WORK SESSION 5: Alcohol & Liver Metabolism

AIMS

• To appreciate central role of liver in whole body metabolism.
• To be able to relate the damaging effect of alcohol on tissues, the liver in particular, to the metabolic consequences arising from that damage.
• To look at the impact of alcohol consumption on the individual and the population in general.

OBJECTIVES

• To revise your knowledge of alcohol metabolism.
• To identify the biochemical basis for the toxic effects of alcohol on the liver and other tissues.
• To summarise the characteristics of liver disease.
• To be able to interpret liver function tests.
• To use differential diagnosis, incorporating patient history, in making a diagnosis
• To be able to explain the processes by which jaundice arises
• To be able to explain how portal hypertension and oesophageal varices arise
• To be able to describe how nutritional deficiency arises in alcohol addicts
• To be able to explain why alcohol is contraindicated when taking other medication.
• To abstract data from studies on alcohol consumption
• To explain the rationale for treatment of alcohol dependency

ASSESSMENT

At the end of this session you will be able to download from Nathan Bodington some short answer questions to complete. Answer these questions on the sheet provided and hand in to your demonstrator at Work Session 7.You should also upload a copy of your answers to the pigeonhole on Nathan Bodington. This assessment contributes 30% of your final in-course mark

PREPARATION

• Before you come to this work session, work through the questions 1-8 and complete Table 1 and Figure 1, using information from textbooks such as Kumar and Clark(Chaps. 5, 7 and 22), Marks'Basic medical Biochemistry, 2nd Ed, by Smith, Marks & Lieberman (e.g. Jean Ann Tonich, Al Martini), Lippincotts Illustrated Reviews: Biochemistry 2nd Ed. by Champe & Harvey, and also in your lecture notes.
• You will find it useful to remind yourself of ethanol metabolism (from ICU1 Biological Molecules Work Session 4) and you will need to look up the pathway of haem catabolism.
• Bring a textbook to the Session.
• To help you understand the crucial nature of a properly functioning liver, fill in the table below with a list of the major metabolic processes that occur in the liver, and a brief outline of the functional significance of each one.

Table 1: metabolic processes carried out by the liver and their functional significance in the body

INTRODUCTION

Alcoholism

Mortality and morbidity in UK far outstrips other drugs in its effects on individuals and society. It is hard to accurately assess the social effects of alcohol misuse, but it is generally accepted that it is a factor in family disputes, marital breakdown, child neglect and abuse, absenteeism from work, vandalism, physical assault and petty crime. There is a direct relationship between the overall level of alcohol consumption within a population and the number of alcohol-dependent people. Nations with widespread use and high consumption per head, have a proportionately higher rate of alcohol-related diseases than those with a lower consumption per head.

Unlike most drugs, there are no specific receptors in the body for alcohol, and it affects all organs. The effect of alcohol falls into two categories:

1. those related directly to blood concentration at the time
2. metabolic implications from long term effects

Alcohol depresses the brain functions initially by inhibiting the reticular activating system (RAS), which regulates the front part of the brain, the cerebral cortex. The effect of this is to diminish intellectual faculties and also to reduce the inhibitory effect of the cerebral cortex on other areas, resulting in a lack of integration between sensory and motor control. The outcome is loss of coordination, judgement and control over movement.

People who misuse alcohol become physically dependent, and require alcohol to prevent unpleasant consequences of abstinence, called rebound hyperactivity. This occurs because the inhibitory effect of alcohol on the RAS is removed, and results in persistent tremor, extreme agitation and restlessness, sleeplessness, sweating, sometimes accompanied by frightening visual hallucinations.

Alcohol damages many tissues with which it has contact. Liver damage may occur in people who regularly consume even just slightly more than the recommended limit, and this often has knock-on effects on other organs, resulting in a variety of potentially serious conditions.

The table below summarises the effects of different concentrations of alcohol in the blood. (One unit represents approximately 200mmol or 8g alcohol).

1. What are the UK Government recommendations for sensible drinking per week for men and women?
2. For which conditions does moderate alcohol consumption have some beneficial effects?
3. How many people are estimated to drink more than the recommended amount in the UK?
4. Using textbooks and your lecture notes, describe: (a) the gross structural changes that occur in the liver of cirrhotic patients; (b) changes occuring at a cellular level. You may find these images useful.
5. How do these changes arise from excess alcohol consumption?
6. What other conditions may cause cirrhosis of the liver?
7. Distinguish hepatitis from cirrhosis of the liver
8. Complete the diagram in your workbook to illustrate the pathway for the degradation of haemoglobin. Indicate where direct and indirect bilirubin are found. How do they differ?

THE CASE STUDIES

Bill C., an unemployed labourer, aged 55, had been a heavy beer drinker for years and was admitted to hospital after collapsing in the street. He was clearly unsteady on his feet, confused and with a strong smell of alcohol on his breath. His blood alcohol concentration was 78 mM. Physical examination revealed tender enlargement of the liver. He complained of general loss of appetite, fatigue, early morning nausea and frequent gastro-intestinal problems. Occasional vomiting of blood had been reported. Mary P., aged 42, also presented with gastro-intestinal problems and frequent diarrhoea. She had been under considerable stress at work and admitted to concerns about her alcohol consumption.

It was felt advisable to perform a set of liver function tests on both patients and the results are shown below:

9. Why are the particular tests shown in Table 1 indicative of liver function?
10. In addition to patient history, physical examination and biochemical tests, what other techniques could be used to investigate these patients further?
11. Which patient has the more severe liver degeneration?
12. What other conditions might elevated levels of alkaline phosphatase or transaminases indicate?
13. Why was Bill prone to vomiting blood?
14. Explain the higher incidence in alcoholics of:
    (a) Jaundice
    (b) Itchy skin
    (c) Steathorrea
    (d)Bruising and bleeding

15. Heavy drinkers are regularly admitted to Accident and Emergency departments, in a comatose state due to hypoglycaemia.
    Why is hypoglycaemia more likely to occur amongst alcohol addicts?
    Why arethese patients always given an i.v. injection of thiamine (vitamin B₁) before administration of glucose?

16. Why should alcohol be consumed with caution when taking other drugs? Give examples of drugs that are contra-indicated.

MANAGEMENT OF THE CONDITION

17. What advice is given to alcohol addicts?
18. What medication can be used to reduce alcohol addicts' dependence on alcohol, and how does each drug work?
19. What treatment can be given to patients with severely damaged livers, and is it successful?

Further reading

You may be interested in the following paper, written by Leeds medical students, about alcohol intake in second year medical students.

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