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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3156_Библиотеки_им_академика_М_И_Перельмана.pdf
CHAPTER 17
Laboratory Abnormalities:
Blood Chemistry and
Immunology
Nathan Falk
I. BACKGROUND. Serum alkaline phosphatase (ALP) is an enzyme that arises primarily from the
liver and bone, although small amounts are derived from the intestines and the vascular endothe-
lium. The placenta is also a source of ALP in pregnant women. In the liver, ALP is bound to the
cell membranes on the canalicular side of the hepatocytes. Osteoblasts and intestinal epithelial
cells also produce their own ALP (1). The normal range of serum ALP varies by age and clinical
history. The normal ranges for adolescents, adults older than 60 years, and pregnant women are
higher than for nonpregnant women and men younger than 60 years (see Table 17.1.1) (1).
Serum ALP should be ordered only if bone or liver disease is suspected. ALP results should
be compared with appropriate normal ranges on the basis of the age and clinical history.
Abnormal results should be repeated, because spurious elevations can be caused by a recent
albumin infusion, by the use of an anticoagulant tube for blood collection, or by serum samples
left standing at room temperature for prolonged periods (2, 3).
II. PATHOPHYSIOLOGY
A. Etiology
1. Identifying the source of ALP elevation is based upon measuring γ-glutamyltransferase
(GGT) or 5′-nucleotidase levels. Elevated ALP from liver sources results in elevated
GGT or 5′-nucleotidase, while ALP elevation in the setting of normal GGT or
5′-nucleotidase suggests a bone source (2, 3).
Alkaline Phosphatase,
Elevated
Peter F. Cronholm, Joseph Teel, and Nasreen Ghazi
TABLE 17.1.1 Normal ranges for serum ALP (1)
Age Group Normal Range (U/L)
Infant 50–165
Child 20–150
Adult 20–70
>60
30–75
17.1
358
2. Uncommon causes of ALP elevation include hyperthyroidism and intestinal conditions
such as bowel obstruction, inflammatory bowel disease, and infarction. Additionally,
infarction of any solid organ may cause ALP elevation owing to the presence of ALP in
the vascular endothelium (2).
III. EVALUATION. Further testing should be carried out on the basis of the results of a care-
ful history and physical examination and should be targeted at specific clinical suspicions
(Table 17.1.2) (1–3).
IV. DIAGNOSIS. See Table 17.1.2 (1–3).
TABLE 17.1.2 Evaluation of the Patient with Elevated ALP (1–3)
History Physical examination Testing Diagnosis
A. Bone disorders (1)
Primary bone
• Asymptomatic or
bone pain
• Male
• Frontal bossing
• Dilated supercial
vessels
• 24-h urine
hydroxyproline
• Serum phosphate
Paget’s disease
• Hearing/vision
problems
• Saber tibia
• Deafness
• Serum calcium
(normal)
• Headaches
• Pain increased
with walking (tibia
involved)
• Congestive heart
failure
• X-ray involved
bone(s)
• Bone scan
• Female
• >60 y
• Neck mass (rare)
• Muscle weakness
• Parathyroid
hormone
Hyperparathyroidism
• Diffuse aches and
pains
• Vague abdominal
pain
• No clinical evidence
of malignancy
• Serum calcium
• Urinary calcium/
blood
• Serum phosphate
• Depressive
symptoms
• Serum chloride
• 10–30 y
• Male
• Pain near joint
• Very high ALP
• Mass near joint
• Tender over mass
• X-ray area (mixed
sclerotic/lytic
lesion of bone)
• Magnetic
resonance imaging
of affected region
• Bone scan
• Biopsy
Osteosarcoma
• Recent trauma • Bone pain in area • X-ray (callous
formation)
Healing fracture
• Smoker • Dull to percussion • Serum calcium Homer’s syndrome
• Cough
(Continued)
359
TABLE 17.1.2 Evaluation of the Patient with Elevated ALP (1–3)
History Physical examination Testing Diagnosis
• Hemoptysis
• Shortness of breath
• Limited sunlight
exposure
• Fatigue
• Diarrhea
• Recent bariatric
surgery
• History of
malabsorptive
processes
• Bowed legs (rickets) • 25-OH vitamin D
• Gliadin antibody
• Basic metabolic
panel
Vitamin D deciency
