Circulatory disorders of the liver can arise from impaired blood inflow or outflow. The liver receives dual blood supply from the portal vein and hepatic artery. Portal vein thrombosis is a common cause of impaired inflow and can be due to hypercoagulable states, inflammation, or cirrhosis. Budd-Chiari syndrome represents outflow obstruction of the hepatic veins and is often associated with myeloproliferative disorders. Sinusoidal obstruction syndrome involves fibrous occlusion of small hepatic veins and sinusoids, leading to congestion and necrosis.
2. GENERAL CONSIDERATION
Liver has enormous flow of blood , & has dual blood
supply
Portal Vein : provides 60-70% of hepatic blood flow
Hepatic artery : supplies 30-40%
Portal vein & hepatic artery enter the liver through
the hilum (porta hepatis)
Within the liver the branches of the portal
veins, hepatic arteries & bile ducts travel in parallel
in portal tracts
4. IMPAIRED BLOOD INFLOW
Hepatic Artery Compromise
Liver infarcts are rare because of its dual blood supply
However, thrombosis / compression of an intrahepatic branch of hepatic artery can occur
due to
Embolism
Neoplasia
Polyarteritis Nodosa or
Sepsis
This results in localised infarct which can be anemic & pale tan / hemorrhagic
Retrograde arterial flow through accessory vessel when coupled with the portal venous
supply is usually sufficient to sustain the liver parenchyma
Exception : In a transplanted liver, when the hepatic artery is thrombosed , it leads to
infarction of the major ducts of biliary tree & finally loss of the organ
5.
6. PORTAL VEIN THROMBOSIS
ACQUIRED DISEASE OF LARGE PORTAL VEINS
Thrombosis of the portal vein is associated with the presence
of a hypercoagulable state, vascular injury,or stasis.
Associated hypercoagulable state includes
Pregnancy
O.C.P‟s
Prothrombin mutation
Protein C/S deficiency
Myeloproliferative disorders etc.
7.
Inflammation of the portal vein can be induced by
infection
chemical injury initiated by pancreatitis
accidental or surgical trauma
Stasis is a cause of portal vein thrombosis in
Cirrhosis
primary or secondary neoplasm
retroperitoneal fibrosis.
8.
9.
Portal vein obstruction with tumor and or thrombus
occurs in 23-70% of patients with hepatocellular
carcinoma and in 5-8% of patients with metastatic
tumor in liver.
Thrombosis in the presence of cirrhosis or hepatic
neoplasm may precipitate hepatic
decompensation,variceal bleeding or ascites.
10. ACQUIRED DISEASE OF SMALL PORTAL VEINS
Patients with portal hypertension due to obliteration of small
portal veins may also have evidence of systemic microvascular
disease as seen in
Rheumatoid artheritis
Myeloproliferative disease
S.L.E
Polyarteritis Nodosa etc.
Obliteration of small portal veins occur early in the course of
primary biliary cirrhosis,
primary sclerosing cholangitis
Sarcoidosis
11.
According to the concept of „menage a foie’ :
“Development of injury to one portal structure because
of inflammation primarily directed at a neighbouring
portal tract structure”
This explains that a local portal venous obliteration may be
secondary to arteritis or to ductal inflammation.( eg : Primary
biliary cirrhosis & primary sclerosing cholangitis)
Portal vein obliteration may also be caused by
Granulomas in sarcoidosis ,
Mineral oil granulomas
Exposure to Throtrast.
12.
13.
Emboli or local thrombosis are important in
Schistosomiasis
Normal ageing
C.C.F
Increased A.L.P, is seen in patients with
Temporal/ rheumatoid arteritis
Nodular regenerative hyperplasia
Idiopathic portal hypertension
Sarcoidosis
NOTE : The reason for above (raised ALP ) is : Ducts may also
be injured by inflammation primarily involving the arteries &
other portal tract structures
14. SCHISTOSOMIASIS
It is the most common cause of portal hypertension in
this world.
Eggs deposited in the rectal veins float into the small
portal veins where a transient eosionophilic infiltrate is
followed by a granulomatous reaction.
The veins are obliterated with fibrous tissue and PAS
positive egg cuticle is seen in surgical wedge biopsies.
Secondary proximal thrombosis causes dense fibrosis of
the main perihilar portal tracts,so called Symmer‟s pipestem fibrosis.
15.
