LIVER CIRRHOSIS AND HEPATIC ENCEPHALOPATHY

GROUP 3A

What is Cirrhosis?

Extensive destruction of liver cells.

Cells attempt to regenerate.

Regenerative process is disorganized.

Functional liver tissue is destroyed and scarring of liver occurs.

Overgrowth of fibrous connective tissue, distorting liver structure;

obstructing blood flow.

Cirrhosis facts
Progressive, leads to liver failure.
Insidious, prolonged course.
9th leading cause of death in U.S.
Twice as common in men.
Highest incidence between ages 40 and 60.

Types of cirrhosis

Alcoholic

Post-necrotic

Biliary/obstructive

Cardiac

Alcoholic cirrhosis

Usually associated with alcohol abuse

Most common cause of cirrhosis

Causes metabolic changes in liver

fat accumulates in liver (fatty liver)

Fatty liver potentially reversible

If alcohol abuse continues, widespread liver scar formation occurs.

Post Necrotic cirrhosis

Complication of:

viral infections

toxicity

autoimmune hepatitis

20% of patients with chronic hepatitis C will develop cirrhosis.

Broad bands of scar tissue form within the liver.

Biliary cirrhosis
Associated with chronic biliary obstruction and/or infection.
Primary sclerosing cholangitis
Diffuse fibrosis of liver.
Jaundice is main feature.

Cardiac cirrhosis

Develops from long-standing right sided heart failure

Results in patients with cor-pulmonale, constrictive pericarditis, and

tricuspid insufficiency

Pathophysiology

There are 2 primary ingredients:

Hepatic fibrosis.

Regenerating liver cells.

In response to injury and loss, growth regulators induce hepatocellular hyperplasia

(producing regenerating nodules) and arterial growth (angiogenesis). Among the
growth regulators are cytokines and hepatic growth factors (eg, epithelial growth
factor, hepatocyte growth factor, transforming growth factor-, tumor necrosis
factor).

Insulin, glucagon, and patterns of intrahepatic blood flow determine how and where
nodules develop.

Angiogenesis produces new vessels within the fibrous sheath that surrounds
nodules. These vessels connect the hepatic artery and portal vein to hepatic
venules, restoring the intrahepatic circulatory pathways. Such interconnecting
vessels provide relatively low-volume, high-pressure venous drainage that cannot
accommodate as much blood volume as normal.

As a result, portal vein pressure increases. Such distortions in blood flow contribute
to portal hypertension, which increases because the regenerating nodules compress
hepatic venules.

The progression rate from fibrosis to cirrhosis and the morphology of cirrhosis vary
from person to person. Presumably, the reason for such variation is the extent of
exposure to the injurious stimulus and the individual's response.

Diagnostic Studies

Enzyme levels (AST, ALT)

In end-stage liver disease

initially elevated due to release from damaged liver cells.

AST & ALT may be normal.

Decrease in:

total protein.

Albumin.

Increase in:

serum bilirubin.

globulin levels.

Prothrombin time is prolonged.

Early Signs of cirrhosis

Nausea and vomiting

Anorexia

Diarrhea or constipation

Pain

Fever

Weight loss

Later Manifestations
Jaundice
Skin Lesions/Spider angiomas.
Palmer erythema.
Thrombocytopenia, Leukopenia, Anemia .
Coagulation disorders.
Endocrine disturbance.
Peripheral neuropathy & peripheral edema.

Hematologic Problems

Thrombocytopenia

Leukopenia

Anemia

Vitamin K deficiency

Endocrine Problems

Inactivation of adrenocortical hormones in Men and Women.

Hyperaldosteronism.

Complications
Portal Hypertension
Esophageal & Gastric Varices
Peripheral Edema & Ascites
Hepatic Encephalopathy

Hepatic encephalopathy
What is Hepatic encephalopathy?

Hepatic encephalopathy is a complex, potentially reversible disturbance in

central nervous system that occurs as a consequence of severe liver
diseases.

It is generally divided into four stages, manifestating from slightly altered

mood or behavior, through to somnipathy, and inappropriate behavior, to
drowsy and psychopathy, and even finally to deep coma.

Hepatic encephalopathy stages

Stage 1 - MILD HEPATIC ENCEPHALOPATHY
Patients may have sleep problems and trouble concentrating. They may have
severe mood swings. Their hands might shake and they may have difficulty
writing.
Stage 2 - MODERATE HEPATIC ENCEPHALOPATHY
Patients may not have much energy. They keep forgetting things and have
problems with basic math. They may behave strangely and slur their speech.
Stage 3 - SEVERE HEPATIC ENCEPHALOPATHY
Patients are very sleepy and sometimes pass out. They can't do basic math at
all. They act strange and can be very fearful and jumpy.
Stage 4 - FINAL STAGE
The final stage of hepatic encephalopathy is comathe patient is unconscious.

HEPATIC ENCEPHALOPATHY SYMPTOMS

Pathogenesis

Terminal complication of liver disease

Disorder of protein metabolism and excretion

Ammonia

enters the systemic circulation without liver detoxification

crosses blood-brain barrier, causing neurologic toxic manifestations.

Pathogenesis

Ammonia intoxication hypothesis

False neurotransmitter hypothesis

Amino acid imbalance hypothesis

The gamma-aminobutyric acid hypothesis

Ammonia intoxication hypothesis

Causes for elevated ammonia :

Decreased ammonia clearance.

impaired Krebs-Henseleit urea cycle .

Increased ammonia production.

urea in the blood is emitted into intestinal lumen and degraded by urease
in bacteria to produce ammonia.

ammonia is produced in the kidneys and muscles.

gastrointestinal hemorrhage and absorption dysfunction.

Intoxication of ammonia on the brain

Impairment of energy metabolism in brain :

ammonia reacts with -ketoglutatrate to produce glutamate and

glutamine

consumption of -ketoglutatrate, NADH and ATP, inhibition of

pyruvate decarboxylase leading to the reduction of acetyl CoA and
acetylcholine.

Alteration of neurotransmitters

decreased excitatory neurotransmitters.

glutamate and acetylcholine.

increased inhibitory neurotransmitters.

glutamine and gamma-aminobutyric acid.

Inhibiting action on nerve cell membrane.

False neurotransmitter hypothesis

phenylalanine phenylethanolamine.

tyrosine octopamine.

Dopamine and norepinephrine can not be produced.

Amino acid imbalance hypothesis

Branch chain and aromatic amino acid

Increased production of aromatic AA and increased uptake and utilization
of branch chain AA.

Inhibiting the production of normal neurotransmitters.

Promoting the production of false neurotransmitters.

Increased production of 5-hydroxytryptophan(5-HT).

Prevention and treatment

Eliminating or correcting precipitating factors

Reducing plasma ammonia

Reduce ammonia formation

Lactulose

Correcting plasma amino acid imbalance and supplying normal

neurotransmitters.

Liver transplantation.