Fatty liver??

[Guest guest]

I was just wondering what does a fatty liver have to do with

pancreatitis? I was told several years ago that I had a fatty liver,

when I asked the primary care Dr. what it meant he just shrugged his

shoulders. Just curious.

Atwell LPN

[Guest guest]

Nobody knows much about fatty liver for sure, there are just a lot of

theories. They used to think it was because people were obese, female

and had high blood sugar-but then it turned out even skinny people and

little kids get it so nobody has the foggiest idea what the actual

cause is!Or the expected outcome. Thus the shoulder shrug.

Margaret

>

> I was just wondering what does a fatty liver have to do with

> pancreatitis? I was told several years ago that I had a fatty liver,

> when I asked the primary care Dr. what it meant he just shrugged his

> shoulders. Just curious.

>

[Guest guest]

Margaret;

Fatty liver (hepatic steatosis): Excessive accumulation of lipid in

hepatocytes, the most common response of the liver to injury.

The liver occupies a central position in lipid metabolism. A small,

rapidly used pool of free fatty acids (FFAs), absorbed from the diet

or released into the blood from chylomicrons or fat cells,

accommodates almost all of the energy requirements of a fasting

animal. FFAs are taken up by the liver to join the hepatic pool of

FFA, a portion of which the liver synthesizes. Some FFAs are oxidized

to CO2 in the liver for energy, but most are rapidly incorporated

into complex lipids (eg, triglycerides, phospholipids, glycolipids,

cholesterol esters). Some of these complex lipids enter a slowly used

pool that comprises the structural lipids of liver cells and their

storage site. Most triglycerides enter an active pool where they

combine with specific apoproteins to form lipoproteins (eg, very low

density lipoproteins [VLDLs]), which are secreted into plasma. The

liver is also responsible for lipid degradation (eg, low density

lipoproteins, chylomicron remnants).

Fatty liver occurs when lipid accumulation exceeds the normal 5% of

liver weight. In the macrovesicular type, large fat droplets balloon

the liver cell, displacing the nucleus to the periphery of the cell,

like an adipocyte. Triglyceride accumulates most commonly because it

has the highest turnover rate of all hepatic fatty acid esters. Liver

uptake of FFA from adipose tissue and the diet is unrestrained,

whereas FFA disposition by oxidation, esterification, and VLDL

secretion is limited.

In microvesicular fatty liver, small fat droplets accumulate, cells

appear foamy, and nuclei are central. Triglycerides collect in

subcellular organelles (eg, endoplasmic reticulum), reflecting

widespread metabolic disturbance. Mitochondrial injury limits FFA

oxidation, while apoprotein synthesis necessary for VLDL secretion is

depressed, leading to triglyceride accumulation.

In phospholipidosis, phospholipids accumulate in association with

certain drug use (eg, amiodarone). Liver cells are large and foamy.

Etiology

Diffuse fatty change of the liver, often zonal in distribution, is

associated with many clinical situations. Alcoholism, obesity, and

diabetes are the most common causes of macrovesicular fatty liver in

developed countries. Other causes include malnutrition (especially

the protein-deficient diet of children with kwashiorkor), inborn

metabolic disorders (of glycogen, galactose, tyrosine, or

homocysteine), drugs (eg, corticosteroids), or systemic illnesses

with fever. Microvesicular fatty liver occurs in acute fatty liver of

pregnancy, Reye's syndrome, certain drug toxicities (valproic acid,

tetracycline, salicylate), or inborn metabolic defects (of the urea

cycle enzymes or involving mitochondria in FFA oxidation).

Focal fatty change is much less common and less well recognized.

These nodules of fatty liver cells are subcapsular. They are usually

an incidental finding on ultrasound or CT, presenting as multiple

space-occupying lesions of the liver. Such focal fat may appear in

patients apparently at risk of developing this change (eg, obese or

alcoholic patients).

Pathogenesis

Triglycerides accumulate in the liver because of increased input

through synthesis from FFA or decreased export as VLDL from the

hepatocytes. Increased triglyceride synthesis may result from

increased delivery or availability of FFA (from the diet or mobilized

from adipose tissue), from acetylcoenzyme A, or from decreased

oxidation of FFA in the liver. Reduced elimination of triglyceride

involves depressed packaging with apolipoprotein, phospholipid, and

cholesterol, resulting in decreased VLDL secretion.

The several possible mechanisms involved in the pathogenesis of the

fatty liver may operate alone or together. In obesity, delivery of

dietary fat or mobilization from adipose tissue is increased.

Decreased oxidation of FFA may contribute to the fatty liver induced

by carbon tetrachloride, yellow phosphorus, hypoxia, or certain

vitamin deficiencies (niacin, riboflavin, pantothenic acid). Blocked

production and secretion of lipoproteins is often the main cause of

triglyceride accumulation in the liver. Impaired apolipoprotein

synthesis is the most important pathogenetic factor in several types

of toxic fatty liver and in the fatty liver produced by protein-

calorie malnutrition. Toxic inhibition of protein synthesis can lead

to a fatty liver through inhibition of mRNA synthesis or translation.

In microvesicular fatty liver, small droplets of triglyceride plus

FFA, cholesterol, and phospholipid collect in subcellular organelles.

