8 Flashcards
CIRRHOSIS Definition
Definition:
- Cirrhosis is a
(1) chronic diffuse irreversible liver disease characterized (2)- Progressive diffuse necrosis of liver cells, (? + ?)
(3)- Formation of regeneration nodules surrounded by
(4) bands of fibrosis, nodules of regenerating hepatocytes
(5)- Loss of the normal hepatic lobular architecture.
Gross Picture:
Of CIRRHOSIS
1-Size: Commonly reduced (shrunken). May be enlarged (as in biliary cirrhosis
2- Consistency is firm due to fibrosis.
3- Outer surface & Cut section are Nodular - According to size of regeneration nodules, (smaller or larger than 3 mm), cirrhosis is classified into:
a) Micronodular cirrhosis:
Regeneration nodules are less than 3 mm in diameter.
b) Macronodular cirrhosis:
Regeneration nodules are more than 3 mm, up to 1-6 cm
c) Mixed micronodular and macronodular cirrhosis:
4- Colour:
changes may be characteristic e.g.
yellow in cases of alcoholic cirrhosis,
green in case of biliary cirrhosis and
dark brown in case of haemochromatosis.
Microscopy of cirrhosis
Loss of normal hepatic lobular architecture which is replaced by:
1- Regeneration nodules: These consist of
- proliferating liver cells with an irregular sinusoidal pattern. - Central veins are absent or eccentric.
2- Fibrous septa
around the regeneration nodules showing chronic inflammatory cells
Pathogenesis (Mechanisms):
Of cirrhosis
Liver injury (frequently due to toxins & viruses) → destruction & necrosis of liver cells & also the supporting delicate connective tissue framework → leading to:
1- Regeneration of liver cells → Regeneration nodules presinonsiaspaces
2- Activated stellate cells (Ito cells) in the space of Disse (perisinusoidal space) → transform into myofibroblast-like cells → production & deposition of collagen → progressive fibrosis
The common causes of cirrhosis are:
The common causes of cirrhosis are:
1- Chronic alcoholism (Alcoholic liver disease) is the most common
2- Chronic hepatitis B and C (→ Postnecrotic (post hepatitic) cirrhosis)
3- Obstructive biliary diseases
4- Metabolic disease:
a- Hemochromatosis (iron overload) b- Wilson’s disease c- α1-Antitrypsin deficiency
5- Chronic venous congestion of liver, longstanding
6- Cryptogenic cirrhosis: unknown etiology about 10% of cases join This is cirrhosis of undetermined cause i.e. idiopathic about 10% of cases
Alcoholic Cirrhosis:
Pathogenesis, Microscopy , Gross
Pathogenesis: - Chronic alcoholism → lead to Severe fatty change of liver (steatosis) followed by → gradual progressive liver cell loss → cirrhosis.
Gross: Liver is reduced in size, firm yellowish & shows a Micronodular pattern.
Microscopy: The liver cells in the regeneration nodules show fatty change.
Chronic alcohol consumption adverse effects :
collectively referred to as alcoholic liver disease
(1) Hepatic steatosis (fatty liver) (90-100% of heavy drinkers ),
(2) Alcoholic hepatitis, (10-35%) fibrous tissue develops around the central veins & extends into the adjacent sinusoids. degenerating hepatocytes with Mallory bodies (eosinophilic cytoplasmic inclusions? I.F.)
if mallorybody
(3) Cirrhosis (10-20%), perivenular & sinusoidal fibrosis → portal tract to portal tract → micronodular cirrhosis
Post-Hepatitic Cirrhosis: (Postnecrotic Cirrhosis) Pathogenesis, Microscopy , Gross
Gross : Liver is reduced in size, firm & shows a mixed micro- and macronodular pattern.
Microscopy:
Picture of cirrhosis (regeneration nodules and fibrosis) +
Picture of chronic active hepatitis (piecemeal necrosis, chronic inflammation… etc
Biliary Cirrhosis
A) Primary Biliary Cirrhosis (Intrahepatic biliary obstruction): Etiology:
wet Bile I
3- Biliary Cirrhosis:
A) Primary Biliary Cirrhosis (Intrahepatic biliary obstruction): Etiology:
1- Autoimmune disease: characterized by chronic inflammation & granulomatous destruction of intrahepatic bile ducts in P.T. ending in cirrhosis
2- Other suggested etiological factors as drug hypersensitivity.
