ADH, Sodium Flashcards
Neural response to acute and chronic HYPO tonicity
ACUTE:
hypotonicity → increased hydrostatic pressure in interstitial compartment → forced loss of Na-containing ECF into the CSF → resulting brain water content is a lot less than anticipated
Concurrent movement of K out of cells provides further protection
CHRONIC
After 24-48h there is reduction in neuronal organic solutes (Na, K, glutamine, glutamate, taurine, polyols) which reduces their osmotic concentration
Neuronal response to HYPERosmolality
ACUTE:
osmotic movement of water out of neuronal cells. → rapid ↓ in brain volume → haemorrhage (seen when serum Na exceeds >170mEq/L)
CHRONIC
production of osmolytes/idogenic osmoles prevents movement of water out of neural cells
Mechanisms controlling ECV (water balance)
Increase - detected by atrial stretch receptors –> release of ANP –> inhibits Na reabsorption, increases GFR
Also reduced SNS firing due to increased firing from carotid body sensors –> reduced ADH release and reduced aldosterone
DECREASE
Carotid sinus –> increased SNS firing increases vascular tone and stimulates RAAS
Renal juxtaglomerular cells detect drop in perfusion and activate RAAS –> ANgII, aldosterone and ADH –> isotonic fluid reabsorption
How are changes to osmolality detected and adjusted
Hypothalamic osmoreceptors adjust production of ADH dependent on Na/Osm
–> increase ADH if osmolality/Na is high thus promoting retention of water
Opposite if Na is low.
Cause of hypernatraemia and 3 classifications
Generally a H20 deficit so approach by assessing volume status
- Hypovolaemia (isotonic water loss generally have the greatest vol depletion)
- Renal: appropriate (osmotic or drug induced diuresis); inappropriate (CKD, nonoliguric AKI, post-obstructive diuresis)
- Extra-renal: GI (V, D, obstruction); 3rd space (pancreatitis, pleural eff); Cutaneous - Normovolaemia = pure water deficit
- insensible loss (fever, tachypnoea)
Hypodypsia (neurological dz, thirst centre defect, ADH defect)
- CDI/NDI - ADH dysfunction
Lack of water access - Hypervolemia (solute gain):
- Salt poison
- Hypertonic fluids
Hyperaldosteronism
- HAC
Tx for different types of hyperNa
Hypovolaemic - isotonic fluids, may need 4x initial calculated deficit
Normovolemic - 5% dextrose to replace pure water deficit
Hypervol - 5% dextrose, or if CHF/CKD then use loop diuretic
Correct over 48h if chronic (10-12mEq/L/24h)
Hyponatraemia causes and classifications
Generally caused by excess water
Most are LOW OSMOLALITY
1. Hypervolemic: renal failure, nephrotic syndrome, CHF, liver failure
(all cause perception of reduced ECV thus nonosmotic ADH release and water retention despite low osmolality) Renal failure may also be unable to excrete sufficient water.
Also water intoxication
- Normovolaemia: SIADH (paraneoplastic, drugs); hypothyroidism (myxoedema), Hypotonic fluids, Psychogenic polydipsia, reset osmostat
(Low Na, high Urine osmolality and high Ur Na) - Hypovolaemia:
Addison’s, Nephropathy (salt losing); GI loss, 3rd space loss; excessive diuretic use
NORMAL OSMOLaLITY - pseudo/spurious due to increased protein or lipid (measured osmolality will be normal)
HIGH OSMOLALITY - hyperglycemia, mannitol or severe azotaemia
Adverse effect of rapid hypoNa correction
increase in serum Na concentration provokes osmotic water movement out of the cells and brain cell shrinkage occurs. Brain shrinkage can cause vascular rupture leading to cerebral bleeding –> acute neurological signs (seizures, coma)
Delayed effects = osmotic demyelination syndrome. Inability to regenerate osmolytes (K. glutamine etc) –> seems pons is most affected possibly due to reduced ability to replace these solutes
Correction speed of hypoNa
Many hyponatremic patients do not have a Na deficit but rather an excess of free water
secondary to ADH secretion because of low ECF (ie, interstitial dehydration with or
without hypovolemia). In such cases, hyponatremia will resolve if patients are provided
with an appropriate volume of isotonic crystalloid fluid
Symptomatic acute hyponatremia can be corrected relatively quickly (1–2 mEq/L/h or more rapidly)
Severe clinical signs (eg, seizures) due to hyponatremia also can be corrected rapidly, with the goal of increasing serum Na concentration by 3 to 7 mEq/L then reducing
(0.6 X BW [kg]) X ([desired serum Na – measured serum Na] x1000)
divided by (Na concentration of fluid [mEq/L] x hours)
Restrict water intake to match UOP
Discontinue drugs with antidiuretic effects
symptomatic hyponatremia without evidence of hypovolemia should be treated with 0.9% NaCl and diuretics, such as furosemide, combined with water restriction. This approach is used primarily in patients with liver failure.
Control of ECV/water consumption and urine production
Water consumption and urine production are controlled through the interaction between
Plasma osmolality
Fluid volume in the vascular compartment
Thirst centre
Kidney
Pituitary gland
Hypothalamus
Receptors and functions of ADH
V2 receptor activation mediates antidiuretic effects (through cAMP 2nd messenger) through aquaporin incorporation into collecting duct membrane –> passive movement of water via concentration gradient)
Also enhances Na Cl and reabsorption in the thick ascending loop - helps to keep the medulla hypertonic.
