C39 Alcohol Induced Cirrhosis of the Liver

1. C39 Alcohol Induced Cirrhosis of the Liver

2. Objectives • State thesis • Explain what cirrhosis is • Review Liver anatomy • Explain how alcohol is metabolized • Identify Complications/Signs of cirrhosis • Review imaging modalities used to diagnose • Discuss treatments • Report risk factors/ prognosis

3. Thesis Statement Repetitive alcohol consumption in excessive amounts over an extended period of time can cause irreparable damage to the liver resulting in alcohol induced cirrhosis of the liver.

4. Cirrhosis of the liver • Alcohol induced cirrhosis is the third stage of liver disease referred to as end-stage liver damage. • Damage at this point is irreversible. • Scar tissue consists of dead liver cells. • Accumulation of scar tissue replacing the healthy tissue of the liverdisrupts blood flow and proper function.

5. Anatomy of the liver Functions Anatomy/structure

6. Functions The main function of the liver is to filter out toxins from the blood before getting distributed to the body. Other functions include: • Metabolize drugs • Break down proteins • Secrete bile • Produce clotting factors and enzymes • Store fuel for the body

7. Anatomy • Largest visceral organ positioned underneath the diaphragm in the right upper quadrant. • Composed of 4 lobes: Right, Left, Caudate, and the Quadrate. • Supplied by 2 major sources of blood: Portal veinand Hepatic artery.

8. Sources of Blood • The Portal vein supplies the liver with blood coming from the Gastrointestinal tract containing nutrients and toxins to be filtered out before being sent to the heart. • The Hepatic artery supplies oxygenated blood from the heart providing the Liver with half of it’s oxygen supply. • These blood vessels then divide into small capillaries that end up in the lobules of the liver, the functional units of the liver. • The blood is removed from the liver and distributed to the heart through 3 hepatic veins that are connected to the Inferior vena cava. The blood is filtered as it leaves the liver. *Benefit of having 2 blood supplies is if one vessel is damaged the second vessel will keep the liver functioning.

9. https://crukcambridgecentre.org.uk/patient-care/clinical-research/liver-and-bile-ducthttps://crukcambridgecentre.org.uk/patient-care/clinical-research/liver-and-bile-duct

10. Cell Functions within a Healthy Liver • Hepatocytesare the main tissue cells that compose the majority of the liver. In a healthy liver, these cells form and secrete bile and are responsible for the conversion of alcohol to Acetaldehyde. • Kupffer cells produce collagen which is a connective tissue within the liver. They also aid in blood formation and anti-body production. • Stellate cells are considered to be dormant and play a key role in liver regeneration and wound healing within a healthy liver.

11. HEPATOTOXIC Alcohol is hepatotoxic! Damage to the liver is related to the toxic effect of alcohol. When consumed in small and infrequent amounts, alcohol is not detrimental to a person’s wellbeing. However, organs in the body begin to suffer with repetitive alcohol consumption over a long period of time. https://www.dreamstime.com/toxic-stamp-red-grunge-seal-toxic-stamp-red-grunge-seal-rubber-stamp-isolated-white-background-image116722009

12. Ethanol AKA Alcohol • Ethanol also known as alcohol, is made from fermenting the sugars in barley and grapes, but starches from potatoes and corn can also be used. • Ethanol is used in alcoholic beverages, but also in fuel for cars, hairspray, and hand sanitizer.

13. Metabolizing Alcohol 90% of alcohol is metabolized in the liver. The other 10% is absorbed in the stomach lining. 1. Alcohol is consumed. 2. It reaches the stomach where it then goes into the Gastrointestinal vein. 3. The Gastrointestinal vein drains into the portal vein which is connected to the liver. 4. The Liver begins to break down the alcohol. https://www.youtube.com/watch?v=f46VFQG2S84&t=101s

14. A healthy liver can only process about 1 drink/ hour = • 12 oz. beer • 5 oz. wine • 1.5 oz. of whiskey NOTHING will make the process go faster. Only time can break down the alcohol in the system! https://www.topsimages.com/images/glow-hourglasses-34.html

15. Metabolic Interaction • 2 liver enzymes within the hepatocyte begin to break apart the alcohol molecule. • Alcohol dehydrogenase (ADH): converts alcohol into Acetaldehyde. Acetaldehyde is toxic and associated with symptoms experienced during a hangoverand the production of fat in the liver. • Cause hepatocytes to be recognized as being “foreign” and therefore destroyed by neutrophils. • As cells become damaged and die off, scar tissue begins to form. • Hepatic steatosis is caused by an excessive build up of fat making the liver heavier and larger. • Aldehyde dehydrogenase (ALDH): gets rid of Acetaldehyde by breaking it down into acetate which is further broken down into water, a less toxic substance, before being distributed throughout the body.

