Electrolytes Flashcards
What is the definition of osmolality? Osmolarity?
Osmolality = number of particles of solute per kg of solvent
Osmolarity = number of particles of solute per liter of solvent
What is the normal osmolality for dogs and cats
Dogs: 290-310 mOsm/kg
Cats: 290-330 mOsm/kg
How can serum osmolality be measured
Using a freezing point depression osmometer
What is the osmolal gap and what can cause an increased osmolal gap
Osmolal gap = difference between measured and calculate serum osmolality
Should be close to 0 -> any increase indicates presence of other osmole(s) in circulation:
- lactate
- ethanol
- ethylene glycol
- phosphates
- sulfates
- acetylsalicylic acid
- mannitol
- methanol
- radiographic contrast
- sorbitol (/!\ in patients having received activated charcoal with sorbitol - can falsely elevate osmolal gap)
- propylene glycol
What is the difference between osmolarity and tonicity
Osmolarity includes all the osmoles in solution whereas tonicity only refers to effective osmoses
What is the repartition of total body water between the different compartments
Water = 60% total body weight
1/3 intracellular, 2/3 extracellular (75% interstitial, 25% intravascular)
What are the receptors in charge of osmolality regulation? How sensitive are they?
Osmoreceptors in the hypothalamus.
Detect changes of 2-3 mOsm/L
What are the 2 triggers for ADH release and they respective receptors
- Decreased effective circulating volume -> baroreceptors (aortic arch and carotid bodies)
- always prioritized
- Increased plasma osmolality -> osmoreceptors (hypothalamus)
Secreted by the pituitary gland
What are the 2 mechanisms of regulation of plasma osmolality
- Antidiuretic hormone
- Thirst
What does total body sodium determine
Hydration status (independent from natremia)
What are the mechanisms of cerebral adaptation to hypernatremia / hyponatremia
- Hypernatremia
- Within minutes to hours: loss of neuronal water -> decreased interstitial hydrostatic pressure -> fluid drawn from CSF to interstitium, which brings more sodium -> water reabsorption
- Within 24 hours (2-7 days for full compensation): neuronal accumulation of idiogenic osmoses (inositol, glutamate) -> draw water into cells
- Hyponatremia: the opposite (increased interstitial pressure -> fluid loss into CSF + neurone expel sodium and organic osmolytes)
Free water deficit formula
Free water deficit (L) = [(current Na / normal Na)-1] * 0.6 * body weight (kg)
What is the rate of Na correction in a chronically hypernatremic patient without clinical signs? With clinical signs? In acute hypernatremia?
- Without signs: 0.5-1 mEq/L/h (as per Silverstein ; in other sources: 8-12 mEq/L per 24h)
- With signs: 2 mEq/L/h until signs resolved
- Acute: correct in <12h
(as per Silverstein - achieved by giving D5W following the total body water deficit)
In a hyponatremic patient, how is total body sodium likely to be:
- in a dog with CHF
- in a dog with GI losses
- CHF -> increased total body Na (from RAAS activation) but ADH secretion due to decreased effective circulating volume
- GI losses -> loss of Na and water causing hypovolemia and ADH secretion (decreased total body Na)
List 5 causes of hyponatremia and 5 causes of hypernatremia
- Hyponatremia
- Decreased effective circulating volume (CHF, GI / urinary losses)
- Hypoadrenocorticism (decreased Na reabsorption and ADH due to low effective circulating volume and low cortisol)
- Renal tubular dysfunction (inability to dilute urine + hyperkalemia causing entry of Na into cells)
- SIADH
- Increased water intake (psychogenic polydipsia) - Hypernatremia
- Salt poisoning (seawater, beef jerky, salt-flour dough)
- Restricted access to water
- Syndrome of hypodypsic hypernatremia (Min Schnauzers)
- Urinary, GI, 3rd space, cutaneous water losses with inadequate water intake (osmotic diuresis: DM, mannitol administration)
- Diabetes insipidus with inadequate water intake
Where are myelinolysis (= osmotic demyelination syndrome) lesions commonly seen
Thalamus
What is the treatment recommendation for clinical acute hyponatremia? Chronic?
