Term
| What is the major route for solute and water excretion from an animal? |
|
Definition
|
|
Term
| How small does a molecule need to be to pass through the glomerulous? |
|
Definition
<2.5 nm
**almost no molecules with a diameter > 3.4 nm pass through |
|
|
Term
| Molecules of what charge can better pass through the glomerulus? |
|
Definition
positive or neutrally charged molecules
b/c glomerular basement mb contains mostly negatively charged molecules |
|
|
Term
| Which species can have a small amount of albumin in the urine in health? |
|
Definition
|
|
Term
| What are the major contributors to GFR? |
|
Definition
dependent on renal plasma flow which depends on
Blood volume
Cardiac output
Number of functional glomeruli
Degree of constriction or dilation of renal afferent and efferent arterioles
** factors outside RPF include hydrostatic pressure in bowman's space (if increased, GFR decreases) and plasma oncotic pressure (if decreased, GFR increases) |
|
|
Term
| What characteristics of creatinine make it an ideal substance for evaluating GFR? |
|
Definition
| creatinine is non-protein bound and freely filtered, it is not reabsorbed and very little is secreted by renal tubules |
|
|
Term
| How can renal tubular function be assessed through rate of inulin excretion? |
|
Definition
| Inulin is freely filtered, not reabsorbed and not secreted. If excretion of a solute is greater than that of inulin there is net secretion by the tubules. If there is less solute than inulin in the urine there is either 1) net solute resorption, 2) the solute is not freely filtered |
|
|
Term
| Where is most sodium reabsorbed in the nephron? |
|
Definition
| proximal tubule (75%), follows a concentration gradient maintained by Na-K-ATPase, and NA-H antiporter |
|
|
Term
| What are the mechanisms through which sodium is mostly reabsorbed in the proximal tubule? |
|
Definition
| Concentration gradient (established by NA-K-ATPase and NA-H antiporter) Electrical gradient (established by conservation of HCO3-) |
|
|
Term
| Which hormone stimulates increased sodium reabsorption in the proximal tubule? |
|
Definition
| Angiotensin II (stimulates proximal reabsorption of sodium, chloride, and water) |
|
|
Term
| How does ADH stimulate sodium and chloride reabsorption in the medullary thick limb of the loop of henle? |
|
Definition
| ADH activates a NA-K-Cl2 cotransporter in the medullary thick limb of the loop of hence --> sodium and chloride reabsoprtion |
|
|
Term
| How does aldosterone stimulate sodium resorption in the collecting tubules? |
|
Definition
| Enhanced Na-K-ATPase, opening of luminal Na and K channels into epithelial cells, activation of NA-CL-cotransporter |
|
|
Term
| What is the action of atrial natriuretic peptide? |
|
Definition
| Inhibition of sodium reabsorption in the distal nephron via reduction of the number of open sodium channels by a guaylate cyclase pathway (g-protein) |
|
|
Term
| Where is the majority of chloride reabsorbed in the nephron? |
|
Definition
| Proximal tubule (via Na and water gradient [Na-K-ATPase] AND formate-Cl exchanger) |
|
|
Term
| Which renal tubular cells secrete chloride and in what conditions? |
|
Definition
Type A intercalated cells secrete chloride when they are stimulated to secrete H+
** As Cl is secreted HCO3 is produced in the type A intercalated cell and enters the plasma |
|
|
Term
| Where in the nephron is the majority of HCO3 conserved? |
|
Definition
Proximal tubule, HCO3 is indirectly conserved during H+ secretion
** this depends on the amount of sodium resorption by the Na-H-antiporter. As sodium is reabsorbed H+ is secreted and combines with HCO3 in the filtrate to form H2CO3 which dissociates into CO2 and H2O -> these are reabsorbed also in the proximal tubule and and are converted back into H+ and HCO3 |
|
|
Term
| How and where is excess HCO3 secreted by the nephron? |
|
Definition
| Type B intercalated (in the collecting tubule) cells secrete HCO3 via Cl-HCO3-exchanger |
|
|
Term
| T/F Most filtered K+ is reabsorbed prior to distal tubule |
|
Definition
|
|
Term
| What substance promoted most K+ secretion, and where does this occur? |
|
Definition
| Aldosterone stimulates K+ secretion by opening K+ channels in the principle cells of the collecting tubules <-- enhanced K+ secretion when urinary flow rate is high and vice versa |
|
|
Term
| What is the effect of ADH on K+ in the collecting tubule? |
|
Definition
| ADH promotes K+ secretion in the collecting tubule |
|
|
Term
| Which cells conserve potassium when hypokalemia is present? |
|
Definition
| Type A intercalated cells |
|
|
Term
| Where in the nephron is most H+ secreted? |
|
Definition
| Distal nephron, by type A intercalated cells via H+-ATPase |
|
|
Term
| Which hormone promotes H+ secretion from the distal nephron? |
|
Definition
|
|
Term
| How is most H+ excreted from the kidneys? |
|
Definition
incorporated into NH4, HPO4 or H2PO4
** very little is present as free H+ |
|
|
Term
| Describe the net movement of water and solutes as filtrate moves through the proximal tubules |
|
Definition
Net resorption of water and solutes from the tubular fluid
**the osmolality of the fluid is largely unchanged (~300 mol/Kg) but the volume is greatly diminished |
|
|
Term
| Describe the net movement of water and solutes in filtrate moving through the descending limb of the loop of henle |
|
Definition
Water is passively resorbed, solutes are retained
** tubular fluid is concentrated (1500 mmol/kg in horses and cattle to >2400 mol/kg in cats) and volume is reduced |
|
|
Term
| describe the net movement of water and solutes in the ascending limb of the loop of henle |
|
Definition
Water is retained and solutes (mostly Na, Cl, K) are passively reabsorbed via Na-K-2Cl carrier
**tubular fluid is diluted (~100 mmol/kg) |
|
|
Term
| Where in the renal tubule does PTH stimulate active reabsorption of calcium and magnesium? |
|
Definition
Ascending limb of the loop of henle
PTH promotes Ca absorption by activating adenylate cyclase pathway in the ascending limb of the loop of henle (and also distal tubule)
** most calcium and magnesium is reabsorbed passively in the proximal tubule and loop of henle via an electrochemical gradient. |
|
