Clinical Lab Guide

By
Medgeeks

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Urine Dipstick

Collecting the Sample

The initial thing to do is collect the urine for testing. The external genitalia should
be cleansed, and then a midstream, clean-catch sample is collected. There is some
debate on whether cleansing of the genitalia is needed, and recent studies have
found that contamination rates have been similar between both approaches.

Urine Color and Odor

Once the specimen is collected, the first thing that should be assessed is the odor
and color of the urine sample. Multiple things can alter the color of the urine, such
as medications, infection, foods, or metabolic by-products.

A common medication that will alter the color of a urine sample is Azo, which is
an over the counter medication often used to offset the dysuria symptoms that
can be caused by a UTI. Another common appearance seen in a urine sample is
cloudy urine. This is often present if there is pyuria or if there are phosphate
crystals present in alkaline urine.

The odor of a urine sample can be altered with several medical conditions. If
the sample smells fruity or sweet, this can be indicative of diabetic
ketoacidosis. An ammonia smelling sample can be present if the urine sample
has been held in the bladder for an extensive period of time.

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Urinary tract infections will often have a pungent odor, an intestinal-urologic
fistula would have a fecal odor, and cysteine decomposition would present with
a sulfur smell.

False Positives and False Negatives

A point of care urinalysis often can have several things that may lead to a false
positive or false negative result. These vary from medications, exercise,
dehydration, and even if the UA test strip is excessively exposed to air. A full list
of things to keep in mind is listed below.

Specific Gravity
Specific gravity on dipstick tells us about the patient's hydration.

This can range from 1.003 to 1.030. If the value is less than 1.010 the patient is
well hydrated, if the value is over 1.020 the patient is relatively dehydrated. Other
than increased or decreased fluid intake, what else could affect specific gravity?

If the specific gravity is increased, this could also be related to excess sugar or
glucose in the urine related to uncontrolled diabetes, or diabetic ketoacidosis, or
SIADH where there is too much anti-diuretic hormone being released causing
concentrated urine.

Causes of decreased urinary specific gravity could be related to diabetes

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insipidus, where there is a reduction or lack of antidiuretic hormone being
produced, causing dilute urine, along with adrenal insufficiency, or
hyperaldosteronism.

Dipstick PH
The pH on a urinalysis can span from 4.5 to 8, but often will be slightly acidic
around 5.5 to 6.5. Dietary habits such as eating cranberries can even affect the
pH of the urine, causing an acidic pH, whereas diets that have high levels of
citrate will lead to a higher urine pH.

More times than not, the urine pH will mirror the serum pH. However, this is not
the case in renal tubular acidosis. In distal renal tubular acidosis, the serum pH
will be acidic, however the urinary pH will be alkaline. This is due to the
kidneys being unable to secrete protons into the urine.1

In proximal renal tubular acidosis, the kidney is unable to reabsorb bicarbonate

ions, leading to alkaline urine in the beginning, but then subsequently leads to
an acidic pH of the urine.

Urine that has an alkaline pH along with findings consistent with a UTI can be
indicative of a urea-splitting organism that can lead to the formation of
magnesium ammonium phosphate crystal, subsequently cause staghorn calculi.
An acidic pH can be more likely associated with uric acid calculi.1

Hematuria on Dipstick
The next result, on a urinalysis I look at, is hematuria or lack thereof. Blood can
be from things such as menses in females, but can also be due to more serious
causes, such as renal calculi or malignancy. Hematuria etiologies are broken down
into glomerular, renal, or urologic causes.

For a full workup and evaluation of hematuria, see the article Asymptomatic
Hematuria on the Medgeeks blog.

Always remember, if there is blood present on an in-office UA, this needs to be

confirmed by microscopy and entirely worked up!

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!

Proteinuria on Dipstick
Proteinuria is diagnosed when there is more than 150 mg of protein present in the
urine per day.

