DDx SGD Session 2
may be intermittent, all these diseases present with
Impression
1. CHRONIC OBSTRUCTIVE PANCREATITIS
2. ALCOHOLIC FATTY LIVER DISEASE
3. CHOLEDOCHOLITHIASIS
CHRONIC OBSTRUCTIVE PANCREATITIS
Chronic pancreatitis is defined as prolonged infammation
of the pancreas associated with irreversible destruction
of exocrine parenchyma, fibrosis, and, in the late stages,
the destruction of endocrine parenchyma.
Long-standing obstruction of the pancreatic duct by
calculi or neoplasms
Chronic pancreatitis may present in many different ways.
It may follow repeated bouts of acute pancreatitis. There
may be repeated attacks of mild to moderately severe
abdominal pain, or persistent abdominal and back pain.
Attacks may be precipitated by alcohol abuse, overeating
(which increases demand on the pancreas), or the use of
opiates and other drugs that increase the tone of the
sphincter of Oddi. In other patients the disease may be
entirely silent until pancreatic insuf ciency and diabetes
mellitus develop due to destruction of the exocrine and
endocrine pancreas.
The diagnosis of chronic pancreatitis requires a high
degree of suspicion. During an attack of abdominal pain
there may be mild fever and mild-to-moderate elevations
of serum amylase. When the disease has been present
for a long time, however, the dropout of acinar cells may
be so great as to eliminate these diagnostic clues.
Gallstone-induced obstruction may be evident as
jaundice or elevations in serum levels of alkaline
phosphatase. A very helpful finding is visualization of
calci cations within the pancreas by computed
tomography and ultrasonography. Weight loss and
edema due to low albumin from malabsorption caused by
pancreatic exocrine insuffciency also support the
diagnosis.
OBSTRUCTIVE JAUNDICE
When jaundice is due to an obstruction in the flow of bile:
(1) The patient's stools are pale
(2) His urine is dark, and contains little or no urobilinogen
(3) His skin itches.
These features are most marked in complete obstruction,
as when carcinoma blocks the common duct. Stones
typically cause an intermittent obstruction, and a less
characteristic picture.
Causes
1) Secondary carcinoma of the liver.
2) A secondary tumour in the porta hepatis, usually from
a primary in the stomach.
3) Carcinoma of the head of the pancreas.
4) Gall-stones.
5) Hepatoma; although this is a common disease,
presentation as obstructive jaundice is unusual.
6) Carcinoma of the extrahepatic bile-ducts.
7) Carcinoma of the gall-bladder.
With the exception of gallstones, in which the jaundice
progressively deepening jaundice over weeks or months,
usually without the fever and rigors of cholangitis that so
often complicate the jaundice of gallstones. The patient
may have no pain, but if he has, it is usually not severe; it
is deep, penetrating, and present most of the
time[md]quite unlike the agonizing episodic biliary colic
that gallstones cause. He is anorexic, and nauseated,
and may lose so much weight that he becomes severely
emaciated, with no other symptoms than jaundice.
Hepatitis A
Hepatitis A is a vaccine-preventable, communicable
disease of the liver caused by the hepatitis A virus (HAV).
It is usually transmitted person-to-person through the
fecal-oral route or consumption of contaminated food or
water. Hepatitis A is a self-limited disease that does not
result in chronic infection. Most adults with hepatitis A
have symptoms, including fatigue, low appetite,
stomach pain, nausea, and jaundice, that usually
resolve within 2 months of infection; most children
less than 6 years of age do not have symptoms or have
an unrecognized infection. Antibodies produced in
response to hepatitis A infection last for life and protect
against reinfection. The best way to prevent hepatitis A
infection is to get vaccinated.
Hepatitis B
Hepatitis B is a liver infection caused by the Hepatitis B
virus (HBV). Hepatitis B is transmitted when blood,
semen, or another body fluid from a person infected with
the Hepatitis B virus enters the body of someone who is
not infected. This can happen through sexual contact;
sharing needles, syringes, or other drug-injection
equipment; or from mother to baby at birth. For some
people, hepatitis B is an acute, or short-term, illness but
for others, it can become a long-term, chronic infection.
Risk for chronic infection is related to age at infection:
approximately 90% of infected infants become
chronically infected, compared with 2%–6% of adults.
Chronic Hepatitis B can lead to serious health issues, like
cirrhosis or liver cancer. The best way to prevent
Hepatitis B is by getting vaccinated.
Alchoholic Fatty Liver Disease
Hepatic steatosis may cause hepatomegaly, with mild
elevation of serum bilirubin and alkaline phosphatase
levels. Severe hepatic dysfunction is unusual. Alcohol
withdrawal and the provision of an adequate diet are suf
cient treatment. In contrast, alcoholic hepatitis tends to
appear acutely, usually following a bout of heavy
drinking. Symptoms and laboratory manifestations may
range from minimal to those that mimic acute liver failure.
Between these two extremes are the nonspeci c
symptoms of malaise, anorexia, weight loss, upper
abdominal discomfort, and tender hepatomegaly, and the
laboratory ndings of hyperbilirubinemia, elevated serum
aminotransferases and alkaline phosphatase, and often a
neutrophilic leukocytosis. In contrast to other chronic liver
diseases where serum ALT tends to be higher than
serum AST, serum AST levels tend to be higher than
serum ALT levels in a 2:1 ratio or higher in alcoholic liver
disease. This can be helpful in differential diagnosis of
chronic liver injury when adequate history is not BILIRUBIN FORMATION AND EXCRETION
available. An acute cholestatic syndrome may appear,
resembling large bile duct obstruction.