|
Term
| Where in the nephron does ADH have it's effect an what are the major actions of ADH? |
|
Definition
| ADH promotes reabsorption of water and urea in the distal tubule and collecting tubule |
|
|
Term
| Where in the nephron does aldosterone have it's effect an what are the major actions of aldosterone? |
|
Definition
| aldosterone promotes reabsorption of Na and Cl (and water) and excretion of K and H+ in the distal tubule and collecting tubule |
|
|
Term
| In a healthy kidney list the solutes that are excreted |
|
Definition
| urea, creatinine, K, H+, NH4+, PO4+ |
|
|
Term
| In a healthy kidney list the solutes that are conserved |
|
Definition
| Na, Cl, HCO3, Ca (except horses that excrete excess Ca), Mg, glucose, amino acids, and water |
|
|
Term
| Where in the nephron is most of the filtered calcium reabsorbed? |
|
Definition
proximal tubule and loop of henle
** Ca is passively reabsorbed via electrochemical gradient established by Na-K-Cl2 cotransporter |
|
|
Term
| How does vitamin D promote calcium reabsorption in the distal nephron? |
|
Definition
| Increased production of calcium-binding-protein |
|
|
Term
| What stimulates calcitriol (1,25-DHCC, aka active vitamin D) formation in the proximal renal tubules? |
|
Definition
|
|
Term
| Where in the nephron (and via what transport mechanism) is the majority of phosphorus reabsorbed and how? |
|
Definition
| Proximal tubule via Na-PO4 cotransporter ** this cotransporter is ENHANCED by hypophosphatemia and insulin and DIMINISHED by hyperphosphatemia and PTH |
|
|
Term
| Where in the nephron, and through what mechanisms, is most Mg reabsorbed? |
|
Definition
| ascending limb of loop of henle ** mostly passive reabsorption via electrochemical gradient established by Na-K-2Cl cotransporter and K+ recycling (Ca is also passively reabsorbed here) |
|
|
Term
| What substances stimulate magnesium reabsorption in the ascending limb of the loop of henle? |
|
Definition
ADH, PTH, glucagon, calcitonin, beta-adrenergic agonists
all stimulate Mg reabsorption in the ascending limb of the loop of henle |
|
|
Term
| How is glucose reabsorbed in the proximal tubule? |
|
Definition
Na-glucose cotransport system
*glucose reabsorption is also called secondary active reabsorption because its secondary to Na reabsorption and occurs against a concentration gradient |
|
|
Term
| How are amino acids and small peptides reabsorbed in the proximal tubule? |
|
Definition
specific carriers exist for each of the seven amino acids
**small peptides are hydrolyzed to amino acids for reabsorption this way |
|
|
Term
| How are larger proteins (e.g albumin and smaller) reabsorbed in the proximal tubule? |
|
Definition
They enter the tubule cells via endocytosis and are degraded to amino acids
** caveat- in some apparently healthy dogs not all the albumin is not reabsorbed and there can be a small amount of albuminuria |
|
|
Term
| What receptor proteins are important for facilitating protein reabsorption (via endocytosis) in the proximal tubule? |
|
Definition
Megalin, aminionless, and cubulin
** these proteins also facilitate intrinsic factor-cobalamin uptake in the small intestine |
|
|
Term
| Where in the nephron is the majority of urea (60-65%) reabsorbed? |
|
Definition
proximal tubule, urea is passively reabsorbed down a concentration gradient created by water reabsorption
** this is enhanced in hypovolemic states when there is even greater proximal tubular reabsorption of water and a slower urine flow rate |
|
|
Term
| What are the major medullary solutes? |
|
Definition
|
|
Term
| What hormone substantially increases urea reabsorption in the distal nephron? |
|
Definition
|
|
Term
| What species can secrete a small amount of creatinine in the proximal tubule? |
|
Definition
dogs
*creatinine secretion in people occurs through a pathway that is also used to secrete organic cations (+), so serum [creatinine] can increase if there are increased cations (e.g. cimetidine, TMS, quinidine) that interfere with creatinine secretion |
|
|
Term
| Where is the majority of water in the ultra filtrate reabsorbed in the nephron? |
|
Definition
|
|
Term
| What segments of the nephron are impermiable to water? |
|
Definition
ascending limb of loop of henle and collecting tubule
**collecting tubule can become permeable to water under the action of ADH and activation of aquaporin proteins |
|
|
Term
| What specific gravity corresponds with isothenuria? And what plasma osmolality corresponds with this specific gravity? |
|
Definition
| 1.007-1.013 corresponds with a plasma osmolality of ~300 mol/kg |
|
|
Term
| How is the osmolality of the tubular fluid altered in the descending limb of the loop of henle? |
|
Definition
| Osmolality of the tubular fluid increases (due to secretion of Na, Cl, and urea and passive reabsorption of H20) |
|
|
Term
| Where in the nephron is medullary interstitial hypertonicity established? |
|
Definition
Ascending limb of the loop of henle
*Na and Cl (and K, Ca, Mg) are actively pumped out of the tubular fluid into the intersitium and the tubule is impermiable to water so it can't follow the concentration gradient. |
|
|
Term
| How is the osmolality of the tubular fluid altered in the ascending limb of the loop of henle? |
|
Definition
| The osmolality of the tubular fluid is decreased due to active reabsorption of Na, Cl (K, Ca, Mg) and imperbiability to water |
|
|
Term
| T/F osmolality of tubular fluid is further diluted in the distal tubule (as it moves from the ascending limb of the loop of henle) |
|
Definition
| True- the distal tubule is also largely impermiable to water and further Na Cl reabsorption occurs (3Na-Cl exchanged for secretion of K) |
|
|
Term
| where in the nephron does urine concentration occur? |
|
Definition
| collecting tubule (via ADH mostly) |
|
|
Term
| How does ADH enhance water reabsorption in the collecting tubule? |
|
Definition
AH binds to basolateral membrane of renal epithelial cells --> activate cAMP dependent second messenger system --> aquaporin is transported to apical membrane
ADH also increases production of aquaporin proteins |
|
|
Term
