Hepatic Encephalopathy: Precipitating Factors & Pathogenesis PDF

Summary

This document provides an overview of hepatic encephalopathy, a brain dysfunction often associated with liver insufficiency. It details the precipitating factors, including infections, electrolyte imbalances, and medications, as well as the key steps in the pathogenesis of the condition. The document also includes prevalence and recurrence rates.

Full Transcript

# Precipitating Factors ## Episodic - Infection - GI Bleeding - Diuretic Overdose - Electrolyte Disorder - Constipation - Unidentified ## Recurrent - Electrolyte Disorder - Infection - Unidentified - Constipation - Diuretic Overdose - GI Bleeding ## CNS Depression - Psychoactive drugs / Natal...

# Precipitating Factors ## Episodic - Infection - GI Bleeding - Diuretic Overdose - Electrolyte Disorder - Constipation - Unidentified ## Recurrent - Electrolyte Disorder - Infection - Unidentified - Constipation - Diuretic Overdose - GI Bleeding ## CNS Depression - Psychoactive drugs / Natal - Ammonia Diffusion across the BBB - Systemic alkalosis - Activation of GABA-BDZ receptors - Benzodiazepines - Toxin Metabolism - Hepatoma - Shunts ## Renal Failure - Azotemia - Arterial hypotension - Dehydration - Arterial hypoxemia ## ↑ Ammonia Production - GI Hemorrhage - Hypokalemia ## Other - Sepsis - Hyponatremia - Constipation - Excess dietary protein - Infection # Multiple Factors Can Lead to HE Breakthrough | Category | Specific Factors | |---|---| | **Benzodiazepines** | | | | - Ammonia Production | | | - Activation of Central GABA-Benzodiazepine Receptors | | **Systemic Alkalosis** | - GI Hemorrhage - Hypokalemia - Azotemia - Constipation - Infection | | **Inflammation** | | | | - ↑ Diffusion of Ammonia Across BBB | | **Progressive Parenchymal Damage ** | **Psychoactice Drugs** | |---|---| | - Dehydration | - Hyponatremia | | - Anemia | | | - Arterial Hypotermion | | | - Arterial Hypoxemia | | | - Hepatoma | | | - Shunts | | | **↓ Toxin Metabolism ** | | | | - CNS Depression | # Pathogenesis ## Cirrhosis - Inflammation, bacterial translocation and vasoactive mediators - Hepatocyte dysfunction - Ammonia - Glutamine - Hyponatremia - Depletion of osmolytes - Manganese - Mitochondrial Dysfunction - ROS/RNS - Astrocyte Swelling - Astrocyte Dysfunction - Neuronal Dysfunction - Altered gene expression - Protein tyrosine nitration - Splanchnic and peripheral vasodilation - Portosystemic shunting - Endotoxins - Inflammatory cytokines - Benzodiazepines (exogenous/endogenous) - Increased BBB permeability - False NT - Neurosteroids - "GABA-ergic tone" # Hepatic Encephalopathy # Definition - It is a brain dysfunction caused by liver insufficiency and/or portosystemic shunt (PSS) - It manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. - Reversible impairment of neuropsychiatric function in hepatic patients. # Prevalence - Overall 30%-40% of those with cirrhosis at some time during their clinical course. - The prevalence of OHE at the time of diagnosis of cirrhosis is 10%-14% in general. - In decompensated cirrhosis is 16-21%. - After TIPS 10-50%. - CHE: 20-80%. - The risk for first bout of OHE is 5%-25% within 5 years after cirrhosis diagnosis. ## Recurrence - 40% within 1st year after index OHE. - Recurrent OHE have a 40% cumulative risk of another recurrence within 6 months, despite lactulose treatment.

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