4.2. Tubular transport processes. Flashcards
I. What are the characteristics of Glomerular filtration?
- Ultrafiltration of plasma by the glomerulus is the 1st step in the formation of urine
- The plasma ultrafiltrate is devoid of corpuscular elements and pretty much protein-free
- [salts] and [organic molecules] are similar in plasma and the ultrafiltrate
II. determinants of Glomerular filtration
1. What are the determinants of Glomerular filtration?
- The glomerular filtration barrier determines the composition of plasma ultrafiltrate, based on:
1. The size of molecules: smaller molecules easily squeeze through filtration slits, whereas larger molecules have a hard time passing through
2. The charge of the molecules: filtration barrier is negatively charged, thus neutral/positively charged molecules are filtered easily
II. determinants of Glomerular filtration
2. Characteristics of The size of molecules as a determinant of Glomerular filtration?
smaller molecules easily squeeze through filtration slits, whereas larger molecules have a hard time passing through
II. determinants of Glomerular filtration
3. Characteristics of The charge of molecules as a determinant of Glomerular filtration?
filtration barrier is negatively charged, thus neutral/positively charged molecules are filtered easily
III. Dynamics of ultrafiltration
1. What is the role of Starling forces in ultrafiltration?
- Starling forces combine to drive fluid from the glomerular capillaries into the Bowman’s space
- It contains:
1) Hydrostatic pressure
2) Oncotic pressure
=> Those pressures that promote filtration are positive, and those who do not are negative
III. Dynamics of ultrafiltration
1A. What is the role of Hydrostatic pressure (Starling forces) in ultrafiltration?
Hydrostatic pressure: affects filtration by pushing fluid and solute out of the place
1. In the capillaries, hydrostatic pressure forces fluid and solutes OUT of the blood
2. In the Bowman’s space, hydrostatic pressure forces fluid and solutes INTO the blood
III. Dynamics of ultrafiltration
1B. What is the role of Oncotic pressure (Starling forces) in ultrafiltration?
Oncotic pressure: affects filtration by preventing fluid from leaving the place
1. In the capillaries: oncotic pressure keeps fluid and solutes in the blood
2. In the Bowman’s space: oncotic pressure keeps fluid and solutes in the ultrafiltrate
III. Dynamics of ultrafiltration
2. What is the formula for the Net ultrafiltration pressure (NUP)?
Net ultrafiltration pressure
(NUP) = (PC – PB) – (πc – πB)
III. Urine formation
1. What are the values for GFR and Urine excretion?
- GFR is 120 ml/min = 180 L/day
- Urine excretion is = 1-2 L/day
=> 99% of filtered water is reabsorbed
III. Urine formation
2. How is urine formed?
The formation of urine involves 3 processes:
1) Ultrafiltration: removal of plasma components by the glomerulus
2) Reabsorption: taking up water and solutes from the ultrafiltrate
3) Secretion: of solutes into the tubular fluid
=> Composition and volume of urine is determined by reabsorption and secretion
IV. Proximal tubule
1. What are the characteristics of proximal tubule?
- 65-70% of the filtered Na+ is reabsorbed
- The transport of several other substances is coupled to Na+-transport (H+, Cl-, HCO3-,
glucose amino acids, lactate, water) - Filtered proteins (e.g. albumin) are reabsorbed
- The wall of the tubules consists of a ‘’leaky’’ epithelium
-> The transport of osmotically active substances is followed by equivalent amount of water (65-70% of filtered water reabsorbed)
-> Large gradients (osmotic, electric or pH) are not generated
IV. Proximal tubule
2. The wall of proximal tubule is a ‘’leaky’’ epithelium.
-> What are the characteristics of this epithelium?
- The transport of osmotically active substances is followed by equivalent amount of water (65-70% of filtered water reabsorbed)
- Large gradients (osmotic, electric or pH) are not generated
V. Proximal tubule, first half:
1. What are the characteristics of Proximal tubule, first half?
- Na+ primarily reabsorbed with HCO3-
- Smaller amounts of lactate, AAs, glucose and inorganic phosphates are also reabsorbed with sodium
- Altogether, only 20% of the filtrated Na+ is reabsorbed via the mentioned mechanisms in the first half of the proximal tubule.