Metastatic bone
• Female • Breast mass • Mammogram Breast cancer
• >50 y
• Family history
• Breast mass
• Axillary and
supraclavicular
nodes
• Liver enlargement
• Bone scan
• Serum calcium
• Female • Ovarian mass • Pelvic ultrasound Ovarian cancer
• >45 y
• Ascites • Pelvic CT scan
• Family history • CA-125
• Abdominal bloating • CT scan
• Serum calcium
• Unexplained weight
loss
• Male
• >50 y
• Hematuria
• Flank/abdominal
pain
• Unilateral ank mass
• Conjunctival pallor
• Urinalysis
• Abdominal CT
scan
• Serum calcium
Renal cell carcinoma
• Female
• Vaginal bleeding
• Family history
• Cervical mass on
exam
• Pap smear or
colposcopy
Cervical cancer
• Male
• >50 y
• Urinary complaints
• Family history
• Prostate mass on
rectal examination
or diffusely enlarged
hard prostate
• Serum calcium
• Prostate-specic
antigen
• Ultrasound-guided
prostate biopsy
• Bone scan
Prostate cancer
(Continued)
(Continued)
360
TABLE 17.1.2 Evaluation of the Patient with Elevated ALP (1–3)
History Physical examination Testing Diagnosis
B. Biliary/liver
disease (2)
1. Obstructive
processes
• Female
• >40 y
• Obese
• Family history of
gallstones
• Pain after meals/
episodic
• Bloating
• RUQ abdominal
tenderness +
Murphy’s sign (only
in acute cholecystitis)
• Jaundice
• AST/ALT may be
elevated
• Bilirubin elevated
• Ultrasound of
gallbladder
Gallstones
Biliary colic
Acute cholecystitis
• Weight loss
• Anorexia
• Back or RUQ pain
• Jaundice
• Palpable gallbladder
• Cachectic
• Epigastric mass
• Jaundice
• Abdominal CT
scan
• Elevated bilirubin
• CT scan or
ultrasound-guided
biopsy
Pancreatic
carcinoma
Gallbladder
carcinoma
2. Intrinsic hepatic
processes
• Alcohol use/abuse
(chronic)
• Family history of
liver disease
• Risky sexual
practices
• Blood transfusions
• Intravenous drug
use
• Spider nevi
• Leukonychia
• Dupuytren’s
contracture
• Tender RUQ
• Liver may be
enlarged
• Jaundice
• Serum AST/ALT
levels:
↑ in early disease
↓↔ late disease
• Bilirubin (elevated)
• Hepatitis screen
(A, B, C)
• Coagulation screen
• Liver biopsy
Cirrhosis
Hepatitis
Fatty liver
• Obesity
• Fatigue
• Weight loss
3. Infectious causes
• Fatigue
• Pharyngitis
• Fever
• Tender RUQ
• Monospot test
• AST/ALT
Infectious
mononucleosis
• 10–25 y old • Splenomegaly • CBC Toxoplasmosis
• Fever
• Sore throat/fatigue
• Lymphadenopathy
(mainly cervical)
• Toxoplasma titers
Cytomegalovirus
infection
• History of contact
with infected friend/
relative
(Continued)
(Continued)
361
TABLE 17.1.2 Evaluation of the Patient with Elevated ALP (1–3)
History Physical examination Testing Diagnosis
4. Drug induced (3)
• Chlorpropamide
• ACE inhibitors
• Estrogen
• Frequently normal
• RUQ tenderness
• AST/ALT
• Liver biopsy if
problem persists
Drug-induced
elevation of ALP
• Antineoplastic agents
• Immune modulators
5. Immune mediated
• 35–60 y of age
(90%)
• Jaundice
• Excoriations
• Jaundice
• Skin pigmentation
• Antimitochondrial
antibodies
• Liver biopsy
Primary biliary
cirrhosis
• Frequently
asymptomatic
• RUQ tenderness
• Xanthelasma
• Elevated bilirubin
(late)
• Itching (palms/soles
rst)
• Liver/spleen enlarged • Elevated liver
enzymes (late)
• Fatigue • Cholesterol
elevated
• Bone pain
• Steatorrhea
• Male
• 30–60 y of age
• RUQ pain
• Jaundice
• RUQ tenderness
• Jaundice
• Endoscopic retrograde
cholangiopan-
creatography (ERCP)/
Magnetic resonance
cholangiopancreatog-
raphy (MRCP)
Sclerosing
cholangitis
(primary or
secondary)
• Pruritus
• Inammatory bowel
disease
• Fatigue
• 10–40 y of age
• Cough
• Dyspnea
• Chest pain
• Crackles
• Rales
• Maculopapular rash
on face
• Chest X-ray (CXR)
with bilateral hilar
adenopathy
Sarcoidosis
6. Oncologic
• Fatigue/lethargy
• Fever
• Anorexia/weight loss
• Lymphadenopathy • CBC
• Elevated uric acid
• Elevated Lactate
dehydrogenase (LDH)
Lymphoma
• Enlarged lymph
nodes
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBC,
complete blood count; RUQ, right upper quadrant.
