Monovalent Electrolytes, Anion Gap and Osmolality Flashcards
Na, K, Cl from food/fluid
- metabolism is responsible for ICF ECF
- ECF is Na/Cl rich and K poor
- changes in ECF will change plasma electrolyte concentration
Platelets release _____
K+
- [K] serum > plasma
Electrolytes and H2O is excreted or lost via
Kidneys, skin or respiration
Abnormal [electrolyte] in plasma
- decreased or increased intake
- ICF ECF
- increased renal retention
- increased loss via kidney, skin, alimentary tract, respiration
[Na] in plasma is equivalent to ______
[Na] in ECF
- dependent of total body Na and total body H2O
- hydration is important for [Na] interpretation! –> H2O follows Na (except in distal nephron without ADH)
How does [K] affect [Na]
- if [K] decreases, [Na] decreases since it enters the cells to keep electrical balance
- a severe [K] increase would be necessary for [Na] to increase, but severe [K] is not compatible with life
Na concentration is regulated by ______
Blood volume and plasma osmolality regulation
Hypovolemia stimulates RAS –> angiotensin 2 and aldosterone
- angiotensin 2 increases Na, K, Cl resorption in proximal tubules
- aldosterone increases Na resorption in collecting ducts
How does hypovolemia stimulate ADH release?
Hypovolemia –> carotid sinus –> baroreceptors –> ADH release –> increased water resorption
How does hypervolemia stimulate ANP release?
Hypervolemia –> atrial baroreceptors –> atrial natriuretic peptide –> decreased Na resorption
Hyperosmolality
Hyperosmolality –> hypothalamic osmoreceptors –> promotion of water intake and release of ADH –> H2O resorption and Na, K, Cl in ascending loop of Henle
Hypoosmolality
Leads to decreased water intake
[Na] self regulation
- decreased –> aldosterone release, increased retention
- increased –> decreased aldosterone release, decreased retention
What is the most important regulator of aldosterone release?
[K]!!
Dehydration is equivalent to _____
Decreased total body H2O
- only H2O: decreased intake or loss of free H2O
- H2O + Na loss: alimentary, renal or cutaneous loss
Hypernatremic, hyperosmolar, or hypertonic dehydration
Caused by net hypoosmolar or hypotonic fluid loss
- H2O loss > Na loss
Normonatremic, isoosmolar, or isotonic dehydration
Caused by net isoosmolar or isotonic fluid loss
- H2O loss = Na loss
Hyponatremic, hypoosmolar, or hypotonic dehydration
Caused by net hyperosmolar or hypertonic fluid loss
- H2O loss < Na loss
Inadequate H2O intake
Hypernatremia!!
- H2O deprivation due to restricted access
- defective thirst response: hypothalamic dz may damage the osmoreceptor
- thirst center may be damaged
Pure H2O loss without H2O replacement
Hypernatremia!!
