HEPATIC ENCEPHALOPATHY

DEFINITION
Syndrome observed in patients with cirrhosis of the liver. characterized by personality changes,
intellectual impairment, and a depressed level of consciousness.
What is Hepatic Encephalopathy?
Broadly defined: All neurological and psychological symptoms in patients with liver disease that
cannot be explained by presence of other pathologies
Brain and nervous system damage secondary to severe liver dysfunction (most often chronic
disease) resulting from failure of liver to remove toxins
• Multifactorial pathogenesis with exact cause unknown
• Symptoms vary from nearly undetectable, to coma with decerebration
Characterized by various neurologic symptoms
• Cognitive impairment
• Neuromuscular disturbance
• Altered consciousness
• Reversible syndrome

INTRODUCTION
Hepatic encephalopathy (HE) It represents a reversible decrease in neurologic
function, based upon the disorder of metabolism which are caused by severe decompensate liver
disease
Portal-systemic encephalopathy patients with portal hypertension abnormal shunting of blood
Subclinical or latent HE diagnosed only by using precise mental tests or EEG no obvious
clinical and biochemical abnomalities
Incidence & Prognosis
Incidence
10-50% of cirrhotic pts and portal-systemic shunts (TIPS) experience episode of overt hepatic
encephalopathy
True incidence/prevalence of HE unknown
Lack of definitive diagnosis
Wide spectrum of disease severity
Prognosis
40% survival rate 1 year following first episode
15% survival rate 3 years following first episode

Variants of Hepatic Encephalopathy

Acute HE
Associated with marked cerebral edema seen in patients with the acute onset of hepatic failure
(FHF)
Hormonal disarray, hypokalemia, vasodilation (ie, vasopressin release)
Quick progression: coma, seizures, and decerebrate rigidity
Altered mental function attributed to increased permeability of the blood-brain barrier and
impaired brain osmoregulation
Results in brain cell swelling and brain edema
Can occur in cirrhosis, but usually triggered by precipitating factor
Precipitating factors usually determine outcome
Precipitants of Hepatic Encephalopathy
Drugs
• Benzodiazepines
• Narcotics
• Alcohol
Dehydration
• Vomiting
• Diarrhea
• Hemorrhage
• Diuretics
• Large volume paracentesis
Portosystemic Shunting
• Radiographic or surgically placed shunts
• Spontaneous shunts
• Vascular Occlusion
• Portal or Hepatic Vein Thrombosis
Increased Ammonia Production,
Absorption or Entry Into the Brain
• Excess Dietary Intake of Protein
• GI Bleeding •Infection
• Electrolyte Disturbances (ie., hypokalemia)
• Constipation •Metabolic alkalosis

Variants of Hepatic Encephalopathy

Chronic HE
Occurs in subjects with chronic liver disease such as cirrhosis and portosystemic shunting of
blood (Portal Systemic Encepalopathy [PSE])
Characterized by persistence of neuropsychiatric symptoms despite adequate medical therapy.
Brain edema is rarely reported

Refractory HE
Recurrent episodes of an altered mental state in absence of precipitating factors
Persistent HE
Progressive, irreversible neurologic findings: dementia, extrapyramidal manifestations,
cerebellar degeneration, transverse cordal myelopathy, and peripheral neuropathy
Subclinical or “Minimal HE
Most frequent neurological disturbance
Not associated with overt neuropsychiatric symptoms
Subtle changes detected by special psychomotor tests
Stages of Hepatic Encephalophay

Propossed theories of hepatic encephalopathy

Stage Symptoms
I Mild Confusion, agitation, irritability, sleep disturbance, decreased attention
II Lethargy, disorientation, inappropriate behavior, drowsiness
III Somnolent but arousable, slurred speech, confused, aggressive
IV Coma

