Chapter 3- Disorders of Sodium and Water Flashcards
Osmoregulation
- what is sensed
- sensors
- effectors
- what is affected
- plasma osmolality
- hypothalams- osmoreceptors
- vasopressin, thirst
- water excretion, thirst
Volume regulation
- what is sensed
- sensors
- effectors
- what is affected
- ECV (effective circulating volume)
- high pressure receptors (carotid sinus, aortic arch), low pressure receptors (atria, large pulmonary vessels), glomerular arteriole
- RAAS, SNS, ANP, ADH
- Urine sodium excretion
Osmolarity refers to _____?
Osmolality refers to _____?
Osmolarity refers to the number of particles of solute per 1 liter of solution.
Osmolality refers to the number of particles of solute per 1 kg of solution.
Normal plasma osmolality of dogs and cats?
Dog: 290-310 mOsm/kg
Cat: 290-330 mOsm/kg
Equation of calculated plasma osmolality
2Na + BUN/2.8 + Glu/18 (mg/dL)
Causes of abnormal osmolal gap (>10 mOsm/kg)
- unmeasured solute (mannitol, ethylene glycol)
- hyperlipidemia or hyperproteinemia results in pseudohyponatremia
- mannitol
- methanol
- ethylene glycol
- sorbitol
- polyethylene glycol (IV lorazepam)
- propylene glycol (IV lorazepam, diazepam and phenytoin)
- glycine (TURP syndrome)
- maltose (IV IG – Intragram)
Specific gravity depends on 2 things
- number of particles present in the solution
2. molecular weight
Equation of Tonicity (= effective osmolality)
Posm - BUN/2.8
Explain solute diuresis versus water diuresis (cause, difference between plasma osmolality and urine osmolality)
Solute osmolality
- increased urine flow by excessive amount of non-reabsorbed solute within renal tubule (diabetes, mannitol)
- urine osmolality approaches plasma osmolality
Water diuresis
- increased urine flow caused by decreased reabsorption of solute free water in collecting duct (PU secondary with psychogenic polydipsia or diabetes insipidus)
- urine osmolality is less than plasma osmolality
What determines hypo- iso- hyperethenuria?
plasma osmolality
Explain 3 classifications of dehyration (i.e. loss of ___tonic fluid, __ dehydration)
- loss of hypotonic fluid or pure water / hypertonic dehydration
- loss of iso-osmolar fluid / isotonic dehydration
- loss of hypertonic fluid / hypotonic dehydration
Explain causes of each hyponatremia and hypernatremia
Hyponatremia
- patient is unable to excrete ingested water
- urinary and insensible losses have a combined osmolality greater than that of ingested or parenterally administered fluid
Hypernatremia
- water intake has been inadequate
- the lost fluid is hypotonic to ECF
- excessive amount of sodium has been ingested or administered parenterally.
Approximately __% of filtered load of sodium is reabsorbed isosmotically with water in the ______.
67%, proximal tubule
In early proximal tubule, sodium crosses the luminal membrane by _____ with _____, ____, and ____ and in exchange of H+ ions via the _____ (during the latter phase HCO3- is reabsorbed)
In the last proximal tubule, sodium is reabsorbed primarily with ___.
Cotransport, glucose, amino acid, phosphate
luminal Na+-H+ antiporter
Cl-
Approximately __% of filtered load of sodium is reabsorbed in the _________, primarily in the ___ ascending limb.
In the thin ascending limb, Na and Cl are ___ly absorbed.
In the thick ascending limb, Na acrosses the luminal membrane via the Na-H+ anti-porter and by and ________ co-transporter. This cotrasporter is the site of action of the _________.
Loop of Henle, thick ascending limb
passively absorbed in thin ascending limb
Na-K-2Cl cotransporter
Loop diuretics
Approximately __% of filtered load of sodium is reabsorbed in the _____ and _____. In the early distal tubule (up to connecting segment), sodium crosses the luminal membrane by means of an _______. This cotrasporter is inhibited by ________.
5%, distal convoluted tubule and collecting segment.
Na-Cl cotransporter, inhibited by thiazide diuretics.
Approximately __% of filtered load of sodium is reabsorbed in collecting duct. In the late distal tubule and collecting ducts, sodium enters passively through Na+ channels in the luminal membrane of ______. The Na+ channel in the principal cell is blocked by the ______. One of the main effect of _______ is to increase the number of open luminal Na+ channels in the cortical collecting duct, thus altering sodium reabsorption in response to changes in __________.
3% principal cells potassium sparing diuretics aldosterone dietary sodium intake
________ maintains ___ and ___ relatively constant despite fluctuation in systemic arterial pressure, thus, the filtered load of sodium is also kept relatively constant.
autoregulation, renal blood flow, GFR
If spontaneous (primary) fluctuation of GFR occur, the absolute tubular reabsorption of filtered solute changes in a similar direction. Thus, ______ that is reabsorbed remains relatively constant despite spontaneous changes in GFR. This principle is called ______________.
fraction of filtered load
glumerulotubular balance
3 mechanisms of glumerulotubular balance.
