Fluids / AB / Electrolytes Flashcards
Definitions:
Hydration
Euhydration
Hypohydration
Dehydration
Hypovolemia
Hyperhydration
Rehydration
o Hydration: the taking in of water. A patient’s total volume of body water (TBW) is reflected in its hydration status.
o Euhydration: a condition of normal water content and a state of being within the range of minimal and maximal urine osmolality.
o Hypohydration: a condition of reduced water content and a state of being over the maximal range of urine osmolality.
o Dehydration: a dynamic state of reducing water content. It occurs as a result of a decreased water intake (water, food) in relation to water lost (in feces, urine, sweat, respiratory vapor). The term is used interchangeably with the term hypohydration. Clinically, this term represents a water deficit in the interstitial and intracellular fluid compartments and not a water deficit in the intravascular space.
o Hypovolemia: a condition of reduced intravascular volume which occurs with plasma water or whole blood loss.
o Hyperhydration (aka overhydration): a condition of excess water content. It refers to the time the TBW increases above basal levels, between the ingestion of water and the renal excretion of water. It may result in a reduction in urine osmolality.
o Rehydration: dynamic state of replacing water lost. This term is not to be used synonymously with intravascular volume resuscitation.
What is the best way to assess hydration status?
o There is no single index that accurately and easily measures hydration and individual fluid compartment water in the critical patient.
o Although extracellular volume can be determined through a number of tests, the continuum of fluid movement from one moment to the next makes it impossible for a static moment in time to be reflected in any single measurement taken to assess TBW.
o The veterinarian has to be familiar with the distribution and control of body water in order to understand how examination skills and point-of-care laboratory indices can be used to make an estimation of a patient’s TBW and individual compartment hydration status and fluid needs.
How much is normally the total body water?
The TBW that occupies the intra- and extracellular compartments is approximately 0.6 L/kg or 60% of body mass.
Distribution of body fluids compartments
o IC - 66% of TBW or 0.4L/kg
o EC - 33% of TBW or 0.2L/kg
o ECF is further compartmentalized into the intravascular portion, which is approximately 25% of ECF volume (8% of TBW), and the remaining 75% of ECF volume (25% TBW) is interstitial fluid.
o Pregnancy, increased salt intake, exercise, and malnutrition as well as acute and chronic conditions will affect TBW and the division of water between the compartments.
Which membranes determine the body compartments?
Body water is distributed across two compartmentalizing membranes
o The endothelial cell lining of capillaries separating the intravascular from the interstitial space.
o The cell membranes separating the ICF from the ECF.
What forces determine movement of water across IC/EC or IS/IV compartments?
o Water moves without restriction across the cell membranes under the influence of osmosis. The osmotic gradient across the cell membrane is dictated by the concentration of osmotically active particles on either side of the membrane and in the normal state is primarily the product of the relative sodium and potassium concentrations, which is controlled by the Na+/K+-ATPase pump on the cell membrane.
o In contrast, water movement across the capillary wall is dictated by Starling’s forces. It is important to note that osmolality does not affect distribution between the interstitial and intravascular space because the capillary wall is freely permeable to small solutes such as sodium and glucose
How is the volume and distribution of TBW regulated?
The volume and distribution of TBW is under the control of hormonal mechanisms that maintain water and sodium balance by regulating renal water and salt excretion and reabsorption, whereas thirst mechanisms influence water intake.
What would happen if we lose hypotonic fluid (water with little or no solute content)?
o A hypotonic fluid loss (water with little or no solute content) will increase plasma solutes per kilogram water (osmolality).
o An increase in the plasma osmolality is detected by the supraoptic and paraventricular nuclei in the hypothalamus and causes the release of ADH, an increase in water reabsorption by the renal collecting ducts, and more concentrated urine.
o An increase in plasma osmolality and a reduction in baroreceptor stretch will also stimulate the thirst center, located near the supraoptic and preoptic nuclei in the anteroventral region of the third ventricle in the brain, and produce the sensation of thirst resulting in water intake.
___ % of acute changes in body mass can be attributed to a change in total body water.
90%
What is the most practical clinical way of monitoring changes in TBW?
o Body weight measurements is the most practical clinical way to monitor changes in TBW and estimating volumes gained or lost, where 1 kg change in TBW may be equivalent to 1 L change in TBW.
o However, changes in body weight may not reliably correspond to clinical parameters of hydration in the small animal ICU population.
o The critical patient with abdominal effusion and peritonitis associated with acute pancreatitis may have a simultaneous collection of fluid in third space fluid compartments and reduction in interstitial and intravascular water -> the body weight may not have changed, individual fluid compartment water has. T
o Body weight changes should not be used alone in determining a patient’s level of hydration.
Why is important to differentiate between intravascular, intracellular or interstitial water deficits?
Because that will determine the type of fluid that we use for replenishment.
Interstitial volume changes - dehydration
o The interstitial fluid compartment is clinically evaluated by examining mucous membrane moisture, skin tent response, eye position, and corneal moisture as well as other parameters
o Loss of interstitial volume causes mucous membranes to become “sticky” when touched (tacky); causes decreased subcutaneous fluidity, identified by decreased skin turgor and, when severe, results in dry corneas and retraction of the eye within the orbit.
o We must estimate the degree of dehydration as a percentage of body weight in kilograms based on these parameters. As a general guideline the minimum degree of interstitial dehydration that can be detected in the average patient is approximately 5% of body weight.
o Interstitial dehydration greater than 12% is likely to be fatal, so the clinician estimates dehydration in the range of 5% to 12% of body weight. It is important to note that there is substantial clinical variation in the correlation between clinical signs and degree of dehydration, so this is an estimate only.
o As changes to the fluid volume of the interstitial space equilibrate with the intravascular space, all patients with evidence of interstitial dehydration will also have a degree of hypovolemia, although interstitial dehydration has to be severe (>10% to 12%) before clinically detectable changes in perfusion are likely to occur.
Interstitial volume changes - overhydration
o Interstitial overhydration causes increased turgor of the skin and subcutaneous tissue, giving it a gelatinous nature; peripheral or ventral pitting edema can also occur.
o Chemosis and clear nasal discharge may also be evident. As fluid volumes are equilibrated between the interstitial space and the intravascular space, interstitial overhydration is associated with hypervolemia and dilution of the packed cell volume (PCV) and total protein (TP); in severe cases, pulmonary and other organ edema may occur.
Interstitial volume changes - factors that can alter parameters to assess interstitial hydration
o Atropine administration (which reduces mucous membrane [MM] moisture), hypersalivation from nausea or pain, advanced age (which reduces skin elasticity), and changes in body fat content.
o It may be more challenging to appreciate dehydration in obese animals, whereas emaciated animals may appear to have decreased skin turgor even when euhydrated.
o Young puppies and kittens can also be difficult to assess because they have very elastic skin, so changes in skin turgor maybe harder to detect. Frequent reassessment and reevaluation are required to monitor response to treatment and adjust therapy accordingly.
Intravascular volume changes
o Clinically, intravascular volume is assessed through the examination of perfusion parameters (mucous membrane color, CRT, heart rate, and pulse quality) and determination of jugular venous distensibility.
o Although intravascular and interstitial water content equilibrates easily, rapid intravascular losses such as hemorrhage can cause hypovolemia without causing clinically detectable changes in the interstitial fluid compartment.
o Excessive intravascular volume will manifest in increased jugular venous distention, in addition to increased central venous pressure. The most obvious and concerning clinical consequence of hypervolemia is pulmonary edema.
Intracellular volume changes
o Intracellular volume changes cannot be identified on physical examination.
o The clinician must rely on changes in the effective osmolality of ECF (primarily changes in Na concentration) to mark changes in cell volume.
o With decreases in ECF effective osmolality there will be an associated movement of water into the ICF compartment and a subsequent increase in intracellular volume.
o With increases in ECF effective osmolality there will be decreases in intracellular volume.
