Urinalysis Introduction and Vascular Disease in the Kidney Flashcards
Urine: Physical Properties
- color
- turbidity
- specific gravity
- odor
Urine - Color
- Normal urine should be clear to pale yellow to amber due to urochrome pigment
- Abnormal color due to:
- Dark – Bilirubin, carrots, drugs, blood
- Pale – Dilutional (diabetes, increased fluids)
- RED - Beets, hemoglobin, myoglobin
- BLACK - Melanin
- YELLOW-GREEN – Biliverden, rhubarb
- BLUE-GREEN – Pseudomonas, drugs
- WHITE - Chyluria (lymph)
- RED-PURPLE - porphyria
Urine - Turbidity
– Various contaminants:
• Crystals, lipid, sperm, mucus, WBC’s, RBC’s, epithelial cells, fecal matter, bacteria, yeast
Urine - Specific Gravity
– Normal: between 1.015 – 1.025
– Increased SG
• Glucose, proteins, recent IVP, administrations of high molecular weight IV fluids
Urine - Odor
– Highly variable, affected by diet
– Distinct odors:
• Bacterial infections, ketone excretions, certain metabolic diseases
Chemical Examination of Urine
- Glucose
- Protein
- Blood
- pH
- Ketone Bodies
- Bilirubin
- Urobilinogen
- Nitrite
- Leukocyte
- Specific Gravity
pH
- pH has a wide range of acceptable values, usually falling between 4.5 and 8.0.
- Acidic urine is common in diabetes, starvation, and emphysema.
- Alkaline urine is common in vegetable diets and diuretic therapy.
- Respiratory or metabolic acidosis will lead to and acidic urine; respiratory or metabolic alkalosis will lead to an alkaline urine.
- Certain crystals will precipitate depending on the pH of the urine.
- Maintaining a certain pH may change the consequences of certain diseases, such as acid pH decreasing bacterial multiplication (often successfully done by drinking cranberry juice).
Protein
- Normal urine protein is usually less than 10 mg/dL.
- Benign increases in protein include orthostatic or postural proteinuria, exposure to cold, strenuous exercise, fever, dehydration, the acute phase of certain severe illnesses, and pregnancy.
- Increased protein however, may be one of the indicators of renal disease.
- Protein levels may be high in glomerular membrane damage, diseases with podocyte injury, altered tubular reabsorption, and with increased serum protein levels (i.e. Bence Jones protein in multiple myeloma).
- Microalbuminuria is detected early in renal disease due to diabetes.
Glucose
•Glucose will be increased in diabetes, impaired renal tubular absorption, CNS damage, thyroid disorders, pregnancy, and following high glucose content meals.
Ketones
•Ketones are increased in diabetes (and may be helpful in monitoring insulin dosage), starvation (including severe weight reduction diets), and with loss of carbohydrates from severe vomiting.
Blood
•Hematuria may be seen due to urinary tract calculi, glomerulonephritis, pyelonephritis, tumors of the kidney or urinary tract, trauma, chemical or drug exposures, thrombocytopenia, hemophilia, or following strenuous exercise.
Hemoglobin
•Hemoglobinuria (the presence of RBC breakdown products) may be seen following a hemolytic transfusion reaction, with hemolytic anemia, secondary to severe burns, associated with infections, or following strenuous exercise.
Myoglobin
•Myoglobin, or muscle protein, may be present in urine after muscle trauma, prolonged coma, convulsions, extensive exertion/exercise, or hyperthermia. Muscle wasting diseases may also present with increased urinary myoglobin.
Bilirubin
- Conjugated bilirubin, a degradation product of hemoglobin, may appear in the urine secondary to obstruction of bile ducts by calculi or carcinoma, carcinoma of the pancreas or biliary tract, or for other causes of damage to the integrity of the liver such as hepatitis or cirrhosis.
- Unconjugated bilirubin is not soluble in water and will not be seen in the urine in cases of uncomplicated hemolytic anemia.
Urobilnogen
•Increased urobilinogen may be seen in early liver disease, porphyrinuria, or with hemolytic disorders.
Nitrites
- Urinary nitrite constitutes a rapid screening test for urinary tract infections (UTIs) including cystitis and pyelonephritis, as it reflects the presence of bacteria which reduce nitrate to nitrite.
