Renal Function 2

Question 1

what is osmolarity of NaCl? explain

what is osmolarity of blood plasma?

Answer 1

• *- NaCl** dissociates fully in water to become two separate particles: an Na+ ion and a Cl− ion.
• each mole of NaCl becomes two osmols in solution, one mole of Na+ and one mole of Cl−.
• Blood plasma has an osmolarity of about 300 mOsmol.

Question 2

which part of brain detects osmotic pressure - what are the receptors called?
specifically in ^, what are the two main bits/

Answer 2

- hypothalamus detects osmotic pressure: osmoreceptors

• within hypothalamus: series of tightly packed nuclei: supraoptic and paraventricular nuclei

Question 3

describe the pathway that occurs for supraoptic and paraventricular nuclei

Answer 3

- supraoptic and paraventricular nuclei send axons down to capillaries within posterior pituitary

- axons secrete antidiuretic hormone (ADH) into pituitary capillaries

- goes into venous blood

Question 4

ADH aka ? (2)

Answer 4

vasopressin

or

arginine vasopressin

Question 5

what happens (basic) if:

• osmoreceptors detect higher than normal omsolarity
• osmoreceptors detect lower than normal omsolarity

Answer 5

osmoreceptors detect higher than normal omsolarity (blood is too conc)

• **stimulates ADH release
• **stops water from being lost
• activates thirst: drink more

- osmoreceptors detect lower than normal omsolarity (blood not conc enough)

• **inhibits ADH release
• **more water lost
• activates not thirst: drink lesss

Question 6

explain whats going on in nephron xox

Answer 6

• extracellular fluid in renal medulla is much higher than plasma (1200 mm /lt c.f. 300 mm /lt

(- Fluid: proximal tubule –> thin descending loop of Henle –> thick part of the ascending limb)

As the fluid descends DLH:
- water moves out (via aquaporins), which makes the fluid more and more concentrated because it is in equilibrium with the high concentration in the extracellular fluid in the renal medulla.

fluid moves up the ALH:

• the thick ascending wall is impermeable to water
• Na+ & Cl- are pumped out of tube into extracellular space: active transport by ATP-ase
• makes the fluid v. dilute (most of Na / Cl has been removed)

fluid moves to distal tubule:
- aldosterone acts to increase Na reabsorbtion (and other materials)

fluid moves to collecting duct:

• fluid passes down from here to ureter and ladders
• CD has aquaporins that are opened by ADH
• if channels are open: water is reabsorbed & urine is same osmolarity as renal medullary fluid
• if channels are closed: water not reabsorbed & dilute urine produced

Question 7

how is oxygen supplied to pumps in loop of Henle?

where in nephron is the fluid most dilute? AND least dilute?

Answer 7

oxygen supplied by capillaries of the vasa recta

most dilute: at start of distal tubule (~ 100 mOsmol) (lots of Na / Cl has been removed)
least dilute: at bottom of loop of Henle ( ~ 1200 mOsmol) (lots water removed, Na / Cl yet to be removed) . also in the collecting duct, depending on water reabsortion

Question 8

what is name for the process of pumping out salt into the extracellular fluid around the loop of Henle?

Answer 8

countercurrent multiplier mechanism of urine concentration

Question 9

what is the location, function and mechanism of action for the NKCC2 channels?

Answer 9

NKCC2 (Na-K-Cl cotransporter channel

• location: thick ascending limb of the loop of Henle
• function: to get Na / Cl out of the ascending limb and into extracellular fluid
• mechanism of action:
  i) luminal walls of the epithelial cells allows sodium, potassium & chloride ions to move passively together down their concentration gradient into the cells that make thick ascending limb
  ii) then, sodium is actively transported out into extracellular space by Na/K ATP-ase
  iii) Cl- moves passively with the sodium
  iv) most of K+ ions diffuse back into the lumen via K ion channels

https://www.youtube.com/watch?v=sapTNUtrPdY

Question 10

what would happen if you blocked NKCC2, Cl- or K+ channels in ascending loop of Henle??

Answer 10

• leads to reduction of Na / Cl reabsorbtion
• decreases **interstitial osmolality
• get less waterereabsorbtion** in descending limb of Loop of Henle
• causes an increased excretion of water = diuresis

Diuresis is a condition in which the kidneys filter too much bodily fluid. That increases your urine production and the frequency with which you need to use the bathroom.

Question 11

which pump assists the NKCC2 pump?

explain how xix

Answer 11

Renal Outer Medullary potassium channel or ROMK (royal orders make knights)

• K+ out of the tubule cells into the lumen (where fluid is)
• generates postive voltage: 10mV in tubular lumen
• creates an overall voltage difference of 80mV between tubular lumen and tubular cell
• this voltage difference helps propel sodium via NCKK2 transporter into tubular cells

Question 12

what does the countercurrent exchange mechanism ensure? (2)

basic:
what happens in descending loop of H?
what happens in ascending loop of H??

why is countercurrent multiplication called countercurrent multiplication?

