Hepatobiliary system

Dr Rehma Dar
Assistant Professor Pathology
 Crigler Najjar Syndrome
 It is a syndrome of chronic nonhemolytic unconjugated
hyperbilirubinemia.
 Like gilbert syndrome it is inherited disorder of bilirubin

metabolism resulting from a molecular defect within gene

involved in bilirubin conjugation.
 It is divided into two types.
 Type I: where there is complete absence of bilirubin

conjugation.
 Type II: where there is partial absence of bilirubin

conjugation.
 Dubin Johnson Syndrome
 This is autosomal recessive disorder caused by deficiency of
transporter protein (MDR2/cMOAT).
 Removal of conjugated bilirubin from the liver cell and the

excretion into the bile are defective , this condition is

harmless because excretion of conjugated bilirubin is
defective , but not of bile salts.
 Conjugated bilirubin circulates bound to albumin, this is

referrd to as delta bilirubin.

 On liver biopsy dark stained granules appear.(thought to be

pigmented lysosomes)
 Rotor Syndrome
 Just like Dubin Johnson syndrome but the defect is unknown.
 It is hypothesized due to reduction in conc. of intracellular

binding proteins such as ligandin.

 Unlike Dubin Johnson syndrome no pigmentation on liver

biopsy.
 Physiological Jaundice
 Results from the deficiency of enzyme glucuronyl transferase;
one of the last liver functions to be activated in the pre natal
life since bilirubin processing is handled by the mother of the
fetus.
 Deficiency leads to build up of un conjugated bilirubin , when

this type of bilirubin builds up in neonate, it cannot be

processed and deposited in nuclei of brain and degenerate
nerve cells, causing kernicterus.
 Normal babies show jaundice bw days 2 and 8 of life.
 Jaundice on the first day of life is invariably pathological.
 Post Hepatic Jaundice
 Post hepatic jaundice results from biliary obstruction disease
(gallstones or tumor) that prevents the flow of Conjugated
bilirubin into the bile canaliculi.
 As bile is not being brought to the intestine , stool looses its

normal pigmentation and become clay colored

 Cirrhosis

 It is the end result of many inflammatory and metabolic diseases

involving liver.
 Fibrous scar is formed and it distorts the hepatic architecture and

form regenerating nodules.

 Nodules disrupt the hepatocytes blood supply sometime

increasing the pressure in portal vein causing portal hypertension.

 Blood may be shunted from the portal vein to hepatic vein

bypassing the liver and the liver functions are distorted.

 Symptoms of cirrhosis include fatigue, nausea, unintended weight

loss, jaundice, swelling in the legs, bleeding from GIT and intense
itching
 Portal hypertension and impaired lymphatic drainage lead to
accumulation of fluid in the peritoneal cavity (ascites).
 Liver damage cause accumulation of toxins like ammonia which
cause hepatic encephalopathy.
 Hypotension and hypovolemia occur due to loss of fluid in ascites.
 Renal insufficiency due to impaired renal perfusion causing
oliguria, increase plasma creatinine level, increase in ammonia
level and causing hepatorenal syndrome
 Impaired hepatic gluconeogenesis may cause hypoglycemia.
 Pro collagen N-terminal peptide (P3NP) is a marker of fibrosis and
may reduce the need of biopsy
 Causes of cirrhosis
 Hepatitis B,C
 Alcoholic liver disease.
 Non alcoholic steatotic hepatitis or fatty liver(NAFLD)
 Hemochromatosis

 a Antitrypsin deficiency
1
 Wilsons disease
 Galactosaemia
 Reye’s syndrome
 Some drugs like Methotrexate cause fibrosis
 Hepatitis
 Is defined as injury to the liver characterized by the presence
of inflammation in the liver tissue.
 There are multiple causes of inflammation like infectious

causes e.g bacterial viral and parasitic infections as well as

non infectious causes such as radiation, drugs, chemicals,
autoimmune diseases and toxins.
 Viral infections account for the majority of hepatitis major

subtypes are HAV, HBV, HCV, HEV,HDV.

 Symptoms of acute disease are jaundice, dark urine, fatigue,

nausea, vomiting, and abdominal pain

 HAV
 Also known as infectious hepatitis and most common form of
viral hepatitis worldwide.
 Cause by non enveloped RNA virus of Picornavirus family.
 Mode of transmission is fecal-oral route.
 Symptoms of HAV are fever, malaise, anorexia, nausea,
abdominal pain, dark urine, and jaundice…these are self limiting
 IgM antibodies to HAV are detectable at or prior to the onset of
clinical illness and decline within 3 to 6 months.
 IgG antibodies to HAV develop soon after IgM.
 According to FDA/CDC recommendations that all children will
receive HAV vaccine as early as age of 12 to 23 months
 HBV
 Is a long term hepatitis and cause both acute and chronic hepatitis.
 Mode of transmission is parenteral, perinatal, and sexual.
 It is detected in all body fluids e.g saliva, blood, feces, urine,

semen, tears and breast milk.

 HBV is a DNA virus of Hepadnaviridae family.
 Liver is the primary site of HBV replication,,, the core of the antigen

is synthesized in the nuclei of the hepatocytes and then passed

into the cytoplasm.
 An antigen present in the core of virus HBcAg and a surface

antigen HBsAg and another antigen is HBeAg

 Hepatitis B surface Antigen
 HBsAg is a useful serologic marker in patients before the
onset of clinical symptoms because it is present during
prodrome of acute HBV.
 HBsAg is not infectious but its presence in the serum indicate

presence of the hepatitis virus.

 HBsAg can be detected during the first 3 to 5 weeks after

infection in newly infected patients.

 The average time from exposure to detection of HBsAg is 30

days (range 6 to 60 days).

 Anti HBs antibody is suggestive of past infections.
 Hepatitis B Core Antigen
 This antigen is present only in the nuclei of hepatocytes
during an acute infection of HBV not in plasma
 The antibody to core antigen anti HBc develop earlier in the

course of infection than the antibody to surface antigen.

 Test for the presence of IgM antibody to HBcAg is a specific

for acute HBV infection and persists in chronic infection.

 Another marker for acute infection is a viral DNA dependent

DNA polymerase that is closely associated with the presence

of core antigen.
 Hepatitis B e antigen
 It is detected in serum of the acute and chronic HBV infected
patients.
 The e antigen is detected in the serum only when surface antigen
is present.
 Presence of e antigen appears to correlate well with number of
infectious virus particles and the degree of infectivity of HBsAg
positive sera.
 The presence of both HBsAg and HBeAg is unfavorable prognostic
sign and predicts a severe course and chronic liver disease.
 Presence of anti HBe antibody in carriers indicate low infectivity.
 The serological markers used to differentiate among acute,
resolving, and chronic infections are HBsAg, anti-HBc and
anti-HBs.
 Person who is recovering from HBV infection is positive for

both anti-HBs and anti-HBc .

 Person who received vaccine against HBV will be positive

for anti-HBs only.

 Person who is chronically ill will not developed anti-HBs

resulting in persistence HBsAg as well as anti-HBc in

patient serum for life.