renal transport mechanism Flashcards
1
Q
what happens after filtration ?
A
at peritubular capillaries
the body will reabsorb whatever it needs back into the peritubular capillary
and what will secrete what it doesnt need into tubular fluid be excreted out
2
Q
what is the main purpose of modifying this ultrafiltrate ?
A
Reabsorption most important process
3
Q
describe reabsorption ?
A
Happens at large quantities
HIGHLY SELECTIVES
around 180 liters a day is filtered in the kidney —> Glomerular filtration
Plasma will undergo ultra filtration in the glomerulus
The filtrate will get collected in BOWMANS CAPSULE
this will continue as the TUBULAR FLUID in the kidney tubule FOR MODIFICATION by reabsorption of wanted substance and excretion of excess of unwanted substances
lastly the modified is the passed into collecting duct to get excreted
4
Q
compare the courses of reabsorption and secretion?
A
Reabsorption :
Stuff will go from tubular lumen to PERItubular capillary
Secretion :
Stuff will go from the PERITUBULAR capillary to tubular lumen
5
Q
what substances gets completely reabsorbed ?
A
glucose
amino acids
nothing goes to urine
6
Q
what substances are highly reabsorbed ?
A
Sodium
chloride
Bicarbonate
but the rates of their reabsorption are variable and depend on the needs of the body
For example if someone intakes a lot of sodium more will be excreted
7
Q
which substances are poorly reabsorbed ?
A
Waste products
Urea and creatinine
creatinine is end product of muscle metabolism and freely filtered at the glomerular filtration and then is neither reabsorbed nor secreted so its simply excreted out
8
Q
what is secreted in tubulars ?
A
significant amount of :
POTASSIUM IONS ( K )
Hydrogen ions
few other substances that appear in urine
9
Q
What is special about potassium ions filtration ?
A
Kidney can either :
Absorb
or
Secrete it
this doesnt happen to all solutes/ions
10
Q
how is tubular reabsorption happens?
A
Reabsorption of filtered water and solutes
FROM the tubular lumen across the tubular epithelial cells
through the renal interstitium
back into the blood
Solutes are transported by through cells ( transcellular path ) by :
1- Passive diffusion
2- Active transport
OR
between cells ( paracellular path ) by :
1- Passive diffusion
11
Q
how is water transported through cells and between the tubular cells ?
A
Osmosis
12
Q
how is water and solutes transported from the Interstitial fluid into Peritubular capillaries ?
A
Ultrafiltration ( BULK FLOW )
13
Q
what are the characteristics of active tubular reabsorption ?
A
ATP energy is used
Against concentration gradient
14
Q
what are the characteristics of passive tubular reabsorption ?
A
No energy is used up
Along concentration gradients
some substances can move by simple diffusion without ATP and pumps
15
Q
what are the 2 active transport mechanisms ?
A
in active transport pumps are used to push substances against gradient using ATP
Primary : Direct use of ATP
- Na/K atpase pump ( NOKIA, Na out and K in )
Secondary : Energy due to the movement of ions
- Mainly Na/Glucose and AA/GLUCOSE -> sodium dependent
16
Q
whats transcellular ?
A
Go from one side to the other side by passing THROUGH :
Luminal membrane then
Inside the cell then
Basolateral membrane then
Interstitial fluid then
Peritubular capillary
COULD BE ACTIVE OR PASSIVE OR SIMPLE OR FACILITATED OR PINOCYTOSIS
17
Q
What is paracellular ?
A
Goes from the side to the other side by going through :
Tight junctions between the cells
follows the concentration gradient
18
Q
what happens to the substances that accumulate in interstitial fluid ?
A
they go into blood through process known as :
BULK FLOW/ SOLVENT DRAG
regulated by hydrostatic and oncotic forces
19
Q
what are the primary active transporters in kidney?
A
Sodium potassium atpase
Hydrogen atpase
Hydrogen potassium atpase
Calcium atpase
20
Q
what are the secondary active transporters ?
