INTEGRATED CASE: Liver
Monica Kristine D. Reyes
1. Name: GB
2. 50 years old
4. 5 children
Signs and Symptoms
1. 5 days: intermittent fever
3. Body malaise
4. Vague abdominal pain
6. 2 episodes of soft stools
Answer to Number 1
Additional History Taking
1. Which sign/symptom appeared first?
2. Abdominal pain:
a. quality: colicky, diffused, gaseous, spiking, sharp, shooting, dull, burning,
cramping, stabbing, severe cramping
b. Quadrant: localize
c. Quantify: 1-10 (10 being the most painful)
d. Alleviating: medications, position, movement (sitting, standing, walking),
e. Aggravating: same as above
f. Referred pain? Shifting pain? Radiating pain?
g. Timing of pain: after eating, before meals, after alcohol ingestion
h. Dyspnea? Right lung is compromised
k. Types: visceral, somatic, referred, inflammatory, from stretching, tension of
gut wall, traction
l. Weight loss?
m. Has he ever had it before?
n. Does it awake him at night?
Additional History Taking
a. (may occur with fluid and electrolyte imbalance, infection, metabolic,
endocrine, labyrinthine and cardiac disorders; use of certain drugs, surgery
c. gastric and peritoneal irritation?
d. from alcohol intoxication, severe pain, overeating, ingestion of distasteful
food or liquid.
e. last meal?
f. meds taken?
g. consistency of vomitus? Amount? Color? Frequency? Odor?
i. timing? After eating? Since when?
j. alleviating factors?
k. Aggravating factors?
l. odor of breath?
Additional History Taking
4. Two episodes of soft stool
b. color? Odor? Consistency?
d. changes in bowel habits?
e. last bowel?
f. hematochezia? Melena?
g. onset? Duration?
h. history of travel?
i. food intake?
j. lactose intolerant?
k. medications taken before and taken to address diarrhea?
m. arthralgia? (ulcerative colitis)
PAST HEALTH HISTORY
1. Have you had similar symptoms before? Have you sought
2. Major acute or chronic illnesses requiring hospitalization?
4. Allergies? (food, meds)
5. Chronic diseases? (DM, cardiac, renal, cancer)
6. Possible genetic diseases? (family/ friends with the same S/Sx)
7. GI disorders? (ulcer, liver, pancreas, gallbladder, IBD, hiatal
hernia, IBS, diverticulosis, GERD, hemorrhoids, GI bleeding, CA,
rectal/ abdominal surgery or trauma)
8. Lifestyle? (exercises? Coffee? Tea? Caffeinated bev like colas?
Drank within 24 hours? Diet? Eating patterns? Late-night eating or
habitual large meals? Fiber intake? Smoking? Alcohol intake?
Nature of work? Educational background? Normal day?)
9. Medications chronically taken? (dosages; ANTIBIOTICS-
Clostridium difficile, NSAIDS, opioids, herbal remedies such as
ginger and gingko biloba, vitamins)
FAMILY/ SOCIAL HISTORY
1. Did family members have similar problems?
2. (familial links): ulcerative colitis, colorectal cancer,
peptic ulcers, gastric ulcers, alcoholism, Crohn’s
3. Ethnic background? (Crohn’s: more common in
4. Family size
6. Home environment
7. Occupational/ Environmental hazards
8. History of blood transfusions and tattoos
9. Financial Status
Answer to Number 2
PERCUSSION and PALPATION
a. redness: inflammation
b. Bruising on flank or Turner’s sign:
c. Cutaneous angiomas: liver disease
d. Visible rippling in abdomen: obstruction
PERCUSSION and PALPATION
a. Normal bowel sounds: high-pitched gurgling noises
caused by air mixing with fluids during peristalsis (5-34
times per minute); noise vary in frequency, pitch and
b. loudest before mealtimes
c. Borborygmus: stomach growling; loud, gurgling,
splashing bowel sound heard over the large intestine as
gas pass through it.
d. Classified as normal, hypoactive, hyperactive
e. HYPERACTIVE BOWEL SOUNDS: loud, high-pitched
tinkling sounds that occur frequently-indicate increased
intestinal motility and have been related to DIARRHEA,
constipation, gastroenteritis, laxatives and life-
threatening intestinal obstruction.
