Flashcards in Clinical Pathology of the Urinary System Deck (40):
URINE PRODUCTION- to regulate body water, eliminate waste, maintain normal blood Na, Ca, K and P concentrations, and maintain pH.
ENDOCRINE FUNCTION- erythropoetin, vitamin D, renin.
30% of the plasma that reaches the kidney gets filtered at the GLOMERULUS- forms ultrafiltrate.
-PCT- REABSORPTION of protein (nutrients)
-DESCENDING arm of Loop of Henle- WATER REABSORPTION.
-ASCENDING arm of Loop- ION REABSORPTION.
-DCT- HORMONE (aldosterone, PTH) MEDIATED reabsorption.
-Collecting duct- hormone mediated water reabsorption, acid base balancing, and collection of urine
PRODUCING CONCENTRATED URINE
1. Appropriate concentration gradient
2. Antidiuretic hormone (ADH)
3. Kidney must respond to signal (hormones etc)
ie. the kidney must be functioning in order for concentrated urine to be produced.
Excess water intake -> dilute urine production
Insufficient water intake -> concentrated urine production.
ASSESSMENT OF URINE PRODUCTION
Refractometer used to measure urine specific gravity (USG)- read right hand side!
USG is a ratio of solution's (urine) weight:weight of an equal volume of water.
Refractometry is indirect measurement of USG
Change in light refraction is proportional to concentration of solute.
Artefacts- glucosuria (glucose in urine) and proteinuria can falsely elevate USG.
Some scales are temperature compensated, others must be adjusted depending on room temperatures.
Urine osmolality is LESS than isosthenuric values.
Urine osmolality is EQUAL TO plasma osmolality.
Urine osmolality is high; the kidney is actively concentrating urine.
Rarely used term.
Lack of ADH OR kidney is not responding to normal ADH.
GLOMERULAR FILTRATION RATE
BEST PREDICTOR OF RENAL FUNCTION.
Rate at which fluid move through glomerular filtration barrier from plasma to glomerular filtrate.
Measured by determining the rate at which a substance that is not excreted or reabsorbed is cleared from plasma- expensive and difficult.
An estimate is used in practice.
UN and creatinine can be used in practice to estimate GFR.
Used to estimate GFR.
A byproduct of muscle metabolism.
Muscle mass and therefore production rate are relatively constant.
Freely filtered by glomerulus and not reabsorbed by renal tubules.
AN INCREASE IN CREATININE CONCENTRATION REQUIRES 75% LOSS IN FUNCTIONING NEPHRONS.
Specific, especially in ruminants and horses (where non-renal factors are not as significant)- creatinine is used for GFR instead of urea in ruminants, as urea is excreted in to the rumen so blood levels are relatively constant.
Due to decreased urinary excretion eg. in dehydration, hypovolaemia, kidney dysfunction, obstruction of outflow.
High muscle mass- elevated creatine can be seen normally in certain breeds (greyhound)
Rare, but can be seen in animals with low muscle mass/cachexia.
Used to estimate GFR.
Synthesised from protein breakdown in the liver.
Excreted by kidneys.
RUMINANTS- Urea is excreted in to the rumen to be used for amino acid synthesis by urease bacteria. Therefore, creatinine should be used to estimate GFR in ruminants.
Due to decreased urinary excretion- dehydration, hypovolaemia, kidney dysfunction, outflow obstruction.
Increased protein catabolism or digestion will also increased urea- eg. GI haemorrhage, high protein diets, starvation.
Liver insufficiency, low protein diets, urea cycle problems.
Increased non-protein nitrogenous compounds in the blood (creatinine and/or nitrogen)
Can be PRE-RENAL, RENAL or POST-RENAL. USG is required to differentiate between these types.
Types can occur alone or in combination.
CLINICAL SIGNS reflecting renal failure- vomiting, diarrhoea, coma, ulcers, ammoniac breath.
-Reduced renal blood flow eg. dehydration, hypovolaemia.
-> decreased GFR
-> concentrated urine production- the kidney is actively concentrating to preserve water.
-> USG increased- >1.025 (cattle/horses), >1.030 (dogs) >1.035 cats -hypersthenuria.
