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===Microscopic Pathology===
===Microscopic Pathology===
Microscopically, cirrhosis is characterized by regeneration nodules surrounded by fibrous septa. In these nodules, regenerating [[hepatocyte]]s are disorderly disposed.  Portal tracts, [[central vein]]s and the radial pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate ([[lymphocyte]]s, [[macrophage]]s). If it is a [[secondary biliary cirrhosis]], biliary ducts are damaged, proliferated or distended - bile stasis.  These dilated ducts contain inspissated bile which appears as bile casts or bile thrombi (brown-green, amorphous).  Bile retention may be found also in the parenchyma, as the so called "bile lakes".<ref>[http://www.pathologyatlas.ro/Cirrhosis.html Pathology atlas], "cirrhosis".</ref>
Microscopically, cirrhosis is characterized by regeneration nodules surrounded by fibrous septa. In these nodules, regenerating [[hepatocyte]]s are disorderly disposed.  Portal tracts, [[central vein]]s and the radial pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate ([[lymphocyte]]s, [[macrophage]]s). If it is a [[secondary biliary cirrhosis]], biliary ducts are damaged, proliferated or distended - bile stasis.  These dilated ducts contain inspissated bile which appears as bile casts or bile thrombi (brown-green, amorphous).  Bile retention may be found also in the parenchyma, as the so called "bile lakes".<ref>[http://www.pathologyatlas.ro/Cirrhosis.html Pathology atlas], "cirrhosis".</ref>
==Microscopic Pathology==


{| class="wikitable"
 
| colspan="2" |
 
*The main microscopic [[histopathological]] findings in portal hypertension are related to [[Cirrhosis (patient information)|cirrhosis]], [[esophageal varices]], [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]], and congestive [[hepatopathy]] due to [[heart failure]] or [[Budd-Chiari syndrome]].
|-
|
=== Cirrhosis ===
Robbins definition of microscopic [[histopathological]] findings in cirrhosis includes (all three is needed for diagnosis):<ref>{{cite book | last = Mitchell | first = Richard | title = Pocket companion to Robbins and Cotran pathologic basis of disease | publisher = Elsevier Saunders | location = Philadelphia, PA | year = 2012 | isbn = 978-1416054542 }}</ref>
* Bridging [[fibrosis]]
* [[Nodule]] formation
* Disruption of the [[hepatic]] architecture
|
[[image:Cirrhosis.jpg|thumb|200px|Cirrhosis with bridging fibrosis (yellow arrow) and nodule (black arrow) - By Nephron, via Librepathology.org<ref name="urlFile:Cirrhosis high mag.jpg - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:Cirrhosis_high_mag.jpg#filelinks |title=File:Cirrhosis high mag.jpg - Libre Pathology |format= |work= |accessdate=}}</ref>]]
|-
|
=== Esophageal varices ===
The main microscopic [[histopathological]] findings in [[esophageal varices]] are:
* Large dilated submucosal [[veins]] ('''key feature''')
* [[Blood]] (fresh)
* [[Hemosiderin]]-laden [[macrophages]].
|
[[image:Eso-varices.jpg|thumb|200px|Esophageal varices with submucosal vein (black arrow), via Librepathology.org<ref name="urlEsophageal varices - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/Esophageal_varices#cite_note-3 |title=Esophageal varices - Libre Pathology |format= |work= |accessdate=}}</ref>]]
|-
|
=== Hepatic amyloidosis ===
The main microscopic [[histopathological]] findings in [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]] is amorphous extracellular pink stuff on H&E staining.
|
[[image:Amyloidosis - high mag.jpg|thumb|200px|Hepatic amyloidosis with amorphous amyloids (black arrow) and normal hepatocytes (blue arrow), via Librepathology.org<ref name="urlFile:Hepatic amyloidosis - high mag.jpg - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:Hepatic_amyloidosis_-_high_mag.jpg |title=File:Hepatic amyloidosis - high mag.jpg - Libre Pathology |format= |work= |accessdate=}}</ref>]]
|-
|
=== Congestive hepatopathy ===
The main microscopic [[histopathological]] findings in congestive [[hepatopathy]] (due to [[heart failure]] or [[Budd-Chiari syndrome]]) are:
* [[Atrophy]] of zone III
* Distension of portal [[venule]] ([[central vein]])
* Perisinusoidal [[fibrosis]] which may progress to centrilobular [[fibrosis]] and then diffuse [[fibrosis]]
* [[Sinusoidal]] dilation in ''all'' zone III areas ('''key feature)'''
|
[[image:Congestive hepatopathy.jpg|thumb|200px|Congestive hepatopathy with central vein (yellow arrowhead), inflammatory cells, Councilman body (green arrowhead), and hepatocyte with mitotic figure (red arrowhead), via Librepathology.org<ref name="urlFile:2 CEN NEC 1 680x512px.tif - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:2_CEN_NEC_1_680x512px.tif |title=File:2 CEN NEC 1 680x512px.tif - Libre Pathology |format= |work= |accessdate=}}</ref>]]
|}


