Wernicke-Korsakoff Syndrome [WKS]

Slides:



Advertisements
Similar presentations
Joanna Prickett North Bristol NHS Trust
Advertisements

Thiamin (Vitamin B1): Beriberi Sara Parnell. Thiamin Discovered to be an important nutrient during the 1800s when rice was being made with only the endosperm.
Wernicke-Korsakoff Syndrome
Refeeding Syndrome Management Issues Stella Hahn Pulmonary/Critical Care Fellow 2013.
Hepatic insufficiency Severe damage in liver cells will result in serious dysfunction in metabolism, secretion, synthesis, detoxification and immune system,
Alternative ways of monosaccharides metabolism.. Glucose The fate of glucose molecule in the cell Glucose-6- phosphate Pyruvate Glycogen Ribose, NADPH.
CHAPTER 14 Glucose Utilization and Biosynthesis –Harnessing energy from glucose via glycolysis –Fermentation under anaerobic conditions –Synthesis of glucose.
Chapters 9 & 10: V itamins. © 2010 Pearson Education, Inc. Vitamins  Tasteless, organic compounds  Required in small amounts  Functions Regulate metabolism.
Nutritional Therapy For psychiatric patient Prepared by Mrs/ HAMDIA MOHAMMED.
PENTOSE PATHWAY & ANTIOXIDANTS BIOC DR. TISCHLER LECTURE 30.
Hepatic Encephalopathy in End-Stage Liver Disease Megan Dudley End of Life Care for Adults and Families The University of Iowa College of Nursing 1.
Treatments for the stages of alcoholic liver disease may include abstinence from alcohol completely, corticosteroids and enteral nutrition for severe alcoholic.
Vitamins B 6 and B 12 General biochemistry Functions Deficiency diseases.
ALCOHOL AND THE NERVOUS SYSTEM DR M KAKAZA. COMMON COMPLICATIONS Nutritional deficiency Diseases partly nutritional in origin Direct effects of alcohol.
By: Michelle Russell Case Study Presentation NUR 4216L
Chapter 9 Alcohol Acute effects Mechanisms of action Long-term effects
Water Soluble Vitamins By: DR Norhasmah bt. Sulaiman Department of Resources Management and Consumer Studies Faculty of Human Ecology.
Animal Nutrition All animals must eat. Whether a herbivore, carnivore, or an omnivore the ingestion of nutrition and calories must satisfy the following.
Chapter 9 Alcohol Acute effects Mechanisms of action Long-term effects
ALZHEIMER’S DISEASE BY OLUFOLAKUNMI KEHINDE PRE-MD 1.
Pentose phosphate pathway A.Functions 1. NADPH for reductive biosyntheses. 2. ribose-5-phosphate for nucleic acid biosynthesis. 3. a route for the conversion.
Hepatic encephalopathy/ Portal-systemic encephalopathy /hepatic coma
1 Sources of Alcohol Contains 7 kcal/g Beer, wine, distilled spirits, liqueurs, cordials, and hard cider –Vary in alcohol and caloric content Standard.
Lecture 11a- 17 November 2014 This lecture is based largely on CHAPTER 23 IN KRAUSE'S FOOD NUTRITION AND DIET THERAPY (ON RESERVE IN LIBRARY) AND CHAPTERS.
Lewis R. Goldfrank, MD Professor and Chairman of Emergency Medicine New York University Medical Center Bellevue Hospital Center New York University School.
The Banana Bag: Small Potatoes against Wernicke’s Encephalopathy The Banana Bag: Small Potatoes against Wernicke’s Encephalopathy Neha Patel MD, Devika.
Lecture 6 TOXICITY Toxicity from excessive dietary intake of major minerals rarely occurs in healthy individuals. Kidneys that are functioning normally.
MLAB 2401: Clinical Chemistry Keri Brophy-Martinez
How Is Chemotherapy Used to Treat Cancer?
Nikita Alicea.
Chapter 22 Metabolic Pathways
Chapter 8: Nutrients Involved in Energy Metabolism
MINERALS IN HUMAN HEALTH
Nutrition and Metabolism
Zinc(Zn) At. No. 30 At. Wt. 60. Zinc(Zn) At. No. 30 At. Wt. 60.
Oxidative Decarboxylation and Krebs Cycle
FATE OF PYRUVATE OR Pyruvate Metabolism
TOPIC- CARBOHYDRATE METABOLISM
Oxidative Decarboxylation and Krebs Cycle
Phosphorus. Phosphorus Learning Objectives Dietary sources Daily Requirements Metabolism Important functions and Deficiency diseases.
Yard. Doç.Dr. N. Berfu AKBAŞ
22.7 Gluconeogenesis: Glucose Synthesis
Vitamin E Vitamin E refers to a group of eight fat-soluble compounds that include both tocopherol and tocotrienol. The vitamin is synthesized by plants,
Chapter 5: Nutritional Considerations
The vitamin B-complex refers to all of the known essential water-soluble vitamins except for vitamin C. Each member of the B-complex has a unique structure.
Chapter 8 The Water-Soluble Vitamins
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate (PLP)
Pentose Phosphate Pathway
Chapter 19 Inborn Errors of Metabolism
Vitamins, Minerals and Food components
Chapter 27 Nutrition and Metabolism
Chapter 38 Drug Abuse II: Alcohol 1.
Hepatic Encephalopathy and Coma
Micro and macro elements in food products
11/15/2018 Nutrition 11/15/2018.
IRON IN HEALTH AND DISEASE
Glucose-6-Phosphate Dehydrogenase
The Krebs Tricarboxylic Acid Cycle
OBJECTIVES To understand the function of the pentose phosphate pathway in production of NADPH and ribose precursors for nucleic acid synthesis. To examine.
بسم الله الرحمن الرحيم.
Water Soluble Vitamins
Delirium
2/15/2019 Shadab Salehpour.
Clinical Pharmacokinetics
14. Vitamins & Trace Elements
Vitamins B6 and B12 General biochemistry Functions Deficiency diseases.
Biochemistry UREA CYCLE
Lactic Acidosis Cardiovascular Block.
Scientific Background
What’s All The Buzz About B’s?
Presentation transcript:

Wernicke-Korsakoff Syndrome [WKS] PHM142 Presentation Instructor: Dr. J. Henderson Wernicke-Korsakoff Syndrome [WKS] Andrew Trickey, Ahmed Karaki, Jeffrey Ta, Zhi Lun Zhang

Table of Contents Overview Causes Symptoms Pathophysiology Diagnosis Treatment Summary References

Overview Discovered by Carl Wernicke and Sergei Korsakoff Combination of two seperate disorders Wernicke’s Encephalopathy/Disease (WE/WD) Characterized by lesions in the CNS caused by thiamine deficiency Korsakoff Syndrome (KS) Characterized by amnesia caused by thiamine deficiency and alcohol abuse WE occurs first, if left untreated, KS will develop and you will have two separate diseases occuring at the same time WKS associated with thiamine deficiency affects essential cellular processes in the brain impairing memory, coordination, vision and mental state

Causes of Wernicke-Korsakoff Syndrome Deficiency in thiamine (vitamin B1) causes lesions on the brain which results in Wernicke’s Encephalopathy Reversible acute phase if immediately treated If left untreated, Korsakoff Syndrome will develop Irreversible chronic phase with permanent brain damage Chronic alcoholism Alcohol interferes with conversion of thiamine to thiamine pyrophosphate (active form of thiamine) Prevents absorption of thiamine in the small intestines Alcohol abuse can cause cirrhosis interfering with storage of thiamine Malabsorption from stomach cancer or inflammatory bowel disease which impairs thiamine absorption (Chandrakumar et al. 2018)

Symptoms of Wernicke-Korsakoff Syndrome Wernicke Encephalopathy Confusion and loss mental activity (may lead to violent behaviour) Loss of muscle coordination (ataxia) Affected vision such as abnormal eye movements, double vision and upper eyelid drooping Korsakoff Syndrome Inability to learn new information Anterograde amnesia (inability to create new memories) & retrograde amnesia (inability to recall previous memories) Confabulation (exaggerated storytelling to fill gaps in memory) House Scene diagnosing WKS patient: https://www.youtube.com/watch?v=KgxV-kfOnJE (Chandrakumar et al. 2018)

Pathophysiology: Deficiency with Alcohol Consumption Alcohol affects thiamine uptake at the cellular level in two ways: Reduces absorption from the gastrointestinal tract into cells Thiamine is transported via active transport and is associated with phosphorylation by thiamine diphosphokinase (TPK) which has decreased activity with alcohol exposure Utilization Phosphorylated thiamine (ThDP) enzyme binding requires magnesium which is usually deficient in alcoholics as well (Martin et al., 2003)

Pathophysiology: The Molecular Level (Brain) Thiamine is a cofactor for the enzyme transketolase This is essential for the pentose phosphate pathway The pathway creates ribose-5-phosphate and NADPH Ribose-5-phosphate is needed for nucleic acid and complex sugar molecule synthesis NADPH provides hydrogen for the synthesis of many other essential cellular elements as well as neurotransmitters NADPH is also involved the synthesis of glutathione, an antioxidant https://pubs.niaaa.nih.gov/publications/arh27-2/IMAGES/Page137b.gif (Martin et al., 2003)

