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Clinical Aspects of Liver Diseases 21 Clinical and Morphological Principles

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Clinical Aspects of Liver Diseases 21 Clinical and Morphological Principles Clinical Aspects of Liver Diseases 21 Clinical and morphological principles Page: 1 Attempt at a systematic approach 392 1.1 Difficulties of systematization 392 1.2 Need for systematization 392 2 Clinical forms of liver disease 392 2.1 Primary and secondary liver diseases 392 2.2 Diffuse and focal liver diseases 393 2.3 Acute and chronic liver diseases 393 2.4 Aims of liver diagnostics 394 2.4.1 Rational and expedient diagnostics 394 2.4.2 Diagnostic and clinical issues 394 3 Basic morphological processes of the liver 394 3.1 Cellular adaptation 394 3.1.1 Membrane hyperplasia 394 3.1.2 Hyaline drops 395 3.1.3 Lipofuscinosis 395 3.2 Hepatocellular degeneration 395 3.2.1 Cellular changes 395 3.2.2 Nuclear changes 396 3.2.3 Cellular metabolic disorders 396 3.3 Mesenchymal reactions 397 3.3.1 Peliosis hepatis 398 3.3.2 Granulomas 398 3.4 Cell death and necrosis 400 3.4.1 Programmed cell death 400 3.4.2 Provoked cell death 400 3.4.3 Cell necrosis 400 3.5 Regeneration 402 3.6 Fibrogenesis 403 4 Hepatitis and hepatosis 404 4.1 Hepatitis 404 4.2 Hepatosis 404 5 Fibrosis and cirrhosis 405 5.1 Fibrosis 405 5.1.1 Scarred liver 405 5.1.2 Portal/periportal fibrosis 406 5.1.3 Perisinusoidal fibrosis 406 5.1.4 Perivenous fibrosis 407 5.1.5 Septal fibrosis 407 5.1.6 Liver collapse fibrosis 407 5.2 Cirrhosis 407 5.2.1 Basic criteria 407 5.2.2 Systematic approach 408 5.2.3 Morphological diagnosis 408 6 Liver tumours 409 6.1 Benign tumours 409 6.2 Malignant tumours 409 ț References (1Ϫ55) 410 (Figures 21.1Ϫ21.16; tables 21.1Ϫ21.5) 391 21 Clinical and morphological principles 1 Attempt at a systematic approach 2 Clinical forms of liver disease Any attempt at setting up a systematic approach to 2.1 Primary and secondary liver diseases liver disease has to incorporate the correlation All liver diseases can be classified into two groups with between morphological and functional changes. At the diverse clinical, therapeutic and prognostic relevance: same time, such an approach has to take account of aetiological and pathogenic factors. • However, any classification made is provisional by its very nature, 1. Primary liver diseases since there is no uniform standpoint in this respect, 2. Secondary liver diseases and advances in medical knowledge can alter any such classification. (see references 2, 4, 9, 20) Primary liver diseases The liver is primarily affected, and the involvement of 1.1 Difficulties of systematization the liver in the disease is paramount. A typical example would be acute viral hepatitis resulting from primary ᭤ It must be borne in mind that only relatively minor hepatotropic viruses. (s. tab. 5.16) morphological changes might be evident in functional liver insufficiency. • Moreover, apparently normal It is not possible to make a reliable clinical differentiation hepatic functions may also prevail despite pronounced between the primary hepatotropic types of hepatitis; there are, morphological changes in the liver. however, certain distinctive hints derived from histology or immunohistology (e.g. HAV, HBV or HCV infection). Modern ᭤ Further consideration has to be given to the fact that methods of serology and immunology render precise differenti- different pathogenic factors may also trigger similar or ation possible. • Acute viral hepatitis does not exhibit any isol- ated specific morphological findings; it is the sum of the individ- even identical morphological changes as well as iden- ual phenomena which results in the diagnosis. (s. tab. 22.1) tical biochemical reactions. hepatopathy ergmann Ϫ The term (G. v. B , 1936) (s. p. 74) which Secondary liver diseases cannot be defined precisely Ϫ must be viewed as a noble attempt to classify all liver diseases with their respective The liver is secondarily affected by a systemic disease morphological and functional changes as one single entity. It should be noted that in those days there was little chance of or shows a coreaction to extrahepatic organ processes. making a detailed diagnosis of a liver disease during the Involvement of the liver in the disease is not obvious. • patient’s life. Occasionally, the aetiology of the underlying disease can be diagnosed from liver biopsy material by means of characteristic morphological substrates or by the detec- 1.2 Need for systematization tion of pathogens. • In the majority of cases, these find- ings are ambiguous and are thus grouped together alk As early as 1947, H. K strongly emphasized the need under the generic term “non-specific reactive hepatitis”. to systematize liver disease in line with morphological aspects. Initially, his approach was founded on laparo- scopic criteria, i.e. size, colour and superficial structures Non-specific reactive hepatitis of the liver. • Pathohistological examination, however, is Concomitant hepatic lesions can occur as a conse- indispensable in the classification of most liver diseases. quence of a number of viral, bacterial, parasitic and Liver diagnostics is based on