16. PATHOLOGY OF PORTAL VEIN DISEASE
After thrombosis, followed by organisation , large veins
may have subtle white intimal plaques/ mural
calcification
When recanalisation is less complete, the lumen may be
obliterated or contain complex webs
Portal veins > 200 µm in diameter have eccentric intimal
fibrous thickening which may be layered suggesting
recurrent thrombosis
Veins < 200 µm in diameter dissapear as the wall
becomes incorporated into fibrous scar while large veins
may have residual wall best seen with elastic trichome/
Movat stain
17.
18. PATHOLOGY OF PORTAL VEIN
DISEASE(CONTD.)
Some portal veins remain patent & becomes dilated
if the supplying portal veins are patent because the
elevated portal pressure is transmitted to the the
small vein
Now, this dilated vein often expand outside the
portal tract stroma into the adjacent parenchyma
giving an „ectopic‟ appearance
Acute thrombosis of small portal vein results in a
pseudo infarct( of Zahn)
19.
20.
21. HEPATIC VEIN THROMBOSIS: BUDDCHIARI SYNDROME.
•
Budd chiari syndrome is a clinicopathologic syndrome
variously defined as hepatic vein thrombosis,noncardiac
venous outflow obstruction or venous outflow obstruction of
any cause or site.
•
Classical findings are :
•
Hepatomegaly
• Ascites
• Abdominal pain
• Varying degrees of hepatic dysfunction
22.
Hepatic vein thrombosis is associated with
primary myeloproliferative disorders,
inherited disorders of coagulation,
antiphospholipid syndrome,
paroxysmal nocturnal hemoglobinuria and intraabdominal cancers.
23. AETIOLOGY OF BUDD-CHIARI SYNDROME
75% of patients in U.S, U.K and France with BuddChiari syndrome have a recognized pre disposing
factor belonging to Virchow‟s triad
The most common is hypercoagulable state
specially Myeloproliferative disease such as :
polycythemia vera etc.
24.
25. PATHOLOGY OF BUDD-CHIARI SYNDROME
The acute lesions after hepatic vein thrombosis are
dilatations of veins & sinusoids & variable degree of
necrosis
Sinusoids are congested & R.B.C‟s infilterate the space
of disse
As the disease advances, the sinusoids become
collagenized & dilated & hepatocytes become atrophic &
are lost
The small hepatic vein dissappear as they get
incorporated into septa which eventually link hepatic
vein to establish a cirrhosis with relative sparing of portal
triads so called “reversed lobulation cirrhosis or venocentric cirrhosis”
26.
27. MORPHOLOGY
The liver is swollen and red-purple and has a tense
capsule.
Microscopically the affected hepatic parenchyma
reveals severe centrilobular congestion and
necrosis.
The major veins may contain totally occlusive fresh
thrombi, subtotal occlusion, or in chronic cases,
organized adherent thrombi.
28. BUDD-CHIARI SYNDROME-TREATMENT
o
o
Address underlying cause; high mortality
without treatment
Acute interventions:
o
Surgical creation of portal-systemic shunt (portal vein to
systemic circulation), which allows reverse flow through
portal vein, but hepatic artery inflow preserved to
prevent infarction.
o
Angiographic thrombectomy and/or dilation of hepatic
vein.
29. PASSIVE CONGESTION.
Right sided cardiac decompensation leads
passive congestion of liver.
The liver is slightly enlarged,tense and cyanotic,
with round edges.
Microscopically there is congestion of centrilobular
sinusoids.
30. CENTRILOBULAR NECROSIS
Left-sided cardiac failure or shock may lead to heaptic
hypoperfusion and hypoxia, causing ischemic
coagulative necrosis of hepatocytes in the central region
of the lobule (centrilobular necrosis).
The combination of hypoperfusion and retrograde
congestion acts synegistically to cause centrilobular
hemorrhagic necrosis.
Central lobular congestion, producing “nutmeg” liver.
Microscopy there is sharp demarcation of viable
periportal and necrotic pericentral hepatocytes, with
suffusion of blood through the centrilobular region.
32. VENO-OCCLUSIVE DISEASE
Veno occlusive disease is characterized by fibrous
occlusion of small hepatic veins less then 1mm in
diameter with secondary parenchymal congestion.
Originally described in Jamaican drinkers of
pyrolizidine alkaloid-containing bush tea.
The disease usually affects young children but
adults are also susceptible.
The onset may be acute or insidious.
33.
Patients usually present in the 3 weeks after therapy with
weight gain
Thrombocytopenia
Jaundice
hepatic failure
increased serum aminotransferases and alkaline transferases
and alkaline phosphtase.
34. CLINICAL FEATURE
o
Disease is characterized by
rapid onset of abdominal pain,
o hepatomegaly
o ascites usually without jaundice,splenomegaly or fever
o
35.