Thiamine is also a cofactor for pyruvate dehydrogenase (PDH) of glycolysis and alpha-ketoglutarate dehydrogenase (α-KGDH) of the citric acid cycle https://pubs.niaaa.nih.gov/publications/arh27-2/IMAGES/Page138.gif (Martin et al., 2003)

Pathophysiology: Result Transketolase can be up to 90% inhibited in some areas of the brain with thiamine deficiency Glutathione cannot combat oxidative stress in the cell Decreased efficiency of glycolysis and ATP production can lead to cell apoptosis Cell necrosis leads to lesions on the brain PDH is needed for myelin and acetylcholine synthesis α-KGDH helps maintain GABA levels and protein synthesis Cell death and hindered neuron function leads to the disease https://pubs.niaaa.nih.gov/publications/arh27-2/IMAGES/Page137a.gif (Martin et al., 2003)

Diagnosis: physical examinations Liver function test Look for signs of alcoholism Kidney function test Eye exam Checking freedom of eye movement Reflex and gait Blood test Serum albumin test. Serum vitamin B1 test RBC enzyme activity test Low levels of albumin may signal nutritional deficiencies as well as kidney or liver problems. Low enzyme activity in the RBCs signals a vitamin B-1 deficiency.

Diagnosis: imaging tests CT scan to look for brain lesions related to Wernicke-Korsakoff MRI scan to look for changes in brain metabolism An electrocardiogram before and after taking vitamin B1

Treatments: Thiamine Vitamin B1 (thiamine hydrochloride) Intravenous (IV) Intramuscular (IM) Oral supplements Diet Foods naturally high in B1 (meats, vegetables, nuts, etc.) Foods fortified with B1 (grain products) Acute treatment: 500 mg in normal saline IV, tid for at least 3 days 250 mg in normal saline IV, qd for 3 days 100 mg PO tid for the rest of the hospitalization 100 mg PO daily after discharge

Treatments: Others Magnesium (magnesium sulfate) Phosphorylated B1 binding and uptake requires magnesium Cofactor for carbohydrate metabolism through B1-dependent pathways Potassium (potassium acid phosphate) Alcoholics tend to have low potassium levels Reduce Alcoholism (long-term solution) Stop inhibition of thiamine diphosphokinase Reduced renal excretion of magnesium (and other electrolytes) Long-term care Permanent cognitive disabilities (cognitive and memory, confabulation) Permanent physical disabilities

Summary WKS is combination of Wernicke Encephalopathy and Korsakoff’s Syndrome caused by deficiency of thiamine (Vit. B1) Alcoholism decreases thiamine uptake and utilization Permanent cognitive/physical damage Thiamine deficiency hinders biochemical pathways: Pentose phosphate pathway decreasing glutathione synthesis and increasing oxidative stress Glycolysis leading to apoptosis and the citric acid cycle impairing acetylcholine and GABA synthesis WKS is diagnosed with a series of physical examination and brain imaging tests Liver/kidney function tests (alcoholic damage), eye exam, reflex and gait, blood test (B1, albumin, RBC enzyme) CT scan (brain lesions), MRI (metabolic changes), ECG (see changes before/after treatment with thiamine) Acute treatment with IV thiamine to restore hindered pathways and further supplementation of thiamine afterwards IV to bypass impaired thiamine B1 absorption Reduce alcohol consumption and give magnesium sulfate to restore phosphorylated-thiamine binding and uptake by active transporters

References Martin, P.R., Singleton, C.K., & Hiller-Sturmhofel, S. (2003). The role of thiamine deficiency in alcoholic brain disease. Alcohol Research & Health, 27(2); 134-142. Retrieved November, 2018, from https://pubs.niaaa.nih.gov/publications/arh27-2/134-142.htm?fbclid=IwAR0oV9JuhoyJEo0puEeALP6DE0x0w_DdxJjHT8GQCK4rYrPUcS8DLqeEaio Mccormick LM, Buchanan JR, Onwuameze OE, Pierson RK, Paradiso S. Beyond Alcoholism. Cognitive And Behavioral Neurology. 2011;24(4): 209–16. (Accessed on November 2018) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551444/ Rivlin RS. Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review). Journal of the American College of Nutrition. 1994;13(5): 416–23. (Accessed on November 2018) https://www-tandfonline-com.myaccess.library.utoronto.ca/doi/abs/10.1080/07315724.1994.10718430 Chandrakumar A, Bhardwaj A, Jong GW. Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. Journal of Basic Clinical Physiology and Pharmacology. 2018;1-10. Doi: https://doi.org/10.1515/jbcpp-2018-0075