L18 Flashcards
what % of the body is water
The body is around 60% water (60% - men; 55% - women)
what is the most important function of the kidney
Water homeostasis is therefore one of the most important functions of the kidneys.
what is the kidneys role in water homeostasis
Any increases in body water (decreased osmolarity) - need to increase excretion of water by kidneys eg in a high water iet we will urinate a lot more water
Any decreases in body water (increased osmolarity) - need increase reabsorption of water by the kidneys
how is body water/osmolarity monitored (what reflex)
and what detects that change
This is monitored by the theist reflex which occurs when the body sensors changes in the body.
This is detected by osmoreceptors and baroreceptors (BP).
where are the osmoreceptors located
In the kidney the juxtergolmerior apporatis and the maculardencer cells have osmoreceptor function
Hypothalamus also has osmoreceptors
where are the baroreceptors located
Baroreceptors in the the carotid arch and in the aortic sinus
in water homeostasis, water intake = water output. what does this mean in terms of net flow
net flow = 0 (normally)
what factors can effect water homeostasis
menstruation, vomiting and diarrhea
what is the equation of water excretion in the nephron
H2O excreatin = H2O filtered - H2O reabsorbed
Which segments of the nephron ARE permeable to H2O?
Proximal Tubule
Thin Descending Limb of Loop of Henle
Late Distal Tubule*
Collecting Duct*
- Under influence of Vasopressin (AVP)/ Antidiuretic Hormone (ADH)
Which segments of the nephron are NOT
permeable to H2O?
Ascending Limb of Loop of Henle (Thin and Thick)
Early Distal Tubule (there is still debate about this)
Which segments of the nephron ARE permeable to H2O under the influence of a hormone (and what hormone is it)
Late Distal Tubule*
Collecting Duct*
- Under influence of Vasopressin (AVP)/ Antidiuretic Hormone (ADH)
Which of the following statements is TRUE?
A. 65% of a male’s body is composed of water.
B. Normally, a person has 4 litres of plasma in their blood.
C. The net water intake and water output of person per day is 0.
D. A person can live without water for 3 months.
A. should be 60%
B. should be 3L
C is correct
what is the proximal tubules mechanism for water movement
Moves through peri and transcellular pathway
what is the Membrane shuttle hypothesis and freeze fracture technique
(the discovery of how water was reabsorbed)
It was assumed that water ‘leaked’ through the cell membrane.
But the very rapid movement of water through some cells was not explained by this theory (too fast to be osmosis)
Membrane shuttle hypothesis – James Wade (1980). he used Freeze fracture microscopy. This is where you froze membranes and then snapped them apart to see what was in them. He found vesicles moving towards a membrane
Presence of water channels (aquaporins) in cells discovered by US
scientist Peter Agre and his team (1988).
what are aquaporins
A family of plasma membrane proteins that form channels permitting a high rate of water flow (Higher rate then just by simple diffusion).
where are AQP found
Found in organisms as diverse as bacteria, plants and animals.
how do AQP allow for water movement
Specific for H2O, single-file movement through pore.
what are AQP impermeable to
how many different types of AQP are there
Impermeable to charged species. Therefore some of the 13 different AQ let other uncharged ions through as well
how many liters of water does the proximal tubule receive per day
Receives 180 L H2O per day
same as daily filtered load
how many liters of water does the proximal tubule reabsorbe per day
Reabsorbs 2/3 of this amount (120 L/day)
67% of the filtered load of H2O
what kind of epithelium is the proximal tubule made up of and what does that allow for
Leaky absorptive epithelium
Paracellular and Transcellular movement of H2O
what kind of AQP is located in the proximal tubule
Aquaporin 1 (AQP1) Transcellular movement of water
Present in both apical and basolateral membranes
how many liters of water does the thin descending limbs of henle receive per day
Receives 60 L H2O per day
what kind of epithelium is in the thin descending limb
Leaky absorptive epithelial cells
how much water does the thin descending limb reabsorb per day
Leaky absorptive epithelial cells of Thin Descending Limbs reabsorb about 30 L of H2O per day
(16% of the filtered load of H2O)
how does reabsorption of water occur in the thin descending limb
Reabsorption occurs via AQP1 in both apical
and basolateral membranes
how much water does the thin and thick ASCending limbs reabsorbe
NONE!! they are impermeable to water
what do the thick and thin ascending libs play an important role in
the concentration of urine
how many liters of water does the late distal tubule receive per day
Receives 30 L H2O per day
what kind of epithelium is located in the late distal tubule
Tight absorptive epithelium
how much water does the late distal tubule reabsorbe per day
Tight absorptive epithelium of Late Distal Tubule reabsorbs 10 – 20 L H2O each day
(~5-10% of the filtered load of H2O)
in the late distal tubule what is water reabsorption regulated by
ADH and aquaporin 2,3,4
Reabsorption regulated by vasopressin (AVP) also called antidiuretic hormone (ADH)
The distribution of AQPs is the same as the Collecting Duct (AQP2 in apical membrane and AQP 3 and 4 in basolateral)
what AQP are in late distal tubule and collecting duct.