Answer 12

• *-** adequate blood flow and oxygen supply to the medulla
• without causing a washout of the high concentration of solutes needed for concentration of urine.

descending loop of H: water moves out. impermeable to ion movement. by the end = v concentrated
ascending loop of H: (opposite). impermbeable to water. ions move out

^ this process = countercurrent multiplcation
-countercurrent = bc the descending and ascending limb go in opposite directions.
- multiplication = when we rebabsorb ions in ascending limb and make the medulla salty, this drives the passive water absorbtion on descedning limb. bc have used energy to AT ions out, dont need to use energy for water, as gradient already exists

https://www.khanacademy.org/test-prep/mcat/organ-systems/the-renal-system/v/countercurrent-multiplication-in-the-kidney

Question 13

which part of nephron controls blood pressure?

Answer 13

juxtaglomerular apparatus

Question 14

define:

Water diuresis

diabetes insipidus

osmotic diuresis

Answer 14

water diuresis: (is increased urination and the physiologic process that produces such an increase)
blood becomes dilute; ADH release inhibited: result high volume of dilute urine

Diabetes insipidus; damage to the hypothalamus or posterior pituitary leading to loss of ADH secretion. Result high volume of dilute urine.

osmotic diuresis is caused by an excess of urinary solute, typically nonreabsorbable, like glucose.
Sugars like glucose are normally completely reabsorbed in the proximal tubule; if they are not, due to excess glucose in the blood, then the glucose passing through the collecting duct provides an osmotic force tending to pull water into the urine, opposing the osmotic force of the medulla which is tending to pull water out. Result; high volume of sugary urine. this condition = diabetes mellitus

Question 15

why do cells in the renal medulla have high metabolic rate?

what should u do after trauma / haemorrhage?

Answer 15

• high metabolic rate: constantly active Na pumps
• bc of this ^, reduced blood & o2 can causes severe damage to kidneys: should do renal function (creatinine clearance) after trauma / haemoorage

Question 16

what does a diuretic do?

Answer 16

diuretics = increase urine flow. help rid your body of salt (sodium) and water

Question 17

loop of henle is responsible for filtering what % of Na and H20, from urine -> blood?

Answer 17

20% Na

15% H20

back into blood

Question 18

Furosemide:

indications?

MoA?

Answer 18

_Furosemide removes excess water in the body

indications:_

• oedema
• resistant hypertension

mechanism of action:

• blocks the transport of sodium (and chloride) out of the loop of Henle and into interstitial fluid of medulla
• causes a lower concentration of sodium & other solutes in interstial fluid
• SO, less water is reabsorbed in descending loop of Henle (remember, water follows Na)
• means Na, & water is kept in the urine: prevents reabsorbtion of 20% Na & 15% H20
• SO, more water excreted

* furosemide, and other loop, diuretics act independently of ADH *

Question 19

Answer 19

Question 20

what type (e.g. cuboidal etc) make up cells of

i) thick ascending loop of henle?
ii) thin descedning loop?

Answer 20

i) thick ascending loop of henle: cuboidal cells
ii) thin descedning loop: squamous cells (permeable to water)

Question 21

how do Thiazide diuretics work?

what is an AE of using Thiazide diuretics long term?

Answer 21

Thiazide diuretics like bendroflumethiazide (Aprinox) inhibit reabsorption of sodium and chloride ions from the _distal convoluted tubule_s in the kidneys by blocking a Na+/Cl− cotransporter.

The increased sodium concentration in the collecting ducts prevents water reabsorption and hence increases urine output.

Thiazides also have a moderate stimulating effect on aldosterone secretion, which again increases sodium reabsorption.

One important adverse effect of long-term thiazide use is loss of potassium resulting in hypokalaemia.

Question 22

Spironolactone works by?

Answer 22

Spironolactone and similar drugs block the mineralocorticoid receptor that aldosterone binds to in the distal tubule. It is thus an aldosterone antagonist

Question 23

where in body are cells that detect stretch - and what does this cause a release of?

Answer 23

Specialised muscle cells: right atrium and inferior vena cava.

In response to stretch (indicating increased preload) these cells release atrial natriuretic peptide (ANP)

Question 24

explain mechanism of action of ANP ?

Answer 24

ANP decreases Na+ reabsorption in the distal tubule and collecting duct of the kidney.

This leads to increased Na+ loss in urine and (by osmosis) also increased water loss.

The increased fluid and sodium loss reduces the circulating blood volume and brings it back to normal

Increased sympathetic activity can also stimulate ANP release via an action on β-adrenoceptors

Question 25

ANP ??? sodium excretion: thus it opposes the action of aldosterone, which ??? sodium excretion

Answer 25

Remember: ANP **increases** sodium excretion: thus it **_opposes the action of aldosterone,_** which **decrease** ssodium excretion

Question 26

where is lots of blood stored in body? what does this mean after a haemorrhage?

Answer 26

veins and venules are a **reservoir of blood** SO by **constricting veins,** the sympathetic nervous system can **restore preload after haemorrhage**

Question 27

what is the difference between osmoreceptors and baroreceptors?

Answer 27

**Osmoreceptors** reside in hypothalamus and respond to changes of extracellular fluid (ECF) osmolality. **Baroreceptors** are mechanoreceptors that sense blood pressure in the vessel wall. ## Footnote * Osmoreceptors respond to changes in osmotic pressure, which is the "pressure" of solutes in water trying to equalize their concentrations across a semipermeable barrier.* * Baroreceptors respond to actual mechanical pressure, like when you touch or press on something, or when it touches or presses on you. They're also found in the muscular walls of arteries where they sense the physical pressure of blood flowing through them.*