osmosis via ADH

tubular secretion fine tunes the filtrate composition

movement of substances from capillaries to the filtrate

• reverse of reabsorption

• need to correct some of the reabsorption that has happened

1. remove drugs

2. remove wastes (40-50% urea)

3. remove excess K+ (aldosterone driven secretion)

4. maintaining optimal blood pH

collecting duct is critical in maintain acid/base balance of blood

increased H+

• type A cells secrete H+ into filtrate

• Type A cells release HCO3- into blood to bind to H+ to increase pH

decreased H+

• type B cells release H+ into blood

• type B cells secrete HCO3- into filtrate

diuretics

medications that promote water and salt removal from body in urine

carbonic anhydrase inhibitors (acetazolamide)

• diuretic that decreases Na+ reabsorption in renal tubule (PCT)

• mild diuretics- thick ascending loop is load dependent so a decrease in Na+ reabsorption in PCT results in increased Na+ reabsorption in nephron loop

loop diuretics (Furosemide, Lasix)

• affect K+, 2 Cl-, Na+ pump (ascending limbs)

• affect H2O balance because countercurrent is affected and changes osmotic gradient for H2O balance

thiazide diuretics (indapamide)

affects Cl-, Na+ pump in DCT

kidney stones

• hardened or crystallized deposits formed in kidney

  • renal pelvis through bladder

  • most passed but >5 mm can block ureter

    • pain from peristaltic contractions against stone

  • dehydration, high salt/protein diets, obesity

• symptoms:

  • pain in back to groin

  • peristaltic generation of pain

  • frequent urination

• classification

  • calcium

  • struvite

  • uric acid

glomerulonephritis

• inflammation contributes to a variety of disorders within the kidneys

  • degradation of basement membrane

  • hypertrophy and proliferation of cells

  • complement mediated cell lysis

• structural damage to glomerular filtration membrane reduces surface area

end-stage renal disease

characterized by extreme inhibition of normal kidney function; result of progressive CKD

• fluid imbalances

• metabolic acidosis

• anemia

• urea retention in blood

• untreated patients can become comatose and die

diagnosed by:

• complete physical history

• blood tests

• urinalysis

treated with dialysis or kidney transplant

• filtering blood across artificial glomerular filtration membrane

hemodialysis

blood drained from arm and replaced back into arm

• dialysate and blood flow in opposite directions for better exchange

peritoneal dialysis

• dialysate fills abdomen behind peritoneum and blood is filtered across directly cross peritoneum

• waste fluid removed every 4-6 hrs and replaced with fresh dialysate

• not as efficient as hemodialysis, higher risk of peritoneal infection

• allows for activity during dialysis dwell time

kidney transplant

• new kidney transplanted in anterior portion of abdominopelvic region

• damaged or diseased kidneys usually left in place

• ABO blood typing, HLA matching