f. Friction rubs over liver: splenic infarction or hepatic
PERCUSSION and PALPATION
a. listen for tympani or dullness
b. Liver span (N=6.5-12cm): more than
c. spleen (10th rib); often not percussed
due to the tympani of bowel obscuring the
dullness of the spleen (resonance: kidney
PERCUSSION and PALPATION
b. rebound tenderness
c. skin turgor: dehydration
Answer to Number 3
1. Clostridium difficile infection
2. Pancreatitis, chronic
6. Acute Pyelonephritis
9. Pyogenic/ amebic abscess (Histolytica)
Laboratory tests generally are effective in detecting hepatic dysfunction,
assessing the severity of liver injury, refining the diagnosis concerning any
identified abnormalities, monitoring the course of liver disease, and
evaluating the response to treatment. Many tests of liver biochemistry and
excretory performance are called liver function tests. However, some of
these tests, rather than assessing liver function, assess liver necrosis or
injury by measuring liver enzymes released into the bloodstream (eg,
aminotransferases). Only some liver function tests actually assess liver
function by evaluating hepatobiliary excretion (eg, bilirubin) or the liver's
synthetic capability (eg, PT [usually reported as the INR]). Tests that detect
liver inflammation, altered immunoregulation, or viral hepatitis include
hepatitis serology (see Hepatitis: Serology), immunoglobulins, antibodies,
and autoantibodies. These tests reflect B lymphocyte rather than
hepatocyte function. Other laboratory tests may reflect specific disorders,
such as α-fetoprotein in hepatocellular carcinoma.
The most useful laboratory tests, particularly for screening for evidence of liver
disease, are serum aminotransferases, bilirubin, and alkaline phosphatase.
Certain patterns of liver biochemical abnormalities help distinguish
hepatocellular injury from impaired bile excretion (cholestasis—see Table 1:
Testing for Hepatic and Biliary Disorders: Common Patterns of Laboratory
Test Abnormalities ). A few laboratory tests are diagnostic by themselves
(eg, hepatitis B surface antigen [HBsAg] for hepatitis B virus, serum copper
and ceruloplasmin for suspected Wilson's disease, serum α1-antitrypsin for
Tests for Liver Injury
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leak
from damaged cells, making them sensitive indicators of liver injury. Acute
hepatocellular necrosis or injury (eg, hepatitis) typically results in high
values (500 to > 2000 IU/L; normal, ≤ 40 IU/L), usually for days or, in viral
hepatitis, weeks. Serial measurements better reflect severity and prognosis
than do single values: a fall to normal indicates recovery unless
accompanied by a rise in bilirubin and PT or INR (which may predict
massive liver failure). Modest elevations (100 to 300 IU/L) persist in chronic
liver diseases. In biliary obstruction, values usually are < 300 IU/L, except
where passage of a common duct stone transiently increases levels to the
thousands. Values < 100 IU/L are nonspecific.
• Although ALT is somewhat specific for liver disease, AST may be elevated
because of rhabdomyolysis or damage to heart or brain tissue. In most liver
diseases, the ratio of AST to ALT is < 1, but in alcohol-related liver damage,
the ratio characteristically is > 2; pyridoxine, which is deficient in most
alcoholic patients, is required for ALT synthesis but is less essential for AST
• Lactate dehydrogenase
• LDH, commonly included in routine analysis, is insensitive for hepatocellular
injury but sensitive for cancers involving the liver. Elevations may also
indicate hemolysis, MI, or pulmonary embolism.
Tests for Cholestasis
• Bilirubin is the pigment in bile produced from the breakdown of heme proteins. Unconjugated
bilirubin is lipid-soluble and is transported in plasma bound to albumin. It is conjugated in the liver
to form water-soluble conjugated bilirubin. Conjugated bilirubin is then excreted through the biliary
system into the duodenum, where it undergoes metabolism to form unconjugated bilirubin,
colorless urobilinogens, and then orange-colored urobilins, most of which are eliminated in feces.
• Hyperbilirubinemia results from increased bilirubin production, decreased liver uptake or
conjugation, or decreased biliary excretion (see Approach to the Patient With Liver Disease:
Overview of Bilirubin Metabolism). Total bilirubin normally is mostly unconjugated, with values of <
1.2 mg/dL (< 20 μmol/L). Fractionation can measure the proportion of bilirubin that is conjugated
(or direct, ie, measured directly). Fractionation is required only in neonatal jaundice or if bilirubin is
elevated, but other liver test results are normal, suggesting that hepatobiliary disease is not the
• Unconjugated hyperbilirubinemia (indirect bilirubin fraction > 85%) reflects increased bilirubin
production (eg, hemolysis) or defective liver uptake or conjugation (eg, Gilbert syndrome). Such
increases in unconjugated bilirubin are generally less than 5-fold (< 6 mg/dL [< 100 μmol/L])
unless concurrent liver disease exists.
