Term
| Does plasma [electrolyte] correspond to the [electrolyte] in ICF or ECF? |
|
Definition
|
|
Term
| Where does most of the body's HCO3 come from? |
|
Definition
| generated by carbonic anhydrase in the lungs, gastric mucosa, kidney and RBC |
|
|
Term
| What are the typical concentrations of Na, Cl, and K in the ECF vs. ICF? |
|
Definition
ECF is typically high in NA and Cl, and low in K
ICF is typically high in K but low in Na and Cl |
|
|
Term
| What accounts for the slight difference in [K] between serum and plasma? |
|
Definition
serum [K] is slightly higher than plasma because of potassium release by activated platelets forming the clot
* the magnitude of increase can be significant when there is thrombocytosis |
|
|
Term
| In terms of total body water to total body sodium, what three general situations can result in hypernatremia? |
|
Definition
Increased sodium with normal water
normal sodium with decreased water (hypotonic fluid loss)
decreased sodium with proportionally more decreased water |
|
|
Term
| In terms of total body water to total body sodium, what three general situations can result in hyponatremia? |
|
Definition
decreased sodium with normal water
normal sodium with water retention
proportionally greater sodium loss than water loss |
|
|
Term
| Describe the relationship between plasma [Na] and [K] |
|
Definition
The total body exchangeable (i.e. non-ion bound) [K] influences plasma [Na] because these cations are also involved in maintenance of electroneutrality.
With hypokalemia, intracellular potassium moves along its concentration gradient into the vasculature and sodium then moves into the cell to maintain electroneutrality --> hyponatremia can develop with hypokalemia
**hyperkalemia does not typically result in hypernatremia because of stimulation of thirst centers resulting in dilution of both due to intake of pure water |
|
|
Term
| Although water typically follows sodium along the gradient in osmotic pressure what two locations in the kidney are impermeable to water? |
|
Definition
Ascending limb of the loop of henle
distal nephron (in the absence of ADH) |
|
|
Term
| What are the two major mechanisms that control serum [Na]? |
|
Definition
regulation of blood volume
regulation of plasma osmolality |
|
|
Term
| Describe how regulation of decreased blood volume by the juxtaglomerular apparatus in the kideny is accomplished and how this affects serum [Na] |
|
Definition
decreased blood volume is sensed by juxtaglomerular apparatus in kidney --> renin --> RAAS --> Angiotensin II is produced in the lungs which causes vasoconstriction, proximal tubular reabsorption of sodium, chloride, and water AND stimulates release of aldosterone from adrenal cortex --> aldosterone increases sodium reabsorption in the distal nephron
Angiotensin II- proximal tubular reabsorption of NA (cl and water)
Aldosterone- distal tubular reabsorption of Na (and renal wasting of K+) |
|
|
Term
| Describe how regulation of decreased blood volume by the baroreceptors in the carotid body is accomplished |
|
Definition
| carotid body baroreceptors stimulate secretion of ADH in response to hypovolemia (increased water reabsorption in the distal nephron) |
|
|
Term
| Where is hypervolemia sensed and what is the biochemical response? |
|
Definition
| hypervolemia is sensed by atrial baroreceptors --> release of atrial natiuretic peptide --> decreased sodium reabsorption in the distal nephron (via reduction in number of open sodium channels through the guanylyl cyclase pathway) |
|
|
Term
| How does the gaunylate cyclase pathway relate to [sodium] |
|
Definition
| guanylate cyclase pathwat is invovled in regulating the number of functional sodium channels in the distal nephron. In response to atrial naitruetic peptic (secreted by heart when there is hypervolemia) less sodium chanels are open in the distal nephron --> less sodium reabsorption |
|
|
Term
| In addition to increased permeability of the distal nephron to water, what direct actions on Na and Cl does ADH also have? |
|
Definition
ADH stimulates Na and Cl reabsorption in the ascending limb of the loop of henle through Na-K-2Cl cotransporter
**this is a relatively minor role of ADH compared to the aquaporin business.... |
|
|
Term
| What are the major factors that control aldosterone secretion? |
|
Definition
effective blood volume (via RAAS)
plasma [K]
**hyponatremia will stimulate aldosterone secretion (and thus Na retention) and vice versa (hypernatremia inhibits aldosterone secretion) but sodium is a minor player in regulating aldosterone secretion compared to blood volume and [K] |
|
|
Term
| What two transport mechanisms in the distal nephron are involved in sodium and chloride resorption? |
|
Definition
Na-K-ATPase (aldosterone)
Na-Cl cotransporter (increased sodium reabsorption occurs with increased delivery of sodium to the distal nephron)**
**thiazie diuretics block sodium reabsorption (and hence impair water reabsoprtion) by binding to the Cl receptor of this Na-Cl cotransporter |
|
|
Term
| What conditions result in hypotonic dehydration (free water deficit only)? |
|
Definition
Water deprivation
Loss of free water (central or renal diabetes insipidus, insensible respiratory loss of free water) |
|
|
Term
| What conditions result in isotonic or hypertonic dehydration (free water and sodium deficit)? |
|
Definition
GI losses (vomit, diarrhea, sequestration, excessive salivation)
Renal losses (most polyuric states)
cutaneous loss (sweating- horses) |
|
|
Term
| What methodology is used to measure serum [Na]? |
|
Definition
| potentriometry, can be direct (non-diluted sample) or indirect (diluted sample). Sodium interacts with an nonselective electrode. Only the electrical potential of the sodium ion in water is measured. |
|
|
Term
| What effect does hyperproteinemia or hyperlipidemia have on measurement of [Na] by direct vs. indirect potentiometry? |
|
Definition
If a sample has increased protein or lipid there is a decrease in the water component. If using direct potentiometry there is no effect on [Na] because it measures the electrical activity of sodium ions only in water.
