Renal - Reabsorption and Secretion Flashcards
Define
Glomerular Filtration
Indiscriminate filtration of a protein-free plasma from the glomerulus into Bowman’s Capsule - 20% of plasma and everything in it
no cells or protein
Define
Tubular Reabsorption
Selective movement of filtered substances from the tubular lumen into the peritubular capillaries
Glomerulus -> Bowman’s Capsule -> Tubular lumen -> Peritubular capillary
Brought back into the bloodstream after going through the glomerulus
Define
Tubular Secretion
Selective movement of nonfiltered substances from the peritubular capillaries into the tubular lumen
AA -> Glomerulus -> EA -> Peritubular Capilary -> Tubular lumen
What are 3 major characteristics of tubular reabsorption?
Tremendous
Highly Selective
Variable
What does it mean that tubular reabsorption is tremendous?
What makes it classified that way?
99% of filtered water is reabsorbed
100% of filtered sugar reabsorbed
99.5% of filtered salt reabsorbed
What does it mean that tubular reabsorption is highly selective?
Only specific substances get reabsorbed
% of filtered substance excreted:
* water: 1%
* Glucose: 0%
* Sodium: 0.5%
* Urea (waste product): 50%
* Phenol (waste product): 100%
What does it mean that tubular reabsorption is variable?
It varies based on the body’s needs.
what’s reabsorbed at one point is different from another
Define
Transcellular
Through epithelial cells
Define
Paracellular
Between cells, through tight junctions
How do solutes enter the cell?
Transporters (carriers) and channels
How does water get into the cell?
Aquaporins
“Leakiness” of tight junctions
How do ions get into the cell?
Transporters (carriers) and channels
“Leakiness” of tight junctions
Define
Proximal Convoluted Tubule (PCT)
Lumen contains filtrate which leaked out of glomerular capillaries -> Bowman’s capsule -> PCT
What lines the lumen of the PCT?
Tubular Cells
What is the purpose of the tubular cells that line the lumen of the PCT?
Contain transporters, channels, etc that allow some solutes to diffuse into the cell (apical) and out (basolateral) into the peritubular capillaries surround the PCT
The major site for reabsorption of solutes is the…
Proximal Convoluted Tubule (PCT)
What is reabsorbed in the PCT?
100% of glucose and amino acids
50% of urea
60-70% of the Na+, K+, PO4-3, Ca2+, H20, and Cl-
90% of HCO3-
How is water reabsorbed in the PCT?
It mostly gets reabsorbed because it follows ions like Na+ in even when ADH is high
How does ADH effect water reabsorption?
Most water is still reabsorbed in PCT but it causes reabsorption of remaining water in the collecting duct
How is Na+ filtered?
Na+ is freely filtered across glomerular caps
Na+ in tubular fluid = Na+ in plasma
Where is sodium reabsorbed in the nephron?
along the entire nephron but to varying extents
What is the purpose of Na+-K+ ATPase in the nephron?
It influences Na+ reabsorption
Low Na+ and negative cell interior
generates low intracellular Na+ for easier reabsorption
Located on the basolateral side
The process of sodium reabsorption in the nephron is…
Isotonic
For all Na+ reabsorbed, water is absorbed with it
Reabsorption of Na+ = Reabsorption of Water
What mechanisms cause the reabsorption of Na+ in the first half of the proximal tubule?
Cotransportation with HCO3-, glucose, aa’s, phosphate, and lactate
Reabsorbed by Na+-H exchange (pump out H+ reabsorb HCO3)
Secondary active transport
What stimulates Na+-H+ exchange reabsorption of Na+?
Angiotensin II
SNS
Low blood volume (hemorrage)
How is sodium reabsorbed in the 2nd half of the proximal tubule?
Na+ is reabsorbed with Cl- paracellularly
Cl- anion antiporter (penicillin, salicylate)
Why does Na+ get reabsorbed with Cl- in the 2nd half of the proximal tubule?
Cl- is in high concentration and crosses tight junctions into the cell
Causes the lumen to become positive and Na+ follows Cl- into the cell
What is the main mechanism of K+ reabsorbtion in the PCT?
paracellularly by solvent drag
passive
Define
Solvent Drag
Paracellularly reabsorbed due to reabsorption of water and other solutes
Define
Transport Maximum (Tm)
The maximum rate of shuttling solutes
The total transport maximum throughout all of the nephrons in the kidney
There is a point at which transporters can be saturated
How does transport maximum effect elevating glucose?
Elevated blood glucose -> increase glucose load in Bowman’s capsule -> water remains in filtrate
No glucose transporters after PCT, glucose acts as an osmotic force
When is transport maximum reached?
