You are on page 1of 36

Enchepalophaty Hepaticum

Gatot Sugiharto, MD, Internist


Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma University
Surabaya

Hepatic Failure (severe liver disease)


> 80 to 90% of hepatic function is lost
Regeneration is rare (Hepatic transplantation only treatment)
Mortality - 70 to 95%
Patient dies in 2 to 3 weeks
Other causes :
Drugs (Halothane, Tetracyclines, mushroom
poisoning)
Acute fatty liver of pregnancy

Clinical features
Jaundice, hypoalbuminemia, hyperammonemia
Fetor hepaticus (a peculiar body odor related to
mercaptan formation)
Hyperestrogenemia : palmar erythema, spider
angiomas of the skin (one or two are normal esp. in
pregnancy), hypogonadism, Gynecomastia
Complications

Coagulopathy ( hepatic synthesis of clotting factors)


Multi- organ failure
Hepatic encephalopathy ( Ammonia)
Hepatorenal syndrome

Cirrhosis (1)

Liver Cirrhosis is a histopathologic term (xirros =


shrunken & hard)
The eleventh leading cause of death by disease
in the United States
In the United States, chronic alcoholism and
hepatitis C are the most common causes

Cirrhosis (2)
Three characteristics
Fibrosis : delicate bands or broad septa from portal
triad to central vein or c vein to c vein.
Fibrosis - irreversible and result in Portal HTN

Nodules - regeneration of hepatocytes


Loss of architecture of the entire liver

Patterns of Hepatic Injury


Normal Liver

Inflammation
(Hepatitis)

Fibrosis
(Cirrhosis)

LIVER CIRRHOSIS
Major causes :
Alcohol - (60-70%) called ASH (common in western)
Cryptogenic cirrhosis called NASH
Viral hepatitis B & C (tropical countries)

For clinical practice, liver cirrhosis could be


diagnosed if there are two clinical syndromes:
Hepatocellular failure, or
Portal Hypertension syndrome

Hepatocellular Failure Syndrome (HFS)


HFS consists of:

Loss of hair
Hyperpigmentation
Jaundice
Spidernaevi (neck, upper chest (front-back), upper
arm)
Gynaecomastia,testes atrophi,disturbance of
periodicity
Ascites
Liver palm
White nail

palmar erythema

Spider angiomas

Portal Hypertension Syndrome (PHS)


PHS consists of:
Varices of the esofagoes & rectum (haemorrhoid)
It can be detected if the varix undergoes
rupture as:
Hematemesis melena
Rectal bleeding (haematochezia/enterorrhagia)

Vascular collateral in the abdominal wall


It is important to define the direction of the
passage
Splenomegali
Ascites
Oedema of the lower extremeties

Complications of cirrhosis
Portal hypertension
Varices, ascites, hypersplenism
Synthetic dysfunction
Coagulopathy, encephalopathy hepaticum
Immunodeficiency, infection spontaneus bacterial
peritonitis
Hypoalbumine, malnutrition
Hepato-cellular carcinoma
Hepato-renal syndrome

Hepatic Encephalopathy
Disorder of CNS & neuromuscular transmission
Disturbances of consciousness & sleep, (behavioral
abnormalities, confusion, stupor, coma, death)
EEG changes, limb rigidity and Hyperreflexia,
Seizures & asterixis (a flapping tremor of
outstretched hands)
Pathogenesis : Severe loss of Hepatocellular function
& Exposure of the brain to excess ammonia levels

Etiology
Fulminant hepatic failure due to acute
hepatocellular necrosis
Acute severe viral hepatitis, drug/toxin, acute fatty
liver of pregnancy

Chronic liver disease due to one or more


potentially reversible precipitating factors
Cirrhosis of all types (70%),primary liver cancer,
surgically induced portal-cava shunts

Common precipitating factors


Nitrogenous
Encephalopathy

Non-Nitrogenous
Encephalopathy

Uremia/azotemia

Sedative

Gastrointestinal bleeding
Dehydration

Benzodiazepines

Metabolic alkalosis

Hypoxia

Hypokalemia

Hypoglycemia

Constipation
Excessive dietary protein
Infection

Hypothyroidism
Anemia

Pathogenesis (1)
Toxic materials derived from nitrogeneous substrate in
the gut and bypass the liver
Postulated factors/mechanisms:
Ammonnia neurotoxicity
Synergistic neurotoxins
Excitatory inhibitory neurotransmitters and plasma
amino acid imbalance hypothesis
-Aminobutyric acid hypothesis