A
Coupled indirectly to the energy source such as :
ion gradient :
Na-glucose co transporter
Na-H counter transport in luminal membrane of PCT
Explain more : When sodium and potassium are moved around through Na/K atpase creating a gradient ( Low Na inside the cell )
This will result in Na easily moving from the filtrate ( urine ) into the cell as a gradient has been established
on the luminal surface we have co transporters to which sodium will attach to :
Na+ is moving downhil following other nutrients ( Glucose, AA,etc)
these nutrients travel upHILL through secondary active transport
21
Q
how do you measure filtered load?
A
Glomerular filtration rate X plasma concentration
22
Q
how do you measure excretion rate?
A
Urine concentration X urine ml/min
23
Q
how do you measure Reabsorption or secretion rate?
A
Filtered load - Excretion rate
24
Q
when is a substance is net reabsorbed?
A
Filtered load is higher than excretion rate
So less is excreted than filitered
like sodium
25
when is substance is net secreted?
when filtered load is LESS than excretion rate
so more is excreted than in filtered load
like para aminohippuric acid
26
which part of the nephrons has the highest capacity of reabsorption and secretion?
Proximal convoluted tubule
65% of filtered load of Na and K, HCO3 and CL is reabsorbed
27
what happens to Na along the proximal convoluted tubule ?
the amount of Na decrease because its getting reabsorbed
BUT THE CONCENTRATION and OSMOLARITY
because the water is also being reabsorbed as well so i balances out
water is reabsorbed by osmosis
28
what substances are reabsorbed in PCT?
Glucose and AA
29
what substances are excreted in PCT?
organic acid like bile salts
oxalate
Urate , etc
bases
H
PAH
30
what ion is needed for effective reabsorption of glucose and amino acids?
Sodium
IF nephrons are defective in NA reabsorption ---> Glucose and AA reabsorption will be defective as well
31
how is water reabsorbed ?
osmosis
happen through both paracellular and transcellular
transcellular --> aquaporins
32
what is the characteristic of tubular fluid at the end of PCT?
isosmotic
because we are effectively reabsorbing solutes and an equal amount of water
33
describe what happens in early proximal convoluted tubule ?
Active reabsorption of SOIDUM occur by :
Na-K atpase pump on the basolateral membrane (leading to less sodium inside the cell )
due to this :
Concentration gradient is established and -70
potential attracts sodium ( CUZ now we have less sodium )
THEN ON THE LUMINAL SIDE :
Secondary active transport-cotransport :
Sodium will move into the cell (Cuz gradient made by the primary Na/K pump ) ALONG THE ELECTROCHEMICAL GRADIENT BY FACILITATED DIFFUSION
Whereas glucose, AA, phosphate citrate and lactate move AGAINST their electrochemical gradient (along NA using the Na gradient ) at the luminal surface
Counter transport :
Sodium moves into cell whereas H moves out of the cell ( H to luminal and Na to basolateral )
once the substances like glucose and AA build up inside the cell leading to increased amount inside the cell = LEADING to them leaving the cell through basolateral membrane , they move into intersititial fluid then to blood
34
how is bicarbonate is reabsorbed in PCT?
Depends the counter transport in early PCT :
where Na is pumped and H is secreted to the lumen
This transporter is responsible for reabsorbing bicarbonate indirectly
the hydrogen will combine with filtered bicarbonate ( which was the filtered in bowmans capsule ) TO FORM CARBONIC AICD
carbonic acid will split into carbon dioxide and water by CARBONIC ANHYDRASE
Carbone dioxide and water enter the cell where they are converted into carbonic acid by carbonic anhydrase again
it dissociate to form hydrogen and bicarbonate
Hydrogen is excreted back through the brush border
Bicarbonate gets transported into Blood by NA/HCO3- CO transporter or CL/HCO3 anti transporter
35
describe what happens in late proximal convoluted tubule ?