If using indirect potentiometry addition of a large volume of diluent will dilute the water component of the sample more than usual (same volume of diluent but less water in the sample due to proteins etc.) resulting in a falsely low [Na] |
|
|
Term
| What disease in dogs is associated with hypernatremic dehydration due to defective thirst response? |
|
Definition
| Lobar holoprosencephaly in miniature schnauzers -> damaged osmoreceptors in hypothalamus results in impaired thirst response |
|
|
Term
| Why are animals with diabetes insipidus (decreased secretion or responsiveness of ADH) not necessarily hypernatremic despite pure water loss in the kidney ? |
|
Definition
| If they have unrestricted access to water they may drink enough to prevent hypernatremia |
|
|
Term
| Describe the pathogenesis of hypernatremia in cattle with rumen acidosis (grain overload) |
|
Definition
| accumulation of solutes in the rumen (including lactic acid) causes osmotic movement of water into the rumen and resultant hypernatremia |
|
|
Term
| Why is hyperaldosteronism not typically associated with hypernatremia? |
|
Definition
excessive aldosterone promotes excessive renal retention of sodium (and chloride) --> water follows sodium --> increased blood volume* --> increased GFR increased renal loss of sodium
*increased blood volume also stimulated atrial baroreceptors --> increased production of atrial naitureitic peptide --> increased renal excretion of sodium in the distal nephron |
|
|
Term
| What is the proposed mechanisms for post-race hypernatremia in greyhounds? |
|
Definition
| water shifts from ECF to ICF due accumulation of L-lactate in muscle fibers (creates an osmotic gradient) |
|
|
Term
| How do most diuretics work? |
|
Definition
| furosemide and thiazide diuretics cause sodium and water loss through interference with renal reabsorption of chloride |
|
|
Term
| Describe the pathogenesis of edema/effusion formation in congestive heart failure |
|
Definition
decreased cardiac output is is sensed by baroreceptors in the kidney (RAAS), carotid body (ADH) --> if hypervolemia increases vascular hydrostatic pressure sufficiently ---> promotes movement into tissue (pulmonary or dependent edema) and into serous cavities (modified transudates)
** this individuals will be normonatremic regardless of water retention because the aldosterone and angiotensin II all promote renal sodium retention |
|
|
Term
| What are the three major hypotheses for the development of a peritoneal effusion due to increased hydrostatic pressure in animals with hepatic cirrhosis (none related to hypoalbuminemia)? |
|
Definition
Underfilling theory- increased hydrostatic pressure (due to fibrosis or passive congestion) + leaky capillaries (hepatic sinusoidal endothelium are normally permeable to plasma proteins) --> underfilled hepatic vasculature --> stimulates RAAS and ADH --> further contributes to increased hydrostatic pressure due to retention of sodium and water --> further effusion production
Overflow theory- initiating event is renal retention of sodium and water, other factors not understood
Peripheral arterial vasodilation theory: Peripheral vasodilation reduces effective blood volume --> stimulates RAAS and ADH --> increased hydrostatic pressure in hepatic sinusoids |
|
|
Term
| Why do dogs with PLN often not develop edema (i.e. a component of nephrotic syndrome)? |
|
Definition
| dogs with PLN may also have concurrent tubular dysfunction, as such the kidney has a lower capacity to retain sodium and water |
|
|
Term
| What proportion of sodium to water is lost in hypotonic dehydration? |
|
Definition
sodium loss >> water loss
*that is, the patient is dehydrated AND has hypotonic plasma. The [Na] lost in fluid is usually not greater than plasma [Na], but the plasma [Na] may be secondarily decreased due to pure water intake (e.g. drinking) and renal retention of water (ADH) |
|
|
Term
| Describe the pathogenesis of hyponatremia in the case of hypoadrenocorticism |
|
Definition
| Aldosterone deficiency results in less renal reabsorption of Na (and Cl) --> decreased plasma osmolality and decreased renal medullary hypertonicity --> inability to reabsorb water from ultrafiltrate (+GI losses) results in hypovolemia --> stimulates hypothalamic secretion of ADH (this is also further enhanced by hypocortisolemia through unknown mechanisms) which increases renal water reabsorption to further dilute plasma [Na] |
|
|
Term
| Describe the mechanism of increased renal loss of K+ with thiazide diuretics |
|
Definition
Thiazide diuretics inhibit Na-Cl cotransporter in distal nephron (interfere with Cl binding) --> increased natriuresis and renal water loss--> hypovolemia stimulates release of aldosterone --> promotes renal excretion of potassium
-> increased flow rate through nephron also reduces K reabsorption
-> ADH (release from hypothalamus in response to hypovolemia) promotes reabsorption of free water thus diluting remaining Na, Cl, and K |
|
|
Term
| What conditions are associated with a dilutional hyponatremia, in part due to the action of ADH in conserving water in the presence of hypo-osmolality (i.e. secondary to loss of sodium containing fluids)? |
|
Definition
Alimentary fluid losses
Renal losses (hypoadrenocorticism, prolonged diuresis)
Sweating (horses)
Repeated drainage of cavitary effusions (chylous) |
|
|
Term
| What electrolyte is lost as a results of ketonuria? |
|
Definition
| Sodium- the presence of ketones (which are anions) in the urine necessitates concurrent increased excretion of cations (i.e. sodium) |
|
|
Term
| What conditions have been associated with syndrome of inappropriate ADH secretion and what is the effect on plasma [Na]? |
|
Definition
SIADH has been associated with neurologic, pulmonary, thyroid disorders and many drugs (although rarely reported in veterinary literature)
Non-physiologic secretion of ADH in hypervolemic and hypo-osmolar animals with unrestricted access to water --> progressive decreased [Na], concurrent release of ANP promotes naturesis (cGMP phosphorylation of sodium channels in distal nephron) which further contributes to decreased [Na] |
|
|
Term
| Why is primary (psychogenic) polydipsia not typically associated with hyponatremia? |
|
Definition
