Regulation of urine volume and fluid balance

Question 1

What are the signs and symptoms of hypovolaemia?

Answer 1

Symptoms - thirst, dizziness on standing, confusion

Signs - low JVP, postural hypotension, weight loss, dry mucous membranes, reduced skin turgor, reduced urine output

Question 2

What are the signs and symptoms of hypervolaemia?

Answer 2

Symptoms - ankle swelling, breathlessness

Signs - raised JVP, oedema (peripheral +/- pulmonary), weight gain, hypertension

Question 3

What ions mainly control ECF osmolarity?

Answer 3

80% total osmolarity of ECF = NaCl-

Question 4

What ion mainly controls ICF osmolarity?

Answer 4

~50% of total osmolarity of ICF = K+

Question 5

What are the inputs and outputs of total body water?

Answer 5

Inputs: drinking, food, metabolism

Outputs: lungs, skin, faeces, urine

Question 6

How do you calculate osmoses excreted/day?

Answer 6

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

Question 7

Define obligatory urine volume

Answer 7

Obligatory urine volume is the minimum urine volume of urine that needs to be produced each day to excrete waste solutes

Question 8

What things does obligatory urine volume depend on?

Answer 8

1) Maximum urinary concentrating ability of the kidneys (typically 1200mOsm/L)
2) Amount of solutes that need excreting (typically 600 mOsm)

Therefore, typical obligatory urine volume = 0.5L / day
(600 mOsm / 1200 mOsm/L = 0.5 L)

Question 9

What causes polyuria?

Answer 9

Increased water excretion:

• Excessive water ingestion
• Inability to concentrate urine (tubular damage, diabetes insipidus)

Increased solute excretion:

• Diuretics (or failure to reabsorb sodium)
• Glycosuria (diabetes mellitus)

Question 10

What causes oliguria?

Answer 10

Decreased water/solute excretion:

• Dehydration/low extracellular volume
• Poor renal perfusion

Question 11

How is urine concentrated in the collecting duct?

Answer 11

1) Insertion of water channels (aquaporins) - regulated by antidiuretic hormone (ADH)
2) An osmotic gradient - generated by the countercurrent system in loop of Henle

Question 12

Where is ADH produced?

Answer 12

Produced in supraoptic & paraventricular nuclei of hypothalamus

Transported to the posterior pituitary where it is packaged into storage granules & released by exocytosis

Short plasma half life.

Question 13

What are the two functions of ADH?

Answer 13

Reduce water excretion (antidiuretic)

Stimulate vasoconstriction

Question 14

What stimulates ADH release?

Answer 14

Raised plasma osmolarity (hypertonicity) is the main stimulus for ADH release

Hypovolaemia / low blood pressure (triggering release of angiotensin II)

Nausea (‘precaution’ for vomiting & fluid loss)

Drugs (e.g. morphine, nicotine)

Question 15

What inhibits ADH release?

Answer 15

Reduced plasma osmolarity (hypotonicity)

Hypervolaemia / raised blood pressure

Drugs (e.g. alcohol)

Question 16

What is the cellular mechanism of ADH?

Answer 16

1) ADH binds to vasopressin 2 receptor
2) cAMP is produced
3) cAMP activates PKA
4) PKA phosphorylates proteins
5) The phosphorylated proteins increase aquaporin synthesis in the nucleus and cause vesicles with inactive water channels to fuse with the luminal membrane

Question 17

Define the counter current multiplier mechanism and what are the 4 features that contribute to it?

Answer 17

Counter current multiplier mechanism is method by which medullary interstitium is concentrated.
1) Hairpin arrangement of Loop of Henle with both limbs close to each other

2) Fluid travelling in opposite directions in the two limbs
3) Different water permeabilities of the two limbs
4) Ability of the Na / K / 2Cl transporter to actively transport solutes against a concentration gradient

Question 18

What is the result of the counter current multiplier mechanism?

Answer 18

1) A dilute filtrate entering the distal nephron (allows water to move out of tubule to the circulation by osmosis)
2) Generates a large increase in [NaCl] in the medulla, so contributing to the increase in the osmotic gradient (which allows the movement of water)

Question 19

What are the vasa recta?

Answer 19

Vasa recta are long thin walled (specialised) peritubular capillaries that parallel the loops of Henle in juxtamedullary nephrons.

For the countercurrent multiplier to work the salt released from the loop of Henle must remain in the medulla, while most of the water is removed.

Low blood flow ~5-10% renal blood flow (just enough to provide nutrients) without ‘washing out’ solutes in medulla.