at midpoint of PCT
100% of glucose reabsorbed
85% of bicarbonate reabsorbed
phosphate, lactate, citrate and sodium is reabsorbed
so most of the substance have been reabsorbed
the remaining fluid in PCT has HIGH CHLORIDE CONCENTRATION + urea
Chloride concentration is very low inside the cell = ions will move along the concentration gradient through an anti porter on the LUMINAL MEMBRANE via TRANSCELLULAR
Cl is also reabsorbed paracellularly along NA
36
how does reabsorption of chloride ions aid the reabsorption of sodium?
chloride ions are negative
reabsorption of chloride ion from the filtrate increase the + lumen charge as the negative charge of chloride is being removed
Eventually + charge develops in the lumen
sodium is also + charge
so the + charge pushes the + charge so it gets pushed from the lumen to the blood
37
what are 2 types of sodium ?
Positive sodium balance
Negative sodium balance
38
what happens to + sodium?
+ sodium intake is
Higher than
Excretion
LEADING TO EDEMA CUZ WATER FOLLOWS and retention
39
what happens to - sodium?
Negative sodium intake
is LESS than
Excretion of sodium
leading to ECF volume contraction cuz fluid is lost
40
describe what happens to Na in the nephron ?
most of reabsorption of NA happens in PCT
PCT=67%
DCT=5%
thick ascending limb=25%
Cortical CT=3%
99.4% is reabsorbed and 1% is excreted
Na+ reabsorption decreases as we go towards the end of then nephron as you would have already reabsorbed a lot before
we dont have specific transporters for sodium so we cant say they got satured
For sodium , its movement depends on how much is present
by the time it does reach the end of the nephron , we need something to help us reabsorb sodium ---> ALDOSTERONE
this will mainly target the late distal convoluted tubule and the cortical collecting duct as they have similar functions
41
describe the net reabsorption of NA+ isosmotic reabsorption?
1-
Na ions will diffuse down the electrogradient chemical established on the luminal side due to the low intracellular sodium concentration due to the action of Na/K atpase on the basolateral membrane ( the other side )
The filtrate has HIGH concentration of Na ions, this difference form the gradient
2-
Due to the action of Na/K atpase pump on the basolateral membrane ( 3 na out and 2 K in )
this movement of the sodium will drag water with it so water moves out of the cell
3-
The water moving with Na to the interstitial space will make the bulk diffusion or ultrafiltration process
Ultrafiltration will result in absorption of sodium , water and others into the peritubular capillaries
this process is favoured by the peritubular oncotic pressure therefore HIGH capillary oncotic pressure favors ulttrafiltration or bulk diffusion
67% of solutes and water are reabsorbed
42
what are the mechanisms by which water , chloride and urea reabsorption are coupled with sodium reabsorption?
1- Sodium reabsorption also results in passive reabsorption of chloride ions and urea because as sodium (+) is being reabsorbed , the lumen becomes more negative and Chloride is - and negative pushes negative this negative lumen will passively reabsorb chloride ( gets pushed )
2- Sodium reabsorption also results in water reabsorption ( ISOSMOTIC REABSOPRTION ), This increases the concentration of both urea and chloride ( cuz water is going down ) so this will make chloride and urea move passively to be reabsorbed
so we have 2 mechanisms for chloride by either charge or concentration
1 mechanism for urea ( concentration )
43
what happens when we change ECF volume ?
ECF volume change = change in osmotic reabsorption in PCT
44
what are the main regulatory forces controlling ECF volume?
Starling forces in peritubular capillaries
( oncotic and hydrostatic , etc )
leading to 2 events : ECF VOLUME EXPANSION, ECF VOLUME CONTRACTION
45
describe ECF volume expansion ?
expansion = increased volume of blood
increase in blood volume = dilution in the plasma proteins
Leads to decreases the plasma protein concentration
leading decreased capillary oncotic pressure decreases ( cuz low protein, force pulling the water in is less in the capillary )
Leading to increases HYDROSTATIC PRESSURE in capillaries ( cuz high volume , force pushing the water to the tubule is high )
THEREFORCE leading to REDUCED absorption ( cuz these forces oppose absorption )
46
describe ECF volume contraction?
