Alcoholic Liver Disease/Cirrhosis PDF

Alcoholic Liver Disease/Cirrhosi s MED 1214: Integrated Case Seminars Group 10 Facilitator: Dr. Sharlene Goberdhan Illustration by Smart-Servier Medical Art  Group Members Bishema Goberdhan 1034250 Latwana Victorine - 10...

Alcoholic Liver Disease/Cirrhosi s MED 1214: Integrated Case Seminars Group 10 Facilitator: Dr. Sharlene Goberdhan Illustration by Smart-Servier Medical Art  Group Members Bishema Goberdhan 1034250 Latwana Victorine - 1030053 Shaquana October- 1033280 Andrea Kuardat- 1044727 Oumadavi Manoo - 1031723  Table of contents 01 02 Case Study Anatomy 04 Biochemistr 03 y Histology  Case Study A 43-year-old woman comes to the physician because of a 2-week history of malaise, nausea, and a 3-kg (6.6-lb) weight loss. She has been drinking eight to ten alcoholic beverages daily for the past 20 years. Her temperature is 37.8°C (100.0°F) and pulse is 105/min. Examination shows jaundice and hepatosplenomegaly. A photomicrograph of a section of a biopsy specimen of the liver is shown. Figure: Patient’s biopsy specimen Anatomy  Discuss the surfaces, ligaments and segments of the liver. The Liver is the largest visceral organ in the human body. There are 2 surfaces; Diaphragmatic & Visceral Surfaces. Liver is mostly covered by Peritoneum. (Roberts-Martin, 2024) Below the peritoneum is the Glisson’s Capsule  Discuss the surfaces, ligaments and segments of the liver. (Roberts-Martin, 2024) (Winslow, 2023) Discuss the surfaces, ligaments and segments of the liver. (Roberts-Martin, 2024) Discuss the surfaces, ligaments and segments of the liver Superior & Inferior Coronary Ligament connects the superior surface of the liver to the inferior surface of the diaphragm. (Roberts-Martin, 2024) What is the Blood Supply of the Liver? (Roberts-Martin, 2024) Discuss the Portocaval Anastomosis The four (4) main sites are: 1. Esophageal- anastomosis of the Esophageal branch of the left gastric vein and the esophageal veins of the azygos system. 2. Umbilicus- between the paraumbilical vein and the superficial veins of the anterior abdominal wall. 3. Rectal- superior rectal vein and the middle and inferior rectal veins. 4. Retroperitoneal- between the retroperitoneal veins draining the colon and the smaller branches of the renal, suprarenal and gonadal veins (Okpe, 2021). Which portocaval anastomosis is commonly affected in ALD? Alcohol liver disease (ALD) damages the liver, causing inefficient blood flow and portal hypertension. This leads to congested anastomotic veins. Common anastomosis affected by ALD is esophageal anastomosis. As pressure builds, it shunts through the portal systemic anastomosis into the esophagus. Consistent portal hypertension can cause veins to rupture, the blood leaves by hemoptysis or Cleveland Clinic, n.d) in the stool. Histology Histology- Spectrum of Alcoholic Liver Disease Figure: Spectrum and progression of Alcoholic Liver Disease, (Singal, 2023)  Histopathology of Alcoholic Liver Disease A B Figure: Mallory-Denk bodies appear as cytoplasmic hyaline inclusions of ballooned hepatocytes (arrow) (B: H&E; original magnification 60x). Biochemistry  If this patient was pregnant, what would be the effects of alcohol on her foetus? Alcohol enters the fetus through the placental barrier and accumulates in the amniotic sac. Fetus's liver is responsible for alcohol metabolism, with acetaldehyde as its main metabolite. Underdevelopment of the fetus results in lower levels of ADH (alcohol dehydrogenase) activity, causing slower metabolization. This results in fetal developmental toxicity (fetal alcohol syndrome) and potential long-term health problems. FAS can cause visible changes in face and limbs, delayed body development, and microcephaly in infants. (Ophthalmology Review, 2016) (Alhowail, 2022)  Vitamin absorption Fetal Neurotransmitters Gamma-aminobutyric acid (GABA) is a primary vitamin A & B9, which are necessary inhibitory neurotransmitter. for the development of the central Alcohol exposure during pregnancy alters GABA nervous system and NMDA receptor activity. Alcohol and acetaldehyde interfere Increased GABAergic activity and reduced with fetal brain development. glutamatergic signaling lead to delayed Decreased levels lead to congenital production and insufficient incorporation of birth defects and developmental GABAergic interneurons. abnormalities. These changes impair frontal cortex (Naidoo, n.d.) development, causing long-term cognitive and behavioral deficits. (Alhowail, 2022)  Discuss the variations and consequences of alcoholic metabolism among ethnic groups, gender and body weight, and its effects on drug metabolism. Variations and consequences of alcoholic metabolism among ethnic groups: The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are variants of some of genes that encode these enzymes with different characteristics, and which have different ethnic distributions. Many individuals of East Asian descent possess a genetic variant of the enzyme aldehyde dehydrogenase (ALDH2), known as ALDH2*2. This variant significantly reduces the enzyme's activity. (Edenberg, 2007)  Variations and consequences of alcoholic metabolism among ethnic groups: Europeans and Africans