BIOQUI - 01/08/2023

Transporte y Almacenamiento de Lípidos

Introducción al Transporte de Lípidos

• El tema del día es el transporte de lípidos, con implicaciones clínicas en aterosclerosis, insuficiencia hepática por exceso de grasa e infarto de miocardio.

Estructura y Funciones de los Lípidos

• Los lípidos están compuestos por uno o más ácidos grasos, que determinan sus características bioquímicas. La cadena hidrocarbonada es hidrófoba, mientras que el grupo ácido carboxílico interactúa bien con sustancias polares.

• Las funciones principales de los lípidos incluyen la formación de membranas celulares y almacenamiento energético, especialmente a través de triglicéridos y gliceroles.

Rol en la Absorción y Transporte

• Los lípidos también facilitan la absorción de vitaminas durante la digestión. Sin embargo, debido a su naturaleza hidrófoba, no pueden transportarse libremente en el plasma sanguíneo.

• Para su transporte, los lípidos se asocian con proteínas anfipáticas formando lipoproteínas.

Estructura de las Lipoproteínas

• Las lipoproteínas encapsulan los lípidos en un glóbulo proteico; tienen una parte interna lipofílica y una externa hidrofílica para facilitar el transporte a través del sistema circulatorio.

• Este proceso es continuo ya que los tejidos requieren fosfolípidos, triglicéridos y colesterol para diversas funciones.

Clasificación y Tipos de Lipoproteínas

• Existen diferentes tipos de proteínas como ApoB, ApoA1 y Apo4 que ayudan en el transporte lipídico. Estas proteínas son clasificadas según su densidad.

Understanding Lipoproteins and Their Role in Atherosclerosis

The Impact of Carbohydrates and Fats on HDL Levels

• Excessive intake of carbohydrates and fats can lead to increased levels of low-density lipoproteins (LDL), which are risk factors for atherosclerosis. High-density lipoproteins (HDL) are considered beneficial.

Differentiating Between Good and Bad Cholesterol

• The terms "good" and "bad" cholesterol refer to HDL and LDL, respectively. HDL helps remove excess lipids from vascular endothelium, while LDL contributes to lipid accumulation.

Composition of Lipoproteins

• Different types of lipoproteins include chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), LDL, and HDL. Each has varying compositions of proteins, triglycerides, and cholesterol.

Digestion and Absorption of Lipids

• Lipids are digested in the small intestine by various enzymes known as lipases that target different lipid types such as phospholipids, triglycerides, and cholesterol.

Liver's Role in Lipid Processing

• The liver processes absorbed lipids to form various lipoproteins that transport these substances throughout the body via the circulatory system.

Consequences of Excess Fat Accumulation

Clinical Implications of Excessive Lipid Production

• An imbalance in lipid metabolism can lead to significant clinical issues including hepatic steatosis (fatty liver disease), which may progress to cirrhosis if not managed properly.

Causes of Hepatic Steatosis

• Hepatic steatosis is primarily caused by excessive lipid production or inadequate utilization. Common causes include poor diet high in carbohydrates/fats and genetic predispositions.

Types of Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD)

• NAFLD is often linked with sedentary lifestyles, high carbohydrate diets, diabetes type 2, and metabolic syndrome which includes hypertension.

Alcoholic Fatty Liver Disease

• Chronic alcohol consumption leads to excessive lipid production due to altered metabolism involving ethanol conversion into acetaldehyde then acetate—contributing further to fatty liver conditions.

Metabolism Pathways Related to Alcohol Consumption

Ethanol Metabolism Overview

• Ethanol is metabolized primarily in the liver through alcohol dehydrogenase converting it into acetaldehyde followed by aldehyde dehydrogenase converting it into acetate.

Acetate's Role in Energy Production

• Acetate produced during ethanol metabolism can enter the Krebs cycle or be converted into acetyl-CoA for fatty acid synthesis when energy levels are high from either food or alcohol consumption.

