Jackson 6 Flashcards
Two modes of transport
transcellular –
paracellular –
transcellular –
molecules move through tubular cells
paracellular –
molecules move between tubular cells
osmosis – diffusion of water
solvent drag results from ——-
rate of water diffusion can be regulated by ——-
solutes being carried by water in paracellular transport
aquaporins
endocytosis and exocytosis –
vesicular transport
Sodium can be reabsorbed in all but one segment of a nephron - reabsorption occurs in the
proximal tubule, the ascending limbs of the loop of Henle, the distal tubule, and the collecting duct. The transport mechanism used varies.
proximal tubule reabsorption–
Most of the reabsorption (65%) occurs in the
proximal tubule. In the latter part it is favoured by an electrochemical driving force, but initially it needs the cotransporter SGLT and the Na-H antiporter. Sodium passes along an electrochemical gradient (passive transport) from the lumen into the tubular cell, together with water and chloride which also diffuse passively. Water is reabsorbed to the same degree, resulting in the concentration in the end of the proximal tubule being the same as in the beginning. In other words, the reabsorption in the proximal tubule is isosmotic.
thick ascending limb reabsoprtion–
Sodium is reabsorbed in the thick ascending limb of loop of Henle, by
Na-K-2Cl symporter and Na-H antiporter. It goes against its chemical driving force, but the high electrical driving force renders the overall electrochemical driving force positive anyway, availing some sodium to diffuse passively either the transcellular or paracellular way..
distal tubule reabsoprtion –
In the distal convoluted tubule sodium is transported against an
electrochemical gradient by sodium-chloride symporters.
collecting duct reabsorption -
The principal cells are the
sodium-transporting cells in the collecting duct system.
Reabsorption in the proximal tubule
1. Glucose and amino acids are rebsorbed with
Na+ using symporters
Reabsorption in the proximal tubule
- Active transport on
basal side, keeps intracellular Na+ low
Reabsorption in the proximal tubule
- Water (and solutes) move via
paracellular transport; keeps the osmolarity of the tubular fluid constant
Reabsorption in the proximal tubule
- Na+ reabsorption also occurs in conjunction with
bicarbonate reabsorption using a Na+/H+ antiporter
reabsorption is not direct……H+ secretion = HCO3- reabsorption
Reabsorption in the proximal tubule
CA reaction produces
H+ and HCO3- in tubule cell à HCO3- is transported into blood à H+ transported into tubular fluid where it recombines with a filtered HCO3-
Net effect is bicarbonate reabsorption
The proximal tubule also has transporters for
organic cations and anions so such molecules are secreted into the tubular fluid. Many drugs are organic ionic compounds. They are commonly bound to plasma proteins so they are not filtered at the glomerulus, must be secreted in order for them to be excreted in the urine.
Proximal tubule The transporters have low
specificity and can be saturated.
To summarize: by the end of the proximal tubule –
To summarize: by the end of the proximal tubule –
Reabsorption in the loop of Henle
In the loop of Henle,
25% of filtered NaCl and 15% of water is reabsorbed
Descending thin limb -
impermeable to salt, but permeable to water
Ascending thin limb -
impermeable to water, but permeable to salt.
Reabsorption in thin limb segments is
passive
In the ascending thick limb (ATL; see diagram at right), fluid is
diluted
ATL: Na+ K+ 2Cl- symporter in
apical membrane
ATL: Na+ K+ ATPase in
basolateral membrane
ATL: paracellular transport of monovalents and divalents NOT due to
solvent drag.
Tubular fluid becomes positive when
Cl- reabsorbed so cations diffuse along an electrical gradient
Fluid leaving loop is
hyposmotic, but the renal countercurrent mechanism has established an osmotic gradient required for formation of hyperosmotic urine.
Concentration of the tubular fluid will occur in the
collecting duct if antidiuretic hormone (ADH/vasopressin) is present.
The peritubular capillaries are permeable to
NaCl and water so plasma osmolarity changes as the capillaries follow the loop, but the osmolarity of the blood leaving the kidney (to veins) is normal.
