5a.) Control of Plasma Osmolality

Question 1

What is osmolality?

Answer 1

Measure of the number of osmotically active particles per kilogram of solvent

Question 2

Why did chemists invent osmolarity to use instead of osmolality?

Answer 2

Osmolality is number of osmoles per kilogram of solvent (this is one kg of solvent, not one kg of solvent and solutes combined). It is impractical to measure mass of H20 in an already mixed solution hence chemists invented osmolality- number of osmoles per litre of solution (this is total volume of solution)

Question 3

Are osmolality and osmolarity the same/can we use them interchangeably?

Answer 3

For dilute solutions they are practically the same hence could be used interchangeably

Question 4

What parameter do we use for bodily fluids; osmolarity or osmolality?

Answer 4

Osmoality

Question 5

What is the osmolality of body fluid?

Answer 5

275 -310 mOsm/kg

We usually say about 300mOsm/kg

Question 6

Most bodily fluids are isotonic to cells osmolality; true or false?

Answer 6

True

Urine is not isotonic to cells osmolality BUT IT IS ALSO NO INSIDE BODY/A BODILY FLUID

Question 7

State effects on plasma osmolality if:

• Water intake < water excretion
• Water intake > water excretion

Answer 7

• Water intake < water excretion = increase osmolality
• Water intake > water excretion= decrease osmolality

Question 8

What is the normal urine osmolality of a healthy hydrated person?

Answer 8

500 - 700 mOsm/Kg

Question 9

State the range within which urien osmolality can vary

Answer 9

50 - 1200 mOsm/Kg

Question 10

State the relationship between solute concentration of urine and volume of urien produced

Answer 10

Solute concentration is inversely proportional to volume of urine produced

Question 11

Problems regulating what substance lead to problems with osmolality?

Answer 11

Problems with water balance

Question 12

In order to maintain water balance, what must we be able to do in terms of water and urine when osmolality is:

• Increased
• Decreased

Answer 12

• Osmolality increased: need to be able to remove water from urine (ultrafiltrate) without solute and add this water to ECF
• Osmolality decreased: need to be able to leave excess water in urine and excrete it

Question 13

Osmolality of interstitial fluid is approx 290mOsm/kg whereas osmolality of total plasma volume is 291mOsm/Kg; what causes this 1mOsm/Kg difference?

Answer 13

Plasma proteins cannot cross capillary wall; hence interstitial fluid equilibrates with protein free part of plasma-giving the interstitium an osmolality of 290mOsm/kg. The extra 1mOsm/kg in total plasmavolume is the osmotic pressure of plasma proteins; we call this the oncotic pressure or colloid osmotic presure

Question 14

Why do plasma proteins contribute such a small amount (~1mOsm/kg) to total plasma osmolality?

Answer 14

Although collectively they have a large mass, they have a high molecular weight so infact there are actually few particles

Question 15

Which nephrons are responsible for making concentrated urine?

Why are these nephrons suited to this role?

Answer 15

Juxtamedullary nephrons

They have a long loop of Henle which means they can establish a greater concentration gradient in the medullary interstitium and therefore create more concentrated urine

Question 16

Briefly summarise how concentrated urine is formed

Answer 16

• Juxtamedullary nephrons created corticomedullary osmotic gradient
• Vasa recta preserve this gradient
• Collecting duts of all nephrons use this gradient (along with ADH) to produce urine of varying concentrations
• Urea also helps in urine concentration?

Question 17

The process of creating the corticopapillary osmotic gradient is?

Answer 17

Medullary counter current exchange mechanism

Question 18

Describe the corticopapillary gradient

Answer 18

• Osmotic gradient in the interstitial fluid of the medulla
• Isotonic at corticomedullary junction
• Medullary interstitium can be hyperosmotic up to 1200mOsm/kg at papilla

Question 19

Remind yourself what is transported in:

• Descending limb of Loop of Henle
• Ascending limb of Loop of Henle

State consequence on filtrate osmolality

Answer 19

Descending limb

• Water (10-15%): highly permeable due to AQP1 which are always open
• Na+= NONE

Filtrate osmolality increases

Ascending limb

• Water= NONE
• Na+ (25%): via NKCC2

Filtrate osmolality decreases and fluid enter DCT is hyposmotic compared to plasma

Question 20

Whether urine is concentrated or not depends on reabsorption in what segments of nephron?