V. Proximal tubule, first half
2. What are the processes happening in Proximal tubule, first half?
- Na+- reabsorption with bicarbonate
- Na+ - reabsorption with glucose
- Na+ - reabsorption with amino acids, lactate and phosphate
V. Proximal tubule, first half
3. What is the mechanism of Na+- reabsorption with bicarbonate?
- Na/H-antiporter on the luminal membrane of tubular epithelial transports Na into and H out of the cell
- CO2 comes into the cell, and CO2+H2O combine to form H+ and HCO3- (from H2CO3) via carbonic anhydrase in the cell
- On the basolateral membrane, Na+/K+- ATPase transports absorbed sodium out and a 1Na+/3HCO3—symporter transports HCO3- out for a net reabsorption
=> The H+-secretion into the tubular lumen decreases the pH of tubular fluid (+pCO2↑)
V. Proximal tubule, first half
4. What is the mechanism of Na+ - reabsorption with glucose?
- Glucose and Na+ are absorbed into the epithelial cell from tubular fluid via SGLT- 2 (1:1 transport – active Na+-transport, cannot reduce glucose-levels. SGLT-1 is more effective, can reduce glucose- levels. Reabsorbs 2 Na+)
- Glucose reabsorbed into interstitium via GLUT2
- Na+ reabsorbed into interstitium via Na/K-ATPase (the negative potential formed in the tubular fluid drives paracellular Cl—transport further down the proximal, where Cl- is the primary anion reabsorbed with Na)
- Water is also reabsorbed (aquaporins – Aq1 , due to the osmotic gradient formed)
V. Proximal tubule, first half
5. What is the mechanism of Na+ - reabsorption with amino acids, lactate and phosphate?
- Amino acids and lactate are also reabsorbed on the luminal side via Na+-coupled symporters
- Basolateral reabsorption of Na+ via Na/K-ATPase
- Water is also reabsorbed
- Filtered phosphate can be reabsorbed with Na+
+) This process can be inhibited by basolateral binding of parathormone from the parathyroid gland leading to increased cAMP (via Gs -> ↑cAMP -> PKA activity)
VI. Proximal tubule, second half
1. What are the characteristics of filtration in Proximal tubule, second half?
- Because Na+ was taken up primarily with other substances in the first half of the proximal tubule and water was reabsorbed as well, the [Cl-] in the second half is now high
=>This will drive the rest of the filtration
VI. Proximal tubule, second half
2. What are the processes happening in Proximal tubule, second half?
1) High tubular [Cl-] drives paracellular Cl—reabsorption, leaving a positive potential in the tubule
2) Cations (Na+,K+,Ca2+) follow Cl- paracellularly due to this new positive potential difference
3) Increased osmolarity of the interstitium, due to this ion reabsorption, influences water reabsorption via aquaporin-1 (Aq1) channels on the luminal and basolateral sides of the tubular epithelium -> water reabsorbed
VII. Factors effecting proximal tubule reabsorption
1. What are the factors effecting proximal tubule reabsorption?
- Acetazolamide
- Mercury containing compounds
- Non-reabsorbed osmolytes
VII. Factors effecting proximal tubule reabsorption
2. What is the effect of Acetazolamide?
inhibits carbonic anhydrase, thereby inhibiting Na+/HCO3 reabsorption
VII. Factors effecting proximal tubule reabsorption
3. What is the effect of Mercury containing compounds?
Mercury containing compounds: inhibit aquaporins, thereby inhibiting H2O reabsorption
VII. Factors effecting proximal tubule reabsorption
4. What is the effect of Mercury containing compounds?
mannitol, inulin, excessive filtered glucose/ketone bodies can draw water back into the tubule, causing osmotic diuresis seen in diabetes mellitus
