Regulation Of Urine Volume And Fluid Balance

Question 1

ACE inhibitors cause a marked reduction in renal function in patients with bilateral renal artery stenosis. Why?

Answer 1

W/o drug: Kidney will think BP is low due to narrowing even though it is normal -> RAAS will be activated producing angiotensin II
-> constricts the EA trying to increase BP = manages to maintain GFR
With drug: RAAS + angiotensin II is reduced -> EA will remain dilated = reducing GFR + renal function

Question 2

How do the kidneys regulate fluid balance?

Answer 2

Regulate volume + composition by altering volume of plasma which in turn influences other fluid compartments (e.g. interstitial fluid)
Maintenance of volume linked to regulation of EC [Na] + [H2O] which in turn controls BP

Question 3

What are the symptoms + signs of hypovolaemia?

Answer 3

Symptoms: thirst, dizziness on standing + confusion
Signs: low JVP, postural hypotension, weight loss, dry mucous membranes, reduced skin turgor + reduced urine output

Question 4

What are the symptoms + signs of hypervolaemia?

Answer 4

Symptoms: ankle swelling + breathlessness
Signs: Raised JVP, oedema (peripheral +/- pulmonary), weight gain + hypertension

Question 5

Why is it important to regulate osmolarity and how does the kidney do it?

Answer 5

To avoid excessive movements between compartments and subsequent cell dehydration or swelling
Control of osmolarity + volume linked to kidneys ability to alter urine volume/composition in response to wide range of fluid inputs/outputs

Question 6

What is the minimum, normal + maximum urine production per day?

Answer 6

Minimum: ~500ml/day
Normal: ~1500ml/day
Maximum: ~20,000ml/day
Diurnal variation

Question 7

What would happen if someone suddenly ingested 1 L of water?

Answer 7

Big increase in urine volume rapidly to maintain body fluid volume however, amount of solutes excreted remains unchanged so urine osmolarity will decrease, but plasma osmolarity remains constant so cells will not swell

Question 8

What is the equation for urine osmolarity?

Answer 8

Osmoles excreted/day (Osm) = urine osmolarity (Osm/L) x urine output (L/day)

Question 9

Explain how urine osmolarity can vary and why it does this.

Answer 9

Urine osmolarity changes according to needs of body to preserve/excrete water. Every day a certain amount of waste solute must be secreted and this can either be done in a small amount of very concentrated urine (>4x [plasma]) or lots of dilute urine (1/6th [plasma])

Question 10

What is obligatory urine volume? What does it depend on?

Answer 10

Minimum volume of urine that needs to be produced each day to excrete waste solutes
Depends on:
- Max urinary concentrating ability of kidneys (~1200mOsm/L)
- Amount of solutes that need excreting (~600mOsm)
= 600/1200 = 0.5L/day obligatory urine

Question 11

Why should you not drink salt water on a raft?

Answer 11

If you drink 1L of 1800 mOsm solution: 1800/1200 (max urinary concentrating ability of kidneys) = 1.5 L so you are taking in 1L of water but losing 1.5L -> high levels of solute cause a diuresis even though we are trying to retain water -> more dehydrated

Question 12

What can cause increased urine volume i.e. polyuria?

Answer 12

Increased water excretion due to excessive water indigestion or inability to concentrate urine (e.g. tubular damage, DI)
Increased solute excretion due to diuretics (or failure to reabsorb Na+) or glycosuria (DM)

Question 13

What can cause reduced urine volume i.e. oliguria?

Answer 13

Decreased water/solute excretion due to dehydration/low EC volume or poor renal perfusion

Question 14

Where does reabsorption of water and fine tuning + hormonal regulationoccur in the nephron and what does it require?

Answer 14

Water reabsorption: PT + LOH
Fine tuning + hormonal regulation: medullary collecting ducts
Reabsorption from collecting ducts is passive + requires:
- Insertion of aquaporins (regulated by ADH)
- Osmotic gradient (via countercurrent system in LOH)

Question 15

For what to be absorbed, filtrate has to be ____ relative to interstitium.