have higher levels of active ALDH2 and ADH enzymes, leading to more efficient alcohol metabolism and fewer acute adverse effects from acetaldehyde accumulation Native Americans show a variation in the enzymatic activity and as such there are some individuals that metabolize alcohol slowly (Edenberg, 2007)  Gender and body weight Women would have higher blood alcohol concentration than men because women have lower levels of ADH lining their stomach walls Hormonal changes affect alcohol concentration as it causes alcohol metabolism to increase at certain times Women also have a higher percentage of body fat and less lean body mass than men resulting in a higher concentration of blood alcohol level As it relates to body weight generally however, both men and women with higher lean body weight would experience faster metabolism (Vatsalya et al., 2023)  Effects on drug metabolism. Pharmacodynamic interactions between alcohol and prescription drugs are common An example is alcohol interaction with benzodiazepines and opioids which enhance sedation and respiratory depression Alcohol induces cytochrome P450 2E1 which can affect the pharmacokinetics of drugs by altering gastric emptying or liver metabolism The combination of nonsteroidal anti-inflammatory drugs and alcohol intake increases the risk of gastrointestinal haemorrhage. (Fraser, 2012)  What are the metabolic effects of alcohol metabolism on the development of fatty liver, cirrhosis and cancer? The metabolism of alcohol involves several steps that can lead to the accumulation of fat in the liver cells, ultimately contributing to the development of fatty liver disease.The key metabolic effects include: Increase NADH/NAD+ Ratio Impaired fatty acid Oxidation Altered lipid transport Oxidative stress Inflammation and Fibrosis (Odriozola et al., 2023)  Alcohol and Liver Cirrhosis Alcohol metabolism plays a significant role in the development of cirrhosis, a severe liver condition characterized by scarring and loss of liver function. The key metabolic effects include: Ethanol metabolism Oxidative stress Inflammation and immune response Activation of Stellate cells (Hyun et al., 2021)  Alcohol and Liver cancer Alcohol metabolism has several metabolic effects that can contribute to the development of liver cancer. The key metabolic effects include: Acetaldehyde toxicity Inflammation Disruption in cell signaling pathway Epigenetic Alterations (Chen et al., 2023)  References Alhowail, A. (2022). Mechanisms Underlying Cognitive Impairment Induced by Prenatal Alcohol Exposure. Brain Sciences, 12(12), 1667. https://doi.org/10.3390/brainsci12121667 Chen, M., Zhong, W., & Xu, W. (2023, July 09). Alcohol and the mechanisms of liver disease. Journal of Gastroenterology and Hepatology, 38(8), 1233-1240. https://doi.org/10.1111/jgh.16282 Cleveland Clinic. (n.d). Esophageal Varices; Causes, Symptoms, Diagnosis & Treatment. https://my.clevelandclinic.org/health/diseases/15429-esophageal-varices Edenberg, H. J. (2007). The genetics of alcohol metabolism: Role of alcohol Dehydrogenase and aldehyde Dehydrogenase variants. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860432/ Fraser, A. G. (2012). Pharmacokinetic interactions between alcohol and other drugs. Springer Link. https://link.springer.com/article/10.2165/00003088-199733020-00001  References Hyun, J., Han, J., Lee, C., Yoon, M., & Jung, Y. (2021, May 10th). Pathophysiological Aspects of Alcohol Metabolism in the Liver. International Journal of Molecular Sciences, 22(11), 5717. https://doi.org/10.3390/ijms22115717 May, H. (2024, April 20). The liver. https://teachmeanatomy.info/abdomen/viscera/liver/ Naidoo, D. (n.d.). The Role of Alcohol Dehydrogenase Genes in the Development of Fetal Alcohol Syndrome in Two South African Coloured Communities Provided by Wits Institutional Repository on DSPACE. Retrieved May 25, 2024, from https://core.ac.uk/download/pdf/39664815.pdf Odriozola, A., Santos-Laso, A., Cabezas, J., Iruzubieta, P., Arias-Loste, M. T., Rivas, C., Rodríguez Duque, J. C., Antón, Á., Fábrega, E., & Crespo, J. (2023, April 24th). Fatty Liver Disease, Metabolism and Alcohol Interplay: A Comprehensive Review. International Journal of Molecular Sciences, 24(9). https://doi.org/10.3390/ijms24097791  References Roberts-Martin, R. (2024). Gastrointestinal System 3 [Powerpoint Slides]. PDF Singal, A. K. (2023, October 3). Nonadvanced Alcohol-Associated Liver Disease. Gastroendonews.com. https://www.gastroendonews.com/Review-Articles/Article/09-23/alcohol-associated-liver-disease/ 71352 Vatsalya, V., Byrd, N. D., Stangl, B. L., Momenan, R., & Ramchandani, V. A. (2023, March). Influence of age and sex on alcohol pharmacokinetics and subjective pharmacodynamic responses following intravenous alcohol exposure in humans. Science Direct. https://www.sciencedirect.com/science/article/abs/pii/S0741832922000945 Winslow, T. (2023, March 02). Anatomy - Digestive/Gastrointestinal System. https://visualsonline.cancer.gov/details.cfm?imageid=13017 Thank you CREDITS: This presentation template was created by Slidesgo, and includes icons by Flaticon and infographics & images by Freepik Please keep this slide for attribution Illustration by Smart-Servier Medical Art