Reabsorption in the distal tubule and collecting duct
The initial segment of the distal tubule, reabsorbs
~8% of filtered NaCl via a Na+ Cl- symporter in apical membrane and Na+ K+ ATPase in basolateral membrane
reabsorption of K+, H+ and water in distal tubule is
variable
Sodium reabsorption in the latter half of distal tubule and the collecting duct is
similar
There are two cell types in the collecting duct and late distal tubule
principal cells have epithelial sodium channels (ENaC)
intercalated cells
epithelial sodium channels (ENaC) that reabsorb
Na+ and secrete K+
ENaC:
Na+ reabsorption drives
paracellular Cl- reabsorption
ENaC:
K+ secreted due to
Na+ K+ ATPase activity in basal membrane
intercalated cells involved with
acid-base balance; can also reabsorb K+
The activity of transport mechanisms can be modified to maintain
blood volume. A positive or negative shift in water balance shifts extracellular volume away from euvolemia (normal volume). Hormonal and neural responses to this shift help re-establish euvolemia
Hormonal regulation of blood volume -
ADH
Vasopressin or antidiuretic hormone (ADH) released from the posterior pituitary
Vasopressin or antidiuretic hormone (ADH)
release is stimulated by
high pressure baroreceptors in aortic arch and carotid sinus response to a decrease in blood pressure
changes in osmolality of body fluids
Vasopressin or antidiuretic hormone (ADH
respond to osmolality above a set point of
275-290 mOsm/kg H2O
Vasopressin or antidiuretic hormone (ADH
release can also be stimulated by
changes in blood volume/pressure
Vasopressin or antidiuretic hormone (ADH
low pressure baroreceptors in
left atrium and large pulmonary vessels respond to a decrease in blood volume
Actions of ADH:
increases the permeability of the late distal tubule and the collecting duct to water by increasing
aquaporins into the apical membrane (basolateral membrane is freely permeable to water)
Actions of ADH
also increases permeability of
medullary collecting duct to urea
Actions of ADH
If ADH low (diuresis) – solutes reabsorbed in
distal tubule and collecting duct, but no water reabsorption; urine as dilute as 50 mOsm/kg H2 O
Actions of ADH
If ADH high (antidiuresis) – water reabsorbed as
fluid passes through collecting duct; urine can be concentrated up to 1200 mOsm/kg H2O
The renin-angiontensin-aldosterone system stimulates events that increase
reabsorption of sodium and water (combat volume contraction)
renin-angiontensin-aldosterone system:
renin released in response to a drop in
perfusion pressure, decreased NaCl delivery to macula densa, or sympathetic input to juxtaglomerular cells
renin-angiontensin-aldosterone system
renin converts
angiotensinogen to angiotensin I
renin-angiontensin-aldosterone system
angiotensin I converted to
angiotensin II by angiotensin converting enzyme (ACE)
renin-angiontensin-aldosterone system
angiotensin II has multiple effects
vasoconstriction
stimulate release of ADH
increase sympathetic activity
stimulate aldosterone secretion
renin-angiontensin-aldosterone system
aldosterone from the adrenal cortex acts to increase
NaCl reabsorption in the distal tubule and collecting duct by increasing transport protein synthesis
Natriuretic peptides are hormones secreted when the
heart dilates (during volume expansion)
Natriuretic peptides:
Atrial natriuretic peptide
from the atria
Natriuretic peptides
Brain natriuretic peptide from the
ventricles
Natriuretic peptides
The effects of natriuretic peptides include
vasodilation of afferent arterioles
vasoconstriction of efferent arterioles
inhibition of renin (and aldosterone)
inhibition of ADH secretion
Natriuretic peptides
Net effect is to increase the excretion of
NaCl and water.
Why is potassium regulation important?
K+ is a major determinant of
membrane resting potential. Therefore, it can affect electrically excitable cells.
Why is potassium regulation important?
hyperkalemia will
depolarize Vm
Why is potassium regulation important?
hypokalemia will
hyperpolarize Vm
Why is potassium regulation important?
changes in K+ can cause
cardiac arrhythmias
How is potassium regulated?
ingested K+ is
fast shifted into cells – mediated by insulin, epinephrine, and aldosterone
kidneys typically excrete ——– of ingested K+
90-95%
Reabsorption and secretion of K+ in the nephron
In the glomerulus K+
is freely filtered.
In the proximal tubule about 67% of filtered K+ is
reabsorbed, mostly by paracellular transport / solvent drag as previously discussed for Na+.
In the thick ascending limb have reabsorption by
Na+K+2Cl- symporter and paracellular transport (non-solvent drag)
In the late distal tubule and collecting duct
K+ secreted by
principal cells depending on ATPase activity, K+ gradient, and/or apical K+ permeability
or intercalated cells reabsorb K+ when potassium is depleted
Factors affecting excretion of potassium include
plasma [K+] - increased K+ stimulates
aldosterone release, and aldosterone increases Na+ K+ ATPases in principal cells
Factors affecting excretion of potassium include
flow rate of tubular fluid – increased flow rate increases
K+ secretion
local response to bending of cilia
Factors affecting excretion of potassium include
↑ flow –> ↑ —- in collecting duct –> ↑Na+ —– –> favors ↑ —– secretion
Na+
reabsorption
K+
Compare renal handling of potassium relative to plasma concentrations of potassium:
Reabsorption in proximal tubule and thick ascending limb changes
very little
Compare renal handling of potassium relative to plasma concentrations of potassium
Distal tubule and cortical collecting duct will
reabsorb potassium when plasma concentrations are low
Compare renal handling of potassium relative to plasma concentrations of potassium
If plasma K+ is high, secretion
increases in distal tubule and cortical collecting duct