| What are the stimuli for ADH secretion? |
|
Definition
hyperosmolality
decreased cardiovascular pressure (e.g.. hypovolemia)
+/- increased [angiotensin] |
|
|
Term
| What three things must be functioning for kidney to concentrate ultrafiltrate? |
|
Definition
ADH must be present
Epithelial cells of the distal nephron must be responsive to ADH
There must be a concentration gradient (i.e. renal medullary insterstitium must have greater osmolality compared to tubular fluid in the collecting tubule) |
|
|
Term
| What is necessary for the kidney to be able to dilute ultrafiltrate? |
|
Definition
Na and Cl must be actively transported from tubular fluid to medullary interstitium in the ascending limb of the loop of henle (via Na-K-2Cl cotransporter) <-- this initially dilutes the ultrafiltrate because the ascending limb of henle is impermeable to water)
Then little to no water is reabsorbed by the distal tubule (e.g. No ADH, or impaired responsiveness of epithelial cells to ADH, or loss of medullary hypertonicity) |
|
|
Term
| What are the two main reasons animals with chronic renal failure lose concentrating ability? |
|
Definition
Increased single nephron GFR contributes to an increased concentration of solutes in the ultra filtrate --> SOLUTE DIURESIS (less water is passively reabsorbed in the descending limb of the loop of henle because the concentration gradient between the tubular fluid and medullary interstitium is diminished)
LOSS OF MEDULLARY HYPERTONICITY |
|
|
Term
| What three factors contribute to loss of medullary hypertonicity in animals with chronic renal failure? |
|
Definition
Medullary tissue is damaged or medullary blood flow is abnormal
Decreased Na Cl reabsorption in the ascending limb of the loop of henle (Ka-K-2Cl cotransporter)
Epithelial cells in the collecting tubules are damaged and less responsive to ADH (responsible for most urea reabsorption) |
|
|
Term
| T/F the magnitude of azotemia cannot be used as a discriminant between acute and chronic renal failure |
|
Definition
True (azotemia in either state can range from mild to severe)
** however, the rate of increase in azotemia is faster in acute conditions where marked azotemia can develop in days following an insult vs. chronic renal failure where it may take weeks to months for azotemia of the same magnitude to develop |
|
|
Term
| Why is acute kidney failure more often associated with oliguria/anuria than chronic renal failure? |
|
Definition
Because the drop in GFR is abrupt there is no time for compensatory hypertrophy of healthy nephrons in AKI so kidneys may simply filter less blood
vs. CKD where anuria/oliguria only develops as an end stage change preceded by a long period of polyuria due to impaired concentrating ability |
|
|
Term
| What triggers the kidneys to release renin (ultimately to increase [angiotensin II])? |
|
Definition
| stretch receptors in the juxtaglomerular apparatus of the afferent arteriole sense diminished blood flow stimulating the kidney to secrete renin --> net result is increased angiotensin II which causes vasoconstriction, proximal tubular reabsorption of sodium and increased aldosterone secretion from adrenal cortex (Na, H20 resporption at collecting tubule) |
|
|
Term
| Describe the pathogenesis of post-renal azotemia when associated with urinary tract obstruction |
|
Definition
Release of vasoactive substances (eg. prostaglandins, angiotensin) -->vasoconstriction of glomerular arterioles --> decreased GFR
Impaired urine outflow causes a transient increase in intracapsular hydrostatic pressure (these decreases over time as GFR is diminished and tubular fluid diffuses into tubular epithelial cells) |
|
|
Term
| Describe the pathogenesis of azotemia associated with leakage of urine within the body |
|
Definition
urea and creatinine are reabsorbed across the peritoneum or directly into the vasculature (if just leakage into tissue surrounding the urinary tract),
** urea is smaller and reabsorbed faster than Cr, that's why comparison of serum Cr to effusion Cr is used to evaluate effusions for uroperitoneum |
|
|
Term
| Which dog breed has been associated with severe combined immunodeficiency (autosomal recessive)? Describe the clin path manifestations |
|
Definition
Jack Russel Terrier
No B or T lymphoytes, lymphopenia and lymphoid tissue aplasia/hypoplasia |
|
|
Term
| Which dog breeds inherit a Severe Combined Immunodeficiency that is largely limited to CD8 T lymphocytes? How is it inherrited and what clinical pathology manifestations is it associated with? |
|
Definition
Basset hound, Corgi
X-linked inheritance
Lymphopenia (due to depeltion of CD8 T lymphs), lack IgG and IgA but normal IgM |
|
|
Term
| What kind of inherited immunodeficiency has been reported in Dobermans? Clin path manifestation? |
|
Definition
Selective IgM Deficiency
Very low levels of IgM, decreased IgG, Increased IgA |
|
|
Term
| What dog breeds have been associated with inherited selective IgA deficiency? Clin path manifestation? |
|
Definition
German Shepherd, Shar-pei, Beagle
Decreased IgA, normal IgG and IgM
|
|
|
Term
| What type of inherited immunodeficiency has been reported in weimeraners? |
|
Definition
| Selective IgG and IgA deficiency |
|
|
Term
| What USG is considered adequate in the face of dehydration in dogs? cats? horses/cattle? |
|
Definition
dogs: > 1.030
cats: > 1.040
horses/cattle: > 1.025 |
|
|
Term
| In what situations might you have renal azotemia with a USG >1.013 (e.g. not isothenuria, but still inappropriately concentrated given presence of azotemia)? |
|
Definition
1. Renal disease is targeting glomeruli > tubules
2. Very high concentrations of glucose or protein in the urine can increase the refractive index so that the USG overestimates the urine osmolality
3. Plasma osmolality is increased, so urine osmolality is increased despite impaired tubular function |
|
|
Term
| How does hypercalcemia impair renal concentrating ability? |
|
Definition
| Decreases sensitivity of tubular epithelial cells in the distal nephron to ADH (aka one etiology of nephrogenic diabetes inspidus) |
|
|
Term
| T/F any condition that increases renal tubular flow rate impairs renal concentrating ability |