If the kidneys are functioning they will excrete excess water
**so expect dilute (<1.008) USG |
|
|
Term
| What circumstances are associated with decreased plasma [Na] due to shift of water from ICF to ECF (i.e. into the vasculature) ? |
|
Definition
marked or persistent increase in plasma osmolality usually secondary to diabetes mellitus* or infusion of mannitol
**concurrent osmootic diuresis +/- ketonuria also contribute to natiuresis and therefore decreased plasma [Na] |
|
|
Term
| What electrolyte changes are expected in severe rhabdomyolysis (horses)? |
|
Definition
Damaged muscle cell membranes allow analytes to equilibrate between ECF and ICF. So muscle injury is associated with:
hyponatremia and hypocalcemia (normally lower concentrations intracellularly)
hyperkalemia and hyperphosphatemia (normally higher concentrations intracellularly) |
|
|
Term
| Describe the pathogenesis of hyponatremia and hypochloridemia in the case of uroabdomen |
|
Definition
urine is typically low in sodium and chloride so they diffuse from plasma into the peritoneal cavity along osmotic gradient
hyponatermia and hypochloridemia were detected within 1-2days after induction of experimental uroabdomen in dogs |
|
|
Term
| Describe the effect of total body potassium depletion of plasma [Na] |
|
Definition
total body depletion of K+ results in extracellular translocation of K+ along concentration gradient-
Sodium moves from ECF to ICF to maintain electroneutrality
Dilution of plasma [Na] due to decreased intracellular osmolality:
Other ways to maintain electroneutrality when there is extracellular translation of K+ include: concurrent extracellular translocation of Cl- or concurrent intracellular translocation of H+ (which binds to buffers and doesn't contribute to intracellular osmolality), both of these situations result in decreased intracellular osmolality --> water moves from ICF to ECF --> dilutes plasma [Na] |
|
|
Term
| Describe how potassium depletion results in a metabolic alkalosis? |
|
Definition
| With hypokalemia potassium shifts from ICF to ECF --> H+ then shifts from ECF to ICF to maintain electroneutrality |
|
|
Term
| What is the effect of an alkalosis on serum [K]? |
|
Definition
Hypokalemia (typically mild)
with alkalosis H+ shifts from ICF to ECF --> K+ shifts from ECF to ICF to maintain electroneutrality |
|
|
Term
| Why does organic acidosis not typically associated with hyperkalemia? |
|
Definition
At a physiologic pH organic acids are almost completely dissociated into their anionic forms. Organic anions can move into the cell along with H+ therefore maintaining electroneutrality without shifts in K+
K+ is excreted in the urine along with the organic anions (e.g. ketones, lactate) and doesn't accumulate in the blood |
|
|
Term
| What is the effect of inorganic acidosis (e.g. renal failure, diarrhea with loss of HCO3) on serum [K+]? |
|
Definition
Increased [K]
H+ moves from ECF to ICF --> K+ moves from ICF to ECF to maintain electroneutrality |
|
|
Term
| T/F respiratory acid base disturbances don't effect serum [K] |
|
Definition
|
|
Term
| T/F if the acid-base status is normal, serum [K] tends to reflect total body [K] |
|
Definition
True
**however, potassium depletion can occur prior to the development of hypokalemia due to the predominance of intracellular K+ |
|
|
Term
| What hormones promote the intracellular uptake of K+ via Na-K-ATPase? |
|
Definition
epinephrine and insulin*
*this effect of insulin is indecent of its actions with regards to glucose uptake |
|
|
Term
| Where in the kidney, and by what cells, does most of the renal excretion of potassium occur? |
|
Definition
Collecting tubules, principal cells
via Na-K-ATPase and luminal K+ channels (all augmented by aldosterone) |
|
|
Term
| What are the major stimulants for aldosterone secretion? |
|
Definition
Angiotensin II (via RAAS) and hyperkalemia
**ACTH and hyponatremia also stimulate aldosterone secretion. Effect of hyponatremia is diminished if effective blood volume is adequate |
|
|
Term
| How does hypochloridemia affect renal handling of potassium? |
|
Definition
Promotes renal secretion of K+
Reabsorption of sodium without chloride creates an electrochemical gradient (tubular fluid is more negative than the cell) this promotes secretion of K+ |
|
|
Term
| Where in the kidney, and by what cells, does renal reabsorption of potassium occur (in hypokalemic states with total body K+ depletion)? |
|
Definition
Distal nephron, type A intercalated cells
via H+-K+-ATPase (in the presence of total body K+ depletion) |
|
|
Term
| How does ADH affect renal secretion of K+? |
|
Definition
ADH promotes K+ secretion
this counteracts the decreased K+ secretion associated with decreased tubular flow rates (more time for passive movement of K+ from tubular fluid into cells) and prevents hyperkalemia from developing in severe dehydration where urine output is decreased |
|
|
Term
| What four major processes affect serum [K]? list from greatest to least impact |
|
Definition
Acid-Base status (inorganic metabolic acidosis [increased K], metabolic alkalosis [decreased K])
Renal secretion (promoted by Aldosterone [aldosterone secretion is stimulated by angiotensin II, hyperkalemia, ACTH and hyponatremia] and a high flow rate through nephron [decreased passive reabsorption of K])
loss in feces and cutaneous (sweating horses)
Intestinal absorption |
|
|
Term
| What is the net electrochemical effect of renal principle cell reabsorption of sodium and secretion of potassium in the presence of aldosterone? |
|
Definition
slight negative charge in tubular fluid (only 2K secreted for every 3Na reabsorbed)
**this is normally negated by paracellular reabsorption of Cl- and passive equilibration of H+ between principle cell and tubular fluid (if there is hypochloridemia, more H+ moves into tubular fluid to maintain electroneutrality) |
|
|
Term
| What are some proposed mechanisms for hyperkalemia associated with strenuous exercise? |
|
Definition
myocyte damage or release of intracellular K+
Translocation of K+ from ICF to ECF secondary to decreases in non-diffusible intracellular anions (e.g. hydrolization of phosphocreatine to neutral creatine)