- insensible loss of H2O by panting, hyperventilation, or fever
- diabetes insipidus (central or nephrgenic) –> unrestricted access to H2O may drink sufficiently to prevetn the hypernatremia
H2O loss > Na loss
Osmotic diuretic agents (glucose and mannitol) –> inhibit passive H2O resorption = hypernatremia
Hypernatremia due to the alimentary system
- accumulation of osmotic agents will inhibit H2O absorption
- phosphate enema will pull H2O from ECF to the colon
- rumen acidosis causes accumulation of solutes in the rumen –> osmotic movement of H2O into the rumen –> hypernatremia
- dogs with paintball toxicosis
Na excess with concurrent restricted H2O intake
- salt poisoning: cattle with excessive Na and with concurrent restricted access to H2O –> increased tb-Na = hypernatremia
- administration of hypertonic saline or Na bicarbonate –> increased tb-Na and hypernatremia
Decreased renal excretion of Na
Hyperaldosteronism
- excessive aldosterone promotes excessive renal Na retention –> hypernatremia (and hyperchloremia) may occur if H2O is restricted or defective ADH activity
Decreased renal excretion of Na due to aldosterone
Aldosterone escape –> hyperaldosteronism does not typically cause hypernatremia
- once Na retention occurs, there is corresponding H2O retention = natriuresis –> prevents development of hypernatremia
- naturiesis may be promoted by ANP
Dehydration with net loss of isotonic fluids
Normonatremia
- alimentary: vomit, diarrhea, sequestration
- renal: polyuric renal dz with defective tubular functions, osmotic diuresis, increased diuresis
- cutaneous: profuse sweating in horses
Edema or transudation with net retention of isotonic fluids
Creates normonatremia or hyponatremia
Congestive heart failure
Forward hypothesis
- decreased CO –> sensed as decreased effected blood volume –> sympathetic nervous system and RAS
- continued RAS –> renal resorption of Na and Cl –> increased osmolality, stimulating ADH release and thirst center –> increased H2O intake and hypervolemia
- if venous hydraulic pressure increases enough = edema/transudation
Hepatic cirrhosis with abdominal transudation
Underfilling theory
- initiating event: increased hydraulic P and loss of H2O and protein rich plasma to peritoneal cavity –> underfilling of vascular spaces and hypovolemia –> RAS and aldosterone release –> increased Na and H2O retention
- clinically: animal has increased tb-Na, tb-H2O, increases concentration of renin, norepinephrine, and ADH, and reduced renal excretion of Na
Hepatic cirrhosis - Peripheral arterial vasodilation theory
Decreased effective blood volume –> RAS –> increases hydraulic pressure in the hepatic sinusoids –> transudation
Nephrotic syndrome
Protein losing nephropathy (leads to abdominal transudation)
- H2O and Na retention mechanism is not understood
- involves several processes
Hyponatremia occurs due to decreased _____
Na/water ratio, or IC to EC water shifting
Na deficit
Hypotonic dehydration
- loss of Na fluid (isotonic) followed by water intake = dilution of Na
- alimentary loss: vomit, diarrhea, sequestration, excess salivation, canine whipworms, bovine hemorrhagic bowel
Hypoadrenocorticism
Low aldosterone –> decreased resorption of Na and Cl –> decreased plasma osmolality and decreased renal medullary hypertonicity –> decreased ability to resorb H2O and hypovolemia
- hypovolemia stimulated ADH release and thirst centers water intake –> dilute ECF Na (and Cl)
Renal loss of Na
Prolonged diuresis by diuretics
- osmotic or by furosemide: Na poor
- thiazide: Na, K, and Cl loss
Ketonuria
Ketone bodies in tubular lumen –> obligate excretion of cations, thus increased excretion of Na
Na wasting nephropathies
Especially tubular diseases or pyelonephritis
- mostly seen in horses
Sweating
Cutaneous loss in horses
- Na, K, Cl rich = hyponatremia
Third space loss
Repeated drainage of chylous throacic effusions
- acute internal hemorrhage or acute exudation
- hyponatremia
H2O excess
Water retention > Na retention
- edematous disorders: CHF, hepatic cirrhosis, nephrotic syndrome
= hyponatremia
Water ICF –> ECF