Hypotonic fluid loss
o If TBW loss is due to loss of a fluid with little or no salt content (compared with ECF), the clinical consequences are different than the loss of isotonic fluid from the body (the more common clinical scenario).
o Hypotonic fluid losses will result in increases in ECF osmolality, reflected by increases in serum sodium concentration. As a consequence, water will move from the ICF compartment to the ECF compartment until osmolality is equalized.
o The loss of ICF volume has the greatest impact on the central nervous system, and if the degree of solute-free water loss is severe and acute it can result in neurologic abnormalities and possibly death as a result of neuronal cell shrinkage.
o In cases of substantial hypotonic fluid losses, as might happen with uncontrolled diabetes insipidus, the neurologic consequences will be fatal before there is sufficient ECF volume depletion for it to be clinically identified (i.e., less than approximately 5%).
Isotonic fluid loss
o The net loss or gain of fluid with a salt concentration similar to that of the ECF will cause changes in the ECF volume with little change in ECF osmolality, and hence there will be no change in the ICF volume.
o Isotonic fluid loss will lead to interstitial dehydration, causing associated clinical signs. Isotonic fluid gain would cause interstitial overhydration.
o There will be minimal change in serum sodium concentration with isotonic fluid gain or loss. Isotonic fluid losses are a common cause of fluid imbalance in clinical medicine (often the product of hypotonic fluid loss combined with oral water intake) and are associated with gastrointestinal fluid loss, renal fluid loss, and third space translocation of fluid.
o Changes in the ECF volume affect both the interstitial and intravascular volumes and manifest in changes in PCV and TP measurements. Measurements of PCV and TP may not reflect the ECF hydration status if the patient is anemic, polycythemic, or hypoproteinemic unless a baseline sample can be used for comparison. If the decrease in ECF volume is significant, it can be associated with elevations in kidney enzymes (prerenal azotemia).
How can USG and urine osmolality be useful regarding extracellular fluid hydration status?
o Urine osmolality and specific gravity (SG) may also provide valuable information regarding ECF hydration status.
o Urine osmolality reflects the total number of solutes per kilogram of urine whereas urine SG is a measurement of the density (mass) of urine compared with water (which has a specific gravity of 1.000).
o Urine osmolality and urine SG measured by refractometer show linear changes when urine water content changes.
o Urine osmolality and SG will increase as water is reabsorbed from the urine filtrate in states of ECF dehydration and decrease as water is excreted from the urine in states of ECF hyperhydration.
o Evaluation of urine concentration will be limited if the patient has received intravenous (IV) fluid therapy or diuretic administration before urinalysis. Urine output can also reflect fluctuations in ECF volume, although it is a late marker for changes in the body fluid compartment, particularly in situations of rapid volume turnover.
How can monitoring ins and outs can help us in critically ill patients?
o In the critically ill patient, comparing the volume of fluids taken in (e.g., IV fluid therapy, enteral support, voluntary ingestion) with the volume of fluid lost (e.g., in the urine, vomitus, stool, and drain production) can identify a potential state of ECF hyperhydration or hypohydration.
o Should the volume of fluid lost greatly exceed the volume taken in, the patient is assessed for signs of hyperhydration or causes of polyuria.
o Should the volume of fluid taken in greatly exceed the volume of fluid lost, the patient is assessed for signs of persistent hypohydration, third space fluid compartment sequestration, or oliguric renal failure.
Why is it even more challenging to assess hydration / volume status in a critically ill patient compared to a healthy animal?
o Although the intravascular and interstitial compartments interact in a dynamic and continuous manner, alterations in any component of Starling’s forces can result in an imbalance, making interpretation of physical examination findings challenging.
o For example, a patient with severe systemic inflammation may have increased capillary permeability leading to hypovolemia in conjunction with interstitial overhydration.
o A congestive heart failure patient can have local increases in pulmonary vascular volume leading to local interstitial hyperhydration (pulmonary edema) yet have reduced total circulating volume and global interstitial hypohydration because of chronic treatment with diuretics and afterload reducers.
Tonicity
The tonicity of a fluid is determined by the concentration of effective osmoles (osmoles not freely permeable through cell membranes between intracellular and extracellular space).
T/F The osmolarity and tonicity of intracellular versus extracellular fluid compartments are equal during homeostasis.
TRUE
The volume of distribution of a crystalloid solution in the body depends on?
o On its tonicity relative to the extracellular fluid.
o The lower the tonicity of a crystalloid solution, the higher proportion of the fluid volume administered that will move into the intracellular space as a result of osmotic pressure differences.
________ includes all osmoles in solution, whereas ________ refers solely to effective osmoles, which do not freely permeate most cell membranes.
Osmolarity
Tonicity
It is changes in tonicity that will drive fluid movement in or out of cells.
What are the main effective osmoles?
o Na+ and its associated anions (Cl-) are the predominant extracellular effective osmoles
o K+ and its associated anions are the predominant intracellular effective osmoles.
What is the primary regulator of cell volume?
o The Na+/K+-ATPase pumps on the cell membrane are the primary regulators of cell volume by maintaining an appropriate distribution of intracellular potassium and extracellular sodium.
o Most sodium ions of the body stay extracellular because of these Na+/K+-ATPase pumps
What determines how much fluid is filtered across the endothelial membrane?
o Starling’s forces (i.e., hydrostatic and colloid osmotic pressures [COP] in the intravascular and interstitial spaces).
o Vascular endothelial permeability
o They govern the magnitude of fluid filtration through the capillary into the interstitial compartment.
Plasma albumin accounts for __% of plasma COP, which is essential for minimizing fluid loss from the intravascular compartment into the interstitial space.
80%
What are potential adverse effects of fluid therapy
o Volume overload (e.g., pulmonary, peripheral tissue and other organ edema), inappropriate fluid shifts (e.g., cerebral edema as an example of intracellular overhydration), and electrolyte and acid-base derangements.
o Large volumes of fluid therapy may lead to a coagulopathy secondary to hemodilution and functional disturbances of primary hemostasis (synthetic colloidal fluids).
o Aggressive volume resuscitation may exacerbate hemorrhage in bleeding patients.
What are crystalloid solutions?
o They are fluids containing small solutes with molecular weights less than 500 g/mole (1 g/mole = 1 dalton [Da]).
o The majority of solutes are electrolytes (<50 g/mole), which readily cross the capillary endothelium and equilibrate throughout the extracellular fluid compartment. There is a lag time of 20 to 30 minutes for electrolytes to distribute evenly in the extracellular fluid compartments (i.e., intravascular and interstitial fluid compartments).
o The net result of fluid shifts (i.e., osmosis) is dictated by the relative tonicity between different fluid compartments.
What are the most abundant effective osmoles in most crystalloids?
Na and Cl
Other small solutes such as glucose and lactate are readily metabolized; hence 5% dextrose in water is considered “free water” because it does not contain an effective osmole
How are crystalloid usually classified?
o Based on their tonicity - isotonics, hypotonics and hypertonic
Isotonic crystalloid fluids
o The osmolarity and sodium concentration of isotonic fluids are similar to that of plasma and extracellular fluid.
o Normal plasma osmolarity is 290 to 310 mOsm/L for dogs and 311 to 322 mOsm/L for cats, and isotonic fluids generally have an osmolality in the range of 270 to 310 mOsm/L.
o These fluids are therefore useful for treatment of hypovolemic shock when rapid intravascular volume expansion is desired.
o Strictly speaking, isotonic fluid does not cause significant fluid shifts between intracellular and extracellular fluid compartments in normal animals (tonicities of the intracellular and extracellular fluids are unchanged; therefore there is no net osmotic shift).