- “increased filtered load of other solutes”
spontaneous increase in GFR increase the filtered load of all of these solutes, and their increased concentration in proximal tubule enhances sodium reabsorption. - “efferent arterioles favoring water and solute reabsorption”
changes in peritubular capillary hydrostatic and oncotic pressures. If GFR spontaneously increases without changes in FPR, the blood leaving the efferent arterioles has lower hydrostatic pressure and higher oncotic pressure, thus favoring water and solute reabsroption in the proximal tubules. - “autoregulation”
when renal perfusion pressure is increased, afferent arteriolar constriction prevents transmission of the increased hydrdostatic pressure to the glomerular capillaries and minimizes any increase in GFR and filtered solute load.
T/F: Glomerulotubular balance is evoked by the spontaneous (primary) increase, not the compensatory increase in GFR.
True
Aldosterone is synthesized in the ____ of the adrenal ____.
Zona glomerulosa of adrenal cortex
Release of aldosterone is stimulated by _____.
Release of aldosterone is inhibited by ______.
Stimulated by
AG2, hyperkalemia, ACTH
Inhibited by
dopamine, ANP
Aldosterone increases sodium reabsorption by increasing the ____ and ____ of open ___ channels in luminal membrane of the _____ in the _______.
number and activity of open sodium channel in luminal membrane of the principal cells in the collecting duct
[Peritubular capillary forces]
Increased sodium intake leads to expansion of ECF volume and compensatory increase in both ___ and ___. (i.e. the filteration fraction remains _____). This increases hydrostatic pressure and decreases oncotic pressure in the peritubular capillaries thus reducing sodium and water reabsorption in the proximal tubule.
Decreased sodium intake leads to volume contraction. In this setting, RPF decreases more than GFR. (i.e. filteration fraction ____). This results in decreased hydrostatic pressure and increased oncotic pressure in the peritubular capillaries and enhanced proximal tubular reabsorption of sodium and water.
Increased sodium intake: both RBF and GFF increases, FF remains unchanged.
Decrease sodium intake: RPF decrease morethan GFR (thus FF increases)
Catecholamine-induced vasoconstriction usually affects the ____ more than the ____ arterioles. The resultant ____ filter fraction alters peritubular capillary hemodynamics so as to favor water and sodium reabsroption. Catecholamine also directly stimulate proximal tubular sodium reabsorption through an __ adrenergic effect & stimulate ___ release from the granular cells of the juxtaglomerular apparatus through a ___ adrenergic effect. This direct effect of catecholamine on proximal tubular sodium reabsorption are important because they offset the tendency of the increase in ______ to cause ______.
efferent more than afferent, increased filter fraction.
alpha1- proximal tubular sodium reabsorption
beta1- renin release from JXA
offset the increase in systemic arterial pressure to causre pressure natriuresis.
Angiotensin 2
- angiotensin 2 induced vasoconstriction causes ____ more than ____ arterioles, result in increase in _____ and changes in ______ that facilitate proximal tubular reabsorption of sodium and water.
- AG2 also directly stimulates the ________ in the proximal tubules which facilitate sodium reabsorption.
- AG2 stimulates secretion of ______ from the adrenal gland.
- efferent more than afferent, increase in FF and changes in peritubulra capillary starling force
- Na-H antiporter
- aldosterone
ANP (atrial natriuretic peptide)
ANP is released in response to _____ caused by ______. ANP causes dilation of _____ and constriction of ______ to ______ GFR.
ANP also inhibits ____, _____, and ____.
atrial distention caused by volume expansion.
ANP dilate afferent and constrict efferent to increase GFR.
Renin, AG2, aldosterone.
Vasopressin is synthesized in _____ and is released at the level of _____.
hypothalamus, neurohypophysis
Vasopressin attaches to _______ on the basolateral membrane of principal cells of the cortical and medullary collecting ducts.
Vasopressin attaches to___ located in vascular smooth muscle and cause ______.
Vasopressin binds ___ in hypothalamus where AVP binding leads to increased secretion of _______.
V2: collecting duct
V1a: vascular smooth muscle
V1b: hypothalamus, increase secretion of corticotropin
Vasopressin _____ the reabsorption of water in the _____ of the kindeys, and _____ the permeability of ____ to urea.
increase, collecting duct
increase, collecting duct
Major stimulus for vasopressin release is ______ of plasma reaching the _______ of the hypothalamus.
The next most important stimulus for vasopressin release is _______ sensed by _____ in the left atriu, aortic sinus, and carotid sinuses.
Nonosmotic stimulation of vasopressin by actual or perceived volume depletion plays a major role in the generation and perpetuation of hyponatremia in states of _______ and in some conditions (____, ____, ____) associated with hypervolemia.
hypertonicity, osmoreceptor
volume contraction sensed by baroreceptors
true volume depletion
heart failure, liver failure, nephrotic syndrome
Three conditions must be met for kidneys to excrete a water load normally.
