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Hepatobiliary disease: jaundice
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- By Omer Aziz, Mark Thursz
- Omer Aziz, Sanjay Purkayastha, Paraskevas Paraskeva
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- Book:
- Hospital Surgery
- Published online:
- 06 July 2010
- Print publication:
- 16 February 2009, pp 386-389
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Summary
Definition
Jaundice (icterus) refers to the yellow pigmentation of skin, sclerae and mucosae due to raised plasma bilirubin (>35 mmol/l).
Pathophysiology
Bilirubin is a normal breakdown product of haemoglobin produced in the reticuloendothelial system following destruction of old red blood cells. The resulting unconjugated bilirubin is insoluble and carried to the liver bound to albumin. In the liver, the enzyme uridine diphosphateglucuronyl transferase conjugates this with glucuronic acid into water soluble conjugated bilirubin. This is then secreted into bile canaliculi, and ultimately enters the duodenum. Bilirubin is converted into urobilinogen in the terminal ileum and colon, of which up to 20% is reabsorbed into the portal circulation. This is then either re-excreted back into the bile or excreted by the kidneys into the urine. Increased production, failure of uptake, or conjugation all result in unconjugated bilirubinaemia and jaundice.
Classification
Pre-hepatic: excess unconjugated bilirubin production (from red blood cells) exhausts the liver's capacity to conjugate e.g. haemolytic anaemias (hereditary spherocytosis, sickle-cell disease, hypersplenism).
Hepatic: unconjugated hyperbilirubinaemia due to inborn failure of conjugation (Crigler Najjar syndrome) and inborn failure of bilirubin uptake (Gilbert's syndrome). Hepatocellular causes include cirrhosis, viruses (hepatitis A, B, C, E; Epstein-Barr), autoimmune diseases, drugs (paracetamol, halothane).
Post-hepatic: obstructive conjugated hyperbilirubinaemia may be due to intrahepatic obstruction (primary biliary cirrhosis, some hepatocellular disease) or extrahepatic obstruction (gallstones, carcinoma of the head of pancreas, cholangiocarcinoma, portal lymphadenopathy, and sclerosing cholangitis).
Symptoms
Pain, typically RUQ biliary colic, occurs when there is choledocholithiasis. Dull persistent pain may be present with acute hepatitis or bulky tumours in the liver.
Hepatobiliary disease: liver tumours
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- By Omer Aziz, Mark Thursz
- Omer Aziz, Sanjay Purkayastha, Paraskevas Paraskeva
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- Book:
- Hospital Surgery
- Published online:
- 06 July 2010
- Print publication:
- 16 February 2009, pp 399-403
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- Chapter
- Export citation
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Summary
Liver tumours may present with clinical symptoms but are increasingly presenting at a pre-clinical stage due to surveillance in patients with cirrhosis. This has led to a significant change in the ‘natural history’ of liver tumours and provides an opportunity to alter prognosis in what has been a uniformly dismal diagnosis.
Definition and classification
Liver tumours may be benign or malignant, primary or secondary. The two ‘common’ primary tumours are hepatocellular carcinoma (HCC) or cholangiocarcinoma. Rarer tumours include haemangiosarcoma and hepatoblastoma. Secondary tumours are the most common cause of liver malignancy and may arise from any organ but most commonly from the stomach, colon, pancreas, breast and ovary. Benign tumours of the liver include haemangiomas, focal nodular hyperplasia and hepatic adenomas.
Incidence
In patients with cirrhosis and chronic viral hepatitis HCC occurs at a rate of 1–4% per year. Incidence is higher in males and those over the age of 40. HCC is a common malignancy in China, South-East Asia and Sub-Saharan Africa. The incidence of HCC is increasing in Europe and the USA due to hepatitis C virus infection. The incidence of cholangiocarcinoma is increasing rapidly in developed countries.
Aetiology
Almost all HCCs arise from a background of cirrhosis. All causes of cirrhosis may cause HCC but viral hepatitis, haemochromatosis and alcohol are the most important aetiologies. Exposure to aflatoxin increases the risk of HCC particularly in populations where hepatitis B virus infection is common. In developed countries the risk factors for cholangiocarcinoma are primary sclerosing cholangitis and inflammatory bowel disease. In tropical countries the tumour is associated with chronic liver fluke infection.
4 - Genetic diversity in the major histocompatibility complex and the immune response to infectious diseases
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- By Leland J. Yee, Imperial College, Faculty of Medicine at St. Mary's Hospital, London, United Kingdom; London School of Hygiene and Tropical Medicine, London, United Kingdom, Mark R. Thursz, Imperial College, Faculty of Medicine at St. Mary's Hospital, London, United Kingdom
- Edited by Richard Bellamy, Kintampo Health Research Centre, Ghana
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- Book:
- Susceptibility to Infectious Diseases
- Published online:
- 14 August 2009
- Print publication:
- 22 December 2003, pp 77-116
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Summary
INTRODUCTION: THE NATURAL HISTORY OF INFECTIOUS DISEASES
The natural history of many infectious diseases is characterised by a broad range of clinical outcomes. For example, infection with bacterial agents such as Mycobacterium tuberculosis may be asymptomatic in some individuals; in others, clinical manifestations of disseminated tuberculosis may develop. Infection with viral agents such as the hepatitis B virus (HBV) may result in spontaneous clearance in some individuals, whereas in others, chronic infection may develop. Among those with chronic HBV infection, disease progression proceeds at varied rates, with some individuals developing liver cirrhosis and others only mild amounts of liver fibrosis despite similar durations of infection. Protozoan organisms, such as Plasmodium, are similarly characterised by a broad spectrum of outcomes. Some individuals may suffer from a severe course of malaria with cerebral manifestations or malarial anaemia, whereas others may naturally avoid such severe sequelae.
What factors influence this broad clinical spectrum in so many different diseases? Infectious disease natural history is affected by four main factors. First, pathogen virulence may determine outcome. For example, some strains of influenza virus cause only mild flu symptoms, whereas others have resulted in a global pandemic, such as the strain that killed millions of individuals across the world in 1918. Second, external modulators, or environmental factors, may affect outcome. For example, some strains of influenza virus cause only mild flu symptoms, whereas others have resulted in a global pandemic, such as the strain that killed millions of individuals across the world in 1918.