Renal Transport Flashcards
Where are all glucose and amino acids reabsorbed?
Proximal tubule
What powers Proximal Tubule reabsorption?
Na/K ATPase on the basolateral membrane
What four places do substances being reabsorbed in PT have to cross?
- Cross apical border
- Go through epi cell
- Cross basolateral border
- Enter peritubular capillary
How do solutes cross the apical border?
- Symporter
- Na Glucose
- Na AA
- Na Pi
- Na HCO3-
- Anti-porter
- Na H
- Na organic solutes
How does stuff cross basolateral border of prox tubule?
- Na gets out with Na/K ATPase
- Special transporters handle rest
How does Glucose get out of the basolateral membrane?
- GLUT transporters
what channel allows sodium and glucose through the apical membrane of the proximal tubule together?
- SGLT
What antiporter brings Na in and H out across the apical membrane of the proximal tubule?
- NHE
How does water leave the proximal tubule?
- AQP channels in the apical and basolateral membrane
- It moves by bulk flow from areas of high hydrostatic pressure to areas of low (peritublar capillary)
- If ECV is low reabsorption will be high
- If ECV is high reabsorption will be low
Characteristics of the thick ascending limb?
- Impenetrable to water
- Important site for Na K Ca and Mg reabsorption
- most Mg reabsorption occurs here
- NKCC2 channel
What is the function of the NKCC2 channel and what happens to the solutes?
- Brings Na, K, 2 Cl into the cell from TAL across the apical membrane
- Electroneutral movement
- Na goes to Na/K ATPase
- 2 Cl exit basolateral mem using Cl channel
- K can do two things:
- Can go across BLM using K channel and gets reabsorbed like others
- Can also use ROMK and return to the TAL
What happens in TAL if K uses ROMK?
- Positive charges begin to build until the tubule lumen reaches 8 mV
- This will impact Ca and Mg by repelling them forcing them to travel paracellularly to the interestitial fluid for reabsorption
What happens in the distal tubule?
- Regulation of solutes, but the least amount of reabsorption occurs here
- Variable secretion/reabsorption of water and urea
What makes up Distal tubule
- DCT
- CCD
- MCD
- CT
Cell types in the distal tubule?
- Principal cells with cilia reabsorb Na and water and secrete K
- Alpha intercalated reabsorb K, HCO3 and secrete H
- B intercalated reabsorb H, CL and secrete K, HCO3
Distal Convoluted tubule characteristics?
- Relatively impermeable to water but continued NaCl reabsorption
- This dilutes tubular fluid
- NaCl is transported via thiazide sensitive Na Cl co transporter called NCC
What happens with Ca in the DCT?
- It crosses the apical membrane via TRPV5
- PTH is ligand for this allowing Ca in
- Crosses basolateral membrane via Na-Ca exchanger (NCE)
What happens in the late distal tubule and cortical collecting duct?
- Principal cells allow Na and water reabsporption and K secretion using ENaC
- Aldosterone works here
How does Na travel across apical membrane in the collecting tubule?
- ENaC rather than a cotransporter and it diffuses down its electrochemical gradient from lumen into the cell
How does aldosterone impact the collecting tubule?
- Increases expression of ENaC and Na/K ATPase leading to an increase in Na reabsorption and K secretion via ROMK
What do Principial cells and beta intercalated cells have in common?
- Secretes K
- Na/K ATPase moves K into cell from interstitial fluid
- Passive diffusion of K out of the cell into the tubular lumen
- Two channels alllow for rapid K diffusion out of cell
- BK and ROMK
what unique way does K get secreted from a beta intercalated cell?
- H/K ATPase located on basolateral membrane
- pulls K into cell from interstitium and pushes H out into interstitium
how do alpha cells reabsorb K?
- H/K ATPase is on the apical membrane pumping out hydrogen and bringing K in
- K leaves cell crossing BLM using K channel
What are the most important factors stimulating sodium reabsorption?
- Na deficiency
- Low Na diet
- Hyponatremia
- Na loss via severe diarrhea
What are the most important factors that stimulate Na secretion?
- Hypernatremia
- ANP
- Renal prostaglandins
Most important factors that stimulate potassium secretion?
