Hepatic encephalopathy

Introduction to hepatic encephalopathy Hepatic encephalopathy (HE), also known as hepatic coma, is a comprehensive symptom of central nervous system dysfunction caused by severe liver disease caused by severe liver disease. The main clinical manifestations are disturbance of consciousness, behavioral disorder and coma. There are acute and chronic encephalopathy points. basic knowledge The proportion of sickness: 0.00009% Susceptible population: people with severe liver disease Mode of infection: non-infectious Complications: cerebral edema, gastrointestinal bleeding, renal insufficiency

Cause of hepatic encephalopathy

Cause of disease

The primary diseases causing hepatic encephalopathy include severe viral hepatitis, severe toxic hepatitis, drug-induced liver disease, acute fatty liver in pregnancy, various types of cirrhosis, portal-to-body venous shunt, primary liver cancer, and other diffuse The end stage of liver disease, and hepatic encephalopathy in patients with cirrhosis is the most common, accounting for about 70%.

Pathophysiology

The mechanism of hepatic encephalopathy has not yet been fully elucidated. The hypotheses currently proposed are: ammonia toxicity theory, pseudo neurotransmitter theory and r-aminobutyric acid (GABA) theory.

Hepatic encephalopathy prevention

1. Prevention and timely treatment of gastrointestinal bleeding: The most fundamental way to prevent portal hypertension and upper gastrointestinal bleeding is to reduce portal hypertension or treat esophageal varices. Once the upper gastrointestinal bleeding occurs, hemorrhage should be given in time, and the stomach should be removed in time. Intestinal blood.

2. Prevention and control of various infections: such as intestinal infection, primary bacterial peritonitis, hypostatic pneumonia, acne infection and sepsis, etc., are often an important cause of hepatic encephalopathy, and should be given anti-infective treatment in a timely and reasonable manner.

3. Prevention and treatment of constipation can be given lactulose, sorbitol, fruit guide, senna, rhubarb, sorbitol, magnesium sulfate, etc., as appropriate, can also be given to open the plug anal, if necessary, to give a clean enema.

4. Prevent and correct electrolyte and acid-base balance disorders.

5. Use sedatives with caution, ban sulfur-containing, ammonia-containing drugs, prohibit a large amount of ascites, reduce surgery, trauma and excessive diuresis, and eliminate iatrogenic factors.

Hepatic encephalopathy complications Complications, brain edema, gastrointestinal bleeding, renal insufficiency

1. Cerebral edema cerebral edema has been confirmed as a complication of fulminant hepatic failure, the incidence rate can reach more than 80%. There is no consensus on the existence of cerebral edema in chronic liver disease, but most scholars believe that chronic hepatic encephalopathy can be concurrent Cerebral edema, the incidence of each report is also inconsistent, most believe that 21% to 58%, but recently through the autopsy found that cirrhosis cerebral edema detection rate as high as 89.5%, of which mild edema was 23.7%, severe edema accounted for 65.8 %, 21% of patients with clear encephalopathy, indicating that the incidence of cerebral edema in chronic liver failure is also high, and is one of the main causes of death.

2. Gastrointestinal bleeding.

3. Renal insufficiency.

4. Water and acid acid-base balance disorders.

5. Infection.

Hepatic encephalopathy symptoms Common symptoms Liver failure, weakness, sleepiness, sensory disturbance, dysfunction, coma, ataxia, jaundice, drowsiness, mental retardation

1. Clinical manifestations The clinical manifestations vary depending on the type of liver disease, the degree of hepatocyte damage, the onset of the disease, and the cause of the cause. The clinical manifestations of the hepatic encephalopathy are different, and the clinical manifestations are more complicated. Variability, the variability of early symptoms is a characteristic of this disease, but it also has its common features: it is reflected as neuropsychiatric symptoms and signs, both the performance of the primary liver basic disease, and its unique clinical manifestations, generally expressed as Characters, behaviors, intellectual changes, and disturbances of consciousness are now outlined in the clinical manifestations of their encephalopathy as follows:

(1) Onset: It can be urgent and slow, acute hepatic encephalopathy is onset, the prodromal period is extremely short, and it can quickly enter a coma. Most of the coma occurs after the appearance of jaundice. There is also a disturbance of consciousness before the appearance of jaundice and is misdiagnosed as a mental illness. The onset of chronic hepatic encephalopathy is insidious or gradual. It is often difficult to find at first, and is easily misdiagnosed and missed.