Marked or persistent osmolality by hyperglycemia or mannitol infusion –> osmotic draw of water into the blood –> dilute Na
Na ECF –> ICF
- acute muscle damage: allows Na to enter cells
- concurrent influx of water and total Ca and efflux of K and PO4
- results in hypovolemia, hypocalcemia, hyperkalemia, hyperphosphatemia
Na IV –> EV
Uroperitoneum
- urine is Na and Cl poor –> diffusion of Na and Cl to peritoneal cavity
K depletion
Total K loss due to :
- GI and renal disorders
- K from ICF to ECF
- electrical neutrality maintained by: Na moving from ECF to ICF
- Cl from ICF to ECF with K –> low intracellular osmolaltiy –> water shifts from ICF to ECF and dilutes plasma Na
Potassium concentration is dependent on
Total body K and movement into and out of cell in response to changes in acid-base status
- most cells are K rich, due to Na/K ATPase pump
- plasma K regulated via ECFICF and renal excretion
- intake and absorption, loss in feces and sweat
[K] should be interpreted with consideration of ____
Acid base status
- an inorganic acidosis (renal failure, some diarrheas, ammonium chloride administration) may cause hyperkalemia shift ICF to ECF
- organic acidosis will not typically cause hyperkalemia
- treatment of acidosis may cause hypokalemia
- metabolic alkalosis may cause mild hypokalemia
____ and ____ promote K uptake
Epinephrine and insulin
- Na/K ATPase pump
- hyperkalemia –> cellular uptake of K
Renal excretion of K
Typically resorbed before distal nephron
- secreted by principal cells of collecting tubules, promoted by aldosterone
- hyperkalemia and angiotensin 2 are major stimulants of aldosterone secretion –> increased flow rate promotes secretion, slow flow inhibits it
- hypochloremic states: resorption of Na without Cl establishes electrochemical gradient that promotes K secretion
- ADH promotes K secretion
Shifting of K ICF –> ECF
- metabolic inorganic acidosis: when H moves in
- rhabdomyolysis: selenium deficiency, malignant hyperthermia, seizures, strenuous exercise
- massive intravascular hemolysis
- hypertonicity: diabetes mellitus
- pseudo-hyperkalemia: in vitro hemolysis (horses, Akitas, Shibas)
Increased total body K
- renal insufficiency: oliguric, anuric (decreased flow of tubular fluid –> decreased secretion)
- urinary tract obstruction or leakage: K enters ECF and is not removed (seen in cats)
- trimethoprin-induced K retention, blocks luminal Na channels –> K sparing diruetics
Hypoaldosteronism
Decreased activity of Na/K ATPase pumps
- decreased resorption of Na and decreased movement of K
Repeated chylous effusion drainage
May be related to hyponatremia + hypovolemia –> less Na resorbed in the distal nephron, less K excretion
Acidotic
Normokalemia
- inorganic (renal failure, diarrhea): expected to increase concentration = hypokalemia
- organic: may not have hyperkalemia due to increased K excretion or shift into cells with organic anions
Alkalotic
Expected to decrease concentration, thus it suggests concurrent hyperkalemia (usually causes normokalemia)
Hypokalemia due to metabolic alkalosis
K into cells when H moves out (minor)
- hypovolemia –> renin angiotensin aldosterone system –> increases secretion of K
- bicarbonaturia –> excretion of cations (including K)
- anorexia or vomiting –> decreased intake of K
- increased insulin activity: cellular uptake of K
Decreased total body K due to increased excretion
Renal loss
- increased tubular flow
- increased renal excretion of anions (ketones, lactate, bicarbonate)
- vomiting or sequestration of H and Cl that causes hypochloremic metabolic alkalosis: excess bicarb in distal nephron –> promotes tubular K secretion
Hyperaldosteronism
Promote renal K secretion by stimulation of Na/K ATPase pump
Hypokalemia is also caused by
- increased excretion via increased alimentary loss
- increased excretion via increased cutaneous loss
- hypokalemic renal failure in cats
Na:K ______ may be diagnostic of hypoadrenocorticism
<27, 25, or 22
Decreased Na:K due to hypoadrenocortisim
Decreased aldosterone
- hyponatremia by increased renal excretion
- hyperkalemia by decreased renal secretion
Decreased Na:K due to diarrhea
Dogs, cats, and horses