- Increased serum concentration K
- Aldosterone
- targets ENaC which cause Na reabsorption and K secretion
- Principal cells and Beta Intercalated cells secrete K (located in Collecting Tubules/Ducts)
What are the most important factors that stimulate potassium reabsorption via alpha intercalated cells?
- K deficiency
- Low K diet
- Hypokalemia
- K loss via severe diarrhea
alpha intercalated cells reabsprb K
What factors stimulate ADH?
- Hyperosmolality
- Volume depletion
- much more sensitive to small changes in osmolarity than similar percent change in blood volume
What does ADH do?
- Increase water permeability of principal cells of late distal tubule and collect ducts by adding aquaporins in the apical membrane of principal cells
- Increases urea permeability of inner medullary collecting duct
- Increases activity of NKCC2 of Thick ascending limb
What AQP are on the BLM?
- AQP 3 and 4 and they are always there
- allows water to move out of principal cells
How does ADH impact the apical membrane of the principal cells?
- Inserts AQP2 on the apical surface allowing water from the tubular lumen to enter the cell and then return to the blood via AQP2 and 3 on basolateral membrane
Iin the absence of ADH what happens to AQP2?
It remains in the intracellular space in the principal cells and water will travel through the tubule into the bladder
What happens to Urea during antidiuresis?
- Gets recycled
Principal cellsa re only located in the __.
cortical medullary duct
In the presence of ADH what happens to urea?
- Water is reabsorbed in the CCD but not urea so its concentration goes up
- this occurs until urea is very concentrated when it reaches outer medullary and innner medullay CD
- Now it is so concentrated it can passively leave the tubule into the interstital fluid and get reabsorbed by the loop of henle and repeat the cycle (as long as ADH is present)
What does ADH do in the thick ascending limb?
- Increases activity of NKCC2 so you reabsorb more of those solutes than normal
What is the kidney interstitium?
- Space between tubule glomeruli and vessels
- Contains interstitial fluid, extracellular matrix, and cells
- ISF osmolarity changes
- close to cortex its low
- deep in medulla interstitial fluid osmolarity is high
Describe countercurrent multiplication.
- Single effect: NaCL leaves ascending limb and the interstitium becomes hyperosmotic. Water leaves descending limb to equalize the interstitium osmolarity.
- Fluid Flow: Fluid is always flowing through the tubule, and new fluid enters the descending limb from above, it pushes tubular fluid down developing a gradient
What is counter current exchange?
- Passive moevement of water from the descending limb into the interstitium and reabsorption into vasa recta
- Increased osmotic gradient will result in more water reabsorption
- Blood flow will impact equilibration, it makes the ISF more dilute if it is too quick
What happens to urine concentration if a patient is on a vasodilator or has large increase in arterial pressure?
- Washout of [ISF] gradient resulting in a dilute gradient and therefore more diuresis
What is osmolar clearance?
- Total clearance of all soutes from blood expressed as Cosm
- Cosm= [Urineosm] x V / Posm
What is free water clearance?
- Difference between water excretion and osmolar clearance, the rate the body excretes solute-free water
- CH2O= V-Cosm
When CH2O is negative what does it mean?
- Excess solutes are removed, water is conserved
- The osmolar clearance number is large
When CH2O is positive what does it indicate?
- Flow of blood is quick, water is being excreted forming dilute urine, water excess
Obligatory urine volume?
- minimum amount of solutes in the water that have to be excreted for life ~600mOsm/day
- OUV: Min solute excretion per day/ max urinve concentrating ability
- 600/1200= 0.50 L/day
Why does drinking salt water dehydrate us?
- You can only concentrate your urine up to 1200 mOsm but now you are adding a lot of extra salt so you need to excrete a lot more urine
- You will need water for this and that water will come from body reserves so the more salt water you drink the more water you pull from ECF, ICF, CSF to excrete out the excess solutes
What happens with antidiuresis?
- High ADH levels and high osmolarity of renal medullary interstitial fluid
- Cortical collecting duct has higher concentration of urea bc DT is impermeable to urea
- Urea build up results in passive diffusion out of CD into medullary interstitium
- Contributes to medullary hyperosmolarity
- Dark urine infrequent urination
what is natriuresis?
- Excretion of excessively large amount of sodium in the urine that is especially disproportional to the excretion of water.
- Caused by Drugs, Hormones (ANP), and significantly elevated renal perfusion pressure