Answer 15

Hypo-osmotic

Question 16

Where is ADH/vasopressin/AVP produced + transported? What are 2 its functions?

Answer 16

Produced in supraoptic + paraventricular nuclei of hypothalamus -> posterior pituitary -> packaged into storage granules + released by exocytosis (short plasma T1/2)
Functions:
1. Reduce water excretion
2. Vasoconstriction

Question 17

What 4 factors stimulate ADH release?

Answer 17

1. Raised plasma osmolarity (main one)
2. Hypovolaemia/low BP/angiotensin II release
3. Nausea (‘precaution’ for vomiting + fluid loss)
4. Drugs e.g. morphine, nicotine

Question 18

How will cells in hypothalamus trigger ADH release?

Answer 18

Osmoreceptors will detect increased plasma osmolarity
Peripheral volume receptors will detect hypovolaemia
= ADH release

Question 19

What is thirst? How does it occur?

Answer 19

Thirst = conscious desire for water
Thirst centres in hypothalamus respond to change in plasma osmolarity + ECV to regulate intake (similar stimuli to ADH release)

Question 20

What 3 factors inhibit ADH release?

Answer 20

1. Reduced plasma osmolarity
2. Hypervolaemia/high BP
3. Drugs e.g. alcohol

Question 21

What is the mechanism of action of ADH?

Answer 21

1. ADH from blood binds to V2 receptor on collecting duct cell
2. IC signalling cascade: ATP -> cAMP -> activates PKA -> protein phosphorylation
3. Vesicles with inactive AQP2 channels (synthesized in nucleus) fuse with apical cell membrane
4. AQP2 start to reabsorb water from tubular lumen

Question 22

How does water permeability vary across the nephron?

Answer 22

PT + thin descending LOH: naturally very permeable
CCT/MCT: variable permeability based on ADH presence
Ascending LOH: relatively impermeable in absence of ADH

Question 23

Where + how is dilute urine formed?

Answer 23

Ascending LOH relatively impermeable to water in absence of ADH so pump moves solutes out of tubule lumen + water cannot follow leaving behind a dilute tubular fluid/hypoosmotic when compared to plasma = dilute urine excreted

Question 24

Where + how is concentrated urine formed?

Answer 24

DT + CT permeable to water in presence of ADH so water will move so that there is osmotic equilibrium with surrounding interstitium (medullary interstitium is high at ~ 1200mOsm/L/H2O) = concentrated urine excreted

Question 25

ADH induced water movements need an ____ ___ to occur.

Answer 25

Osmotic gradient

Question 26

How is the medullary concentration gradient formed?

Answer 26

Osmotic potential of kidney interstitum (particularly medullary) depends on urea + NaCl. High concentrations of these drive reabsorption of water from collecting duct (in presence of ADH). Urea recirculation, Loop of Henle + vasa recta play key roles in generating/maintaining this osmotic gradient.

Question 27

What is the recirculation of urea?

Answer 27

Some filtered urea is recirculated + due to differing permeability along the nephron becomes trapped at high concentration within the medullary interstitium so makes a key contribution to the osmotic gradient. High protein diet + thus, more urea improved ability to concentrate urine.

Question 28

What parts of the loop of henle can reabsorb water + solutes?

Answer 28

Thin descending: water permeable, no reabsorption/secretion of solutes
Thin ascending: water impermeable, no reabsorption/secretion of solutes
Thick ascending: water impermeable, active reabsorption of Na + others

Question 29

What 4 factors makes the counter current mechanism of concentrating the medullary interstitium possible?

Answer 29

Hairpin arrangement of LOH with both limbs close together
Fluid travelling in opposite directions in 2 limbs
Different H2O permeabilities of 2 limbs
Ability of NaK2Cl transporter to transport solutes against a concentration gradient (generating a ~200mOsmol difference)

Question 30

What is the result of the counter current mechanism?

Answer 30

Dilute filtrate entering distal nephron which allows H2O to move out of tubule to blood via osmosis
Large increase in [NaCl] in medulla contributing to osmotic gradient + movement of water

Question 31

When the counter current gradient is fully established, what will be the situation in the nephron?