|
Definition
True (e.g. osmotic diuresis)
** high flow rate through the tubule decreases reabsorption of tubular fluid (this can also contribute to medullary washout because solute reabsorption is also diminished at high flow rates) |
|
|
Term
| What five conditions are associated wit the development of decreased medullary hypertonicity? |
|
Definition
1) prolonged hyponatremia or hypochloremia (Na and Cl are major constituents of medullary hypertonicity- also urea)
2) Impaired Na Cl transport (loop diuretics)
3) Decreased urea production due to liver disease
4) increased tubular flow rate (solute overload or prolonged diuresis) |
|
|
Term
| T/F serum urea nitrogen = blood urea nitrogen = plasma urea nitrogen |
|
Definition
True
*urea is freely diffusibe for most cell membranes so it equilibrates between cellular and extracellular components of the blood |
|
|
Term
| Describe the principle of the vitros dry reagent slide method for detecting urea |
|
Definition
sample is incubated with urease --> urea is hydrolyzed to form NH3 and CO2. The NH3 reacts with an indicator to generate a colored dye which is detected by reflectance spectrophotometry
* hemolysis can cause positive interferenace |
|
|
Term
| What anticoagulant can cause negative interferance with the vitros dry reagent slide method of urea detection? |
|
Definition
| Sodium Flouride <-- flouride inhibits urease activity |
|
|
Term
| Describe the principle of the roche wet reagent assay for detection of urea |
|
Definition
| sample is incubated with urease --> urea is hydrolyzed to NH4 and CO2 --> NH4 reacts in a coupled reaction that consumes NADH --> the magnitude of urea in the sample corresponds to the degree of decreased absorbance measured via kinetic spectrophotometry |
|
|
Term
| Why are portosystemic shunts associated with decreased BUN? |
|
Definition
1. Less NH4 is delivered to hepatocytes from the intestine
2. Decreased functional hepatic mass (decreased urea synthesis) |
|
|
Term
| What disorders are associated with increased renal excretion of urea? |
|
Definition
1. when less water is reabsorbed in the proximal tubule (e.g.. glycosuria) --> less urea is also reabsorbed because there is less of a concentration gradient between tubular and interstitial fluid
2. Central and nephrogenic DI --> reduced ADH acitivity or response causes decreased reabsorption of urea (in addition to water) |
|
|
Term
| Describe how urea that is not excreted in urine is removed from monogastric animals vs. ruminants |
|
Definition
monogastrics: urea enters intestine and is degraded by enteric bacteria (via urease) --> excreted in feces or passively reabsorbed in portal blood back to the liver
ruminants: urea enters the rumen (via saliva and blood) and is degraded into NH4 by rumen microflora |
|
|
Term
| T/F creatinine can be excreted via saliva in cattle |
|
Definition
true
*also possibly some Cr is excreted via the GI tract in monogastrics because its diffusible across most cell membranes |
|
|
Term
| Describe the principle of the vitros dry reagent slide method for detecting creatinine |
|
Definition
creatinine is hydrolyzed to creatine --> additional reactions ultimately result in generation of a colored dye via H202 and an indicator --> quantified via reflectance spectrophotometry
**may yield lower values than Jaffe's reaction |
|
|
Term
| Describe the principle of the Jaffe's reaction for detection of creatinine (Roche and others) |
|
Definition
Creatinine reacts with picric acid to form a colored complex, the rate of formation of the complex is measured via spectrophotometer
** a correction factor of 0.3 mg/dL is subtracted from the assay result to account for positive interference from serum proteins, this occurs in ALL samples so could be excessive (eg. hypoproteinemia) or inadequate (eg. hyperproteinemia) |
|
|
Term
| What non-creatinine chromogens can cause positive interference in the Jaffe reaction to detect creatinine? |
|
Definition
proteins, glucose, ketones, ascorbic acid, pyruvate, cephalosporins
** however in some studies these also caused negative interference (acetoacetic acid) also bilirubin and lipid produced a negative bias
** biases are less of an issue when using kinetic Jaffe reactions (vs. end point) |
|
|
Term
| Why might neonatal foals have increased serum creatinine concentrations at birth that quickly resolve over a few days? |
|
Definition
| Placental dysfunction can prevent normal clearance of fetal creatinine, however, after birth normal renal function quickly allows for excess creatinine to be excreted in the urine |
|
|
Term
| Why is creatinine not normally increased in animals with muscle damage? |
|
Definition
Renal excretion of creatinine occurs very quickly if there is normal renal function
*** that being said, some animal with high muscle mass (e.g. greyhounds) may have normally mildly increased or high normal creatinine, and those with diminished muscle mass (e.g. old cats) might have decreased creatinine however these changes should be mild provided normal renal function |
|
|
Term
| What is the formula for creatinine clearance rate? |
|
Definition
([Crt]urine/[Crt]serum X volume of urine)/time/body weight
**units are mL/min/kg |
|
|
Term
| What are the indications to measure creatinine clearance rate? |
|
Definition
1) assess GFR in non-azotemic, non dehydrated animals, suspected of renal dz due to polyuria
2) Assess degree of GFR impairment in azotemic animals to guide therapy and assess prognosis |
|
|
Term
| In which species is phosphorus elevated secondary to decreased GFR? |
|
Definition
dogs, cats, and horses*
**horses with CKD can have normal to hypophosphatemia in due to decreased renal conservations of PO4 (proximal tubule) or external excretion of PO4 |
|
|
Term
| Why do cattle often have minimal change in serum phosphorus concentration secondary to decreased GFR? |
|
Definition
| Cattle excrete PO4 predominantly via saliva or rumen |
|
|
Term
| Why do dogs, cats, and cattle usually have low normal Ca or mild hypocalcemia with CKD? |
|
Definition
Decreased functional renal mass results in decreased renal production of activated Vit D (1,25-DHCC).