16. Cell Reaction to Alcohol • Hepatocytes- Within the hepatocytes, the Acetaldehyde attaches it self to structures within the cell and inhibits them. This ultimately causes the body to recognize the hepatocyte as being foreign and begins to send in neutrophils to “clean it up” leading to its destruction. • Kupffer cells- When alcohol is consumed it has a reaction within the stomach releases a bacteria that reaches the liver through the Portal vein. This bacteria is then recognized by the Kupffer cell’s pathogen recognition receptors. The Kupffer cell then releases enzymes that stimulate the Stellate cells. • Stellate cells- When these cells are stimulated and begin producing additional collagen. The collagen is a factor in creating the fibrotic tissue. As these cells are activated they expand within the perisinusoidal space and compresses the central veins contributing to portal hypertension and ascites.

17. https://www.youtube.com/watch?v=f46VFQG2S84&t=101s • Damaged tissue converge to form nodules, creating the bumpy fibrotic surface that is a characteristic of cirrhosis. • The connective tissue and collagen go in between these nodules.

18. Normal liver on the left is smooth compared to the nodular liver on the right with cirrhosis. http://www.zealthdoc.com/blog/slug/liver-cirrhosis-what-it-means-how-it-occurs-and-why-it-can-kill-you.php

19. Complications/Signs Compensated Decompensated

20. Compensated Still damaged, but can continue to function as long as the drinking stops. • Experience few to no symptoms • Weight loss • Weakness • Fatigue • Fluid retention/swelling in legs • Confusion • Pain in abdomen People with compensated cirrhosis may experience very few symptoms or none at all and can live many years without undergoing any serious complications.

21. Decompensated Extensively scarred, unable to perform important functions • Jaundice- yellowing of the skin and eyes caused by low levels of albumin. • Pruritus- severe itching. • Bleeding and bruising- caused by the loss of clotting factors that a healthy liver produces. • Ascites- build up of fluid in the abdomen causing it to protrude. Patients with decompensated cirrhosis suffer serious complications that can be life threatening.

22. Decompensated • Portal hypertensionis scarring in the portal vein that causes a back up of blood and fluid, increasing the pressure within the veins. Blood is trying to get through, and so it creates other “highways” around the liver. • Development of varices, enlarged and swollen veins, is commonly seen in the esophagus, stomach, rectum, and the abdomen. With the potential to burst, these varices are a danger to the patient. • Hepatic encephalopathy occurs when toxins migrate to the braincausing confusion, disorientation, and changes in sleep habits.

23. Diagnostic Methods Diagnosing CT MRI US

24. Diagnosing • Early detection is important to identify the severity of damage to the liver in order to begin treatment right away. • Detailed patient history should be obtained to council patient with lifestyle changes that need to be made. • Complete physical is done. • Help from radiology with diagnostic imaging is essential.

25. Terms Used to Measure Test Performance Sensitivity Specificity Measures the percentage of healthy people who are correctly identified as not having the condition. • Measures the percentage of sick people who are correctly identified as having the condition. **A higher number is strived for in both categories**

26. http://www.startradiology.com/internships/general-surgery/abdomen/ct-abdomen-general/http://www.startradiology.com/internships/general-surgery/abdomen/ct-abdomen-general/ Hepatic steatosis is easily detected in a CT without contrast. The changes in size and volume are easily visible.

27. MRI is the modality most sensitive and specific for detecting hepatic steatosis. 95% sensitivity: 5% of patients are undetected 98% specificity: 2% are misdiagnosed https://www.researchgate.net/figure/Nodular-hepatic-margins_fig4_296936036

28. http://www.startradiology.com/internships/emergency-medicine/abdomen/ultrasound-abdomen-general/http://www.startradiology.com/internships/emergency-medicine/abdomen/ultrasound-abdomen-general/ Normal: smooth contours are evaluated by scanning the right kidney and the right lobe of the liver together for comparison. Cirrhotic: Appears brighter (echogenic) because of the accumulated fat, and the surface appears uneven. Liver volume will also decrease. 71% sensitivity: 29% of patients are undiagnosed 88% specificity:12% of patients misdiagnosed

29. Treatments Eliminate alcohol Treating complications Liver transplant

30. The sooner you stop drinking, the sooner symptoms can subside. Depending on how damaged the liver is, it may be able to regenerate to a certain point, but not completely. If you keep drinking, things will only get worse. https://www.amazon.com/Alcohol-Beyond-Point-Aluminum-Metal/dp/B07CSJ886L

31. The liver is the only visceral organ that can regenerate! • The liver can regrow to its previous size without losing function as long as a minimum of 25% of the tissue remains healthy. • It needs to be kept healthy for it to regrow.

32. Treatments • Treating the complications associated with cirrhosis may slowly improve the liver scarring. • Medications can be given, along with performing therapeutic treatments such as paracentesis. • Paracenteses are done to relieve pressure in the abdomen by removing fluid using ultrasound.

33. Liver Transplant The only “cure” to cirrhosis • Considered if damage is extensive. • Person is obligated to have an alcohol free period of 6 months to be an eligible candidate. • Placed on waitlist after selected by committee. • Patient is contacted as soon as a compatible liver is obtained.