where are they located
AQP2 is associated with apical membrane
AQP3 and AQP4 are associated with basolateral membrane
how many liters of water does the collecting duct receive per day
Receives 10 - 20 L H2O per day
what kind of epithelium is located in the collecting duct
Tight absorptive epithelial cells
how much water does the collecting duct reabsorbe per day
Tight absorptive epithelial cells of the Collecting Ducts reabsorb about 15 L per day – ‘fine-tuning’
(~8% of the filtered load of H2O)
what is water reabsorption regulated by in the collecting duct
Water reabsorption is regulated by vasopressin (AVP) also
called antidiuretic hormone (ADH)*
also AQP 2,3,4
what are the 2 major cell types in the collecting duct
Principal cells (NaCL and K transport
Intercalated cells is for H+ and K+ balance
If you had diabetes you would absorbed very little water in what area of the nephron
collecting duct
order the AQP from smallest to largest
AQP1,2,3,4
how many membrane domains do AQP have
6
where are the different AQP located in the nephron
1 = PT and TDL
2 and 3 = LDT and CD
4 = LDT and CD (and PT in mise)
what membranes are the AQP located in
1= apical and basolateral
2 = apical
3 and 4 = basolateral
is AQP 1 regulated by ADH
no
which APQ does ADH have short and long term effects on
2 = short and long term
3 = short term (mRNA) and long term
4 = short term (mRNA) but NOT long term
Which of the following statements is TRUE?
A. Aquaporins are only found in animals.
B. AQP2 is located on the apical membrane of Thick Ascending limb cells.
C. AQP3 is located in the basolateral membrane of collecting duct cells.
D. An osmotic gradient is NOT required for water movement
A. found in lots of things
B. ascending limbs are NOT permeable to water
C is correct
where is ADH produced
Produced in hypothalamus
- paraventricular nuclei
- supraoptic nuclei
what stimulates ADH to be released
Increased body osmolarity (osmoreceptors)
Decreased plasma volume (baroreceptor reflex)
where is ADH stored and released from
Stored and released from the posterior pituitary
what kind of hormone is ADH/AVP
a peptide hormone therefore it is hydrophilic and will need to bind to a membrane receptor
where does ADH act on the nephron
• Late Distal Tubule and the Collecting Duct
what is the name of and where is the vasopressin receptor located
• vasopressin binds to V2 receptor on basolateral membrane
once ADH has bound to the V2 receptor what happens intracellularly
• activates Adenylate Cyclase which
increases cAMP levels
cAMP activates Protein Kinase A (PKA)
phosphorylation leads to sub-apical AQP2
vesicles moving to membrane via exocytosis
• increased Apical membrane H2O permeability
THEREFORE ONLY AQP2 IS REGULATED BY ADH!!!!!
how long does it take to get significantly more AQP into the membrane
Within 45 min then you can get more vesicles in the apical membrane
what does ADH regulate
ONLY AQP2
make sure you know the membrane shuttle hypothesis
pores are sitting in vesicles under the membrane and when they get phosphorylated they move into it
The amount of AQP2 can be correlated with
certain physiological conditions
What would happen to water reabsorption if there were too few AQP2 channels?
diabetes
when could you get too many AQP2 channels would lead to?
Upregulated in congestive heart failure
When you are pregnant you have an increase in weight gain and water inside the body
what is Diabetes Insipidus (DI)
Disease characterised by excessive urination
20-30L of urine per day
there are 2 types of Diabetes Insipidus (DI). what are they
Neurogenic (Central) Diabetes Insipidus
Nephrogenic Diabetes Insipidus (Kidney)
what is Neurogenic (Central) Diabetes Insipidus
Failure to produce or secrete vasopressin
to do with the release from the posterior pituitary. you still make in/is sensed that you need to make it in the hypothalamus but for some reason it is never released
what is Nephrogenic Diabetes Insipidus (Kidney)
could be because of a …
Mutation of AQP2 channel
Mutation of V2 receptor
what is bulk reabsorption of water carried out by
AQP1 in the PT
fine tuning of water reabsorption is carried out by…
AQP2,3,4 in the LDT and CD