In which situations are isotonic crystalloids used?
o Isotonic fluids are also commonly used for treating interstitial dehydration.
o Normal or abnormal body fluid losses are generally hypotonic or isotonic in nature.
o Although isotonic crystalloids are best suited for the treatment of dehydration secondary to isotonic fluid loss, they are commonly used to replace hypotonic loss as well.
o Although excess electrolytes are typically excreted by the kidneys, patients with compromised renal function should have their electrolytes closely monitored.
o Examples of isotonic fluids include P- Lyte 148, P-Lyte A, Normosol-R, LRS, and 0.9% NaCl.
o 0.9% NaCl contains a much higher chloride concentration (154 mmol/L) than canine or feline plasma. It is useful for treating animals with a hypochloremic metabolic alkalosis, as in the case of pyloric obstruction. Conversely, patients with normal chloride concentration may develop a hyperchloremic metabolic acidosis when 0.9% saline is administered in large volumes.
Hypotonic crystalloid fluids
o In comparison to ECF and plasma, the osmolarity and sodium concentration of hypotonic fluids are much lower (0.45% saline has an osmolarity of 154 mOsm/L with a sodium [and chloride] concentration of 77 mEq/L).
o Five percent dextrose in free water is a unique isoosmotic solution (250 mOsm/L) with hypotonic effects because dextrose is rapidly metabolized and free water remains (tonicity of 0mOsm/L).
o Sterile water with an osmolarity of 0 mOsm/L should never be administered directly into the vascular system because of the risk of intravascular hemolysis and endothelial damage.
o Hypotonic fluids replenish free water deficits and are useful for treating animals with hypernatremia secondary to hypotonic fluid loss (although bolus therapy is contraindicated).
o Hypotonic fluids distribute throughout both intracellular and extracellular fluid compartments, with less remaining extracellularly (both intravascular and interstitial space) in comparison to isotonic fluids.
o The large volume of distribution and free water content make hypotonic fluid a safer choice for slowly treating animals that have a decreased ability to excrete excess sodium or tolerate an elevated intravascular volume (e.g., kidney and heart diseases, respectively).
o Additionally, the low chloride content minimizes bromide loss in animals receiving potassium bromide therapy for seizure control.
o Hypotonic fluids should never be used as bolus therapy for intravascular volume resuscitation. Not only are these fluids ineffective at expanding the intravascular volume, they may also lead to life- threatening cerebral edema.
o A rapid intravenous administration of hypotonic fluids drops plasma and extracellular fluid osmolarity (mainly determined by sodium level) quickly; as a consequence, water shifts from the extracellular fluid space to the intracellular space. Frequent sodium level monitoring during hypotonic fluids administration is recommended.
Hypertonic crystalloid fluids
o The high osmolarity and sodium concentration of hypertonic solutions, such as 7.5% saline, causes a free water shift (i.e., osmosis) from the intracellular space to the extracellular space, expanding the extracellular fluid volume by 3 to 5 times the volume administered.
o Osmotic fluid shifts from the interstitial space into the intravascular space start immediately after intravenous administration of hypertonic solution, even sooner than the uniform distribution of the electrolytes throughout the extracellular space.
o Free water from the intracellular fluid compartment then moves into the extracellular fluid compartment as the interstitial fluid osmolarity rises.
In which situations are hypertonic crystalloid fluids commonly used?
o Hypertonic saline ranging from 3% to 7.5% is used for the therapy of hypovolemic shock, intracranial hypertension, and severe hyponatremia.
o It is often administered for patients with both hypovolemic shock and concerns for intracranial hypertension such as the head trauma patient.
o Similar to isotonic and hypotonic crystalloids, the intravascular volume expansion effect of hypertonic saline is transient (<30 minutes) because of the redistribution of electrolytes (i.e., sodium and its associated anions) throughout the extravascular space.
o The ensuing osmotic diuresis also facilitates excess sodium excretion. To prolong the intravascular volume–expanding effect of hypertonic saline, it is often combined with a colloidal solution.
Beneficial effects of hypertonic saline?
o Hypertonic saline has several beneficial effects on the cardiovascular system beyond increasing vascular volume. It transiently improves cardiac output and tissue perfusion via arteriolar vasodilation (decreased afterload), volume loading (increased preload), reduced endothelial swelling, and a weak positive inotropic effect.
o It is important that administration rates do not exceed 1 mL/kg/min because hypotension may result from central vasomotor center inhibition or peripheral vasomotor effects mediated by the acute hyperosmolarity (bradycardia and vasodilation).
o Also has immune-modulatory effects including suppression of neutrophil respiratory burst activity and cytotoxic effects. The antiinflammatory effects of hypertonic saline may be especially advantageous in trauma patients.
o Improves cerebral perfusion pressure in head trauma patients by augmenting mean arterial blood pressure and decreasing intracranial pressure. At equal osmolar dosages, similar osmotic effects are achieved with either hypertonic saline or mannitol to reduce cerebral edema.
How much volume expansion will hypertonic crystalloids cause?
o A dose of 4 ml/kg of 7.5% saline will expand intravascular volume by 12 to 16 ml/kg (a fraction of total shock dose), but the effect is transient secondary to the fluid redistribution to the interstitial space and osmotic diuresis that follows.
o Therefore additional volumes of isotonic crystalloids, colloids, or blood products are required to stabilize a patient suffering from hypovolemic or distributive shock.
o Hypernatremia is a potential side effect that prevents the safe use of repeated doses of hypertonic saline
o Repeated administration of hyperosmotic solutions may lead to hemolysis and phlebitis if given into small peripheral veins.
What is normally the pH of IV fluids and why?
o The pH of intravenous fluids is usually acidic; largely this is due to dissolved CO2 and the acidic nature of dextrose solutions.
o This low pH does not influence the acid-base balance of patients because of the lack of titratable acidity.
o Essentially, the total quantity of free H+ in an intravenous fluid is small and easily buffered in the body and should not be considered as relevant to the acid-base effects of fluid therapy.
o Acetate, gluconate, and lactate are weak buffers included in some crystalloids such as Normosol-R, lactated Ringer’s solution, and Plasma-Lyte 148. Metabolism of these buffers consumes H+, yielding an alkalinizing effect. As such they are considered beneficial when treating patients with a metabolic acidosis.
Which is the fluid of choice for hypochloremic metabolic alkalosis?
0.9% NaCl
Which fluid is better for neonates?
LRS solution may be the ideal fluid for neonates because lactate is the preferred metabolic fuel in early life.
Does the lactate contained in crystalloid solutions contribute to metabolic acidosis?
o The lactate anion found in crystalloids such as LRS does not contribute to metabolic acidosis; it can, however, cause falsely elevated lactate meter readings if it is not yet metabolized.
Where are acetate and gluconate metabolized (crystalloid buffers)?
o Acetate is metabolized primarily in the skeletal muscle and most cells in the body metabolize gluconate.
o Hypotension due to vasodilation is associated with rapid infusion of acetate and has been reported in humans and experimental dogs. This has led to concerns of use of acetate containing crystalloids for shock resuscitation.
What are synthetic starch colloids?
o Most synthetic starch colloid solutions are hyperoncotic relative to plasma and polydiverse (i.e., contain a wide spectrum of molecular weights).
o These solutions effectively increase and maintain intravascular COP; fluids are pulled into the vascular space because of the increased intravascular/ interstitial COP ratio.
o Hydroxyethyl starch molecules are branched polymers of glucose derived from hydrolysis of amylopectin.
How are synthetic colloids characterized
o Concentration in the solution
o Molecular weight
o Degree of hydroxyl substitutions by hydroxyethyl groups
o Ratio of hydroxyethyl group substitutions at the C2 versus C6 position.
Which characteristics are associated with a longer half-life of synthetic colloids?
o Larger MW, higher degree of substitutions, and higher C2:C6 ratio
o For example, VetStarch, a veterinary formulation of Voluven, is a 6% tetrastarch solution with a weight average MW of 130,000 Da, 4 hydroxyethyl group substitutions per 10 glucose molecules (designated as 130/0.4), and a C2:C6 ratio of 9:1. The molecular weight range of VetStarch and Voluven is 110,000 to 150,000 Da.
o In comparison to Hextend (670/0.75,4:1), the half-life of VetStarch and Voluven is shorter (38h vs. 10h in healthy humans). A high cumulative dosage can also prolong the half-life of synthetic starch colloids because of a saturable degradation process.
o Dextrans are another example of synthetic starch colloid solutions but are currently off the market, primarily because of their propensity to cause AKI and allergic reactions in humans.