*in cattle PO4 excreted in saliva can bind to Ca in the GI and decrease it's intestinal absorption contributing to hypocalcemia |
|
|
Term
| Which species is most likely to be hypercalcemic with CKD and why? |
|
Definition
horses, esp. if diet is rich in Ca
Because kidneys excrete excess dietary Ca in horses. They can be hypocalcemic too with CKD, mostly depending on the amount of Ca in the diet |
|
|
Term
| How does decreased GFR affect K+ and H+ concentrations in dogs, cats, and horses? |
|
Definition
Increased K+ and H+ concentration due to impaired renal excretion of both cations, usually oliguric/anuric renal failure
**inorganic acidemia (usually associated with primary loss of bicarbonate (GI/pancreas) or accumulation of Phosphoric and/or sulfuric acids) can accentuate K+ through redistribution of ions from intracellular to extracellular space |
|
|
Term
| What electrolyte and acid base disturbances are most commonly observed in cattle with decreased GFR? |
|
Definition
Hypokalemia (due to decreased dietary intake, increased salivary excretion of potassium and concurrent alkalosis*)
* often have a hypochloremic metabolic alkalosis (abomasa atony with H+ Cl- sequestration)
Often have hyponatremia suggesting concurrent renal loss of Na |
|
|
Term
| In which species are lipase and amylase most reliably elevated secondary to decreased GFR? |
|
Definition
Dogs
*mild hyperamylasemia is sometimes observed in cats with CKD |
|
|
Term
| What pigments contribute to the yellow color of urine? |
|
Definition
| urochormes, of which riboflavin is one |
|
|
Term
| Why can horse urine turn red to red-brown during storage or when exposed to snow? |
|
Definition
| Pyrocetechin (pyrocatechol), an aromatic portion of catecholamines <-- this is not associated with any pathologic state |
|
|
Term
| Why can equine urine be more turbid than that of other species in health? |
|
Definition
Presence of mucoproteins (produced by kidneys) and/or calcium carbonate crystals
*urine clarity is assessed on fresh, well mixed urine |
|
|
Term
| What is specific gravity? Is it really how we assess urine concentration? |
|
Definition
it's a physical property of a solution, the ratio of a solution's weight to the weight of an equal volume of water (i.e., the ratio of their densities)
NO- we assess urine concentration via refractive index, which is an estimate of specific gravity (as long as the proportions of solutes in the urine is constant) <-- refractive index also correlate well with osmolality is the solutes proportions are constant |
|
|
Term
| The refractive index of a solution is highly dependent on what three factors? |
|
Definition
1. Solute concentration
2. Chemical composition of the solute
3. Temperature
**suspended particles (e.g. cells, casts, crystals) do not alter the refractive index but can make it challenging to read the demarcation line <-- usually not enough to completely obscure however |
|
|
Term
| In what direction do non-temperature compensating refractometers differ from accurate readings when temp increases above 68F (20C)? |
|
Definition
| non-temp compensated refractometers underestimate USG when ambient temps are >68F (20C), the degree of error is proportional the the increase in ambient temp |
|
|
Term
| Describe the principle for freezing-point osmometry to measure osmolality of a solution |
|
Definition
| The freezing point of a solution is inversely related to the solute concentration (increased solute concentration --> decreased freezing point). So, the freezing point osmometer detects the freezing point of a solution and converts that value to osmolality |
|
|
Term
| What are the units for osmolality? |
|
Definition
osmol/kg or mol/kg
ex. for a substance that does not dissociation in solution, 1mol = 1 osmol, for a substance that completely dissociates into 2 ions/mol each mol of the substance generates 2 osmol of particles |
|
|
Term
| How could you compare the solute concentration of a urine with USG of 1.010 to 1.020? |
|
Definition
| The concentration of the urine with USG 1.020 is approximately twice that of the urine with USG 1.010 |
|
|
Term
| What is the effect of marked proteinuria or glycosuria on USG? |
|
Definition
proteinuria and glycosuria increase refractive index but NOT (well glucose can contribute a bit) osmolality
1 g/dl protein adds about 0.003-0.005 to USG
1 g/dl glucose adds about 0.004-0.005 to USG |
|
|
Term
| why is the reagentstrip method of measuring USG not reccomended for veterinary species? |
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Definition
the method falsely underestimates USG at urine pH equal or higher than 7. indicators produce different colors when dipped in urine samples of different ionic strength
glucosuria can also falsely lower USG and proteinura can falsely elevate USG via this method |
|
|
Term
| What is the pathogenesis of central diabetes insipidus? |
|
Definition
ADH deficiency
** hypothalamic or pituitary disease results in decreased production of ADH |
|
|
Term
| What mechanism is responsible for impaired renal concentrating ability in AKI? |
|
Definition
| decreased tubular response to ADH |
|
|
Term
| In what conditions is polyuria associated with impaired tubular response to ADH alone? |
|
Definition
| acute renal failure, hypercalcemia, canine pyometra, hypokalemia |
|
|
Term
| What USG is most suggestive of defective ADH secretion in dehydrated, polyruic, and/or electrolyte depleted dogs? |
|
Definition
< 1.007
Indicates renal diluting ability, therefore not renal failure, however as the kidney should be trying to conserved water and solutes in these cases the diluted urine suggests ADH deficiency |
|
|
Term
| What should you think of when you have a polyuric dog with a USG = 1.020-1.035? |
|
Definition
| osmotic diuresis e.g. glucosuria (DM or renal glucosuria) <-- although renal concentrating ability may be only partially impaired with CKD, USG is generally lower in polyuric CKD states. |
|
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Term
| Describe the pathogenesis of polyuria with diabetes mellitus |
|
Definition
| glucosuria cases osmotic diuresis --> high flow rate impairs resorption of Na, Cl, and urea thus medullary hypotonicity develops |
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|
Term
| Describe the proposed mechanisms for polyuria in hyperadrenocorticism |
|
Definition
| glucocorticoids may inhibit ADH secretion as well as responsiveness of collecting duct to ADH |
|
|
Term
| How can hypercalcemia impair renal concentrating ability, other than decreased sensitivity of renal tubules to ADH? |
|
Definition
Calcium can reduce reabsorption of sodium and chloride in the ascending loop of henle, reducing osmotic gradient needed for water resorption in collecting duct
If calcium is persistently elevated soft tissue mineralization can cause renal insufficiency or failure by damage to nephron |
|
|
Term
| Describe the mechanisms associated with polyuria in liver failure? |
|
Definition
Decreased urea synthesis --> impaired medullary hypertonicity
also, psychogenic polydipsia, defects in portal vein osmoreceptros, impaired renal concentrating mechanisms due to increased ammonia excretion |
|
|
Term
| describe the pathogenesis of polyuria secondary to hypokalemia |
|
Definition
decreased tubular responsiveness to ADH
disruption of countercurrent exchange (K-Na-2Cl cotransporter in ascending limb of loop of henle) --> impaired resorption of sodium and chloride --> medullary washout |
|
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Term
| Why can any condition associated with hypochloremia and hyonatremia be associated with impaired renal concentrating ability? |
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Definition
sodium and chloride contribute to medullary hypertonicity so any condition associated with hyponatremia and hypochloremia is associated with impaired medullary tonicity
Hyponatremia and hypochloridemia will also reduce plasma osmolality and thus reduce the stimulus for ADH secretion |
|
|
Term
| What is the equation that describes the relationship of urine solute concentration, urine volume, and daily urinary excretion of solutes? |
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Definition
Daily urinary solute excretion= [solute] X urine volume/day
e.g. daily urinary protein excretion= 70mg/dl x 1000 ml/day
= 700 mg/day |
|
|
Term
| What is the relationship between urine volume and GFR? |
|
Definition
If renal function is normal, urine volume is inversely proportional to USG
(e.g. if urine excretion of solutes is constant, but urine volume doubles from one day the the other, the USG is reduced by 50%- urine volume increases, USG decreases) |
|
|
Term
| What is the typical urine pH in carnivores? In herbivores? |
|
Definition
carnivore (6-7.5)
herbivore (7.5-8.5) * herbivores on a milk diet will have a more acidic urine |
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Term
| Where in the nephron is excess H+ secreted in response to decreased extracellular pH (e.g. acidosis)? |
|
Definition
Mostly by type A intercalated cells in distal nephron (H+-ATPase)
proximal tubule does a bit (usually combines with other molecules to for NH4, HPO4, or H2PO4) |
|
|
Term
| How does hypokalemia contribute to aciduria? |
|
Definition
| hypokalemia stimulates a H-K-ATPase in the collecting duct (type A intercalated cells) causing reabsorption of K and renal secretion of H. |
|
|
Term
| Describe the urine pH in proximal and distal renal tubular acidosis |
|
Definition
usually the urine pH is alkaline in both conditions
1. proximal- less HCO3 is reabsorbed in the proximal tubule and buffers excess H+ (urine pH may not be alkaline, but also not appropriately acid for an acidotic patient). HCO3 can become depleted in which case aciduria may develop.