**dogs with experimentally induced hypothyroidism developed mild hyperkalemia following mild exercise (5 min run), possibly related to decreased Na-K-ATPase activity in skeletal muscle |
|
|
Term
| How do the type A intercalated cells of the distal nephron respond to sytemic acidemia? |
|
Definition
increased activity of H-ATPase (this is augmented by aldosterone) results in pumping of H+ from intercalated cell into tubular lumen
Simultaneously OH- (from dissociation of water) combines with CO2 and carbonic anhydrase catalyzes the formation of HCO3- which is reaborbed into the blood via the HCO3-Cl exchanger*
*Cl is also secreted into the tubule to maintain electroneutrality (given increased H+ secretion) |
|
|
Term
| Describe the proposed pathogenesis of hyperkalemia in english springer spaniels with phosphophructokinase deficiency? |
|
Definition
| Episodes of hemolysis may involve younger RBC that have higher intracellular [K] |
|
|
Term
| What species and particular breeds have higher RBC [K] (enough to affect serum [K] if there is hemolysis or prolonged clot contact)? |
|
Definition
Horses, cattle
Some breeds of dogs: Shiba inu, Akita
***No hyperkalemia is expected with hemolysis of RBC from cats or most other dog breeds |
|
|
Term
| Describe the pathogenesis of hyperkalemia associated with oliguric/anuric renal failure |
|
Definition
Markedly diminished tubular flow rate allows potassium to accumulate in the tubular fluid diminishing the concentration gradient between the cells of the collecting duct and the tubular fluid --> impairs passive secretion of K into the tubular fluid, also as K+ secretion is diminished K+ from diet and cells accumulates as well
If there is a concurrent inorganic metabolic acidosis (e.g. uremic acids) --> K+ shift from ICF to ECF further contributing to hyperkalemia |
|
|
Term
| What is the effect of trimethoprim sulfa on renal handling of electrolytes? |
|
Definition
TMS blacks luminal sodium channels of collecting ducts (esp. in acidic urine) --> reduced sodium (and water) reabsorption --> decreased electrical gradient across cells and tubular fluid (more cations in the tubular fluid) --> decreased K+ secretion**
**K+ secretion also depends on adequate flow rate of tubular fluid to cary secreted K+ away, thus maintaining the high intracellular to lumen K+ gradient. So if there is low flow rate the effects of TMS on K+ retention are magnified |
|
|
Term
| Describe a proposed mechanism for hyperkalemia in the case of repeated drainage of chylous thoracic effusions |
|
Definition
| likely related to hyponatremia. Most of the filtered sodium is reabsorbed in the proximal tubule and ascending limb of loop of henle --> less sodium to be reabsorbed in the distal nephron --> reduced electrical gradient to stimulate secretion of K+ |
|
|
Term
| What pathophysiologic states might be associated with normokalemia and inorganic academia? |
|
Definition
This implies depletion of total body K+ (b/c inorganic acidosis usually causes shift of K from ICF to ECF)
disease states that might be associated with these abnormalities include renal failure and secretional diarrhea |
|
|
Term
| Why does organic metabolic acidosis not result in hyperkalemia? |
|
Definition
| Due to the presence of unmeasured anions. When H+ moves from the ECF to ICF those anions also move with it therefore negating the need for K+ to move to the ECF, similarly, when H+ is excreted in the urine the anions are also excreted essentially neutralizing the H+ from an electrical staindpoint |
|
|
Term
| What are the four major contributors to hypokalemia with metabolic alkalosis? |
|
Definition
1. H+ moves from ICF to ECF due to the alkalemia --> K+ shifts from ECF to ICF to maintain electroneutrality
2. concurrent hypovolemia activates RAAS --> aldosterone stimulates renal excretion of K+
3. Renal excretion of bicarbonate necessitates concurrent renal excretion of cations (including K+) to maintain electroneutrality
4. decreased dietary intake of K+ (vomiting and diarrhea) |
|
|
Term
| How does insulin affect serum [K+]? |
|
Definition
insulin promotes cellular uptake of K+ (likely via Na-K-ATPase)
*this is most likely to happen with administration of exogenous insulin, or sudden release of endogenous insulin in animals receiving IV dextrose, and possibly also in animals with endotoxemia |
|
|
Term
| What circumstances result in hypokalemia secondary to increased renal excretion of potassium? |
|
Definition
1. increased tubular flow i.e. polyuric states (rapid flushing of potassium from tubular fluid enhances passive secretion of potassium in the distal tubule)
2. Increased renal excretion of anions (ketones, lactate, HCO3), negative charge obligates the concurrent loss of cations such as K+ |
|
|
Term
| Describe the pathogenesis of hypokalemia in hyperaldosteronism |
|
Definition
| Aldosterone promotes the basolateral Na-K-ATPase and luminal K+ channels in the distal nephron promoting renal excretion of potassium |
|
|
Term
| What body fluids are potassium rich compared to serum? |
|
Definition
| Saliva (horses and cattle) and sweat (horses) |
|
|
Term
| What cat breed is associated with an inherited hypokelamic myopathy? |
|
Definition
Burmese
*the pathogenesis of the hypokalemia is not established, but may be due to sudden shift of K+ from ECF to ICF. These animals had high CK, muscle weakness and hypokalemia |
|
|
Term
| What conditions are associated with a low Na:K? |
|
Definition
Hypoadrenocorticism
diarrhea, esp whipworm infection
oliguric renal failure, urinary tract obstruction/rupture
Repeated drainage of cavitary effusions |
|
|
Term
| Where and through what mechanism does most chloride absorption occur in the kidney? |
|
Definition
| 75% of filtered chloride is reabsorbed in the proximal tubule down a concentration gradient created by sodium and water (this is enhanced by Angiotensin II) AND via a formate-chloride exchanger |
|
|
Term
| What transporter is involved in chloride reabsorption in the ascending limb of the loop of henle? |
|
Definition
Na-K-2Cl transporter
This process is blocked by loop diuretics and stimulated by ADH |
|
|
Term
| What is the effect of acidemia (and therefore aciduria) on renal handling of chloride? Whats the effect of alkalemia/uria? |
|
Definition