The presence of this much protein in the urine is a classic finding in renal disease.
However, the presence of small amounts of protein in the urine, 30 to 150 mg per
day, is an earlier sign of renal disease, microalbuminuria, which can be seen in
diabetic patients.1

Normal urinary protein that can be present in smaller amounts include albumin and
serum globulins. However, your routine in-office UA looks for albumin in the
urine and may not find other types of proteinuria.

One question I had when I first started practicing was, what does 1+, 2+, 3+
protein on a UA even mean? And how much should be there before I get worried?

If the UA in office shows trace protein, this is equal to 5-10 mg/dL, which is below
the significant threshold for proteinuria. If 1+ protein is seen, it is equal to 30 mg/
dL, and is considered positive or significant.

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A result of 2+ is equal to 100 mg/dL of protein, 3+ is equal to 300 mg/dL, and 4+
is equal to 1000 mg/dL of protein in the urine.

Proteinuria can be transient or persistent. Transient causes of proteinuria are

typically related to intermittent changes in glomerular filtration or perfusion
which leads to the seen protein excess.

The most commonly observed transient cause of proteinuria is orthostatic

proteinuria, which is a benign etiology. This can be diagnosed with negative UA
results for protein, after having the patient lay down for eight hours, and then
having the patient provide a urine sample.

Persistent proteinuria can be split into glomerular, tubular, or overflow etiologies.

Glomerular proteinuria is the most common type, in which excess urinary albumin
is often the cause.

Tubular proteinuria often occurs when the renal system is not breaking down or
absorbing the regularly filtered protein from the glomerulus. In tubular proteinuria,
the amount of proteinuria is not routinely over 2 grams daily.

Lastly, overflow proteinuria is seen when the renal system cannot overcome and
absorb the amount of protein that is present in the filtrate. In any of these cases of
persistent proteinuria, further evaluation is indicated with a 24-hour urinary protein

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evaluation or a urinary protein to creatinine ratio, microscopic urinalysis, urine
protein electrophoresis, and BMP.

Glucose and Ketones on Dipstick

Glucose is regularly filtered by the kidneys and is all customarily reabsorbed.
However, when the amount of glucose is too much for the kidney to reabsorb,
glycosuria occurs. This typically happens when the serum glucose is over 180 mg/
dL, and is often seen in uncontrolled diabetes, liver disease, pancreatic disease,
Fanconi syndrome, and Cushing syndrome.

Ketones are present when the body is breaking down fat for energy; they are
generally not seen in the urine. It is commonly seen in uncontrolled diabetics, but
can also be seen in patients that may be doing a ketogenic diet (carbohydrate
reduced or free), in pregnancy, or starvation.

Nitrites and Leukocyte Esterase on Dipstick

Nitrites are seen in the urine when bacteria are present that convert nitrates to
nitrites. Gram-negative and gram-positive bacteria, both are capable of this
conversion, and if positive, is an indication that there are bacteria present in the
urinary tract of the patient.

Nitrites in the urine is specific, but not very sensitive, meaning that if positive,
there is a good chance a UTI is present, but if negative, it does not mean that a UTI
is not present.

The UA dipstick is very sensitive to air, so the container should be closed ASAP. If
not, this could lead to false positive nitrite results.

Leukocyte esterase is present if neutrophils are present in the urinary tract, and can
be present if pyuria is present with a UTI.

Bilirubin on Dipstick
Lastly, bilirubin is not generally seen on a urinalysis. Indirect bilirubin is not water
soluble and cannot be filtered by the kidneys. However, direct bilirubin is water
soluble, and if present in the urine, a further workup for liver abnormalities or
biliary obstruction is needed.

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Urine can have a small amount of urobilinogen present, which occurs due to the
process of direct bilirubin being broken down in the intestine, reabsorbed into the
portal circulation, and then filtered through the kidneys.

