L10 - Physiology of Thirst and Fluid Balance COPY

Question 1

PHYSIOL OF WATER HOMEOSTASIS

i) what does regulation of water balance ensure for the plasma?
ii) what is the narrow range of plasma osmolality?
iii) what are the three key determinants of water homeostasis?

Answer 1

i) ensures maintenance of plasma osmolality
ii) narrow range of 285-295mosmol/kg
iii) ADH (osmotically stimulated), the kidney, and thirst

Question 2

OSMORECEPTORS

i) what do they detect?
ii) where are they located? what allows them to do their job?
iii) how do osmoreceptor cells alter their volume? what is this in response to?
iv) what does a change in volume initiate? which two brain areas does this affect?
v) which brain area synthesises ADH and which registers thirst?

Answer 2

i) groups of specialised cells that detect changes in the plasma osmolality (especially sodium)
ii) located in the anterior wall of the 3rd ventricle and fenestrations in the BBB allow solute to influence the osmoRs
iii) change in volume by a transmembrane flux of water in response to changes in plasma osmolality
iv) change in volume initiates neuronal impulses to the hypothalamus and the cerebral cortex

v) HT releases ADH
- ceb cortex registers thirst

Question 3

ADH

i) is it water conserving or water excreting?
ii) how many aa chain is it? what hormone is this the same as?
iii) where is it synthesised?
iv) where does it travel after synthesis and where is it released from?

Answer 3

i) water conserving (released in dehydration)
ii) nonapeptide (9aa) same as oxytocin
iii) synthesised in the supraoptic and paraventricular nuclei in the hypothalamus
iv) travels down the axons to the post pit where it is released

Question 4

ADH ACTION ON THE KIDNEY

i) which receptors does ADH bind to in the kidney? in what area of the nephron?
ii) what does ADH binding its receptor consequently cause?
iii) what is the ultimate effect of ADH on the kidney?
iv) what happens when ADH is cleared?
v) what second messengers is this mediated by? (2)

Answer 4

i) binds V2 receptors in the collecting dict
ii) ADH binding causes translocation of AQP2 to the apical membrane of the collecting duct cell
iii) ADH causes water reabsorption from the luminal fluid into the blood
iv) when ADH is cleared the AQPs are removed by endocytosis
v) mediated by PKA and cAMP

Question 5

OSMOREGULATION

i) in relation to ADH levels, urine concentration and urine output - what is seen in a) low plasma osmolality and b) high plasma osmolality?
ii) how is thirst affected in a) high osmolality and b) low osmolality
iii) how is an overshoot of ADH avoided when rehydrating?

Answer 5

i) a) low osmol (hydrated) = low ADH levels, dilute urine, high urine output
b) high osmol (dehydrated) = high ADH levels, conc urine and low urine output

ii) high osmol = thirsty and low osmol = not thirsty
iii) drinking immediately and transiently supresses ADH secretion and thirst to avoid overshoot

Question 6

POLYURIA AND POLYDIPSIA

i) which diagnosis needs to be excluded first?
ii) what are the three other main causes?
iii) what happens in each condition?

Answer 6

i) exclude diabetes mellitus
ii) cranial diabetes incipidus, nephrogenic diabetes incipidus, primary polydipsia

iii) cranial (central) DI = lack of ADH secretion
- nephrogenic DI = lack of response of renal tubule to ADH
- primary polydipsia = habitual/psychogenic

Question 7

CRANIAL DIABETES INCIPIDUS

i) whats the problem?
ii) what % is idiopathic and what % is genetic? name two genetic abnormalities that can cause it
iii) what is the most common cause?
iv) how does it effect urine output?
v) how is thirst sensation affected?

Answer 7

i) ADH is not being produced/secreted

ii) 27% idiopathic
- <5% genetic - familial dominant mut in the AVP gene or Wolfram syndrome

iii) most common cause is secondary DI eg damage from surgery or trauma
iv) increases solute free water water excretion (polyuria)
v) if thirst sensation is in tact and there is access to fluids then there will be excess thirst (polydipsia)

Question 8

HYPOTHALAMIC SYNDROME

i) what is it?
ii) give five things that may be disordered
iii) is it easy to treat?
iv) what may cause it?

Answer 8

i) cluster of problems if the hypothalamus doesnt work properly
ii) disordered thirst/DI, increased appetite, disordered temp reg, disordered sleep rhythm and hypopituitarism
iii) hard to treat
iv) may be caused by a hypothalamic tumour

Question 9

NEPHROGENIC DIABETES INCIPIDUS

i) what is it?
ii) how are urine output and thirst affected?
iii) name five causes
iv) where is the mutation if genetic cause? (2)
v) how may the patient present if there is a metabolic cause?
vi) name a drug that can cause it

Answer 9

i) renal tubules are resistant to ADH
ii) causes polyuria and polydipsia
iii) idiopathic, genetic, metabolic, drug, chronic kidney disease
iv) mutation of V2 receptor or AQP gene
v) high calcium or low potassium
vi) can be caused by lithium treatment

Question 10

PRIMARY POLYDIPSIA

i) what is it?
ii) how is fluid intake, plasma osmolality, ADH secretion affected?
iii) how is urine osmolality and output affected?
iv) how is the kidney impacted?