VIII. Loop of Henle
2. How can Thin descending limb (TDL) participate in filtration?
- Passive transport
- Highly permeable to water via Aq1, but poorly to NaCl
- Results in water-reabsorption without solutes, leaving the tubular fluid hyperosmotic
- At the end of TDL (inner medulla), osmolarity increases from 300 mOsm to 1200 mOsm = hyperosmotic↑↑↑ and NaCl↑
VIII. Loop of Henle
2. How can Thin ascending limb participate in filtration?
- Passive transport
- Impermeable to water (due to lack of Aq1),
but permeable to NaCl and urea - NaCl diffuses out of tubule lumen and into medulla, as the tubular fluid moves towards the cortex (upwards)
- Tubular fluid becomes hypoosmotic
VIII. Loop of Henle
3A. How can Thick ascending limb (TAL) participate in filtration?
- Active transport mechanisms return and removal of osmolytes of tubular fluid continues
- No water reabsorption due to lack of Aq1
- Active reabsorption occurs by using Na+/K+-ATPase and Na+/K+/2Cl—cotransporter
- K+/Cl– symporter: aids K+ and Cl- from crossing the basolateral membrane into the interstitium
- ROMK: allows the K+ to flow back to the tubular lumen, creating a positive potential and driving the paracellular cation (Na+, K+, Ca2+) – reabsorption
VIII. Loop of Henle
3B. How does Active reabsorption occur occur in Thick ascending limb (TAL)?
- Na+/K+-ATPase in basolateral membrane maintains a low [Na+]IC
=> Provides concentration gradient for Na+ to move from tubular fluid into the cell - Na+/K+/2Cl—cotransporter: mediates movement of Na+ across apical membrane
=> couples movement of 1Na+ with 2Cl- and 1K+
=> movement of K+ is uphill (against concentration gradient)
=> Furosemide blocks this cotransporter
VIII. Loop of Henle
3B. How can ROMK be inhibited?
ROMK: allows the K+ to flow back to the tubular lumen, creating a positive potential and driving the paracellular cation (Na+, K+, Ca2+) – reabsorption
=> This K+-channel can be inhibited by acidosis (↓pH)
IX. Distal convoluted tubule:
1. What is the role of Distal convoluted tubule in filtration?
Responsible for 5-7% of NaCl-reabsorption
IX. Distal convoluted tubule:
2. How does filtration occur in Distal convoluted tubule?
- Na+/Cl—cotransporter on the luminal membrane reabsorbs NaCl
- Na+/K+-ATPase expels Na+ out of the cell through basolateral membrane (and maintains the gradient)
- Cl—channel allows basolateral Cl-diffusion
- No water is reabsorbed, further decreasing tubular osmolarity and increasing interstitial osmolarity
- EXRTRA: in the DCT, there is also Ca2+-reabsorption – regulated by parathormone
IX. Distal convoluted tubule:
3. What is the effect of Thiazide?
Na+/Cl—cotransporter on the luminal membrane reabsorbs NaCl
=> Thiazide inhibits the NaCl-transporter, leaving more osmolytes in the tubular fluid
X. Connecting, cortical and outer medullary collecting ducts
1. How can Connecting, cortical and outer medullary collecting ducts participate in filtration?
- ENaCs (epithelial sodium channels) on the luminal side of tubular epithelia allows Na+ into the cell (creates a negative potential in the lumen)
+) Aldosterone can enhance Na-reabsorption via ENaC expression
upregulation (= more negative potential in lumen)
+) ANP decreases Na-reabsorption via ENaC inhibition (resulting in
natriuresis = Na+-excretion) - The negative potential in lumen drives Cl- paracellularly
- Luminal K+-channel allows K+ to flow into the lumen
+) Influx depends on negative potential in lumen: if aldosterone present = Na+-reabsorption increases = negative potential increases = K+-influx also increases
+) Amiloride increases Na+-excretion by inhibiting ENaC, but does not affect K+- actions
