Renal Transport Processes - Lecture 5 Flashcards
What does the proximal tubule filter? Reabsorb?
- Approx - 2/3 of filtered water, Na, Cl, and K
2. Reabsorbs all the glucose & amino acids ultra filtered by the glomerulus
In the first half of the proximal tubule, what is Na uptake coupled with? Via which transporter?
Coupled with either H+ or organic solutes
Na- H antiporter (Na in, H out)
SYMPTORTERS: Na - Glucose, Na - Amino Acid, Na-Pi, and Na- Lactate
What is the result of H+ secretion?
Reabsorption of NaHCO3 (sodium bicarbonate)
How do glucose and other organic solutes exit across the basolateral membrane?
Via Passive Mechanisms
How does Na that enters the cell across the apical membrane leave the cell to enter the blood on the basolateral side?
Na-K ATPase
What provides the driving force/gradient for the passive reabsorption of water?
Reabsorption of NaHCO3 and Na Organic Solutes
What anion is Na mainly reabsorbed with across both the transcellular and paracellular pathways in the SECOND half of the proximal tubule?
Cl- (more so than organic solutes or HCO3-)
67% transcellular
33% paracellular
What are the two main mechanisms that Na enters the cell across the luminal membrane?
- Na - H antiporter
2. Na- Cl anion antiporter
How does Cl- leave the cell to enter the blood on the basolateral membrane?
Via K-Cl - symporter
What specific gradient drives the passive reabsorption of water? What establishes this gradient?
- Osmotic Gradient
2. Active Solute Reabsorption
Water moves from high to low osmolality areas. True or False?
FALSE!
Water moves from low to high osmolality concentrations established by Na, Cl- and organic solutes in the lateral intercellular spaces
How does Na that does not utilize the Na-K Atpase enter the lateral intercellular space?
NaCl enters via diffusion across the tight junctions (paracellular pathway)
What happens to solutes that are entrained in reabsorbed fluid as osmotic water flows across the transcellular and paracellular pathways in the proximal tubules?
Solvent Drag
How much protein is filtered by the glomerulus each day? How much is reabsorbed?
- 7.2 g of protein are filtered by the glomerulus
- 100% is usually reabsorbed in the proximal tubule
- enzymatic degradation of proteins to amino acids
- encapsulation of proteins by ponocytotic processes
What happens if protein transport is saturated?
Protein appears in the urine (Proteinuria)
What is the process of secretion of organic cations & anions into the proximal tubule? (active or passive?)
What substances fall under this category?
- ACTIVE
- Endogenous end-products of metabolism
Exogenous Drugs
What cations each elevate the plasma concentration of one another?
Cimetidine & Procainamide
What is the function of the Distal Nephron?
Low volume, high gradient pumping of solutes & water
1/3 of filtered load is typically reabsorbed
What do the following signify:
Urine/Plasma concentration < 0
Urine/ Plasma Concentration > 0
in terms of:
- ADH
- Urine Concetrated/Dilute
- Color of Urine
- Less than zero - LOW ADH, dilute, pale urine
2. Greater than zero - HIGH ADH, concentrated, dark urine
What is actively reabsorbed in Henle’s Loop? Which part of the loop?
What is this area impermeable to?
- about 25% of Na and other constituents are actively reabsorbed
- The thick ascending Limb
- Area is impermeable to WATER -H20
How is Na reabsorbed in the thick ascending limb of Henle’s Loop? (Via which transporter)
Na-K ATPase
Which part of the loop is permeable to H20? Which is impermeable?
Which area is thus permeable to passive reabsorption of NaCl ?
Thin Descending Loop - permeable to H20 (Passive reabsorption)
Thin Ascending Loop - impermeable to H20
- permeable to passive transport of Nacl!
thin = h20
Thin ascending = NaCl (at the thick ascending it is actively transported)
What characteristic of the lumen plays a major role in driving the passive paracellular reabsorption of cations?
Positive Charge in the lumen
What causes Bartter’s Syndrome?
- Mutations in membrane K+ channel
- Apical Membrane Na-K-2Cl symporter
- Basolateral Cl channel
Where is the remaining 8% of the Na processed/reabsorbed?
Distal Tubule & Collecting Ducts
via Na-K ATPase
What is the distal convoluted tubule impermeable to?
Water!
Which Hormones are activated by a decrease in ECFV?
- Angiotensin II
- Sympathetic Nerves
- ADH
- due to low blood volume, etc..
Describe the mechanism of Angiotensin II during low ECFV.
- low ECFV
- Increase RAA system
- Increase Angiotensin - II
- Increase reabsorption of Na, Cl, and H20 in the PROXIMAL TUBULE
What hormones are activated by an INCREASE in ECFV and function to decrease Na and Cl reabsorption ?
- ANP & Urodilation
2. Dopamine
What triggers the release of Aldosterone? Describe the Mechanism.
Reabsorption of what substance is increased?
Which areas of the nephron?
- Increase Angiotensin II or increased plasma K
- Increased Aldosterone
- Increased reabsorption of Cl in the THICK ASCENDING limb go Henle’s loop, distal tubule, and collecting duct
What triggers the release of ANP or Urodilator substances?(2)
What changes does it cause to TPR?
How does it affect reabsorption?
State the mechanism of action of ANP.