- Stabilization (for acute and chronic): 2 mL/kg of 3%NaCl over 20 min, repeat as needed to increase Na by 5 mmol/L
- If acute (<48h): infuse 3% NaCl at 0.5-2 mL/kg/h until Na reaches low-normal
- If chronic or unknown, goal to increase Na by no more than 10 mEq/L over first 24h and 8mEq/L over each following 24h - use sodium deficit to know how much sodium to give
Sodium deficit formula
Sodium deficit (mmol) = (target Na+ - patient Na+) * 0.6 * body weight (kg)
What level of hyponatremia puts patients at risk of osmotic demyelination syndrome
Na < 110 mmol/L
How do blood pH and osmolality influence K concentration
- Alkalosis -> intracellular movement of K in exchange for H+ -> hypoK
- Hyperosmolarity -> extracellular movement of water -> extracellular movement of K by solvent drag -> hyperkalemia
What hormones are involved in changes in K concentration
Catecholamines, insulin, aldosterone
What is the kaliuretic feedforward control
Changes in K concentration are sensed in the stomach and hepatic portal region and send signals to the kidneys to adjust kaliuresis based on intake
List causes of hypokalemia
- Disorders of internal balance:
- Metabolic alkalosis
- Insulin therapy
- Beta2-agonist intoxication
- Catecholamines
- Refeeding syndrome - Disorders of external balance
- Prolonged inadequate intake
- Diuretic drugs, osmotic or post-obstructive diuresis
- Renal tubular acidosis
- Hyperladosteronism
- DKA
- Severe diarrhea
What are the 4 categories of consequences of hypokalemia
- Metabolic -> glucose intolerance (altered insulin release)
- Neuromuscular -> muscle weakness (hyperpolarized myocytes)
- Cardiovascular -> prolongation of action potential, AV dissociation, tachyarrhythmias, Vfib (hyperpolarized cardiomyocytes)
- Renal -> impaired tubular function
List causes of hyperkalemia
- Increased intake
- IV supplementation
- Expired pRBC transfusion
- Drugs - Translocation from intracellular to extracellular
- Insulin deficiency
- Mineral acidosis
- Tumor lysis syndrome
- Tissue reperfusion
- CPA - Decreased urinary excretion
- Oligoanuric AKI
- Ureteral / urethral obstruction
- Uroabdomen
- Hypoadrenocorticism
- GI disease (trichuriasis)
- Drugs (ACE inhibitors, angiotensin receptor blockers, aldosterone inhibitor
ECG changes associated with hypokalemia / hyperkalemia
- Hypokalemia
- ST segment depression
- Increased P-wave amplitude
- Prolonged PR interval
- Widened QRS - Hyperkalemia
- Tented T-wave
- Wide QRS
- ST segment depression
- Depressed P-wave / atrial standstill
- Vfib
What is the physiologic response to hypocalcemia
- Secretion of PTH by chief cells of the parathyroid gland
- Increased bone resorption
- Increased Ca reabsorption and decreased P reabsorption by the kidneys
- Hydroxylation of calcidiol to calcitriol in the kidneys -> increased Ca and P intestinal absorption
What is the metabolism leading to calcitriol
- Vitamin D (cholecalciferol) intestinal absorption
- Hydroxylation to 25(OH)D3 (calcidiol) in liver
- Hydroxylation to 1,25(OH)2D3 (calcitriol = 1,25-dihydroxycholecalciferol) in the kidney (proximal tubular cells) by 1α-hydroxylase
Where is calcitonin produced? What are its effects?
- Parafollicular C cells in the thyroid gland
- Inhibits bone resorption and decreases renal tubular absorption of Ca
What is the effect of pH on iCa
Alkalosis increases binding of Ca to albumin -> decreased iCa
What ECG changes can be associated with hypercalcemia / hypocalcemia
- Hypercalcemia
- Prolonged PR interval
- Widened QRS
- Shortened QT interval
- Shortened ST segment
- Widened T wave
- Bradycardia - Hypocalcemia
- Prolonged QT interval
- Deep, wide T waves
- AV block
- Bradycardia
What calcium-phosphorus product indicates a risk of soft tissue mineralization
Calcium * phosphorus > 60 (in mg/dL)
4calcium * 3phosphorus > 60 (in mmol/L)
What are treatments for hypercalcemia and their mechanisms
- 0.9%NaCl diuresis: competition for tubular reabsorption with Na ions
- Furosemide: increases urinary Ca excretion
- Glucocorticoids: reduced bone resorption, decreased intestinal Ca absorption, increased renal Ca excretion
- Calcitonin: decreases activity of osteoclasts
- Sodium bicarbonate: increase Ca protein binding
- Dialysis
- Biphosphonates (pamidronate, zoledronate, alendronate): decrease osteoclast activity - can take up to 3 days, should not be used for crisis
List 5 causes of hypercalcemia and 5 causes of hypocalcemia
- Hypercalcemia
- Hyperparathyroidism
- Hypoadrenocorticism
- Acute or chronic renal disease
- Idiopathic
- Bone resorption (osteosarcoma, osteomyelitis, HOD)
- Neoplasia (lymphoma, multiple myeloma, anal sac apocrine gland adenocarcinoma, carcinoma, etc.)
