Liver Anatomy and Physiology Quiz

Anatomy and Pathophysiology of the Liver

• The liver is the largest gland in the human body, wedge-shaped, and shaped by adjacent organs and muscles.
• It plays a crucial role in metabolism, including glycogen storage, plasma protein synthesis, and removal of toxic substances from the blood.
• Bile production is an essential liver function, crucial for digestion.
• The liver is the primary hematopoietic organ until the 6th month of intrauterine life.
• In the case of splenectomy, it can take over the spleen's function.
• The liver is located in the supramesocolic region of the abdomen, below the diaphragm and extending to the right hypochondrium and epigastrium.
• The liver is covered in parietal peritoneum except for the "bare area" where it contacts the diaphragm.
• It is enveloped by Glisson's capsule but shape is not significantly determined by this capsule.
• The liver weighs approximately 1.5-2 kg (males) and 1.5-2.1 kg (females), constituting approximately 2.5% of body weight in adults.
• In infants, can reach up to 5% of the total body weight, larger relative development compared to the rest of the body.
• Its size peaks around 18 years old, with a gradual decrease with age.
• The hepatic surface is generally smooth, soft, and reddish-brown.
• Visible as yellowish in obese individuals due to widespread adipose tissue (steatosis) within the hepatic parenchyma.
• The liver is divided into four lobes (right, left, caudate, and quadrate) based on its external appearance.
• The liver's functional lobes are right and left lobes, being roughly equal in size based on arterial/portal venous drainage, and biliary systems.
• Hepatocytes are large, polygonal cells, typically 20-30 μm in diameter.
• Binucleated hepatocytes exist in about 30% of cases.
• Hepatocytes are polarized epithelial cells with distinct plasma membrane domains (sinusoidal, canalicular, and contiguous surfaces) for interactions with sinusoids/bile canaliculi/other hepatocytes.
• Sinusoidal endothelial cells (LSECs) make up approximately 20% of the liver's total cell population, are important in direct contact with the plasma/hepatocyte.
• Unlike capillary endothelium, LSECs do not form tight junctions.
• The liver's space of Disse is the space between the endothelium and the hepatocytes.
• Kupffer cells are specialized tissue macrophages active in removing particulate/toxic/foreign substances from the portal blood (from the intestines' blood), with an abundance of lysosomes.
• Their numbers and activity increase due to chemical, infectious, or immunological liver damage.
• Hepatic stellate cells (HSCs), also known as Ito cells, represent 5-8% of liver cells, are also vitamin A-storing cells located between the endothelial lining and hepatocytes.
• HSCs become activated myofibroblasts, transforming into elongated cells producing matrix components after liver injury.
• Collagen, proteoglycans, and adhesive glycoproteins are examples of components of extracellular matrix.
• Liver lobules are organized in a prismatic layout, with hepatocyte plates that converge to a central vein (centrolobular vein).
• Portal or portobiliary spaces are present at the lobule corners, containing a branch of hepatic artery, portal vein, and bile canaliculi.
• The portal vein carries venous blood from the intestines.
• Bile ducts collect bile from hepatocytes, flowing toward the portal space.
• Hepatocytes synthesize and secrete bile.
• Bile (800-1000 mL/day) is produced by hepatocytes.
• Bile flows from canaliculi into bile ducts, subsequently into the hepatic duct.
• The liver performs metabolic functions, including carbohydrates, lipids, and protein regulation and metabolism.
• Liver function also includes plasma protein synthesis (albumins, globulins, coagulation factors) and excretion with bile production.
• Other storage functions for glycogen, triglycerides, iron, copper, and fat-soluble vitamins.
• Catabolism of exogenous/endogenous molecules.
• Liver receives non-esterified fatty acids (NEFAs) from the intestines, or mobilization from adipose tissue.
• They convert proteins/carbohydrates into fats and synthesize cholesterol, part used to form bile salts.
• Fatty acids transform into triglycerides with apolipoprotein synthesis, forming VLDLs (very-low-density lipoproteins) discharged into the bloodstream.
• Beta-oxidation of fatty acids through Acetyl-CoA to ketone bodies crucial energy source.

Liver Diseases

• Infectious Hepatitis
• Drug- and Toxin-Induced Hepatitis
• Alcoholic Liver Disease
• Non-Alcoholic Fatty Liver Disease (NAFLD)
• Liver Tumors (hepatocellular carcinoma)
• Drug-induced liver damage accounts for about 10% of adverse drug reactions, and is a significant cause of fulminant hepatitis.