===Chronic active hepatitis - Cirrhosis===
===Chronic active hepatitis - Cirrhosis===

Revision as of 17:16, 21 December 2017

Pathophysiology prev

https://https://www.youtube.com/watch?v=5szNmKtyBW4%7C350}}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Overview

Cirrhosis occurs due to long term liver injury which causes an imbalance between matrix production and degradation. Early disruption of the normal hepatic matrix results in its replacement by scar tissue, which in turn has deleterious effects on cell function.

Pathophysiology

Pathology

  • There are four stages of Cirrhosis as it progresses:
    • Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
    • Development of biliary stasis and fibrosis
  • Periportal fibrosis progresses to bridging fibrosis
  • Increased proliferation of smaller bile ductules leading to regenerative nodule formation.





Microscopic Pathology

Microscopically, cirrhosis is characterized by regeneration nodules surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. Portal tracts, central veins and the radial pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate (lymphocytes, macrophages). If it is a secondary biliary cirrhosis, biliary ducts are damaged, proliferated or distended - bile stasis. These dilated ducts contain inspissated bile which appears as bile casts or bile thrombi (brown-green, amorphous). Bile retention may be found also in the parenchyma, as the so called "bile lakes".[1]



Chronic active hepatitis - Cirrhosis

{{#ev:youtube|CzKGvWZrUpU}}

Micronodular cirrhosis

{{#ev:youtube|CV8OYeIUXko}}

Primary biliary cirrhosis

{{#ev:youtube|Jj8ozr_IttM}}

References

  1. ↑ Pathology atlas, "cirrhosis".

Template:WS Template:WH

the end

-

Portal HTN results from the combination of the following:

  • Structural disturbances associated with advanced liver disease account for 70% of total hepatic vascular resistance.
  •  Functional abnormalities such as endothelial dysfunction and increased hepatic vascular tone account for 30% of total hepatic vascular resistance.

Pathogenesis of Cirrhosis due to Alcohol:

  • More than 66 percent of all American adults consume alcohol.
  • Cirrhosis due to alcohol accounts for approximately forty percent of mortality rates due to cirrhosis.
  • Mechanisms of alcohol-induced damage include:
    • Impaired protein synthesis, secretion, glycosylation
  • Ethanol intake leads to elevated accumulation of intracellular triglycerides by:
    • Lipoprotein secretion
    • Decreased fatty acid oxidation
    • Increased fatty acid uptake
  • Alcohol is converted by Alcohol dehydrogenase to acetaldehyde.
  • Due to the high reactivity of acetaldehyde, it forms acetaldehyde-protein adducts which cause damage to cells by:
    • Trafficking of hepatic proteins
    • Interrupting microtubule formation
    • Interfering with enzyme activities
  • Damage of hepatocytes leads to the formation of reactive oxygen species that activate Kupffer cells.[1]
  • Kupffer cell activation leads to the production of profibrogenic cytokines that stimulates stellate cells.
  • Stellate cell activation leads to the production of extracellular matrix and collagen.
  • Portal triads develop connections with central veins due to connective tissue formation in pericentral and periportal zones, leading to the formation of regenerative nodules.
  • Shrinkage of the liver occurs over years due to repeated insults that lead to:
    • Loss of hepatocytes
    • Increased production and deposition of collagen


Pathology

  • There are four stages of Cirrhosis as it progresses:
    • Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
    • Development of biliary stasis and fibrosis
  • Periportal fibrosis progresses to bridging fibrosis
  • Increased proliferation of smaller bile ductules leading to regenerative nodule formation.