GALLSTONES

Gallstones may be present for decades before symptoms

develop, and 70% to 80% of patients remain
asymptomatic throughout their lives. Asymptomatic
individuals probably convert to being symptomatic at a
rate of up to 4% per year, although the risk diminishes
with time. Prominent among symptoms is biliary colic that
may be excruciating. Despite its characterization as
“colic” it is usually constant and not colicky. It usually
follows a fatty meal which forces a stone against the gall
bladder outlet leading to increased pressure in the gall
bladder causing pain. Pain is localized to right upper
quadrant or epigas- trium that may radiate to the right
shoulder or the back. In ammation of the gallbladder
(cholecystitis, discussed later), in association with
stones, also generates pain. More severe complications
include empyema, perforation, stulas, in ammation of the
biliary tree (cholangitis), obstructive cho- lestasis and
pancreatitis. The larger the calculi, the less likely they are
to enter the cystic or common ducts to produce
obstruction; it is the very small stones, or “gravel,” that
are more dangerous. Occasionally a large stone may
erode directly into an adjacent loop of small bowel,
generating intestinal obstruction (“gallstone ileus” or
Bouveret syn- drome). Lastly (but not least), gallstones
are associated with an increased risk of gallbladder
carcinoma, discussed later.

CHOLEDOLITHIASIS

Choledocholithiasis is the presence of stones in bile

ducts; the stones can form in the gallbladder or in the
ducts themselves. These stones cause biliary colic,
biliary obstruction, gallstone pancreatitis, or cholangitis
(bile duct infection and inflammation). Cholangitis, in turn,
can lead to strictures, stasis, and choledocholithiasis.

Bile duct stones may pass into the duodenum

asymptomatically. Biliary colic occurs when the ducts
become partially obstructed. More complete obstruction
causes duct dilation, jaundice, and, eventually,
cholangitis (a bacterial infection). Stones that obstruct the
ampulla of Vater can cause gallstone pancreatitis.
CHOLESTASIS (Robbins)
Cholestasis is caused by impaired bile formation and bile
ow that gives rise to accumulation of bile pigment in the
hepatic parenchyma. It can be caused by extrahepatic or
intrahepatic obstruction of bile channels, or by defects in
hepatocyte bile secretion.
Patients may have jaundice, pruritus, skin xanthomas or
symptoms related to intestinal malabsorption, including
nutritional de ciencies of the fat-soluble vitamins A, D, or
K. A characteristic laboratory nding is elevated serum
alkaline phosphatase and γ-glutamyl transpeptidase
(GGT), enzymes present on the apical (canalicular)
membranes of hepatocytes and bile duct epithelial cells.
Bilirubin is the end product of heme degradation (Fig.
18-27). The majority of daily production (0.2 to 0.3 gm,
85%) is derived from breakdown of senescent red cells
by the mononuclear phagocytic system, especially in the
spleen, liver, and bone marrow. Most of the remainder
(15%) of bilirubin is derived from the turnover of hepatic
heme or hemoproteins (e.g., the P-450 cytochromes) and
from premature destruction of red cell precursors in the
bone marrow (Chapter 13). Whatever the source,
intracellular heme oxygenase converts heme to biliverdin
(step 1 in Fig. 18-27), which is immediately reduced to
bili- rubin by biliverdin reductase. Bilirubin thus formed
outside the liver is released and bound to serum albumin
(step 2). Albumin binding is necessary to transport biliru-
bin because bilirubin is virtually insoluble in aqueous
solu- tions at physiologic pH. Hepatic processing of
bilirubin involves carrier-mediated uptake at the
sinusoidal mem- brane (step 3), conjugation with one or
two molecules of glucuronic acid by bilirubin uridine
diphosphate (UDP) glucuronyl transferase (UGT1A1,
step 4) in the endoplas- mic reticulum, and excretion of
the water-soluble, nontoxic bilirubin glucuronides into
bile. Most bilirubin glucuro- nides are deconjugated in the
gut lumen by bacterial β-glucuronidases and degraded to
colorless urobilinogens (step 5). The urobilinogens and
the residue of intact pigment are largely excreted in
feces. Approximately 20% of the urobilinogens formed
are reabsorbed in the ileum and colon, returned to the
liver, and reexcreted into bile. A small amount of
reabsorbed urobilinogen is excreted in the urine.
Two thirds of the organic materials in bile are bile salts,
which are formed by the conjugation of bile acids with
taurine or glycine. Bile acids, the major catabolic
products of cholesterol, are a family of water-soluble
sterols with carboxylated side chains. The primary
human bile acids are cholic acid and chenodeoxycholic
acid. Bile acids in bile salts are highly effective
detergents. Their primary physiologic role is to solubilize
water-insoluble lipids secreted by hepatocytes into bile,
and also to solubilize dietary lipids in the gut lumen.
Ninety- ve percent of secreted bile acids, conjugated or
unconjugated, are reab- sorbed from the gut lumen and
recirculate to the liver (enterohepatic circulation), thus
helping to maintain a large endogenous pool of bile acids
for digestive and excretory purposes.