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Question 1

What is the difference between osmolality and osmolarity?

Answer 1

Osmolality: measure of the number of osmotically active particles per kg of H2O
Osmolarity: number of osmotically active particles per litre of total solution

Question 2

What is the range for the body fluid osmolality?

Answer 2

275-295 mOsm/kg
Remember 300 mOsm/kg
-body fluids are isotonic except urine since it is outside the body

Question 3

Does the osmolality and osmolarity differ in very dilute solutions?

Answer 3

No

Question 4

How does plasma osmolarity change depending on water intake and excretion?

Answer 4

• If water intake < water excretion then plasma osmolarity increases
• If water intake > water excretion then plasma osmolarity decreases

Question 5

What is the range for urine osmolality?

Answer 5

• can vary between 50-1200 mOsm/kg
• from very dilute to very very concentrated (max)
• the solute concentration of urine is inversely proportional to volume of urine produced

Question 6

How can osmolality change in the ECF?

Answer 6

Disorder of water balance manifest as changes in body fluid osmolality

• measure as changes in PLASMA osmolality
• normally plasma osmolality is 280-310 mOsm/Kg
• lots of Na+ in plasma but Na+ balance is not the problem
• water balance is what affects osmolality

Question 7

What can we do to balance water so that it does not affect the osmolality?

Answer 7

• Remove water from urine without solute and add that water to ECF if plasma osmolality has INCREASED
• Leave excess water in urine if plasma osmolality is LOW and excrete it

Question 8

What is the vasa recta?

Answer 8

• They are long, straight vessels that wrap around juxtamedullary nephrons
• Comes of EA and is a capillary bed found only in JM nephrons
• cells are endothelium
• flow direction is opposite to filtrate flow
• no active transport only passive
• these are within the peritubular capillaries
• concentration gradient created by the counter-current multiplier is MAINTAINED by vasa recta which acts as a counter-current exchanger
• osmotic gradient created by the loop would not last long if osmoles were washed
• flow through capillaries generally act to wash out concentration gradient (by fresh fluid bringing nutrients and O2)
• medullary tissue needs to be kept alive so needs nutrients and fresh blood but must not wash out gradient

Question 9

What are peritubular capillaries?

Answer 9

• small vessels that surround the cortical nephrons

- help with reabsorption

Question 10

Why is the osmolality of the interstitial fluid the same as the osmolality of the protein-free portion of blood plasma?

Answer 10

Because there is no protein there since they are too big to pass through

Question 11

Where in the nephron does the hormonal regulation of plasma osmolality occur?

Answer 11

In the late DCT and CD

Question 12

How do we generate a vertical concentration gradient in the kidney?

Answer 12

• concentration of urine is due to:
• juxtamedullary nephron: has long loop of Henle to create vertical osmotic gradient
• vasa recta help to maintain the osmotic gradient
• CD of all nephrons use the gradient along with hormone ADH to produce urine of varying concentration
• urea also helps in urine concentration mechanism, but it is useless everywhere else in the body
• THIs FuncTIONAL ORGANIZATIOn Is KNOWN AS MEDULLARY COuNTER CuRRENT MEChaNiSM
• concentration in kidney starts in cortex and increases as it goes to medulla
• counter current multiplication establishes an important gradient
• is preserved by vasa recta

Question 13

What mechanisms are used to establish the vertical osmolality gradient?

Answer 13

• established due to active transport in the ascending loop
• active NaCl transport in thick ascending limb
• recycling of urea (effective osmole)
• unusual arrangement of blood vessels in medulla descending components in close opposition to ascending components

Question 14

Explain how the transporters create the medullary gradient in the thick ascending limb

Answer 14

• diluting action on the filtrate
• removes solute without water and therefore increases osmolarity of the interstitium
• block NaKCC transporters with a loop diuretic
• medullary interstitum becomes isosmotic and copious dilute urine is produced
• if channels are blocked, no formation of interstitial gradient so not as much water reabsorbed in descending limb
• K+ will efflux from lumen to ICF to raise osmolarity
• as a result water follows but these cells are impermeable to water so may go through tight junction
• rise in interstitial osmolarity creates a concentration gradient, allowing ions to move into capillaries

Question 15

What are the differences in descending and ascending limb in terms of concentration gradient?

