Lecture 34 4/8/24 Flashcards
How must a substance be transported in order to be reabsorbed?
-across the tubular epithelial membranes into the interstitial fluid
-through the peritubular capillary membrane back into the blood
How can water and solutes be transported?
-through the cell membranes (transcellular)
-between the cell junctions (paracellular)
What mediates ultrafiltration?
hydrostatic and colloid osmotic forces
How does primary active transport differ from secondary active transport?
-primary is coupled directly to an energy source
-secondary is coupled indirectly to an energy source
Which active transporters are present in the kidneys?
-sodium/potassium ATPase
-hydrogen ATPase
-hydrogen/potassium ATPase
-calcium ATPase
What are the characteristics of the sodium glucose co-transporters (SGLT1 and SGLT2)?
-located on brush border of proximal tubular cells
-carry glucose into the cell cytoplasm against the concentration gradient
-90% of filtered glucose reabsorbed by SGLT2; 10% by SGLT1
What are the characteristics of GLUT1 and GLUT2 in the kidney?
-on the basolateral side of the membrane
-allow glucose to diffuse out of cells and into interstitial spaces
What is pinocytosis?
active transport mechanism allowing for the reabsorption of small peptides
What is the transport maximum?
limit to the rate at which a solute can be transported
What causes the existence of a transport maximum?
saturation of the transport systems involved
How does renal tubular transport maximum impact glucose reabsorption?
with large increases in GFR and/or plasma glucose concentration, excess glucose cannot be reabsorbed above the transport maximum; excess glucose is passed into the urine
What is the threshold for glucose?
the point at which glucose begins to appear in the urine before the transport maximum is reached
Why is there a difference between threshold and transport maximum?
not all nephrons have the same transport maximum, so some of the nephrons will max out and excrete glucose before others
When is transport maximum reached?
once all nephrons have reached their maximum capacity to reabsorb glucose
Which factors can impact rate of transport and lead to some substances NOT having a transport maximum?
-electrochemical gradient for diffusion
-permeability of the membrane for the substance
-time that the fluid containing the substance remains in the tubule
What is gradient-time transport?
transport in which the rate of transport depends on the electrochemical gradient and the time the substance is in the tubule (depends on tubular flow rate)
What does the rate of “backleak” depend on?
-permeability of tight junctions
-interstitial physical forces
What is an example of gradient-time transport?
sodium reabsorption in the proximal tubule
How does the concentration of sodium in the proximal tubule impact its reabsorption rate?
higher conc. of sodium leads to higher reabsorption rate
How does flow rate of the tubular fluid in the proximal tubule impact sodium reabsorption?
slower flow rate of tubular fluid allows for a greater percentage of sodium to be reabsorbed
Which part of the renal tubule is especially permeable to water?
proximal tubule
What are the characteristics of proximal tubule permeability?
-high permeability to water due to aquaporins and tight junctions
-permeability to most ions that is less than that to water, but still significant
What is solvent drag?
movement of solutes across tight junctions due to them being carried by water
Why are the more distal parts of the nephron less permeable to water?
-tight junctions become less permeable
-epithelial cells have a greatly decreased membrane surface area
Which hormone greatly increases water permeability of the distal and collecting tubules?
ADH
Which hormone can increase the transport maximum of sodium?
aldosterone
How does water permeability change throughout the kidney?
-high in proximal tubule
-medium in the descending loop of Henle
-low in the thin and thick ascending LOH
-variable in distal tubule, collecting tubule, and collecting ducts
How does tight junction permeability and surface area change throughout the nephron?
both decrease as you move through the nephron
What creates the electrochemical gradient that allows for chloride resorption?
-transport of positively charged sodium ions out of the tubular lumen, which leaves the lumen neg. charged
-transport of water out of the tubular lumen, which concentrates the chloride ions
Which region of the nephron has the most passive reabsorption of urea?
inner medullary collecting duct
What allows for the proximal tubule to have a high capacity for reabsorption?
-large numbers of mitochondria
-extensive brush border
-lots of intercellular and basal channels
-lots of protein carriers
What are the characteristics of early proximal tubule reabsorption?
-sodium is reabsorbed via co-transport along with glucose, amino acids, and other solutes
-sodium is also reabsorbed via counter-transport that secretes substances like H+ ions
What are the characteristics of late proximal tubule reabsorption?