If there is an increased amount of urobilinogen noted on UA, this can be due to

liver disease or hemolysis, and decreased amounts can be due to biliary obstruction
or antibiotic use.

White Blood Count

Leukocytosis is over 11,000 cells/microL

Most commonly due to an increased in the absolute number of mature

neutrophils.

Common causes include:

1. Acute phase reactant

2. Infectious
3. Bone marrow disorder (polycythemia vera and leukemia)
4. Tobacco (most common cause of mild elevations)
5. Stress (physical, emotional [PTSD, panic disorder, depression], exercise)
6. Steroids
7. Pregnancy
8. Asplenia

The most important disease to rule out in a patient who has a WBC
> 50,000 is CML.

AML = >15,000
CML = 30,000 and 400,000

When evaluating the hospitalized patient - most common causes include

infection - most common of which include:

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1. Pneumonia
2. UTI
3. Soft tissue infection
4. C. difficile infection

Leukopenia is under 4,400 cells/microL

Causes include:
1. Benign ethnic neutropenia (seen most commonly in the African American
population) - most common
2. Drug induced - most common. Less likely to be associated with other
cytopenias.
3. Nutritional deficiency (vitamin B12, folate, copper) - bariatric surgery
4. Infection (self resolves after infection) - can also be a result of
neutropenia
5. Aplastic anemia
6. Myelodysplastic syndromes/Malignancy
7. Congenital causes - will occur in the child

Neutrophils are the most important component and neutropenia is defined as an

absolute neutrophil count below 1,500-1,800 cells/microL.

HGB | HCT | RBC

A decrease in any is considered anemia. But, values vary according to labs.

Typically, the hemoglobin or hematocrit are used for anemia.

MCV = size of the RBC

MCH = average hemoglobin content in a RBC
MCHC = average hemoglobin concentration per RBC
RDW = measure of the variation in RBC size

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Decreased MCH = iron deficiency and thalassemia
Low MCHC = iron deficiency anemia
High MCHC = spherocytosis or RBC agglutination

The most common type of anemia is iron deficiency - most commonly

secondary to bleeding. Important to find the source.

Microcytic = < 80 fl
Perform iron studies:

low iron + low ferritin + high TIBC = iron deficiency

low iron + normal/high ferritin + normal/low TIBC = anemia of chronic disease
normal/high iron + normal/high ferritin = sideroblastic or thalassemia (get a
peripheral smear).

Normocytic = 80 - 100 fl:

1. Get a peripheral smear - helps differentiate cause. May be normocytic if the
MCV is drawn to early in microcytic and macrocytic anemias.
2. Look for hemolysis (increased LDH, increased indirect bilirubin,
decreased haptoglobin)
3. Look for blood loss (could be heavy menses)
4. Get a reticulocyte count. low = bone marrow suppression. high =
hemolysis or blood loss.
5. Get a creatinine. Elevated = renal insufficiency

Macrocytic = > 100 fl

1. Other cytopenias present = myelodysplastic syndrome
2. Get a B12 level and folate (MMA and homocysteine levels).
3. Increased reticulocyte production can be a cause
4. Liver disease (LFT and PT/INR)
5. Hypothyroidism (TSH)

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Platelets
Thrombocytopenia = < 150,000/microL

Patients with wet purpura (mucosal) and/or those with prior bleeding at a certain
platelet levels are at increased risk for bleeding. Spontaneous bleeding most
commonly occurs when the platelets reach a level < 30,000 - but this can vary
patient to patient.

Those who are asymptomatic most commonly have:

1. ITP (shouldn’t have anemia or neutropenia)
2. Chronic liver disease
3. Splenomegaly
4. Pregnancy (gestational thrombocytopenia occurs in the 3rd trimester) - no
need to do anything and self resolves.

Lupus is associated with secondary ITP in up to one half of patients.

Common drugs which can lead to this include antibiotics, antiepileptics, and
quinine - develops in 1-2 weeks.