-Increased urea production- high protein diet, GI haemorrhage etc. Creatinine is less affected.
Any renal disease that causes a major decrease in GFR.
Caused BY THE KIDNEYS.
75% non functioning nephrons are needed to see increased creatinine/UN and renal azotaemia.
USG is usually 1.007-1.012- ISOSTHENURIC
Azotaemia caused after urine has been formed by the kindeys.
USG is variable.
Caused by urinary tract blockage or urine leakage.
FUNCTIONAL RENAL MASS
Two-thirds of functional renal mass can be lost before urine concentrating ability diminishes and isosthenuria is seen.
Three-quarters (75%) of functional renal mass must be lost before increased creatinine/UN- azotaemia- are seen.
OTHER LAB ABNORMALITIES IN AZOTAEMIC PATIENTS
-Total calcium- variable, usually low in dogs/cats/cattle with chronic renal disease (decreased Ca reabsorption due to decreased vitamin D production by kidneys).
HORSES excrete much Ca through the kidneys (and have a different active form of vitamin D), so calcium carbonate crystals in the urine and hypercalcaemia are normal.
-Phosphorous- Decreased renal clearance in dogs/cats leads to increased blood phosphorous (hyperphosphataemia). Cattle/horses show extrarenal excretion of phosphorous (GI tract), so may not show hyperphosphataemia.
-Potassium- Kidneys are main route of K excretion from the body, so anuric/oliguric (no/low urine) kidney disease will cause hyperkalaemia.
Cattle are more likely to have hypokalaemia.
SECONDARY RENAL HYPERPARATHYROIDISM
Hyperphosphataemia and hypocalcaemia in renal failure causes PTH stimulation.
-> INCREASED PHOSPHATURIA (phosphate in urine)
-> INCREASED Ca REABSORPTION by kidney, bone.
Parathyroid hyperplasia may develop.
Consequences- Tissue mineralisation (due to high phosphorous), fibrous osteodystrophy ('rubber jaw')
ACUTE RENAL FAILURE
-Reversible or irreversible- the magnitude of the azotaemia does not differentiate between these.
-Isosthenuria (urine is more concentrated if it was formed before the insult that lead to failure)
-Anuria- no urine, or oliguria- little urine. Leads to hyperkalaemia.
eg. Ethylene glycol poisoning- causes vomiting, ataxia, CNS depression. Can be detected early on with UV fluorescence (look for staining round mouth of animal).
Metabolism of ethylene glycol produces CALCIUM OXALATE MONOHYDRATE crystals 3 hours/6 hours post exposure in the cat/dog.
Causes titrational metabolic acidosis with increased anion gap, hypocalcaemia (Ca is precipitated in to crystals), hyperphosphataemia (some antifrezes contain phosphorous)
CHRONIC RENAL FAILURE
Not always able to determine acute or chronic based on laboratory date- consider duration of clinical signs.
-Chronic renal failure causes isosthenuria and azotaemia.
-Non-regenerative anaemia (decreased EPO production)
-Hypocalcaemia due to decreased active vitamin D production (not seen in horses- different active form)
WHENEVER KIDNEY FUNCTION IS BEING ASSESSED, URINALYSIS- USG + DIPSTICK (minimum)- SHOULD BE UNDERTAKEN.
-Physical examination- colour, clarity
-USG- using refractometer
-Chemical examination- dipstick
-Sediment examination- centrifuge and microscopy.
METHODS OF SAMPLE COLLECTION
-Cystocentesis- preferred method in dogs and cats, assesses pure urine before it passes through the lower urinary tract and becomes contaminated. Controversial in animals with bladder masses (TCC)- may contribute to tumour spread.
-Catheterisation- can be technically difficult in females, see contamination with erythrocytes, epithelial cells, external contaminants if inappropriate technique is used.
-Voided sample- midstream free catch is best, potential for contamination from skin, urethra and reproductive tract.
Whichever method is used, the lab should be told on submission of the sample.
CHEMICAL EVALUATION- URINE pH
ACIDURIA- normal to an extent in carnivores
-Metabolic or respiratory acidosis
ALKALURIA- herbivores naturally have more alkali urine.