• Conjugated hyperbilirubinemia (direct bilirubin fraction > 50%) results from decreased bile
formation or excretion (cholestasis). Serum bilirubin is insensitive for liver dysfunction and does
not distinguish cholestasis from hepatocellular disease. Severe hyperbilirubinemia, however, may
predict a poor prognosis in primary biliary cirrhosis, alcoholic hepatitis, and acute liver failure.
• Unconjugated bilirubin, because it is water-insoluble and bound to albumin, cannot be excreted in
urine. Thus, bilirubinuria generally indicates high serum conjugated bilirubin and hepatobiliary
disease. Bilirubinuria can be detected at the bedside with commercial urine test strips in acute
viral hepatitis or other hepatobiliary disorders before jaundice appears. However, the urine test
strip has limited value because it may be falsely negative with prolonged storage of the urine
specimen, vitamin C ingestion, or nitrates in the urine (eg, from UTIs). Similarly, increases in
urobilinogen have limited value; they are neither specific nor sensitive.
2. Alkaline phosphatase
• Increases in levels of this hepatocyte enzyme suggest cholestasis.
However, alkaline phosphatase consists of several isoenzymes and
originates in various tissues, particularly in bone.
• Alkaline phosphatase levels increase 4- fold or higher 1 to 2 days after the
onset of biliary obstruction, regardless of the site of obstruction. Levels may
remain elevated for several days after the obstruction resolves because the
half-life of alkaline phosphatase is about 7 days. Increases of up to 3 times
normal occur in many liver disorders, including hepatitis, cirrhosis, space-
occupying lesions, and infiltrative disorders. Isolated elevations (ie, when
other liver test results are normal) occur often in focal liver lesions (eg,
abscess, tumor) or in partial or intermittent bile duct obstruction. Isolated
elevations also occur in the absence of liver or biliary disease, such as
some malignancies without apparent liver involvement (eg, bronchogenic
carcinoma, Hodgkin's lymphoma, renal cell carcinoma), after fatty meals
(originating in the small intestine), in pregnancy (from placenta), in growing
children and adolescents (from bone growth), and in chronic renal failure
(from intestine and bone). Fractionating these alkaline phosphatases is
technically difficult. Elevation of enzymes more specific to the liver, 5′-
nucleotidase or γ-glutamyl transpeptidase (GGT), can differentiate hepatic
from extrahepatic sources of alkaline phosphatase. An isolated alkaline
phosphatase elevation in an otherwise asymptomatic elderly person usually
originates from bone (eg, Paget's disease) and does not require further
• Increases in levels of this enzyme are as sensitive as
alkaline phosphatase for detecting cholestasis and biliary
obstruction but are more specific, almost always
indicating hepatobiliary disease. Because levels of
alkaline phosphatase and 5′-nucleotidase do not always
correlate, one can be normal while the other is
4. γ-Glutamyl transpeptidase (GGT)
• Levels of this enzyme rise in hepatobiliary disease,
especially cholestasis, and correlate loosely with levels
of alkaline phosphatase and 5′-nucleotidase. Levels do
not increase with bone lesions, during childhood, or
during pregnancy. However, levels increase with
induction of microsomal enzymes (eg, by ingesting
certain drugs, such as anticonvulsants, and particularly
in alcoholics), limiting its specificity.
Tests of Hepatic Synthetic Capacity
1. PT and INR
• PT may be expressed in time (sec) or, preferably, as a ratio of
measured PT vs control PT, termed the INR (see Hemostasis:
Testing). The INR is the more accurate laboratory reference with
which to monitor patients taking anticoagulants. The PT or INR is a
valuable measure of the liver's ability to synthesize vitamin K–
dependent clotting factors: factors II (prothrombin), V, VII, and X.
Changes can occur rapidly, because some of the involved clotting
factors have short biologic half-lives (eg, 6 h for factor VII).
Abnormalities indicate severe hepatocellular dysfunction, an
ominous sign in acute liver disease. In chronic liver disease, a rising
PT or INR indicates progression to advanced cirrhosis. The PT or
INR does not increase in mild hepatocellular dysfunction and is
often normal in cirrhosis.
• A prolonged PT and abnormal INR can result from other coagulation
disorders, such as a consumptive coagulopathy or a deficiency of
vitamin K. Fat malabsorption, including cholestasis, can cause
vitamin K deficiency. In chronic cholestasis, marked hepatocellular
dysfunction can be ruled out if vitamin K replacement (10 mg sc)
corrects the PT within 2 days.