Alcohol can lead to thrombocytopenia secondary to bone marrow toxicity, nutrient

deficiencies, and/or hypersplenism.

Potassium
Potassium levels: 3.5-5.0mEq/L

Hyperkalemia
The most common cause of hyperkalemia is lab error (hemolyzed - repeated fist
clenching during blood draw). Does the patient have kidney disease and/or are
they taking medication which could lead to a sudden rise?

Insulin pushes potassium into cells. If a non diabetic ingests glucose - this
releases endogenous insulin to lower the potassium concentration.

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But, this is not the case in the diabetic. Patients are often hyperkalemic on the
labs - but have low total body stores of potassium. The elevated glucose leads to
an elevated serum osmolality and the decrease in insulin means there isn’t
movement of potassium into cells. But, the body is still losing potassium due to
an osmotic diuresis.

Crush injuries, radiation therapy (tumor lysis syndrome), and

rhabdomyolysis can all cause intracellular potassium to spill out.

Beta 2 activity drives potassium into the cell. Beta blockers (non selective) can
elevate serum levels.

ACE inhibitors, NSAIDs, and heparin can decrease aldosterone release, and in
turn, decrease potassium excretion - this leads to hyperkalemia and metabolic
acidosis - type 4RTA.

Aldosterone resistance can elevate potassium levels: potassium sparring

diuretics, AKI, and CKD (may require dialysis).

The first thing to do is to rule out psuedohyperkalemia.

Chronic hyperkalemia is most common secondary to impaired excretion,

impaired aldosterone release/sensitivity, volume depletion, and/or kidney
disease.

Hypokalemia
Most common causes include decreased intake, increased push into the cells,
and/or increased losses in the urine, gastrointestinal tract, or sweat.

Giving insulin, such as when treating DKA, can precipitate a drop. Transient
hypokalemia can occur when beta agonists are given for asthma, CHF, COPD, and
pre-term labor. Diuretics + beta agonists can predispose the patient to arrhythmias.

GI loss can occur with vomiting, diarrhea, and laxative use.

Increased urinary excretion of potassium can occur secondary to

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increased mineralocorticoid activity (aldosterone-producing adrenal adenoma)
and/or diuretic therapy.

Don’t forget about magnesium. Hypomagnesemia is present in up to 40 percent

of patients with hypokalemia - this often needs to be addressed in order to
adequately correct the hypokalemia.

Calcium
Hypocalcemia
Due to decreased PTH secretion/resitance, vitamin D deficiency/resistance, and
abnormal magnesium levels

Etiologies include:

1. Head/neck surgery
2. CKD
3. Autoimmune disease (polyglandular autoimmune syndrome type I).
Triad: chronic mucocutaneous candidiasis, hypoparathyroidism, and
adrenal gland insufficiency.
4. Drugs (bisphosphonates, phenytoin, calcitonin)
5. Acute pancreatitis
6. Rhabdomyolysis

Elevated phosphate = hypoparathyroidism

Decreased phosphate = secondary hypoparathyroidism (excess PTH)
Normal phosphate = hypomagnesemia

Vitamin D deficiency, leads to low calcium levels, which leads to an increase in

PTH secretion (secondary hypoparathyroidism).

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Hypercalcemia

The most common causes include hyperparathyroidism and cancer (over 90%
of the etiology). Patients with cancer will have more symptoms and higher
levels of calcium when compared to hyperparathyroidism.

Less common causes include granulomatous disease (sarcoidosis, vitamin D

intoxication, hyperthyroidism, and vitamin A intoxication.

Don’t forget to correct for albumin levels.

1. Elevated PTH = primary hyperparathyroidism
2. Upper limit normal PTH = primary hyperthyroidism or familial
hypocalciuric hypercalcemia - order 24-hour urinary calcium or calcium-to-
creatinine ratio.
3. Low normal/low PTH = other causes discussed above. Order 1,25
hydroxyvitamin D, 25 hydroxyvitamin D, and PTH related protein.