(Continued)
362
REFERENCES
1. McPherson R, Pincus M. Henry’s clinical diagnosis and management by laboratory methods, 22nd ed.
Philadelphia, PA: Elsevier, 2011.
2. Aragon G, Younossi, Z. When and how to evaluate mildly elevated liver enzymes in apparently healthy
patients. Cleve Clin J Med 2010;7(3):195–204.
3. Giannini EG, Testa R, Savarino V, et al. Liver enzyme alteration: a guide for clinicians. CMAJ
(OTTAWA) 2005;172-3:367–373.
I. BACKGROUND. Liver function tests (LFTs) are common, useful tools for evaluating the
differential diagnosis of hepatic pathology. The standard panel includes tests to evaluate for
the presence of hepatocellular injury, disorders of bile formation and excretion, and synthetic
dysfunction (1). Tests for hepatocellular injury include aspartate aminotransferase (AST) (or
serum glutamic oxaloacetic transaminase) and alanine aminotransferase (ALT) (or serum
glutamic pyrunic transaminase). Bile formation and excretion tests include alkaline phospha-
tase, total and direct serum bilirubin, and sometimes γ-glutamyl transpeptidase (GGT) or
5′-nucleotidase. Synthetic function tests include albumin, total protein, and sometimes pro-
thrombin time. The focus of this chapter will primarily be elevation of the aminotransferases
AST and ALT.
II. PATHOPHYSIOLOGY. The aminotransferases are cytosolic enzymes found in the hepatocytes;
they are released into the serum as a result of hepatocellular damage, thereby elevating the
serum levels from their low, but present, baseline (2). ALT is very specific to the hepatocytes,
whereas AST is not specific to hepatocytes and is found in numerous other body tissues (3). The
presence of elevated AST and ALT is not in and of itself specific to any condition— etiologies
include viruses, toxins, alcohol, cirrhosis, neoplasm, cholestasis, and vascular/circulatory com-
promise (4, 5). As such, the pattern of elevation must be evaluated and considered in light of
a thorough history and physical examination, as well as review of the remaining LFTs, other
appropriate lab tests, and imaging.
III. EVALUATION. Evaluation of abnormalities should include an assessment of medication use
(including over-the-counter and herbal medications), travel, country of origin, alcohol con-
sumption, recreational drug use (particularly a history of intravenous drug use), sexual history,
signs and symptoms of hepatic injury, and a thorough physical examination. ALT and AST
may also be elevated in association with myocardial infarctions, hemolytic anemia, trauma, and
intramuscular injections. A thorough clinical history and examination are essential in guiding
the testing and interpretation of the results, because patterns of abnormalities in liver testing
are better predictors of clinical disease than any single component.
