Pathophysiology
In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the centrizonal distribution and progressing towards portal tracts. The degree of parenchymal inflammation is variable and  is proportional to duration of disease.Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia. Zone 2 (mid-zonal), although rare, is seen in yellow fever. Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. In acute acetaminophen overdose, toxification occurs, mostly in Zone III which has the highest level of P450 micro-enzymes. That fact along with Zone IIIs decreased oxygen level helps to explain why it is preferentially one of the initial sites of damage. Diagnosis
All patients with clinical or laboratory evidence of moderate to severe acute hepatitis should have an immediate measurement of prothrombin time and careful evaluation of mental status. If the prothrombin time is prolonged by ≈ 4–6 seconds or more (INR ≥ 1.5),
and there is any evidence of altered sensorium, the diagnosis of ALF should be strongly suspected, and hospital admission is mandatory. Initial laboratory examination must be extensive in order to evaluate both the etiology and severity.
One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5 to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain. Depression often coexists with physical disorders common among the elderly, such as stroke, other cardiovascular diseases, Parkinsons disease, and chronic obstructive pulmonary disease. History
The Ancient Greek physician Hippocrates described a syndrome of melancholia (μελαγχολία, melankholía) as a distinct disease with particular mental and physical symptoms; he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment. It was a similar but far broader concept than todays depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included. The term depression itself was derived from the Latin verb deprimere, meaning "to press down". From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author Richard Bakers Chronicle to refer to someone having "a great depression of spirit", and by English author Samuel Johnson in a similar sense in 1753. The term also came into use in physiology and economics.