2. distal- decreased H+ secretion in the distal nephron leads to inappropriately high urine pH (>6) in the face of acidosis, urine may not be alkaline |
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|
Term
| What type of protein is a major component of hyaline casts? |
|
Definition
| Tamm-horsfall protein - a mucoprotein secreted by ascending limb of loop of henle and part of the distal tubule and collecting duct |
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|
Term
| Describe the principle for urine protein identification via dipstick? |
|
Definition
amino groups of negatively charged proteins bind a dye (tetrabromphenol blue- indicates acidic pH) and change the color of the pad the magnitude of color change corresponds to urine protein concentration
* detects albumin best (remember, Ig are neutral to positively charged and protein in cells reacts very poorly with reagent pad) |
|
|
Term
| What can interfere with urine protein as measured using a dipstick? |
|
Definition
| alkaline urine can cause falsely elevated urine protein readings |
|
|
Term
| Describe the principle of the SAA turbidity test to measure protein in urine |
|
Definition
proteins are denatured by acids --> this forms a precipitate and the solution appears hazy. Results are often assessed semi-quantitatively, but can also use a spectrophotometer with standards to quantitative results
**urine should be centrifuged prior to running this test, highly buffered alkaline urine can falsely decrease results |
|
|
Term
| What proteins are most commonly implicated in over-flow/pre-renal proteinuria? |
|
Definition
paraproteins associated with lymphoid/plasma cell neoplasia, hemoglobin, myoglobin, post-colostral in food animals <-- these are all detected by routine urine protein assays
** not associated with hypoproteinemia |
|
|
Term
| T/F tubular proteinuria is not associated with hypoalbuminemia |
|
Definition
True, glomerular filtration barrier is still intact
**most are associated with AKI (hypoxic, toxin) but can also be congenital |
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|
Term
| T/F dogs with PLN will become proteinuric BEFORE they become azotemic |
|
Definition
TRUE- the ability of the proximal tubule to reabsorb large quantities of filtered proteins is exceeded before the is enough damage to nephrons to incite azotemia
Proteinuria develops BEFORE azotemia |
|
|
Term
| What are bene jones proteins? |
|
Definition
immunoglobulin light chains (most in animals are lambda) that have unique thermal properties:
precipitate between 40-60C, become soluble at 100, and precipitate when cooled |
|
|
Term
| What methods can be used to identify bence jones proteins in the urine? |
|
Definition
Heat test: urine is acidified and heated to 56C look for protein precipitates (bence jones proteins precipitate between 40-60C), if precitates are observed the sample is placed in a boiling water bath to see if they become soluble at the higher temp (100)
They will also react with SSA turbidity test and to a lesser extent the dipstick pad if high concentrations are present in the urine
Immunoelectrophoresis is the preferred method (have to use human anti-serum, which likely cross reacts with most domestic mammal immunoglobulin light chains) |
|
|
Term
| What non-neoplastic conditions have been associated with bence jones proteinuria in dogs? |
|
Definition
| leishmania, ehrlichia, babesia |
|
|
Term
| What electrolyte is the glucose cotransporter in the proximal tubule associated with? |
|
Definition
|
|
Term
| What is the renal threshold for glucose in dogs? cats? horses? |
|
Definition
dogs: 180-220 mg/dl
cats: 290 mg/dl
horses: 150 mg/dl
probably lower in mature cattle |
|
|
Term
| Describe the principle of the reagent strip method for identifying glucosuria |
|
Definition
| glucose is converted to gluconic acid via glucose oxidase, which liberates H2O2 that reacts with an indicator to incite a color change |
|
|
Term
| Describe the principle of the copper-reduction method for identifying glucosuria |
|
Definition
Glucose (and other sugars e.g. fructose, lactose, galactose etc.) reduces copper to cuprous oxide and cuprous hydroxide --> color change
Results are semiquantitative and a higher glucose concentration is required to induce a positive reaction (>250mg/dl) |
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|
Term
| how does glycosuria (e.g. in the case of DM, fanconi syndrome, or acquired proximal tubular injury e.g. toxicity, hypoxia) contribute to polyuria? |
|
Definition
|
|
Term
| What are the three ketone bodies? |
|
Definition
| Acetoacetate, beta-hydroxybutryate, acetone |
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|
Term
| Which ketone bodies can be reabsorbed (up to a point) once filtered through the glomerulus? |
|
Definition
| acetoacetate and beta-hydroxybutyrate |
|
|
Term
| Which ketone body is not identified on urine reagent strip |
|
Definition
|
|
Term
| Describe the principle for the reagent strip method to detect ketonuria |
|
Definition
| Acetoacetate (mostly) and acetone, form colored complexes with nitroprusside |
|
|
Term
| What analytical method can be used to detect ketones in urine, blood, plasma, and milk? |
|
Definition
Acetest tablet (Bayer diagnostics)
same methodology as reagent strip (acetoacetate and acetone form colored complexes with nitroprusside) but the color change is easier to detect so it can identify lower concentrations of ketones (down to 5 mg/dl) and can be valuable in confirming trace or questionable reactions on reagent pads |
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|
Term
| Describe the pathogenesis of ketonemia/uria in animals with a negative energy balance |
|
Definition
| Decreased available glucose results in a shift in energy production to breakdown of lipids. Beta-oxidation of lipid occurs in hepatocytes --> excess acetyl-coenzyme A is generated --> stimulate hepatocytes to produce ketoacids |
|
|
Term
| What is the primary ketone excreted in the urine in ketotic states? |
|
Definition
betahydroxybutyrate
**which isn't identified using the dipstick or acetest tablet methods |
|
|
Term
| Describe the principle of the urine reagent pad to identify the presence of hematuria? |
|
Definition
| peroxidase activity of heme catalyzes a color change (oxidation of o-toluidine blue or a chromogen such as tetramethylbenzadine) |
|
|
Term
| What can cause a positive heme reaction of a urine dipstick? |
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Definition
| hemoglobin, methemoglobin, myoglobin |
|
|
Term
