ALCOHOLIC LIVER DISEASE



RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

PROFORMA FOR REGISTRATION OF SUBJECT

FOR

DISSERTATIONS

|1 |NAME OF THE CANDIDATE |DR. ANURADHA. JANGAM |

| |& ADDRESS (IN BLOCK LETTERS) |DEPARTMENT OF BIOCHEMISTRY, |

| | |DR.B.R.AMBEDKAR MEDICAL COLLEGE AND HOSPITAL, |

| | |K.G.HALLI, BANGALORE – 560045. |

| | | |

| | | |

| | | |

| | | |

|2 |NAME OF THE INSTITUTION |DR.B.R.AMBEDKAR MEDICAL COLLEGE AND HOSPITAL |

|3 |COURSE OF STUDY & |M.D. |

| |SUBJECT |BIOCHEMISTRY |

|4 |DATE OF ADMISSION TO THE COURSE |19TH AUGUST 2013 |

|5 |TITLE OF THE TOPIC |A STUDY OF THYROID HORMONES IN ALCOHOLIC LIVER DISEASES |

ALCOHOLIC LIVER DISEASES

INTRODUCTION

In India alcohol consumption has been steadily increasing. It has been estimated that there are 62.5 million alcohol users in India. The mean age of initiation of alcohol use has decreased from 23yrs in 1950-1960 to 19yrs in 1980-2000.This is due to changing social norms, urbanization, increased availability, high intensity marketing.

ALCOHOLISM:-

Alcoholism or alcohol dependence is a maladaptive pattern of chronic alcohol leading to tolerance, dependence and severe behavior impairment.

Tolerance is defined as need for markedly increased amounts of alcohol to achieve the desired effect. Dependence may be physical or psychological. Physical dependence is characterized by presence of withdrawal symptoms and tolerance. Withdrawal symptoms include sweating, hand tremors, vomiting. Psychological symptoms include insomnia, anxiety, psychomotor agitation and hallucination.

An alcoholic beverage contains ethanol in varying percentages. Quantity and duration of alcohol intake are the most important risk factors involved in the development of alcoholic diseases.

Continuous alcoholic drinkers are at a high risk of developing alcoholic disease than binge drinkers.

EFFECTS OF ALCOHOL ON ORGAN SYSTEMS

1. Neurological – Peripheral neuropathy, Cerebellar degeneration, cerebral

haemorrhage.

2. Cardiac - Cardiomyopathy, Hypertension

3. Respiratory - Pulmonary TB, Pneumonia.

4. G.I.T – Oesophagitis, Gastritis, Pancreatitis, Oesophageal cancer, Mallory

Weiss syndrome, Malabsorption Oesophageal varices

5. Reproductive- Hypogonadism, Fetal alcohol syndrome

6. Musculoskeletal – Myopathy, fractures

7. Endocrine and metabolism – Pseudo-Cushing syndrome, hypoglycemia,

Gout

8. Hepatic – Alcoholic liver diseases.

CLINICAL FEATURES

The three types of alcoholic liver disease are

1: ALCOHOLIC FATTY LIVER DISEASE

It usually presents with elevated transaminases in the absence of hepatomegaly.Steatosis usually disappears after 3 months of abstinence.

2: ALCOHOLIC HEPATITIS

Clinical features are

Jaundice

Malnutrition

Hepatomegaly

Features of portal hypertension i.e. Ascites, encephalopathy.

3: CIRRHOSIS

It often presents with complications such as ascites, variceal haemorrhage

Large, normal or small liver

Stigmata of chronic liver disease

Hepatocellular carcinoma.

ALCOHOLIC LIVER DISEASES

Alcoholic liver disease is among the ten most common causes of death. Quantity and duration of alcohol are the most important risk factors involved in the development of alcoholic liver disease. The threshold of developing alcoholic liver disease in men is an intake of >60-80 g/d of alcohol for 10yrs while in women are at increased risk of developing similar degrees of liver injury by consuming 20-40 g/d. Ingestion of 160 g/d is associated with 25 fold increased risk of developing alcoholic cirrhosis

PATHOPHYSIOLOGY

Alcohol is metabolized by the liver via one of the two main pathways

80% of alcohol is metabolized to acetaldehyde by the mitochondrial enzyme, alcohol dehydrogenase. Acetaldehyde forms adduct with the cellular proteins in hepatocytes and activates the immune system leading to cell injury.

20%is metabolized by the mixed function oxidase enzymes of the smooth endoplasmic reticulum. Cytochrome CYP2E1 is an enzyme which oxidize ethanol to acetate during this process it releases oxygen free radicals which can induce mitochondrial damage.