chloride is secreted along with H+ by the type A intercalated cells in the distal nephron, a process that is promoted by acidemia/uria
Bicarbonate is secreted and chloride is conserved by the type B intercalated cells of the distal nephron when there is alkalemia/uria |
|
|
Term
| How is bicarbonate involved in gastric/abomasal secretion of HCL? |
|
Definition
Cloride enters the parietal cell via a bicarbonate chloride exchanger (it is then secreted into the gastric lumen via along with either sodium or potassium via an ATPase)
without bicarbonate generation inside the parietal cells (from CO2, H2O and carbonic anhydrase) there is not a gradient for chloride absorption into the cell |
|
|
Term
| What anions can react with chloride selective electrodes resulting in falsely increased [Cl]? |
|
Definition
Bromides (e.g. KBr)
lactate
betahydroxybutyrate |
|
|
Term
| What general conditions are associated with hypernatremia and hyperchloridemia due to a deficit in total body water? |
|
Definition
Inadequate water intake: water deprivation, hypothalamic defect resulting in defective thirst reflect
pure water loss: insensible loss (panting, fever, hyperventilation), diabetes insidious (central or renal)
water loss > Na and Cl loss: renal osmotic diuresis, GI losses (osmotic diarrhea, osmotic sequestration, phosphate enema) |
|
|
Term
| What non-iatrogenic cause of excess total body chloride (usually concurrent excess Na) should be considered? |
|
Definition
Hyperaldosteronism (renal retention of sodium and chloride), if water intake is restricted and/or ADH activity is reduced
*although this is theoretically a cause of hypernatremia and hyperchloridemia, in reality animals with hyperaldosteronism frequently have normal [Na] and [Cl], because as sodium retention occurs there is corresponding water retention and renal excretion of sodium (likely as a result of atrial naituretic peptide - cGMP phosphorylation of distal nephron sodium channels) |
|
|
Term
| What acid base disorders result in hyperchloremia? |
|
Definition
ALKALOSIS
metabolic-
ALIMENTARY: loss of HCO3- rich intestinal secretions [vomit or diarrhea], and in cattle loss of HCO3- rich saliva; these HCO3- secretions are also rich in Na but low in Cl-
RENAL: loss of HC03-
proximal and distal renal tubular acidosis (if there is loss of HCO3- then there must be retention of Cl- to maintain electroneutrality)
**chronic respiratory alkalosis results in renal retention of H+ with decreased renal retention of HCO3- |
|
|
Term
| What process must be concurrent for proximal tubular reabsorption of bicarbonate? |
|
Definition
Tubular secretion of H+
H+ binds to HCO3- in tubular fluid --> H2CO3 --> C02 + H20
C02 is reabsorbed into proximal tubular cell where it combines with OH- (from dissociation of cellular water) to form HC03-, which passively moved into the ECF (blood) down an electrical gradient |
|
|
Term
| What are changes in serum [HCO3] linked to changes in [Cl) |
|
Definition
| because both are anions so they must shift in opposite directions to maintain serum electroneutrality |
|
|
Term
| Describe the mechanism of hypochloridemia with metabolic acidosis |
|
Definition
Cl- secretion accompanies H+ in the type A intercalated cells of the distal nephron in order to maintain electroneutrality
**however, usually hypochloremia is associated with metabolic alkalosis due to an attempt to maintain serum electroneutrality |
|
|
Term
| What two conditions should be considered if there is hypochloridemia in the absence of hyponatremia? |
|
Definition
If there is a concurrent increase in [HCO3-] = metabolic alkalosis
Or an increased anion gap (there must be an increase in unmeasured anions to account for the loss of negatively charged chloride in order to maintain electroneutrality) |
|
|
Term
| Describe the pathogenesis of alkalosis associated with renal failure in cattle |
|
Definition
likely secondary to abomasal atony with sequestration of chloride --> hypochloremic metabolic alkalosis
Cattle may also excrete more potassium via saliva (to compensate for impaired renal secretion of potassium), which when swallowed may limit absorption of chloride |
|
|
Term
| Describe how increased gap metabolic acidosis can result in hypochloremia |
|
Definition
increased renal filtration of unabsorbable anions obligate renal excretion of sodium (to maintain electroneutrality), because chloride reabsorption depends on the electrochemical gradient established by sodium reabsorption decreased sodium reabsorption results in concurrent decreased chloride reabsorption
if there is adequate renal function there is increased excretion of H+ and Cl- in order for type A intercalated cells of the distal tubule to produce more HCO3 to buffer the acidosis |
|
|
Term
| What factors can result in pseudohyponatremia and hypochloriedmia? |
|
Definition
Hyperproteinemia (if measured by indirect potentiometry)
lipemia (if measured by coulometric assay- just chloride) |
|
|
Term
| What is the major buffer in the body that helps maintain blood pH at physiologic concentations? |
|
Definition
|
|
Term
| What cells contain carbonic anhydrase (to produce bicarbonate from CO2 and H2O)? |
|
Definition
| erythrocytes, proximal renal tubular cells, type A and B intercalated cells of the collecting tubules, parietal cells (stomach and abomasum), exocrine pancreatic epithelial cells |
|
|
Term
| How does the increased diffusion of glutamine into the proximal renal epithelium (from the plasma and tubular fluid), help to buffer an acidosis? |
|
Definition
Provides a mechanism for H+ excretion: Glutamine is metabolized to glutamate (by glutaminase) and glutamate is metabolize to alpha-ketoglutarate (by glutamine dehydrogenase), in both of these reactions NH3 and H20 are liberated. NH3 combines with 2 hydrogen ions to from NH4 which is excreted in the urine
Contributes to HCO3 production: further metabolism of alpha-ketoglutarate results in generation of HCO3 which moves back into the plasma from the proximal tubular epithelial cell |
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Term
| Why does proximal renal reabsorption of bicarbonate depend on sodium reabsorption? |
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Definition
H+ is secreted into the tubular lumen in exchange for Na in the proximal tubule.