Answer 10

i) psychogenic excess drinking
ii) increased fluid intake, decreased plasma osmolal, decreased ADH secretion
iii) urine osmolality is decreased and output is increased = polyuria
iv) lose renal interstitial solute which reduces the renal concentrating ability

Question 11

INVESTIGATING POLYURIA AND POLYDIPSIA

i) what must first be excluded in the diagnosis?
ii) what should be documented over 24 hrs?
iii) which calcium/potassium levels must be excluded? why?
iv) which test can aid diagnosis?
v) when do patients with primary polydipsia experience less severe problems?
vi) do patients with central/nephrogenic DI experience diurnal variation in symptoms?

Answer 11

i) diabetes mellitus
ii) fluid balance should be documented over 24hrs (urine output and fluid intake in the day and night)
iii) hypercalcaemia and hypokalemia - this is diagnostic of nephrogenic DI
iv) water deprivation test
v) primary polydipsia = less severe at night
vi) no - central/nephro DI is bad all the time

Question 12

WATER DEPRIVATION TEST

i) what happens first?
ii) what is given IV to the patient? why?
iii) what would be expected to be seen post dehydration and post treatment in a) normal response, b) cranial DI, c) nephrogenic DI

Answer 12

i) period of dehydration and measuer plasma/urine osmolal and compare to weight
ii) give IV synthetic vasopressin (desmopressin) and then measure the plasma and urine osmolal - does the kidney respond?
iii) normal response post dehydrat = normal plasma osmol but high urine osmol

cranial DI = poor urine concentration post dehydration and a rise in urine osmolality after desmopressin

nephro DI = poor urine conc post dehyration and no rise in osmolality post desmopressin as they kidney cant respond

Question 13

TREATMENT

i) what is the primary treatment for cranial DI? what can overtreatment cause?
ii) what is the primary tx for nephro DI? what two drugs may be given?
iii) what name two treatments for primary polydipsia?

Answer 13

i) desmopressin (DDAVP)
- overtreatment can cause hyponatremia

ii) correct the cause of the DI eg metabolic or drugs
- may also give thiazide diuretics or NSAIDS

iii) primary polydipsia - explanation or psychotherapy

Question 14

HYPONATRAEMIA

i) what concentrations of sodium define it? what is defined as severe?
ii) what do symptoms depend on? (2)
iii) what happens in mild hyponatremia?
iv) name four none specific symptoms
v) name four severe/sudden symptoms

Answer 14

i) Na <135mmol/L
severe = <125 mmol/L

ii) symptoms depend on absolute values of sodium and the rate of fall
iii) if mild - the brain can adapt
iv) headaches, nausea, mood change, lethargy
v) confusion, drowsiness, seizures, coma

Question 15

CLASSIFICATION OF HYPONATRAEMIA

i) what could be a drug cause?
ii) high concs of what can cause it aka pseudo hyponatraemia? (3)
iii) what else can it be classified by?
iv) what causes hypovolaemia? name two ways this can happen
v) what causes hyponatremia with normovolaemia? (3)
vi) name four things that can cause hyponatremia with hypervolaemia

Answer 15

i) thiazide diuretics
ii) plasma lipids, proteins, glucose
iii) can also be classified by extracellular fluid volume status eg hypo, normo and hyper

iv) hypovolaemia caused by loss of salt and water
- can be a renal loss or non renal loss (D&V, burns, sweating)

v) normovolaemia = endocrine causes such as hypoadrenalism and hypothyroidism
- or syndrome of appropriate ADH (SIADH)

vi) hypervolaemia caused by renal failure, cardiac fail, cirrhosis, excess IV dextrose (IV fluid)

Question 16

SYNDROME OF INAPPROPRIATE ADH SECRETION

i) what is it? where is water travelling from and to?
ii) how will the patient appear in relation to volume?
iii) how is plasma sodium and plasma osmolality implicated?
iv) how is urine sodium and urine osmolality implicated?
v) function of which three organs should be assessed?
vi) name four possible causes

Answer 16

i) excess ADH release causes water to move out of the urine and into the renal tubules
ii) patient will be euvolemic
iii) low plasma sodium and osmolality
iv) high urine sodium and osmolality
v) assess kidney, adrenal and thyroid function
vi) many causes - neoplasia, neuro disorder, endocrine (check 9am cortisol) , lung disease

Question 17

SIADH TREATMENT

i) what must first be addressed?
ii) how much fluid should the patient be restricted to per day? what is the aim of this?
iii) which drug can be given that may induce mild nephro DI?
iv) what other drug can be given? what do they do? are these commonly given? why?
v) what happens if severe hyponatremia is not corrected slowly? (2)
vi) what group of people are particularly at risk of this?

Answer 17

i) the underlying cause
ii) restrict patients to <1000ml per day with the aim to normalise sodium levels
iii) demeclocycline

iv) can also give V2 receptor antagonists = vaptans
- induce a water diuresis
- not commonly given as expensive, variable response, lack of clinically significant outcome data

v) if not corrected slowly = neurological symptoms
- oligodendrocyte degeneration and CNS myelinolysis

vi) alchoholics and malnourished patients are most at risk of the neurolog complications