Causes

Drugs and Toxins Infections Autoimmune Metabolic Biliary obstruction(Secondary bilary cirrhosis) Vascular Miscellaneous
Alcohol Hepatitis B Primary Biliary Cirrhosis Wilson's disease Cystic fibrosis Chronic RHF Sarcoidosis
Methotrexate Hepatitis C Autoimmune hepatitis Hemochromatosis Biliary atresia Budd-Chiari syndrome Intestinal

bypass operations for obesity

Isoniazid Schistosoma japonicum Primary Sclerosing Cholangitis Alpha-1 antitrypsin deficiency Bile duct strictures Veno-occlusive disease Cryptogenic: unknown
Methyldopa Porphyria Gallstones
Glycogen storage diseases (such as Galactosaemia, Abetalipoproteinaemia)

Cirrhosis

Pathophysiology [2][3][4][5][6][1]

  • When an injured issue is replaced by a collagenous scar, it is termed as fibrosis.
  • When fibrosis of the liver reaches an advanced stage where distortion of the hepatic vasculature also occurs, it is termed as cirrhosis of the liver.
  • The cellular mechanisms responsible for cirrhosis are similar regardless of the type of initial insult and site of injury within the liver lobule.
  • Viral hepatitis involves the periportal region, whereas involvement in alcoholic liver disease is largely pericentral.
  • If the damage progresses, panlobular cirrhosis may result.
  • Cirrhosis involves the following steps: [7]
    • Inflammation
    • Hepatic stellate cell activation
    • Angiogenesis
    • Fibrogenesis
  • Kupffer cells are hepatic macrophages responsible for Hepatic Stellate cell activation during injury.
  • The hepatic stellate cell (also known as the perisinusoidal cell or Ito cell) plays a key role in the pathogenesis of liver fibrosis/cirrhosis.
  • Hepatic stellate cells(HSC) are usually located in the subendothelial space of Disse and become activated to a myofibroblast-like phenotype in areas of liver injury.
  • Collagen and non collagenous matrix proteins responsible for fibrosis are produced by the activated Hepatic Stellate Cells(HSC).
  • Hepatocyte damage causes the release of lipid peroxidases from injured cell membranes leading to necrosis of parenchymal cells.
  • Activated HSC produce numerous cytokines and their receptors, such as PDGF and TGF-f31 which are responsible for fibrogenesis.
  • The matrix formed due to HSC activation is deposited in the space of Disse and leads to loss of fenestrations of endothelial cells, which is a process called capillarization.
  • Cirrhosis leads to hepatic microvascular changes characterised by [8]
    •  formation of intra hepatic shunts (due to angiogenesis and loss of parenchymal cells) 
    • hepatic endothelial dysfunction
  • The endothelial dysfunction is characterised by [9]
    • insufficient release of vasodilators, such as nitric oxide due to oxidative stress
    • increased production of vasoconstrictors (mainly adrenergic stimulation and activation of endothelins and RAAS)
  • Fibrosis eventually leads to formation of septae that grossly distort the liver architecture which includes both the liver parenchyma and the vasculature. A cirrhotic liver compromises hepatic sinusoidal exchange by shunting arterial and portal blood directly into the central veins (hepatic outflow). Vascularized fibrous septa connect central veins with portal tracts leading to islands of hepatocytes surrounded by fibrous bands without central veins.[10][11][12]
  • The formation of fibrotic bands is accompanied by regenerative nodule formation in the hepatic parenchyma.
  • Advancement of cirrhosis may lead to parenchymal dysfunction and development of portal hypertension.
  • Portal HTN results from the combination of the following:
    • Structural disturbances associated with advanced liver disease account for 70% of total hepatic vascular resistance.
    •  Functional abnormalities such as endothelial dysfunction and increased hepatic vascular tone account for 30% of total hepatic vascular resistance.

Pathogenesis of Cirrhosis due to Alcohol:

  • More than 66 percent of all American adults consume alcohol.
  • Cirrhosis due to alcohol accounts for approximately forty percent of mortality rates due to cirrhosis.
  • Mechanisms of alcohol-induced damage include:
    • Impaired protein synthesis, secretion, glycosylation
  • Ethanol intake leads to elevated accumulation of intracellular triglycerides by:
    • Lipoprotein secretion
    • Decreased fatty acid oxidation
    • Increased fatty acid uptake
  • Alcohol is converted by Alcohol dehydrogenase to acetaldehyde.
  • Due to the high reactivity of acetaldehyde, it forms acetaldehyde-protein adducts which cause damage to cells by:
    • Trafficking of hepatic proteins
    • Interrupting microtubule formation
    • Interfering with enzyme activities
  • Damage of hepatocytes leads to the formation of reactive oxygen species that activate Kupffer cells.[1]
  • Kupffer cell activation leads to the production of profibrogenic cytokines that stimulates stellate cells.
  • Stellate cell activation leads to the production of extracellular matrix and collagen.
  • Portal triads develop connections with central veins due to connective tissue formation in pericentral and periportal zones, leading to the formation of regenerative nodules.
  • Shrinkage of the liver occurs over years due to repeated insults that lead to:
    • Loss of hepatocytes
    • Increased production and deposition of collagen


