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302 Laboratory Medicine in Psychiatry and Behavioral Science
Urine white blood cells (WBCs) and WBC casts
Type of test Component of routine urinalysis
Background and explanation
of test
An increase in the number of WBCs in urine is termed
pyuria. A significant increase suggests the presence of infec
-
tion or inflammation, usually within the genitourinary sys-
tem. Significant WBC elevation should be followed up with
a urine culture.
Relevance to psychiatry and
behavioral science
This test is helpful in the diagnosis of urinary tract infection
(UTI), which can be associated with delirium and other
mental status changes, particularly in elderly patients.
Preparation of patient None needed
Indications Component of routine urinalysis
Reference range WBCs: 0–4/hpf. In females, slightly more WBCs can be
normal.
WBC casts: 0/lpf
Critical value(s) > 30 WBCs/hpf indicates the presence of acute bacterial in-
fection in the genitourinary system.
The presence of WBC casts requires further investigation to
rule out pyelonephritis, which may otherwise be asymp
-
tomatic.
Increased levels Increased urine WBCs
• UTI or inflammation (e.g., of bladder, prostate, or
urethra)
• Renal disease (especially with WBC clumping)
• Appendicitis
•Pancreatitis
• Strenuous exercise
•SLE
The presence of WBC casts may indicate disease of
the kid-
ney itself (most commonly pyelonephritis) or acute glomer-
ulonephritis, interstitial nephritis, or lupus nephritis.
Decreased levels Not applicable
Interfering factors Vaginal secretions can cause false elevation in urine WBCs.
Cross-references Urinalysis
Urinary Tract Infection
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed October 2021.
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Simerville JA, Maxted WC, Pahira JJ: Urinalysis: a comprehensive review. Am Fam Physician 71:1153–
1162, 2005
https://t.me/med1917
303 Laboratory Tests
Urobilinogen
Type of test Component of routine urinalysis
Background and explanation
of test
Bilirubin is converted to urobilinogen in the GI tract by bac-
terial enzymes. Some of this product is excreted in feces, and
some travels in the portal circulation to the liver, where it is
metabolized and excreted with bile. Traces of bilirubin that
circumvent these processes are excreted in urine. Urobilino-
gen is increased in diseases associated with increased biliru-
bin levels and in diseases that prevent the liver from
metabolizing bilirubin. Increased urobilinogen is one of the
earliest signs of liver disease
and of hemolytic disorders.
•
In the absence of disease, urine bilirubin is negative, and
urobilinogen is normal.
• In hemolytic disease, urine bilirubin is negative, and
urobilinogen is increased.
• In hepatic disease, urine bilirubin may be positive or
negative, and urobilinogen is increased.
• In biliary obstruction, urine bilirubin is positive, and
urobilinogen is low or absent.
Relevance to psychiatry and
behavioral science
Increased urobilinogen levels may be found in patients with
hepatitis, cirrhosis, or pernicious anemia.
Preparation of patient None needed
Indications Component of routine urinalysis
Reference range Random spot urine: 0.1–1 Ehrlich U/dL (<1 mg/dL)
Critical value(s) None
Increased levels • Increased rate of RBC destruction: hemolytic anemia,
pernicious anemia, malaria
• Hemorrhage into tissues: pulmonary infarction, exces-
sive bruising
• Hepatic injury: biliary disease, acute hepatitis, cirrhosis
(viral or chemical)
• Cholangitis
Decreased levels • Partial or complete obstruction of bile ducts: gallstones,
severe inflammation, or pancreatic cancer involving the
head of the pancreas
• Antibiotic therapy with suppression of gut flora and re-
duced conversion of bilirubin to urobilinogen
Interfering factors Diurnal variation: peak urobilinogen excretion occurs from
noon to 4:00
P.M.
Urobilinogen decomposes quickly at room temperature
when exposed to light.
Highly colored urine affects reading of the test strip.
Cross-references Anemia
Bilirubin
https://t.me/med1917
304 Laboratory Medicine in Psychiatry and Behavioral Science
Urobilinogen (continued)
Cross-references (continued) Cirrhosis
Hepatitis, Viral
Urinalysis
Urine Bilirubin
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed October 2021.
