Education + Advocacy = Change

Click a topic below for an index of articles:

 

New Material

Home

Donate

Alternative Treatments

Financial or Socio-Economic Issues

Forum

Health Insurance

Hepatitis

HIV/AIDS

Institutional Issues

International Reports

Legal Concerns

Math Models or Methods to Predict Trends

Medical Issues

Our Sponsors

Occupational Concerns

Our Board

Projects

Religion and infectious diseases

State Governments

Stigma or Discrimination Issues

 

If you would like to submit an article to this website, email us at info@heart-intl.net for a review of this paper

any words all words
Results per page:

“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”


Effects of Systemic Vascular Problems on the Liver

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

There is a striking effect on the liver in situations where significant cardiac dysfunction occurs. These effects will vary greatly depending on how acutely the hemodynamic changes occur and whether or not they are predominantly affecting the right or left side of the circulation (Figure 3-1). In most instances there will be a combination of events affecting the entire circulation occurring over a variable period of time, perhaps modified by pre-existing conditions in the host liver. For purposes of clarity, classic examples of nearly "pure" conditions will be considered separately, although one must be cognizant that these circumstances are much less common than combined lesions.

Acute Right Heart Failure

The cardinal hepatic manifestations of significant right sided heart failure are sinusoidal dilatation and congestion with subsequent atrophy of hepatocyte cords

Atlas of Liver Pathology: Chapter 3, Vascular Alterations in the Liver

Figure: 2

Figure: 2

Pure, right sided congestive failure; note the dilated sinusoids in zone 3 with some degree of atrophy of the hepatocyte cords. Most of the blood has drained from the biopsy (Klatskin, x25).

Figure: 3

Figure: 3

The central vein is intact but there is striking zone 3 sinusoidal dilatation and atrophy (PAS, x40).

These changes are clearly zonal, with the centrilobular area (zone 3) being most severely affected; with time and increasing severity there may also be involvement of zone 2 and finally of zone 1. This condition has been referred to as chronic passive congestion and is closely related to elevated pressures in the right atrium or with other conditions leading to an increase in systemic venous pressure. The space of Disse may become more prominent

Figure: 4

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 4

Edema fluid has expanded the space of Disse; most of the red cells are still contained within the sinusoids (x100).

and may contain red blood cells in the more severe lesions. The appearance of the sinusoids can be dramatically altered due to the process of biopsy, particularly with needle biopsies. Blood may drain out of the specimen collapsing the sinusoids, but attention to detail such as atrophic cords and the widened space of Disse provide helpful clues. There is minimal if any necrosis, correlating with the observation that such patients may have normal transaminases or, less commonly, minor elevations (less than 2-fold).

Acute Left Heart Failure

Significant failure of the left side of the circulation is characterized by necrosis of hepatocytes in the centrilobular area

Figure: 7

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 7

The result of almost pure left sided heart failure; there is substantial loss of zone 3 hepatocytes around the central vein (x40).

Figure: 8

Figure: 8

At higher power the loss of cellular detail in zone 3 of the Rappaport acinus is affected while other acini contributing to the hepatic lobule are spared (Masson trichrome, x40).

This necrosis is coagulative rather than lytic. It may appear to be asymmetric in zone 3, owing to the variability of blood flow through the various acini  

Figure: 9

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 9

Ischemic necrosis due to left heart failure; the zone 3 of the Rappaport acinus is affected while other acini contributing to the hepatic lobule are spared (Masson, x40).