The important functions of liver

1. Nutrient metabolism – Carbohydrate

Proteins

Lipids

2. Protein synthesis - Coagulation factors

Complement factors

Haptoglobin

Ceruloplasmin

Transferin

Protease inhibitors

Albumin

Hormone binding proteins

3. Storage – of iron, copper, vit A,D and B12.

4. Formation and secretion of bile.

5. Excretion of drugs, cholesterol, phospholipids, bilirubin, and bile salts.

6. Immune regulation

The functions of liver on thyroid

The liver being involved in the conjugation and deiodination of Thyroxine (T4) and tri-iodothyronine (T3)

Synthesis and secretion of major thyroid hormone binding proteins, thyroxine-binding globulin, prealbumin and albumin

The peripheral conversion of T4 to T3 takes place in tissues such as liver, kidney and thyroid .

THYROID GLAND

It is the largest endocrine gland. It consists of two large lateral lobes which are connected in the midline by a broad isthmus from which an occasion a pyramid lobe may protrude superiorly. It develops as tubular invagination of the endoderm from the root of the tongue called Foramen caecum about the third week of the embryonic life.

PHYSIOLOGY

Thyroid secretes two significant hormones T4 and T3.

Synthesis of thyroid hormones

Trapping of inorganic iodide from the blood.

Oxidation of iodide to iodine

Binding of iodine with tyrosine to form iodotyrosines.

Coupling of mono-iodotyrosines and di-iodotyrosines to form tri-iodo thyronine (T3) and thyroxine (T4).

T3 is also produced in the periphery by conversion from T4 in tissues such as liver, kidney and thyroid catalyzed by type 1 de-iodinase.

The hormone T3 andT4 are bound to thyroglobulin within the colloid

HORMONE TRANSPORT AND METABOLISM

When hormones are required the complex is resorbed into the cell and the thyroglobulin broken down.T3 and T4 are liberated and enter the blood where they are bound to serum protein, albumin, thyroxine binding globulin (TBG) and prealbumin (TBPA).A small amount of hormone remains free in the serum in equilibrium with protein-bound hormone and is biologically active.

Thyroid hormone undergo 70%metabolism through sequential removal of iodine. In case of T4 deiodination yields T3 and reverse T3 (has no metabolic action).

The second pathway of T3/T4 metabolism is conjugation with glucuronide in liver which are deiodinated and excreted in the bile.20%of T4 disposal occur via fecal loss.

6 NEED FOR THE STUDY

Alcoholic liver disease effects most of the organs in our body. On this alcoholic liver diseases various studies have been done .It is observed that not many Indian studies on thyroid hormone functional studies in case of alcoholic liver diseases are available. The study of thyroid hormone function tests will throw a light on the functional aspects of liver diseases and gives some better understanding of the alcoholic liver disease and their interrelationship with thyroid function and thus helps in the management of alcoholic liver diseases.

6.1 REVIEW OF LITERATURE

The liver, a plays an important role in thyroid hormone metabolism, being involved in the conjugation and de-iodination of thyroxine (T4) and tri-iodothyronine (T3) as well as synthesis and secretion of major thyroid hormone binding proteins, thyroxine-binding globulin (TBG), thyroxine-binding prealbumin and albumin .1

A large group of alcoholic liver disease patients were studied for the endocrine changes and these changes were correlated to the severity of liver diseases in order to examine the underlying mechanism accounting for endocrine dysfunction. In the majority of patients examined marked changes were found in circulating thyroid hormones T3 below the normal level in the absence of significant changes in TSH. Total T4 was normal or low. They were clinically euthyroid.1

In patients with alcoholic cirrhosis the levels of serum T4, T3, reverse T3 (rT3) were determined. The results showed Serum T4, T3 levels were decreased and serum rT3 levels increased in patients with alcoholic cirrhosis. Serum T4 and T3 were lower and rT3 higher in cirrhotic patients who died within three months of study compared with those who survived. It suggests that assay of serum thyroid hormone levels may be helpful in assessing the course and prognosis of patients with liver disease.3

In alcoholic cirrhosis with clinically euthyroid patients the serum concentrations of thyroid hormones showed the mean serum Total T4 was low and the mean serum total T3 was significantly lower than the normal. The mean serum TSH is increased.5

6.2 OBJECTIVES

To study the Thyroid hormones in alcoholic liver diseases.

7. MATERIALS AND METHODS

7.1 SOURCE OF DATA

INCLUSION CRITERIA

Test subjects :- Includes 30 males of age 40-60 yrs of alcoholic liver diseases

Control subjects :- Includes 30 males of age 40-60yrs who are non alcoholics.

EXCLUSION CRITERIA

Patients with clinical evidence of Diabetes mellitus, Renal diseases, Hypertension, thyroid disorders, non alcoholic liver diseases, obesity, females, vomiting, diarrhea.

STUDY PERIOD: JAN 2014 TO JAN 2015

7.2 METHOD OF COLLECTION OF DATA

Test subjects are male patients of alcoholic liver disease from Dr.B.R.A.M.C.H. having no history of diseases like diabetes mellitus, hypertension, non alcoholic liver diseases, renal diseases, thyroid disorders.

Control subjects are healthy males who are hospital employees of Dr.B.R.A.M.C.H. With no current/lifetime history of alcohol drinking

All these subjects were subjected to medical examination as per a fixed proform. Their blood pressure, height, weight, BMI is recorded in both groups.