The oncotic effect of synthetic colloids depends on what?
o On the number of colloidal molecules.
o Small starch colloid molecules (e.g., hetastarch < 50,000 Da) are filtered through the glomeruli and rapidly excreted, causing a transient osmotic diuresis.
o Colloidal molecules in the urine increase urine viscosity and specific gravity measurement by the refractometer. Urine osmolality is a more accurate measure of urine concentration in animals receiving colloidal fluids.
o Larger starch molecules are metabolized slowly to smaller molecules. Synthetic starch molecules are degraded by the reticuloendothelial system (i.e., liver, spleen, and lymph nodes). Also, amylase in the blood metabolizes hydroxyethyl starches.
o If colloid molecules leak into the interstitial space, especially in patients with increased vascular permeability, they are returned to the circulation by the lymphatics or engulfed by macrophages.
o Kidneys are the main route for excretion of synthetic starch colloids.
What are adverse effects of synthetic colloids?
o Synthetic starch colloids interfere with the function of platelets, von Willebrand’s factor, and factor VIII, leading to a primary hemostatic coagulopathy and prolonged activated partial thromboplastin time, all of which are dose dependent.
o Hetastarch solutions typically prolong bleeding times when administered at doses greater than 20 ml/kg/day.
o The same characteristics of hydroxyethyl starches that enable a longer half-life also confer the greatest coagulopathic effects (higher molecular weight, degree of hydroxyethyl group substitution, and C2 : C6 ratio of hydroxyethyl group substitution).
o Clinical bleeding is not typically observed with the available commercial hydroxyethyl starch solutions in stable, noncoagulopathic animals, even with doses greater than 40ml/kg/day; however, caution is advised when using higher doses in critically ill or coagulopathic animals.
o LMW hydroxyethyl starch solutions may be preferable in patients with a higher risk of bleeding (e.g., surgical or coagulopathic patients) because of their decreased coagulopathic effects.
o Allergic reaction to the synthetic starches is a possible side effect of synthetic colloids in humans but has not been reported in veterinary medicine.
o Evidence for the increasing concern regarding AKI secondary to synthetic starch colloid use in the critically ill humans is accumulating and has led to their withdrawal from the market in some countries.
o Decreased glomerular filtration, hypertonicity of glomerular filtrate, and direct hydroxyethyl starch deposits are thought to contribute to the renal toxicity of these products.
o A direct association between hydroxyethyl starches and the occurrence of AKI has not been reported in VM; however, similar risks are possible in the critically ill animals.
How is albumin distributed and what are its main functions?
o 66 - 69 kDa. Has a negative charge
o Colloid osmotic pressure hepatocytes is what will stimulate its synthesis.
o 30-40% intravascular / 60-70% extravascular, minimal amount intracellularly
o Albumin contributes to a large portion of COP in animals (80%). Other essential physiologic functions of albumin involve wound healing, coagulation, and scavenging of free radicals.
o Albumin serves as a carrier for multiple substrates, including hormones, bilirubin, fatty acids, divalent cations, toxins, and drugs. Additionally, albumin also exerts a weak buffer effect via binding of hydrogen ions.
Natural colloids and its components
o Several colloidal blood products are derived from canine or feline donors.
o FFP provides all the clotting factors and plasma protein.
o Plasma that remains at room temperature for > 8h or is stored frozen for > 1 year loses the labile clotting factors (FV and FVIII) and is then considered frozen plasma.
o Frozen plasma provides plasma proteins and clotting factors II, VII, IX, and X.
o Cryosupernatant is the top portion of partially thawed fresh plasma after a hard spin (5000× g for 7 minutes) and contains albumin, globulin, antithrombin, protein C, protein S, and clotting factors II, VII, IX, X, XI and XII.
o The remaining portion is cryoprecipitate, which is rich in fibrinogen, fibronectin, factor VIII, and von Willebrand’s factor.
o Fresh whole blood transfusion provides platelets and red blood cells in addition to plasma proteins and clotting factors.
In order to raise the recipient’s plasma albumin by __g/dL , approximately __ to __ml/kg of plasma from a normal dog is required
1g/dL
40 to 50mL/Kg
HSA
o Pooled HSA has been administered to CI dogs to raise serum albumin and COP. Five percent (5 g/dl) HSA is isoosmolar and isooncotic, whereas the most commonly used 25% (25 g/dl) HSA exerts 5 times the osmolar and oncotic effects of 5% human albumin.
o As expected, the high oncotic pressure of 25% albumin expands intravascular volume much more than the volume administered. Judicious dosing and close monitoring for volume overload are crucial for patient safety.
o Human and canine albumin molecules share only 79% homology -> the xenogenic transfusion of HSA comes with the potential life-threatening risk of an immediate or delayed hypersensitivity reaction. Naturally occurring antibodies against HSA have also been documented in healthy dogs with no prior HSA transfusion.
o Several retrospective studies have found that the rate of severe adverse reaction is rare when used once in critically ill animals.It is hypothesized that the immune system is compromised in severely ill animals and therefore unable to mount an immune response to the antigenic HSA.
o Therefore HSA is reserved only for critically ill animals with severe hypoalbuminemia, after carefully weighing the benefit and risks of human albumin administration.
o Because immunoglobulin G (IgG) formation is well documented in dogs after exposure to human albumin, repeated administration within the lifetime of a given animal is not advised.
o Hypoalbuminemia is associated with poor clinical outcomes, but the effect of human albumin on mortality in small animals is currently unknown.
Hb based oxygen carrying solutions
o Oxyglobin is the only veterinary FDA-approved HBOC for the treatment of canine anemia. It contains 13 g/dl of polymerized bovine hemoglobin that is ultrapurified and free of antigenic red blood cell stroma and is suspended in a modified LRS solution.
o Has a P50 of 34 mm Hg, similar to that of canine and feline hemoglobin (P50 of canine and feline hemoglobin in red blood cells are 31.5 and 35.6 mm Hg, respectively).
o Polymerization of bovine hemoglobin tetramers creates a more stable, larger molecule, which prolongs its half-life and eliminates renal toxicity associated with hemoglobin dimers (derived from rapid breakdown of individual hemoglobin tetramers).
o Oxyglobin is a polydiverse colloidal solution with an average weight molecular weight of 200 kDa (molecular weight range of 64 to 500 kDa). It is isoosmotic (300 mOsm/kg) and hyperoncotic (COP of 43 mm Hg). The viscosity of Oxyglobin is low (<2 cP).
o Increased preload, stroke volume, and cardiac output are observed after Oxyglobin administration. However, the hemodynamic effect of Oxyglobin is complicated by its NO scavenging effect.
o NO has a vasodilatory effect. Peripheral vasoconstriction subsequent to the decrease in NO with Oxyglobin therapy may ironically compromise tissue perfusion and oxygen delivery. In addition, the local regulatory response to improved tissue oxygenation may also lead to peripheral vasoconstriction after Oxyglobin administration.
o Blood typing and cross-matching are not necessary before Oxyglobin administration. Hematocrit is no longer a useful measure of blood carrying capacity and may actually decrease after Oxyglobin administration because of its dilutional effect.
o The most concerning side effect of Oxyglobin is volume overload.
Most prevalent anions and cations intracellularly
o The most prevalent cation in the ICF is potassium, with much smaller contributions made by magnesium and sodium.
o The most prevalent anions in the ICF are phosphate and the polyanionic charges of the intracellular proteins.