Answer 15

Descending limb

• highly permeable to water due to aquaporin channels that are always open
• not permeable to Na= so Na+ remains in descending limb, allowing osmolality to increase
• max osmolality at tip of LH is 1200 mOsm/kg

Ascending limb

• actively transports NaCl out of tubular lumen into interstitial fluid (NKCC2)
• impermeable to water
• as NaCl, water remains so osmolality decreases
• fluid entering PCT is hypoosmotic compared to plasma

Question 16

Explain the counter current mechanism

Answer 16

• LOOK AT DIAGRAMS
• initially everything is isotonic (usually seen in transplant patients or after prolonged loop diuretic)
• active salt pump (NaKC2) in ascending limb pumps NaCl into interstium until it established a 200mOSM gradient at EACH level
• water leaves descending limb until concentration between descending and interstitium is same, resulting in descending being more concentrated then before
• as fluid flows further into loop at different “levels”, fluid exits into DCT so that a new mass of 300mOsm fluid enters PCT
• ascending limb pump and descending limb passively fluxes reesatblish the 200mOSM gradient at each level
• fluid flows forwards several “frames”
• keeps going to build up a stratified gradient
• final vertical osmotic gradient is established at 1200mOsm and is maintain by ongoing countercurrent multiplication of the loop of Henle

Question 17

How is urea an effective osmole?

Answer 17

• hydrophilic and doesn’t readily permeate artificial lipid bilayer
• useless in other parts of body but useful only in kidney
• is not completely permeable but isnt completely impermeable
• urea is reabsorbed in PCT

Question 18

How is urea recycled in the nephron?

Answer 18

• urea reabsorption from medullary CD
• cortical CD cells are impermeable to urea
• movement into interstitium and diffusion back into loop
• medullary CD only permeable to urea in the presence of ADH
• urea comes out through aquaporin channels with water
• goes into interstitium to increase osmolality
• medullary CD allows movement into interstitium and diffusion back into loop
• urea helps to increase osmolality
• will eventually be picked up by ascending limb and go back to CD
• cycle repeats if ADH is present

Question 19

How does the vasa recta help to provide nutrients to medullary but not wash out the concentration gradient?

Answer 19

• compromise by not perfusing the tissues rapidly, but rather at a very slow pace
• two fluids moving in opposite directions to each other
• blood in vasa recta moving opposite to ultrafiltrate
• capillaries are leaky using concentration gradient
• need low flow
• blood flow through Renal medulla is 510% of RPF
• need to maintain hyper-toxicity
• blood picks ions up from ascending limb, slowly becoming more concentrated
• water is coming out in descending limb because interstitial conc. Gradient
• at same time blood is ascending and picking up the water, finally entering a 300mOSM fluid
• by carrying the water it prevents the concentration gradient from being washed out

Question 20

Describe the pressures in the descending and ascending vasa recta

Answer 20

Descending

• low hydrostatic pressure since very slow
• some oncotic proteins to allow gradient to form
• high conc. Of ions in interstitium flow into vasa recta in order to equilbrate
• isosmotic blood in vasa recta enters hyperosmotic fluid
• Na, Cl, urea diffuse into vasa recta at slow flow so it equilibrate at each stratified level
• osmolality of blood in vasa recta increases as it reached the top if the loop

Ascending

• low hydrostatic pressure since slow flow
• high water coming into vasa recta since vasa recta now has high conc. Of ions
• blood ascending towards cortex will have higher solute content than surrounding interstitium
• water moves in from descending limb

Question 21

What are osmoreceptors?