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Simerville JA, Maxted WC, Pahira JJ: Urinalysis: a comprehensive review. Am Fam Physician 71:1153–
1162, 2005
https://t.me/med1917
305 Laboratory Tests
Valproate level
Type of test Blood
Background and explanation
of test
Valproate (sodium valproate, also known as valproic acid
and divalproex sodium) is an antiepileptic drug indicated
for generalized tonic-clonic, partial complex, and petit mal
seizures. It is also used to treat bipolar disorder, mood insta
-
bility in the context of dementia, TBI, myoclonus, and many
other neuropsychiatric conditions. If there is any concern
about altered protein binding in the valproate-treated pa
-
tient, a free valproate rather than total valproate level should
be checked.
Relevance to psychiatry and
behavioral science
Reference ranges reported for valproate relate to seizure
rather than behavioral indications. As a rule, levels correlate
poorly with mood and behavioral control. The reason levels
are checked in psychiatric practice is to monitor compliance
(to exclude very low or zero levels) or toxicity (to exclude
levels that are orders of magnitude above the upper limit of
normal for seizure). Other labs are also monitored when val
-
proate is used, as discussed in the Va lp r oa t e entry in the
Psychotropic Medications chapter.
Preparation of patient To check level, patients taking valproate twice daily should
be instructed to hold their morning dose until after blood is
drawn. For patients taking divalproex extended-release for
-
mulation once daily in the morning, blood should be drawn
before the morning dose. For those taking divalproex ex-
tended-release formulation once daily in the evening, blood
should be drawn 18–21 hours after the last dose.
Indications • Overdose
• Signs/symptoms of valproate toxicity
• Concern regarding noncompliance
Reference range Total valproate: 50–125 μg/mL
Free valproate: 6–22 μg/mL
% Free valproate: 5%–18% (calculated)
Critical value(s) Total valproate: >150 μg/mL
Free valproate: >50 μg/mL
Increased levels • Overdose
• Hepatic insufficiency or failure
Decreased levels Noncompliance
Interfering factors Timing of blood draw influences results, as noted above.
Coadministration of carbamazepine decreases valproate
levels, and fluoxetine increases valproate levels, but these
are actual level changes that do not represent test inter-
ference.
https://t.me/med1917
306 Laboratory Medicine in Psychiatry and Behavioral Science
Valproate level (continued)
Cross-references Bipolar and Related Disorder Due to Another Medical
Condition
Manic Episode
Seizures
Va l pr o a t e
American Society of Health-System Pharmacists: AHFS Drug Information. Bethesda, MD, American So-
ciety of Health-System Pharmacists, 2016
Fleming J, Chetty M: Therapeutic monitoring of valproate in psychiatry: how far have we progressed?Clin
Neuropharmacol 29(6):350–360, 2006
Reed RC, Dutta S: Does it really matter when a blood sample for valproic acid concentration is taken fol-
lowing once-daily administration of divalproex-ER?Ther Drug Monit 28(3):413–418, 2006
https://t.me/med1917
307 Laboratory Tests
Vitamin B
12
level
Type of test Blood
Background and explanation
of test
Vitamin B
12
is required for protein synthesis, fat and carbo-
hydrate metabolism, absorption and digestion of food, for-
mation of RBCs, production of acetylcholine, maintenance
of nerve cells, and fertility in females. Vitamin B
12
deficiency
due to inadequate intake is rare in developed countries; de
-
ficiency usually is due to malabsorption—which is common
in elderly patients—and can occur with conditions such as
cystic fibrosis, pernicious anemia, reduced gastric acid pro
-
duction, excessive use of antacids, chronic use of histamine
H
2
blockers, gastric bypass surgery, and other GI diseases
such as tapeworm. Increased loss of B
12
may be seen in alco-
hol use disorder and in liver and kidney disease.
Vitamin B
12
deficiency is associated with a megaloblastic
anemia, in which fewer and larger RBCs are produced. The
syndrome of subacute combined degeneration of the spinal
cord due to B
12
deficiency is discussed in the Vitamin B
12
Deficiency entry in the Diseases and Conditions chapter.
Relevance to psychiatry and
behavioral science
Vitamin B
12
deficiency is associated with a variety of symp-
toms of interest to psychiatrists and other behavioral health
practitioners, including confusion, delirium, psychosis,
somnolence, irritability, depression, mania, apathy, person
-
ality change, delusions, cognitive impairment (particularly
involving memory), and the nonspecific symptoms of dizzi-
ness, weakness, and fatigue. Patients with vague neurolog-
ical symptoms such as clumsiness, unsteadiness, tinnitus,
speech impairment, or visual changes are sometimes misdi-
agnosed with functional neurological symptom disorders.
