FUNCTIONS OF BILE ACIDS AND SALTS WITH ASSESSMENT OF LIVER FUNCTIONS.pptx
- 1. BCH 311 BILE: Constituents & Functions. Biochemical Changes and Assessment of Liver Function.
- 2. BILE: Constituents • Bile (from latin bilis), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. • In humans, bile is produced continuously by the liver (liver bile), stored and concentrated in the gallbladder. • After eating, this stored bile is discharged into the duodenum.
- 3. BILE: Constituents • The composition of hepatic bile is (97–98)% water, 0.7% bile salts, 0.2% bilirubin, 0.51% fats (cholesterol, fatty acids, and lecithin), and 200 meq/l inorganic salts. • The two main pigments of bile are bilirubin, which is orange–yellow, and its oxidized form biliverdin, which is green. • When mixed, they are responsible for the brown color of faeces. • About 400 to 800 millilitres of bile is produced per day in adult human beings.
- 4. BILE: Constituents • Bile salts and bile acids are polar cholesterol derivatives, and represent the major route for the elimination of the steroid from the body. • They are molecules with similar but not identical structures, and diverse physical and biological characteristics. • They are synthesized in the liver, stored in the gallbladder, secreted into the duodenum, and finally, for the most part, reabsorbed in the ileum. • Because at physiological pH these molecules are present as anions, the terms bile acid and bile salts are used herein as synonyms.
- 5. Chemical structure of bile salts • Bile salts have similarities and differences with cholesterol molecule. • Like the steroid, they have a nucleus composed of four fused rings: three cyclohexane rings, labeled A, B and C, and a cyclopentane ring, labeled D. • This structure is the perhydrocyclopentanophenanthrene, more commonly known as steroid nucleus.
- 6. Structure of Bile Acids & their Conjugates
- 7. Functions of Bile 1. Bile or gall acts as a surfactant, helping to emulsify the lipids in food. • Bile salt anions are hydrophilic on one side and hydrophobic on the other side; consequently, they tend to aggregate around droplets of lipids (triglycerides and phospholipids) to form micelles, with the hydrophobic sides towards the fat and hydrophilic sides facing outwards. • The hydrophilic sides are negatively charged, and this charge prevents fat droplets coated with bile from re-aggregating into larger fat particles.
- 8. Functions of Bile • Ordinarily, the micelles in the duodenum have a diameter around 1–50μm in humans. • The dispersion of food fat into micelles provides a greatly increased surface area for the action of the enzyme pancreatic lipase, which actually digests the triglycerides, and is able to reach the fatty core through gaps between the bile salts. • Without bile salts, most of the lipids in food would be excreted in faeces, undigested.
- 9. Functions of Bile 2. Since bile increases the absorption of fats, it is an important part of the absorption of the fat-soluble substances, such as the vitamins A, D, E, and K. 3. Bile serves also as the route of excretion for bilirubin, a by-product of red blood cells recycled by the liver. 4. It also has the function of neutralizing excess stomach acid before it enters the duodenum as bile tends to be alkaline on average. • The pH of common duct bile (7.50 to 8.05) is higher than that of the corresponding gallbladder bile (6.80 to 7.65).
- 10. Functions of Bile • Bile in the gallbladder becomes more acidic the longer a person goes without eating, though resting slows this fall in pH. • As an alkali, it also has the function of neutralizing excess stomach acid before it enters the duodenum, the first section of the small intestine. 5. They are the major route for the elimination of cholesterol from human body as humans do not have the enzymes to break open the cyclohexane rings or the cyclopentane ring of the steroid nucleus, nor to oxidize cholesterol to CO2 and water.
- 11. Functions of Bile • The other mechanism to eliminate the steroid from the body is as cholesterol per se in the bile. 6. At the intestinal level, they modulate the secretion of pancreatic enzymes and cholecystokinin. 7. In the small and large intestine, they have a potent antimicrobial activity, mainly deoxycholic acid, in particular against Gram-positive bacteria. • This activity may be due to oxidative DNA damage, and/or to the damage of the cell membrane.
- 12. Functions of Bile • Therefore, they play an important role in the prevention of bacterial overgrowth, but also in the regulation of gut microbiota composition. 8. They also play a regulatory role in the control of energy metabolism, and in particular the hepatic glucose handling.
- 13. Biochemical Changes and Assessment of Liver Function
- 14. Introduction to the Liver The liver is the largest internal organ, weighing approximately 1.5 kg. It performs over 500 vital functions, including metabolism, detoxification, and synthesis of important proteins and enzymes. Main functions: metabolism of carbohydrates, proteins, and fats; detoxification of blood; storage of vitamins and minerals; production of bile.
- 15. Introduction to the Liver Anatomy of the liver showing its lobes, blood vessels, and bile ducts.
- 16. Overview of Liver Metabolism Content: o Carbohydrate Metabolism: Glycogen storage and glucose release. o Protein Metabolism: Breakdown of amino acids and urea production. o Lipid Metabolism: Fatty acid synthesis and oxidation.
- 17. Overview of Liver Metabolism
- 18. Carbohydrate Metabolism Glycogen Synthesis: Process of storing glucose as glycogen (glycogenesis). Glycogen Breakdown: Conversion of glycogen back to glucose (glycogenolysis). Gluconeogenesis: Production of glucose from non-carbohydrate sources. Glycogen Storage Diseases: Examples include Von Gierke's disease and McArdle's disease.