The pathogenesis of the lesions is believed to be a
primary injury to the endothelial cells of sinusoids
and small venules.
The mechanism of endothelial injury after cytotoxic
drugs may involve depletion of cellular glutathione.
36. MORPHOLOGY
Characterised by obliteration of hepatic vein radicle
by varying amounts of sub endothelial swelling &
finally reticulated collagen
In acute disease there is striking centrilobular
congestion with hepatocellular necrosis &
accumulation of hemosiderin laden macrophages
As the disease progresses obliteration of lumen of
venule is easily identified with special stain for
connective tissue
40. SINUSOIDS
Sinusoids are lined by modified endothelial cells
containing fenestrations 50-300 nm in diameter which
allow passage of lipoproteins and other large
molecules but provide a barrier to blood cells.
Sinusoidal endothelial cells have numerous bristlecoated pits,pinocytotic vacuoles.
41.
Sinusoidal endothelial cells differ from venous and
arterial endothelial cells in expressing variety of
markers including CD32 and CD16,aminopeptidase
N,CD32,CD4 and CD54.
Sinusoidal endothelial expression of CD34 and
CD31 is an indicator of angiogenesis, seen focally
in cirrhosis, focal nodular hyperplasia, and
dysplastic nodules.
42. SINUSOIDAL DILATION
Sinusoidal dilation occurs when there is increased
pressure in the hepatic veins, atrophy of hepatocytes or
disruption of the sinusoidal reticulin fibres.
It often shows a zonal distribution:
centrolobular,periportal or irregular.
43.
Centrolobular sinusoidal dilation is most common with
prominent involvement of the perivenous region extending
to the midzonal region .
It is observed in some drug induced lesions in rheumatoid
arthritis,and in malignant or granulomatous diseases.
44.
Periportal dilation affects the periportal sinusoids,
eventually extending more centripetally.
Long term contraceptive use is a cause, as is
preeclampsia and eclampsia in association with
sinusoidal fibrin thrombi and periportal ischemic
hepatocellular necrosis.
45. PELIOSIS HEPATIS
Peliosis hepatitis is primary diffuse dilation of
sinusoids.
It occurs in any condition in which efflux of hepatic
blood is impeded.
The liver contains blood filled cystic spaces, either
unlined or lined with sinusoidal endothelial cells.
46.
Peliosis hepatis is associated with many diseases
including cancer,tuberculosis,AIDS,or post
transplantation immunodeficiency.
Macroscopic lesions are usually induced by
anabolic, estrogenic or adrenocortical steroids.
Microscopic lesions occur in patients receiving
thiopurines for renal transplantation,liver transplantation
or various malignancies.
47.
Peliotic lesions found in AIDS and other
immunosuppressed patients are caused by bacterial
organisms (Bartonella species)
Patients often have peliosis of spleen and lymph nodes
and cutaneous angiomatous lesions.
Acute polyarteritisnodosa with marked inflammation of adjacent portal veinHealed arteritis & adjacent organised portal vein thrombosis
ALP = ALKALINE PHOSPHATASE
Egg of Schistosomajaponicum obstructing a small portal vein
ECTOPIC VENULE IN A PATIENT WITH NON-CIRRHOTIC PORTAL HYPERTENSION & AdJACENT SMALL PORTAL TRACT HAS NO VENULE(ARROW)
INFARCT OF ZAHN WITH ACUTE PORTAL VEIN THROMBUS.
(A) MACROSCOPIC APPEARANCE SHOWS A LARGE HEPATIC VEIN OBSTRUCTED BY ORGANIZED THROMBUS.(B)THERE IS MARKED CONGESTION WITH DILUTED SINUSOIDS AND EXTRAVASATION OF RED CELLS INTO THE LIVER CELL PLATE(C) VENO CENTRIC TYPE OF CIRRHOSIS.THE REGENARATIVE NODULE CONTAINS PORTAL TRACT WITH PATENT AND DILATED PORTAL VEINS.ELASTIC TRICHOME.(D)VENO PORTAL TYPE OF CIRRHOSIS.THIS TYPE OCCUR WHEN THERE IS OBSTRUCTION OF PORTAL VEINS AS WELL AS HEPATIC VEINS
CENTRILOBULAR HEMORRHAGIC NECROSIS.THE CUT LIVER SECTION IN WHICH MAJOR BLOOD VESSELS ARE VISIBLE,IS NOTABLE FOR MOTTLED RED APPEARANCE (NUTMEG LIVER)
Reticulin stains reveals the parenchyma framework of the lobule and the marked deposition of collagen within the lumen of central vein.