It is clear that the presence of centrilobular necrosis correlates closely with the severity of hypotension, whether sustained or episodic. Overt clinical shock need not be present for severe necrosis to develop. When such necrosis is present, there may be dramatic increases in serum transaminases, sometimes leading to a mistaken clinical impression of a viral hepatitis


Figure: 10

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 10

This patient with severe cardiac valvular disease was denied cardiac surgery because the surgical team feared viral hepatitis based on a transaminase of 1800; this is a percutaneous needle biopsy obtained post-mortem (Masson trichrome, x40).

 this has been referred to by some as ischemic hepatitis. In most cases with significant necrosis there will also be seen evidence of co-existing right sided failure with prominent congestive changes. As necrosis progresses, there may be replacement of hepatocytes within the cords by red blood cells. Associated with this zone 3 necrosis the adjoining intact hepatocytes have been known to contain PAS positive spherical inclusions

Figure: 11

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 11

 

There is marked coagulative necrosis in the centrilobular area of this child dying from intractable congestive heart failure secondary to congenital heart disease (PAS diastase, x50).

Figure: 12

Figure: 12

A higher power of the junction of zones 2 and 3 in the same child; note the spherical PAS positive inclusions representing giant lysosomes in the hepatocytes adjacent to the area of necrosis (PAS with diastase, x132).

While these resemble alpha-1-antitrypsin deficiency inclusions they differ in their location (zone 3 rather than zone 1); they represent damaged enlarged lysosomes.

Chronic Passive Congestion (Cardiac Sclerosis)

Active deposition of perisinusoidal collagen has been noted with right sided failure, and both passive collapse of the reticulin framework as well as active deposition of stromal connective tissue are seen in left sided failure. With long-standing circulatory failure some degree of fibrosis will develop. This is most pronounced in zone 3. This phenomenon of centrilobular fibrosis with sparing of periportal hepatocytes leads to an appearance referred to as "reverse lobulation"

Figure: 13

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 13

A normal portal triad sits in the center of what resembles a classical lobule; the periphery is composed of sclerotic central veins in this patient with long-standing cardiac failure (Klatskin, x10).

 The central congestion and fibrosis with pale periportal areas (and perhaps some degree of fatty change in the zone 2 hepatocytes) combine to give an appearance which has commonly been referred to as "nutmeg liver"

Figure: 14

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 14

The liver in this patient dying of failure was firm and diffusely mottled.

Figure: 15

Figure: 15

The surface showed a slight degree of irregularity; some degree of fatty change was present. A transected nutmeg is present for comparison.

 

Figure: 16

Figure: 16

A close-up reveals the alternating areas of sclerosis and retained hepatic parenchyma in this nutmeg liver.

 If the scarring is allowed to progress, the centrilobular collagen will eventually link with the portal connective tissue. At this stage the condition has been referred to as cardiac cirrhosis

Figure: 17

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 17

Full fledged cardiac sclerosis characterized by irregular skeins of mature collagen linking adjacent central veins and occasionally extending to portal areas (Klatskin, x5).

 but the term cardiac sclerosis is more accurate in that overall architectural integrity is maintained (see Chapter 9). Even at such a late stage clinical manifestations are usually minor with regards to signs of liver disease, there being minor elevations of serum bilirubin and even less impressive elevations of alkaline phosphatase and transaminases. The clinical picture is dominated by the signs of the underlying cardiovascular disease. In fact, with modern pharmacologic agents, valve replacement technology, and availability of cardiac transplantation, it is quite unusual to see significant hepatic sclerosis based on purely cardiovascular problems.

Shock Liver

The liver can be significantly damaged in shock from a variety of causes. With severe hemorrhage, burns, etc. the type of centrilobular necrosis described in left sided failure is seen. Such lesions are uncommon if shock is transitory (less than 10 hours) but are almost invariable if shock persists for 24 hours or more. Similar centrilobular necrosis occurs with severe hyperpyrexia or with heat stroke; in such circumstances the hepatocytes may contain small vacuoles. With septic shock, there may be striking cholestasis and even a prominent cholangitis (see Chapter 8).