Ammonia neurotoxicity (1)

Ammonia production : resulting from the


degradation of urea or protein
Primary site : gut (generating ammonia: 4g/day)
Other site :kidney and skeletal muscles
Equilibrium of ammonia and ammonium:

Ammonia neurotoxicity (2)

Elevation of ammonia : detected in 60%~80%


Ammonia intoxication interfere cerebral
metabolism:
Depletion of glutamic acid, aspartic acid and
ATP
Depression cerebral blood flow and oxigen
consumption

Synergistic neurotoxins

Ammonia
Mercaptans fetor hepaticus
Short-chain fatty acids
Phenols

Excitatory inhibitory neurotransmitter


Increased aromatic amino acids (AAAs) :
Tyrosine, Phenylalanine, Tryptophan
Due to the failure of hepatic deamination
Decreased branched-chain amino acids (BCAAs) :
Valine, Leucine, Isoleucine
Due to increased metabolism by skeletal muscle and
kidneys or increased insulin
Decreased synthesis of normal neurotransmitters :
L-Dopa, Dopamine, Noradrenoline
Enhanced synthesis of false neurotransmitters :
Octopamine, Tryptophan, Serotonin

- Aminobutyric acid hypothesis


- Aminobutyric acid (GABA):
Principle inhibitory neurotransmitters
Generated in the gut by bacteria
Bypasses the diseased or shunted liver

Pathohistology

Brain may be normal or cerebral edema


(particularly in fulminant heptic failure)
In patients with chronic liver disease : increase
in number and enlargement of Astrocytes
In a very long-standing case : Thin cortex, loss
of neurons fibers, laminar, necrosis , pyramidal
tracts demyelination

Clinical manifestation(1)

In acute liver failure :


Spontaneously appearing
High fever, tachycardia, tachypnea,
hyperventilation
Severe fatal hepatic dysfunction + abrupt mental
deterioration coma/death

Clinical manifestation(2)
In chronic liver disease
Insidious onset
Characterized by subtle and/or intermittent changes in
consciousness, personality, intelligence speech
Disturbed consciousness: slowness, somnolence,
Disorientation, confusion, deep coma
Personality changes: Childishness, irritability
Intellectual deterioration : inability to produce simple
designs with blocks or matches, Reitan trail-making test,
Daily writing chart
Speech: slow, slurred, monotonous voice
Flapping tremor (asterixis)
Fetor hepaticus

Clinical stages of HE(1)

Clinical stages of HE(2)

Laboratory and other tests


Serum ammonia : Elevation of serum ammonia:
60%~80%
Particularly in chronic HE with portosystemic
shunting
Electroencephalogram (EEG)
Severe slowing with frequencies in the theta and
delta
Evoked potentials
Variation, lack of specificity and sensitivity

Differential diagnosis

Hypoglycemia
Uremia
Diabetic ketoacidosis
Nonketotic hyperosmolar syndrome
Subdural hematoma
Cerebrospinal infection

Treatment
Strategy for the management of HE
Identify and correct the precipitating cause(s)
Initiate ammonia-lowering therapy
Minimize the potential medical complications of
cirrhosis and depressed consciousness

Identification and treatment of precipitating factors

Essential management
Bleeeding : it must be controlled
Azotemia : rehydration, attention to other prerenal
factors
Eliminate sedative/tranquilizers/similar drugs

Initiate ammonia-lowing therapy

Decreasing
nitrogen
load

Decreasing
ammonia
production

Decreasing
absorption
of enteric
toxins

Management
Supportive care
Correction of fluid, electrolyte, glucose, acid-alkaline
abnormalities
Management of cerebral edema, bacteremia
Initiate ammonia-lowing therapy
Bowel cleaning
Antibiotics : Neomycin: 2~4g/D (4~6g/D), Metronidazol:
0.2g qid as effective as neomycin
Dietary protein restriction: 40-60 g/day
Lactulosa
Administration of BCAAs: oral or parenteral administration
Livert ransplantation

You might also like