- Occurs more often in women between 40 and 50 years of age
- Most patients have another autoimmune disease (scleroderma, RA, or SLE
-Antimitochondrial autoantibodies (AMA) are present in more than 90% of cases cases
- Serum alkaline phosphatase and cholesterol levels are almost elevated
B) Secondary Biliary Cirrhosis (Extrahepatic biliary obstruction): Etiology:
- Chronic obstruction of extra-hepatic bile ducts: due to
1- Stricture: e.g., congenital biliary atresia live.abjso.seobstruction
2- Gall stones 3- Tumors: e.g., cancer head of pancreas.
4- Compression by large lymph nodes
Gross: Liver is enlarged (early), green (bile-stained) with micronodular cut surface.
Biliary Cirrhosis Presentation
Laboratory findings:
Presentation:
- Pruritus: due to ↑ plasma bile acids or salts (→ deposited in skin)
- Obstructive jaundice:
- Icterus,
- Dark urine (bilirubinuria),
- Pale clay-colored stools: (Due to a lack of urobilin) - malabsorption
- Cirrhosis (late complication)
Laboratory findings:
- Elevated conjugated bilirubi
- Elevated alkaline phosphatase - Antimitochondrial autoantibodies (AMA):
are present in more than 90% of Primary biliary cirrhosis (PBC)
-increased in serum cholesterol
- mildly increased serum ALT& AST
-bilirubinuria
- absent urine urobilinogen
Hereditary hemochromatosis: → Pigmentary cirrhosis Distribution of disease:
Distribution of disease:
1- Liver: Micronodular cirrhosis
2- Pancreas: Diabetes mellitus “Bronzed diabetes“ ad
due to destruction of β-islet cells → Type I DM
3- Skin: Hyperpigmentation
Iron deposits in skin and increases melanin production
4- Heart: Congestive heart failure (?Restrictive cardiomyopathy) talks can ‘tdorelaxation
5- The testes may be small and atrophic
, and atypical arthritis (hemosiderin deposition in the joint synovial linings + excessive deposition of calcium pyrophosphate → pseudogout)
Hereditary hemochromatosis: → Pigmentary cirrhosis Laboratory findings:
Increased serum iron,
- Increased serum ferritin,
- Increased % saturation of iron binding protein (Transferrin) (N: 33%)
- Decreased total iron-binding capacity (TIBC) (N: 300 μg/dL) - liver biopsy: → Prussian blue stain → increased tissue iron level
Wilson Disease (Hepatolenticular Degeneration)
Definition , Mechanism
Definition:
- Genetic disorder of copper metabolism resulting in accumulation of toxic levels of copper in various organs Mechanism:
- Autosomal recessive (chromosome 13). Gene mutation leads to:
- ↓ hepatocyte transport for excretion of copper into bile
- ↓ synthesis of ceruloplasmin in the liver (binding protein for copper in blood) Ceruloplasmin, the binding protein for copper, is secreted into the plasma where it represents 90% to 95% of the total serum copper concentration. The remaining 5% to 10% of copper is free copper
Wilson Disease (Hepatolenticular Degeneration)
Distribution of disease: Presents in childhood or adolescence , Laboratory finding
1- Liver: chronic hepatitis → Micronodular cirrhosis
2- Cornea: Kayser-Fleischer rings (green to brown copper deposition in Descemet’s membrane in cornea)
3- Brain: Dementia, neurological & a movement disorder resembling parkinsonism toxic injury primarily affects the basal ganglia, particularly the putamen
Laboratory findings:
- Increased serum free copper
& Decreased total serum copper (dt ↓ceruloplasmin)
- Decreased serum ceruloplasmin levels (useful in diagnosis → for early stages )
- Increased urinary excretion of free copper (useful in diagnosis → for later stages)
- Increased hepatic copper concentration in liver biopsy