(2) Personality change: It is often the earliest symptom of this disease, mainly because the original extroverted personality showed depression, while the original introverted personality showed euphoric multilingual.

(3) Behavioral changes: Initially it may be limited to some "disregarding" behaviors, such as scribbling, sprinkling water, spitting, throwing confetti, cigarette butts, chaos, squatting, table in the room The chair is free to mess up and let go of meaningless movements.

(4) changes in sleep habits: often manifested as sleep inversion, also known as impending coma (impending coma), this phenomenon has been found to be related to the patient's serum melatonin secretion disorder, suggesting the patient's central nervous system excitement and Inhibition is in a state of disorder, often indicating that hepatic encephalopathy is imminent.

(5) The appearance of liver odor: due to liver failure, a characteristic of sulfur-containing amino acid metabolism intermediates (such as methyl mercaptan, ethanethiol and dimethyl sulfide) exhaled through the lungs or excreted through the skin. Sexual scent, this smell has been praised by scholars for rotten apple flavor, garlic flavor, fishy smell and so on.

(6) flapping tremor: it is the most characteristic neurological sign of hepatic encephalopathy, which has early diagnostic significance, but unfortunately not all patients can have flapping tremor by: the paralyzed patient extends the forearm. When the five fingers are extended, or the wrist is overstretched and fixed, the patient's palm-finger and wrist joints may have rapid flexion and extension exercises, which may occur 1 or 2 times per second, or 5 to 9 times per second. And often accompanied by the lateral movement of the finger, the patient can be accompanied by the entire upper limb, tongue, chin, jaw tremor and gait ataxia, or on one side, can also appear in On both sides, this kind of tremor is not characteristic. It can also be seen in patients with heart failure, renal failure, lung failure, etc. The tremor often disappears after the patient sleeps and coma, and can still appear after waking up.

(7) Visual impairment: not common, but in recent years, literature reports at home and abroad have gradually increased. Patients with visual impairment may appear when hepatic encephalopathy occurs. Blindness is the main clinical manifestation. This visual impairment is transient and functional. As the hepatic encephalopathy deepens and worsens, it can be recovered with the recovery of hepatic encephalopathy. The pathogenesis is unknown. Most of them are considered to be as complex as hepatic encephalopathy. As a result of the combined effects of various factors, this visual impairment phenomenon The current naming has not been completely unified. To fully reflect the relationship between the liver, brain and eyes, the author has referred to this type of performance as "liver-brain-eye syndrome".

(8) Intelligent obstacles: As the disease progresses, the patient's intelligence changes, manifested as time, the concept of space is unclear, the concept of the characters is vague, the words are unclear, the words are difficult to write, the writing is difficult, the calculation, the counting ability is declining, the digital connection is wrong. It is also a simple and reliable method for early identification of hepatic encephalopathy.

(9) Disorder of consciousness: Following the mental retardation, there is a relatively obvious disturbance of consciousness. From sleepiness to lethargy, it gradually enters a coma state. Various reactions and reflexes disappear, and some people gradually enter the coma from a manic state.

The main clinical manifestations of hepatic degenerative hepatic encephalopathy are: mental retardation, difficulty in articulation, memory loss, slow thinking, ataxia, tremor, and paraplegia (hepatic myelopathy), but no obvious disturbance of consciousness.

2. Clinical staging is convenient for early diagnosis and guidance of treatment, often according to the patient's clinical manifestations of clinical stage of hepatic encephalopathy, but its clinical staging is not consistent, some are divided into three, four, five, or even six At present, most scholars agree that Davidson divides hepatic encephalopathy into a prodromal phase, a pre-coma period, a slumber period, and a coma period according to its clinical manifestations, but there is no clear boundary between the stages.

(1) Stage I (prodromal period): mild personality changes and behavioral disorders, manifested as: depression or euphoria in personality changes, unconscious movements in behavioral changes, sleep reversal in sleep time changes, flapping tremor (-) Normal reflex exists, pathological reflex (-), and EEG are normal.

(2) Stage II (pre-coma): mainly caused by confusion, sleep disorders, and behavioral disorders, manifested as disorientation, timing disorders, decreased computational power, written confusion, unclear language, blurred concept of characters, flapping wings Symptoms of tremor ( ), normal reflexes, pathological reflexes ( ), common knee reflexes, convulsions ( ), muscle tension can be enhanced, involuntary movements and movement disorders can occur, EEG symmetry waves appear (per 4 to 7 seconds).

