Renal Transport Flashcards
Histology of Nephron: Proximal Tubule
Proximal Tubule: Cuboidal epithelium with microvilli or brush border (large surface area)
- Polarized surface facing lumen/filtrate
- Basallateral side facing blood supply
- Mitochondria facing basal lateral
Histology of Nephron: Loop of Henle
Thin: squamous cells (decending and acending
Thick: cuboidal cells (acending)
Histology of Nephron: Distal Tubule
Cuboidal epithelium
Macula densa (tall and dark)
Histology of Nephron: Collecting duct
Principal cells: Tall epithelial cells
Intercalated cells: Epitherlial cells with microvilli and mitochondria
Transcellular Transport
Going through cell, encounter cytoplasm and other organelles
Passive Transport (downhill - down concentration gradient)
- Passive Diffusion: No ATP
- Facilitated Diffusion: No ATP for charged particles
Active Transport (Uphill)
- Symport: Both go same direction
– First molecule generate ATP from going down the concentration gradient and use that ATP for the second molecule
- Antiport: Go different direction
– First molecule generate ATP from going down the concentration gradient and use that ATP for the second molecule
- Primary active transport: ATP => ADP
Paracellular Transport: In between cells; through tight junctions
Proxima Tubules
Reabsorption: Tubular fluid is Isosmotic as plasma (Apical (Lumen-Urine) to Basolateral (Blood-interstitium))
- 65% of filtered Na+/K+/Ca2+/Mg2+
- 85% of NaHCO3
- 100% of glucose and amino acids
- Water reabsorbed passively (no ATP)
– needed to dilute out the molecules
Machanisms of Reabsorption:
- Transcellular Trasport: NaHCO3, NaCI, glucose, amino acids, organic solutes
- Paracellular Transport: K+
Secretion:
- H+
Proximal Tubules
Key Players
NHE3: Na+/H+ exchanger 3
CA: Carbonic anhydrase (rxr with H+ to form H2CO3)
vH+ ATPase: secretion of H+
CBE/CKE:
- Cl-/Base- exchanger
- Late PT
- K+/Cl- Exchanger (possible wrong and instead cotransporter)
NBCe1: Na+/bicarbonate cotransporter
Na+/K+ ATPase: 3 Na reabsorbed for 2 K+
K+ is reabsorbed paracellularly
Proximal Tubules
Reabsorption examples
Albumin
Ascorbate
Fructose
Galactose
Glutamate
Glucose
Phosphate
Sulfate
Proximal Tubules
Secretion examples
Choline
Creatinine (weak base): Breakdown of skeletal muscles; if levels are too high will cause kidney damage
Histamine
p-aminohippurate: If admitted with penacilin it prevents the secretion of penacillin and allow it’s levels to be elevated in tissue and in circulation
Penicillin (weak acid)
Probenecid (weak acid): will competes with urate for reabsorption if taken together
Salicylates
Thiamine
Urate: secreted and absorbed by proximal tubules
Bile salts
Oxalates
Atropine
Cimetidine (weak base)
Dopamine (weak base)
Quinine (weak base)
Procainamide (weak base)
Proximal Tubule Transport
Active Transport:
- Uptake
- Efflux (out of cell)
- Direction
Loop of Henle
Found in inner and outer stripes of outer medulla
Loops include:
- Thin descending limb
- Thin ascending limb
- Thick ascending limb
Reabsorption:
- Water reabsorbed only in THIN DECENDING limb
- Solutes is reabsorbed to varying degree depending upon location
Thin Limbs of Henle
Descending:
- Reabsorption of water leading to concentrated tubular fluid (hyperosmotic)
– Permeable to water
– Impermeable to solutes
Ascending:
- Reabsorption of Na+, Cl-
– Impermeable to water
– Permeable to solutes
- Secretion of urea
- Site of dilute tubular fluid (hyposmotic)
Thick Ascending Limb
Reabsorption:
- Na+/K+/Ca2+/Mg2+
- No water reabsorption (hyposmotic)
Mechanism of Reabsorption
- Transcellular Transport: NaCl
- Paracellular Transport: Ca2+, Mg2+
– Use paracellins or claudins in tight junctions
Secretion:
- K+
Think Ascending Limb
Key Players
- NKCC2: Na+/K+/2Cl- Cotransporter (Lumen to Blood)
- ROMK: K+ channel (Blood to Lumen)
- CLC-K2: Cl- Channel (Lumen to Blood)
- Na+/K+ ATPass (3 Na will be reabsorbed to 2 K+ secretion)
ROMK and CLC-K2 will cause positive charge in lumen (10mV) => cause a repulsion => Mg2+ and Ca2+ will be transported paracellular to blood
Distal Tubules
Functions:
- Reabsorb Na+, Ca2+, Cl-
- Secretion of H+
- Water reabsorbed in Distal SEGMENT of distal tubules
- Contain macula densa cells:
Macula Densa Cells
- Monitor electrolyte levels in filtrate
- Secrete prostaglandins in response to LOW Na+ and Cl- in filtrate => stumulates RENIN production by juxtaglomerular cells of afferent arterioles
- Renin increase ANGIOTENSIN II levels leading to Na+ and water retention
Distal Tubule
Key Players
- NCC: Na+/Cl- Cotransporter (reabsorption)
- TRPV5: Ca2+ Channel (reabsorption)
- gCl-: Cl- Channel (reabsorption)
- Na+/Ka+ ATPase and Ca2+/H+ ATPase (Ca2+ and 3Na+ will be reabsobed while H+ and 2K+ will be secreted)
- NCX1 Na+/Ca2+ exchanger (Na+ secreted, Ca2+ reabsorbed)
Hyposmotic or isosmotic in late DT
Collecting Tubules
Function:
- Reabsorb H2O, NaCl, HCO3-
- Secrete K+, H+
- Final urine concentration determined
Cell Types:
- Principal Cells: Na+, K+, Water transport
- Intercalated Cells: H+ secretion and reabsorb HCO3-
Regulation:
- Aldosterone activiates mineralocorticoid receptor in nucleus
– Increase ENaC expression
– Increase Na+/K+ ATPase expression
— Both cause sodium reabsorption
Cortical Collecting Tubules
Key Player
Principal Cells: Affected by aldosterone
- ENaC: Na+ Channel (Reabsorption)
- K+ Channel (Secretion)
- Na+/K+ ATPase (3 Na+ Reabsorbed with 2 K+ secreted)
Type A Intercalated Cells
- H+ ATPase: proton pump (secretion)
- AE1: HCO3- and Cl- exchanger (HCO3- reabsorbed, Cl- secreted)
Cl- will be reabsorbed through paracellular transport
Cortical Collecting Tubules
Regulation
- Antidiuretic hormone (ADH) control insertion of water channels(AQP2) => into apical membrane by G- protein coupled and cAMP process
- High ADH => High H2O permeability => more concentrated urine
Key Players
- ADH: Antidiuretic hormone/vasopressin
- V2 Receptor: Vasopressin receptor (Interact with ADH
- AC: Adenylyl cyclase (Turn ATP into cAMP)
- AQP2/3/4: Aquaporin (reabsorption of H2O)