BIOCHEMICAL TESTS

THYROID FUNCTION TESTS (ELISA METHOD)

Serum T3

Serum T4

Serum TSH

LIVER FUNCTION TESTS (Routine methods using Auto Analyzers)

1. Total bilirubin - Direct

- Indirect

2. Total protein

Serum albumin

A:G ratio

3. Serum AST

Serum ALT

Serum ALP

Serum GGT

7.3. Does the study require any investigation or intervention to be conducted on

Patient or other human or animal?

Yes, investigation required as mentioned above, are non invasive

No interventions are required.

7.4 Has ethical clearance has been obtained from your institution in cases above

mentioned ?

Yes

8. LIST OF REFERENCES

1 . P. Burra, J.A. Franklyn, D.B.Ramsden, E.Elias and M.C.Sheppard .Severity

of alcoholic liver disease and markers of thyroid and steroid status Post

graduate medical journal 1992 october;68(804-810).

2 . George C. Schussler, M.D.,Fenton Schaffner, M.D., and Felice korn M.S.

Increased serum thyroid hormone binding and decreased free hormone in

chronic liver disease. The New England Journal of Medicine 1978; 299:510-

515

3. Hepner GW, Chopra IJ .Serum thyroid hormone levels in patients with liver

disease. Archive Internal Medicine .1979 Oct; 139(10); 1117-20.

4. S Nomura, C S Pittman, J B Chambers, Jr, M W Buck and T Shimizu. .Reduced

peripheral conversion of thyroxine to triiodothyronine in patients with hepatic

cirrhosis. The Journal of Clinical investigation 1975 September; 56(3) 643-652.

5. Inder J., Chopra, David, Solomon et al .Alterations in circulating thyroid

hormones and thyrotropin in hepatic cirrhosis. Evidence for Euthyroidism

despite subnormal serum triiodothyronine Journal of Clinical Endocrinology

& Metabolism September 1, 1974 vol.39 no.3 501-511.

6. L`age M, Meinhold H, Wenzel KW ,Schlesinger H. Relations between serum

levels of TSH,TBG,T4,T3,rT3 and various histological classified chronic

liver diseases. Journal of Endocrinology investigations 1980 oct-dec; 3(4);

379-83.

7. Y Israel, PG Walfish, H Orrego, J Blake, H Kalant. Thyroid hormone levels

in alcoholic liver diseases. Gastroenterology Vol.76, issue 1, January 1979;

116-122

8. M Borzio, R Caldara, F Borzio, V Piepoli et al. Thyroid function tests in

chronic liver disease: evidence for multiple abnormalities despite clinical

euthyroidism. GUT, an International Journal of Gastroenterology and

Hepatology; 1983 July; 24(7); 631-636.

9. Mc Connon j, Row VV, Volpe R.J The influence of liver damage in man on

the distribution and disposal rates of thyroxine and triiodothyronine. Clinical

Endocrinology Metabolism.1972 Jan; 34 (1):144-151

10. JanniA, etal. The prognostic value of thyroid function tests in liver cirrhosis.

In Langer M Chiandussi L,Chopra I J and Martin L,eds, The Endocrines and

The Liver, London, Academic Press, 1982; 232-6

11. Malik R, Hodgson H. The relationship between the thyroid gland and the

Liver. Q J MED; 2002; 95:

A study of the endocrine manifestations of hepatic cirrhosis. (Q J M 1976.

12. The thyroid hormone picture of alcoholics in connection with their liver

Status. Minerva Med.1990.

13. Harnold Varley, etal, Practical Clinical Biochemistry – 5th Edition.

14. Carl AB, Edward RA, et al, Teitz Fundamental for Clinical Chemistry, 5th

Edition.

15. Oxford Text book of Clinical hepatology; Vol_2

16. Devlin Text book of Biochemistry with Clinical Correlation – Sixth

Edition.

17. Williams Text book of Endocrinology Edition 11.Henry M. Krokenberg, Shlomo Melmed Kenneth S.Polonsky, and P.Reed Larsen.

| | | |

|9 |Signature of the candidate | |

| | | |

| | |Good study. Not done in RGUHS in the past five years. |

|10 |Remarks of the Guide | |

| | | |

|11.1 |Name and designation of guide |Dr.Prof.Hemalatha, M.D., |

| | |Professor and Head, |

| | |Dept. of Biochemistry |

| | |Dr. B.R.Ambedkar Medical College |

| | |Bangalore-560045 |

| | | |

|11.2 |Signature | |

| | | |

| | | |

|11.3 |Co Guide (if any) |_____ |

| | | |

| | | |

|11.4 |Signature | |

| | | |

| | |Dr.Prof.Hemalatha, M.D., |

|11.5 |Head of Department |Professor and Head, |

| | |Dept. of Biochemistry |

| | |Dr.B.R.Ambedkar Medical College |

| | | |

|11.6 |Signature | |

| | | |

|12. |Remarks of the Principal | |

| | | |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download