Ammonia hypothesis
produced in the G.I. tract by bacterial degradation of amines, amino acids, purines, and urea.
Normally, ammonia is detoxified in the liver by conversion to urea and glutamine by the Krebs-
Henseleit cycle.
In liver disease or in the presence of portosystemic shunting, portal blood ammonia is not
efficiently converted to urea.
Increased levels of ammonia may enter the systemic circulation
Normal skeletal muscle aids in the metabolism of ammonia in the conversion of glutamate to
glutamine.
The muscle wasting that is observed in patients with advanced cirrhosis may potentiate
hyperammonemia.
multiple neurotoxic effects:
altering the transit of amino acids, water, and electrolytes across the neuronal membrane. can
also inhibit the generation of both excitatory and inhibitory postsynaptic potentials.
clinical observation: strategies designed to reduce serum ammonia levels tend to improve hepatic
encephalopathy.
An argument against the ammonia hypothesis includes the observation that approximately 10%
of patients with significant encephalopathy have normal serum ammonia levels.
many patients with cirrhosis have elevated ammonia levels without evidence of encephalopathy
Ammonia does not induce the classic electroencephalographic (EEG) changes associated with
hepatic encephalopathy when it is administered to patients with cirrhosis.
GABA hypothesis
GABA is a neuroinhibitory substance produced in the gastrointestinal tract. Of all brain nerve
endings, 24-45% may be GABAergic. Increased GABAergic tone is observed in patients with
cirrhosis, perhaps because of decreased hepatic metabolism of GABA.
When GABA crosses the extrapermeable blood-brain barrier of patients with cirrhosis, it
interacts with supersensitive postsynaptic GABA receptors. The GABA receptor, in conjunction
with receptors for benzodiazepines and barbiturates, regulates a chloride ionophore.
Binding of GABA to its receptor permits an influx of chloride ions into the postsynaptic neuron,
leading to the generation of an inhibitory postsynaptic potential. Administration of
benzodiazepines and barbiturates to patients with cirrhosis increases GABAergic tone and
predisposes to depressed consciousness.

Clinical features
 Asterixis- flapping hand tremors ---early sign
 ÜLOC – lethargy progressing to coma
  Ü mental status, confusion, disorientation
 dullness, slurred speech
 behavioral changes, lack of interest in grooming/ appearance
 twitching, muscular incoordination, tremors
 Fetor hepaticus
 elevated serum ammonia level
Symptoms of Hepatic encephalopathy
Changes in mental state, consciousness
Confusion, disorientation
Delirium
Dementia (loss of memory, intellect)
Mood swings
Decreased altertness, responsiveness
Coma
Course muscle tremors
Muscle stiffness or rigidity
Loss of small hand movements (handwriting)
Seizures (rare)
Decreased self-care ability
Speech impairment
Flapping Tremor

LABORATORY ABNORMALITIES IN HEPATIC ENCEPHALOPATHY

An elevated blood ammonia level is the classic laboratory abnormality reported in patients with
hepatic encephalopathy. This finding may aid in correctly diagnosing patients with cirrhosis who
present with altered mental status
EEG
EEG changes are high-amplitude low-frequency waves and triphasic waves. However, these
findings are not specific for hepatic encephalopathy. When seizure activity must be ruled out, an
EEG may be helpful in the initial workup of a patient with cirrhosis and altered mental status.
CT and MRI
Computed tomography and magnetic resonance imaging studies of the brain may be important in
ruling out intracranial lesions when the diagnosis of hepatic encephalopathy is in question.
MRI
additional advantage of being able to demonstrate hyperintensity of the globus pallidus on T1-
weighted images, a finding that is commonly described in hepatic encephalopathy.
Drawing Tests