- A)Increased ECFV
OR
B) increased BP - Atrial Stretch
- Increased ANP
- Increased Natriuresis and a decrease in TPR
- Decreased reabsorption of Na & Cl and decreased ADH secretion
RESULT: decreased ECFV
What is the end result of ANP?
Decreased ECFV via a decrease in TPR and urodilation
- increased GFR and thus sodium excretion and large urine volume (to decrease blood volume)
The release of these ANP by the heart is stimulated by atrial and ventricular distension, as well as by neurohumoral stimuli, usually in response to heart failure.
The main physiological actions of natriuretic peptides is to reduce arterial pressure by decreasing blood volume and systemic vascular resistance.
What is natriuresis?
Na excretion in the urine
When are sympathetic nerves activated?
What hormones and NT do they release?
How does this affect Na and CL reabsorption?
Where is this affect localized in the nephron?
- When ECFV decreases
- Release NE and E
- Increase Na & Cl reabsorption
- Proximal & Distal Tubules
When is Dopamine activated?
How does this affect Na and Cl reabsorption?
Where is this affect localized in the nephron?
- When ECFV is HIGH (increased)
- Decreased Na & Cl reabsorption
- PROXIMAL tubule only
When is ADH activated?
How does this affect Na and Cl reabsorption? H20?
Where is this affect localized in the nephron?
- When ECFV is LOW
or when Plasma Osmolality is HIGH
Does NOT affect Na Cl excretion, and instead causes an increase in Reabsorption of the H20 in the COLLECTING DUCT
(to increase blood volume during dehydration for example)
What forces govern solute & water reabsorption?
Starling Forces
What is the glomerulotubular balance (not glomerulotubular feedback via macula densa)
Describe how this affect is utilized during an increased GFR.
- A constant fraction of Na and H20 are still reabsorbed from the proximal tubule despite changes in GFR
Increased GFR means Increased filtered load of glucose and amino acids, thus increased reabsorption of Na and H20 in the proximal tubule
- Increased Glomerulus Capillary FILTRATION
- Increase Peritubular Capillary REABSORPTION
What are the major mechanisms of entry across the apical membrane of the Proximal Tubule?
What are the main regulatory hormones here?
- Na - H antiporter
- Na symporter w/ amino acids & organic solutes
- Na-H - 2 Cl antiporter
- Paracellular Transport
- Angiotensin II
- NE
- E
- DOPAMINE (only acts here)
What are the major mechanisms of entry across the apical membrane of the Loop of Henle?
What are the main regulatory hormones here?
- Na - K - 2Cl Symporter
- Aldosterone
- Angiotensin II
What are the major mechanisms of entry across the apical membrane of the Distal Tubule?
What are the main regulatory hormones here?
- NaCl Symporter (early)
- Na channels (late) (impermeable to water) in the thin ascending limb, permeable to NaCl
- Aldosterone
- Angiotensin II
What are the major mechanisms of entry across the apical membrane of the COLLECTING DUCT?
What are the main regulatory hormones here?
- Na Channels
2. Aldosterone, ANP, BNP, Urodilatin, Angiotensin II, Uroguanylin, Guanylin
What hormones regulate water permeability? Where does this occur?
- ADH, ANP, BNP
- COLLECTING DUCT ONLY
- all other areas have passive transport of water (ascending thin limb is impermeable to water)
- majority of passive H20 reabsorption occurs in the Proximal tubule
Which of the following cause a decrease in H20 and NaCl reabsorption?
- ANgiotensin II
- Aldosterone
- ANP, BNP, Urodilatin
- Sympathetic Nerves
- Dopamine
- ADH
- Uroguanylin, Guanylin
- ANP, BNP, and Urodilatin
- Dopamine
- Uroguanylin, Guanylin
Which part of the nephron does dopamine act on? What is the affect?
Proximal Tubule
- Causes a DECREASE in ECFV by preventing H20 and NaCl reabsorption (increased fluid volume)
What are the 2 possible stimuli for Aldosterone Release?
For ADH release?
- Increased Angiotensin II
- Increased plasma K
ADH:
- Increase Plasma Osmolality
- Decreased ECFV
(causes an increase in H20 reabsorption)
Which substances have TF/P values of the following:
Explain Why.
- TF/P = 1
- TF/P >1
- TF/P < 1
- Na has a TF/P of 1 since the substance is reabsorbed PROPORTIONALLY with water
- Cl - has a TF/P of >1 since it is reabsorbed LESS than water (more appears in the urine)
- Amino Acids, Glucose, and HCO3 - have a TF/P <1 since they are reabsorbed MORE THAN water
- less appears in urine
What is the main transporter of the following:
- Proximal Tubule
- Thin Descending Limb
- Thick Ascending Limb
- Distal Tubule
- Late Distal Tubule & Collecting Ducts
- Proximal Tubule - Na-Glucose, Na-AA, Na-Lactate, Na- Phosphate via COTRANSPORT
- countertransport via Na - H (linked to reabsorption of HCO3-) - Thin Descending Limb: Passive flow of H20
- Thick Ascending Limb: Na-K-2Cl cotransporter in luminal membrane 25% Na reabsorbed in this method
- impermeable to water - Distal Tubule - Na - Cl Cotransporter
- Late Distal Tubule & Collecting Ducts
- Principle Cells: reabsorb Na and H20, secrete K, Aldosterone increase Na reabsorption & decrease K secretion
alpha - Intercalated cells: secrete H+ stimulated by aldosterone
- reabsorb K+
Which cells does ADH act on?
Principle cells