four essential pillars, of mycotic infections as well as due to toxic effects. Owing which histology is still the most important and, in cases to their ambiguity, however, these lesions do not allow of doubt, the decisive factor in determining the diagno- closer aetiological specification. • Therefore, the term sis. (s. pp 75, 76) “non-specific reactive hepatitis” is not actually considered Even though it is still difficult today to systematize liver to be a pathological entity in its own right. diseases, any such attempt can be of help, providing it From the pathohistological point of view, the findings are (1.) takes due account of the aetiology, the clinical picture degenerative liver cell changes with single focal liver cell necrosis, and the morphological changes. This facilitates an over- (2.) concomitant reaction of the Kupffer cells and formation of view of the different liver diseases, including their vari- Kupffer cell nodules with a generalized reaction of the mono- nuclear phagocytosis system, usually inside dilated sinusoids, (3.) ants and complications, and makes for a better under- histiocytic and portal round-cell infiltration, and (4.) cholangitic standing of certain individual forms of disease and the reaction with sparse infiltrations of neutrophilic granulocytes way in which the various forms are interrelated. around small bile ducts. (s. fig. 21.1) 392 Clinical and morphological principles portal lesions of different degrees of diffusion are wit- nessed (e.g. in bacterial cholangitis), or there are intra- parenchymal diffusely localized changes (e.g. in cases of listeriosis). • In diffuse liver diseases, the bioptic histo- logical finding is representative in 80Ϫ100% of cases. (s. pp 157, 160) Focal liver diseases: In contrast, it is frequently impos- sible to detect localized findings in the biopsy material, which is 1.5Ϫ2 cm in length and generally comprises up to 20 portal fields, especially since percutaneous biopsy can only reach a certain area of the right liver lobe. Consequently, “negative” biopsy findings do not necessar- ily rule out the presence of localized hepatic changes!(s. Fig. 21.1: Non-specific reactive hepatitis in sepsis due to cervical p. 160) • Larger focal lesions are detected by imaging lymph node abscess: sparse single cell necrosis and periportal procedures and can be assessed by guided biopsy, fine inflammation needle biopsy or laparoscopy. ᭤ The pluriaetiological spectrum involved in this condi- tion already suggests the problematic nature of the gen- 2.3 Acute and chronic liver diseases erally accepted term non-specific reactive hepatitis. • The confusion in terminology is rendered all the more With regard to the time period involved in the course of complex because the diagnosis of a non-specific reaction a liver disease, distinction has to be made between two does not necessarily justify using the rather implicative further groups, excluding the prodromal stage and the term “hepatitis”. • Moreover, an individual who is healing process (s. tab. 4.1) (s. p. 75): affected by non-specific reactive hepatitis cannot really be referred to as a “liver patient”. We are also familiar 1. Acute liver diseases with inflammatory secondary phenomena, such as leu- In the individual case of acute liver disease, it is cocyte cellulations in alcoholic hepatitis or mesenchy- necessary to differentiate between peracute (i.e. ful- mal reactions due to drug abuse. In these cases, it can be minant), subacute-necrotic and protracted courses. equally problematic to apply terms like “non-specific”, 2. Chronic liver diseases “hepatitis” or “liver disease”. Chronic liver diseases may show protracted This is why the pathologist will deliver a purely mor- (subchronic), “persistent” or “aggressive” courses. phological description depending on the facts of the The new classification of chronic hepatitis empha- case, whereas it will be the task of the clinician to sizes its respective aetiology while at the same time categorize these “non-specific” inflammatory second- categorizing the degree of inflammatory and ary phenomena with respect to their aetiology and necrotic activity as well as any fibrosis and add- clinical significance. itional changes in the hepatic architecture. Chronic liver disease is characterized by inflammatory 2.2 Diffuse and focal liver diseases infiltrates and/or degenerative changes which have per- sisted for 6 to 12 months or longer; its prognosis is In concordance with the morphological pattern associ- dubious. Chronic liver disease is thus defined by the ated with the liver condition, two further groups of dis- following triad: eases may be distinguished (s. tab. 4.1!): 1. Prolonged course of disease (>6 months) 1. Diffuse liver diseases 2. Inflammatory and/or degenerative morphological The disease of the liver is largely diffuse; its occur- findings rence can be either primary or secondary. 3. Dubious prognosis 2. Focal liver diseases Ϫ no general healing tendency The liver only exhibits focal processes of disease, Ϫ tendency towards progression which may be primary or secondary and of non- Ϫ occurrence of complications specific or specific genesis.
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