34. Risk Factors/ Prognosis

35. Chronically drinking an extensive amount of alcohol is the most significant risk factor. Women have a greater risk than men because of the difference in the amount of gastric enzymes that help break down alcohol particles, making the liver work harder. Risk Factors

36. Prognosis • The outlook is better for people with compensated cirrhosis than for people living in a decompensated condition. • The average survival rate of someone with a compensated liver is approximately 9-12 years. • A person’s condition can decline from a compensated state to decompensated at a rate of approximately 5-7% each year.

37. Conclusion • Excessive and repetitive drinking over a long period of time causes severe scarring in the liver. • Interruptions in the liver functions occur due to metabolic effects created in the body. • Early detection is important to begin managing the cirrhosis with abstinence, medications, and therapeutic procedures. • Continuous drinking will worsen the condition to the point where a liver transplant will be the only method of treatment.

38. References • 1. Berg J, Tymoczko J, Stryer L. Ethanol Alters Energy Metabolism in the Liver. Ncbi.nlm.nih.gov. https://www.ncbi.nlm.nih.gov/books/NBK22524/. Published 2018. Accessed October 14, 2018. • 2. Pubs.niaaa.nih.gov. https://pubs.niaaa.nih.gov/publications/AlcoholFacts&Stats/AlcoholFacts&Stats.pdf. Published 2018. Accessed October 14, 2018. • 3. Newman T, Elaine K. Luo M. The liver: Structure, function, and disease. Medical News Today. https://www.medicalnewstoday.com/articles/305075.php. Published 2018. Accessed October 10, 2018. • 4. Laflamme M. Alcoholic Liver Cirrhosis: Causes, Symptoms & Diagnosis. Healthline. https://www.healthline.com/health/alcoholic-liver-cirrhosis. Published 2018. Accessed October 10, 2018. • 5. Beck K. What Is the Difference Between Ethanol & Alcohol?. Sciencing. https://sciencing.com/difference-between-ethanol-alcohol-8169825.html. Published 2018. Accessed November 19, 2018.

39. References • 6. Ethanol. Labtestsonline.org. https://labtestsonline.org/tests/ethanol. Published 2018. Accessed November 12, 2018. • 7. Liver | anatomy. Encyclopedia Britannica. https://www.britannica.com/science/liver. Published 2018. Accessed October 20, 2018. • 8. Knights K. What are Kupffer Cells? (with pictures). wiseGEEK. https://www.wisegeek.com/what-are-kupffer-cells.htm. Published 2018. Accessed November 19, 2018. • 9. Liver: Anatomy and Functions | Johns Hopkins Medicine Health Library. Hopkinsmedicine.org. https://www.hopkinsmedicine.org/healthlibrary/conditions/liver_biliary_and_pancreatic_disorders/liver_anatomy_and_functions_85,P00676. Published 2018. Accessed October 20, 2018. • 10.Liver – Anatomy and Function of the Human Liver. InnerBody. http://www.innerbody.com/image_digeov/card10-new2.html. Accessed October 23, 2018.

40. References • 11. Osmosis. Alcohol-related liver disease - causes, symptoms & pathology. YouTube. https://www.youtube.com/watch?v=RudR2_VVoaw. Published February 14, 2017. Accessed October 24, 2018. • 12. Eisenberg RL, Johnson NM. Gastrointestinal. In: Comprehensive Radiologic Pathology. 6th ed. ; :202-202. • 13. Franciscus A. What is Cirrhosis? www.hcvadvocate.org. http://hcvadvocate.org/hepatitis/factsheets_pdf/Cirrhosis.pdf. Published September 2017. Accessed November 2, 2018. • 14. T B. Bruising Is Just One of the Complications of Cirrhosis. Verywell Health. https://www.verywellhealth.com/complications-of-cirrhosis-63380. Published May 17, 2018. Accessed October 15, 2018. • 15. Radiological Society of North America, RSNA, American College of Radiology. Cirrhosis of the Liver. RadiologyInfo.org. https://www.radiologyinfo.org/en/info.cfm?pg=cirrhosisliver. Published January 23, 2017. Accessed November 15, 2018.

41. References • 16. Soresi M, Giannitrapani L, Cervello M, Licata A, Montalto G. Non invasive tools for the diagnosis of liver cirrhosis. World J Gastroenterol. 2014;20(48):18131-50. • 17. Dugum M, McCullough A. Diagnosis and Management of Alcoholic Liver Disease. J Clin Transl Hepatol. 2015;3(2):109-16. • 18. Soresi M, Giannitrapani L, Cervello M, Licata A, Montalto G. Non invasive tools for the diagnosis of liver cirrhosis. World J Gastroenterol. 2014;20(48):18131-50. • 19. Yeom SK, Lee CH, Cha SH, Park CM. Prediction of liver cirrhosis, using diagnostic imaging tools. World J Hepatol. 2015;7(17):2069-79. • 20. Thornton, MD, MPH K. Core Concepts - Evaluation and Prognosis of Patients with Cirrhosis - Evaluation, Staging, and Monitoring of Chronic Hepatitis C - Hepatitis C Online. Hepatitisc.uw.edu. https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/evaluation-prognosis-cirrhosis/core-concept/all. Published 2018. Accessed November 9, 2018.