| T/F myoglobin is rapidly cleared from plasma, thus in the case of myoglobinuria, plasma color is expected to be clear, while urine is red/brown |
|
Definition
True
myoglobin is rapidly cleared from plasma |
|
|
Term
| In what species can a small amount of billirubinuria be normal? |
|
Definition
| dogs (renal tubular cells can convert heme to bilirubin and then conjugate the bilirubin and excrete it in the urine) |
|
|
Term
| Describe the reagent strip method to detect bilirubinuria? |
|
Definition
Bilirubin couples with diazonium salt in a strongly acidic environment, resulting in a color change
ictotest uses the same methodology but has a lower limit of detection and can be used to confirm trace reactions on dipsticks |
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|
Term
| Why does urine need to be protected for UV light when being stored for UA? |
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Definition
| UV light degrades bilirubin into biliverdin which is not detected by the reagent pad or ictotest (color change is induced by coupling of bilirubin to a diazonium salt in an acidic medium) |
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|
Term
| T/F hyperbilirubinemia without bilirubinuria suggests a false negative urine bilirubin test or degradation of the urine bilirubin prior to sample analysis |
|
Definition
True-
There is a low renal threshold for bilirubin so it is evident in the urine before it accumulates enough in serum to exceed reference interval |
|
|
Term
| How is urobilinogen formed and excreted? |
|
Definition
| urobilinogen is formed from degradation of bilirubin in the intestine --> absorbed into portal blood and is either removed by hepatocytes excreted by the kidneys |
|
|
Term
| Which urine dipstick reactions are not typically valuable in veterinary species? And why? |
|
Definition
urobilinogen (typically increased in hemolytic disease but also variably increased in animals with hepatic or biliary disease)
nitrate (associated with gram negative bacterial infections, however, significant bactiruria may not be identified by this test)
leukocyte esterase (false negative results in dogs, false positive results in cats) |
|
|
Term
| What type of casts indicate renal tubular injury? |
|
Definition
Epithelial or fatty casts form from cellular degradation and therefor reflect tubular degeneration or necrosis
**granular casts may reflect similar processes but can also be composed of normal sloughed cells and plasma proteins so may not reflect underlying pathology in all cases |
|
|
Term
| What is the proposed pathogenesis of waxy casts? |
|
Definition
| deterioration and solidification of granular casts (therefore typically associated with CKD and tubular degeneration) |
|
|
Term
| What nematode larvae can be seen on urine sediment? |
|
Definition
Dioctophyma renale
Capillaria plica
Stephanurus
**r/o fecal contamination when parasitic structures are observed in urine sediment |
|
|
Term
| What considerations must be made when measuring creatinine in urine with assays developed for use in serum? |
|
Definition
Because creatinine concentrations are so much higher in urine the sample must be diluted to get the creatinine concentration into the assay's analytical range which can be a source of inaccuracy.
Also non-creatinine chromogens can interfere, however, kinetic assays minimize this error |
|
|
Term
| In order to measure urine [total calcium] how does the sample need to be modified |
|
Definition
| must acidify the urine so that the calcium is solubilized and thus able to react with the reagents |
|
|
Term
| What methodology must be used to measure urine [K] in cats, horses, and cattle? |
|
Definition
| Flame photometry - urine in these species inhibits the reaction of K with ion specific electrodes |
|
|
Term
| What assumptions are made when assessing the rate of urinary excretion of a substance using urine to plasma ratios? |
|
Definition
| Assumes urine volume, time, and body weight are constants for a given animal |
|
|
Term
| How could you use urine to plasma ratio to differentiated pre-renal from renal azotemia? |
|
Definition
Urine osmolality : plasma osmolality
increased ratio (increased urine osmolality) indicates capacity of kidneys to reabsorb water hence, azotemia if present would be pre-renal
If isothenuric (renal azotemia), would expect a ratio around 1 |
|
|
Term
| Describe the principle for the trichloroacetic acid method of determining quantitative urine protein |
|
Definition
proteins are denatured by acid to form a precipitate
**this method is less affected by albumin:glob than SAA (which reacts 2-4x better with albumin than globulins)
Temperature sensitive, must be completed at 20-25C |
|
|
Term
| Describe the principle for the coomassie brilliant blue assay for determining quantitative urine protein |
|
Definition
The amount of dye binding to amine groups of amino acids is proportional to the quantity of protein present
**minimally affected by alb:glob and will also detect bence jones proteins |
|
|
Term
| Describe the principle for the benzethonium chloride assay for determining quantitative urine protein |
|
Definition
benzethonium chloride reacts with proteins to form a precipitate and the degree of turbidity of the solution is proportional to the protein concentration
*reacts equally well with albumin and gamma globulins, but hemoglobin will also react with the reagent |
|
|
Term
| What are the interpretation guidelines for protein:cr in normal, borderline, and dogs with proteinuria? |
|
Definition
normal < 0.5
Boarderline 0.5-1.0
proteinuira >1.0 |
|
|
Term
| How is microalbuminuria defined in dogs and cats? |
|
Definition
urine [alb] between 1-30 mg/dl in urine with USG adjusted to 1.010 *this standardizes the solute concentration so that protein concentrations can be compared without correction for differences in urine concentration
* urine [alb] > 30mg/dl is overt albuminuria |
|
|
Term
| Describe the methods that can be used to detect microalbuminuria in dogs and cats |
|
Definition
Quantitative immunologic: species specific ELISA or nephelometric assays (urine samples may need to be diluted a ton to be in the working range since the standard curve uses purified albumin, so this can be a source of error)
Semiquantitative immunologic assay: immuno-dip/early renal disease health screen test. USG is adjusted to 1.010 and a color change corresponds to the concentration of albumin
Albumin creatinine ratio: reagent pad using a dye binding method for albumin and a peroxidase like assay for creatinine, color change is read by reflectance photometry. The albumin reaction is not specific so this is not a very reliable method |