(3) Stage III (sleeping period): Mainly due to lethargy and mental disorder, the patient is in a state of lethargy most of the time, the reaction exists (can be awakened), or the arrogant disturbance, flapping tremor ( ), muscle tension is obvious Enhanced, EEG with Phase II.

(4) Stage IV (coma): During this period, the patient's consciousness is completely lost and cannot be awakened. In the case of shallow coma, there is still a reaction to painful stimuli (such as positive pressure reflex) and discomfort, and tendon reflexes and muscle tone are still hyperactive. Flapping-like tremor can not be elicited because the patient can't cooperate with the examination. When the coma is deep, the various reflexes disappear, the muscle tension is reduced, and the pupil is often scattered. It can be manifested as paroxysmal convulsions, convulsions ( ), excessive ventilation, Very slow delta waves (1.5 to 3 times/s) appear on the EEG.

3. Clinical classification

(1) Clinically, according to the rapid development of hepatic encephalopathy, it is often divided into acute type and chronic type.

1 acute type: hepatic encephalopathy caused by fulminant hepatic failure caused by acute or subacute severe viral hepatitis or drugs, poisons, etc., due to massive or large necrosis of hepatocytes, residual hepatocytes can not maintain normal metabolism of the body Desirable, resulting in metabolic imbalance, the body's metabolic toxicants can not be effectively cleared and accumulated, leading to central nervous system dysfunction, also known as endogenous hepatic encephalopathy or non-ammonotic hepatic encephalopathy.

Clinical manifestations: often no incentives, rapid onset, short duration, short or no prodromal period, patients often enter the coma in a short period of time, the digestive tract and systemic symptoms are obvious, signs: early liver can be swollen, touch, pressure, cramps Gradually, the liver dullness is narrowed, and there is no portal hypertension. Occasionally, the flapping tremor is occasionally seen, and the liver function jaundice is obviously increased. The transaminase can be significantly increased. In severe cases, the separation of enzyme bile can occur, prothrombin time is prolonged, and blood cholesterol is lowered. This type of disease is critical, the prognosis is extremely poor, the mortality rate is extremely high, more than short-term death, survivors can develop into necrotizing cirrhosis.

2 Chronic type: due to various reasons of chronic liver disease, cirrhosis or portal shunt, often with hepatocyte degeneration and necrosis, but also liver cell regeneration and repair, but regenerative hepatocyte insufficiency, resulting in metabolic imbalance The toxic substances in the body can not be effectively removed, or the toxic substances in the portal body directly enter the systemic circulation and cause central nervous system dysfunction. The brain tissue of this type of patients often has pathological changes such as stellate cell hypertrophy, increase, cerebral cortex thinning, and focal Necrosis, this type belongs to exogenous hepatic encephalopathy, also known as ammoniatic or portal shunt encephalopathy.

Clinical manifestations: often have incentives, slow onset, different severity of illness, recurrent attacks, digestive tract and systemic symptoms, but mild, sometimes no neuropsychiatric symptoms, recurrent neurological spirit can gradually appear after repeated episodes Symptoms, physical examination can have cirrhosis and portal hypertension manifestations, often with flapping tremors during the attack, liver function changes can be not serious, advanced can be aggravated, this type of sputum removal incentives, active treatment can be restored, prognosis is good, but the disease Late or often due to other complications.

(2) Hepatic encephalopathy In addition to the above-mentioned acute and chronic types, there are other special types.

1 hepatic degeneration type: due to spontaneous or portal shunt patients, intestinal toxic substances are continuously shunted to the systemic circulation, repeatedly acting on the central nervous system, causing neuronal degeneration, clinically slow thinking, memory loss, consciousness Abnormal, dull or ataxia, but unconscious disorder, also known as acquired hepatic degeneration.

2 Hepatic encephalomyelitis: In addition to extensive degeneration of brain cells, patients with advanced cirrhosis may also have corticospinal tract, cortical cerebellar tract, demyelinating lesions in the posterior spinal cord, clinical weakness of the lower extremities, unstable gait, and thin limbs. Tremors, hyperreflexia, EEG showed extensive changes in the damage, including those with clinical manifestations of the brain and spinal cord called hepatic encephalomyelopathy; those with prominent spinal cord lesions were called hepatic myelopathy.

