hepatic enchepalophaty (gsh)
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Gatot Sugiharto, MD, InternistInternal Medicine DepartmentFaculty of Medicine, Wijaya Kusuma University Surabaya
Enchepalophaty Hepaticum
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
Normal Liver
Inflammation (Hepatitis)
Fibrosis (Cirrhosis)
Patterns of Hepatic Injury
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
Spider angiomas
palmar erythema
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
Uremia/azotemia
Gastrointestinal bleeding
Dehydration
Metabolic alkalosis
Hypokalemia
Constipation
Excessive dietary protein
Infection
Non-Nitrogenous
Encephalopathy
Sedative
Benzodiazepines
Hypoxia
Hypoglycemia
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• γ-Aminobutyric acid hypothesis
• 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 (1)
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
γ- Aminobutyric acid hypothesis
γ- 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
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 manifestation(2)
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
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