Hepatic encephalopathy

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Definition: • Hepatic encephalopathy (HE) encompasses a wide array of transient and reversible neuropsychiatric manifestat...EASAL…..2014 • Hepatic encephalopathy is a brain dysfunction caused by liver insufficiency and/or PSS; it manifests as a w...West Haven grading of mental state • 0 no abnormality • I Euphoria, anxiety, lack of awareness & impaired addition or subt...Classification Of Hepatic Encephalopathy Classification Clinical features of HE: Grade 0: Minimal HE:  Minimal changes in memory, concentration, intellectual functions and coord...subclinical Multivariate analysis shows that male sex, the Child-Pugh score (B/C) and the presence of varices, together wi...The five SIP statements found to have have independent predictive value for subclinical hepatic encephalopathy are: I. I s...1(According to the underlying disease, HE is subdivided into • Type A resulting from ALF • Type B resulting predominantly ...)2(According to the severity of manifestations. • The continuum that is HE has been arbitrarily subdivided. For clinical a...You Can Know that • The expression hepatic encephalopathy (HE) is a collective term covering five clinical forms of diseas...•)3(According to its time course, HE is subdivided into •Episodic HE •Recurrent HE denotes bouts of HE that occur with a •...Reye’s syndrome • denotes an acute, noninflammatory syndrome with acute liver failure and encephalopathy. Such a “hepatoce...Some investigators contend that HE is a disorder of astrocyte function. Astrocytes account for about one third of cortical...A number of factor occurring alone or in combination have been implicated in the development of HE which may differ in acu...Ammonia hypothesis:  Ammonia is produced mainly in colon by the bacterial degradation of proteins and other nitrogen base...In liver cirrhosis hyper-ammonemmia occurs due to: • Decreased mass of functioning hepatocytes • Porto-systemic shunting m...Skeletal muscles are important sites for ammonia metabolism I liver cirrhosis due to increase in glutamine synthetase acti...Brain astrocytes also posses glutamine synthetase. However brain is unable to increase glutamine synthetase activity in th...Neurotoxic effect of ammonia:  Astrocyte swelling and brain oedema.  Alter neuronal membrane permeability  Alter neurot...GABA hypothesis: • It is a neuroinhibitory substance produced in GIT. • GABA receptor complex contains binding sites for G...Recently it is postulated that GABA receptor complex contains binding site for neurosteroids. Today some investigators con...serotonin, nitric oxide, oxygen free radicles and circulating opioid contribute to encephalopathy. Other factors that affe...Precipitating factors: • Renal failure • GI bleeding • Sepsis • Hyponatremia and hypokalemia • Dehydration (water restrict...Differential diagnosis of HE: • Intracranial lesion • Infections; meningitis, encephalitis, abscess • Metabolic encephalop...Management of HE: Approach considerations: It depends upon the severity of changes in mental status and upon certainty of the diagnosis. As ...General management recommendations: *Exclude non hepatic cause *Check arterial ammonia level *Check precipitant of HE *Avo...Most current medications designed to treat the hyperammonimia. A.Diet: Protein restriction may be appropriate in some patients immediately following a sever flare of symptoms. However, ...B.Cathartics: 1-Lactulose:  It is non-absorbable disaccharides.  It is metabolized in lactic and acetic acids which resu...DOSE: Initial dose 30ml orally daily or twice daily. It is to be increased as tolerated. Patients should take sufficient d...2-L-Ornithine L-Aspartate: • It stimulates urea cycle loss of ammonia • Both are substrates for glutamate transaminase glu...C.Antibiotics: Neomycin and Metronidazole are administered in an effort to decrease the colonic concentration of ammoniage...Rifaximin: (non-absorbable derivative of Rifampin): It has a broad spectrum anti-bacterial activity and thus may be an app...D.Combination of Lactulose and antibiotics:  Has synergistic effect in reduction of ammonia  Achieve significant faster ...E.Probiotics A recent, open-label study of either lactulose, probiotics, or no therapy in patients with cirrhosis who reco...BCAAs • An updated meta-analysis of eight randomized, controlled trials (RCTs) indicated that oral BCAA-enriched formulati...Glutaminase inhibitors Portosystemic shunting up-regulates the intestinal glutaminase gene so that intestinal glutaminase ...Albumin • A recent RCT on OHE patients on rifaximin given daily IV albumin or saline showed no effect on resolution of HE,...Flumazenil • This drug is not frequently used. It transiently improves mental • status in OHE without improvement on recov...Adjuvant therapy Neuropharmaceuticals: Given the neuropsychiatric symptoms of HE and considering the disorders of the neur...Liver transplantation (LT( • Liver Transplantation remains the only treatment option for HE that does not improve on any o...Prognosis Depends on the extend of liver cell failure  Best in chronic patients with extensive collateral circulation  W...Hepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien AhmedHepatic encephalopathy by Dr: Mohammed Hussien Ahmed