When carriers are saturated
What happens when transport maximum is met?
Remaining substance is excreted
Define
Threshold
the appearance of glucose in the urine before you reach the overall Tm of the kidney
The plasma concentration at which a substance begins to appear in urine
Threshold is met before Tm
Hyperglycemia causes….
excessive urine production (diuresis)
How does hyperglycemia cause excessive urine production?
Filtered load is greater than the capacity of tubules to reabsorb it
Transporters become saturated, glucose ends up in the urine
How does glucose draw water into the urine?
Osmosis
Osmosis - a process by which molecules of a solvent tend to pass through a semipermeable membrane from a less concentrated solution into a more concentrated one, thus equalizing the concentrations on each side of the membrane.
What happens to urea in the nephron?
50% reabsorbed in the PCT
later secreted back into the tubule
What happens to urea by the end of the descending limb of the loop of henle?
Urea in the blood is greater than the tubule so urea diffuses from the vasa recta into the tubule
What is the purpose of urea cycling in the nephron?
It helps concentrate the interstitium
helps with water reabsorption
What happens to HCO3- in the kidney?
Normally, all filtered HCO3- is reabsorbed mainly in the PT
the rest is reabsorbed in the TAL and CD and involves H+ secretion
Why is it critical that all filtered HCO3- is reabsorbed?
Any loss of HCO3- in urine disturbs acid base balance
How is HCO3- cycled through the cell?
- Na+-H+ antiporter - Na+ in , H+ out
- H+ secreted + filtered HCO3- -> H2CO3 -> CO2+H20 -> diffusion
- CO2 passively reabsorbed + H20
- “New HCO3- leaves cell via Na+-HCO3 cotransporter
HCO3- ions reabsorbed not the same as the ones filtered
What is the net effect of HCO3- cycling in the cell?
One HCO3- returned to systemic circulation for every H+ that is secreted
reabsorption of virtually all filtered HCO3-`
Salt Concentration in the PCT
how are PCT filtrate salt and plasma salt related
PCT Filtrate [salt] = plasma [salt]
What is the function of the loop of henle?
Concentration of the urine so we can conserve H20 if we need to
How can you make a solution more concentrated?
Take out water or add solute
How can we make a solution more dilute?
add water or take out solute
Generally,
How does the kidney concentrate and dilute urine?
Solutes and water must be seperated so several parts of the nephron are impermeable to water
water follows solutes, expect in impermeable regions
What are the 3 segments of the loop of henle?
Descending Limb
Thin Ascending Limb
Thick Ascending Limb
Define:
Descending Limb of Loop of Henle
What is it permeable/impermeable to?
(Low) Impermeability to ions
Permeable to water
Define:
Thin Ascending Limb of Loop of Henle
What is it permeable/impermeable to?
Impermeable to water
Permeable to ions
Define:
Thick Ascending Limb of Loop of Henle
What is it permeable/impermeable to?
Impermeable to water, Na-K-2Cl cotransporter; Ca2+, Mg2+
How does the Descending Loop of Henle function to assist in urine concentration/dilution?
Receives isotonic fluid from PT
DL loses H20 to the higher concentration of the peritubular capillaries outside the loop
DL increases in osmolarity until it reaches its max at the hairpin turn
Where in the nephron is the highest concentration found?
The hairpin turn between the Ascending and Descending limbs of the loop of henle.
The collecting duct can reach this same osmolarity with maximum ADH effect
Fluid received by the descending limb from the proximal tubule is….
isotonic
%
Water reabsorption
how is it reabsorbed throughout the nephron
67% in the PCT
20% in the descending limb
the finall 13% depends on the bodies need
What happens to the final 13% of water if the body is well hydrated?
It is destined for the toilet
What happens to the final 13% of water if the body is dehydrated?
Hormones acting further down the nephron will reabsorb increasing H20
%
Urea Cycling
What happens to it as it travels through the nephron, generally
50% of urea is reabsorbed in the PCT
By the time it reaches the tip of the LOH, all reabsorbed urea is secreted back into the lumen+more
Descending limb contains 110% of the urea initially filtered
Although it is a waste product, urea is used to…
Create an osmotic gradient to reabsorb water from the collecting duct
creates a hypertonic medullary interstitium
How are Na+ and Cl- moved through the Thin Ascending Limb of the LOH?
Passive reabsorption
How is Na+ and Cl- moved through the Thick Ascending Limb of the LOH?
Na+-K+-2Cl- Cotransporter
How does the Na+ - K+ - 2Cl- Cotransporter function in the Thick Ascending Limb of the LOH?
Na+ and Cl- move down gradient
K+ vs. gradient
K+ return to lumen thru K+ channel (ROMK)
Net charge of tubular fluid is positive - anions want to leave
Why is the ROMK channel important to the Na+ - K+ - Cl- Cotransporter?
It creates a positive lumen causing reabsorption of several cations
Furosemide - Cotransporter - less positve lumen - increase loss of K+, Ca2+, Mg2+
Summary
What are the two main things that occur in the Descending Limb of the LOH?
H20 reabsorbed
Tubular fluid reaches max osmolarity
Summary
What are the main functions of the Ascending Limb of the LOH?
Thick and Thin
Impermeability to H20
NaCl reabsorption
K+, Ca2+, Mg2+ reabsorbed paracellularly
Responsible for a large portion of solute reabsorption -> diluting tubular fluid
NaCl reabsorption - passive in Thin and Na-K-2Cl cotransporter in thick
Which segment of the loop of henle is considered the “diluting segments”?
Early distal tubule
Low osmolarity
What is reabsorbed in the Distal Convoluted Tubule?
Na, K, 2Cl, Ca, Mg, NaCl,
In the early distal convoluted tubule, how is NaCl reabsorbed?
By a Na+ - Cl- cotransporter
Distal tubule is neutral
What inhibits the Na+ - K+ - 2Cl- Cotransporter in the TAL?
Loop diuretics
What inhibits the Na+-Cl- Cotransporter in the DCT?
Thiazide diuretics
increase diuresis
increase Ca2+ reabsorption by decreasing intracellular Na+ concentration and in increasing activity of Na+/Ca2+
What is the major site of regulated (hormone stimulated) reabsorption in the nephron?
The late distal tubule and collecting duct
What are the two cell types found in the late distal tubule/collecting duct?
Principal Cells
Intercalated cells (alpha and beta)
What is the function of principal cells in the late distal tubule/collecting duct?
Involved in Na+ reabsorption (via ENaC) and K+ secretion
ENaC = Epithelial Na Channel
What effect does ADH have on principal cells in the late distal tubule/collecting duct?
inceases H20 permeability
What is the function of intercalated cells in the late distal tubule/collecting duct?
alpha secrete H+ via H+-ATPase
What effect does aldosterone have in the late distal tubule/collecting duct?
Increases ENaC - Na reabsorption
Increases ROMK - K+ secretion
Increases Na+ - K+ ATPase
Increases H+ secretion into urine
What type of calcium is filtered?
free ionized
What are the 3 paracellular mechanisms used for Calcium filtration and reabsorption in the PT and TAL?
Solvent drag (follows water)
Concentration gradient (higher in lumen than interstitium)
+ charge in lumen pushes it through
What are the 2 transcellular mechanisms of Ca filtration in the PT, TAL, and DCT?`
Ca2+ ATPase
Na-Ca2+ anti-transport
What effect does PTH have on calcium reabsorption in the DT and CD?
it increases calcium reabsorption by increasing insertion and open configuration of Ca channels
What effect does PTH have on PO4-3 excretion?
It increases PO4-3 excretion
removes it, prevents reabsorption when Ca2+ reabsorption increases
What are the most potent stimulators of NaCl and H20 reabsorption?
Angiotension II
Aldosterone
Sympathetic Nerves
What is the major stimulus of angiotensin II?
Stimulating NaCl and H2O reabsorption
Renin
Where is the site of action of angiotensin II?
Stimulating NaCl and H2O reabsorption
PT
via stimulation of the Na+-H+ exchanger
What is the effect of angiotensin II stimulation in regards to NaCl and H2O reabsorption?
Increasing NaCl and H2O reabsorption
What is the major stimulus of aldosterone?
Stimulating NaCl and H2O reabsorption
Angiotensin II
Increasin potassium concentration
secretion - low extracellular volume
Where is the site of action for aldosterone?
Stimulating NaCl and H2O reabsorption
PT, CD
ENaC, ROMK, Na+ATPase
What is the effect of aldosterone on NaCl and H2O reabsorption?
Increasing NaCl and H2O reabsorption
What is the major stimulus of sympathetic nerves?
Stimulating NaCl and H2O reabsorption
Decreasing ECF Volume
Hemorrage
Where is the site of action of sympathetic Nerves?
Stimulating NaCl and H2O reabsorption
JGA (release of Renin)
PT(via Na+-H+ exchanger)
What is the effect of sympathetic nerves on NaCl and H2O reabsorption?
Stimulating NaCl and H2O reabsorption
Increasing NaCl and H2O reabsorption
Where is the major site of regulated Na+ reabsorption?
DT and CD
Angiotensin II stimulates the secretion of….
Aldosterone
What structure detects changes in the delivery of Na+ to the TAL/DCT?
Macula Densa
This factor is the rate-limiting step in the production of angiotensin II
Renin
The sympathetic nervous system stimulates renin secretion from the _ cells
Granular
Where are granular cells located?
Afferent Arterioles
In what part of the nephron is the juxtaglomerular apparatus located?
where thick AL meets DT
What is the flow of tubular secretion?
blood - interstitium - peritubular cavity
opposite of TR
adds missed things to filtrate
What are the steps of reabsorption?
Passive diffusion from the peritubular capillary to interstitial fluid
Active transport into the renal epithelium or into the lumen
reverse of secretion
Define
Excretion
simply
Removal of material from the body
Define:
Secretion
Simply
Movement of material from one point to another
How is K+ homeostasis maintained?
Shifting into/out of cells (transient fix, buys time)
Adjusting K+ excretion (corrective mechanism)
K+ secretion is under control of …
aldosterone
Most K+ in urine is from…
Controlled K+ secretion
If K+ depletion:
Tubular Secretion of K+
K+ secretion minimal
Note: K+ secretion is adjusted not reabsorbed
If K+ excess:
Tubular Secretion of K+
K+ secretion increased
Note: K+ secretion is adjusted not reabsorbed
How does sodium in the CD effect K+ secretion?
HIgh Na+ delivery increases Na+ in CD which increases K+ secretion
How does K+ in the blood effect K+ secretion?
High plasma K+ concentration in the blood which increases K+ secretion
How does urine flow rate effect K+ secretion?
High urine flow rate results in lower K+ in the lumen next to principal cell
How does the presence of non-reabsorbable anions in the lumen effect tubular secretion of K+?
Increases negativity in the lumen
helps pull K+ into filtrate due to negative change
Where is K+ reabsorbed in the nephron?
PT
Thick AL
Where is K+ secreted in the nephron?
Late DT
CD
Which of the following will cause an increase in K+ secretion?
Hyperaldosteronism
Increased delivery of Na+ to the distal tubule
Both
Why is tubular secretion of H+ so important?
in acid-base balance
Tubular secretion of H+ is always accompanied by…
generation of new HCO2- which is added to the ECF
Where does tubular secretion of H+ occur?
in intercalated cells late DT and CD
What is the purpose of tubular secretion of organic ions?
elimination of many toxic compounds
In regards to the tubular secretion of organic ions, elevated plasma levels of one ion….
decreases secretion of others
What hormones affect the kidney?
Renin
Angiotensin II
Aldosterone
ADH
Adenosine
When is renin released? By who?
released by kidney when BP is too low
How does angiotensin II affect the kidney?
causes arterioles to constrict (increasing arterial BP)
increases Na+ reabsorption
stimulates release of aldosterone
How does aldosterone affect the kidney?
Secreted from the adrenal cortex
increases BP by increasing Na+ reabsorption
increases excretion and secretion of K+ and H+
How does ADH affect the kidney?
Promotes aquaporin insertion in the cell membranes of the collecting duct
How does adenosine affect the kidney?
macula densa uses this to change the radius of afferent arteriole
In the glomerulus, capillary hydrostatic pressure is…
Very high (~55 mmHg)
In Bowman’s Capsule, colloid osmotic pressure is…
essentially zero
What occurs in the PCT?
Site of most Na+, K+, PO4-2, C2+, H2O, and Cl- reabsorbed
Site of Na+-glucose and Na+-amino acid co-transport
Tubular fluid is isotonic to plasma despite reabsorption
Secretes H+ and accounts for most bicarbonate reabsorption
What is permeable in the descending limb?
low permeability to ions
moderate permeability to urea
highly permeable to water
What occurs at the tip of the LOH?
Tubular fluid here is always maximally hyperosmotic to plasma and is not hormone sensitive
What are the characteristics of the Thick Ascending Limb?
Na+-K+-Cl- cotransporter
sensitive to the diuretic furosemide (lasix)
impermeable to H2O, reabsorbs solutes
considered the diluting segment
Macula densa located here
What are the characteristics of the DCT?
NaCl cotransporter
site of hormonally regulated K+ secretion
the intercalated cells of this region secrete H+ and make new bicarbonate
thiazide sensitive
What occurs in the colllecting duct when ADH levels are high?
The osmolarity of the urine is about the same as the osmolarity at the tip of the LOH
reabsorb alot of water