AND inn arterioles release of vWF, tissue plasminogen activator; ANP and synthesis of NO.
V1a receptors → vascular smooth muscle contraction
This causes an effective increase in ECV by vasoconstriction → return of baroreceptor tonic inhibition of ADH release
V1b receptors stimulate ACTH release as well as catecholamine and insulin secretion.
Differentials for PUPD (19)
Diabetes mellitus
Rising blood glucose exceeds renal threshold
Glucose appears in urine and acts as an osmotic diuretic
Primary renal glycosuria
Congenital renal tubular disorder resulting from the inability to reabsorb the glucose from the ultrafiltrate in the nephron
In falconi there is loss of other solutes
Glucose appears in urine and acts as an osmotic diuretic
CRF
Osmotic diuresis that is further complicated by a reduced medullary concentration gradient
Post obstructive diuresis
Marked osmotic diuresis can develop once the obstruction is relieved
CDI
Lack of ADH production
NDI (primary and secondary)
Lack of response to ADH receptors in the kidney
Hypercalcaemia
Down regulation of aquaporin 2 water channel and decreased function of AVP to its binding site
Receptor site issues (inhibition of binding, inactivation of adenylate cyclase, or decreased transport of Na and Cl)
Hepatic insufficiency and shunts
Exact cause unknown
Loss of impaired urea production, or altered blood flow, changed GFR
Impaired metabolism of cortisol
Primary polydipsia
hypokalemia
Hyperadrenocorticism
Glucocorticoids inhibits ADH release with a direct effect in the hypothalamus
Increase in the osmotic threshold and a decrease in the sensitivity of the AVP response to increasing osmolality
Increase GFR, proximal tubular epithelial sodium transport
Causes resistance to AVP at the level of the kidney
Could also have deficiency from direct compression from a pituitary mass
Primary hyperaldosteronism
Exact mechanism unknown
Mineralcorticoid induced renal resistance to the actions of AVP and disturbed osmoregulation of AVP release has been reported
Hypokalaemia could contribute
Pyelonephritis
Infection and inflammation can destroy countercurrent mechanism in the renal medulla and the collecting ducts
E.coli can bind to AVP receptors
Hypokalaemia
Thought that hypokalaemia renders the terminal nephron of the is less responsive to ADH
Down regulation of aquaporins
Addison’s disease
Mineralocorticoid deficiency results in chronic sodium wasting, renal medullary solute washout, loss of medullary hypertonic gradient
Hypercalcaemia may also contribute
Hyperthyroidism
Exact cause of PU/PD unknown
Increased blood flow may decrease the medullary hypertonicity and impair water reabsorption from the distal portion of the nephron.
Thyroidoxicosis may cause psychogenic polydipsia
Acromegaly
Polyuria from associated with osmotic diuresis induced by glycosuria
Possibly also due to the development of renal disease.
Polycythemia
Increased blood volume and hyperviscosity simulates atrial natriuretic peptide secretion (ANP)
ANP inhibits the release of ADH from the hypothalamus and also its responsiveness to AVP.
Renal medullary solute washout
Loss of renal medullary solutes (Na and urea) results in a loss of medullary hypertonicity and impaired ability of the nephron to concentrate the ultrafiltrate
May interfere with modified water deprivation test
Psychogenic polydipsia
May be induced by another disease or be associated with a learned behaviour
Iatrogenic/ Drug induced
Approach to PUPD
Any USG <1.012 should be investigated for PUPD
Water >100 ml/kg/day (often >5x this in CDI/NDI)
Urine >50 ml/kg/day
Approach to PUPD - after confirming one of the above
1) Assess for other evidence of endocrine disease (skin, polyphagia, pot-belly); entire female pyometra; ADH antagonistic medications; evidence of malignancy
2) Urinalysis: osmotic diuresis (glucose or ketones); infectious; proteinuria (CKD, hypertension)\
NB - prerenal azotemia can develop with water dep.
3) USG: <1.006 (CDI/NDI); >1.030 (Psych?)
4) CBC (inflam, polycythemia); Bio (endocrine changes, Ca; liver dz, kidney dz; TT4)
5) Ultrasound: adrenals, liver, kidneys
→ rule out HAC, Addisons, hyperTH, hyperCa, CKD, liver disease, pyelonephritis/pyometra, hypertension
6) MWDT or DDAVP trial - can only interpret if acquired NDI causes have been ruled out.
Findings in psychogenic polydipsia
Hyperactive, young working dogs most common - behavioural cause
Secondary to hypothalamic lesion affecting the thirst centre also reported.
Plasma osmolality normally low - compared to high in CDI/NDI dogs
Hypertonic saline IV: increases urine osmolality in PP dogs but not CDI/NDI
MWDT - PP: may not dehydrate, USG increases, DDAVP does not increase further
DDAVP trial mild change for PP (may develop hyponatraemia if keep drinking)
Differentials for secondary NDI
Cushings, pyometra, pyelonephritis, liver disease, hyperCa, hypoNa, hypoK)
→ tend to have less severe/persistent hyposthenuria (1.006-1.020)