Preparation of patient Patients should fast overnight before the test, and on the
day of testing should hold heparin and avoid vitamin C, flu
-
oride, and alcohol.
Indications •
Standard component of workup for dementia or mem-
ory impairment
• Identifying cause of delirium
•
Evaluating mental status changes in an elderly patient
• Identifying the cause of peripheral neuropathy
• Presence of symptoms of subacute combined degenera-
tion (weakness, sensory abnormalities)
• Workup for macrocytic anemia (folate also measured)
• Workup for macrocytosis (MCV >110 fL)
• Evaluating nutritional status
•
Monitoring effectiveness of treatment for vitamin B
12
deficiency
Reference range 250–1,000 pg/mL
https://t.me/med1917
308 Laboratory Medicine in Psychiatry and Behavioral Science
Vitamin B
12
level (continued)
Critical value(s) For geriatric or adult patients with the neurological or psy-
chiatric symptoms listed in Relevance section above, many
clinicians prescribe vitamin B
12
supplementation when lev-
els are <400 pg/mL. Among elderly patients, loss of muscle
mass and strength are found with levels below this thresh
-
old.
Increased levels • Supplementation
• Leukemia
• Liver dysfunction
High B
12
levels are not associated with toxicity and are of
uncertain significance.
Decreased levels • Inadequate intake (e.g., strict vegetarian diet)
• Poor absorption
• Increased excretion
Interfering factors Serum B
12
level may be increased by the use of chloral hy-
drate or omeprazole.
Serum level may be decreased by the use of anticonvulsants,
ascorbic acid, cholestyramine, chlorpromazine, colchicine,
levodopa, metformin, neomycin, octreotide, oral contracep
-
tives, ranitidine, or rifampin.
Cross-references Dementia
Folate Deficiency
Folate Level
Vitamin B
12
Deficiency
Andrès E, Loukili NH, Noel E, et al: Vitamin B
12
(cobalamin) deficiency in elderly patients. CMAJ
171(3):251–259, 2004
Ates Bulut E, Soysal P, Aydin AE, et al: Vitamin B
12
deficiency might be related to sarcopenia in older
adults. Exp Gerontol 95:136–140, 2017
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Langan RC, Goodbred AJ: Vitamin B
12
deficiency: recognition and management. Am Fam Physician
96(6):384–389, 2017
Lerner V, Kanevsky M, Dwolatzky T, et al: Vitamin B
12
and folate serum levels in newly admitted psychi-
atric patients. Clin Nutr 25:60–67, 2006
Stabler SP: Clinical practice: vitamin B
12
deficiency. N Engl J Med 368(2):149–160, 2013
Zik C: Late-life vitamin B
12
deficiency. Clin Geriatr Med 35(3):319–325, 2019
https://t.me/med1917
309 Laboratory Tests
Vitamin D level
Type of test Blood
Background and explanation
of test
Vitamin D is a fat-soluble vitamin ingested in foods and
supplements and synthesized in the skin on exposure to sun
-
light. It becomes biologically active through hydroxylation in
the liver and kidney. Vitamin D works with other hormones
to regulate calcium balance through absorption from the GI
tract and resorption from bone and to regulate phosphorus
and magnesium absorption. Adequate levels of vitamin D
are needed at all ages for bone growth and health. In older
age, females are particularly prone to developing deficiency,
especially those with dark skin, those who lack sunlight
exposure, and those with malabsorption. The 25-hydroxy
vitamin D level is recommended in preference to the 1,25
-
dihydroxy level in testing for deficiency.
Relevance to psychiatry and
behavioral science
Low vitamin D levels have been associated with cognitive
decline, Alzheimer’s disease, and depression, although treat-
ment studies have largely failed to demonstrate improve-
ment with vitamin D replacement. Older adults are at
particular risk of deficiency, which is especially common
among females in nursing home settings. Other adverse
effects of deficiency involve the musculoskeletal system and
the heart. In addition, the risk of developing certain cancers
and autoimmune diseases may be greater in deficient indi-
viduals.