In the lumen of the proximal tubule H+ then binds to bicarbonate to form carbonic acid --> converted into co2 and water by luminal carbonic anhydrase, both of which diffuse into the proximal renal tubular cells and are converted back into bicarbonate by cellular carbonic anhydrase. This bicarbonate formed in the proximal renal tubular epithelial cell is transported to the plasma via a sodium bicarbonate co-transporter. |
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Term
| How is bicarbonate secreted (when there is a metabolic alkalosis) by the kidney? |
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Definition
| through Cl-HCO3 exchanger in type B intercalated cells of the distal nephron |
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Term
| Which of the intercalated cells of the collecting duct produce bicarbonate and which secrete bicarbonate? |
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Definition
type A produce bicabonate (if stimulated by acidemia or aldosterone)- H20 + CO2 are converted to bicarbonate via carbonic anhydrase in the cell and transported into the plasma in exchange for chloride.
Type B secrete bicarbonate (if stimulated by alkalemia)- H20 + CO2 are converted into bicarbonate via carbonic anhydrase in the cell and bicarbonate is transported into the tubular fluid in exchange for chloride |
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Term
| What percentage of total CO2 in a serum sample is bicarbonate? |
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Definition
95%
the other 5% is dissolved CO2 and a small fraction is also cardamon compounds |
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Term
| Why does prolonged contact with erythrocytes (especially in under-filled tubes) result in a lowered [HCO3]? |
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Definition
Erythrocytes contain carbonic anhydrase and will continue to covert bicarbonate to CO2. Because the dead space in under-filled tubes has almost no CO2 it will diffuse out of the sample into the space lowering the bicarbonate in the sample
*an even greater loss of bicarbonate will occur with exposure of the sample to air, either before or after centrifugation |
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Term
| Describe the principle of the vitros, hitachi, and olympus enzymatic tCO2 assay? |
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Definition
The sample is placed in very alkaline environment so that nearly all CO2 is in the form of HCO3, which reacts with phosphoenolpyruvate to form oxaloacetate. Oxaloacetate is coupled to a reaction that consumes NADH, and the magnitude of NADH consumption is quantified via reflectance spectrophotometry
*increased serum lactate dehydrogenase can cause positive interference because it also promotes consumption of NADH via conversion of lactate to pyruvate <-- some assays have inhibitors (oxamate) to reduce this interference |
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Term
| Describe the principle of the Beckmann tCO2 assay? |
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Definition
| In a very acid environment nearly all tCO2 is converted to gaseous CO2. The liberated CO2 gas diffuses into a bicarbonate solution with a pH electrode and the shift in pH (ie. how acidic does the solution become) correlates with the amount of liberated CO2 (and therefore bicarbonate) |
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Term
| What is the prevailing theory for the development of a metabolic alkalosis in cattle with renal failure? |
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Definition
| Suspect concurrent abomasal atony with hypochloremic metabolic alkalosis |
|
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Term
| Describe how hypochloremia promotes the development of a metabolic alkalosis |
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Definition
If an animal is chloride depleted reabsorption of sodium from the lumen of the renal collecting duct (via sodium channels) occurs without concurrent paracellular reabsorption of chloride. This results in a net negative charge in the tubular lumen which promotes passive diffusion of H+ out of the the principle cell and into the tubular fluid.
**this is why hypochloremic metabolic alkalosis is often associated with paradoxical aciduria |
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Term
| Through what two mechanisms does hypokalemia promote alkalosis? |
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Definition
With hypokalemia potassium shifts from ICF --> ECF and H+ moves the opposite direction (into ICF) to maintain electroneutrality
Hypokalemia stimulates the activity of a H+-K+ ATPase (exchanger) in type A intercalated cells of the distal nephron resulting in increased reabsorption of K+ and increased excretion of H+ |
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Term
| What is the mechanism of renal compensation for a chronic respiratory acidosis (3-5 days)? |
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Definition
| Acidemia stimulates proximal renal tubular cells to increase H+ secretion. H+ binds to filtered HCO3- and forms carbonic acid. Lumina carbonic anhydrase breaks this down into CO2 and H20 that are passively reabsorbed into the proximal tubular epithelial cell. Intracellular carbonic anhydrase catalyzes the formation of intracellular HCO3-, which is transported into the plasma via a Na-HCO3-cotransporter. |
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Term
| What is a potential source of increased Lactate (and therefore titration metabolic acidosis) in neonatal ruminants (other than hypovolemia and increased anaerobic glycolysis)? |
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Definition
| ruminal and enteric fermentation of lactose (esp. calf diarrhea) may be a source of D-lactate and H+ |
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Term
| What pathologic states can impaired bicarbonate secretion by type B intercalated cells in the distal nephron (normally secrete bicarbonate when there is an alkalemia)? |
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Definition
tubular disease (distal tubular acidosis)
urinary tract obstruction
hyperkalemia |
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Term
| What cells are most affected by aldosterone (via aldosterone induced proteins)? |
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Definition
Principle cells (cortical collecting tubule)- Aldosterone facilitates activity of 3Na-2K-ATPase (exchanger), and luminal Na channel (sodium reabsorption) and K channel (potassium excretion)
Type A intercalated cells (collecting duct)- aldosterone facilitates the activity of the H+-ATPase pump (pumps out H+ generated from HCO3- production from CO2 and H2O in the cell) |
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Term
| What are the two underlying defects that result in proximal tubular acidosis (impaired HCO3- conservation by proximal renal tubular cells)? |
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Definition
Impaired sodium reabsorption (H+ is secreted from the tubular cell via Na-H exchanger, H+ binds to filtered HCO3- to form H2CO3)