IV. DIAGNOSIS. See Table 17.2.1.
Aminotransferase
Levels, Elevated
Peter F. Cronholm, Giang T. Nguyen, and
N. Corry Clinton
17.2
363
TABLE 17.2.1 Evaluation of the Patient with Elevated Aminotransferase
History Physical examination Testing Diagnosis
• Patient often
asymptomatic or
transient u-like illness
• Antecedent illness of
several days to weeks
with nausea, vomit-
ing, anorexia, malaise,
diarrhea, arthralgias, or
low-grade fever
• Recent shellsh
ingestion
• Incarceration
• Multiple sexual partners
• Past or present
intravenous drug use
• History of blood
transfusions before
1992 or tattoos
• From country with
endemic hepatitis virus
• Sexual or household
contacts with hepatitis
virus
• HIV infection
• Hemodialysis
• Jaundice
• Clay-colored stools
• Dark urine
• Left upper quadrant
tenderness
• Hepatomegaly
• Urticaria
• Maculopapular skin
eruptions
• Isolated joint swelling,
redness, or tenderness
• AST and ALT can be
markedly elevated
with ratio usually <1
• Alkaline phosphatase
and serum bilirubin
may be elevated or
normal
• Begin serial testing of
AST and ALT
• CBC
• Hepatitis A IgM
• Hepatitis B surface
antigen, IgM anti-
hepatitis B surface
antigen antibody, and
IgM anti-hepatitis B
core antibody
• IgG anti-hepatitis C
antibody
• Epstein-Barr virus or
cytomegalovirus titers
• Liver biopsy if
diagnosis cannot
be determined or to
guide treatment for
hepatitis C
• Acute viral
hepatitis
• Excessive somnolence
• Obtundation
• History of rectal or
upper GI bleeding
• Rapidly progressive
course in 65–95% of
patients
• Symptoms of sepsis
with or without
multi-organ failure
• Prior hepatitis
• History of aspirin
ingestion in children
younger than 17 y with
inuenza or chickenpox
• Toxic doses of
acetaminophen
(paracetamol in many
countries)
• Liver may be reduced
in size
• Ascites
• Refractory hypotension
• Petechiae
• Bleeding from mucous
membranes
• Edema
• AST and ALT can be
markedly elevated
with ratio usually <1
• Prothrombin
time (profoundly
prolonged)
• Low blood glucose
• Low total serum
protein and serum
albumin
• CBC
• Serum ammonia
(may be severely
elevated)
• Fulminant
hepatitis
• Acute hepatic
failure associated
with Reye’s
syndrome
• 1% of the elderly
or immunocom-
promised patients
with hepatitis
(Continued)
364
TABLE 17.2.1 Evaluation of the Patient with Elevated Aminotransferase
(Continued)
History Physical examination Testing Diagnosis
• Chronic or acute alcohol
ingestion
• Younger age drinker
• History of pancreatitis
or erosive gastritis
• Cirrhotic liver disease
• Hepatitis C history
• Anorexia
• Nausea
• Vomiting
• Abdominal pain
• Jaundice
• ± Fever
• Weight loss
• Hepatomegaly with
mild tenderness
• Advanced disease
can be characterized
by spider angiomas,
ascites, palmar
erythema, caput
medusae, gyne-
comastia, parotid
enlargement, and
testicular atrophy
• AST:ALT > 2:1
• γ-glutamyl
transferase elevation
• CBC (possible
anemia)
• Alcoholic
hepatitis (5)
• Often asymptomatic
• Previous episode of
acute hepatitis
• Coagulopathy
• History of risk factors
for acute hepatitis as
above
• May be no ndings
• Thin
• Jaundiced
• Small, nodular liver
• AST and ALT are
variably elevated
• Hepatitis B surface
antigen, IgM anti-
hepatitis B surface
antigen antibody,
and IgM/G anti-
hepatitis B core and
envelope antibody
• IgG anti-hepatitis C
antibody
• Albumin (often low)
• Prothrombin time
(may be elevated)
• Liver biopsy
• Chronic hepatitis
• RUQ pain, often after
eating fatty foods
• History of gallstones
• Middle aged
• Overweight
• Female
• Jaundice
• Intermittent fever
• Rigors
• RUQ tenderness ±
rebound
• Alkaline phosphatase
elevated more than
AST or ALT
• Elevated serum
bilirubin
• CBC
• RUQ ultrasound
• Endoscopic