The basic pathological change of hepatic myelopathy is cirrhosis. The spinal cord is mainly demyelination. The pyramidal tract in the lateral cord is most obvious, with axonal degeneration, disappearance, etc., replaced by glial cells. Multi-wave and spinal cord below the cervical spinal cord, and there is no essential difference between the pathological changes of the large and cerebellum and hepatic encephalopathy. The clinical manifestations are mainly on the basis of acute and chronic liver disease: generally starting from the difficulty of walking on both lower limbs, it is scissors or gait, gradually appear paraplegia of both lower extremities, muscle weakness of both lower extremities, increased muscle tone, hyperreflexia of the knee, positive pyramidal tract sign, general incontinence caused by sensory and sphincter disorders, individual muscles Atrophy, cerebrospinal fluid is generally normal, EEG may or may not be abnormal, brain CT, myelography, spinal MRI and other examinations are normal, electromyography shows changes in motor neurons, and the treatment of this disease is not special, mainly taking comprehensive treatment, In addition, large doses of vitamins, compound salvia, prostaglandins, etc. can be given. Some scholars believe that the portal-body shunt narrowing or liver transplantation can treat this disease.

3 Subclinical hepatic encephalopathy: This study has been proposed in recent years. This type of patient often has no hepatic encephalopathy in clinical practice, and is qualified for general work. There is no obvious abnormality in routine examination, only after completing routine mental exercise tests (such as drawing or When the digital connection) is impaired, due to the atrophy of the patient's brain, the cerebral blood flow is reduced, and its intelligence detection (especially the ability to operate) and brain evoked potential abnormalities, such as high-altitude, mechanical, driving and other types of work are prone to accidents or car accidents, such as Early diagnosis or replacement work can avoid potential accidents or further develop into clinical hepatic encephalopathy. This type may also be a subclinical stage of hepatic encephalopathy. With the aggravation of liver disease, it may develop into chronic hepatic encephalopathy. Rikker et al. followed up on 9 patients with subclinical hepatic encephalopathy for 1 year and found that there were no changes in blood ammonia and intelligence tests in 6 patients. Only 3 patients with elevated blood ammonia had mental retardation and developed clinical hepatic encephalopathy.

Examination of hepatic encephalopathy

1. Abnormal liver function, abnormal blood coagulation often only reflects the functional status of hepatocytes, such as separation of enzymes, hyperbilirubin, hypoproteinemia, decreased cholinesterase activity and decreased serum cholesterol, etc. The severity of sexual encephalopathy, blood biochemical tests such as water, electrolytes and acid-base balance disorders can promote and aggravate hepatic encephalopathy. Renal function (creatinine, urea nitrogen) examination, such as abnormalities, only indicates that kidney failure is about to occur or has occurred in recent years. It is considered that the dynamic observation of serum melatonin level has important reference value for predicting, diagnosing the occurrence of hepatic encephalopathy and judging the changes of the condition.

2. Blood ammonia determination of about 75% HE patients with increased blood ammonia concentration, increased in chronic patients, acute patients with increased, but elevated blood ammonia, not necessarily hepatic encephalopathy, so The increase of blood ammonia concentration has certain reference significance for diagnosis, and it also has reference significance for guiding treatment. For example, it is more meaningful to determine the increase of arterial blood ammonia concentration than venous blood ammonia.

3. Determination of plasma amino acid If the concentration of branched chain amino acids is decreased, the concentration of aromatic amino acids (especially tryptophan) is increased, and the ratio of the two is inverted <1, which is more obvious in the chronic type, and the GABA is also measured at the same time.

4. EEG examination EEG changes have a certain significance for the diagnosis and prognosis of the disease. The normal EEG has a low amplitude, a high frequency, and the waveform is wave. As the disease changes and develops, the frequency slows down. The amplitude gradually increases, and the wave shape changes from wave to 4 to 7 times per second. The wave is prompted to be in the early stage of coma. If it becomes symmetrical, the high amplitude, the wave of 1.5 to 3 times per second is the coma. For suspicious EEG changes, EEG changes can be made after eating high-protein and intramuscular low-dose morphine, and EEG changes in hepatic encephalopathy can also be seen in uremia, lung failure and hypoglycemia. Etc., should be distinguished.

5. Visual-evoked potential (VEP) After flash stimulation, the cortex of the occipital lobe can be stimulated to produce a synchronous discharge effect, causing a potential change, ie, VEPs, which represent the cortical and subcortical nerve cell population. The sum of post-synaptic excitability and inhibitory potential is specific for assessing brain dysfunction in hepatic encephalopathy, and can be quantitatively analyzed. It can more accurately reflect brain potential activity than general EEG, and can be used to detect the liver before symptoms appear. For encephalopathy (such as subclinical hepatic encephalopathy), there are also people who use auditory event-related potential P300 and somatosensory evoked potential to diagnose subclinical hepatic encephalopathy. It is considered that the diagnostic value of auditory event-related potential P300 is more sensitive and specific than somatosensory evoked potential.