|
|
Term
| T/F exercise does not increased urinary excretion of albumin in dogs |
|
Definition
True
**this is in contrast to people |
|
|
Term
| How do you calculate the fractional excretion of a substance in urine? |
|
Definition
([X]urine/[X]serum) x ([Cr]serum/[Cr]urine)
* when creatinine is within the reference interval and relatively constant |
|
|
Term
| Numerically describe the fractional excretion of a substance that is freely filtered and then partially reabsorbed |
|
Definition
fractional excretion will be < 1.0
** if a substance is freely filtered and not reabsorbed, fractional excretion will = 1.0 |
|
|
Term
| Describe the mechanisms that can contribute to increased fractional excretion of a solute |
|
Definition
1. Increased plasma concentrations of the analyze (e.g. increased in filtered load, such as increased dietary intake)
2. Increased tubular secretion
3. Decreased tubular reabsorption
4. Decreased creatinine excretion (usually associated with decreased GFR with concurrent maintenance of tubular secretion or concurrent decreased tubular reabsorption) |
|
|
Term
| How should you interpret an increased fractional excretion of sodium in a hyponatremic animal? |
|
Definition
| renal excretion of sodium is contributing to the hyponatremia (e.g. aldosterone deficiency, increased atrial natriuretic peptide, renal tubular disease) |
|
|
Term
| How should you interpret decreased fractional excretion of sodium in a hyponatremic animal? |
|
Definition
| This indicates that kidneys are attempting to conserve sodium through the actions of aldosterone, angiotensin II (also stimulates aldosterone production and ADH secretion) and/or ADH (e.g. pre-renal azotemia) |
|
|
Term
| How should you interpret increased fractional excretion of PO4 in a hypocalcemic animal? |
|
Definition
Suggests increased PTH activity (increases serum calcium and decreases serum phos <- mainly through inhibition of renal phosphorus reabsorption)
e.g. nutritional (low calcium high phos diet) or renal secondary hyperparathyroidism (hyperphosphatemia due to decreased GFR ) |
|
|
Term
| How should you interpret decreased fractional excretion of PO4 in a hypocalcemic animal? |
|
Definition
| This suggests that hypoparathyroidism may be contributing to the hypocalcemia |
|
|
Term
| How would the fractional excretion of PO4 be affected in a hypercalcemic patient with primary hyperparathyroidism? |
|
Definition
| Fractional excretion of PO4 would be increased |
|
|
Term
| How should you interpret increased fractional excretion of GGT? |
|
Definition
Renal tubular cells contain GGT so increased fractional excretion is consistent with active renal tubular damage or necrosis
**but it doesn't reflect GFR and cannot be used to diagnose renal failure. Additionally there can be active renal tubular damage without increased fractional excretion of GGT |
|
|
Term
| Why might you choose a gradual water deprivation test to assess renal concentrating ability over an abrupt one? |
|
Definition
To assess if impaired renal concentrating ability is secondary to prolonged polyuria with resultant medullary hypotonicity rather then true inhibition of renal concentration (e.g. central or nephrogenic diabetes insipidus)
** also less danger of causing severe hypovolemia in markedly polyuric animals but can take a really long time to perform (over 1 week) |
|
|
Term
| What test can be used to distinguish between central and nephrogenic diabetes insipidus? |
|
Definition
ADH (vasopressin) response test - ad lib water available during the study, assess renal concentrating ability (USG or urine osmolality) after administration of aqueous vasopressin or DDAVP
If urine is concentrated after administration this is consistent with central diabetes insipidus (absolute ADH deficiency)
If urine is not concentrated this is consistent with nephrogenic diabetes insipidus (but can also occur with medullary washout associated with any primary PU/PD disorder)
**the modified H20 deprivation test can also distinguish in that dogs with central DI will have more hypotonic urine in the deprivation phase (< 300 mmol/lg) and a marked increased in urine tonicity (>100%) after ADH administration, while dogs with partial renal or central DI have a more concentrated urine (<600) and a blunted response to ADH (20-50% increase in urine tonicity) |
|
|
Term
| What are the two main methods of assessing urolith composition? |
|
Definition
Optical crystallography- ground urolith material is placed within oils that have different refractive indices, the mineral is classified when its refractive index matches with one of the oils (i.e. it disappears)
X-ray diffraction: ground urolith material is bombarded with x-rays and the diffraction pattern of the x-ray is specific to a each crystal |
|
|
Term
| What is heterogenous nucleation? |
|
Definition
| When urinary cations and anions combine to form crystals on the surface of particulate material in the urine (e.g. debris, casts etc.) <-- they can be flushed out in the urine, or combine into aggregates that provide a surface for additional crystallization and aggregation |
|
|
Term
| What protein produced by renal tubular cells is a natural inhibitor of crystal aggregation? |
|
Definition
| Tamm-horsfall proteins (these proteins also comprise the matrix of tubular casts) |
|
|
Term
| What predisposing factors are associated with struvite crystalluria? |
|
Definition
UTIs (esp. if urease producing bacteria are present --> degrade urea and make the urine more ALKALINE)
** UTIs are also predispose to calcium phosphate uroliths (in addition to calicuria secondary to hypercalcemia) |
|
|
Term
| What factors predispose formation of calcium oxalate uroliths? |
|
Definition
| Increased urinary excretion of calcium (hypercalcemia, hypervitaminosis D, dietary calcium supplementation) AND increased renal excretion of oxalate (associated with increased dietary intake of oxalates ex. nuts, spinach etc.) |
|
|
Term
| What conditions are associated with urate crystalluria? |
|
Definition
PSS and hepatic insufficiency
also dalmatians and english bulldogs have a mutation that results in a defect in uric acid transporter in the kidney and liver and high serum and urine concentrations of uric acid |
|
|
Term
| Which dog breeds are predisposed to cystine urolithiasis? |
|
Definition
| English bulldogs, newfoundlands, dachshunds, mastiffs, bullmasiffs, australian cattle dogs, and scottish deerhounds |
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