Distal Tubule and Collecting duct Flashcards
Structures that make up the Loop of Henle (LOH)?
- thin descending limb
- thin ascending limb
- thick ascending limb
Major function of the LOH?
About 25% NaCl is reabsorbed in this segment by an active transport mechanism
Major function of the rest of the distal tubule (i.e. the distal convoluted tubule and collecting duct)?
Regulated reabsorption of about 5% of NaCl
Structure and location of the thin descending limb of the LOH?
Starts at the distal end of PT and runs from cortex to outer medulla
- composed of Thin epithelial cells with few mitochondria
How does the interstitial environment of the renal medulla differ from other organs?
The fluid is Markedly hyperosmotic to plasma.
- It is isosmotic to plasma at the border between cortex and medulla, but increases progressively downwards to a max of 1200 mOsml/L at the papillary tip.
Specific function of the thin descending limb of the LOH? How is this done?
- Concentration of Tubule Fluid (TF).
- This is achieved by the unique transport characteristics:
- no active transport mechanisms.
- IMPERMEABLE to NaCl and urea.
- But, Highly water permeable due to the presence of aquaporins in the epithelial membranes.
How does the osmolarity change as the TF flows down the thin descending limb of the LOH?
Osmolarity of TF increases progressively as you move from the cortex down into the medulla (due to the reabsorption of water)
- @cortex: 280 mOsmoles/kg H2O
- @ Medulla: 1200 mOsmoles/kg H2O
What is the main driving force of water reabsorption in the thing descending limb of the LOH?
The osmotic gradient between the luminal fluid and IF.
Structure of the thin ascending limb?
Same as the thin descending:
- composed of Thin epithelial cells with few mitochondria
Difference in permeability between thin descending limb and thin ascending limb?
- Thin ascending limb is impermeable to water to water (lacks aquaporins)
- Thin ascending limb is high permeability to NaCl
- *opposite the thin descending limb
How does the osmolarity change as the TF flows up the thin ascending limb of the LOH?
Osmolarity of TF decreases as it moves up.
- due to the lack of water permeability and the high permeability of NaCl
Describe the flow of NaCl and H20 in the thin descending limb vs the ascending.
Thin descending: Concentration of TF
- NaCl stays in
- H20 flows out
Thin ascending:
- NaCl flows out
- H20 stays in
Permeability of Urea in the LOH?
impermeable
Structure of the thick ascending limb of the LOH?
- consists of thick epithelium with lots of mitochondria in the cells
Major function of Thick ascending limb of LOH?
The main function is NaCl reasbsorption
- occurs by active transport mechanism.
- segment is impermeable to water
Flow of ions and water in the Thick Ascending limb of the LOH?
NaCl active transport by:
- Na+/K+/2Cl- transporter (luminal membrane of epithelium)
- electro-neutral and driven by the electrochemical gradient produced by Na/K pump - Na+/K+ ATPase pump (basolateral mem.)
- Other channels
- Apical K-channel and Basolat. Cl-channels
-*H20 impermeable in Thick AL
How and where do diuretics act? result?
N/K/2Cl is sensitive to diuretics such as furosemide and bumetanide.
- They have high affinity to Cl binding site and block the activity of this channel (blocking NaCl reabsorption)
Result is: Delivery of more NaCl and isotonic fluid into the distal segments (i.e. more fluid excretion)
Effect of Vasopressin and ADH? How and where?
Stimulate NK2C and stimulate NaCl reabsorption
- cause opposing effect on diuresis.
Fact:
Loop diuretics are more efficient than other diuretics that act in DT due to high NaCl reabsorption in the loops compared to that in DT.
Fact:
Loop diuretics are more efficient than other diuretics that act in DT due to high NaCl reabsorption in the loops compared to that in DT.
Structure of the Distal tubule (i.e. Distal to LOH?)
- Distal Convoluted Tubule (DCT) starts after the thick ascending limb of LOH.
- 6-8 DCTs join together to form the Collecting Duct.
- DCT and CD have distinct cell types, but the functions are similar
Describe the tubular fluid processing that occurs in the Distal Convoluted Tubules and Collecting Duct
Receive about 10% of filtered water, less than 10% of filtered Na, K and Cl, and 50% of urea.
- Na is actively transported across the epithelium.
- K is secreted into the lumen.
- Na reabsorption > K secretion, and therefore Cl is reabsorbed
Result: Dilution of tubular fluid (if the tubule is impermeable to water- depends on plasma level of ADH)
When is water permeable and impermeable in the Distal tubule? What determines this?
- Plasma osmolarity low due to excessive water drinking => low ADH => less water permeability in DCT => diuresis.
- plasma osmalarity high due to water deprivation => High ADH => More water permeability in the DCT => hyperosmotic urine (i.e. concentrated and yellow)
Transport mechanisms in the DCT and CD
- Electrically conductive Na+ channel (ENAC)
- diffusion of Na down electrochem. gradient
- found in both DCT and CD - Na-Cl co-transporter
- ONLY in DCT
- electro-neutral
Which diuretics block ENAC in the distal tubule?
- Amiloride
2. triamterene
Which diuretics block the Na-Cl co-transporter of the DCT?
Thiazide diuretics
Which diuretics are more efficient, Loop-diuretics or diuretics acting in the distal tubule?
Loop-diuretics
- 10 fold more efficient
What is unique about the epithelial membrane of the DCT and more so the CD?
both have: Lumen-negative transpithelial voltage
- due to the activity of electro conductive Na channels creating more negativity in the lumen causing the membrane to depolarize
- Major key for K+ secretion
- CD > DCT
Where and how does potassium secretion occur?
Occurs in the DCT and CD
- via passive diffusion through the apical K channel
What two factors drive potassium secretion?
- High intracellular K concentration
2. Lumen-negative potential
Factors that regulate potassium secretion?
- fluid flow – higher the fluid flow higher is K secretion.
2. Na delivery to DT – higher the Na delivery to DCT and CD greater the lumen-negative voltage and greater K secretion.
effects of diuretics on K secretion?
Loop diuretics: increase K secretion (increased Na flow to DCT and CD and therfore higher lumen-negative voltage)
Thiazides: only minimal increase due to increased flow.
Amiloride: DECREASE K+ secretion. (reduce lumen-negative voltage, but slightly compensated by increased flow)
What is Aldosterone and what/where is it’s effect?
Mineralocorticoid secreted by the adrenal cortex
- regulator of Na reabsorption in distal tubule.
- actions include Na reabsorption and K secretion.
- Aldosterone acts exclusively in the DCT and CD!
How does Aldosterone work? (MOA)
It’s cell permeable and binds to cytosolic and nuclear receptors and regulate gene expression related the expression of electro conducting Na channel, Na-Cl co-transporter, NKA and K channel in the DCT and CD epithelial cells.
- It also increases the expression of Kreb’s cycle enzymes and ATP synthesis, all factors needed to increase Na reabsorption and K secretion.
Aldosterone induced changes in cells? (7)
- open Na+ channel in apical membrane of DCT and CD
- inc transepithelial voltage
- inc Na+Cl- cotransporter
- inc synthesis of NKA, Kreb’s cycle enzymes, ATP synthesis
- inc basolateral surface area
- inc activity of apical membrane K+ channel
- inc Na+ reabsorption and K+ secretion
Disease characterized by the complete absence of aldosterone production?
Addison’s disease
- Results in increased excretion of NaCl in the urine.
Disease characterized by Aldosterone secreting tumors that maintain a high plasma level of aldosterone
Conn’s disease
- Results in increased Na reabsorption, K+ secretion and reduced urinary excretion of Na
(Hypokalemia, hypernatremia, hypertension)
Conditions that increase aldosterone secretion (5)
- Reduced ECF vol. and C.O.
- Decreased plasma Na+
- Increased plasma K+
- High plasma Angiotensin II
- Trauma, stress
Conditions that decrease aldosterone secretion
- Increased ECF
- Increased plasma sodium
- Decreased plasma K+
- Low plasma angiotensin II
- Low plasma ACTH levels
What are the two cell types of the DCT and CT?
- Principal cells
2. Intercalated Cells
What is the function of Principal cells of the DCT and CD?
involved in Na reabsorption and K secretion
What is the function of intercalated cells of the DCT and CD? How does this occur?
- proton secretion
- HCO absorption (sometimes secretion)
-active transport process via a proton pump (Proton-Activated ATPase
How does proton secretion in the DCT/CD differ from that in the PT?
DCT/CD = proton pump (NO diffusion)
PT = Na-H exchanger AND some diffusion
How does the Proton-Activated ATPase of the DCT/CD work?
ATP hydroslysis drives the transport of proton against the concentration gradient from the cell to the lumen.
- Proton secretion is coupled to HCO reabsorption via HCO-Cl antiport.
What occurs to intercalated cells of the DCT/CD under high acidosis conditions?
Cells express a new proton pump, HK-ATPase
- Transport via this channel is eletroneutral.
What occurs to the proton-activated ATPase of the intercalated cells of the DCT/CD under conditions of alkalosis?
Proton-activated ATPase and Hco-Cl antiport switch directionality with proton-ATPAse in the basolateral membrane.
- There are two types of intercalated cells (A and B-cells).
- A-cells have proton channel in the luminal membrane
- B-cells have proton channel in basolateral membrane.
- Different cells are activated under conditions of acidosis and alkalosis.
Where do A-type intercalated cells reside?
luminal membrane
Where do B-type intercalated cells reside?
Basolateral membrane
