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home - Liver - Alcohol - Alcoholic Metabolic Injury Written by Dr Sebastian Zeki
Knowledge


Recognises the rising incidence of acute and chronic liver disease in
the UK related alcohol abuse and in particular the increasing alcohol
consumption in adole nts young adults women and growth in
obesity

Recognises alcoholic hepatitis and understands the prognostic
scores determined by Maddrey’s discriminant function the Glasgow
alcoholic hepatitis score and their role in identifying which patients
may benefit from corticosteroids Can treat alcohol withdrawal

Aware of appropriate use of benzodiazepines in alcohol withdrawal
and can recognise the early signs of delirium tremens

Skills
Is able to take a relevant history and perform appropriate examination
Recognises those patients who would benefit from corticosteroids
instituting treatment and has awareness of indications for withdrawing
their use
Aware of the potential complications of alcoholic hepatitis chronic
liver disease and able to prevent or intervene where appropriate

Behaviours
Appreciates the role of other specialists nurse specialists
intensivists radiologists dieticians psychiatrists and addiction
specialist

Communicates effectively with patients their relatives in the context
of their disease its severity prognosis and substance abuse

Identifies the abstinent alcoholic who would benefit from
transplantation

Considers all therapeutic modalities and preparedness to refer to
specialist centre where diagnosis remains in doubt or appropriate
management cannot be performed as per national guidelines

Alcoholic Metabolic Injury

Action of injurious cytokinesIncreased TNFalpha, IL-6 and cyclooxygenase 2 (COX-2), and reduced eNOS has been foundEndotoxin Alcoholics have increased serum endotoxin (lipopolysaccharide) LPS binds to cell surface receptors and causes cytokine production acutelyChronic LPS production may be tolerated in alcoholics however so may be less important in chronic injuryDendritic Cell FunctionDendritic cell function may be altered in alcoholic liver disease, an effect that could impair the cell mediated response to chronic hepatitis C virus infection.Altered dendritic function may also lead to increased release of proinflammatory cytokines.Another study identified reduced expression of a glucocorticoid-induced leucine zipper protein, GILZ, which amplifies macrophage responses and sensitivity to lipopolysaccharide.Inflammatory cell infiltration and activationInflammatory mediators from Kupffer cells (liver macrophages) may also have a role in ethanol-induced hepatic injury.Inflammation may also be influenced by dietary fat.As an example, saturated fat is capable of downregulating liver injury in experimental alcohol feeding.Neutrophil infiltration and activationProbably stimulated by chemoattractants IL-8 and an arachidonic acid metabolite related to leukotriene B4. Its generation probably results from free radical attack on membranes.One source of these reactive oxygen species may be non-ADH pathways of ethanol oxidation, such as the MEOS.Centrilobular hypoxiaThis theory suggests that a zone of hypoxia develops around central veins because this region, which is furthest from oxygenated blood, is most likely to suffer oxygen debt as ethanol metabolism consumes oxygen.Experimental studies in rats fed ethanol offer support for this hypothesis, since an oxygen gradient was demonstrated between periportal and pericentral zones.These changes mimic those induced by thyroid hormone.Furthermore, studies in animals have shown that the antithyroid medication propylthiouracil (PTU) abrogates alcohol-related hypoxic injury.These findings have led to clinical trials of PTU in patients with ongoing alcoholic liver injury. Alcohol Toxicity Mechanisms Alcohol P450 Alcohol dehydrogenase Hydroxethyl Radical Oxygen radicals Acetaldehyde Adducts Oxidative stress Lipid peroxidation (with adduct formation) Adducts Adducts= acetaldehyde and hydroxyethyl radicals binding proteins to make them antigenicBind various intracellular proteins and can lead to cell dysfunction as well as provoking immune reaction. HCS activation Liver fibrosis Hepatocyte Injury Immune reactions to Alcohol Induced Hepatocyte Damage Written by Dr Sebastian Zeki

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