retrograde cholangio-
pancreatography or
imaging equivalent
• HIDA scan
• Biliary tract
obstruction with
or without an
infection (cho-
lestasis vs. chol-
angitis)
(Continued)
365
TABLE 17.2.1 Evaluation of the Patient with Elevated Aminotransferase
(Continued)
History Physical examination Testing Diagnosis
• Known or unknown
malignancy
• Abdominal pain
• Weakness
• Anorexia
• History of hepatitis B or
C infection
• Weight loss
• Ascites
• GI malignancies may
have left supracla-
vicular (Virchow’s) or
periumbilical (Sister
Mary Joseph) lymph
node enlargement
• Other ndings specic
to the primary site
malignancy
• Can present as
hepatocellular injury,
obstructive or a com-
bination prole
• MRI
• Serum a-fetoprotein
• Workup for source of
primary malignancy
• Malignancy
(primary or
metastatic)
Use of
• HMG-CoA reductase
inhibitor
• Isoniazid
• Phenothiazine
• Erythromycin
• Progesterone
• Halothane
• Opiates
• Indomethacin
• Corticosteroids
• Some herbal drugs
• Polypharmacy
• Often none • Increased AST and
ALT
• Repeat AST and ALT
after discontinuation
of the medication
• Other testing specic
to medication effects
(e.g., creatinine
kinase levels with
toxicity of HMG-CoA
reductase inhibitors)
• Medication effect
• Fatigue, malaise, and
vague right upper
abdominal discomfort
• Hepatitis with no clear
etiology
• Obesity
• Hepatomegaly
• Splenomegaly
• AST:ALT ratio <1
• Fasting lipids
• Fasting glucose
• Ultrasound, CT scan,
or MRI
• Liver biopsy is neces-
sary to determine
inammation
• Hepatic steatosis
and nonalcoholic
steatohepatitis
• Family history of
hemochromatosis
• Polyuria, polyphagia,
and polydipsia
• Weakness and lethargy
• Arthralgia
• Impotence or decreased
libido in men
• Amenorrhea in women
• Weakness
• Skin hyperpigmentation
• Diabetes mellitus
• Hepatomegaly
• Electrocardiographic
abnormalities
• Serum iron
• TIBC
• Iron saturation (ratio
of serum iron to
TIBC) >45%
• Ferritin
• Liver biopsy for
determination of
hepatic iron index
• Family screening
• HbA1c
• Hemochromatosis
(Continued)
366
TABLE 17.2.1 Evaluation of the Patient with Elevated Aminotransferase
(Continued)
History Physical examination Testing Diagnosis
• Muscle pain or
weakness
• Muscle tenderness
or weakness on
examination
• Creatine kinase
• Aldolase
• Muscle biopsy
• Muscle disorders
• Unintentional weight
loss or gain
• Skin and hair changes
• Heat or cold intolerance
• Goiter and/or thyroid
nodule(s) in certain
conditions
• Hair loss
• Abnormal reexes
• TSH
• Thyroid function
testing if TSH is
abnormal
• Thyroid
disorders
• Hepatitis or liver failure
• Emphysema when
young or out of
proportion with smoking
history
• Family history of
pulmonary pathology
• Physical examination
ranging from acute
hepatitis to end-stage
liver disease
• Pulmonary examina-
tion suggestive of
end-stage pulmonary
disease
• α-1-antitrypsin level
• α-1-antitrypsin
phenotype
• Serum protein
electrophoresis
• α-1-antitrypsin
deficiency
• Child or young adult
(5–25 y)
• Hepatitis
• Dysarthria
• Dysphagia
• Kayser-Fleischer rings
in cornea
• Tremor or other
movement disorders
• Behavioral and
psychiatric symptoms
• Liver function tests
often nonspecic
• Ceruloplasmin
(reduced in 85% of
patients)
• 24-h urine for
quantitative copper
excretion (>10 µg/d
is suggestive)
• Serum protein
electrophoresis
• Wilson’s disease
• Female
• History of
autoimmune
disorder
• Antibody to liver/
kidney
• Microsomal
antibody type 1
• ANA
• Smooth muscle
antibody
• Autoimmune
hepatitis
• Diarrhea, abdominal
pain, malabsorption
• Tissue
transglutaminase
• Celiac disease
• G6PD deciency • Lactate
dehydrogenase
• Haptoglobin
• Reticulocyte count
• Hemolysis
• Sickle cell anemia
• Infection
(Continued)
367