- They may also serve as a way to monitor effectiveness of antibiotic therapy or to monitor patients who are high-risk for recurring UTIs.
Leukocyte Esterase
- The presence of leukocyte esterase indicates the presence of leukocytes or fragments of leukocytes, and is a good sign that the patient has a UTI.
- Increased leukocyte esterase can also be seen in the absence of bacteria, such as following antibiotic therapy, or in inflammatory conditions not caused by infection.
- Leukocyte esterase test may be negative however in the presence of infection in someone immune compromised and unable to mount a significant white blood cell response.
Reducing Substances
- Reducing substances are increased in glycosuria, galactosuria, overt diabetes, and pentosuria.
- This is an inexpensive screening test for sick newborns and children suspected of having errors of carbohydrate metabolism.
- Positive samples that are negative for glucose should be further evaluated by carbohydrate chromatography.
Microscopic Examination of Urine
- Urine must be concentrated before examination
- 12 ml of fresh urine is spun at 400 to 500 RCF (relative centrifugal force) for five minutes
- Urine is decanted off, leaving 1 ml of concentrated sediment
- Sediment is re-suspended and examined on a glass slide under a microscope
Constituents of Normal Urine
Normal RBCs
Crenated RBCs
Uric Acid
Calcium Oxylate
Calcium Carbonate
Constituents of Abnormal Urine
White Blood Cells
- The presence of white blood cells will usually indicate the presence of inflammation, and may lead one towards a diagnosis of infection if other clinical parameters are present.
- Eosinophiluria may help to confirm suspected cases of allergic interstitial nephritis (usually due to penicillin derivatives, sulfa drugs, allopurinol, nitrofurantoin, or erythromycin) or eosinophilic cystitis (possibly due to shistosomiasis).
- Increased numbers of WBC’s can also be seen in cases of glomerulonephritis with a significant inflammatory influx such as acute post-infectious glomerulonephritis.
Casts
Casts are microscopic, cylindrically shaped, formed elements of the urinary sediment that have been molded in the lumen of the renal tubule (usually the distal or collecting tubule). They are composed primarily of plasma proteins of the glomerular filtrate and a glycoprotein called uromodulin (also known as Tamm-Horsfall protein) secreted into the urine by tubular epithelial cells of the ascending portion of the loop of Henle. Urinary casts are some of the most prognostically significant of all elements found in the urinary sediment.
Types of Casts
- Hyaline
- Granular
- Bacterial
- Waxy
- Fatty
- Pigmented
- RBC
- WBC
- Epithelial
- Mixed
- Pseudocasts
Hyaline Cast
- Hyaline casts are smooth and transparent in appearance, and composed primarily of uromodulin.
- They are seen in low numbers (1-2/high power microscopic field) in normal people, and are increased in glomerulonephritis, pyelonephritis, congestive heart failure, mental stress and strenuous exercise.
- They may also increase following use of certain therapeutic and chemical agents.
Granular Casts
- Granular casts are easily visualized and appear to have fine or coarse granules.
- They may be formed from bits and pieces of necrotic cells and are often seen in acute tubular necrosis where they may appear “muddy brown” in color.
- Granular casts can also be derived from other types of cellular casts in which the cells have broken down over time (i.e. from red blood cell casts, white blood cell casts, or epithelial casts)
Bacterial Casts
•Bacterial casts contain organisms that can be identified with special stains. They may contain white blood cells as well. These casts are pathognomonic of pyelonephritis but difficult to detect without special techniques which are rarely used in clinical practice.
Waxy Casts
- Waxy casts appear thick and opaque, may be tortuous in shape/contour, and seem to have “broken-off” ends.
- They are seen in severe or progressive/advanced renal diseases where there is an element of urinary obstruction.
- Their presence indicates a long transit time through the kidney tubules, sufficiently long to produce molding and hardness.
Fatty Casts
- Fatty casts and fat bodies are highly refractile with yellow-tan globules due to high lipid content.
- Fat bodies are lipid-laden renal tubular epithelial cells that may be present in urine as single globular bodies or may contribute to the formation of fatty casts as they pass through renal tubules.
- Fatty casts and fat bodies are seen in nephrotic syndrome.
Pigmented Casts
•Pigmented casts are usually identified when large amounts of abnormal pigment are present (most commonly bile or hemoglobin pigments).
RBC Casts
- Red blood cell casts contain intact or fragmented red blood cells, possibly with additional hemoglobin pigment.