Answer 20

• PCT reabsorbs 2/3 of fluid isosmotically
• Loop of Henle reabsorbs salt in excess of water so fluid leaving LOH and enter DCT is hypo-osmotic
• Whether urine is dilute or concentrated depends on water reabsorption in distal segments:
  
  • Initial & cortical collecting ducts
  • Outer & inner medullary collecting ducts

Question 21

ADH acts on which four segments of nephron

Answer 21

• Initial and cortical collecting tubules
• Outer and inner medullary collect ducts

Question 22

Describe how the corticopapillary gradient is set up

Answer 22

1. Imagine, start with Loop of Henle in which all filtrate in both ascending and descending limb is equal to plasma osmolality (would actually only be case in newly transplanted patient or after prolonged loop diuretic)
2. NaCl is actively pumped out of the ascending limb against it’s concentration gradient (remember AL is impermeable to water, permeable to Na+)
3. H20 then diffuses out of descending limb down water potential gradient until equilibrium is reached between filtrate in descending limb and medullary interstitium.

There can be a 200mOsm gradient at each horizontal level between ascednign and descending limb

4. New filtrate enters descending limb forcing the filtrate to move around the Loop of Henle
5. NaCl continued to be actively pumped out from ascending limb into medullary interstitium. Water follows passively down water potential gradient form descending limb until equilibrium is reached (again a 200mOsm gradient can be achieved). At this point the osmolality of interstitium closer to papilla is starting to increase
6. New filtrate enters descending limb and process continues…. Descending limb always equilibrates with interstitium until 1200mOsm/kg osmolality reached

Question 23

Is urea an effective osmole in body?

Answer 23

Urea is not an effective osmole in body as in the presence of urea transporters it can diffuse across most cell membranes.

HOWEVER, in the kidneys it IS an effective osmole

Question 24

Where is urea reabsorbed in nephron?

Answer 24

• Urea is passively reabsorbed in proximal tubule
• Nephron beyond PCT is impermeable to urea…up until the inner medullary collecting ducts

Question 25

Describe urea recycling

Answer 25

1. **Urea is passively reabsorbed in PCT (~50%)** 2. Rest of nephron impermeabale to urea hence urea stays in neprhon tubules 3. ADH increases water permeability in cortical collecting ducts and the outer medullary collecting ducts but does not increase urea permeability. Hence **water leaves neprhon tubules but urea stays- increasing urea concentration** 4. **Inner medullary collecting ducts are permeable to urea** hence **under influence of ADH urea is passively reabsorbed** by urea transporters (which are actually aquaporins that also transport urea) into interstitium 5. Passes through i**nterstitium and helps to increase osmolality** to increase corticopapillary gradient 6. **Diffuses back into thin ascending limb of Loop of Henle** and then moves around nephron again 7. If ADH is still present process will repeat again

Question 26

What structure of the neprhon is the counter current multiplier?

Answer 26

Loop of Henle

Question 27

We need a slow flow of blood through vasa recta to ensure we can maintain corticopapillary gradient; we must balance maintaining this gradien with....?

Answer 27

Ensuring medullary tissue has an adequete blood supply

Question 28

Describe how the juxtamedullary vasa recta maintains the corticopapillary concentration gradient

Answer 28

Blood flow through vasa recta is **very slow** and is also in **opposite direction to tubular flow.** In **descending limb**, **solutes (Na+, Cl-, urea) move down concentration gradient from interstitium into vasa recta**- at each stratificatioin they equilibrate. So osmolality of vasa recta at hair pin turn= osmolality of interstitium In **ascending limb, water moves from interstitium into the blood** down a water potential gradient- this adds water to blood and hence decreases osmolality of blood back to ~300mOsm/kg (what it entered vas recta as)

Question 29

Blood flow through renal medulla is what % of total RPF?