Contraction = low volume
Low volume in ECF
low volume = higher concentration of proteins
leading to increased capillary oncotic pressure ( cuz higher protein ) = more fluid is reabsorbed in
Leading to decreased hydrostatic pressure in capillary ( cuz low volume ) = less fluid is being pushed
this results in HIGHER ABSOPRTION RATE CUZ THESE AID REABSORPTIONS
during hypovolemia ,RAAS system is activated and promotes reabsorption by stimulating Na/H exchanger which will result in reabsorption of sodium followed by water
47
describe what happens in thin descending segment?
the thin descending segment is HIGHLY permeable to water
20% of water is reabsorbed
Moderately permeable to sodium and urea and most other solutes
48
why is the tubular fluid becomes progressively hyperosmolar in thin descending segment ?
Because we are moving more water than sodium and urea here
the tubular fluid progressively become more concentrated with solutes as it moves through the segment ( cuz water is being absorbed at higher rate than solutes )
by the end of the thin descending segment , the tubular fluid becomes hyperosmolar ( high solutes )
49
what happens in thin ascending segment ?
it is IMPERMEABLE to water ( no water flees )
Permeable to solutes ( solutes leaves )
50
why is the tubular fluid hypo osmolar ?
because in this section
the solutes are absorbed but the water is not this results in the tubular fluid having less and less solutes = hypoosmolar
51
what happens in the thick ascending segment ?
25% of reabsorption of filtrate takes place
ions such as sodium , chloride, potassium. calcium, bicarbonate, magnesium are reabsorbed
Secretion of hydrogen ions take place in THE THICK ASCENDING SEGMENT
52
describe what happens in THICK ascending limb of loop of henle?
On the BASOLATERAL MEMBRANE :
Na/K atpase pump there ( 3 na out, 2 k in )
This leads to LOW concentration of sodium inside the cell ----> CELL BECOMES HIGHLY NEGATIVE ( CUZ ITS LOSING + SODIUM )
- We have Na/CL/K co transporter ( NKCC cotransporter ) ---> ON THE LAMINAL SIDE
this pump helps reabsorb these ions
once they become inside the ion ( Na/CL/K )
they will leave through channels ( EXCEPT FOR NA WILL LEAVE THROUGH ATPASE ) to enter the capillaries
Sodium also gets reabsorbed by Na/H exchanger
for this special co transporter --> Simple math would indicate that an equal number of cations and anions are being exchanged
However K ions LEAK back into the lumen
This gives slightly increased POSITIVE CHARGE IN THE LUMEN ( cuz K is + )
this positive charge will favour the movement of Na , K , Mg2 and Ca2 THROUGH PARACELLULAR ROUTE ( between tight junctions ) resulting in their reabsorption ( cuz + pushes + )
Its impermeable to water so the tubular fluid loses solutes but not water = hypoosmolar
53
what is the first part of EARLY DISTAL TUBULE will do?
First part of early distal tubule will form :
Juxtaglomerular apparatus
this apparatus is IMPORTANT FOR autoregulation of GFR and RBF
54
whats the name of the part following the early distal tubule?
convoluted distal tubule
55
what is the function of convoluted distal tubule?
Responsible for :
Reabsorbing Na, K, Cl
it is IMPEREABLE TO WATER AND UREA ( THEY CAN BE REABSORBED )
DUE TO THIS IMPERMEABILITY :
The urine will now be more dilute ( Low solutes but high volume )
as we stated b4:
Na/K atpase pump on the basolateral side will form a gradient for Na
then the Na ions on the lumina side will move down the concentration gradient into the cell by Na,Cl CO TRANSPORTER
Early DT reabsorbs 5% of filtered sodium and chloride
56
compare the functions between loops of henle and distal tubule?