6. Cerebrospinal fluid examination routine, pressure and biochemistry can be normal, such as simultaneous determination of ammonia, glutamic acid, tryptophan, glutamine concentration can be increased, the pressure can be increased in concurrent cerebral edema.

7. Brain magnetic stimulation test Nolano et al. used brain magnetic stimulation to measure the cerebral cortical motor function of patients with liver cirrhosis. It was found that the central motor nerve conduction time was prolonged, the threshold of motor arousal during sleep increased, the central non-recording period was shortened, and the peripheral circumference was normal, indicating cortex. The spinal cord pathway has been damaged and can be considered as a pre-existing manifestation of cirrhosis with hepatic encephalopathy.

Diagnosis and differentiation of hepatic encephalopathy

diagnosis

1. Early diagnosis test (intelligence test) For the early clinical manifestations of hepatic encephalopathy, in addition to careful examination and close observation of the condition, the following methods are needed for examination, which is helpful for early diagnosis. Inspection is the most valuable diagnostic test method that is practical, simple and fast, without special equipment, and is suitable for primary hospitals.

(1) Digital connection test: 25 Arabic numerals are printed on paper at random, and the patient is connected with a pen according to the natural size. The time of connection is recorded, the frequency of connection errors is checked, and the method is simple and can find early patients. Its abnormality may even be earlier than EEG changes, and can be used as an indicator of efficacy judgment.

(2) Signature test: Allow patients to sign their own names every day, such as irregular handwriting, can find early encephalopathy.

(3) Building blocks test: If you use a match to take a five-pointed star, or draw a sketch, or do a simple addition or subtraction.

2. Diagnosis The diagnosis of this disease is based on clinical diagnosis, combined with laboratory tests for comprehensive analysis, mainly based on patients:

(1) There is a history of severe liver disease and/or extensive portal-body shunt (postoperative portal hypertension or portal shunt), clinical manifestations and abnormal liver function tests.

(2) A series of neurological and psychiatric symptoms appear.

(3) It is often accompanied by an increase in blood ammonia and/or a decrease in the ratio of branch/aromatic amino acids or inversion.

(4) Abnormalities in EEG or visual evoked potentials and exclude other causes.

(5) Cerebrospinal fluid pressure and routine examination are normal; diagnosis can be made.

(6) If you can find the cause of hepatic encephalopathy, it is more conducive to diagnosis.

3. Diagnosis of cerebral edema Brain edema is usually judged according to the signs of elevated intracranial pressure, but the characteristics of intracranial hypertension are often not obvious when the patient is in stage IV hepatic encephalopathy (deep coma), and it is easy to return all kinds of performances in this period. Due to hepatic encephalopathy and neglecting the existence of cerebral edema, many patients missed the diagnosis of cerebral edema during their lifetime. If the degree of coma in patients with hepatic encephalopathy is deepened, blood pressure is increased, the pulse is slow and the lungs are deep, and the breathing is fast. Obvious edema, treatment with dehydrating agents such as mannitol can be quickly effective, the diagnosis of cerebral edema can be established, in addition, head CT and magnetic resonance imaging examination can help diagnose cerebral edema, monitoring intracranial pressure with intracranial pressure monitor It is an important technology for current applications.

Differential diagnosis

The diagnosis of typical hepatic encephalopathy is generally not difficult, but the following points should be noted:

1. The symptoms of prodromal period of hepatic encephalopathy are generally not easy to attract people's attention, and it is easy to miss the diagnosis and delay the disease. Therefore, patients with severe liver disease or portal hypertension or portal shunt must improve their understanding of the disease and carefully check. Close observation of changes in the condition, parallel digital connection test, signature test, painting or graphic test to make early diagnosis.

2. Patients with hepatic encephalopathy often have neuropsychiatric symptoms and some patients with hepatic and brain degeneration. They are easily misdiagnosed as psychosis, and early diagnosis is needed.

3. Patients with hepatic encephalopathy III and IV have fallen into consciousness disorder and need to be differentiated from other diseases that cause coma, such as cerebrovascular accident, craniocerebral trauma, diabetic ketoacidosis, sleeping pills poisoning, alcoholism, uremia, Shock, meningoencephalitis, hypoglycemia coma and other identification.

4. Also need to be differentiated from hepatolenticular degeneration, alcoholic encephalopathy, low sodium syndrome.

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