Understanding Liver Architecture and Its Implications in Fatty Liver Disease

The Structure of the Liver

• The liver's architecture includes a portal triad consisting of a branch of the hepatic artery, bile ductules, and central veins that supply blood to hepatocytes within the hepatic lobule.

• Blood from the liver is returned through the hepatic vein to the inferior vena cava, ultimately reaching the right heart.

Impact of Fatty Liver Disease

• In cases of fatty liver disease, this intricate structure becomes altered, affecting both portal and arterial blood flow as it progresses towards cirrhosis.

• Complications arise from fatty liver disease, including decreased metabolic processes and impaired bile elimination due to obstruction in bile ducts.

Consequences of Cirrhosis

• Cirrhosis leads to severe complications such as metabolic dysfunction in synthesizing essential proteins like albumin, which can result in complete liver failure.

• Hepatic encephalopathy may occur due to excess ammonia levels resulting from impaired liver function.

Symptoms and Clinical Manifestations

• Initial symptoms are often minimal; however, significant conditions like hepatomegaly (enlarged liver), digestive issues, and portal hypertension can develop.

• Portal hypertension can lead to visible signs such as "caput medusae" (dilated veins around the stomach), esophageal varices, and hemorrhoids due to alternative blood flow routes.

Fluid Retention and Edema

• Ascites results from portal hypertension combined with reduced albumin synthesis leading to fluid leakage into tissues causing generalized edema.

• Hepatic encephalopathy manifests through neurological alterations that may progress to coma or death.

Visual Representation of Liver Conditions

• A comparison between healthy livers and cirrhotic livers illustrates structural changes; regenerative nodules form but lack proper architecture for effective function.

Bile Metabolism Issues

• Cirrhosis disrupts bilirubin metabolism leading to jaundice due to inadequate bile flow through damaged hepatic structures.

Ammonia Levels in Hepatic Insufficiency

• Increased ammonia levels during hepatic insufficiency stem from amino acid degradation processes that release free amino groups contributing to toxicity.

Metabolism of Amino Acids and Its Implications

Sources of Ammonia Production

• The amino group from amino acids is converted into ammonia (NH3) through metabolic processes, which can then gain a proton to form ammonium ion (NH4+), acting as a base depending on pH.

• Two primary sources of ammonia in the body are:

• Normal metabolism of amino acids.

• Bacterial metabolism in the intestines, producing ammonia and ammonium ions that enter the bloodstream.

Urea Cycle and Liver Function

• A diagram illustrates how intestinal microbiota produces ammonia, which travels to the liver. Here, hepatocytes convert ammonia and ammonium ions into urea via the urea cycle.

• In cases of severe liver dysfunction (e.g., fatty liver or cirrhosis), the urea cycle fails, leading to increased levels of ammonia and ammonium ions that can cross the blood-brain barrier.

Neurological Effects of Ammonia Accumulation

• Elevated levels of ammonia can cause neurological damage resulting in altered consciousness, confusion, stupor, coma, or even death due to its toxic effects on brain function.

Impact of Lipoproteins on Vascular Health

Role of Low-Density Lipoproteins (LDL)

• Triglycerides and cholesterol contribute to normal physiological functions; however, excess low-density lipoproteins (LDL) accumulate in tissues over time due to factors like obesity and sedentary lifestyle.

• Excessive LDL accumulation leads to chronic inflammation as macrophages attempt to clear out excess fats and cholesterol from tissues.

Development of Atherosclerosis

• Chronic inflammation results in anatomical changes where macrophages transform into foam cells. This process involves migration from smooth muscle tissue towards endothelial surfaces.

• The formation of mature calcified atheromas occurs with deposits including fibrin and collagen. These structures resemble scabs on skin but occur within vascular endothelium.

Complications Arising from Plaque Formation

• Initial lesions develop with monocytes converting into macrophages that consume lipids. Over time this leads to silent chronic inflammation involving lymphocytes and platelets contributing to coagulation processes.

• Mature plaques contain necrotic centers filled with foam cells alongside cholesterol deposits. When platelets adhere or detach from these plaques, they may trigger clotting events leading potentially to heart attacks or other ischemic conditions.

Consequences for Patient Health