Most prevalent anions and cations extracellularly
o The primary cation in the ECF is sodium and the most prevalent anions are Cl– and HCO3–
o The proteins in plasma and the interstitial space also contribute to the negative charges.
T/F Small particles such as electrolytes move freely between the intravascular and interstitial compartment but cannot enter or leave the cellular compartment without a transport system.
TRUE
Which type of molecules are mainly responsible for the colloid osmotic pressure?
o Larger molecules ( >20,000Da) do not easily cross the vascular endothelial membrane and may attract small, charged particles, thus creating the colloid osmotic pressure (COP).
o There are three main natural colloid particles: albumin, globulins, and fibrinogen.
Define hydrostatic pressure
The pressure of fluid within a compartment that pushes against a membrane
What determines fluid distribution between compartments?
o In health, fluid distribution within the ECF is determined by the balance between forces that favor reabsorption of fluid into the vascular compartment (increased COP or decreased hydrostatic pressure) and those that favor filtration out of the vascular space (decreased COP or increased hydrostatic pressure).
o Changes in the osmolality between any of the fluid compartments within the body will cause free water movement across the respective membrane.
In which conditions is isotonic fluid loss more common?
o Isotonic fluid losses, as seen in animals with polyuric renal failure, vomiting, diarrhea, or bleeding, will lead to depletion of the ECF compartment and dehydration.
o If severe ECF losses are not replaced, hypovolemia may become clinically apparent.
o Because isotonic losses will not alter ECF osmolality, there will be no movement of water across the cell membrane and ICF volume will remain unchanged.
o In order to replace the ECF deficit, isotonic crystalloids should be administered. However, if the animal has been drinking water to replace the isotonic fluid losses, hyponatremia may result.
In which conditions will we see hypotonic fluid losses?
o Hypotonic fluid losses, as seen with DI or excessive panting, will cause hypernatremia and an increase in ECF osmolality.
o This leads to movement of water out of the ICF space. Consequently, there is a depletion of both the ICF and ECF compartments.
o Isotonic fluid therapy may be sufficient if the hypernatremia is not severe, but in animals with significant hypotonic fluid losses, free water administration is indicated.
o Care must be taken to lower serum Na slowly to avoid causing potentially life-threatening cerebral edema.
In which cases will we see hypertonic fluid losses?
o Loss of hypertonic fluid occurs infrequently in small animals.
o Excessive loss of solutes in the urine may occur with diseases such as hypoadrenocorticism but more commonly hyponatremia results from excessive free water intake or retention.
o Hyponatremia caused by hypertonic fluid loss is often exacerbated by electrolyte losses combined with hypotonic fluid replacement (i.e., oral water intake).
o If a hypertonic fluid loss does occur, a drop in ECF osmolality results and provides a gradient for water to move into the ICF compartment, leading to cell swelling.
o Significant hyponatremia or hypoosmolality requires careful fluid therapy to avoid rapid (>0.5 mEq/L increase per hour) changes in sodium concentration and subsequent central pontine myelinolysis (also known as osmotic demyelination syndrome).
Increased vascular permeability and body fluid redistribution
o Disease processes that cause an increase in vascular permeability may lead to high-protein fluid extravasation from the intravascular space.
o This can lead to a decrease in intravascular volume, possibly associated with interstitial edema. Because this will not alter the osmolality of the ECF compartment, increased vascular permeability alone is not expected to alter the ICF volume.
o Patient history, physical examination, and laboratory data can provide useful information concerning the route of fluid losses, timeline of these losses, food and water consumption, and current clinical status. This will guide formulation of an appropriate fluid therapy plan.
Increased vascular permeability and body fluid redistribution
o Disease processes that cause an increase in vascular permeability may lead to high-protein fluid extravasation from the intravascular space.
o This can lead to a decrease in intravascular volume, possibly associated with interstitial edema. Because this will not alter the osmolality of the ECF compartment, increased vascular permeability alone is not expected to alter the ICF volume.
o Patient history, physical examination, and laboratory data can provide useful information concerning the route of fluid losses, timeline of these losses, food and water consumption, and current clinical status. This will guide formulation of an appropriate fluid therapy plan.
For animals with evidence of chronic dehydration on physical examination but stable cardiovascular parameters, fluid deficits should be replaced over __ to __ hours.
4 to 24h
What do we need to take in consideration when preparing a fluid plan for a patient?
o Estimated dehydration
o Maintenance needs
o Anticipated ongoing losses
Formula for fluids
[Body weight (kg)×1000]×[percentage dehydration/100] = deficit (ml)
+ estimated ongoing losses (ml)
+ maintenance (ml)
= amount to be given over next 4 to 24 hours
Clinical signs of fluid deficits based on compartment affected
o ICF deficits lead to cerebral obtundation, hypernatremia, and hyperosmolality. ICF deficits alone will not cause clinical evidence of dehydration.
o Interstitial volume deficits are typically associated with a decrease in skin turgor (increased skin tenting) and dry mucous membranes. Skin turgor provides only a rough estimate of dehydration, and severe emaciation or obesity can make this assessment difficult. Serial body weight measurements may also be a useful and more objective indicator of dehydration.
o Intravascular volume deficits are commonly associated with compensatory vasoconstriction, pale mucous membranes, poor pulse quality, tachycardia, prolonged capillary refill time, and cold extremities. These symptoms are suggestive of poor tissue perfusion and require rapid intervention.
What does maintenance fluids take in consideration?
It takes into account the sensible and insensible ongoing fluid losses (feces, urine, panting, sweating)
How does maintenance fluids relates to resting energy requirements? Other formulas to calculate maintenance fluids?
o Daily maintenance fluid volume requirements have been shown to parallel RER; thus, calculations of RER are often used to estimate fluid requirements (1 kcal of energy = 1ml of water).
o The resting energy requirement (RER) is the amount of energy (or water) needed to maintain homeostasis in the fed state in a thermoneutral environment and is equal to 70(BWkg)^0.75 -> this one more accurate for patients <2kg or >40kg
o Additional commonly used formulas for calculating daily fluid needs are as follows:
Formula 1: 30(BWkg) + 70/day
Formula 2: 60(BWkg) + 140/day
o Because there is less water in fat than in muscle, most calculations overestimate the maintenance needs of overweight patients.
Estimation of ongoing losses
o Ongoing fluid losses are estimated from an understanding of the underlying disease process and historical data. For example, when treating animals with GI losses, the approximate volume and frequency of vomiting and diarrhea is estimated.
o Obviously this predicted volume may be inaccurate; it allows calculation of an initial fluid therapy plan, but close patient monitoring and reevaluation are imperative. If the estimate of ongoing fluid losses is significantly inaccurate, the fluid plan should be altered accordingly.
How should we administer maintenance / ongoing losses / dehydration fluids to our patients?
o Although SQ fluid administration can be effective in the management of fluid deficits, it is not adequate for the critically ill patient.
o Fluid therapy should be administered via an intravenous or intraosseous catheter that is assessed regularly for evidence of phlebitis (if venous) or inadvertent subcutaneous fluid administration.
o In general, fluids with an osmolality less than 600 mOsm/L can be given safely through a peripheral venous catheter; those with an osmolality greater than 700mOsm/L should be given through a central catheter to decrease the risk of phlebitis or thrombosis.
What type of fluids are replacement fluids?
o Replacement fluids, also known as isotonic crystalloids, are electrolyte-containing fluids with a composition similar to that of the ECF. They have a similar osmolality as plasma (290 to 310 mOsm/L). They may also contain buffer compounds and dextrose.
o Isotonic crystalloids are commonly used to expand the intravascular and interstitial spaces and maintain hydration. Additional electrolytes, such as potassium, may be added to maintenance or replacement fluids as needed for an individual patient.
