131 - Patterns of Liver Injury 2 Flashcards
Conventions of nomenclature in chronic hepatitis
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- By convention, alcoholic liver disease and NASH are not classified as “chronic hepatitis” although these are forms of chronic liver disease
- By convention, chronic inflammatory liver disease in which the bile ducts are the major targets are not classified as “chronic hepatitis” (primary sclerosing cholangitis and primary biliary cirrhosis)
NASH
Non-alcoholic steatohepatitis
Clinical definition of chronic hepatitis
Persistence of liver injury with raised serum aminotransferase levels > 6 months
Most common causes of chronic hepatitis
Hep B and C
Proportion of hep C patients who develop cirrhosis
~20%
Most predominant inflammatory infiltrate in chronic and acute hepatitis
T lymphocytes
Pattern of injury in acute hepatitis
The hallmark feature of acute hepatitis is predominantly pan-lobular hepatocellular injury.
Pattern of injury in chronic hepatitis
Inflammation in the portal tracts and the periportal liver tissue
Associated with injury of the periportal hepatocytes (inflammatory cells are lymphocytes and plasma cells = mononuclear inflammation).
Interface hepatitis
Periportal hepatocellular injury accompanied by lymphoplasmacytic inflammation
Important determinant of the rate at which liver fibrosis occurs
Grade of chronic hepatitis (or degree of interface hepatitis)
Unusual feature of acute inflammation in the liver
Inflammatory infiltrate is predominantly T lymphocytes, not neutrophils
Lobular features in chronic hepatitis
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- Commonly present, but usually mild.
- Apoptotic bodies.
- Can be severe and then the lobular changes look like acute hepatitis (especially seen in autoimmune hepatitis).
How is chronic hepatitis with lobular disarray diagnosed?
Difficult for pathologists to distinguish between acute and chronic hepatitis unless the clinicians tells us or there is fibrosis.
Hallmark feature of chronic hepatitis
Interface hepatitis.
Inflammation/death of portal hepatocytes.
This is not specific to chronic hepatitis.
Fibrosis in acute vs chronic hepatitis
- Acute hepatitis – fibrosis is absent
* Chronic hepatitis – fibrosis may occur and can be progressive (resulting in cirrhosis)
Histology of chronic hepatitis
Plasma cells, T lymphocytes surrounding periportal hepatocytes.
Death of hepatocytes, mostly by apoptosis.
Cell types that can make fibrous tissue in chronic hepatitis
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1) Portal fibroblasts
2) Hepatic stellate cells
How do hepatic stellate cells contribute to fibrosis?
Cytokine induced hepatic stellate cell activation is central: proliferation and conversion into fibrogenic myofibroblasts.
Where do hepatic stellate cells sit?
In the space of Disse.
Normally quiescent.
Undergo fibrogenic myofibroblast proliferation.
Situation where you can get lobular changes with chronic hepatitis
If have a chronic hep B infection, and a superinfection with hep D (hep D can resemble acute hepatitis).
Stage of chronic hepatitis
Degree of fibrosis in patient. From 0 (normal) to 4 (cirrhosis)
How is fibrosis identified in liver biopsies?
Masson trichrome stain stains collagen blue, hepatocytes stained red.
Look for fibrous (collagenous) septa.
Fibrosis stage 1
Enlarged portal tracts, no septa
Fibrosis stage 2
Enlarged portal tracts with septa.
Not much linkage of septa between portal tracts.
Fibrosis stage 3
Enlarged portal tracts.
Linkage of septa between portal tracts.
Fibrosis stage 4
Cirrhosis.