 

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Hepatic encephalopathy

 

Definition • It is a state of disordered CNS function, resulting from failure of liver to detoxify toxic agents because of...Pathogenesis • Ammonia formed by protein breakdown in GIT • Liver liver dysfunction (abnormal) NH3 Passes BBB Hepatic ence...Pathogenesis (acute & chronic ) The basic cause is same in both forms but the mechanism is somewhat different Diminished d...Endotoxins • Ammonia. • Mercaptans (degradation of methionine in the gut) • Phenols. • Free fatty acids. • Gamma amino but...Causes • Chronic parenchymal liver disease: • Chronic hepatitis. • Cirrhosis. • Fulminating hepatic failure: • Acute viral...Precipitating Agents • (A) Increase Nitrogen Load (a) Constipation. (b) Gastro intestinal bleeding. (c) Excess dietary int...Precipitating Agents • (B) Infections & Trauma (Surgery) • (C) Electrolyte & Metabolic imbalance • Hypokalemia. • Alkalosi...Precipitating Agents • (D) Drugs • Diuretics. • Narcotics, Tranquilizers, Sedatives. Clinical Features • A Disturbance in consciousness • Disturbances in sleep rhythm. • Impaired memory/ apraxia. • Mental co...• B. Changes Personality • Childish behavior. • May be aggressive out burst. • Euphoric. • Foetor hepaticus – Foul–smellin...• C Neurological signs: • Flapping tremor / Asterixis (in pre coma). • Exaggerated tendon reflex. • Extensor plantar refle...Clinical Staging Differential Diagnosis • Subdural Haematoma. • Drug or Alcohol intoxication. • Wernicke’s encephalopathy. • Hypoglycaemia. Management • Supportive Treatment. • Specific Treatment aims at: • Decreasing ammonia production in colon • Elimination or...TREATMENT • Hospitalize the patient. • Maintain ABC. • Identify and remove the precipitating factors. • Iv fluid dextrose ...Lactulose • Lactulose 15-30ml X 3 – 4 times a day- result aims at 2-4 stools/day. • Rectal use is indicated when patient i...Mechanism of action of Lactulose • A non-absorbable disaccharide. • It produces osmosis of water- Diarrhea. • It reduces p...Treat the GIT & other Infections Antibiotics: • Rifaximin • Broad spectrum antibiotic, recently approved in humans for HE....• Metronidazole : 250mg orally T.D.S • Neomycin : 0.5 – 1 g orally 6 or 12 hours for 7 days. • Side effects: Ototoxicity, ...DIET • With held dietary protein during acute episode if patient cannot eat. • Oral intake should be 60 – 80 g/day as tole...Stimulation of metabolic ammonia metabolism: • Sodium benzoate • 5 g orally twice a day. • L-ornithine-L-aspartate • 9 g o...Correct amino acid metabolic imbalance • Infusion or oral administration of BCAA (branched-chain amino acid) • Its use is ...Acarbose • α – glucosidase inhibitor. • Under study. • Other Therapies: • Prebiotics & probiotics. • Extracorporeal albumi...PROGNOSIS • Acute hepatic encephalopathy may be treatable. • Chronic forms of the disorder often keep getting worse or con...REFERENCES • Davidson’s Principles & Practice of Medicine- 21st edition. • Harrison’s Principles of internal Medicine-10th...Hepatic encephalopathyHepatic encephalopathy

 

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