Composition of replacement fluids
What will happen after IV infusion of isotonic crystalloids? Can they only be used as replacement fluids?
o After infusion of isotonic crystalloids into the vascular space, the small electrolytes and water pass freely across the capillary vascular endothelium. These are extracellular-expanding fluids; 75% redistributes to the interstitial space, and only 25% remains in the vascular space after 30 minutes.
o Although so-called replacement fluids are used commonly for maintenance of hydration, most animals are able to easily excrete the electrolyte constituents that are in excess of the body’s needs. This practice is common because most hospitalized animals have ongoing electrolyte losses and poor enteral intake, and it is much easier to hang one bag of isotonic crystalloids than two separate bags (one for replacement and one for maintenance).
How can isotonic crystalloids cause harm?
o Isotonic crystalloids can cause harm, especially in critically ill animals. The interstitial fluid gain can lead to interstitial edema, pulmonary edema, and cerebral edema. Patients with a low COP, pulmonary contusions, cerebral trauma, fluid-unresponsive renal disease, or cardiac disease/failure are at highest risk for complications.
o In addition, substantial hemodilution of blood constituents that are not found in the crystalloids can occur. Anemia, hypoproteinemia, electrolyte derangements, and hypocoagulability can occur after large-volume crystalloid administration.
Specific conditions and preference of fluids
o Animals with diabetic ketoacidosis or liver disease should not receive lactate-containing fluids because of their decreased ability to convert the lactate to bicarbonate in the liver.
o Lactated Ringer’s solution may be preferred in very young animals because lactate is the preferred metabolic fuel in neonates with hypoglycemia.
o Patients with a hypochloremic metabolic alkalosis will benefit from 0.9% sodium chloride because this is the highest chloride-containing fluid, but animals with a severe acidosis may benefit from an alkalinizing fluid containing lactate, acetate, or gluconate.
o Animals with head trauma or increased intracranial pressure may benefit from 0.9% sodium chloride because this isotonic crystalloid is least likely to cause a decrease in osmolality that might promote water movement into the brain interstitium.
Which type of fluids are appropriate for maintenance needs?
o Maintenance fluids refers to the volume of fluid and amount of electrolytes that must be consumed on a daily basis to keep the volume of total body water and electrolyte content within the normal range.
o Obligate fluid losses are hypotonic and low in sodium but contain relatively more potassium than does the ECF.
o Maintenance fluids are therefore hypotonic crystalloids that are low in sodium, chloride, and osmolality but high in potassium compared with normal plasma concentrations.
o The inclusion of dextrose may make the fluid isoosmotic to plasma, but the dextrose is metabolized rapidly to carbon dioxide and water, so these fluids are still hypotonic in nature.
o Maintenance-type fluids are distributed into all body fluid compartments and should never be administered as a rapid bolus because cerebral edema may result.
Maintenance fluids composition
Free water administration + formula
o In order to give free water (fluids with no electrolytes or buffers) IV without using a dangerously hypotonic fluid, sterile water is combined with 5% dextrose to yield an osmolality of 252 mOsm/kg (safe for intravenous administration).
o This fluid is indicated in animals with a free water deficit (i.e., hypernatremia) or severe ongoing free water losses (e.g., diabetes insipidus). In order to safely lower the sodium concentration by 1 mEq/hr, a rate of 3.7 ml/ kg/h of free water is a good starting point and can be adjusted based on the patient’s response.
o Alternatively, the patient’s free water deficit can be calculated by the formula:
Free water deficit =([current[Na+]÷normal[Na+]]−1) × (0.6 × body weight in kg)
o This formula will provide the total volume of free water to be replaced and can be administered as 5% dextrose in water over the number of hours calculated for safe reestablishment of normal plasma sodium concentration (Na+ change of no greater than 0.5 – 1.0 mEq/L/h). Close monitoring of electrolyte status is advised.
o Dextrose 5% in water should never be administered as a rapid bolus because acutedecreases in osmolality will cause potentially fatal cerebral edema
T/F The most commonly used synthetic colloid solutions are made from hydroxyethyl starch (hetastarch and tetrastarch products)
TRUE
The base solution is an isotonic crystalloid (e.g., 0.9% NaCl), and the colloidal particles are suspended within the crystalloid.
Molecular weight of colloid solutions?
o Colloidal solutions contain large molecules (molecular weight > 10,000Da) that do not readily sieve across the vascular membrane.
o These fluids are polydisperse (they contain molecules with a variety of molecular weights) and hyperoncotic to the normal animal and therefore cause the movement of fluid from the extravascular to the intravascular space.
At volumes greater than __mL/kg/day, an increase in incisional bleeding has been reported with hetastarch solutions, which may be due to increased blood pressure and microcirculatory flow as well as dilutional and direct effects of hetastarch on coagulation
40 ml/kg/day
What do hetastarches affect on coagulation?
Platelet function
vWF
FVIII
An increase in the activated partial thromboplastin time (aPTT) may develop in animals that receive large amounts of synthetic colloid therapy, although the quantitative aPTT change is not predictive of clinical bleeding.
Hetastarch
A 6% hydroxyethyl starch solution, with particles ranging from 10,000 to 1,000,000 Da in MW, a number average MW of 69,000Da, a mean average MW of 450,000Da, and a COP of 34mmHg in vitro.
Vetstarch
A 6% tetrastarch solution, with particles ranging from 110,000 to 150,000 Daltons, a mean average molecular weight of 130,000 Daltons, and a COP of 40mmHg.
Because of its lower average molecular weight and low molar substitution, ______ may be less likely to cause adverse renal and coagulation side effects but may also require higher doses to achieve similar effects to that of ______.
VetStarch
Hetastarch
CRI of colloids rate?
Used at a rate of 0.5 to 2 ml/kg/h in animals with acute decreases in COP or total protein levels.
How should we monitor a patient receiving IV fluids?
o BW should be monitored daily (or more often if indicated). A physical examination should be performed at least twice daily to assess the animal’s mental status, skin turgor, heart rate and pulse quality, mucous membrane color, capillary refill time, extremity temperature, and respiratory rate and effort.
o Serial lung auscultation should be performed to monitor for increased breath sounds, crackles or wheezes.
o If an indwelling urinary catheter is present, urine output can be compared with fluid administered to help guide fluid therapy and prevent the administration of too much or too little fluid. Serum blood urea nitrogen and creatinine levels can be evaluated in con- junction with the urine specific gravity to determine whether there is prerenal or renal azotemia (or a combination of both). An increase in blood urea nitrogen and creatinine with an increase in USG would suggest that the animal is receiving insufficient fluid volume.
o Lactate - inadequate tissue perfusion may result in an increase in blood lactate levels secondary to anaerobic metabolism. Serial lactate measurements may help guide fluid therapy as an indicator of tissue perfusion. Moderate to severely elevated lactate levels should alert the clinician that more aggressive treatment may be required.
o If a central venous catheter is in place, central venous pressure monitoring may be used to help guide fluid therapy.
o Additional monitoring techniques that might be helpful include arterial blood pressure; electrocardiogram; and repeated measurements of packed cell volume, total solids, blood glucose, electrolytes, lactate, and acid-base status. Pulmonary capillary wedge pressure monitoring, cardiac output monitoring, and mixed (or central) venous oxygen saturation measurements may be helpful in select patients.
Clinical signs of patients receiving too much fluids?
o Clinical signs in animals receiving too much fluid include serous nasal discharge, chemosis, jugular venous distention, and interstitial pitting edema.
o In the early stages of pulmonary edema, an increase in the respiratory rate will occur, followed by inspiratory crackles, wheezes, and dyspnea.
o It is therefore of utmost importance to monitor the respiratory rate and effort of all patients receiving fluid therapy.
How should we discontinue fluid therapy?
o In most animals, fluid therapy should not be discontinued abruptly, especially if high flow rates are being administered.
o These animals may have renal medullary washout and therefore the urine-concentrating ability will be impaired for several days. This can lead to severe dehydration and hypovolemia in animals that are not drinking large amounts of water.
o Ideally, intravenous fluid therapy should be decreased gradually over a 24h period. Some animals may require slower weaning protocols, especially those receiving high flow rates.
o Owners should be informed that the animal may have increased water requirements for a few days after the discontinuation of intravenous fluid therapy.
