Lec10 Physiology of Thirst and Fluid Balance

Question 1

What is the importance of physiology of water homeostasis?

Answer 1

The regulations water balance ensures that plasma osmolality (and extracellular fluid osmolality) remain stable

Question 2

What is the narrow range of plasma osmolality?

Answer 2

285-295mosmol/kg

Question 3

What are the 3 key determinants?

Answer 3

Anti-diuretic hormone - osmotically stimulated secretion
Kidney - wide variation in urine output 0.5-20l/day
Thirst - osmoregulated - stimulates fluid intake

Question 4

What are osmoreceptors?

Answer 4

Osmoreceptors are specialised cells which detect changes in plasma osmolality - especially sodium

Question 5

Where are osmoreceptors located?

Answer 5

In the anterior wall of the 3rd ventricle of the brain

Question 6

What do fenestrations in the blood brain barrier allow to happen?

Answer 6

Fenestrations in the bbb allow circulating solutes (osmoles) to influence brain osmoreceptors

Question 7

How do osmoreceptors respond to changes in plasma osmolality?

Answer 7

Osmoreceptor cells change their volume by a transmembrane flux of water in response to changes in plasma osmolality which causes a stretch of the cells. This initiates impulses transmitted to the hypothalamus to synthesise ADH and the cerebral cortex to register thirst

Question 8

ADH is also known as what in humans?

Answer 8

Arginine vasopressin (AVP)

Question 9

Which other receptors influence ADH secretion? Where are they found, how do they work and what is their clinical significance concerning severe haemorrhage?

Answer 9

Baroreceptors found in the atria, carotid sinus and aortic arch.
When circulating volume is decreased, stretch receptors are firing less frequently, which stimulates the secretion of AVP. In severe circulatory hypovolaemia, this system overrides the osmoreceptors in the cerebral ventricles.

Question 10

Describe how ADH acts in the kidneys?

Answer 10

Via V2 receptors

Question 11

What does binding of ADH to V2 receptors cause?

Answer 11

ADH binding to the V2 receptor causes aquaporin - which is normally stored in cytoplasmic vesicle - to move and fuse with the luminal membrane

Question 12

What is the consequence of aquaporin in the luminal membrane of kidney tubule?

Answer 12

Increased water permeability of the renal collecting tubes, promoting water reabsorption

Question 13

What happens when ADH is cleared?

Answer 13

The aquaporin channels are taken off the luminal membrane by endocytosis and returned to the cytoplasm

Question 14

Describe the thirst levels, serum AVP conc., urine conc. and volume for both high and low plasma osmolality states respectively.

Answer 14

High plasma osmolality: Increased thirst levels, high serum AVP, urine high osmolality, low urine volume/output

Low plasma osmolality: no thirst, low serum AVP, low urine osmolality, high urine volume/output

Question 15

What does drinking water do to thirst and AVP secretion?

Answer 15

Suppresses AVP secretion and thirst

Question 16

What is polyuria?

Answer 16

Excessive urination or abnormally large volume of urine

Question 17

What is polydipsia?

Answer 17

Excessive thirst or excessive drinking

Question 18

Name four causes of polyuria and polydipsia?

Answer 18

Diabetes mellitus
Cranial (central) diabetes insipidus
Nephrogenic diabetes insipidus
Primary polydipsia (psychogenic diabetes insipidus)

Question 19

List 2 causes of primary and secondary CDI respectively

Answer 19

Primary – Idiopathic CDI, Genetic (AVP polymorphisms, DIDMOAD (Wolfram syndrome))
Secondary – Post-surgical, traumatic.

Question 20

List seven rarer causes of secondary CDI

Answer 20

Tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune

Question 21

List 5 causes of nephrogenic DI

Answer 21

Idiopathic
Genetic – rare – V2 receptor/aquaporin gene mutation
Metabolic – hypercalcaemia, hypokalaemia
Drugs – lithium
Chronic Kidney Disease (CKD)

Question 22

What are the primary treatments for CDI, NDI, and PDI?

Answer 22

CDI – DDAVP (desmopressin)
NDI – Correction of cause (metabolic/drugs etc), thiazide diuretics
PDI – Explanation/persuasion, psychological therapy

Question 23

What is hypothalamic syndrome?

Answer 23

Disordered thirst and DI
Disordered appetite (hyperplagia)
Disordered temperature regulation
Disordered sleep rhythm
Hypopituitarism

Question 24

What happens in Primary polydipsia (psychogenic DI)?

Answer 24

Increased fluid intake - poldipsia
Lower plasma osmolality
Suppressed AVP secretion
Low urine osmolality, high urine output - polyuria
Also lose renal interstitial solute, reducing renal concentrating ability

Question 25

How do you investigate polyuria and polydipsia?

Answer 25

``` Medical history, Exclude diabetes mellitus Document 24 hour fluid balance - urine output and fluid intake, day and night Exclude hypercalaemia and hypokalaemia Water deprivation test ```

Question 26

What is the water deprivation test?

Answer 26

Following a period of dehydration Measure plasma and urine osmolalities and weight Inject synthetic vasopressin (desmopressin DDAVP)

Question 27

What is the normal response to the water deprivation test?

Answer 27

Normal plasma osmolality, high urine osmolality

Question 28

What is the CDI response to water deprivation test?

Answer 28

Poor urine concentration after dehydration | Rise in urine osmolality after desmopressin

Question 29

What is the NDI response to water deprivation test?

Answer 29

Poor urine concentration after dehydration | No rise in urine osmolality after desmopressin

Question 30

What is hyponatraemia?

Answer 30

Sodium below 135mmol/l

Question 31

What is severe hyponatraemia?

Answer 31

Sodium below 125mmol/l

Question 32

What are the symptoms of hyponatraemia?

Answer 32

Depends on the rate of fall and absolute value Gradual drop - brain adapts (chronic) Non-specfic - nausea, headache, mood change, cramps, lethargy Severe/sudden - confusion, drowsiness, seizures, coma

Question 33

List the causes of hyponatraemia in the hypo-, eu-, and hypervolaemic patient.

Answer 33

``` Hypovolaemic – Renal loss / non-renal loss (D+V, sweating, burns) AVP release to preserve circulating volume Euvolaemic – Hypoadrenalism Hypothyroidism SIADH Hypervolaemic – Renal failure Cardiac failure Cirrhosis Excess IV dextrose ```

Question 34

Why is it important to correct severe hyponatraemia slowly?

Answer 34

Rapid correction risks oligodendrocyte degeneration and CNS myelinolysis (osmotic demyelination syndrome) with severe neurological sequelae Alcoholics and the malnourished particularly at risk

Question 35

Regarding the diagnosis of SIADH, describe the patient’s volume status, plasma osmolality, plasma sodium, urine osmolality, urine sodium and give 2 endocrine causes.

Answer 35

``` Volume - euvolaemic PO - low PS - low UO - high US - high Hypoadrenalism Hypothyroidism ```

Question 36

What might be some other causes of SIADH?

Answer 36

Neoplasias, neurological disorders (CNS), lung disease, drugs

Question 37

Describe other tests you would do to diagnose SIADH?

Answer 37

Adrenal function tests Renal function tests Thyroid function tests

Question 38

Describe SIADH management & treatment

Answer 38

Identify and treat the underlying cause Fluid restriction 1000ml daily Demeclocycline - induces mild NDI Vaptans - V2 receptor anatagonists - induce a water diuresis (expensive, variable responses, lack of clinically significant data)