Common precipitating factors

Renal failure: Renal failure leads to decreased clearance of urea, ammonia, and other nitrogenous
compounds.
Common precipitating factors
Gastrointestinal bleeding: The presence of blood in the upper gastrointestinal tract results in
increased ammonia and nitrogen absorption from the gut. Bleeding may predispose to kidney
hypoperfusion and impaired renal function.
Blood transfusions may result in mild hemolysis, with resulting elevated blood ammonia levels.
Infection: Infection may predispose to impaired renal function and to increased tissue
catabolism, both of which increase blood ammonia levels.
Constipation: Constipation increases intestinal production and absorption of ammonia.
Medications: Drugs that act upon the central nervous system, such as opiates, benzodiazepines,
antidepressants, and antipsychotic agents, may worsen hepatic encephalopathy.
Diuretic therapy: Decreased serum potassium levels and alkalosis may facilitate the conversion
of NH4+ to NH3.
Dietary protein overload: This is an infrequent cause of hepatic encephalopathy.
DIFFERENTIAL DIAGNOSIS FOR HEPATIC ENCEPHALOPATHY
Intracranial lesions such as subdural hematoma, intracranial bleeding, stroke, tumor, and abscess
Infections such as meningitis, encephalitis, and intracranial abscess
Metabolic encephalopathy such as hypoglycemia, electrolyte imbalance, anoxia, hypercarbia,
and uremia
Hyperammonemia from other causes such as secondary to ureterosigmoidostomy and inherited
urea cycle disorders
Toxic encephalopathy from alcohol intake, such as acute intoxication, alcohol withdrawal, and
Wernicke encephalopathy
Toxic encephalopathy from drugs such as sedative hypnotics, antidepressants, antipsychotic
agents, and salicylates
Organic brain syndrome
Postseizure encephalopathy
Management of Hepatic Encephalopathy
First and foremost control the underlying precipitant(s).
Medical therapy - optimal agent is controversial (see meta-analysis)
• Lactulose - has multiple actions including cathartic, acidification of the colon to
“ion-trap” ammonia as NH4+, and reduces inoculum of urea-splitting bacteria.
Drawbacks include osmotic diarrhea with hypernatremia due to free water loss
and gaseous bowel distension.
• Neomycin - non-absorbed aminoglycoside which reduces colon bacterial burden. Dose
at 2-6 grams orally per day. Small incidence of ototoxicity and nephrotoxicity with
prolonged usage.
• Metronidazole - oral dosing at 800 mg/day. No large scale reported experience. Is
associated with neurotoxicity in hepatic failure due to accumulation.
• Flumazenil - benzodiazepine receptor (GABA) antagonist.

Encephalopathy Treatment
Step 1 requires attempts to identify the precipitating cause – three most common include
azotemia secondary to aggressive diuresis, and/or persistent vomiting or diarrhea; overuse of
tranquillizers, sedatives, or analgesics; and GI bleeding, other causes include increased dietary
protein intake, alkalosis, infection and hypokalemia
Step 2 requires interventions to reduce the production and absorption of gut-mediated ammonia
and other toxins which is accomplished through reduction and modification of dietary protein,
altering the enteric bacteria and the colonic environment through the use of antibiotics and
lactulose
Step 3 requires the use of agents such as bromocriptine and flumazemil that directly modify
neurotransmitter balance, currently these therapies are not widely used, and have not been shown
to be highly effective
Nursing care
Interventions:
a. ) Ü ammonia production
 Üdietary protein to 20-40 g/day, maintain adequate calories
 Ü ammonia formation in the intestine – give laxative, enema as ordered and
Neomycin - Ü bacterial ammonia production
b.) Protect pt. from injury
 side rails up
 turning to side
 assess mental status, LOC
 proper positioning (semi-Fowler’s)
 prevent aspiration
c.) Prevent further episodes of encephalopathy
 low protein diet
 prescribed medications
 avoid constipation ( to Ü ammonia production by bacteria in the GIT)
 early signs of encephalopathy (restlessness, slurred speech, dec. attention span)