Hepatic Infarction

Because of the dual blood supply of the liver (hepatic artery and portal vein) true infarction of the liver has been considered to be rare. This may not be true; there is considerable variation in the incidence of infarction as reported in several autopsy series. In at least one careful series, hepatic infarction, as defined by coagulation necrosis occupying more than one hepatic lobule, was seen in 14 of 700 autopsies. Most other investigators encounter hepatic infarction much less frequently. The underlying defect is usually hepatic arterial occlusion (usually thrombotic). Portal vein occlusion, or combined hepatic and portal vein occlusion, are occasionally found. Even less commonly, no vascular occlusion is identified. Recent abdominal surgery, particularly cholecystectomy, is frequently present historically in patients with arterial or combined arterial and venous thrombosis. Pure venous thrombosis is commonly related to tumor emboli. Patients without demonstrable vascular occlusion frequently have significant cardiovascular disease and have had significant recent hypotensive episodes. Arteritis has been the underlying mechanism in some cases. Recently a number of reports have documented hepatic infarction in liver transplant recipients secondary to the arteriopathy of chronic rejection (see Chapter 12).

Most hepatic infarcts are discovered incidentally at the time of autopsy. Clinical and laboratory findings are poorly defined, probably because they are masked by the overwhelming manifestations of the underlying disease. Sharp elevations of transaminases and mild hyperbilirubinemia and a mild increase in the alkaline phosphatase have been attributed to sublethal infarcts.

Grossly the infarcts are sharply demarcated and a uniform dark red; there is a mottled peripheral zone of congestion


Figure: 18

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 18

Multiple pale infarcts with a surrounding slightly hyperemic rim are noted in this patient dying from sepsis complicated by shock.

 With time the central area becomes pale. The size ranges from 1 to 15 cm in greatest diameter. Typical coagulative necrosis affects the parenchyma, but mesenchymal elements such as triads and central veins appear relatively viable

Figure: 19 A

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 19 A

(A) A hyperemic rim marks the boundary between the area of coagulative necrosis and intact liver (x10).

Figure 19 B

(B) There is loss of cellular and nuclear detail typical of coagulative necrosis (x40).

Figure 19 B  

True hepatic infarction must be distinguished from the atrophic red "infarct' of Zahn. These are areas of severe acute passive congestion with minimal parenchymal necrosis and atrophy (zone 3) resulting from focal thrombotic obstruction of portal vein branches. They present as sharply delimited areas of hyperemia grossly

Figure: 20

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 20

This infarct of Zahn was secondary to intrahepatic portal vein thrombosis; although hyperemic, significant necrosis was not present (photograph courtesy of Dr. X).

Pylephlebitis

Suppurative thrombophlebitis involving the portal vein and its intrahepatic branches was formerly much more common. It was most commonly seen complicating delayed treatment of appendicitis in the pre-antibiotic era. Multiple hepatic abscesses resulting from this seeding of the liver was frequently lethal

Figure: 21

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 21

Multiple hepatic abscesses were the immediate cause of death in this patient with untreated diverticulitis and complicating pylephlebitis.

 Abdominal sepsis still remains the most likely underlying mechanism for pylephlebitis, but the spectrum of disease has shifted. Clinically silent diverticulitis is the most common mechanism; complicated inflammatory bowel disease can also lead to pylephlebitis. The involved portal triad may have its architecture obscured by the suppurative process, but earlier lesions will show clear evidence of a fibrin neutrophil coagulum in the intrahepatic branches of the portal vein

Figure: 22

Frank A. Mitros, M.D.
Peer Review Status: Internally Peer Reviewed

Figure: 22

Supppurative necrosis within the triad is evident; while centered on the dilated portal vein branch, the infectious process has spread into the substance of the triad and adjacent liver (Masson, x40).

Figure 23 A

(A) The inflammatory change within this triad was slight; the patient was thought to have "pericholangitis" complicating Crohn's disease (x40).

 

  Figure 23 A

Figure 23 B

(B) At a higher power, the coagulum of neutrophils and fibrin represent the suppurative thrombophlebitis of the portal vein complicating this man's Crohn's disease (x100).

 Figure 23 B

 

 

 

Email: