10. Transport of Na+ and Cl- Flashcards
How do kidneys maintain the body’s extracellular fluid (ECF)?
Kidneys help maintain body’s ECF volume by regulating the [Na] and [Cl] in the urine
Na is most important contributor to osmolality (electrolyte water balance) of the ECF
Where Na goes, H2O follows
Movement of solutes and water is driven by transepithelial transport across the different sections of the nephron
What are the mechanisms of epithelial transport?
Transport is governed by law of thermodynamics
Gibbs free energy
Equations on slide 2
Δμx=RTln[x]i/[x]o + zx FVm
Nernst equation
Vm= -(RT/zxF)ln[x]i/[x]o
Slides 2-4 Nov 21
How is epithelial transport done in the cells?
Polarized cells
Right junctions
Six pack model
Slide 5-6 Nov 21
Na has uphill movement in cell (not natural)
What direction is a transport moving into or out of the cell based on its sign?
Negative moves into cell
Positive moves out
Slide 7 Nov 21
How do membrane bound carriers aid epithelial transport?
Membrane bound carriers can couple the flows of 2 or more solutes with the final direction of flow determined by the cumulative thermodynamic gradient (adding up)
Slides 8-10 Nov 21
What is transcellular Na reabsorption?
Transcellular transport
Na and Cl sequentially traverse the apical and basolateral membranes before entering the blood (electrochemical gradients, ion channels, and transporters determine transport rates)
2 steps:
- Passive entry of Na into the cell across apical membrane (low intracellular Na and negative cell voltage allows this), proximal tubule, TAL, DCT have Na cotransporters and exchangers that move Na across
- Active extrusion of Na out of the cell across the basolateral membrane, mediated by Na-K pump (keeps [Na]i low and [K]i high)
Slide 14 Nov 21
Slide 22-23 Nov 21
What is paracellular Na reabsorption?
Paracellular transport
Na and Cl move entirely by an extracellular route through tight junctions between cells
Transepithelial electrochemical driving forces and permeability properties of the right junctions govern ion movements (transport rates)
Occurs in proximal tubule region
Slides 11-14 Nov 21
Slide 22-23 Nov 21
What types of transporters/channels are used in each area used in transcellular transport?
Proximal tubule, loop of Henle, a d distal tubule use a variety of Na coupled co transporters
Collecting ducts use epithelial Na channels (ENaC’s)
How does water move across cells?
Water moves from low solute concentration (high water potential) to high solute concentration (low water potential)
Osmotic gradient
Water cannot be actively pumped (can’t use ATP to move water)
Changes is osmolarity cause a transmembrane osmotic gradient, therefore water moves across the membrane affecting cell volume
Slide 15-16 Nov 21
What is osmolarity?
What is osmolality?
The measure of solute concentration (number of osmolarity per litre)
Osmolality is the number of osmoles per kg of solvent
Na is most important contributor to osmolality (electrolyte-water balance)
Where Na goes H2O follows
Slide 16 Nov 21
What is the osmolarity of the solution transported into the lateral intercellular space in epithelial transport?
What is the osmolarity of the solution transported into restricted basal spaces in epithelial transport?
The solution transported into the lateral intercellular space is slightly hyperosmotic, solution emerging into the interstitial space is nearly isosmotic
The solution transported into restricted basal spaces is slightly hyperosmotic, drawing water into these spaces. The solution emerging into the interstitial space is nearly isosmotic
Slide 17 Nov 21
What do even small variations in the fractional reabsorptive rate (kidneys reabsorb 99.6% of filtered Na) lead to?
Changes in total body Na+ that ultimately leads to altered ECF volume that leads to changes in blood pressure and body weight
What is the breakdown of reabsorption percentages through the nephron?
Reabsorption greatest at proximal tubule and along length on nephron (67%)
25% reabsorbed throughout loop of Henle
5% absorbed along the distal convoluted tubule, connecting tubule, initial collecting duct, and cortical collecting tubule
Nearly all remaining Na reabsorbed in the medullary collecting ducts leaving 0.4% of the filtered load excreted in urine
Slide 21 Nov 21
How is Na transported through loop of Henle?
Thin limbs Na transport is almost entirely passive & paracellular
Thick ascending limb has 2 major transcellular pathways:
1. Na:K:2Cl co transporter (NKCC2) moves 1 Na, 1K, 2Cl across apical membrane
2. Na/H exchanger is anti
porter that exploits gradient caused by Na/K pump across basolateral membrane
Paracellular diffusion accounts for 50% of Na reabsorbed
Slide 24 Nov 21
How is Na reabsorbed in the distal convoluted tubule?
Na reabsorption is almost entirely transcellular
Apically is uses the Na/Cl cotransporter
Basolaterally it uses the Na-K pump
No paracellular transport
Slide 25 Nov 21
Pages 756-758
How is Na reabsorbed in the connecting tubule, cortical collecting tubule, and medullary collecting duct?
Principal cell transport Na
Apical membrane use ENaC’s for Na transport
Basolateral membrane Na/K pump
No paracellular transport
Slide 25 Nov 21
How is Cl- reabsorbed?
2 types?
Cl- reabsorption occurs through transcellular & paracellular pathways
Paracellular transport- dominant in early proximal tubules and follows an electrochemical gradient
Transcellular transport- dominant in later proximal tubules
Slide 26 Nov 21
What does the apical and basolateral transports of Cl reabsorption use?
Apical transport uses Cl- anion exchangers (SLC26A6) (formate, oxalate, HCO3, OH)
Basolateral transport uses a membrane Cl- channel & a K/Cl co
transporter (no ATP needed for basolateral transport)
Slide 26 Nov 21
What happens with Cl- reabsorption in the thick ascending limb and distal convoluted tubule in the loop of Henle?
Loop of Henle thick ascending limb apical membrane majority of Cl reabsorption is through the Na/K/Cl cotransporter
Basolateral membrane exit is through a Cl channel of CIC family
Cl re entry through Cl/HCO3 exchanger no paracellular transport
Distal convoluted tubule apical membrane Na-Cl co transporter
Basolateral membrane Cl channels across
Slide 27 Nov 21
How is Cl reabsorbed through the cortical collecting tubule?
2 different types of cells
Principal cells and β intercalated cells in the collecting ducts
Principal cells reabsorb Cl through paracellular transport
β intercalated cells reabsorb Cl using an apical Cl/HCO3 exchanger & basolateral Cl channel
Slide 28 Nov 21
How is water reabsorbed?
It is passive and secondary to solute transport
Mirrors Na transport
Driven by small osmotic gradients (2-3mOsm)
Osmotic gradient is large enough due to the high water permeability due to aquaporins
Slide 29 Nov 21
How do proximal tubules and loops of Henle/distal nephron reabsorb water?
Proximal tubules- high level of expression of aquaporin 1 (AQP1)
Transcellular and paracellular flow
Loop of Henle & distal nephron- H2O permeability is relatively low in the absence of anti diuretic hormone (AVP)
Na reabsorption combined with low H2O permeability allows distal nephron segments to generate a low luminal [Na] and osmolarity relative to interstitial space
Low luminal [Na] causes large osmotic gradient across the epithelium (makes it ready to absorb H2O)
Slide 29 Nov 21
What is Na transport across the basolateral later of tubular epithelial cells dependant on?
Dependant on ATP-driven Na-K pump
There is a high need of ATP production through oxidative metabolism therefore a constant large supply of O2 is needed
High O2 consumption by kidneys reflects high level of Na transport
Slide 30 Nov 21
What are the 3 major mechanisms through which the body regulates Na?
- Changes in renal hemodynamics
- Factors that responds to decrease in effective circulating volume
- renin-angiotensin-aldosterone axis
- sympathetic activity
- arginine vasopressin (AVP, antidiuretic hormone) - Factors that respond to increase in effective circulating volume
- atrial natriuretic peptide
How does 1. Change in hemodynamics regulate Na and Cl transport?
Spontaneous alterations in filtration fraction (FF=GFR/renal plasma flow)
Alterations in GFR alters Na load presented to kidneys
Proximal convoluted tubule respond by reabsorbing a constant fraction of the Na load (glomerulotubular balance)
Increase filtration fraction= increase Na reabsorption
Decrease filtration fraction= decrease Na reabsorption
Slide 32 Nov 21
How is glomerulotubular balance achieved?
Through peritubular & luminal mechanisms
Starling forces across peritubular capillary wall determine uptake of interstitial fluid & thus net reabsorption of NaCl & fluid from tubule lumen to peritubular capillaries
At normal GFR, low hydrostatic pressure & high oncotic pressure within the capillaries cause an extensive uptake of solutes & fluid into the capillaries
Slide 33-34 Nov 21
What are the luminal factors in the proximal tubule causing glomerulotubular balance?
Increase flow along proximal tubule leads to an increase in fluid & NaCl reabsorption regardless of the peritubular capillary effects
- An increased flow rate causes solutes to be absorbed across the entire length of the tubule
- results in increased reabsorption of Na (via Na driven solute transporters) - Increased flow is thought to bend the central coli I’m in the apical membrane signaling to increase fluid reabsorption
Distal nephron also increases Na reabsorption in response to an increased Na load
How does 2. Factors that respond to decrease in effective circulating volume regulate Na and Cl transport?
Renin-angiotensin-aldosterone axis:
Renin- enzyme produces by JGA leads to production of ANG II
ANG II- binds AT1 receptors and stimulates Na reabsorption
Aldosterone- stimulates Na reabsorption in later region of nephron (initial collecting tubule, CCT, medullary collecting ducts)
Bind to mineralcorticoid receptors stimulating transcription of apical ENaC, apical K channels and basolateral Na/K pumps
Slides 36-38 Nov 21
How does 3. Factors that respond to increase in effective circulating volume regulate Na and Cl transport?
Atrial natriuretic peptide:
- causes renal vasodilation
- increasing blood flow & Na load
- renal vasodilation by increasing blood flow to both the cortex and the medulla
- increased blood flow to the cortex raises GFR and increases the Na load to the proximal tubule and to the TAL
Slide 39 Nov 21