Mechanisms of Liver Damage

• Degeneration, including vacuolar degeneration and cloudy swelling, plus intracellular accumulation, like steatosis (fatty liver disease).
• Necrosis caused by ischemic, toxic, or infectious damage
• Inflammation (Hepatitis): Acute or chronic, inflammatory infiltration, often associated with necrosis.
• Regeneration: disrupts the organ's structure
• Fibrosis: occurs as a result of inflammation or toxic damage.

Liver Toxicity from Paracetamol

• Paracetamol is safe at recommended therapeutic doses (1-4 g/day), but overdoses have shown hepatotoxic potential and are the most common cause of drug-induced liver injury (DILI) in many countries. Significant contributor to acute liver failure.
• Overdoses (10-20 grams over 3 days) in habitual alcohol consumers, fasting individuals, or malnourished, or those taking medications that interact with paracetamol metabolism, may lead to severe hepatic damage or death.
• Single doses exceeding 7-10 grams may lead to liver damage while damaging outcomes are typically associated with doses of 15-25 grams or higher.

Alcoholic Associated Liver Disease

• Excessive alcohol consumption is a leading cause of liver disease.
• Acute alcoholic hepatitis can occur after excessive alcohol intake and is associated with 10–20% mortality rate.
• Alcoholic hepatitis can progress to chronic conditions such as steatosis, hepatitis, and cirrhosis.

Metabolism of Ethanol in the Liver

• Ethanol is primarily metabolized in hepatocytes via alcohol dehydrogenase (ADH) to acetaldehyde, a toxic intermediate.
• Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH).
• The microsomal ethanol oxidizing system (MEOS), involving CYP2E1 (cytochrome P450 2E1), also metabolizes ethanol, especially during chronic alcohol intake.
• CYP2E1 generates ROS (reactive oxygen species) causing oxidative stress which damage cellular components.
• Acetaldehyde reacts with certain proteins.
• Disrupts mitochondrial integrity, impairing ATP production.
• Ethanol disrupts gut barrier function, allowing lipopolysaccharides (LPS) to enter portal circulation and further activate Kupffer cells.
• Chronic inflammation/acetaldehyde stimulates hepatic stellate cells, causing excessive extracellular matrix deposition (fibrosis) which progresses to liver cirrhosis.

Steatotic Liver Disease (SLD)

• A classification and new nomenclature for steatotic liver disease (SLD), categorizing based on alcohol-related disease (ALD), specific etiology SLD, cryptogenic SLD, drug-induced liver injury (DILI), monogenic diseases and other miscellaneous causes.

Pathogenesis (general info)

• MAFLD heterogeneity
• Different disease sub-types
• Variable natural history
• Inter-individual variation
• Variable response to therapy

Therapies

• Lifestyle modifications, such as increased diet/physical activity and avoidance of sugary beverages, are recommended first-line treatments for NAFLD.
• Medications with positive metabolic effects (Omega 3 FAs, high-dose metformin, probiotics).
• Medications with anti-inflammatory effects (Vitamin E, elafibranor, obeticholic acid), and anti-fibrotic effects (cenicriviroc, selonsertib, and combination therapies) are reserved for specific cases.
• Proper control of diabetes, hyperlipidemia, and cardiovascular risks is recommended for NASH patients.
• Statins may be used for NAFLD patients with dyslipidemia.

Other Information

• Diagnostic criteria for metabolic syndrome (fasting blood glucose, blood pressure, triglyceride, HDL)
• Risk factors for MAFLD (Metabolic syndrome, diabetes, obesity, dyslipidaemia, arterial hypertension, intrauterine environment/early infant feeding, sedentary lifestyle, dietary factors)
• Prevalence of MAFLD in adults (~25%) and pediatric cases (~3-10% and possibly up to 40-70% higher among obese children).
• The prevalence of NASH in the US (34-42%, 18-22%) which shows a higher prevalence of more advanced stages.
• NAFLD prevalence in adults in general populations.
• NASH prevalence, and how prevalence rises according to severity and stage of NAFLD.

This quiz covers key concepts related to liver anatomy and physiology, focusing on the anatomical lobes, hepatocyte characteristics, and the impacts of overnutrition on liver function. Explore the intricate details of liver cell types and their roles in metabolic processes.