Fat is __% water, muscle is __% water
10%
75%
A loss off >__% of body water is often fatal
15%
Function of water in the body?
Body fluids derangements
Puppies fluid maintenance rate?
4-6mL/kg/h assuming normal cardiac function + ongoing losses
The intracellular space
The extracellular space
Which space is thought to control the fluid shifts from intravascular space out of the IV lumen?
Subglycocalyx space
Contains about 2% of TBW
Why cannot we correct hypernatremia too quick?
Because of the idiogenic osmoles that have developed in the brain
According to Pouseuille’s law, doubling the diameter of an IV catheter will increase flow of fluids by how much?
By 16
In a multi-lumen catheter (triple lumen), which port should we use to administer resuscitation fluids)
Brown port, it is the largest one
Estimating dehydration
Composition of common veterinary fluids
Why can high chloride cause AKI?
Causes vasoconstriction of afferent arteriole decreasing renal blood flow. This response can be magnified in hypovolemic patients.
Replacement fluid with the lowest Na concentration?
LRS - 130mEq/L
ROSE administration of fluids (Resuscitation, Optimization, Stabilization, Evacuation / Deescalation)
How much isotonic crystalloids are left in the IV space after 30min of administration?
25%
Examples of anticipated fluid distribution
Hydrohyethyl starch
Synthetic colloid solutions characteristics
What coagulation parameter is affected by synthetic colloids?
Intrinsic primarily affected - aPTT
Synthetic colloids classified based on degree of substitution
Hetastarch & Tetrastarch
COP of albumin
o Normal COP of albumin 20mmHg
o Synthetic albumin 200mmHg - because it is also hypertonic, not only with the effects of high MW molecule.
Hypertonic saline 7.5%
Hypertonic saline - dose, indications and side effects
Complications of fluid therapy
Lactate clearance formula
Lactate clearance = (lactate initial − lactate delayed) / lactate initial × 100 (expressed as percentage).
T/F Alterations in sodium concentration are associated with poor outcome in critically ill people
TRUE
Even sodium concentration changes within the reference interval have been associated with increased mortality risk.
T/F - The endothelium, which separates the intravascular fluid compartment from the interstitial space, and the cell membrane, which separates the interstitial and intracellular compartments, are freely permeable to water.
TRUE
Osmolality vs osmolarity
o Osmolality is the concentration of osmoles in a mass of solvent. In biologic systems, osmolality is expressed as mOsm/kg of water and can be measured using an osmometer.
o Osmolarity is the concentration of osmoles in a volume of solvent and in biologic systems is expressed as mOsm/L of water.
o In physiologic systems there is no appreciable difference between osmolality and osmolarity, so the term osmolality os normally used.
Which molecules in the body contribute to osmolality?
o Every molecule dissolved in the total body water contributes to osmolality, regardless of size, weight, charge, or composition.
o The most abundant osmoles in the extracellular fluid are sodium (and the accompanying anions chloride and bicarbonate), glucose, and urea.
o Because they are the most plentiful, these molecules are the main determinants of plasma osmolality in healthy dogs and cats.
Plasma osmolality equation
Effective vs ineffective osmoles
o Osmoles that do not cross the cell membrane freely are considered effective osmoles.
o Osmoles that do cross freely are termed ineffective osmoles.
o The water-permeable cell membrane is functionally impermeable to Na+,K+andglucose. As a result, Na,Kglucose are effective osmoles and they exert osmotic pressure across the cell membrane.
Effective osmolality formula
mOsm/kg = 2xNa + K + Glu / 18
What dictates the net movement of water in and out of the cells?
o Is dictated by the osmotic pressure gradient.
o Osmotic pressure causes water molecules from an area of lower osmolality (higher water concentration) to move to an area of higher osmolality (lower water concentration) until the osmolalities of the compartments are equal.
How sensitive are the hypothalamic receptors to osmolality changes?
Hypothalamic osmoreceptors sense changes in plasma osmolality, and changes of only 2 to 3mOsm/kg induce compensatory mechanisms to return the plasma osmolality to its hypothalamic setpoint.
What are the main physiologic mechanisms to control plasma osmolality?
o ADH
o Thirst
ADH regulation of plasma osmolality
o ADH is a small peptide secreted by the posterior pituitary gland.
o There are two major stimuli for ADH release: elevated plasma osmolality and decreased effective circulating volume.
o Increased plasma osmolality causes shrinkage of a specialized group of cells in the hypothalamus called osmoreceptors. When their cell volume decreases, these hypothalamic osmoreceptors send impulses via neural afferents to the posterior pituitary, leading to ADH release.
o When effective circulating volume is low, baroreceptor cells in the aortic arch and carotid bodies send neural impulses to the pituitary gland that stimulate ADH release.
o In the absence of ADH, renal tubular collecting cells are relatively impermeable to water. When ADH activates the V2 receptor on the renal collecting tubular cell, aquaporin-2 molecules are inserted into the cell’s luminal membrane.
o Aquaporins are channels that allow the movement of water into the renal tubular cell. Water molecules cross through these aquaporins into the hyperosmolar renal medulla down their osmotic gradient.
o If the kidney is unable to generate a hyperosmolar renal medulla because of disease or diuretic administration, water will not be reabsorbed, even with high concentrations of ADH.
o Circulating ADH concentration and ADH’s effect on the normal kidney are the primary physiologic determinants of free water retention and excretion.
Thirst as regulation of plasma osmolality
o Hyperosmolality and decreased effective circulating volume also stimulate thirst.
o The mechanisms by which hyperosmolality and hypovolemia stimulate thirst are similar to those that stimulate ADH release.
o Thirst and the resultant water consumption are the main physiologic determinants of free water intake.
What does the body prioritizes, plasma osmolality or effective circulating volume?
o Under normal physiologic conditions, the RAAAS monitors and fine tunes effective circulating volume, and the ADH system maintains normal plasma osmolality.
o However, maintenance of effective circulating volume is always prioritized over maintenance of normal plasma osmolality.
o Therefore patients with poor effective circulating volume will have increased thirst and ADH release regardless of their osmolality. The resultant increased free water intake (from drinking) and water retention (from ADH action at the level of the kidney) can lead to hyponatremia (and thus hypoosmolality) in patients with poor effective circulating volume.
o An example of the defense of effective circulating volume at the expense of normal plasma osmolality is seen in patients with chronic congestive heart failure that present with hyponatremia.
Total body sodium vs plasma sodium concentration
o Plasma sodium concentration is different than, and independent of, total body sodium content.
o Total body sodium content refers to the total number of sodium molecules in the body, regardless of the ratio of sodium to water.
o Sodium content determines the hydration status of the animal. As it is used clinically, hydration is a misnomer, because findings such as skin tenting and moistness of the mucous membranes and conjunctival sac are determined by both the sodium content and the water that those sodium molecules hold in an animal’s interstitial space.
o The Na/water ratio is independent of the total body Na content: patients may be normally hydrated, dehydrated, or overhydrated (normal, decreased, or increased total body sodium content) and have a normal plasma sodium concentration, hypernatremia, or hyponatremia.
What happens when patients have an increased total body Na+ content?
o When patients have increased total body sodium, an increased quantity of fluid is held within the interstitial space and the animal appears overhydrated, regardless of the plasma sodium concentration.
o Overhydrated patients may manifest a gelatinous subcutis; peripheral or ventral pitting edema; chemosis; or excessive serous nasal discharge.