- hyponatremia by intestinal loss
- hyperkalemia may occur by acidemia associated with bicarb loss
- in whipworm infections, pseudo-Addison’s dz occurs
Decreased Na:K due to renal failure
Decreased ability of tubules to resorb Na and secrete K (oliguria)
Decreased Na:K due to urinary tract obstruction or uroperitoneum
Na may diffuse into peritoneal fluid and creates hyponatremia
- mild hyponatremia might be present in obstruction
- hyperkalemia occurs because of acute oliguria or anuria –> decreased tubular secretion of K
Decreased Na:K due to diabetes mellitus with ketonuria
Hyponatremia due to osmotic diuresis –> increased Na excretion and plasma dilution
- hyperkalemia not expected
Decreased Na:K due to third space loss
Hyponatremia due to dilution by retained water
- hyperkalemia may result from decreased renal excretion or a shift from ICF to ECF due to an associated acidosis
Chloride concentration
- serum [Cl} = ECF [Cl} –> influenced by Na and HCO3
- controlled by renal resorption and secretion, and alimentary tract functions
Hyperchloremia typically occurs with _____
Hypernatremia
- occasionally concurrently with low bicarb (metabolic acidosis)
- changes in Cl: related to attempts to maintain electrical neutrality
- increased [Na] –> increased [Cl]
- decreased [HCO3] –> increased [Cl}
Hyperchloremia due to water deficit
Cl is the major anion to maintain electrical neutrality in the ECF –> increased Na will lead to increased Cl
- water deprivation or loss (same as Na)
Excess Cl
- increased intake of Cl with restricted water (salt poisoning)
- decreased renal excretion of Na: hyperaldosteronism (rare)
Hyperchloremic metabolic acidosis - alimentary
- vomiting, diarrhea with loss of intestinal secretions
- cattle with esophageal obstruction (cannot ingest saliva) –> loss of Na and HCO3 (Cl poor solution)
Hyperchloremic metabolic acidosis - renal
- proximal tubule acidosis: less HCO3 allows more Cl to be reabsorbed
- distal renal acidosis has impaired ability to secrete H –> inability to reabosorb HCO3 and secrete Cl
Respiratory alkalosis (chronic)
Compensatory change to the alkalemia: increased retention of H and decreased conservation of HCO3
- decrease in HCO3 leads to increase in Cl and other anions
Hypochloremia typically occurs with
Hyponatremia or increased serum bicarb
- also metabolic acidosis with increased anion gap
Hyponatremic dehydration
Alimentary, renal, cutaneous or third space loss
- leads to hypochloremia
Hypochloremia due to acid base disturbances
Low [Cl] is present in the absence of hyponatremia –> electrical neutrality must be maintained
- increased bicarb
- increased anion gap
Metabolic alkalosis - hypochloremia
Loss or sequestration of Cl rich secretions (vomiting, displaced abomassum, bovine hemorrhagic bowel syndrome)
- depletion of Cl
- furosemide: inhibits Cl resorption in loop of Henle
- thiazide diuretics
Bovine renal failure
Causes alkalosis
- changes result from abomasal atony –> functional obstruction and sequestration of Cl
- more excretion of K in saliva –> limit absorption of Cl
Metabolic acidosis with increased anion gap
Ketoacidosis and lactic acidosis: obligate excretion of Na –> less resorption of Cl
- foreign substances that generates anions also lead to obligate Na loss
_____ is a major buffer that helps maintain the blood pH
Bicarbonate
- produced from H2O and CO2 by carbonic anhydrase
- RBCs, proximal renal tubular cells, parietal cells from gastric acid and abomasal epithelium, intercalated cells of collecting tubules, exocrine pancreatic epithelial cells
Bicarb measurements
- HCO3 is calculated in blood gas analysis
- total CO2 reflects total amount of CO2 gas that can be liberated from serum
- 95% of potential CO2 gas is in the form of HCO3 –> 5% is dissolved, so [tCO2] is equal to [HCO3]
Increased [HCO3[ or [tCO2] due to gastric loss
Vomiting, pyloric obstruction
- secretion of H by gastric mucosa generates HCO3
- if H lost by vomiting or sequestration before intestines –> not absorbed –> bicarb not used for buffering –> accumulates in plasma
- hypovolemia with concurrent hypochloremia –> resorption of Na in distal nephron with H secretion and generation of bicarb
Metabolic alkalosis in cattle renal failure
Abomasal atony –> HCl sequestration generating alkalosis
- increased [HCO3] or [tCO2]
Renal loss of H due to loop of Henle diuretics
Furosemide and other loop diuretics block resorption of Na, K, and Cl –> decreased water resorption and increased fluid flow –> increased secretion of H and bicarb generation
- hypovolemia and hypochloremia may contribute to the H secretion = increased [HCO3] or [tCO2]
Renal loss of H due to thiazide diuretics
Inhibits Na/Cl cotransporter –> hypovolemia and hypochloremia
- increased [HCO3]
Increased [HCO3] secondary to respiratory _____
Acidosis
- renal compensation
Increased [HCO3] due to hypokalemia
Stimulates H/K ATPase in distal nephron –> K retention, H secretion and HCO3 generation
Increased [HCO3] due to renal loss of H
Endurance races (sweating) and intestinal disorders in horses - lead to hypovolemia and hypochloremia --> secretion of H
Shift of H from ECF to ICF due to hypokalemia
Alkalosis can lead to hypokalemia and hypokalemia can contribute to an alkalosis
- depletion of tbK –> K out of cell and H into = increased [HCO3]
Contraction alkalosis
- loss of Cl rich ECF: vomiting, sequestration, and loop diuretics –> ECV volume contraction and increased [HCO3] (minimal)
- volume contraction –> aldosterone response –> promoting renal secretion of H and Cl
- concurrent loss of H might happen
Decreased [HCO3] or [tCO2] due to metabolic ____
Acidosis (primary or compensating)
Generation of excess H
Depletion of HCO3
- titrational acidosis
- lactic acidosis: anaerobic glycolysis –> excess H
- ketoacidosis: excessive B-oxidation of TGs in hepatocytes
- ingestion of certain compounds (ethylene glycol, methanol): catabolism generates acid
Decreaed renal excretion of H
- renal failure –> decreased acid excretion
- urinary tract obstruction and uroperitoneum
- distal renal tubular acidosis: tubular disease –> decreased secretion of H
- hypoaldosteronism in hypoadrenocoricism
Increased HCO3 loss
- alimentary: intestinal and pancreatic secretion are HCO rich –> vomiting, sequestraiton can cause bicarb depletion and loss of buffering capacity
- renal: proximal renal tubular acidosis (Fanconi’s syndrome) –> defect in HCO3 conservation
Dilutional acidosis
Rapid saline infusion (minor changes)
- decreased [HCO3] or [tCO2]
Cation
Atom or molecule with positive charge
- monovalents
- divalents
Measured cation charge (mC)
Na and K
- monovalents and measured as free ions: [ion] = [charge]
Unmeasured cation charge (uC)
[charge] of all other cations of blood
- fCa, fMg, and cationic globulins
- [charge] > [ion]
Anion
Atom or molecule with negative charge
- monovalent
- divalent
- trivalent
Measured anion charge
Cl and HCO3
- monovalents, are measured as free ions [ion] = [charge]
Unmeasured anion charge
[charge] of all other anions of blood
- PO4, albumin, anions of organic acids, and SO4
- [charge] >[ion]
Total cation or anion charges
Total [charge]
- measured + unmeasured
Anion gap
Difference in the [charge] (not ion) between uA and uC
- is also equal to the difference between measured C and A
- measured cations and anions: charges concentrations are the same as ions concentrations
Serum is always ______
Electrically neutral
- [+charges] = [-charges]
- cations: Na and K (95%)
- anions: Cl and HCO3 (85%)
What is the major purpose of calculating the anion gap
Identify increased uA, thus defect increased circulating anionic molecules (L-lactate and ketone bodies)
Healthy anion gap
uA are greater than uC: charges from proteins, organic ions, PO4 and SO4 are greater than charges from fCa, fMg, and H
- anion gap is almost equivalent to the [anions] from organic acids and proteins, PO4, and SO4 since [uC] are small
Anion gap - normochloremic and hypochloremic metabolic acidosis
Increase AG due to increased uA
- organic acids (lactic)
- inorganic acids (renal failure)
Anion gap - hypochloremic metabolic alkalosis
- decreased [Cl] and increased [HCO3]
- no change in AG
- sum of [Cl] and [HCO3] and sum of [Na] and [K] have not changed
- occurs with vomiting and GI sequestration of H and Cl
Anion gap - hyponatremia and hypochloremia
- concurrent Na and Cl decrease
- no changes in other concentrations
- no change in AG
- same proportion of Na and Cl loss
- intestinal, via diarrhea or renal, in hypoadrenocorticism
Anion gap - hypoproteinemia
- lower concentrations of proteins
- increased sum of [Cl] and {HCO3]
- no change in sum of [Na] and [K]
- decreased AG
Increased anion gap - metabolic acidosis
- increased lactate
- increased ketone bodies
- renal failure –> increased phosphate, sulfate, or citrate
- massive rhabdomyolysis: probably increased lactate and PO4
- ingestion of ethylene glycol, methanol, paraldehyde, metaldehyde, penicillin
Hyperchloremic metabolic acidossi will typically not
Increase
False increase/decreased anion gap
- pseudo-hyponatremia and pseudo-hypochloremia: unreliable AG valvue
- falsely increased if [HCO3] is falsely decreased due to escape of CO2 from sample
Decreased anion gap
Minimal clinical significance
- often due to hypoalbuminemia
- important to know if animal has hypoalbuminemia, AG would be high if normal albumin
- occasionally due to hypercalcemia, hypermagnesemia, or multiple myeloma (increased positively charged Igs)
Skeletal muscle is the major source of ______
Lactate
- diffuses from myocyte to plasma
- taken up by hepatocytes
D-lactate
Produced by bacteria (some produce L lactate)
- very small concentrations in plasma in mammals
Hyperlactatemia
L-lactate concentration
- formation exceeds removal by tissues
- hypoxia is primary reason!! –> anaerobic conditions (pyruvate–>L-lactate) or accumulation of H and acidemia
- may also be due to defective metabolic pathways
- decreased removal potentially can contribute to increase concentration, but is not common
Hyperlactatemia due to stagnant hypoxia
- shock
- equine colic: poor perfusion of tissues, absorbed endotoxin, production of L and D-lactate by intestinal bacteria (higher hyperlactatemia = worse prognosis)
Hyperlactatemia due to demand hypoxia
Strenuous exercise
Hyperlactatemia due to increased production by metabolic pathways
- grain overload –> increases formation of lactate by bacteria
- defective glycolyic pathways: hyperammonemia, pyruvate dehydrogenase deficiency
Other unknown causes of hyperlactatemia
- sepsis
- canine babesiosis
- liver disease
- transfusion of stored RBCs: L-lactate rich
Both, _____ and _____ will contribute to an anion gap
L-lactate and D-lactate
- if there is an increase anion gap and L-lactate is not increased sufficiently for the magnitude, it could be due to D-lactate or other unmeasured anions
Ketogenesis in hepatocytes
AcCoA into ketone bodies
- BHB and AcAc
- acetone
- promoted by glucagon and inhibited by insulin
Ketosis
- excess glucagon or insulin deficiency –> excessive B-oxidation of fatty acids –> excess of AcCoA –> ketogenic pathway (diabetes mellitus and starvation)
- in negative energy status: oxidation of lipids with inadequate amount of oxaloacetate –> accumulation of AcCoA
Ketonemia
- all mammals: starvation, prolonged anorexia, diabetes mellitus
- cattle: bovine ketosis in lactation, displaced abomasum, hepatic lipidosis
- dogs: starvation, lactation, endurance racing
- horses: endurance racing
Osmolality
Concentration of a solute in moles/kg
Osmolarity
Concentration of a solute in moles/L
Major components of osmolality
- Na is major solute in serum, Cl is the second
- at physiological concentrations, urea and glucose are small contributors –> marked azotemia or hyperglycemia will cause hyperosmolality
- protein contribute very little to osmolality
_____ detect increases and decreases in effective plasma osmolality
Hypothalamic osmoreceptors
- increased: ADH is released –> stimulate water resorption, thirst center stimulated –> dilutional correction of plasma solute concentration
- decreased: diminished ADH secretion –> less water resorption
Increased osmolality
- increased Na, urea, glucose
- increased concentration of a nonanionic compound
- mannitol infusion, radiograph contrast media, ethanol, methanol, ethylene glycol
Decreased osmolality
Hyponatremia