Answer 31

Interstitial osmolarity is always the same as in descending loop
Difference in osmolarity between descending + ascending LOH at transverse level is only 200 mOsmol (reflects max capacity of transporters) but affect multiplied over length of LOH due to counter current arrangement
-> dilute filtrate leaves LOH

Question 32

______ ___ play key role in counter current mechanism due to their long loops of Henle that run deep into the medulla

Answer 32

Juxtamedullary nephrons

Question 33

Why are the vasa recta good at helping maintain the countercurrent multiplier?

Answer 33

Salt released from LOH must remain in medulla whilst most H2O is removed
Vasa recta are long thin walled specialised peritubular capillaries that parallel the LOH in juxtamedullary nephrons, they have:
- Low blood flow (enough to provide nutrients w/o washing solutes away)
- Hairpin arrangement important for counter current exchange

Question 34

Why does the hairpin arrangement allow counter current exchange to occur?

Answer 34

Allows nutrients to be delivered + H2O removed whilst minimising disruption to medullary concentration gradient allowing counter current exchange
Constant flow of urea + NaCl (from lumen to interstitium via vasa recta) stops them precipitating in medulla

Question 35

What is the overall effect of the counter current mechanism?

Answer 35

Increasing osmolarity of NaCl + urea as the tubule progresses from cortex down to the medulla papillary tip
Filtrate in DT hypo-osmotic relative to interstitium so water leaves by osmosis down a concentration gradient

Question 36

What is the normal plasma osmolality?

Answer 36

280-285mOsm/kg

Question 37

What are 2 main clinical disorders of water regulation?

Answer 37

1. Too much ADH - syndrome of inappropriate ADH (SIADH)

2. Too little ADH - diabetes insipidus (cranial or nephrogenic)

Question 38

What are the causes and effects of SIADH?

Answer 38

Causes: pneumonia, small-cell lung carcinoma, drugs, meningitis etc.
Effects: Inappropriate water reabsorption = low plasma osmolality, low serum [Na] (may both cause cerebral oedema) + urine too concentrated with high [Na]

Question 39

What is the treatment for SIADH?

Answer 39

Identify/treat cause
Restrict fluid intake
Drugs that inhibit ADH effects (e.g. demeclocycline or V2 antagonists like tolvaptan)
Avoid correcting hyponatraemia with saline infusions mostly

Question 40

What is diabetes insipidus?

Answer 40

Inability to reabsorb water from distal nephron due to either inadequate production from hypothalamus/pituitary (cranial DI;) or ADH insensitivity in renal tubules (nephrogenic DI)

Question 41

What are the causes of the 2 different types of diabetes insipidus?

Answer 41

Cranial: head trauma, neurosurgery, tumours, infections
Nephrogenic: drug e.g. lithium, electrolyte abnormalities (increased Ca2+, decreased K+)

Question 42

What are the symptoms of diabetes insipidus + how would you investigate it?

Answer 42

Polyuria (10-15L/day)
Thirst/polydipsia 
Low urine osmolality 
High plasma osmolality + serum [Na]
Investigate via water/fluid deprivation test

Question 43

What is the water/fluid deprivation test?

Answer 43

Deprivation of fluid over hours which increases plasma osmolality which should prompt ADH release + concentration of urine (must monitor plasma + urine osmolality, weight + BP as can be dangerous in DI):
1st stage - identifies if DI
2nd stage - 10 hrs later administer synthesis ADH (desmopressin) to differentiate cranial + nephrogenic

Question 44

What is the treatment for diabetes insipidus?

Answer 44

Identify/treat cause
Ensure adequate fluid intake
Synthetic ADH (desmopressin) for cranial DI
Drugs to sensitive renal tubules to ADH for nephrogenic DI

Question 45

How can the water/fluid deprivation test differentiate between cranial + nephrogenic diabetes insipidus?

Answer 45

Synthetic ADH (desmopressin) is administered and if patient has cranial DI, this will correct urine osmolality whereas if the patient has nephrogenic DI, the collecting duct cells are insensitive to ADH so urine osmolality will remain low.