-very little glucose and amino acids remain to be absorbed
-sodium is now primarily reabsorbed with chloride ions
Why does sodium concentration remain relatively constant in the proximal tubule?
water permeability of the proximal tubules is so great that water reabsorption keeps pace with sodium reabsorption
Why do substances like glucose, AAs, and bicarb. exhibit marked decreases in concentration along the length of the proximal tubule?
these substances are reabsorbed more avidly than water
Which substances become more concentrated down the length of the proximal tubule?
those that are not readily reabsorbed, such as creatinine
Which substances are secreted by the proximal tubule?
-bile salts
-oxalate
-urate
-catecholamines
-toxins and drugs
What are the general characteristics of the thin descending and ascending LOH segments?
-thin epithelial membranes
-no brush borders
-few mitochondria
-minimal levels of metabolic activity
What are the general characteristics of the thick ascending LOH segment?
-thick epithelial cells
-high metabolic activity
-capable of reabsorption of sodium, chloride, and potassium
What is the function of the thin descending LOH loop?
allow simple diffusion of substances, mainly water, through its walls
Why is the ascending LOH loop important for concentrating urine?
it is virtually impermeable to water
What is the most important component of reabsorption in the thick ascending LOH?
sodium/potassium ATPase pump
What are the characteristics of NKCC2?
-1-sodium, 2-chloride, 1-potassium transporter
-uses the potential energy of downhill sodium diffusion to drive the reabsorption of potassium into the cell
-found in thick ascending loop
Which other mechanisms of absorption are used in the thick ascending loop?
-sodium/hydrogen counter-transporter
-paracellular ion reabsorption
Why does the tubular fluid in the ascending limb become very dilute?
ascending limb is impermeable to water while allowing for lots of solute reabsorption
What is the first portion of the distal tubule?
macula densa
What is the purpose of the macula densa?
provide feedback control of the GFR and blood flow in the same nephron it is found in
What are the characteristics of the distal tubule segment that comes after the macula densa?
-highly convoluted
-avidly reabsorbs ions
-virtually impermeable to water and urea
-“diluting segment” because it dilutes the tubular fluid
What is the target of thiazide diuretics?
sodium/chloride co-transporters in the early distal tubule
Which cell types are found in the late distal tubule?
-principle cells
-intercalated cells
What are the functions of principal cells?
-reabsorb sodium and water
-secrete potassium
What are the functions of type A intercalated cells?
-reabsorb potassium
-secrete hydrogen
What are the functional characteristics of the late distal tubule?
-impermeable to urea
-reabsorb sodium
-sodium reabsorption and potassium secretion rates controlled by aldosterone
-secrete potassium
Why is water reabsorption in the late distal tubule referred to as facultative water reabsorption?
water is only reabsorbed as needed by the body, based on signals from hormones
What are the characteristics of aldosterone?
-increases cell permeability to sodium ions
-increases sodium reabsorption and potassium secretion by increasing number of Na/K pumps
-indirectly increases reabsorption of water and chloride
-stimulates secretion of hydrogen
What are the characteristics of ADH?
-causes water retention and reduces urine output
-causes aquaporins to be inserted into cell membranes to increase water reabsorption
What are the characteristics of atrial natriuretic peptide?
-triggers natriuresis/urinary excretion of sodium
-inhibits release of ADH and aldosterone
What is the role of aldosterone antagonists?
compete with aldosterone for binding sites to inhibit its effects
What is the role of sodium channel blockers?
inhibit entry of sodium into sodium channels
What are the steps of potassium secretion?
-potassium enters cell via Na/K pump, which maintains a high intracellular K+ conc.
-potassium diffuses down its concentration gradient to enter the luminal fluid
Which transporters are used by type A intercalated cells to secrete hydrogen ions?
-hydrogen ATPase transporter
-hydrogen-potassium ATPase transporter
How is hydrogen generated in type A intercalated cells?
carbonic anhydrase acts on water and carbon dioxide within the cell to form carbonic acid, which dissociates into hydrogen and bicarb.
Why is it important that type A intercalated cells have an active hydrogen ATPase?
can move hydrogen against the conc. gradient
What are the functions of type B intercalated cells?
-reduce alkalosis
-reabsorb H+
-secrete HCO3-
-secrete K+
What is the characteristics of the medullary collecting duct?
-final site for urine processing
-water permeability controlled by ADH
-permeable to urea
-involved in acid/base regulation
What determines whether a solute becomes concentrated?
the relative degree of reabsorption of the solute compared to the reabsorption of water