2. Serum proteins
• Hepatocytes synthesize most serum proteins, including α- and
β-globulins, albumin, and clotting factors (but not γ-globulin, which is
produced by B lymphocytes). Hepatocytes also make proteins that
aid in the diagnosis of specific disorders: α1-antitrypsin (absent in
α1-antitrypsin deficiency), ceruloplasmin (reduced in Wilson's
disease), transferrin (saturated with iron in hemochromatosis), and
ferritin (greatly increased in hemochromatosis). Because levels of
these proteins increase in response to tissue damage (eg,
inflammation), elevations are not specific for liver disorders.
• Serum albumin commonly decreases in chronic liver disease
because of an increase in volume of distribution (eg, due to ascites),
a decrease in hepatic synthesis, or both. Values < 3 g/dL (< 30 g/L)
suggest advanced cirrhosis. Alcoholism, chronic inflammation, and
protein malnutrition also depress albumin synthesis.
Hypoalbuminemia can also result from excess albumin loss from the
kidney (ie, nephrotic syndrome), gut (eg, protein-losing
gastroenteropathies), and skin (eg, burns or exfoliative dermatitis).
Because albumin has a half-life of about 20 days, serum levels take
weeks to increase or decrease.
Other Laboratory Tests
• Ammonia is produced by colonic bacteria and metabolism of
glutamine. The liver metabolizes ammonia to urea. Ammonia levels
increase during portal-systemic (hepatic) encephalopathy. In
advanced disease, levels may also increase because of high-protein
meals, GI bleeding, hypokalemia or metabolic alkalosis, or
metabolic diseases involving urea metabolism. Because the degree
of elevation in ammonia correlates poorly with the severity of hepatic
encephalopathy, the ammonia level has limited accuracy in
2. Serum immunoglobulins
• In chronic liver disease, serum immunoglobulins often increase.
However, elevations are not specific and usually are not helpful
clinically. Levels increase slightly in acute hepatitis, moderately in
chronic active hepatitis, and markedly in autoimmune hepatitis. The
pattern of immunoglobulin increase adds little, although generally
IgM is quite high in primary biliary cirrhosis; IgA, in alcoholic liver
disease; and IgG, in chronic active hepatitis.
• Specific antibodies and antigens may be diagnostic (eg,
viral antigens and antibodies in hepatitis).
4. Antimitochondrial antibodies
• These heterogeneous antibodies are positive, usually in
high titers, in > 95% of patients with primary biliary
cirrhosis. They also are occasionally present in
autoimmune chronic active hepatitis, in drug-induced
hepatitis, and in other autoimmune disorders, such as
connective tissue disorders, myasthenia gravis,
autoimmune thyroiditis, Addison's disease, and
autoimmune hemolytic anemia. Antimitochondrial
antibodies can help determine the cause of cholestasis
because they are usually absent in extrahepatic biliary
obstruction and primary sclerosing cholangitis.
5. Other antibodies
• Other antibodies often present in autoimmune hepatitis include smooth muscle
antibodies against actin, antinuclear antibodies (ANA) providing a homogenous
(diffuse) fluorescence, and antibodies to liver/kidney microsome type 1 (anti-LKM1).
Isolated abnormalities of any of these antibodies are never diagnostic and do not
6. α-Fetoprotein (AFP)
• AFP, a glycoprotein normally synthesized by the yolk sac in the embryo and then the
fetal liver, is elevated in the newborn and hence the pregnant mother. AFP decreases
rapidly during the first year of life, reaching adult values (normally < 20 ng/mL) by the
age of 1 yr. Marked elevations (> 500 ng/mL) in a high-risk patient (eg, with a liver
mass detected on ultrasound) is diagnostic of primary hepatocellular carcinoma
(HCC), although not all HCCs produce AFP. Because small tumors can have low
levels of AFP, rising values suggest the presence of HCC. The degree of AFP
elevation, however, is not prognostic. In populations in which chronic hepatitis B
infection and HCC are common (eg, sub-Saharan Africans, ethnic Chinese), AFP
may reach levels as high as 100,000 ng/mL, whereas regions with lower frequencies
of the tumor have more modest levels (about 3000 ng/mL).
• A few other conditions (eg, embryonic teratocarcinomas, hepatoblastomas, some
hepatic metastases from GI tract cancers, some cholangiocarcinomas) cause levels ≥
500 ng/mL. In fulminant hepatitis, AFP can occasionally rise to 500 ng/mL; lesser
elevations occur in acute and chronic hepatitis. These levels probably reflect liver
regeneration. Thus, sensitivity and specificity of AFP vary according to population, but
values ≥ 20 ng/mL range from 39 to 64% and from 76 to 91%, respectively. Because
values ≤ 500 ng/mL are nonspecific, 500 ng/mL has been suggested as the
diagnostic cutoff level.
PROBLEMS in MANAGING
1. Changing lifestyle