Extensive fibrosis
Two basic functions of myofibroblasts
Contract, produce collagen
Pathogenesis of alcoholic liver disease 1 2 3 4 5
- Hepatocellular damage from acetaldehyde
- Oxidative stress
- Impaired carbohydrate and fat metabolism
- Stimulation of collagen synthesis by alcohol
- Genetic susceptibility
Histology of alcoholic liver disease
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- Fatty change – abnormal accumulation of lipid in hepatocytes (reversible and does not cause hepatocellular death or fibrosis)
- Alcoholic steatohepatitis (leads to hepatocellular death and fibrosis)
- Progressive fibrosis leading eventually to cirrhosis
Macrovesicular steatosis
Large fat vacuoles in periventricular hepatocytes.
Displace nuclei to edges of cells.
Steatosis vs steatohepatitis
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- Steatosis is the abnormal retention of lipids in cells
- Steatohepatitis is defined by the presence of fat + hepatocellular injury
- Hepatocellular injury is characterised by ballooning (swelling) and formation of Mallory-Denk bodies.
Mallory-Denk bodies 1 2 3 4
- Characteristic of ALD but not specific.
- Collapse of the hepatic cytoskeleton.
- Intermediate filaments (cytokeratin 8 and 18) and other proteins including ubiquitin.
- Attract neutrophils
Mortality of severe alcoholic steatohepatitis
If severe can cause “acute alcoholic hepatitis” which is a syndrome with features of jaundice, fever, hepatomegaly, markedly impaired liver function, and leucocytosis. This disease carries a 50% 30 day mortality.
Spectrum of severity of alcoholic steatohepatitis
From asymptomatic to extremely severe acute alcoholic hepatitis.
Features of steatohepatitis 1 2 3 4
1) Fat
2) Hepatocyte swelling (ballooning degeneration)
3) Mallory’s hyaline
4) Inflammation (often neutrophils)
Non-alcoholic fatty liver disease
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1) Major associations are obesity, metabolic syndrome and diabetes.
2) Histological spectrum the same as for alcoholic, although severe steatohepatitis with numerous Mallory bodies is much less common.
3) Distinction from alcoholic liver disease is essentially clinical rather than histologic (look pretty much the same pathologically)
Difference in demographic between steatohepatitis and non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease occurs in adults and children
Histology of alcoholic steatohepatitis 1 2 3 4
1) Inflammatory cells (mostly neutrophils)
2) Neutrophils cluster around, within hepatocytes
3) Some hepatocytes contain Mallory-Denk bodies
4) Many hepatocytes contain large fat vacuoles
Pattern of fibrosis in alcoholic liver disease
Collagen surrounds individual hepatocytes.
Collagen begins around central veins.
‘Chicken wire fibrosis’
Difference in patterns of fibrosis between chronic hepatitis and alcoholic liver disease
Chronic hepatitis fibrosis begins around portal triads.
Alcoholic liver disease fibrosis begins around central vein
Difference in severity between alcoholic steatohepatitis and non-alcoholic fatty liver disease
Steatohepatitis more severe normally
Signs of NAFLD
Steatosis with or without steaohepatitis and fibrosis.
Difference between alcoholic steatohepatitis and non-alcoholic fatty liver disease
Difference in causative factors (EG: alcohol), but otherwise the same
Natural history of NAFLD 1 2 3 4 5 6
1) Non-alcoholic fatty liver disaese
2) Over 80% have isolated fatty liver.
3) Rest go on to non-alcoholic steatohepatitis
4) ~11% over 15 years go on to cirrhosis
5) ~31% chance of decompensation over 8 years
6) ~7% go on to hepatocellular carcinoma over 6.5 years
7) Can progress from NASH straight to hepatocellular carcinoma
Painful arc of movement with rotator cuff injury
~60 - 120 degrees of shoulder abduction
Most common way in which shoulder is dislocated
Anterior and inferior.
Due to force applied to abducted and externally rotated arm
How can posterior shoulder dislocations occur?
Epileptic fit, electric shock.
Less common than anterior dislocation.
Possible outcome of shoulder dislocation
Axillary nerve (from the posterior cord of the brachial plexus) is in quadrangular space.
At risk of inferior dislocation.