-Prolonged storage at room temperature
A small quantity of albumin is filtered from the plasma and reabsorbed by tubules. Normal urine contains little to no protein.
-Always interpret urine protein in light of USG- trace protein in very concentrated vs very dilute urine.
-Dipstick primarily measures albumin
-Many false positives can occur eg. alkaline urine, increased contact time.
URINE PROTEIN:CREATININE RATIO
aka. UPC ratio.
A more accurate measurement of urine protein, as it negate the dilution or concentration of urine.
A UPC ratio of >5 is indicative of a glomerular component.
Consider sediment contents before interpreation- active sediment eg. haemorrhage, inflammation, makes UPC ratio unreliable.
SOME CAUSES OF PROTEINURIA
PRERENAL- Fever, strenuous exercise, colostrum, haemoglobinuria, methaemoglobinuria, Bence-Jones proteinuria.
Too much protein is being produced.
RENAL- glomerular or tubular disease- problems with the glomerular filtration barrier or tubular reabsorption means that urine is 'escaping' in to the urine.
POSTRENAL- haemorrhage, inflammation (unless it occurs in the kidney- renal).
Method of urine collection is important- external contamination with proteins can occur with free catch/catheterisation.
Haematuria- intact erythrocytes in urine. RED COLOUR CLEARS ON CENTRIFUGATION. Clear plasma (although very dilute urine may cause erythrocyte lysis).
Haemoglobinuria/myoglobinuria- red colour DOES NOT CLEAR on centrifugation. Red plasma is seen due to Hb/Mb filtering in to urine.
Urine does not normally contain glucose.
It is filtered and completely reabsorbed.
If too much glucose is present, the reabsorbing capacity may be overwhelmed.
Urine reflects glucose status over the PAST FEW HOURS.
False positives- hydrogen peroxide, bleach, penicillins
False negatives- prolonged dipstick storage, vitamin C, tetracycline, urinary tract infection (bacteria utilise glucose)
-Glucosuria and transient hyperglycaemia- any transient cause that exceeded threshold previously.
-Glucosuria and normoglycaemia- rare tubular defects (Fanconi syndrome- defect in tubule glucose reabsorption)
-Glucosuria and PERSISTENT hyperglycaemia- diabetes mellitus until proven otherwise.
Ketosis is seen due to negative energy balance- eg. Diabetes mellitus (diabetic ketoacidosis), bovine ketosis, starvation, late pregnancy/early lactation.
Ketones in urine should ALWAYS be addressed.
Positive- Normal to see +1 in male dogs.
-Urine colour- very dark urine can interfere with reading.
False negative- UV light (converts bilirubin to biliverdin)
URINE SEDIMENT EVALUATION
Cytospin then Romanowksy or Diff-Quick stain.
Look for: CELLS, CASTS, CRYSTALS and OTHER.
URINE SEDIMENT- CELLS
-Squamous epithelial cells- common in voided and catheterised samples- both have passed through the lower urinary tract. Flat, angular cells.
-Round/transitional cells- sources include proximal urethra, bladder, ureters, renal pelvis. Round cells with a distinct nucleus.
-Leukocytes- larger than erythrocytes, granular. Greater than 5 white blood cells per 40x field indicates PYURIA (pus in urine).
-Erythrocytes- smaller than leukocytes, with a smooth texture and crenation or area of central pallor.
Greater than 5 red cells per 40x field indicates HAEMATURIA. Low urine pH and low USG can cause red cell lysis.
URINE SEDIMENT- CASTS
Formed in renal tubules, a few hyaline or granular casts are normal in the healthy animal.
Casts deteriorate in urine quite quickly- can be hard to detect.
Hyaline, fatty, cellular and granular casts can occur.
URINE SEDIMENT- CRYSTALS
Formation of crystals occurs with excess solute, and is temperature and pH dependent.
Presence of crystals does not always mean presence of uroliths as well.
-Struvite- coffin shaped crystals, found in healthy dogs and cats.
-Calcium carbonate- common finding in normal horses, spherical with radiating lines/ovals/dog bone.
-Calcium oxalate monohydrate- Fence picket shape. If seen in an acutely ill cat or dog, ethylene glycol (antifreeze) poisoning should be suspected.