5 Water Balance Flashcards
Q: What is osmolarity? to do with? Depends on?
A: measure of the solute concentration in a solution (osmoles/liter; 1 Osmole = 1 mole of dissolved solutes per liter)
to do with number of particles
depends on the number of dissolved solutes present (The greater the number of dissolved particles, the greater the osmolarity)
Q: Compare plasma and urine osmolarity.
A: plasma = homeostatic set point = maintained at 285/295 mOsmol/L
urine= wide range from hypoosmolar (lower particle content) to hyperosmolar (depends on conditions)
Q: How does water move in terms of osmolarity?
A: Water flows across a semi permeable membrane from a region of low osmolarity to a region of high osmolarity
Q: How can osmolarity be increased? Decreased? What kind of system is this?
A: increased salt
decreased salt
variable osmolarity system that we don’t have
Q: What kind of osmolarity system do we operate under? When do we increase volume? Decrease volume?
A: constant osmolarity
increased salt (would need to increase water to maintain osmolarity)
decreased salt (would need to decrease water to maintain osmolarity)
Q: On average, how does the water we consume compare to water and salt we need to replace? Therefore we must get rid of? (3)
A: On an average day we consume 20-25% more water and salt than we need to replace that lost
- Must get rid of the excess volume (or we will expand)
- Must get rid of any excess water (To keep osmolarity up, or we will expand)
- Must get rid of any excess salt (to stop osmolarity going too high)
Q: What’s the most abundant component of plasma? Most prevalent solute? figure? Where are these 2 answers also correct?
A: water
Na, around 140mmol/L out of 285-295mmol/L
ECF
Q: Why do we balance water? Why do we regulate salt levels?
A: to regulate plasma osmolarity
determine ECF volume
Q: How is our total body water content split? (5) How many litres do we roughly contain?
A: total= around 40L
65% = intracellular fluid compartment (35L)
35% = extracellular compartment (15L)
- interstitual
- plasma
- lymph
- transcellular (cerebrospinal fluid etc)
Q: What’s the main content difference between intracellular fluid and extracellular? (2) 2 examples of extracellular fluid? Main differnece?
A: more phosphate in cells, more chloride outside of cells
more protein in plasma than interstitual fluid
Q: How do we get rid of water and how does each method vary? (4) How much is lost on average via each method?
A: Skin and sweat: variable but uncontrollable
Normally about 450 mls/day - changes with fever, climate and activity
Faeces: uncontrollable
normally about 100 ml/day - Diarrhoea up to 20L/day with cholera
Respiration: uncontrollable
350mls/day - changes with activity
Urine output: variable and controllable
1500 mls/day - largest component
Q: Outline water movement in a nephron. (5) Where does regulation occur? concentration effects also occur where?
A: -lots absorbed in proximal tubule- 30% of input remains
- some movement in descending LoH
- none in ascending LoH
- some in distal CT- left with 20% of input
- water movement in collecting tubule- left with <1% to 10% of the original input
collecting duct, LoH
Q: How does medulla size relate to urine concentration? Example?
A: size affects conc
kangaroos have large medulla to cortical ratio
Q: How does water move? Problem? Solution? How does this present itself in real life?
A: by osmosis
can’t pump
produce region of hyperosmolar interstitual fluid
-as a gradient from cortex->outer medulla->inner medulla (low osmolarity->high)
Q: Osmolarity gradient from cortex to outer to inner medulla. What are the 4 components involved?
A: 1. countercurrent between desc and asc limb- as water comes done desc, water will leave
- cells of desc limb don’t do significant amount of active transport- don’t have many mitochondria but are permeable to water as tight junctions are not that tight
- bottom of LoH is permeable to urea
- thick asc limb has high number of mito and active transport capacity- include triple transport pump of Na, K and Cl entering
Q: Osmolarity gradient from cortex to outer to inner medulla. How is it established? (7)
A: UNIFORM POSITION
- gradient at top of asc limb= made 200mmol/L across membrane (all way down) by pumping Na and Cl out of cells
- descending limb re equibrilates as a result by water moving out -> have 400mmol/L in middle
- tubular fluid enters (around 300mmol/L) and you get some movement of water from tubules to outside until similar osmolarity
- asc limb is still pumped salt out to give gradient across wall -> make 200mmol/L at top of asc limb, then get 350mmol/L just below
- REPEAT -> can generate much higher concentration lower down asc limb -> 500mmol/L
- -> get 600mmol/L at bottom then slightly higher concentration than normal at tpop = 305mmol/L
- keep getting higher osmolarity at lower parts of asc limb than high parts of asc limb
GRADIENT ONCE ESTABLISHED
Q: What parts of the nephron are permeable to urea? (2)
A: lower part of collecting duct and tip of LoH
Q: Describe the loop movement of urea. (5)
A: 1. water leaves desc limb of LoH but urea does not = increases concentration of urea in tube
- as more water leaves the top of the collecting duct= urea concentration increases even more
- urea concentration is high enough to move out of tubeles
- concentration of urea is higher in medulla than tip of LoH
- movement of urea back into LoH tip
Q: Name 4 urea channels are list where they are.