Pathology

  • There are four stages of Cirrhosis as it progresses:
    • Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
    • Development of biliary stasis and fibrosis
  • Periportal fibrosis progresses to bridging fibrosis
  • Increased proliferation of smaller bile ductules leading to regenerative nodule formation.

Video codes

Normal video

{{#ev:youtube|x6e9Pk6inYI}}

Video in table

{{#ev:youtube|5ucSlgqGAno}}

Floating video

Title
https://https://www.youtube.com/watch?v=ypYI_lmLD7g%7C350}}

Redirect

  1. REDIRECTEsophageal web

synonym website

https://mq.b2i.sg/snow-owl/#!terminology/snomed/10743008

Image

Normal versus Abnormal Barium study of esophagus with varices


Image to the right

C. burnetii, the Q fever causing agent
C. burnetii, the Q fever causing agent

Image and text to the right

<figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline> Recent out break of leptospirosis is reported in Bronx, New York and found 3 cases in the months January and February, 2017.

Gallery

References

  1. ↑ 1.0 1.1 1.2 Arthur MJ (2002). "Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C". Gastroenterology. 122 (5): 1525–8. PMID 11984538.
  2. ↑ Arthur MJ, Iredale JP (1994). "Hepatic lipocytes, TIMP-1 and liver fibrosis". J R Coll Physicians Lond. 28 (3): 200–8. PMID 7932316.
  3. ↑ Friedman SL (1993). "Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies". N. Engl. J. Med. 328 (25): 1828–35. doi:10.1056/NEJM199306243282508. PMID 8502273.
  4. ↑ Iredale JP (1996). "Matrix turnover in fibrogenesis". Hepatogastroenterology. 43 (7): 56–71. PMID 8682489.
  5. ↑ Gressner AM (1994). "Perisinusoidal lipocytes and fibrogenesis". Gut. 35 (10): 1331–3. PMC 1374996. PMID 7959178.
  6. ↑ Iredale JP (2007). "Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ". J. Clin. Invest. 117 (3): 539–48. doi:10.1172/JCI30542. PMC 1804370. PMID 17332881.
  7. ↑ Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G (1995). "Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension". Hepatology. 21 (5): 1238–47. PMID 7737629.
  8. ↑ Fernández M, Semela D, Bruix J, Colle I, Pinzani M, Bosch J (2009). "Angiogenesis in liver disease". J. Hepatol. 50 (3): 604–20. doi:10.1016/j.jhep.2008.12.011. PMID 19157625.
  9. ↑ García-Pagán JC, Gracia-Sancho J, Bosch J (2012). "Functional aspects on the pathophysiology of portal hypertension in cirrhosis". J. Hepatol. 57 (2): 458–61. doi:10.1016/j.jhep.2012.03.007. PMID 22504334.
  10. ↑ Schuppan D, Afdhal NH (2008). "Liver cirrhosis". Lancet. 371 (9615): 838–51. doi:10.1016/S0140-6736(08)60383-9. PMC 2271178. PMID 18328931.
  11. ↑ Desmet VJ, Roskams T (2004). "Cirrhosis reversal: a duel between dogma and myth". J. Hepatol. 40 (5): 860–7. doi:10.1016/j.jhep.2004.03.007. PMID 15094237.
  12. ↑ Wanless IR, Nakashima E, Sherman M (2000). "Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis". Arch. Pathol. Lab. Med. 124 (11): 1599–607. doi:10.1043/0003-9985(2000)124<1599:ROHC>2.0.CO;2. PMID 11079009.
  13. ↑ 13.0 13.1 13.2 Neuroendocrine tumor of the pancreas. Libre Pathology. http://librepathology.org/wiki/index.php/Neuroendocrine_tumour_of_the_pancreas

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REFERENCES

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