Answer 29

5-10%

Question 30

Describe the arrangment of vasa recta, include: * Where found * What it is a branch of

Answer 30

* Capillary bed ONLY FOUND IN juxtamedullary nephrons * Branch of efferent arteriole which descends down into medulla

Question 31

Why is it necessary for blood in vasa recta to flow opposite way to filtrate in nephron tubules

Answer 31

???

Question 32

Where are osmoreceptors located? What do osmoreceptors detect?

Answer 32

In the **OVLT** (organum vasculosum of the lamina terminalis) in **hypothalamus. \*\*\****They have fenestrated leaky endothelium exposed directly to systemic circulation on plasma side of blood brain barrier* **Detect changes in osmolality**

Question 33

State the 2 responses pathways osmoreceptors can alter

Answer 33

* Thirst * Concentration of urine

Question 34

Baroreceptobrs send signals to supraoptic nucleus which is located near to OVLT; true or false

Answer 34

True

Question 35

What change is osmolarity causes an increase in ADH?

Answer 35

1% increase in osmolarity

Question 36

Does ADH concentration ever reach 0?

Answer 36

NO

Question 37

How is the sensation of thirst perceived?

Answer 37

* Drying of oral mucosa * Drinking centre in lateral pre-optic area of hypothalamus regulates it centrally

Question 38

Describe what happens to the osmolarity set points when blood pressure: * Increases * Decreases

Answer 38

_Blood Pressure Decreases due to Decrease in ECF Vol_ Since maintaing blood pressure is more important than maintain osmolality, when ECF volume decreases (and hence blood pressure decreases) we prioritise just getting more water into our ECF as oppose to maintaining our osmolality. Hence, our osmolalilty set point is lowered (we don't care if the extra water makes our osmolality lower) _Blood Pressure Increases due to Increase in ECF Vol_ When blood pressure has increased all we care about is decreasing it. To decrease it we will have to remove water but this will increase our osmolality. Set point for osmolality increases as all we care about is regualting this blood pressure

Question 39

What is more important: volume or osmolality?

Answer 39

VOLUME

Question 40

State two conditions in which there is too little ADH

Answer 40

* Central (neurogenic) diabetes insipidus * Nephrogenic diabetes insipidus

Question 41

Describe neurogenic/central diabetes insipidus

Answer 41

* Plasma ADH levels are too low * Due to brain injury e.g. basilar skull fracture, tumour, aneurysum, encephalitis or meningitis * Water is inadequetley reabsorbed from collecting ducts so large volume urine produced

Question 42

Describe neprhogenic diabetes insipidus, include: * What it is * Consequence on water reabsorption * Consequence on urine produced * Treatment

Answer 42

* Acquired insensitivity of kidney to ADH * Water inadequetely absorbed form collecting ducts * Large quantity urine produced * Treat with ADH injections or by ADH nasal treatments

Question 43

What is SIADH? Include: * Full name * What it is * Consequence on total body fluid volume * Consequence on Na+ concentration

Answer 43

* Syndrome of inappropriate antidiuretic hormone secretion * Excessive release of ADH from pituitary or other source * Increased total body fluid volume * Dilution hyponatremia

Question 44

Large deficits in water or increases in salt are only partially compensated for by the kidnyes; what is the ultimate compensation?

Answer 44

Drinking!

Question 45

Drinnking is induced by what 2 things?

Answer 45

* Increase in plasma osmolality * Decrease in ECF

Question 46

Describe the actions of ADH

Answer 46

* Inserts aquaporin channels into apical membranes in collecting ducts to allow water reabsorption * Water then enters plasma * NOTE: basolateral membranes always have aquaporins. ADH only regulates aquaporins in apical* * When ADH is present, so aquaporin (AQP2) inserted into apical membrane this means taht the tubule fluid in collecting ducts can more or less equilibrate with the interstitum to produce concentrated urine. If no ADH then no AQP2 then tubule fluid can't have water removed by reabsorption and hence equilibrate with interstitium*

Question 47

Theh renal medulla is hyperosmotic to blood plasma both during antidiuresis and water diuresis; true or false

Answer 47

True