carbonic anhydrase inhibitor (inhibits breakdown of H2CO3 in the tubule into CO2 and H2O which are passively reabsorbed into the epithelial cell and again, inhibits the genesis of HCO3 in the tubular cell from absorbed CO2 and H2O, carbonic anhydrase catalyzes all these reactions) |
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Term
| What biochemical abnormalities are associated with fanconi's syndrome (inherited or acquired- mostly secondary to toxins or drug reactions in dogs)? |
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Definition
proximal renal tubular acidosis
renal glucosuria, aminoaciduria
hypokalemia
hypophosphatemia |
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Term
| What diseases have been associated with acquired proximal tubular acidosis in dogs? |
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Definition
hypocalcemia (due to hypoparathyroidism and vitamin D deficiency) and some drugs (overdose of amoxicillin, streptozotocin and malice acid - anti-neoplastic agents)
*acquired proximal tubular acidosis has been reported in a mare, but cause was not determined |
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Term
| what acid base disturbance is highly suggestive of renal tubular acidosis (proximal or distal)? |
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Definition
| hyperchloremic metabolic acidosis |
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Term
| What are the major unmeasured cations in the blood? |
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Definition
| fCa, fMg, cationic globulins |
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Term
| What are the major unmeasured anions? |
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Definition
| albumin, PO4, SO4, anions of organic acids |
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Term
| What is the anion gap? How is the equation derived? |
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Definition
AG = unmeasured anions (UA) - unmeasured cations (UC)
because serum is neutral, Total Anions = Total Cations
or, (UA + (Na+K)) = (UC + (Cl+HCO3))
or, UA-UC = (Na+K) - (Cl+HCO3) |
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Term
| What are possible reasons for a mildly increased AG, not associated with increased organic acids? |
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Definition
Hyperalbuminemia
decreased fCa and/or fMg |
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Term
| What exogenous compounds are associated with increased anion gap? |
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Definition
ethylene glycol (due to increased metabolites(glycolate or oxalate)
Methanol (metabolite formate)
metaldehyde (snail bait)
Very high does of penicillin |
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Term
| Although decreased AG is not clinically significant, what disorders can decreased the AG (and potentially mask/confound increased in unmeasured anions as well)? |
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Definition
Decreased unmeasured anions: Hypoalbuminemia
Increased unmeasured cations: multiple myeloma (globulins are mostly positively charged) |
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Term
| T/F Lactate is present mostly in its anionic form at physiologic pH? |
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Definition
True
The acidosis that accompanies lactic acidosis is due to H+ production for ATP consumption, not from generation of lactate |
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Term
| What is the major tissue source of L-lactate? |
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Definition
skeletal muscle
*also comes from erythrocytes (mammalian erythrocytes don't have mitochondria so produce lactate from glycolysis). Red cells can also transport or otherwise be a receptacle for (aka lactate sink) L-lactate from muscle |
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Term
| How does L-lactate (from normal production in skeletal muscle and erythrocytes) get handled in health? |
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Definition
Taken up by hepatocytes -The Cori cycle:
L-lactate is taken up by hepatocytes and either converted to glucose (via gluconeogenesis) or used for ATP production (via Krebs cycle)
or, Excreted via the kidney |
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Term
| What is the major form of lactate produced by bacteria? |
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Definition
D-Lactate
*vs. L-Lactate, which is the primary form of lactate produced by mammalian cells, however a small amount of D-Lactate can be produced via the glycoxalase pathway |
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Term
| What are the two common methodologies used to measure L-lactate? |
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Definition
via lactate dehydrogenase (spectrophotometric assay)
or L-lactate oxidase (point of care analyzers e.g. NOVA, i-STAT)
**assays to measure D-Lactate are not commonly available (liquid chromatography, D-lactate dehydrogenase enzymatic assay) |
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Term
| What is the ideal sample processing/handling when measuring L-lactate? |
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Definition
process the sample quickly as RBC can continue to produce L-lactate in a stored sample (or can use sodium fluoride tube or chill and separate plasma)
Don't use a tourniquet to collect blood (will cause local tissue hypoxia and can increased [L-lactate]) |
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Term
| What substance can interfere with [l-lactate] when measured using the i-Stat analyzer? |
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Definition
| bromide falsely decreases [L-lactate] when measured via i-STAT |
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Term
| What can cause negative interference with the [L-lactate] when measured using the point-of-care analyzers (L-lactate oxidase method)? |
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Definition
free hemoglobin (e.g. hemolyzed sample) or hemoglobin based oxygen carriers result in falsely low [L-lactate] when measured with L-lactate oxidase.
This probably occurs because the peroxidase activity of heme removes the H2O2 produced by the L-lactate oxidase reaction |
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Term
| T/F the severity of hyperlacatemia in colicky horses is inversely proportional to prognosis |
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Definition
true
higher lactate = poorer prognosis |
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Term
| Other than poor tissue perfusion, what is another relatively common cause of increased [lactate]? |
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Definition
Increased production of lactate by metabolic pathways:
1. Grain overload (ruminants and horses)- excess intake of starch results in increased formation of L- and D-lactate by rumen microbes (ruminants) or hindgut bacteria (horses). Increased rumen acidity alters microflora such that further lactate production develops and in both situations is absorbed across the mucosa and into the blood.
2. Defective glycolytic pathways
a) hyperammonemia (e.g. urea toxicosis, hepatic insufficiency, urea cycle defect): high NH4 interferes with krebs cycle so anaerobic glycolysis and L-lactate production is increased.