Preparation of patient None needed
Indications • Detecting vitamin D deficiency in patients at risk
• Confirming deficiency in patients with evidence of bone
disease, bone or muscle weakness, or abnormal calcium,
phosphorus, and/or PTH levels
• Monitoring effectiveness of vitamin D replacement
Reference range Adults: 30–80 ng/mL
Critical values Toxicity is possible with 25-OH vitamin D levels >150 ng/
mL. These high levels can be associated with tissue calcifica-
tion (e.g., kidneys, vasculature), vomiting, constipation, an-
orexia, nausea, and severe electrolyte derangements.
Increased levels Excessive supplementation
Decreased levels • Inadequate vitamin D intake
• Malabsorption of vitamin D
• Inadequate sunlight exposure
Interfering factors Drugs that decrease vitamin D levels include anticonvul-
sants (carbamazepine, phenytoin, primidone, phenobarbi-
tal), aluminum hydroxide, cholestyramine, glucocorticoids,
isoniazid, rifampin, and mineral oil.
Cross-references None
https://t.me/med1917
310 Laboratory Medicine in Psychiatry and Behavioral Science
Vitamin D level (continued)
Anglin RE, Samaan Z, Walter SD, McDonald SD: Vitamin D deficiency and depression in adults: system-
atic review and meta-analysis.Br J Psychiatry 202:100–107, 2013
Annweiler C, Dursun E, Féron F, et al: Vitamin D and cognition in older adults: updated international rec-
ommendations.J Intern Med 277(1):45–57, 2015
ARUP Laboratories: Vitamin D, 25-hydroxy, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories,
2021. Available at: https://ltd.aruplab.com/Tests/Pub/0080379. Accessed October 2021.
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Goodwill AM, Szoeke C: A systematic review and meta-analysis of the effect of low vitamin D on cogni-
tion.J Am Geriatr Soc 65(10):2161–2168, 2017
Landel V, Annweiler C, Millet P, et al: Vitamin D, cognition and Alzheimer’s disease: the therapeutic ben-
efit is in the D-tails. J Alzheimers Dis 53(2):419–444, 2016
https://t.me/med1917
311 Laboratory Tests
White blood cell (WBC) count
Type of test Blood
Background and explanation
of test
WBCs, or leukocytes, are cells of the immune system that re-
side in the lymphatic system, blood, and tissues. These cells
have critical roles in fighting infection and ridding the body
of foreign material. When these processes occur, more WBCs
are produced by the bone marrow, and the WBC count in-
creases, with the degree of elevation corresponding to the se-
verity of the infection or intrusion. There are five types of
WBCs—neutrophils, basophils, eosinophils, lymphocytes,
and monocytes—present in stable proportions. Usually,
when the WBC count is elevated, only one of the five types
is increased in number. If all cell types are increased in num-
ber, it is more likely that hemoconcentration has occurred.
The significance of elevation of each type of WBC is dis-
cussed in the individual WBC differential entries that follow.
Conditions such as cancer and immune disorders and the
use of medications such as clozapine can be associated with
reduced WBC numbers because of decreased production or
shortened survival of these cells. Whether WBC numbers are
elevated or reduced, the pattern of abnormality—which type
of WBC is affected—can suggest the underlying pathology.
The WBC “differential” component of testing breaks down
the numbers by each of the five cell types. A review of the
blood smear also facilitates diagnosis because it can show
abnormally formed or immature cells.
Relevance to psychiatry and Delirium is associated with conditions involving both ele-
behavioral science vated and decreased WBC levels. Lithium often causes an
increase in WBC count. Clozapine and other psychotropic
drugs can cause very low WBC counts, as discussed in the
White Blood Cell Count Differential: Neutrophils entry. In
general, patients with persistently low WBC numbers re-
quire special care, including protection from fresh fruits,
vegetables, plants, and flowers; avoidance of intramuscular
injections, rectal thermometers, and suppositories; and spe-
cial care in using dental floss and razor blades.
Preparation of patient Fasting is not required. Physiological stress should be
avoided just before testing.
Indications • Routine component of CBC
• Ordered as individual test in certain clinical situations
Reference range Black adults: 3.2–10.0×10
3
cells/mm
3
; benign ethnic neutro-
All other adults: 4.5–10.5× 10
3
cells/mm
3
Critical value(s) Severe leukopenia <2.0×10
3
cells/mm
3
Severe leukocytosis >30.0 ×10
3
cells/mm
3
https://t.me/med1917