Answer 21

• located in hypothalamus
• specifically in OVLT (organum vasculosum of the Lamina Terminalis)
• fenestrated leaky endothelium exposed directly to systemic circulation (on plasma side of blood brain barrier)
• sense changes in plasma osmolarity
• signal secondary responses which are mediated via two pathways leading to 2 different complimentary outcomes: concentration of urine, and thirst
• cells of supraoptic nucleus lie close to OVLT with input from baroreceptors

Question 22

How is osmolality regulated by osmoreceptors?

Answer 22

ADH (first solution)

• released from posterior pituitary
• effector: kidney
• what is affected: renal water excretion decreases
• decrease in osmolarity inhibits ADH secretion
• negative feedback loop stabilizes osmolarity

When level of hyperosmotic dehydration begins to surpass the protective capacity of kidneys, then THIRST is activated

• effector: brain “drinking behaviour”
• what is affected: water intake
• thirst occurs when plasma osmolarity goes up by 10%
• stimulated by increase in fluid osmolality or decrease in ECF volume, or salt ingestion
• mechanism stops when sufficient fluid has been consumed
• salt appetite occurs when plasma osmolality is low

Question 23

How do changes in BP have an effect on the response to changes in osmolarity?

Answer 23

• decrease in ECF volume
• set point is shifted to lower osmolarity values and the slope of the relationship is steeper
• if pressure increases then opposite occurs
• set point is shifted higher and slope decreases
• volume is more important than osmolality
• kidneys will draw back water ASAP to push volume up
• LOOK AT GRAPH

Question 24

What conditions are caused by too little ADH

Answer 24

Central Diabetes Insipidus

• plasma ADH levels are too low
• damage done to hypothalamus or pituitary gland
• brain injury, skull fracture
• tumour
• sarcoidosis or tuberculosis
• aneurysm
• some forms of meningitis
• water is inadequately reabsorption from CD, so a large quantity of urine is produced
• stops them from releasing ADH

Nephrogenic diabetes insipidus

• acquired insensitivity of the kidney to ADH
• water is inadequately reabsorbed from the CD, so a large quantity of urine is produced
• managed clinically by ADH injections or by ADH nasal spray treatments
• plasma osmolarity increases

Question 25

What conditions are caused by too much ADH?

Answer 25

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

• characterized by excessive release of ADH from the posterior pituitary or another source
• dilutional hyponatraemia (not because of Na but because of water)
• in which the plasma sodium levels are lowered
• total body fluid is increased

Question 26

How can we produce a hypotonic urine?

Answer 26

• decreased ADH stimulation means decreased AQP 2 on apical membrane and decreased AQP 3 and 4 on basolateral membrane only on late DCT and CD
• tubular fluid rich in water passes through hyperosmotic renal fluid with no change in water content
• loss of large amount of hypoosmotic (dilute) urine
• diuresis
• in CD only the basolateral membrane ALWAYS have AQP channels
• apical membrane only has AQP channels under the influence of ADH

Question 27

How can we produce a hyperosmotic urine?

Answer 27

• kidney must reabsorb as much water as possible
• water moves out from CD into hyperosmotic environment if there are AQP’s in both the apical and basolateral epithelium of tubule cells
• increased ADH causes increased AQP channels on apical side
• antiduresis
• needs the cortex medulla gradient with hypertonic interstitium
• also if osmolality increases by 10%, then third response occurs

Question 28

How does symptomatic hypo-osmality and hyper-osmolality affect the brain?

Answer 28

• symptomatic hypo-osmolality results from brain cell swelling
• symptomatic hypo-osmolality results from brain cell shrinkage

Question 29

What does it take to be an ineffective osmole?

Answer 29

• it can move freely across cell membranes

- so does not cause appreciable shifts in water movement

Question 30

What s the most effective extra-cellular osmole the?

Answer 30

Sodium

Question 31

What 3 things should you consider in a patient with an abnormal serum sodium level?

Answer 31

1. What is the patient’s volume status?
2. How much sodium is being lost in the urine?
3. Is the patient symptomatic?

Question 32

What should I do about Dr. Xu’s lecture?

Answer 32

LOOK AT IT