The basic defect is unknown, even though pathologic and clinical

features from diverse causes are somewhat similar. The biochemical

basis may be a disturbance in the mitochondrial-oxidative pathway,

depressing FFA oxidation and impairing apolipoprotein synthesis for

VLDL assembly.

Fatty liver may result from the accumulation of other neutral lipids.

Fat and cholesterol (seen as rhomboid birefringent crystals under

polarizing microscopy) are present in Wolman's disease and

cholesterol ester storage disease. The fat vacuolization is small to

medium. In Niemann-Pick disease, the phospholipid sphingomyelin

accumulates in hepatocytes and Kupffer cells. Cells appear foamy.

Pathology

When lipid deposition is marked, the liver tends to be grossly

enlarged, smooth, and pale. Microscopically, the general architecture

can be normal. Triglyceride accumulations appear as large droplets

that coalesce and displace the cell nucleus to the periphery. In the

typical example, alcoholic fatty liver, hepatocytes are filled with

fat vacuoles that displace the nuclei to the periphery of the cell,

appearing like a large fat cell (see the discussion of fatty liver

under Pathology in Ch. 40). In microvesicular fatty liver, small

droplets collect in the endoplasmic reticulum and in secondary

lysosomes that do not fuse. Hepatocytes exhibit a foamy cytoplasm and

a central nucleus.

With hepatotoxins primarily affecting protein synthesis or with

protein malnutrition, the lipid tends to collect in zone 1

(periportal). Microvesicular fat tends to collect in zone 3 (central).

Symptoms, Signs, and Diagnosis

Macrovesicular fatty liver most often is discovered on physical

examination as nontender, smooth, diffuse hepatomegaly in an

alcoholic, obese, or diabetic patient. It can present with right

upper quadrant pain, tenderness, and jaundice, or it may be the only

physical abnormality found after a sudden, unexpected, and presumably

metabolic death.

There is a poor association between fatty liver and abnormal findings

on the commonly used biochemical tests for liver disease. A mild

increase may occur in alkaline phosphatase or transaminase.

Ultrasound and especially CT may reveal excess fat. Fatty liver is

diagnosed with certainty only by liver biopsy. Because such

accumulation of fat in the liver may indicate the action of a

hepatotoxin or the presence of an unrecognized disease or metabolic

abnormality, the diagnosis calls for further evaluation of the

patient.

Nonalcoholic fatty liver disease (nonalcoholic steatohepatitis) is an

increasingly recognized accumulation of fat in the liver of females

who tend to be obese or diabetic. It also occurs after jejunal bypass

surgery, with malnutrition, and in association with certain drugs

(eg, glucocorticoids, synthetic estrogens, amiodarone, tamoxifen).

Hepatomegaly may be present. Histologic diagnosis is based on

macrovesicular fatty change and lobular inflammation, sometimes

accompanied by fibrosis and Mallory hyaline bodies. The condition is

often detected on liver biopsy performed for other reasons, usually

in asymptomatic patients who present with a two- to threefold

increase in plasma aminotransferase. For diagnosis, negligible

alcohol intake must be evident.

Microvesicular fatty liver has a pronounced presentation, with

fatigue, nausea, and vomiting soon followed by jaundice,

hypoglycemia, coma, and a disseminated intravascular coagulopathy.

Prognosis and Treatment

Potentially reversible, macrovesicular fatty liver usually is not in

itself harmful. It is reversible even in potentially fatal instances

(eg, in fatty liver of pregnancy, early delivery may be lifesaving).

Alcoholic fatty liver may be accompanied by inflammation and necrosis

(alcoholic hepatitis) and permanent damage in the form of cirrhosis.

Microvesicular fatty liver presents acutely but is reversible if the

patient survives.

No specific therapy is available except to eliminate the cause or

treat the underlying disorder. Even obesity and diabetes mellitus

with fatty liver are thought not to progress to cirrhosis. Although

hepatotoxins such as alcohol and carbon tetrachloride (which also

produce necrosis) can eventually result in cirrhosis, there is no

evidence that a fatty liver per se leads to cirrhosis. Some other

event must occur.

Nonalcoholic fatty liver disease generally has a good prognosis,

without histologic or clinical progression. Some livers may show

increased fibrosis and progression to cirrhosis. Management includes

weight loss for obese patients, although this is of unproven benefit.

Anecdotal reports indicate a benefit from ursodeoxycholic acid

therapy.

>

>

> Nobody knows much about fatty liver for sure, there are just a lot

of

> theories. They used to think it was because people were obese,

female

> and had high blood sugar-but then it turned out even skinny people

and

> little kids get it so nobody has the foggiest idea what the actual

> cause is!Or the expected outcome. Thus the shoulder shrug.

>

> Margaret

> >

> > I was just wondering what does a fatty liver have to do with

> > pancreatitis? I was told several years ago that I had a fatty

liver,

> > when I asked the primary care Dr. what it meant he just shrugged

his

> > shoulders. Just curious.

> >

>

[Guest guest]

Yep, that's Merck. They're more cheerful about NASH than NIH :

http://digestive.niddk.nih.gov/ddiseases/pubs/nash/

> Nonalcoholic fatty liver disease generally has a good prognosis,

> without histologic or clinical progression. Some livers may show

> increased fibrosis and progression to cirrhosis.

Margaret