- Hypervitaminosis D (rodenticide, psoriasis cream, granulomatous disease) - Hypocalcemia
- Eclampsia
- CKD
- Hypoparathyroidism (primary, iatrogenic, nutritional secondary)
- Citrate administration (transfusion)
- Pancreatitis
- Ethylene glycol toxicity
- Tumor lysis syndrome
- Intestinal malabsorption (PLE)
What are treatments for hypocalcemia
- IV calcium (gluconate, or chloride but must be given in central line) -> bolus (0.5-1.5 mL/kg of Ca gluconate) then CRI at 5-15 mg/kg/h of elemental calcium
- Oral calcium 25-50 mg/kg/day (divided BID)
- Calcitriol 5-15 ng/kg/day (divided BID), loading at 20-30 ng/kg/day for 3-4 days
List 4 functions of magnesium
- Coenzyme for Na-K ATPase (effect on potassium concentration)
- Coenzyme for calcium ATPase and proton pump (effect on calcium concentration)
- Participation in protein and nucleic acid synthesis
- Regulation of vascular smooth muscle tone
- Cellular second messenger
What hormones are in charge of magnesium regulation? What are the effector organs?
Hormones increasing Mg:
- PTH
- Calcitonin
- ADH
- Beta-adrenergic agonists
- Epidermal growth factor
Hormone decreasing Mg:
- Prostaglandin E2
Effector organs:
- GI (absorption in small intestine)
- Kidneys (glomerular filtration and reabsorption in distal convoluted tubule and loop of Henle)
What are the 3 categories of hypomagnesemia, with examples for each of them
- Decreased intake
- Increased losses
- GI -> malabsorption, chronic diarrhea
- Renal -> tubular disorders, diuretics, DKA, hyperthyroidism, hyperparathyroidism
- Lactation - Alterations in distribution
- Extracellular to intracellular shift -> glucose / insulin or amino-acid infusion
- Chelation -> elevation in catecholamines (chelation to fat) or massive transfusion (chelation to citrate)
- Sequestration -> pancreatitis (in fat necrosis)
What are the 2 electrolytic disorders commonly associated with hypomagnesemia and why
- Hypokalemia: hypoMg increases renal potassium losses
- Hypocalcemia: hypoMg increases movement of Ca from extracellular to bone and impairs PTH secretion
What is an adverse effect of magnesium sulfate supplementation
Hypocalcemia because sulfate chelates calcium
What is the emergency treatment of hypermagnesemia
Calcium gluconate (calcium is an antagonist of magnesium at the neuromuscular junction)
What are physiologic roles of phosphate
- Incorporated in 2,3-DPG
- Production of ATP
- Organic phosphate: phospholipids, nucleic acids, etc.
- Buffer of acidosis
- Maintenance of bone and teeth matrix (hydroxyapatite)
What hormones are involved in phosphate regulation? What are the effector organs?
- Hormones increasing phosphate:
- Calcitriol
- Growth hormone
- Insulin
- Thyroxine - Hormones decreasing phosphate:
- PTH
- Calcitonin and phosphatonins
- Glucocorticoids
Effector organs:
- GI (absorption in small intestine)
- Kidneys (glomerular filtration and tubular reabsorption in proximal convoluted tubule)
- Bones
List causes of hypophosphatemia
- Decreased GI absorption
- Malnutrition
- Malabsorption
- Diarrhea / steatorrhea
- Phosphate binders (AlOH)
- Vitamin D deficiency - Transcellular shifts
- Alkalosis (increases glycolysis)
- Insulin / dextrose
- Refeeding syndrome
- Catecholamines - Increased urinary losses
- Increased diuresis (osmotic, diuretics, post-obstructive, etc.)
- Hyperparathyroidism (primary or nutritional secondary)
- Glucocorticoids
- Hyperaldosteronism - Spurious
- Hemolysis
- Hyperbilirubinemia
- Mannitol
What are consequences of hypophosphatemia
- Hemolysis (due to decreased RBC ATP and 2,3-DPG)
- Impaired coagulation
- Muscle weakness
- Ileus
- Encephalopathy
What are consequences of hypermagnesemia
- Severe muscle weakness (areflexia, respiratory paralysis)
- Hypotension due to reduced vasomotor tone
- ECG changes and bradycardia
What does urine Na concentration reflect
Effective circulating volume (< 20 mmol/L -> decreased ECV, > 40 mmol/L -> adequate ECV)
Cannot be interpreted in the presence of metabolic alkalosis
What is the transtubular potassium gradient and how is it used
TTKG = (urine K * plasma osmolality) / (urine osmolality * plasma K)
Reflects reabsorption of potassium in the distal convoluted tubule (effect of aldosterone). If <6 in a patient with hyperK, indicates renal cause. If >3 in a patient with hypoK, indicates renal cause.
Cannot be used if urine osmolality is < plasma osmolality of urine Na < 25
What does urine Cl concentration indicate
- Effective circulating volume (< 25 mmol/L -> decreased ECV) ; not affected by metabolic alkalosis, unlike Na urine concentration
- If metabolic alkalosis is chloride responsive (urine Cl < 15-25) or not (urine Cl > 15-25)
What is the urinary free water clearance? What is it used for?
Urinary free water clearance = Urine volume * [1-(urine Na + urine K) / serum Na]
It is used to assess the role of kidneys in dysnatremias:
- in patient with hypoNa, should be positive (if negative, indicates renal cause)
- in patient with hyperNa, should be negative
What are possible mechanisms leading to hypercalcemia in hypoadrenocorticism
- Hemoconcentration
- Decreased GFR
- Metabolic acidosis
- Increased vitamin D activity
- Increased parathyroid activity
What is a simplified relationship between USG and urine osmolality
Multiplying the last 2 digits of USG by 36 gives an estimate of urine osmolality.
Not true if there are some high-molecular-weight solutes in the urine (eg. synthetic colloids)
How do the volume and solute concentration change in the extra-cellular fluid and intra-cellular fluid following:
- pure water loss
- hypotonic fluid loss
- isotonic fluid loss
- hypertonic fluid loss
- isotonic fluid loss with pure water replacement
See picture
What hormones are involved in the regulation of natremia
- Angiotensin II (increases tubular reabsorption)
- Aldosterone (increases tubular reabsorption)
- Catecholamines (increases tubular reabsorption)
- Vasopressin (increases free water diuresis)
- ANP (decreases tubular reabsorption and increases GFR)
What are the possible volume statuses of a hypernatremic patient?
- Hypervolemic -> solute gain (salt poisoning)
- Normovolemic -> free water deficit
- Hypovolemic -> hypotonic loss (renal or extra renal)
What is the treatment for a salt poisoning
D5W potentially combined with a diuretic (furosemide) since the patient is already hypervolemic
What are 2 causes of spurious hyponatremia
Hyperlipidemia and hyperproteinemia (because sodium is only present in the aqueous phase of the serum)
Patient’s measured osmolality will be normal
How can the osmolality be in a patient with hyponatremia
- Increased (hyperglycemia, mannitol causing movement of water from intracellular to extracellular)
- Decreased (decrease in Na without addition of other osmoles)
- Normal (pseudohyponatremia)
Give causes of hypochloremia and hyperchloremia
Hypochloremia:
- GI loss (vomiting of stomach contents)
- Renal loss (loop diuretics)
- Chronic respiratory acidosis
- Hyperadrenocorticism, glucocorticoid administration
Hyperchloremia:
- GI loss of sodium relative to chloride (“loss of HCO3): diarrhea
- Renal chloride retention: RTA, hypoadrenocorticism, chronic respiratory alkalosis
- Therapy with chloride salts, TPN, NaCl fluids
What is the effect of hyperkalemia /
hypokalemia on resting membrane potential
- Hypokalemia “increases” the resting potential = makes it more negative
- Hyperkalemia “decreases” the resting potential = makes it less negative
What is the benefit of calcium administration in hyperkalemia
- Calcium decreases the threshold of depolarization (makes it less negative), re-establishing the difference between the resting membrane potential (decreased by hyperkalemia) and the threshold
- Calcium speeds impulse propagation in SA and AV nodes
=> returns excitability to normal
What is the mechanism of secondary hyperparathyroidism? What is a consequence?
Parathyroid gland becomes hyperplastic with increased secretion of PTH in patients with renal disease or vitamin D deficiency or a low Ca / high P diet.
Due to:
- Increased phosphorus (eg. from decreased phosphorus excretion in renal disease)
- Decreased secretion of calcitriol from vitamin D deficiency or due to diseased kidneys (-> no inhibition of PTH by calcitriol + lower Ca stimulates PTH)
- Lower Ca due to renal losses or low intake
Consequence: bone resorption
What is a cause of hypocalcemia in renal failure
Decreased calcitriol production (decreased activity of 1alpha-hydroxylase in renal tubules)
What are possible causes of hypocalcemia of critical illness
- Decreased PTH secretion
- Hypovitaminosis D
- Hypercalcitonism
- Altered calcium binding to proteins
- Calcium forming complexes with lactate
- Hypomagnesemia (decreases PTH)
(- Underlying disease - Drugs, transfusions)
Where does vitamin D come from in cats and dogs
Diet (intestinal absorption) mostly
Why does hyperphosphatemia lead to hypocalcemia
Mass-law effects: formation of calcium-phosphate salts
Why does bicarbonate administration lead to hypocalcemia
- Alkalosis increases calcium binding to albumin
- Calcium can form complexes with bicarbonates
What is the Adrogue-Madias formula
Gives the expected change in Na after infusion of fluids or the volume of fluid needed to reach a target change in Na
change in serum Na = [(infusate Na + infusate K) - serum Na]*V / (total body water + V)
or
V = (change in Na * total body water) / (infusate Na + infusate K - target Na)
(where V is the volume of fluid administered)
What are the main intracellular / extracellular anions / cations
- Intracellular cations: K+, Mg2+
- Intracellular anions: proteins, phosphates
- Extracellular cations: Na+, Ca2+
- Extracellular anions: Cl-, HCO3-
What is the emergency dose of magnesium sulfate in case of arrhythmias
0.15-0.3 mEq/kg Mg = 0.075-0.15 mmol/kg Mg = 18.75-37.5 mg/kg MgSO4
An animal presents with acute onset of profuse vomiting. The patient is tachycardic, mildly hypotensive, has a decreased ventilation rate and pale MM. Blood gas analysis shows a metabolic alkalosis, hypochloremia, hypokalemia. Explain the pathophysiology behind each abnormality.
+ CV signs:
Decreased blood volume and arterial pressure from vomiting –> activates the baroreceptor reflex –> increased sympathetic outflow to the heart and blood vessels –> tachycardia and vasoconstriction (pale MM)
What are the 3 forms of circulating calcium?
- Ionized (free)
- Protein bound
- Complexed (bound to phosphate, bicarbonate, lactate, citrate, oxalate)
True or false: FGF-23 enhances calcitriol synthesis, while PTH inhibits the synthesis of calcitriol
False! The opposite
What is the cutoff ionized calcium value for hypercalcemia and hypocalcemia in dogs and cats?
Hyper:
Dogs: 1.5 mmol/L
Cats: 1.4 mmol/L
Hypo:
Dogs: 1.25 mmol/L
Cats: 1.1 mmol/L
What is NaCl 0.9% the fluid of choice for hypercalcemia (2 reasons)?
1- Na+ competes with Ca2+ in the renal tubule resulting in calciuresis
2 - NaCl is a calcium free fluid
Ddx for hypocalcemia in the face of hyperphosphatemia?
- Renal dysfunction
- Pancreatitis
- Excessive phosphorus intake
- Primary hypoparathyroidism
In 2018, a prospective multicenter study was done looking at NaHCO3 therapy for patients with severe metabolic academia. What were the outcomes of this study?
- RRT was started earlier in the control groupe vs NaHCO3 group (for AKI patients)
- NaHCO3 therapy was associated with less hyperkalemia
- Number of days free from vasopressors was higher in th NaHCO3 group
- Length of ICU stay did not differ
- NaHCO3 was associated with metabolic alkalosis, hypernatremia, hypocalcemia (not life-threatening)