HEPATIC FAILURE
Introduction
Liver failure is the inability of the liver to perform its normal synthetic and metabolic function
as part of normal physiology. Liver failure occurs when large parts of the liver become damaged
beyond repair and the liver is no longer able to function.
Liver failure is a life-threatening condition that demands urgent medical care. Most often liver
failure occurs gradually and over many years. However, a more rare condition known as acute
liver failure occurs rapidly (in as little as 48 hours) and can be difficult to detect initially.
Two forms are recognized
Acute liver failure - development of hepatic encephalopathy (confusion, stupor and coma) and
decreased production of proteins (such as albumin and blood clotting proteins) within four weeks
of the first symptoms (such as jaundice) of a liver problem. "Hyperacute" liver failure is said to
be present if this interval is 7 days or less, while "subacute" liver failure is said to be present if
the interval is 5-12 weeks.
Chronic liver failure usually occurs in the context of cirrhosis, itself potentially the result of
many possible causes, such as excessive alcohol intake, hepatitis B or C, autoimmune, hereditary
and metabolic causes (such as iron or copper overload or non-alcoholic fatty liver disease)
Fulminant hepatic failure
FHF - acute liver failure & encephalopathy within 8 weeks of signs and symptoms & without
history or physical evidence of chronic liver disease
Subfulminant HF- acute liver failure & encephalopathy 8 and 24 weeks after the onset of signs &
symptoms
A Classification based on the time interval from the onset of jaundice to the development of
encephalopathy
Hyperacute LF - within 7days
Acute LF - within 8 to 28 days
Subacute LF - between 5 to 28 weeks
Causes of liver failure
There are several causes of liver failure. The most common causes of liver failure are:
Hepatitis B
Hepatitis C
Long term, excessive alcohol consumption
Cirrhosis
Hemochromatosis
Malnutrition
Acetaminophen (Tylenol) overdose
Reaction to a prescribed medication
Ingestion of poisonous wild mushrooms

Molecules implicated in the pathogenesis of acute liver failure

The main cause of mortality in patients with acute hepatic failure is brain edema. Ammonia is
perhaps the most thoroughly studied molecule that has been implicated in the Pathogenesis of
hepatic encephalopathy and brain edema.
Effect of ammonia
• Ammonia was converted to glutamine by astrocytes
• Intracellular glutamine increasing intracellular osmolarity and causing cell swelling
• Extracelluar glutamine stimulates n-NOS, causing vasodilatation.
• Increases the cerebral uptake of the albumin-bound neutral amino acids, including tyrosine,
phenylalanine, and tryptophan.
• An accumulation of endogenous benzodiazepines, GABA-like molecules, or both also
impairs neurotransmission

Symptoms of liver failure

The early symptoms of liver failure are similar to symptoms of many other conditions. Because
of this, liver failure may initially difficult to diagnose. Some of the most common initial
symptoms of liver failure are:
Nausea
Loss of appetite
Fatigue
Diarrhea
As liver failure progresses, the symptoms become more serious. The most common symptoms of
advanced liver failure include:
Jaundice
Bleeding easily
Swollen abdomen
Mental disorientation or confusion
Sleepiness
Coma

Management

Goal: To remove toxin

Blood and blood component treatments
Hemodialysis
Hemodiafiltration
Plasmapheresis
Albumin dialysis
Blood and blood component treatments
By 1965, it was generally accepted that acute hepatic failure was a disease of metabolic origin.
Success of exchange transfusions in treating hemolytic disease of the newborn, carbon monoxide
poisoning, and acute renal failure led clinicians to apply exchange transfusions to acute liver
failure.
5-50 L of whole blood were used.
Cross-circulation.
Total body washout.
Hemodialysis
Although ammonia is removed with dialysis, serum ammonia levels are not substantially
lowered with hemodialysis.
Sorbent hemoperfusion:
Charcoal-based sorbents: not effectively remove protein-bound material and ammonia.
Synthetic resins: removing lipid-soluble molecules and protein-bound molecules
Anion exchange resins