b) pyruvate dehydrogenase deficiency (sussex and clumber spaniels). Pyruvate dehydrogenase catalyzes the conversion of pyruvate to acetyl-COA (for krebs cycle), is in its absence pyruvate is converted into L-lactate instead |
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Term
| What is the proposed pathogenesis of increased L-lactate in sepsis? |
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Definition
| decreased utilization of L-lactate by the liver (and other tissues) +/- concurrent decreased tissue perfusion |
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Term
| T/F is hyperlactatemia associated with severe liver disease thought to be due to defective hepatic utilization (cori cycle) or excessive production of lactate? |
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Definition
| Excessive production (e.g. poor perfusion of the liver or decreased mitochondrial function) |
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Term
| What isoform of lactate may be increased in cats with diabetic ketoacidosis? |
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Definition
D-lactate
**however, the magnitude of increase (<1mmol/L) would not be enough to increase the anion gap (ex. most animals with L-lactate acidosis have 10-20mol/L of L-lactate) |
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Term
| In what species/disease states can D-Lactate be a significant contributor to increased anion gap? |
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Definition
Neonatal calves with diarrhea (suspect increased enteric production of D-lactate)
or calves in which failure of the esophageal groove reflex allows milk to enter the rumen where bacterial fermentation results in massive production of D and L-lactatic acids. L-lactate is rapidly metabolized but high gap acidosis develops from D-lactate and H+ ions. |
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Term
| What dietary component can result in increased D-lactate in cats? |
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Definition
Propylene glycol (at concentrations found in commercial foods may increase D-lactate ~ 2mmol/L, enough to increase the AG)
*propylene glycol is converted to D-lactate, probably via alcohol dehydrogenase or methylglyoxal |
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Term
| What conditions favor hepatic production of betahydroxybutyrate vs. acetoacetate? |
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Definition
| abundant NADH --> betahydroxybutyrate production abundant NAD+ ---> acetoacetate production |
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Term
| What hormone promotes (and which inhibits) ketogenesis in the liver? |
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Definition
Glucagon promotes ketogenesis
Insulin inhibits ketogenesis |
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Term
| Which of the ketones facilitate renal excretion of H+? |
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Definition
Betahydroxybutyrate and acetoacetate
**the pKa of these ketones is near the pH of acidic urine, so when the ketones are excreted in the urine they are also bound to H+ |
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Term
| What is the most common method for ketone detection in blood, serum, milk, and urine? |
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Definition
nitroprusside method
*betahydroxybutyrate (BHB) doesn't react. BHB can be measured specifically using a spectrophotometric assay without uses BHB dehydrogenase to convert acetoacetate to BHB. (If the sample has high acetoacetate, the BHB can be falsely low). |
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Term
| What is the pathogenesis of ketone production in diabetes or with starvation? |
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Definition
Excessive beta-oxidiation of fatty acids results in production of more acetyl-coa than can be used in the Krebs cycle --> enters the ketogenic pathway to form acetoacetate, which can then be converted into either betahydroxybutyrate or acetone
*this process is facilitated by excess glucagon and/or insulin deficiency |
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Term
| Describe the pathogenesis of ketone formation in animals with a negative energy balance (e.g. lactatating cattle)? |
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Definition
| when there is a negative energy balance, oxaloacetate is used for gluconeogeneis so there is an inadequate amount of oxaloacetate to react with acetyl CoA which accumulates and promotes ketogenesis |
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Term
| What is the difference between osmolality and osmolarity? |
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Definition
osmolality is moles (solute)/ Kg, depends on the number of molecules or ions in the solution (Na + Cl contribute the most)
osmolarity is moles (of solute)/ L |
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Term
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Definition
1 osmole = 1 mole of osmotically active particles
if a substance does not dissociate in solution 1 mole = 1 osmole. If a substance completely dissociates in solution, 1 mole= 2 osmoles
*most dissociable substances do not completely dissociate in solution |
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Term
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Definition
| The EFFECTIVE osmolality (mmol/kg) of a solution, that is, the solute concentration that can contribute to the movement of H2O across a semipermeable membrane |
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Term
| T/F at physiologic conditions glucose and urea contribute little to serum osmolality |
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Definition
| True- however, marked azotemia or hyperglycemia will contribute to hyperosmolality |
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Term
| What is the physiologic response to hypertonicity (i.e. increased effective osmolality)? |
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Definition
| Hypothalamic release of ADH (water reabsorption in collecting duct) + stimulation of thirst center |
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Term
| Which endogenous molecule is not an effective osmole and why? |
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Definition
Urea can freely diffuse across most cell membranes, so it doesn't contribute to the osmolar gradient and therefore doesn't contribute to tonicity
**some exogenous molecules are also ineffective osmoles (e.g. ethylene glycol, methanol, and ethanol) |
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Term
| Describe the two methods use to measure serum osmolality, which is most accurate? |
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Definition
Freezing-point depression is most common and most accurate (1 mol/kg solution will have a freezing point 1.86C lower than pure water)
Vapor pressure osmometer (1 mol/kg solution will have a vapor pressure 0.03 mmhg lower than pure water) <-- can't measure the contribution of volatile solutes (e.g. alcohols) to total osmolarity |
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Term
| What is the required sample type for measuring osmolality? |
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Definition
serum
*anti-coagulants in plasma would increase the osmolality |
|
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Term
| What equation can be used to calculate the osmolality of serum when BUN and glucose are reported in mg/dL? |
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Definition
| 2(Na) + (BUN)/3 + (glucose)/20 |
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Term
| What is the utility in calculating the osmolality (vs. measured osmolality)? |
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Definition
main utility in calculating osmolality is to use it then to calculate the Osmo. gap
*calculated osmolality is simply an estimate of osmolality base off measured solute concentrations (na, k, urea, glucose) and may or many not estimate the true serum osmolality |
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Term
| Concentrations of what solutes are used to calculate osmo. gap? |
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Definition
| sodium +/- K, urea, glucose |
|
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Term
| In what situation is the Osmo. gap increased? |
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Definition
| Addition of exogenous anionic solute (e.g. mannitol, ethylene glycol, IV contrast material), this will increase the measured osmolality but is not included in the calculated osmolality equation, hence, increased Osmo. gap |
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Term
| In what situation with the measured osmolality be decreased but the Osmo. gap WRI? |
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Definition
hyponatremia
**measured and calculated osmolality are proportionally decreased so Osmo. gap is WRI. Although urea and glucose also contribute to the calculated osmolality they are only a small fraction when compared to sodium |
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Term
| In what situation with the measured osmolality be increased but the Osmo. gap WRI? |
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Definition
hypernatremia, hyperglycemia, azotemia
**measured and calculated osmolality are proportionally increased so Osmo. gap is WRI |
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