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Page 4 of 10 Ramadori. Hepatoma Res 2020;6:28 I http://dx.doi.org/10.20517/2394-5079.2020.43

Figure 2. Autoradiograph of a SDS-PAGE-analysis of immunoprecipitates from cell culture supernatants (hepatoblasts and hepatocytes).
Radioactively labelled albumin was immunoprecipitated with a specific antibody. The strong speed of the release of the newly synthesized
protein is an explanation for the difficulty to detect albumin (as a protein) in the liver sections by using immunostaining techniques.
Histochem Cell Biol 2007;128:431-43. (reprinted with permission) [37]

[37]
The liver is the sole source of serum albumin [Figures 1 and 2] which represents more than 50% of all
proteins synthesized in the liver. Under normal conditions albumin synthesis in the hepatocytes is regulated
by the amount of proteins reaching the intestine after each meal, and the amount of amino acids transported
into the liver through the portal system.

[38]
During fasting, reduced albumin synthesis is due to a reduced uptake of amino acids into the hepatocytes ,
which may be in part compensated by using amino acids from muscle proteins.

During acute phase situations, characterised by tissue damage induced by different insults such as trauma,
bacterial infection, or viral infections such as SARS-CoV-2, the defence mechanisms of the body concentrate
on eliminating the aggressive agent at the site of tissue entry and/or the damaged tissue. The main systemic
reactions during the COVID-19 illness are fever, weakness and loss of appetite. In addition vomiting,
[39]
[40]
diarrhea and abdominal discomfort , which may be accompanied by loss of taste and loss of smell
(anosmia) [41,42] , may be also be present. At the beginning of the illness a dry cough and sometimes dyspnoea
may be present. The systemic defence reaction may last for a few days and the consequences may not be
clinically noted if the person continues to stay home and recovers promptly. If the symptoms last for a week
or longer, two major consequences have to be considered: (1) severe fluid losses leading to dehydration and
ultimately hypovolaemic shock; (2) reduction in caloric intake which worsens symptoms of weakness, and
[43]
accelerates a rapid loss in body weight .
These changes may be aggravated by the simultaneous intake of antihypertensive medication, including
[44]
diuretics, as might be encountered in older patients and/or those patients with multiple comorbidities .

The systemic reaction, a major component of body defence strategy, is induced by different cytokines
that originate the main site of injury, e.g., the lungs. The so called “major acute-phase mediators” are
Interleukin-6, Interleukin-1, TNF-alpha, and IFN-gamma, which are all synthesized in different amounts,
depending on the quality (organ and damaging agent) and the quantity of tissue damage.

[45]
The acute phase cytokines are responsible for the central regulation of body temperature , reduction in
[46]
appetite, and associated adynamia and mental confusion .

The reduction of appetite (anorexia) on the one hand, and abdominal discomfort on the other, can also be
attributed to the direct action of the cytokines on the intestinal neurons, with alterations in the mobility