+) Acidosis inhibits K+-excretion = more retained in body = [K+]IC ↑
X. Connecting, cortical and outer medullary collecting ducts
2. How can Aldosterone affect the filtration process in Connecting, cortical and outer medullary collecting ducts?
Aldosterone can enhance Na-reabsorption via ENaC expression upregulation (= more negative potential in lumen)
X. Connecting, cortical and outer medullary collecting ducts
3. How can ANP affect the filtration process in Connecting, cortical and outer medullary collecting ducts?
ANP decreases Na-reabsorption via ENaC inhibition (resulting in
natriuresis = Na+-excretion)
X. Connecting, cortical and outer medullary collecting ducts
4. How can Amiloride affect the filtration process in Connecting, cortical and outer medullary collecting ducts?
Amiloride increases Na+-excretion by inhibiting ENaC, but does not affect K+- actions
X. Connecting, cortical and outer medullary collecting ducts
5. How can Acidosis affect the filtration process in Connecting, cortical and outer medullary collecting ducts?
Acidosis inhibits K+-excretion = more retained in body = [K+]IC ↑
XI. H2O-reabsorption in CD, CCD, OMCD
1. How does H20-reabsorption in CD, CCD, OMCD occur?
- From the lowest part of the loop (TDL) to the end of DCL= H2O-impermeability
- From the connecting duct to the medullary connecting duct, the water
permeability/reabsorption is regulated by vasopressin (ADH)
+) Vasopressin will bind to basolateral Gs-coupled V2 receptors inducing
↑[cAMP] -> PKA -> releases Aq2-proteins from vesicles to the luminal membrane
-> water can be reabsorbed (dragging force: osmotic gradient)
XI. H2O-reabsorption in CD, CCD, OMCD
2. What is the role of vasopressin (ADH) in water reabsorption?
Vasopressin will bind to basolateral Gs-coupled V2 receptors inducing
↑[cAMP] -> PKA -> releases Aq2-proteins from vesicles to the luminal membrane
=> water can be reabsorbed (dragging force: osmotic gradient)
XII. Late distal tubule and collecting duct
2. What is the role of principal cells?
XII. Late distal tubule and collecting duct
3. What is the role of alpha-intercalated cells?
XII. Late distal tubule and collecting duct
4. What is the role of beta-intercalated cells?
XIII. Potassium handling in the kidney
2A. How is K+ transported along the nephron?
XIII. Potassium handling in the kidney
2B. How is K+ transported along the Proximal tubule?
- K+-reabsorption occurs paracellularly (coupled with Na-reabsorption)
- Driving force: positive tubular potential generated by paracellular Cl—reabsorption
XIII. Potassium handling in the kidney
2C. How is K+ transported along the Thick ascending limb?
- K+-reabsorption with Na-reabsorption via Na+/K+/2Cl—cotransporter
- Driving force: low [Na+]IC due to Na/K-ATPase
- Regulation: acidosis increases reabsorption by inhibiting ROMK1 (hyperkalemia)
XIII. Potassium handling in the kidney
2D. How is K+ transported along the Cortical/outer medulla collecting duct?
- K+-secretion is coupled with Na+-reabsorption
- Driving force: low [Na+]IC due to Na/K-ATPase
=> Aldosterone increases secretion (increased Na-reabsorption via ENaC, negative potential in lumen = K+-influx to lumen increases)
=> Acidosis inhibits secretion by inhibiting ROMK1 (high level remains in cell = hyperkalemia)
XIV. Calcium handling in the kidney
1. How is Calcium handled in the kidney along the nephrone?
XIV. Calcium handling in the kidney
2. How is Calcium handled in the kidney along Proximal tubule?
- Paracellular Ca2+-reabsorption coupled with Na+-reabsorption
- Driving force: positive tubular potential generated by Cl-
- NOT REGULATED
XIV. Calcium handling in the kidney
3. How is Calcium handled in the kidney along Thick ascending limb?
- Paracellular Na+-coupled Ca2+-reabsorption
- Driving force: positive tubular potential generated by K+-rediffusion
- NOT REGULATED
XIV. Calcium handling in the kidney
4. How is Calcium handled in the kidney along Distal convoluted tubule?
- Uncoupled active transcellular Ca2+-reabsorption
- Driving force: luminal diffusion via Ca2+-channel and basolateral extrusion via Ca2+-ATPase
- Regulation: parathormone and calcitriol = ↑Ca2+-reabsorption
