Page 456 - Concise Pathology for Exam Preparation ( PDFDrive )

15 Diseases of the Hepatobiliary System and Pancreas 441

• Low serum ceruloplasmin levels (,20 mg/dL)
• High urinary copper excretion (.100 mcg/day; most specific test)
• High hepatic copper content (.250 mcg/g of dry tissue)
• Serum copper levels can be raised, low or normal so are of no diagnostic use

Q. Write briefly on the aetiology and clinicopathological of a-1
antitrypsin deficiency.

Ans. The following are the salient features of α-1 antitrypsin deficiency:
• a-1 antitrypsin is an a-1 globulin produced by the liver. It comprises 90% of the a-1
globulins.
• It is a serine protease inhibitor (Pi), which inhibits the protease enzymes, particularly
neutrophil elastase, cathepsin G and proteinase 3, to prevent breakdown of elastin and
collagen by them.
• It is encoded by a gene located on chromosome 14, which is extremely polymorphic
and more than 70 forms have been identified. The most commonly encountered forms
of a1-antitrypsin are
• PiM (medium)
• PiS (slow)
• PiZ (very slow)
• PiMM is the normal phenotype, while the phenotype PiZZ gives low a-1 antitrypsin
concentrations (less than 10% of normal levels).
• a-1 antitrypsin deficiency may lead to liver and pulmonary diseases (cirrhosis and
emphysema, respectively).

Clinicopathology
• In neonates, a-1-antitrypsin deficiency produces hepatitis and cholestatic jaundice.
• In adults, the patient may present with any of the following:
• Chronic hepatitis
• Cirrhosis
• Hepatocellular carcinoma (in 2–3% patients with a PiZZ phenotype)
• Emphysema
• Most cases of a-1-antitrypsin deficiency are characterized by presence of intrahepatic
round-to-oval PAS-positive cytoplasmic globular inclusions.

Q. Name the two main autoimmune disorders of intrahepatic bile
ducts. Write briefly on the clinicopathological features of both.
Ans. The two main autoimmune disorders of intrahepatic bile ducts are
1. Primary biliary cirrhosis (PBC)
2. Primary sclerosing cholangitis (PSC)

PBC

Salient Features
• Shows nonsuppurative destruction of small- and medium-sized intrahepatic bile ducts
followed by cirrhosis.
• Large intrahepatic ducts and the extrahepatic biliary structures are not involved.
• Occurs predominantly in women between 30 and 70 years, all of who do not present
with cirrhosis, indicating that the name is a misnomer.
• It often occurs in association with Sjögren syndrome, scleroderma and thyroid
disease.
• Ninety-five percent are AMA-positive, 20% ANA-positive and 60% ANCA-positive.

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