What happens when patients have a decreased total body Na+?
o When patients have decreased total body sodium, a decreased quantity of fluid is held within the interstitial space and the animal appears dehydrated, regardless of the plasma sodium concentration.
o Once a patient has lost 5% or more of its body weight in isotonic fluid (≥5% “dehydrated”), it may manifest decreased skin turgor, tacky or dry mucous membranes, decreased fluid in the conjunctival sac, or sunken eye position. Patients that are less than 5% dehydrated appear clinically normal.
o Patients with dehydration can become hypovolemic as fluid shifts from the intravascular space into the interstitial space as a result of decreased interstitial hydrostatic pressure.
Define hypernatremia
Plasma or serum sodium concentration above the reference interval.
What is most commonly the etiology of hypernatremia, Na acquisition or H2O loss?
Most dogs and cats with hypernatremia have excessive free water loss rather than increased sodium intake or retention.
Free water deficit in hypernatremic patients
o Normal animals can become severely hypernatremic if denied access to water for extended periods.
o Animals with vomiting, diarrhea, or polyuria of low-sodium urine may also develop hypernatremia.
o Hypernatremia can occur after administration of activated charcoal suspension containing a cathartic because the hypertonic cathartic draws electrolyte-free water into the GI tract. Osmotic diuresis with mannitol also causes an electrolyte-free water loss and thus can cause hypernatremia.
o Diabetes insipidus (DI), a syndrome of inadequate release of or response to ADH, can cause hypernatremia. Animals with DI become severely hypernatremic when they do not drink water, because they cannot reabsorb free water in the renal collecting duct. Acute or critical illness can unmask previously undiagnosed DI.
o A syndrome of hypodipsic hypernatremia has been reported in Miniature Schnauzers, one of which was diagnosed with congenital holoprosencephaly. This syndrome most likely is due to impaired osmoreceptor or thirst center function.
o In other dog breeds and cats, hypodipsic hypernatremia has been associated with hypothalamic granulomatous meningoencephalitis, hydrocephalus,and other central nervous system (CNS) deformities and CNS lymphoma.
Sodium excess in hypernatremic patients
Severe hypernatremia can also occur with the introduction of large quantities of sodium in the form of hypertonic saline, sodium bicarbonate, sodium phosphate enemas, seawater, beef jerky, and saltflour dough mixtures
Clinical signs of hypernatremia
o Hypernatremia causes no specific clinical signs in many cases.
o If it is severe (usually >180 mEq/L) or occurs rapidly, it may be associated with CNS signs such as obtundation, head pressing, seizures, coma, and death.
o All cells that have Na+/K+-ATPase pumps shrink as a result of hypernatremia as water moves out of the cell down its osmotic gradient to the relatively hyperosmolar extracellular compartment, but neurons are clinically the least tolerant of this change in cell volume. Thus, neurologic signs are seen most commonly in patients with clinically significant hypernatremia.
o Patients that develop hypernatremia slowly are often asymptomatic.
o An experimental study found decreased myocardial contractility during injection of hypernatremic or hyperosmolar solutions in dogs (but hypertonic solutions increase CO by decreasing afterload - arteriolar vasodilation)
o Hypernatremia has also been associated with hyperlipidemia, possibly a result of the inhibition of lipoprotein lipase.
Physiologic adaptation to hypernatremia
o Hypernatremia causes free water to move out of the relatively hypoosmolar intracellular space into the hyperosmolar extracellular space, leading to decreased cell volume.
o The brain has multiple ways to protect against and reverse neuronal water loss in cases of hypernatremia. In the early minutes to hours of a hyperosmolal state, as neuronal water is lost to the hypernatremic circulation, lowered interstitial hydraulic pressure draws fluid from the cerebrospinal fluid (CSF) into the brain interstitium.
o As plasma osmolality rises, sodium and chloride also appear to move rapidly from the CSF into cerebral tissue, which helps minimize brain volume loss by increasing neuronal osmolality and thus drawing water back to the intracellular space.
o These early fluid and ionic shifts appear to protect the brain from the magnitude of volume loss that would be expected for a given hyperosmolal state.
o Additionally, within 24h, neurons begin to accumulate organic solutes to increase intracellular osmolality and help shift lost water back to the intracellular space. Accumulated organic solutes are called idiogenic osmoles, or osmolytes, and include molecules such as inositol, glutamine, and glutamate.
o Generation of these idiogenic osmoles begins within a few hours of cell volume loss, but full compensation may take as long as 2 to 7 days. Restoration of neuronal cell volume is important for cellular function and is an important consideration during tx of hyperNa..
T/F We should only treat hypernatremia when clinical signs are evident
FALSE
T/F Patients with hyponatremia have a free water deficit, so free water is replaced in the form of fluid with a lower effective osmolality than that of the patient.
FALSE - patients with hyPERnatremia
How should we decrease plasma Na concentrations?
o In patients with mild to moderate hypernatremia (Na+< 180 mEq/L), sodium concentration should be decreased no more rapidly than 1 mEq/L/hr.
o In those with severe hypernatremia (Na+ ≥ 180 mEq/L), it should be decreased no more rapidly than 0.5 to 1 mEq/L/hr.
o This slow decrease in plasma sodium concentration is important to prevent cellular swelling. Idiogenic osmoles are broken down slowly, so rapid drops in plasma sodium concentration (and thus plasma osmolality) cause free water to move back into the relatively hyperosmolar intracellular space and can lead to neuronal edema.
Once we calculated the free water deficit, how should it be replaced?
o The formula gives the total volume of free water that needs to be replaced.
o This volume of free water, usually given as 5% dextrose in water, is infused over the number of hours calculated for safe reestablishment of normal plasma sodium concentration.
o This rate of free water replacement may be inadequate in cases of ongoing free water loss, as seen with diuresis of electrolyte-free water in patients with DI or unregulated diabetes mellitus, but it is a safe starting point in most cases.
o Plasma sodium concentration should be monitored no less often than every 4 hours to assess the adequacy of treatment, and CNS status should be monitored continuously for signs of obtundation, seizures, or other abnormalities.
o The rate of free water supplementation should be adjusted as needed to ensure an appropriate drop in plasma sodium concentration, the goal being a drop of no more than 1mEq/hr and no clinical signs of cerebral edema.
o Water may be supplemented intravenously (as 5% dextrose in water) or orally on an hourly schedule in animals that are alert, willing to drink, and not vomiting.
o Free water replacement alone will not correct clinical dehydration or hypovolemia, because free water replacement does not provide the sodium required to correct these problems.
T/F We need to be very careful with free water replacement in cardiac patients due to severe increase in intravascular volume
FALSE
o Free water replacement in the hypernatremic patient is relatively safe, even in animals with cardiac or renal disease, because two thirds of the volume administered will enter the cells.
Complications of hypernatremia therapy
o Cerebral edema is the primary complication of therapy for hypernatremia.
o Clinical signs of cerebral edema include obtundation, head pressing, coma, seizures, and other disorders of behavior or movement. If these signs develop during the treatment of hypernatremia, immediately stop the administration of any fluid that has a lower sodium concentration than the patient and disallow drinking.
o The patient’s plasma sodium concentration should be measured to confirm that it is lower than it was when treatment was instituted. This is an important step because signs of worsening hypernatremia may be similar to those seen with cerebral edema.
o If the plasma sodium concentration has decreased, even if it has dropped at less than 1mEq/L/hr, cerebral edema should be considered.
o Cerebral edema is treated with a dose of mannitol at 0.5 to 1 g/kg intravenously (IV) over 20 to 30 minutes. Mannitol should be administered via a central vein if possible, but it may be diluted 1 : 1 in sterile water and given through a peripheral vein in an emergency situation.
o If mannitol is not available, or if a single dose does not improve signs, consider a dose of 7.2% sodium chloride at 3 to 5 ml/ kg over 20 minutes. The administration method is similar to that used for mannitol. Hypertonic saline should not be administered as a rapid bolus because it can cause vasodilation.
Clinical approach to the hypernatremic patient
What is fractional excretion of a substance?
The ratio of the amount of substance excreted relative to the filtered load
Fex = Clearance / GFR
Clearance = Ux x V / Px
Normal for Na is <1%