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Fatty liver disease and diet - Coggle Diagram
Fatty liver disease and diet
Liver Anatomy
Lobes
Right lobe
Left lobe
Caudate lobe
Quadrate lobe
Blood Supply
Hepatic Veins
Deoxygenated Blood
Hepatic Artery
~25% of hepatic blood flow
~75% of O2
Portal Vein
~75% of hepatic blood flow
High nutrient content
Poorly oxygenated from GI tract
Ligaments
Coronary ligament
Left triangular ligament
Falciform ligament
Right triangular ligament
Cell types
Hepatocytes - chief functional cells, 80% of liver mass is hepatocytes
Kupffer Cells - phagocytic cell which forms the lining of liver sinusoids, involved in the breakdown of red blood cells (RBCs)
Hepatic stellate cells - pericytes found in the perisinusoidal spaces in the liver
Hepatic lobules
~100,000 hexagonal functional units
Single vein surrounded by hepatocytes, 6 hepatic arteries and 6 hepatic portal veins
Blood vessels connected by sinusoids
Building block of liver tissue
Liver function
Varies from cell to cell
CHO metabolism
Gluconeogenesis
Glycogen synthesis and breakdown
Fat metabolism
Fatty Acid and TAG synthesis
Cholesterol, lipoprotein and bile acid synthesis and excretion
Ketogenesis (production of ketones)
25-hydroxylation of vit. D (metabolism of vit. D)
Dietary fats are packed into chylomicrons before being transported to the liver for synthesis
Protein metabolism
Synthesis of plasma proteins
Urea synthesis
Hormone metabolism
metabolism and excretion of steroid hormone
Metabolism of polypeptide hormones
Drug and foreign compound metabolism and excretion
Storage of glycogen, vits A, D, E, K, B12 and iron
Metabolism and excretion of bilirubin (red blood cell breakdown forms this)
Bile and the Biliary System
Main functions
Drain waste products from the liver into the duodenum
Aid digestion with the controlled release of bile
What is bile?
Yellow/ green fluid containing bile salts, bilirubin, fats and salts
Bile salts help emulsify and breakdown fats during digestion and absorption
Route of excretion for bilirubin
It is excreted from the body in faeces
What is bilirubin?
breakdown product from haem in RBCs
Excreted in bile/gut and urine
Jaundice/ hyperbilirubinemia
caused by the presence of unconjugated bilirubin in the plasma, above 50umol/L it binds to proteins other than albumin in cell membranes
Causes
Post-hepatic/ cholestatic
Cholestasis - bile cannot flow into the duodenum due to blockages in the gallbladder
Cholecystectomy - gall bladder removal - no storage of bile means it is continuously released to the digestive tract
Pre-hepatic/ haemolytic
Hepatic/ hepatocellular
Infections, intra-hepatic obstruction
Liver Function Tests (LFTs)
Function
Doesn't assess functional capacity of the liver
Assists in the differentiation between different types of liver damage
Aminotransferases
Aspartate Transferase (AST) & Alanine Transferase (ALT)
Sensitive but non-specific biomarkers of acute damage to hepatocytes
Causes
Hepatitis (infection)
Toxic injury (drugs, alcohol, supplements)
Shock
Alkaline Phosphatase (ALP)
Increased activity due to increased synthesis of cells lining the bile duct
Causes
Cholestasis (bile duct blockages)
Infiltrative diseases of the liver
Cirrhosis (scarring)
Gamma glutamyl trans peptidase (γGT)
Sensitive biomarker of liver disease, can be raised due to
Cholestasis
Obesitiy
After consumption of alcohol
Plasma Proteins
albumin is a main product of the liver, indicative of synthesis capacity
advanced chronic liver disease raises the levels
Prothrombin time
Measure of clotting time, more sensitive test of liver synthetic capacity as several coagulation factors are made in the liver
Alcoholic Liver Disease (ALD)
Liver manifestation of alcohol overconsumption
