Page 618 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

604 C H A P T E R 15 Liver, Gallbladder, and Biliary Tract Hepatic Failure

Table 15–1 Clinical Consequences of Liver Disease The most severe clinical consequence of liver disease is
Characteristic Signs of Severe Hepatic Dysfunction hepatic failure. It generally develops as the end point of
Jaundice and cholestasis progressive damage to the liver, either through insidious
Hypoalbuminemia piecemeal destruction of hepatocytes or by repetitive
Hyperammonemia waves of symptomatic parenchymal damage. Less com-
Hypoglycemia monly, hepatic failure is the result of sudden, massive
Palmar erythema destruction. Whatever the sequence, 80% to 90% of hepatic
Spider angiomas function must be lost before hepatic failure ensues. In many
Hypogonadism cases, the balance is tipped toward decompensation by
Gynecomastia intercurrent conditions or events that place demands on
Weight loss the liver. These include systemic infections, electrolyte dis-
Muscle wasting turbances, major surgery, heart failure, and gastrointestinal
Portal Hypertension Associated with Cirrhosis bleeding.
Ascites with or without spontaneous bacterial peritonitis
Splenomegaly The patterns of injury that cause liver failure fall into
Esophageal varices three categories:
Hemorrhoids • Acute liver failure with massive hepatic necrosis. Most often
Caput medusae—abdominal skin
Complications of Hepatic Failure caused by drugs or viral hepatitis, acute liver failure
Coagulopathy denotes clinical hepatic insufficiency that progresses
Hepatic encephalopathy from onset of symptoms to hepatic encephalopathy
Hepatorenal syndrome within 2 to 3 weeks. A course extending as long as 3
Portopulmonary hypertension months is called subacute failure. The histologic correlate
Hepatopulmonary syndrome of acute liver failure is massive hepatic necrosis, whatever
the underlying cause. It is an uncommon but life-
CLINICAL SYNDROMES threatening condition that often necessitates liver
transplantation.
The major clinical syndromes of liver disease are hepatic • Chronic liver disease. This is the most common route to
failure, cirrhosis, portal hypertension, and cholestasis. hepatic failure and is the end point of relentless chronic
These conditions have characteristic clinical manifestations liver damage. While all structural components of the
(Table 15–1), and a battery of laboratory tests for their liver are involved in end-stage chronic liver disease,
evaluation (Table 15–2), with liver biopsy representing the the processes that initiate and drive chronic damage to
gold standard for diagnosis. the liver can usually be classified as either primarily
hepatocytic (or parenchymal), biliary, or vascular. Regard-
Table 15–2 Laboratory Evaluation of Liver Disease less of the initiating factors, chronic damage to the liver
often ends in cirrhosis, as described later.
Test Category Serum Measurement* • Hepatic dysfunction without overt necrosis. Less commonly
than the forms described above, hepatocytes may be
Hepatocyte Cytosolic hepatocellular enzymes† viable but unable to perform their normal metabolic
integrity Serum aspartate aminotransferase (AST) function. Settings where this is seen most often are mito-
Serum alanine aminotransferase (ALT) chondrial injury in Reye syndrome, acute fatty liver of
Serum lactate dehydrogenase (LDH) pregnancy, and some drug- or toxin-mediated injuries.

Biliary excretory Substances secreted in bile† Clinical Features
function Serum bilirubin The clinical manifestations of hepatic failure from chronic
Total: unconjugated plus conjugated liver disease are much the same regardless of the cause
Direct: conjugated only of the disease. Jaundice is an almost invariable finding.
Delta: covalently linked to albumin Impaired hepatic synthesis and secretion of albumin lead
Urine bilirubin to hypoalbuminemia, which predisposes to peripheral
Serum bile acids edema. Hyperammonemia is attributable to defective hepatic
Plasma membrane enzymes† (from damage to urea cycle function. Signs and symptoms of chronic disease
include palmar erythema (a reflection of local vasodilatation)
bile canaliculi) and spider angiomas of the skin. Each angioma is a central,
Serum alkaline phosphatase pulsating, dilated arteriole from which small vessels
Serum γ-glutamyl transpeptidase radiate. There may also be impaired estrogen metabolism
Serum 5′-nucleotidase and consequent hyperestrogenemia, which leads to hypo-
gonadism and gynecomastia in men. Acute liver failure may
Hepatocyte Proteins secreted into the blood manifest as jaundice or encephalopathy, but notably absent
function Serum albumin‡ on physical examination are the other stigmata of chronic
Prothrombin time† (factors V,VII, X, liver disease.

prothrombin, fibrinogen) Hepatic failure is life-threatening for several rea­
Hepatocyte metabolism sons. The accumulation of toxic metabolites may have
Serum ammonia†
Aminopyrine breath test (hepatic demethylation)
Galactose elimination (intravenous injection)

*The most commonly performed tests are in italics.
†An elevation indicates liver disease.
‡A decrease indicates liver disease.