Thick ascending segment of loop of henle and EARLY distal tubule = same function
Late distal tubule and CORTICAL COLLECTING TUBULE = same function
but the medullary collecting tubule has different properties
57
describe the function of late distal tubule and cortical collecting duct (CORTEX ONLY NOT MEDULLARY CUZ MEDULLARY HAVE DIFFERENT FUNCTION )?
Principal cells :
Na and water reabsorption, Secretion of K
it can be altered and affected by aldosterone ( it may enhance the effects of the pump, leads to increase Na reabsorption and K secretion ), ( Also increases the permeability of sodium on the luminal membrane )
-normally only 3% of filtered sodium is reabsorbed here
keep in mind if you increase the Na + being pumped out , u will increase K being pumped IN
along with Na reabsorption CL reabsorption take place as well
58
What is the effect of ADH on principal cells?
Increase the permeability of principal cell to water
High ADH = water reabsorption increases
Low/Absent ADH = water reabsorption decreases
ADH bind to specific receptors ( V2 receptors )
binding results in a cascade of events that results in EXPRESSION OF AQUAPORIN 2 (aqp 2) on the luminal site of the cell
Expression of AQP2 increases water reabsoprtion
59
what are the 2 types of intercalated cells?
A and B
60
what is the function of Type A intercalated cells?
Important for eliminating hydrogen ions WHILE reabsorbing bicarbonate in ACIDOSIS ( A= ACIDOSIS )
they help in elimination of H ions and reabsorption of bicarbonate ions
one hydrogen is secreted by the cell and is followed by absorption of bicarbonate ion ( 1:1)
the process goes as follows :
-Cell takes up CO2
-Then combined with water to form carbonic acid
-The carbonic acid dissociates into bicarbonate ions and hydrogen ions
-the hydrogen ion will be secreted out of the cell into lumen by one of 2 mechanisms :
1- H/K atpase
2-H atpase
The bicarbonate ions will then be reabsorbed in exchange for Cl ions through CL/HCO3 exchanger
K is now reabsorbed in the type A intercalated cells through specific channels in the basolateral membrane
61
Describe the function of TYPE B intercalated cells?
Type B intercalated cells have opposite function A cells
secrete bicarbonate into tubular lumen and reabsorb in Hydrogen ions in ALKALOSIS ( B = ALKALOSIS )
K ions are secreted from the cells
the only thing that remains the same is formation of carbonic acid
the protein channels have swapped side ( instead of H atpase and H/k atpase being on the luminal side they become basolateral to reabsorb H )
and the Cl/HCO3 will be on the luminal side instead of basolateral to secrete HCO3 outisde
62
describe the function of medullary collecting tubule?
Final urine processing site
determines the final urine output of water and solutes
reabsorption of less than 5% -10% of sodium and water occur here
the reabsorption of water here is controlled by the level of ADH
high levels of ADH = more water reabsorbed = less urinary volume formed , solutes will be highly concentrated
unlike the cortical tubules the medullary collecting duct is PERMEABLE to urea
Urea is reabsorbed into the interstitium by the urea transporter and this is important for raising the osmolarity of the interstitium and overall helping the kidneys overall ability to form concentrated urine
The medullary collecting duct can secrete hydrogen ions into the tubule AGAINST a concentration so they are playing a role in acid base regulation
63
summaries the function of early proximal tubule?
Isosmotic reabsorption of solutes and water ( equal amount being absorbed )
by :
Na/Glucose, Na/AA, Na/phosphate co transport , Na/H exchanger
Affected by :
PTH inhibits Na/Phosphate cotransport
Angiotensis 2 , stimulates Na/H exchanger
Diuretic actions :
Osmotic diuretics
Carbonic anhydrase inhibition
64
summarize the function of late proximal tubule ?
Isosmotic reabsorption of solutes and water ( equal amounts )
by :
NaCl reabsorption driven by Cl gradient ( cuz most solutes has been reabsorbed in early )
Na, K , 2 Cl , co-transport
not affected by hormone
Diuretic actions : Osmotic diuretics
65
summarize the function of Thick ascending limb of loop henle?
Reabsorption of NaCl WITHOUT WATER ( impermeable to water )
Dilution of tubular fluid ( solutes is lost and water stay )
single effects of countercurrent multiplications
Reabsorption of Ca and Mg driven by lumen positive potential ( cuz K is leaking out to the lumen)
by :
Na K 2Cl co transport
Hormone effect :
ADH stimulates Na/K/2CL cotransport
Diuretic action :
Loop diuretics
66
summarize the function of early distal tubule ?
Reabsorption of NaCl without water ( impermeable )
Dilution of tubular fluid
by :
Na-CL co-transport
Hormone actions :
PTH stimulates Ca reabsorption
Thiazide diuretics
67
Summarize the actions of Late distal tubule and Collecting ducts ( PRINICIPAL CELLS )?
Reabsorption of NaCL
K secretion
by :
Na channels ( ENAC)
K channels
Variable water reabsorption
affected by :
Aldosterone stimulates Na reabsorption
Aldosterone stimulates K secretion
ADH stimulates water reabsorption
Diuretics :
K sparing diuretics
68
summarize the function late distal tubule and collecting duct A intercalated cells ?
Reabsorption of K and HCO3 and secretion of H
by :
H/K atpase, H atpase , CL/HCO3
AFFECTED BY :
Aldosterone simulates H secretion
Diuretics :
K sparing diuretics
B intercalated are opposite
69
describe the the action of angiotensin 2 effect on PCT?
ang 2 potent sodium retaining hormone, formed in response to low bp, low ecf, low sodium chloride levels
acts mainly on PCT, loop of henle, Distal tubule , collecting tubule
work by :
Stimulating Na/H exchanger on the luminal membrane
Stimulates Na/K atpase pump on basolateral side
Na/HCO3 cotransporter on the basolateral membrane
This increases the overall reabsorption of sodium and reabsorption of water as well
this will help return the blood pressure and ECF volume
stimulates release of ADH which also increases sodium reabsorption
Constriction efferent arteriole, increasing GFR and reducing the hydrostatic pressure in peritbular capillaries ( which are after the efferent when we constrict efferent arteiroles less blood reaches the peritubular capillaries )
since increased resistance , decreases blood pressure and these 2 effects favor filtration and reabsorption
70
what is the site of action and effect of aldosterone ?
Site : collecting tubules and duct
Effect :
Increases NaCL and water reasborption
Increases K secretion
71
what is the site of action and effect of ang 2?
Site :
Proximal tubule , thick ascending loop of henle, distal tubule, collecting tubule
Effects :
Increases, NaCl , WATER reabsorption
Increases H secretion
72
what is the site of action and effect of ADH?
Site :
Distal tubule/collecting tubule and ducts
Effects :
Increase water reabsorption
73
what is the site of action and effect of ANP?
Site :
Distal tubule, collecting tubule and duct
Effect :
Decrease NaCl reabsorption
74
what is the site of action and effect of PTH hormone?
Site :
Proximal tubule , thick ascending loop of henle, distal tubule
EFFECT :
Decreases PO4 reabsorption
Increases Ca reabsorption
75
what results from high Na intake?
Decreases sympathetic activity : Dilation of afferent arterioles = increase GFR and decreased Na reabsorption
Increased ANP ( decrease Na reabsorption
Decrease NA reabsorption in PCT
Decreased RAAS system
76
What results from Low Na intake?
Increased Sympathetic activity :
Constriction of afferent , reduce GFR, increase reabsorption of Na
Decreased ANP ( increased Na reabsorption )
Increased Na reabsorption in PCT
Increased RAAS SYSTEM ACTIVITY