Hemodiafiltration
Hemodiafiltration combines charcoal hemoperfusion with a cation exchange resin for improved
clearance of positively charged molecules.
Some improvement in neurologic function.
Did NOT to show any improvement in survival rate for patients with liver failure and
encephalopathy.
Plasmapheresis
Plasma exchange has been used sporadically in the management of acute liver failure during the
past 30 years.
Small series reported some benefit for patients with acute failure secondary to toxic ingestions.
The rationale for treatment is to prevent life-threatening complications.
Total plasma exchange can correct the bleeding diathesis associated with acute liver failure.
Plasma exchange did NOT significantly affect graft survival in patients with primary graft
dysfunction.
Intracellular, protein- and tissue-bound toxins were NOT effectively removed, and there was a
theoretic risk of removing unidentified hepatotrophic molecules from the circulation.
Complications of plasmapheresis included pulmonary edema, infection, and hypocalcemia from
citrate intoxication.
Albumin dialysis
Albumin synthesis was inhibited in ALF.
Some components is elevated in patient of ALF.
Bilirubin, aromatic amino acids, endogenous benzodiazepines, mercaptans, nitric oxide,
prostacyclins, and tryptophan.
Elevated toxic substance may be correlated with clinical status.
The Molecular Absorbent and Recirculating System (MARS)
Ameliorate hepatic encephalopathy and decrease the elevations of intracranial pressure (ICP).
Decrease in cerebral oxygen extraction concurrent with a clinical improvement in neurologic
status.
The effect is independent of plasma ammonia levels or hemodynamic status.
Large increases in factor VII levels, albumin levels, and the ratio of branched-chain amino acids
to aromatic amino acids (phase I trial).
A notable decrease in patient mortality seen with MARS treatment (30-day mortality :8.3% and
50% with MARS or medical treatment alone; p=0.0027) (a prospective RCT,2002).
MARS treatment did result in a marked increase in mean survival time in patient of hepatorenal
syndrome. (25.2 ±34.6 days in the MARS versus 4.6 ± 1.8 days in the hemodiafiltration alone
group,2000).
Nursing management
1. Activity intolerance related to fatigue, anemia from poor nutrition and bleeding,
ascites, dysponea from pressure of ascites to diaphragm, muscle wasting
• Alternate rest & activity
• Monitor hemoglobin and hematocrit to rule out any bleeeding.
• Assist with daily living activities to conserve energy.
• Administer iron supplements or blood transfusion as ordered to treat anemia.
• Assist with measures to decrease edema and ascities to increase the lung capacity.
2. Ineffective protection related to decrease filtering of bacteria by liver and impaired
synthesis of clotting factors.
• Monitor for manifestations of hemorrhage
• Provide assistance with ambulation and activities of daily living.
• Use small-gauge needles for injections and apply prolonged pressure after injection
• Recommend soft – bristle toothbrush.
• Teach to avoid vigorous blowing of nose or straining at stool.
• Administer vitamin K as orederd.
• Follow infection control procedures
3. Imbalanced nutrition: less than body requirements related to impaired utilization
and storage of nutrients from vomiting
• Weigh daily
• Provide oral hygiene before meals.
• Administer antiemetic as ordered.
• Provide small and frequent meals
• Determine food preferences and assist in selection of those that contain low or no protein
and low salt.
 • Prevent constipation.
4. Acute confusion related to portal systemic encephalopathy occuring in conjunction
with gastrointestinal bleeding and accumulation of ammonia in the bloodstream.
• Monitor manifestations of encephalopathy such as disorientation, changes in handwriting
or speech, or coma.
• Encourage fluids
• Give laxatives and enemas
• Provide low-protein diet ; reduces generation of ammonia.
• Limit activity.
• Treat GI bleeding
5. Ineffective breathing pattern related to pressure on diaphragm and reduced lung
capacity.
• Place the client in semi-fowlers or fowler position with arms supported with pillows.
• Assess manifestations such as crackles or increased respirations.
• Administer oxygen
6. Fluid volume excess related to retention of fluids secondary to decreased serum
albumins, increased sodium and water, portal hypertension, and possible shunting
procedures causing hemodilutaion of blood
• Follow sodium and fluid restrictions
• Administer diuretics
• Weigh daily
• Measure abdominal girth every day or shift
• Monitor intake/output.
• Monitor electrolytes, hemoglobin and hematocrit.
• Implement measures to prevent skin breakdown
• Administer albumin
• Assist with paracentesis procedure.
References:
1 Black M. Joyce “Medical-Surgical Nursing” Ed.6th; Saunders publication; 2007; (2); 1330-
60.
2 Nettina M.S. “Lippincot Manual of Nursing practices” Ed. 8th; Lippincot; 2006; 562-80.
3 Robbins “Pathologic basis of disease” Ed. 7th; Saunders Elsevier; 2006; 643-46.
4 Smeltzer Suzanne “Brunner & Suddarth’s Textbook of medical surgical nursing” Ed 11th;
Lippincot; 2008; 1039-42
5 www.mayoclinic.com