T1 L10 Physiology of thirst, fluid balance and disorders Flashcards
What does regulation of water balance ensure?
Plasma osmolality and extracellular fluid osmolality remains stable
What is the range of plasma osmolality?
285-295mosmol/kg
What are the 3 key determinants of water homeostasis?
ADH
Kidney
Thirst
What are osmoreceptors?
Groups of specialised cells which detect changes in plasma osmolality
Where are osmoreceptors located?
In anterior wall of third ventricle
How do osmoreceptors alter their volume?
By transmembrane flu of water in response to changes in plasma osmolality
What is the effect of osmoreceptors altering their volume?
Initiates neuronal impulses that are transmitted to the hypothalamus to synthesise ADH and to the cerebral cortex to register thirst
What is arginine vasopressin (AVP)?
Human form of ADH
Nonapeptide
Where is AVP synthesised?
In neurons in supraoptic and paraventricular nuclei of hypothalamus
What happens to the aquaporins when ADH is released?
Aquaporins are normally stored in cytoplasmic vesicle
Move and fuse with luminal membrane
Increases water permeability of renal collecting tubules to promote water reabsorption
Describe low plasma osmolality
AVP is undetectable
Dilute urine
High urine output
Describe high plasma osmolality
High AVP secretion
Concentrated urine
Low urine output
What happens to thirst in high plasma osmolality?
Increased thirst sensation
Drinking immediately transiently suppresses AVP secretion and thirst to avoid overshoot
What are the main causes of polyuria and polydipsia?
Diabetes mellitus
Cranial diabetes insipidus
Nephrogenic diabetes insipidus
Primary polydipsia
What is cranial diabetes insidious?
Lack of osmoregulated AVP secretion
What is nephrogenic diabetes insidious?
Lack of response of renal tubule to AVP
Thirst is still stimulated - polydipsia
What are the genetic causes of cranial diabetes insipidus?
Familial AD mutation of AVP gene
DIDMOAD
What are the secondary causes of cranial diabetes insipidus?
Post-surgical Traumatic Tumours Histiocytosis Sarcoidosis Encephalitis Meningitis Vascular insults Autoimmune
Describe hypothalamic syndrome
Disordered thirst and diabetes insidious Disordered appetite Disordered temperature regulation Disordered sleep rhythm Hypopituitarism
What can cause nephrogenic diabetes insipidus?
Idiopathic Genetic Metabolic: high calcium concentration or low potassium concentration Drugs: lithium Chronic kidney disease
What is primary polydipsia?
Psychogenic Increased fluid intake Lower plasma osmolality Suppressed AVP secretion Low urine osmolality, high urine output Lose renal interstitial solute which reduces renal concentrating ability
How is polyuria and polydipsia investigated?
Medical history Exclude diabetes mellitus 24 hour fluid balance Exclude hypercalcaemia / hypokalaemia Water deprivation test
What are the steps of the water deprivation test?
1) Period of dehydration
2) Measure plasma and urine osmolalities and weight
3) Injection of synthetic vasopressin
4) Measure plasma and urine osmolalities
What is the normal response of the water deprivation test?
Normal plasma osmolality
High urine osmolality
What is the response of the water deprivation test in cranial diabetes insipidus?
Poor urine concentration after dehydration
Rise in urine osmolality after desmopressin
What is the response of the water deprivation test in nephrogenic diabetes insipidus?
Poor urine concentration after dehydration
No rise in urine osmolality after desmopressin
What is the treatment for cranial diabetes insipidus?
DDAVP (desmopressin)
Over treatment can cause hyponatraemia
What is the treatment for nephrogenic diabetes insipidus?
Correction of cause
Thiazide diuretics / NSAIDs
What is the treatment for primary polydipsia?
Explanation, persuasion
Psychological therapy
What is hyponatraemia?
Sodium concentration below 135mmol/L
<125mmol/L if severe
What are the symptoms of hyponatraemia?
Asymptomatic
Non-specific: headache, nausea, mood change, cramps, lethargy
If severe / sudden: confusion, drowsiness, seizures, coma
What drugs can cause hyponatraemia?
Thiazide diuretics
How can hyponatraemia be classified?
Hypovolaemia
Normovolaemia
Hypervolaemia
What are the causes of hypovolaemic hyponatraemia?
Renal loss
Non-renal loss: D&V, burns, sweating
What are the causes of normovolaemic hyponatraemia?
Hypoadrenalism
Hypothyroidism
SIADH
What are the causes of hypervolaemic hyponatraemia?
Renal failure
Cardiac failure
Cirrhosis
Excess IV dextrose
What can happen if hyponatraemia is corrected too quickly?
Risk of oligodendrocyte degeneration and CBS myelinolysis
What is the diagnosis of SIADH?
Clinically euvolaemic patient
Low plasma sodium and low plasma osmolality
Inappropriately high urine sodium concentration and high urine osmolality
What are the causes of SIADH?
Neoplasias Neurological disorders Lung disease Drugs Endocrine
What is the treatment of SIADH?
Identify and treat underlying cause
Fluid restriction
Demeclocycline
Vasopressin antagonists: vaptans
What does demeclocycline do?
Induces mild nephrogenic diabetes insipidus
