Pathogenesis (disease development)
Hepatic encephalopathy (HE) is a relatively common complication of liver cirrhosis (liver shrinkage). Impaired liver function results in inadequate detoxification of neurotoxic substances (substances toxic to the nervous system) such as ammonia, endogenous benzodiazepines, short-chain fatty acids, gamma-aminobutyric acid (GABA), mercaptan (responsible for the smell of raw liver (“foetor hepaticus”)), phenols, and others. Of central importance in the pathogenesis of hepatic encephalopathy is ammonia. Ammonia is a breakdown product of amino acid metabolism that is normally detoxified by urea synthesis in the cells of the liver. In the context of liver dysfunction, there is increased extrahepatic (outside the liver) metabolism (metabolization) of ammonia by the brain and muscles. In the brain, the so-called astrocytes are the only ones capable of detoxifying ammonia through glutamine synthesis. Astrocytes form the majority of glial cells in the CNS (central nervous system) and participate, among other things, in information processing, storage and transmission. Astrocytes swell due to glutamine accumulation (glutamine accumulation), which increases intracranial pressure. Eventually, cerebral edema (brain swelling) may develop. The following factors favor the development of hepatic encephalopathy – in the presence of liver disease:
- Increased ammonia formation in the intestine after
- Gastrointestinal bleeding (bleeding in the gastrointestinal tract), e.g., variceal (varicose) bleeding
- Protein-rich food
- Constipation (constipation)
- Increased diffusion (transfer of a substance from one distribution space to another) of ammonia into the brain (in metabolic alkalosis (form of acid-base disorder)).
- Increased protein catabolism (protein degradation) and resulting increase in ammonia concentration in febrile infections.
- Iatrogenic (caused by the doctor): therapy with benzodiazepines (drugs that have anxiety-relieving, central muscle-relaxing, sedative (calming) and hypnotic (sleep-inducing) effects), too intensive diuretic therapeutics (dehydrating drugs) with hypovolemia (decreased blood volume) and electrolyte disturbances (hypokalemia (potassium deficiency) or hyponatremia (sodium deficiency)).
- Exudative enteropathy (protein loss enteropathy) – gastrointestinal disease in which there are large protein losses, e.g. diarrhea (diarrhea), vomiting (vomiting).
- Medications such as laxatives (laxatives), sedatives (tranquilizers).
Etiology (causes)
Behavioral causes – in the presence of liver disease.
- Diet
- High protein (protein-rich) diet
- Consumption of stimulants
- Alcohol (woman: > 40 g/day; man: > 60 g/day).
- Drug use
- Ecstasy (also XTC and others) – amphetamine derivative; collective name for a variety of phenylethylamines.
- Cocaine
Disease-related causes – in the presence of liver disease.
- Alcohol abuse (alcohol dependence)
- Dehydration (lack of fluids)
- Diarrhea (diarrhea)
- Emesis (vomiting)
- Gastrointestinal hemorrhage (bleeding in the gastrointestinal tract).
- Hypoxia (lack of oxygen supply to the tissues).
- Infections
Medications – in the presence of liver disease
- Laxatives (laxatives)
- Proton pump inhibitors (PPIs; acid blockers) – may increase the risk of hepatic encephalopathy in patients with advanced cirrhosis in a dose-dependent manner
- Sedatives (tranquilizers)
Further
- Portosystemic shunt (PPS) – Through the vascular connection (= shunt) between the portal vein system and the inferior vena cava (inferior vena cava), the blood from the stomach, intestines and spleen is directed past the damaged liver (liver cirrhosis) to avoid a fatal variceal hemorrhage. However, this eliminates the detoxification of the blood.
