L10 - Physiology of Thirst and Fluid Balance and its Disorders Flashcards
what is the importance of water homeostasis
what are the 3 key determinants
Importance:
• Regulation of water balance ensures plasma osmolality (and extracellular fluid osmolality) remains stable
Narrow range of plasma
osmolality
— 285-295 mosmol/kg
3 key determinants:
Antidiuretic hormone (ADH)
— Osmotically stimulated
secretion
— Acts on renal tubule to allow changes in water excretion
Kidney
Wide variation in urine
output (0.5-20 L/day)
Thirst
— Osmoregulated
— Stimulates fluid intake output (0 5 -20 /day )
Osmoreceptors
what are they
where are they located
what do they do
what does this initiate
• Osmoreceptors are groups of specialised cells which detect changes in plasma osmolality (esp sodium)
• Located in the anterior wall of 3rd ventricle
— Fenestrations in the blood-brain barrier allow circulating solutes (osmoles) to influence brain osmoreceptors
’ Osmoreceptor cells alter their volume by a
transmembrane flux of water in response to changes in plasma osmolality
This initiates neuronal impulses that are transmitted to the hypothalamus to synthesise ADH, and to the cerebral cortex to register thirst
What is ADH
what is the human form
how is it similar to oxytocin (properties wise)
Anti-diuretic hormone (ADH) ADH = 'against a diuresis' — water conserving ' Human form of ADH is arginine vasopressin (AVP)
' Like oxytocin: — Nonapeptide -9 amino acid peptide — Vasopressin synthesised in neurons in supraoptic and paraventricular nuclei of the hypothalamus — Secretory granules migrate down axons to posterior pituitary from where AVP is released ( AVP )
ADH action in the kidney
what is it mediated by
what happens after this
what happens after ADH is cleared
ADH action mediated via V2 receptors
‘ ADH-sensitive water channel (aquaporin) normally stored in cytoplasmic vesicles, moves to & fuses with the luminal membrane
’ Increases water permeability of renal collecting tubules, promoting water reabsorption
’ When ADH cleared — water channels removed
from the luminal surface (endocytosis) and returned to cytoplasm
OSMOREGULATION
what happens with AVP and kidney at high and low plasma osmolality
what happens with thirst at low and high
AVP and the kidney—
• Low plasma osmolality — AVP undetectable — Dilute urine High urine output High plasma osmolality
High AVP secretion
— Concentrated urine
Low urine output
Thirst—-
’ Low plasma osmolality
— No thirst
High osmolality — Increased thirst sensation — Drinking immediately transiently suppresses AVP secretion and thirst • Avoids 'overshoot' Low plasma osmolality
what is the relationship between plasma AVP and plasma / urine osmolality
increases
POLYURIA AND POLYDIPSIA
what do you want to exclude
what are the 3 other main causes
Exclude diabetes mellitus
— Cranial (central) diabetes
insipidus (DI)
• Lack of osmoregulated AVP secretion
— Nephrogenic diabetes
insipidus (DI)
• Lack of response of the
renal tubule to AVP
— Primary polydipsia
• Psychogenic polydipsia,
social/cultural
• All may be ‘partial’
CRANIAL DIABETES INSIPIDUS
what are the various causes of it?
’ Idiopathic (27%)
Genetic (<5%)
— Familial (AD) mutation of AVP gene
— DIDMOAD (Wolfram) (Ar, incomplete penetrance)
’ Secondary (commonest causes)—–
— Post-surgical (pituitary / other brain operations)
— Traumatic (head injury, including closed injury)
— Rarer causes
• Tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune
CRANIAL DI
what causes it
what happens with it
what can help keep a stable plasma osmolality
Decreased osmoregulated AVP secretion
’ Excess solute-free renal water excretion
— polyuria
’ Provided thirst sensation remains intact and there is ready access to fluids, thirst is stimulated to maintain a stable, normal plasma osmolality
— polydipsia
Hypothalamic syndrome
what is it
what the effects of it
Disordered thirst and DI Disordered appetite (hyperphagia) Disordered temperature regulation Disordered sleep rhythm Hypopituitarism
NEPHROGENIC DIABETES INSIPIDUS
what happens here
’ Renal tubules resistant to AVP
— Polyuria
’ Thirst stimulated
— Polydipsia
NEPHROGENIC DIABETES INSIPIDUS
what are the various causes
’ Idiopathic
Genetic (rare) Xr or Ar
— Mutations of V2 receptor gene / aquaporin gene
’ Metabolic
— High [calcium] or low [potassium]
’ Drugs
— Lithium
’ Chronic kidney disease
what is primary polydipsia
what happens with it
what are the various effects
’ Increased fluid intake
— polydipsia
’ Lower plasma osmolality
’ Suppressed AVP secretion
’ Low urine osmolality, high urine output
— Polyuria
Also lose renal interstitial solute, reducing renal concentrating ability
Investigating polyuria and polydipsia
what would you do and what would u exclude and what would you document and tests
’ Medical History
Exclude diabetes mellitus
’ Document 24 hour fluid balance
— Urine output and fluid intake, day & night
’ Exclude hypercalcaemia / hypokalaemia
’ Water deprivation test
Water deprivation test
what happens
what is done what is measured what is given
’ Period of dehydration
’ Measure plasma and urine osmolalities & weight
’ Injection of synthetic vasopressin
- Desmopressin (DDAVP)
’ Measure plasma and urine osmolalities
water deprivation test
what is a normal response to dehydration?