Direct relation between amount consumed and risk of ALD, above 30 g/ day (3.75 units)
Genetic component to alcoholism and ALD
Factors which affect ALD progression
Alcohol consumption
Nutritional factors
Oxidative stress
Gender
Age
Obesity
Drinking patterns
Genetic Factors
Cigarette Smoking
Cytokines
Endotoxins
Lipotoxicity
Abstinence can revert the liver to healthy to an extent even when cirrhosis is present
Non-Alcoholic Fatty Liver Disease (NAFLD)
3 stages
Non-Alcoholic fatty liver (NAFL)
Non-Alcoholic Steatohepatitis (NASH)
Fibrosis/ Cirrhosis (scarring)
Greater than 5% lipid accumulation in the liver in absence of drugs/ alcohol intake and other diseases
NAFLD comorbidities (simultaneous other diseases)
Obesity: 51% of NAFL and 82% of NASH
Metabolic Syndrome: 43% NAFL, 71% NASH
Type 2 Diabetes: 23% NAFL, 44% NASH
Progression is typically slow and is hard to diagnose
Factors affecting progression
Environment
Dietary Factors
Food Intake
Physical Activity
Gut Microflora
Genetics
Oxidative Stress
Immune related
Metabolic
NAFLD Risk Factors
Genetic
Definitions
Genome Wide Association Studies (GWAS)
Single Nucleotide Polymorphisms (SNPs) - a precise position along the chromosome where the DNA of individuals may vary
Non-coding SNPs occur more frequently
Synonymous SNPs don't change protein sequences
Non-synonymous SNPs change protein sequences can be missense, nonsense or nonstop
PNPLA3 Allele
Identified in American DWAS
Associated with hepatic fat but not glucose or lipoprotein alterations
Associated with ALT and AST levels
Associated with histological NAFLD but not metabolic syndrome
Associated with ALD and alcoholic cirrhosis
Influences steaosis (fatty change) and lack of response to antiviral treatment of Hepatitis C
SNPs in ADH1B, ADH1C, ALDH2 (responsible for metabolism of alcohol) can cause increase in amount of production/ oxidation of acetaldehyde (toxic)
Modifiable
Nutrition
Positive
Polyphenol consumption
Mediterranean/ low CHO diet
Vit E. supplements
Omega 3 supplements
Negative
saturated fat consumption
High fructose/ sugar diets
Dietary composition is less important than total energy intake but it is suggested than a low carb diet is better in the short term than other diets
Choline deficiency
Lifestyle Factors
Negative
Weight gain
Results in increased TNFα, IL-6 and lipolysis and reduced adiponectin. Which causes larger adipocytes (fat cells) and a higher number of inflammatory cells which can all lead to FLD
Inactivity
Vit. D deficiency
Positive
Exercise
Aerobic and resistance exercise are equally effective for FLD reduction but not as effective as weight loss
Weight loss
Reduces the size of adipocytes and the number of inflammatory cells resulting in a heatlhy liver
Patients should aim to lose 5-10% of their body weight
Modest hypocaloric diet -500kcal per day
Regular exercise 30-60min 3-5 times a week
Multiple risk factors e.g. diabetes, high alcohol consumption and hepatitis B virus (HBV) substantially increases the risk of cirrhosis (liver scarring) and hepatocellular carcinoma (HCC), a type of liver cancer
Metabolic associated fatty liver disease (MAFLD)
Proposed name change due to there being more metabolic syndromes and genetic risk factors causing FLD as opposed to obesity
Interindividiual variation
Factors
Genetic disposition
Metabolic syndrom
Environmental factors
The dynamic interaction between factors.
Size of different factors and the predominant drivers can result in a large variation between individuals
Complex phenotype shaped by different factors 'interindividual variation'
Evidence based practise guidelines for MAFLD
Lose weight (5-10% over 1 year and maintain)
Exercise (start slow build up to 60min/5 days)
Focus on lower healthier carbs (40% reduction)
Decrease saturated fats (<10%)
Increase MUFAs and Omega 3