A: UT-A1 and 3 are in collecting duct
UT-A2 in descending limb
UT-B1 in descending vasa recta (series of straight capillaries in the medulla that lie parallel to the loop of Henle)
Q: What happens when there are a lack of UT-A1 and 3 receptors in mice? (4)
A: reduced urea in medulla (less urea can move from CD to it)
severe reduction in ability to concentrate urine
increased water intake by 20%
no ability to reduce urine output if water restricted for 24h
Q: What happens when there are a lack of UT-A2 receptors in mice? When are the effects observed?
A: very mild phenotype
only observed on low protein diet (less protein and nitrogen)
Q: What happens when there are a lack of UT-B receptors in mice? (3)
A: increased urine production
reduced urine concentrating ability
weight loss
Q: Describe problems in urea transporters in humans. (3)
A: no UT A1 or 3 mutations have been seen
Point mutations in UT-A2 have been observed: Reduced blood pressure (getting rid of more water)
Loss of function mutations in UT-B are observed: Reduction in urine concentrating ability
Q: What determines a species ability to create a urine osmolarity?
A: Na/K ATPase activity (not size/length of LoH)
Q: We need to provide nutrients, oxygen and glucose to cells at the bottom of the LoH. How does blood get there without removing the established salt gradient created? Explain. (4)
A: make vasa recta completely permeable to salt and water- Blood flow in the vasa recta is another counter-current
- Permeable to water and solutes.
- Water diffuses out of descending limb and solutes diffuse into descending limb.
- In the ascending limb the reverse happens.
- Thus oxygen and nutrients are delivered without loss of Gradient.
Q: How do we get variability in the amount of solute we produce?
A: variability comes from vasopressin /ADH that acts on collecting duct
Q: How large is vasopressin? What is it derived from? What is specific about its synthesis? (2) Secreted from? Stimulated by? (2) What does it act on? (3)
A: Peptide hormone
(9 amino acids)
Derived from a single transcript that also encodes neurophysin II and copeptin
- Synthesised (transcribed and processed) in the hypothalamus
- Packaged into granules
Secreted from the posterior pituitary (neurohypophysis)
In response to increased osmolarity or reduced volume
Binds to specific receptors (V2) on basolateral membrane of principal cells in the collecting ducts, some V1 in vasculature and has some neurological effects too
Q: What does ADH do when it acts on the collecting duct?
A: Causes insertion of water channels (aquaporins) into the cells membranes, hence increasing water permeability (predominantly AQP2 into the luminal membrane).
Also stimulates urea transport from IMCD into thin ascending limb of loop of Henle and interstitial tissue by increasing the membrane localisation of UTA1 and UTA3 in the CCD
Q: What stimulates ADH release? (2) What inhibits release?
A: -Plasma osmolarity is normally 285 - 295mosmol/L;
- ADH release regulated by osmoreceptors in the hypothalamus (if osmolarity rises above 300mOs = triggers release)
- Also stimulated by a marked fall in blood volume or pressure (monitered via baroreceptors or stretch receptors)- need to limit water loss
- Ethanol inhibits ADH release, which leads to dehydration as urine volume increases
Q: Split the nephron into 3 parts based on water permeability.
A: till tip of LoH = permeable
till mid distal CT = impermeable
rest = ADH dependant water movement
Q: What happens with water load? (sequence-6)
A: decreased plasma osmolarity
hypothalamic osmoreceptors lose triggering
ADH release decreases
collecting duct water permeability decreases
urine flow rate increases
increased fluid loss will tend to raise plasma osmolarity
Q: What levels of ADH cause diuresis? How? (3) Describe the osmotic gradient.
A: (diruesis= increased or excessive production of urine)
low ADH
-solute reab
-no water reab
= lower urine osmolarity to 50mosmol/L
urea is not moved out of bottom= don’t generate as high an osmolatity gradient
Q: What happens with dehydration? (sequence-7)
A: plasma osmolarity increases
increased hypothalamic osmoreceptors triggering
increased ADH release//
become more thirsty (increased water intake will tend to lower plasma osmolarity)
increased collecting duct water permeability
decreased urine flow rate
decreased fluid loss will tend to lower flow rate
Q: What levels of ADH cause maximal antidiuresis? Result? Describe the osmotic gradient.
A: high ADH
small vol, conc urine
higher osmotic gradient than water diuresis as it is now permeable to urea
Q: Summarise ADH production and response.
A: hypothalamus, in response to plasma osmolarity, releases ADH
sends FB signals to reduce to photos etc
Q: What keeps plasma osmolarity in a normal range? What else does this do? (2)
A: feedback control via ADH keeps plasma osmolarity in normal range
and determines urine output and water balance
Q: What can cause disorders of water balance? (3) Consequence? What do they all result in? (2) Condition?
A: No / insufficient production of ADH
No detection of ADH (mutant ADH receptor/non functioning)
No response to ADH signal (mutant aquaporin/doesn’t translocate)
= won’t reabsorb water into medulla out of tubule and as a result…
- Excretion of large amounts of watery urine (as much as 30 litres each day)
- Unremitting thirst
diabetes insipidus
Q: What does the loop of henle establish? What does ADH control? doesn’t determine?
A: Loop of Henle establishes concentration gradient of Na and Cl in medulla
-ADH keeps ECF osmolarity in tight range by controlling water reabsorption (but does not determine ECF volume).