what would happen with crainial and nephrogenic DI to urine osmolality / conc after dehydration or desmopressin
Normal response to dehydration
— Normal plasma osmolality, high urine osmolality
’ Cranial diabetes insipidus
— Poor urine concentration after dehydration
— Rise in urine osmolality after desmopressin
’ Nephrogenic diabetes insipidus
— Poor urine concentration after dehydration
— No rise in urine osmolality after desmopressin
what is the treatment for cranial DI, nephrogenic DI and primary polydipsia
(what happens with overtreatment of cranial DI)
’ Cranial diabetes insipidus
— DDAVP (desmopressin)
— Over-treatment can cause hyponatraemia
’ Nephrogenic diabetes insipidus
— Correction of cause (metabolic / drug cause)
— Thiazide diuretics / NSAlDs
’ Primary polydipsia
— Explanation, persuasion
— Psychological therapy
HYPONATRAEMIA
what is the definition? severe?
what are the symptoms
[Sodium] <135 mmol/L
Severe [Na] <125 mmol/L
SYMP
–May be asymptomatic
- -Depends on rate of fall as well as absolute value
- ——-— Brain adapts (chronic)
–Non-specific
———– Headache, nausea, mood
change, cramps, lethargy
–Severe / sudden
——– Confusion, drowsiness,
seizures, coma
CLASSIFYING OF HYPONATRAEMIA
what would you exclude in terms of causes
what would you exclude in terms of high concs
how DO you classify? (3 types)
—causes for each?
Exclude ‘drug’ causes
— Thiazide diuretics, others
Exclude high concentrations of
— Glucose, plasma lipids or proteins
’ Classify by extracellular fluid volume status
— Hypovolaemia
• Renal loss, non-renal loss (D&V, burns, sweating)
— Normovolaemia (euvolaemia)
• Hypoadrenalism, hypothyroidism
• Syndrome of inappropriate ADH secretion (SIADH)
— Hypervolaemia
• Renal failure, cardiac failure, cirrhosis, excess IV dextrose
SIADH
what signs would help diagnose the patent
what would you assess
what are some causes of SIADH
Diagnosis
— Clinically euvolaemic patient
— Low plasma sodium and low plasma osmolality
— Inappropriately high urine sodium concentration and high urine osmolality
’ Assess renal, adrenal and thyroid function
Many causes
— Neoplasias, neurological disorders (CNS), lung disease,
drugs, endocrine (hypothyroid/hypoadrenalism)
SIADH treatment
what are the options what do each of these do
’ Identify and treat the underlying cause
’ Fluid restriction (<1000 ml daily)
— Induce negative fluid balance 500 ml
— Aim ‘low normal’ sodium
Demeclocycline
— Drug that induces mild nephrogenic DI
’ Vasopressin (V2 receptor) antagonists
—“Vaptans” — induce a water diuresis
— Expensive, variable responses, some attenuation
— Lack of clinically significant outcome data
Hyponatraemia treatment
why is it important to correct severe hyponatraemia a certain way
’ Correct severe hyponatraemia slowly
Rapid correction risks oligodendrocyte
degeneration and CNS myelinolysis (osmotic
demyelination)
— Severe neurological sequelae, may be permanent
— Alcoholics & malnourished particularly at risk