- They are seen in diseases with damaged glomerular basement membranes and therefore indicate highly significant glomerular injury.
- Diseases that cause acute nephritic syndrome with active glomerulonephritis (IgA nephritis, lupus nephritis, anti-GBM disease, etc) often create red blood cell casts.
- RBC casts can also be seen with severe ischemic injury such as renal infarction.
WBC Casts
- – White blood cell casts often contain neutrophils and are therefore usually easy to recognize due to the presence of multilobed nuclei and granular cytoplasm.
- They are seen in kidney infections (UTI, pyelonephritis), acute interstitial nephritis (AIN), and acute glomerulonephritis with glomerular inflammation leading to spillage of inflammatory cells into the urine filtrate.
Epithelial Casts
•Epithelial casts contain cells having a single large nucleus and derived from renal tubular epithelium. They can be seen in a variety of diseases that cause tubular necrosis/injury, including hypoperfusion, nephrotoxicity from various agents such as drugs or contrast dye, and infection.
Mixed Casts
•Mixed casts contain any mixture of cellular and noncellular components and may be difficult to classify.
Pseudocasts
•Pseudocasts are really not casts at all but may appear cast-like due to the presence of closely packed cells or crystals made artifactually during slide preparation
Cast Changes
•Cellular casts may change as they pass through the nephron secondary to pH, osmotic and ionic charge alterations along the path. Transit time through the kidney may also affect the way the cast appears in the urine. Cellular casts will progress through stages of granular, finely granular, and waxy appearance depending how long they take to leave the kidney.
Normal Crystals
- Normal crystals in acidic urine include urates, calcium oxalate, and hippuric acid.
- Normal crystals in alkaline urine include phosphates, ammonium urate, and calcium carbonate.
Pathologic Crystals
•Pathologic crystals include
- cystine (hexagonal; seen in the amino acid disorder of cystinuria)
- cholesterol (notched)
- leucine (maltese crosses; seen in severe liver disease and certain rare hereditary disorders of amino acid metabolism)
- tyrosine (needles; seen in severe liver disease and hereditary tyrosinosis)
- sulfonamides (bundles of wheat; seen iatrogenically)
- radiographic dyes (similar to cholesterol in appearance)
- ampicillin (thin colorless needles)
- indinavir (antiretroviral medication used to treat HIV)
- bilirubin (tiny needles that tend to cluster)
Calculi
- In general 80% of all calculi are composed of calcium (calcium oxylate, calcium phosphate), 5 – 10% are uric acid, 2% are cysteine, and the remainder are magnesium ammonium phosphate (struvite or infection stones).
- Stone chemical composition can be analyzed by a variety of laboratory techniques.
- Although uric acid stones comprise only 5-10% of all urinary stones in the general population, the incidence is increased in hot, arid climates (like ours). Uric acid stones are radiolucent and may not be detected with plain radiograph (ultrasound or CT imaging are much better for detection).
Cystine Crystal
hexagonal; seen in the amino acid disorder of cystinuria
Tyrosine Crystal
needles; seen in severe liver disease and hereditary tyrosinosis
Drug Crystals
Indinavir and Acyclovir
Cholesterol Crystals
Struvite (urea splitting bacteria)
Diabetes
‒ Injury to muscular arteries
– intimal thickening (arteriosclerosis)
‒ Injury to smaller arterioles
– hyaline arteriolosclerosis
Hypertension
– “Benign”
• Arteriosclerosis and hyaline arteriolosclerosis
– Malignant
• Acute
– swelling of intima, RBC fragments
• Chronic
– multilayering of intimal layer (“onion skinning”)
Emboli
– Thin, needle-like cleft within vascular lumen “cholesterol cleft”
– May provoke an inflammatory response
Vasculitis
‒ Acute: Inflammatory cells within vessel wall, fibrinoid necrosis
‒ Chronic: Fibrosis/sclerosis of vessel with decreased luminal space
Hypertensive Nephrosclerosis Granular cortical surface
Arteriosclerosis (larger vessels) Diabetes, Hypertension
Arteriolar (smaller vessels) Hyalinosis Diabetes, Hypertension
Malignant Hypertension
Malignant Hypertension Chronic
Embolic Disease (from atherosclerotic plaques)
Vasculitis
Vasculitis
Vasculitis