Elevated PTHrP = malignancy

Elevated 1,25 hydroxyvitamin D = lymphoma or granulomatous disease
Elevated 25 hydroxyvitamin D = vitamin D intoxication

Kidney function
The BUN can increase for reasons other than kidney injury:

1. High protein diet

2. Hemorrhage
3. Trauma
4. Glucocorticoids

Patients with chronic liver disease may have falsely low levels of both the BUN
(decreased urea production) and creatinine (muscle wasting).

But, for the majority of patients, estimation of the GFR is sufficient - and
accurate in chronic disease (not as reliable in acute kidney injury).

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AKI = a rise in the serum creatinine or an abnormal urinalysis that has
developed within hours to days.

CKD = GFR < 60, albuminuria, or abnormal findings on renal imaging

which have been present for at least three months.

We have three types of kidney injury: Pre, intra, and post renal injury.

The most common will be dehydration (pre-renal) - and this is usually readily
apparent. Look for a BUN/Cr ratio >20.

Intra renal injury - typically, the BUN/Cr ratio = < 10. The most common
chronic renal vascular disease is nephrosclerosis.

Chronic glomerular disease may be classified as nephritic or nephrotic.

Nephritic = red blood cell casts, dysmorphic red cells, and proteinuria.
Nephrotic = proteinuria > 3.5 grams/24 hours.

The most common chronic tubulointerstitial disease is polycystic kidney

disease.

Patients are at increased risk of multiple myeloma:

1. > 40 years old
2. Have increased serum creatinine within three to six months
3. Have no other obvious cause for increased creatinine

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Liver Function Testing
ALT, AST, alkaline phosphatase and bilirubin = markers for liver injury.
Albumin and PT/INR = markers of liver function.

An elevated PT/INR will also be seen in patients who are on

anticoagulation and/or have a vitamin K deficiency.

Patterns to know:

AST/ALT = liver
Alkaline phosphatase and GGT = gallbladder Bilirubin

Bilirubin can be elevated in both.

Usually, the AST is lower than the ALT in most liver disease. If the ratio of
AST:ALT = > 2 - consider alcoholic liver disease. An elevated GGT helps
support the diagnosis. But, this ratio might also be seen in hepatitis C with
cirrhosis and in NASH.

Alcohol = ALT < 8 times ULN

NASH = LFT < 4 times ULN
Acute viral hepatitis = > 25 ULN
Ischemic hepatitis = > 50 ULN + elevated LDH

Chronic hepatitis B/C = < 10 ULN - but may be normal. This is why screening is
done with hepatitis C antibody - not LFT.

ALT is primarily found in the liver and is most specific for injury. But, can
also be elevated in patients who are obese. So, an isolated ALT, in an obese
patient, might not indicated liver injury.

AST is also found in cardiac muscle, skeletal muscle, kidney, and the brain. Can be
severely elevated in rhabdomyolysis and heat stroke.

Alkaline phosphatase is found in the liver and bone. But, can also be elevated

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due to pregnancy (3rd trimester), children (increased osteoblastic activity), in
women > 65 years of age, diabetics.

GGT is found mainly in liver and biliary cells - but is also seen in the kidney,
seminal vesicles, pancreas, spleen, heart, and brain. Infants < 7 months also have
elevated GGT levels.

If there isn’t any history of alcohol consumption, LFTs are elevated over 2 ULN on
repeat testing, and the prior tests are negative, screen for:

1. Autoimmune hepatitis (antinuclear antibodies, anti-smooth muscle

antibodies, and anti-liver/kidney microsomal antibodies)
2. Wilson disease (ceruloplasmin)
3. Thyroid disorder (TSH, free T4, free T3)
4. Consider Alpha-1 antitrypsin deficiency (serum alpha-1 antitrypsin level)
and celiac (serum tissue transglutaminase antibodies).

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