- 20. Protein Metabolism Amino Acid Catabolism: Deamination of amino acids to produce urea. Urea Cycle: Conversion of ammonia to urea for excretion. Clinical Significance: Disorders such as Ornithine Transcarbamylase (OTC) deficiency.
- 22. Lipid Metabolism Fatty Acid Synthesis: Creation of fatty acids from acetyl-CoA. Beta-Oxidation: Breakdown of fatty acids to produce energy. Cholesterol Synthesis: Production of cholesterol, a vital component of cell membranes and a precursor for so many important biomolecules. Lipid Storage Diseases: Examples include Gaucher's disease and Niemann- Pick disease.
- 23. Lipid Metabolism Pathways for fatty acid synthesis and oxidation.
- 24. Detoxification and Biotransformation Phase I Reactions: Oxidation, reduction, and hydrolysis (e.g., cytochrome P450 enzymes). Phase II Reactions: Conjugation reactions (e.g., glucuronidation, sulfation). Clinical Relevance: Impact on drug metabolism and potential for drug interactions.
- 25. Detoxification and Biotransformation Phase I and Phase II detoxification and elimination pathways
- 26. Liver Function Tests (LFTs) Purpose: Assess liver function and detect liver damage Common Tests: ALT (Alanine Aminotransferase) AST (Aspartate Aminotransferase) ALP (Alkaline Phosphatase) Bilirubin (total and direct) Albumin Normal Ranges and Interpretation: Explanation of normal values and what deviations might indicate.
- 27. Liver Function Tests (LFTs) A table summarizing common liver function tests, their normal ranges
- 28. Biochemical Markers of Liver Disease
- 29. Liver Disease Case Studies • Hepatitis: Inflammation of the liver, often due to viral infections (Hepatitis A, B, C). • Cirrhosis: Chronic liver damage leading to scarring and liver failure. • Fatty Liver Disease: Accumulation of fat in liver cells, often associated with obesity and alcohol use. • LFT Interpretation: Examples of LFT results in different liver diseases.
- 30. Liver Disease Case Studies
- 31. ASSESSMENT OF LIVER FUNCTIONS - Clinical Evaluation - Laboratory Tests - Imaging Studies - Specialised Tests - Interpretation of Results
- 32. Clinical Evaluation History and Physical Examination: Gathering detailed medical history, including symptoms (e.g., jaundice, fatigue, abdominal pain), risk factors (e.g., alcohol consumption, drug use, family history), and physical examination findings (e.g., hepatomegaly, jaundice). Symptoms: Common symptoms of liver dysfunction include jaundice, dark urine, pale stools, pruritus, fatigue, and abdominal pain.
- 33. Laboratory Tests Liver Function Tests: These blood tests measure levels of liver enzymes, proteins, and bilirubin to assess liver function. o Alanine Aminotransferase (ALT): Elevated levels indicate hepatocellular injury. o Aspartate Aminotransferase (AST): Elevated levels also indicate hepatocellular injury. o Alkaline Phosphatase (ALP): Elevated levels suggest cholestasis or biliary obstruction. o Gamma-Glutamyl Transferase (GGT): Elevated levels indicate bile duct issues or alcohol use. o Bilirubin: Elevated levels indicate impaired bilirubin metabolism or excretion. o Albumin: Low levels suggest impaired liver synthetic function. o Prothrombin Time (PT): Prolonged PT indicates impaired liver function affecting blood clotting. o Lactate Dehydrogenase (LDH): Elevated levels can indicate liver damage.
- 34. Imaging Studies Ultrasound: Non-invasive imaging to assess liver size, structure, and detect abnormalities such as tumours, cysts, or fatty liver. Computed Tomography (CT) Scan: Provides detailed cross-sectional images of the liver and surrounding structures. Magnetic Resonance Imaging (MRI): Offers high-resolution images and can detect liver lesions, cirrhosis, and other abnormalities. Elastography: Measures liver stiffness to assess fibrosis and cirrhosis.
- 35. Specialized Tests Liver Biopsy: Involves taking a small sample of liver tissue for microscopic examination to diagnose liver diseases and assess the extent of liver damage. Hepatic Function Panel: A comprehensive panel of tests that includes LFTs, coagulation tests, and other markers to evaluate liver function. Genetic Testing: Used to identify genetic liver diseases such as haemochromatosis or Wilson's disease.
- 36. Interpretation of Results Pattern Recognition: Abnormal liver test results are often grouped into patterns to help identify the underlying cause: o Hepatocellular Pattern: Predominantly elevated ALT and AST levels. o Cholestatic Pattern: Predominantly elevated ALP and GGT levels. o Mixed Pattern: Elevated levels of both hepatocellular and cholestatic markers. Clinical Correlation: Interpretation of liver tests should be guided by the patient's history, risk factors, and clinical findings.
- 37. Summary • Assessing liver function is a multifaceted approach that involves clinical evaluation, laboratory tests, imaging studies, and specialized tests. • Accurate interpretation of these results, along with clinical correlation, is essential for diagnosing and managing liver diseases effectively.
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