- adequate delivery of tubular fluid to distal diluting sites (ascending limb of Henle’s loop) where NaCl is removed without water, rendering the tubular fluid hyoptonic to the medullary interstitium.
- ascending limb of Henle’s loop must function normally. NaCl must be removed without water.
- in the absence of vasopressin, the collecting duct must remain impearmeable to water throughout their course.
Defense against hypotonicity
- “Fluid out of brain by CSF”
Increase in hydrostatic pressure in the interstitial compartment of the brain immediately forces sodium-containing ECF into CSF. this movement of fluid out of the brain. - “Potassium out”
First 24 hours, movement of potassium out of cells. - ” Organic solute out”
After 24-48 hours, reduction in the cellular content of organic solutes.
If correction of hyponatremia proceeds more quickly than recovery of lost solutes can occur, a devastating complication of treatment called “___________” may occur.
ODS (osmotic demyelination syndrome: myelinolysis)
True/False: hypernatremia is less common than hyponatrmiea.
True (intense thirst normally protects against development of hypernatremia unless water is not available or a neurological disorder is present)
Causes of hypernatremia
- pure water loss (diabetes insipidus, primary hypodipsia e.g. miniature schnauzer, fever, high environmental temperature, inadequate access to water).
- hypotonic fluid loss
1) GI
2) third space loss
3) skin (burn)
4) renal- osmotic diuresis (DM, mannitol)
- chemical diuresis
- CKD
- nonoliguric renal failure
- postobstructive diuresis
- Impermeant solute gain
1) hypertonic fluid (sodium bicarbonate, HTS, parenteral nutrition)
2) salt poisoning
3) hyperaldosteronism
4) hyperadrenocorticism
Explain body’s response to hypertonic saline in 1) normal animal, 2) dogs with hypodipsic hypernatremia
Normal animal
HTS increase osmolality and plasma expansion- osmoreceptor is stimulated by tonicity, but inhibited by volume expansion. But body takes care of tonicity than volume, so will secrete ADH, result in decreased urine volume and increased urine osmolality.
Affected animal with hypodipsic hypernatremia
in response to HTS, they show increased urine volume and decreased urine osmolality, indicating defective osmoreceptor function.
What are the conditions associated with hypodipsic hypernatrmia in dogs?
GME, hydrocephalus and hypopituitarism, dysplasia or rostal diencephalon
What are the common 2 breeds associated with abnormal thirst mechanism- hypodipais-hypernatremia-hypertonicity?
Miniature Schnauzer
Great Dane
CDI is caused by ____ or complete lack of ____ production and release from the _______.
partial, vasopressin, neurohypophysis
Traumatic transient may be ___ in nature. _______ for treatment of hyperadrenocorticism result in transient CDI that may take several weeks to resolve. Marked hypernatremia occurs in dogs in the first 24 hours after hypophysectomy and can be prevented by prophylactic treatment with ______.
Transient, hypophysectomy
DDAVP (desmopressin)
Many older dogs with CDI had ____ in the region of _____ and developed neurological signs.
tumor, pituitary gland
Administration of vasopressin lead to an increase in urine osmolality or specific gravity in dogs and cats with CDI, but the initial response may be less than expected because of _______________.
Renal medullary washout of solute.
DDAVP is a structural analogue of vasopressin that has a more potent _____ effect than vasopressin but a minimal _____ effect and is relatively resistant to metabolic degradation.
more potent anti-diuretic
less potent vasopressive
What are the options for treatment of CDI
- DDAVP
- Thiazide
- Restrict dietary sodium and protein
True/False: hypotonic losses cause a greater reduction in the ECF volume and the animal is more likely to show CS of volume depletion.
True, when hypotonic fluid is lost from the extracellular compartment, the osmotic stimulus for water to move from the intracellular to the extracellular compartment is less than the stimulus for water movement created by pure water loss. More closely the fluid lost approximates ECF in tonicity, the greater the volume loss from the ICF compartment.
_____ fluid losses are the most common type in small animal medicine.
hypotonic fluid loss
Paintball (polyehylene glycol, glycerol, and sorbitol) develop hypernatremia, why?
These ingredient are osmotic laxative, causing a shift in water from the tissues into the lumen of the bowel and resulting in hypernatremia.
Depending on the duration of onset, _____ (acute onset) or ____ (unknown onset) can be administered to gradually correct hypernatremia.
D5W for acute onset, 0.45% NaCl for unknown onset.
True/False: The severity of clinical sign is related more to the rapidity of onset of hypernatremia than to the magnitude of hypernatremia.
True
Onset of CS from hypernatremia is observed when serum sodium concentration is above ____ mEq/L in dogs and cats
170
CS of hypernatremia: if hypotonic losses are the cause of hypernatremia, CS of ______ may be observed. If gain of sodium causes hypernatremia, CS of _____ may be observed.
Hypotonic loss: volume depletion
Solute gain: overload
