Liver Anatomy and Physiology Quiz

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Questions and Answers

What are the externally visible anatomical lobes of the liver?

The externally visible anatomical lobes of the liver are the right, left, quadrate, and caudate lobes.

What criteria are used to define the true functional lobes of the liver?

The true functional lobes of the liver are defined by their arterial and portal circulation, as well as their biliary and venous drainage systems.

What is the primary cell type found in the liver, and what is its arrangement?

The primary cell type in the liver is the hepatocyte. Hepatocytes are arranged in plates, typically one or two cells thick, with spaces between the plates called sinusoids.

Describe the size and morphology of hepatocytes.

Hepatocytes are large, polygonal cells with a diameter of approximately 20–30 µm. Signup and view all the answers

What are the three distinct domains of the hepatocyte plasma membrane?

The three distinct domains of the hepatocyte plasma membrane are the sinusoidal surface, the canalicular surface, and the contiguous surfaces. Signup and view all the answers

What is the space of Disse, and where is it located?

The space of Disse is the space between the sinusoidal endothelial cells and the hepatocytes. Signup and view all the answers

What is a defining characteristic of the endothelial cells of the hepatic sinusoids (LSEC) that distinguishes them from endothelial cells in capillaries?

LSECs are characterized by fenestrae (pores) within their flattened and thin extensions, while endothelial cells in capillaries form intercellular junctions. Signup and view all the answers

What percentage of the total liver cell population do sinusoidal endothelial cells constitute?

Sinusoidal endothelial cells constitute approximately 20% of the total liver cell population. Signup and view all the answers

What are the two primary dietary components that contribute to excessive free fatty acids in the liver?

Dietary fat and carbohydrates. Signup and view all the answers

Name two transcription factors activated by overnutrition, which drive lipogenesis.

SREBP-1c (Sterol Regulatory Element Binding Protein-1c) and ChREBP (Carbohydrate-Responsive Element Binding Protein). Signup and view all the answers

What is the effect of overnutrition on Very Low-Density Lipoprotein (VLDL) synthesis?

VLDL synthesis is impaired. Signup and view all the answers

How does overnutrition contribute to insulin resistance?

Excessive free fatty acids accumulate in the liver, leading to insulin resistance. Signup and view all the answers

Apart from free fatty acids, what other lipid derivatives contribute to hepatocyte lipotoxicity?

Ceramides. Signup and view all the answers

What are the two major consequences of increased free fatty acids in the liver, as mentioned in the text?

Hepatocyte apoptosis and HSC activation with deposition of extracellular matrix. Signup and view all the answers

What is the role of reactive oxygen species (ROS) in the pathogenesis of non-alcoholic fatty liver disease?

ROS cause oxidative damage of lipids, proteins, and DNA. Signup and view all the answers

What is the primary reason for increased lipolysis in adipose tissue in the context of overnutrition?

Insulin resistance. Signup and view all the answers

What are the major factors involved in the development of liver inflammation, as described in the text?

Increased intestinal permeability, migration of bacteria and their products (like LPS) to the liver, and activation of Toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) all contribute to liver inflammation. Signup and view all the answers

What is the prevalence of MAFLD (Metabolic Associated Fatty Liver Disease ) in the general population worldwide?

Around one-fourth (25%) of the general population worldwide is affected by MAFLD. Signup and view all the answers

What is the key difference between MAFLD and MASH?

While MAFLD refers to the general condition of fat accumulation in the liver, MASH (the active form of MAFLD) is characterized by histological lobular inflammation and hepatocyte ballooning. These features contribute to faster fibrosis progression, making MASH more serious. Signup and view all the answers

What is the prevalence of MASH in the general population?

MASH affects around 1.5% to 6.5% of the general population. Signup and view all the answers

What are the major metabolic comorbidities commonly associated with MAFLD?

Metabolic comorbidities associated with MAFLD include obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. Signup and view all the answers

What is the most common cause of death in patients with NAFLD?

Cardiovascular disease is the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Signup and view all the answers

What other organs are potentially affected by MAFLD?

MAFLD can lead to complications such as cirrhosis, end-stage liver disease, hepatocellular carcinoma, and require liver transplantation. Signup and view all the answers

What are the potential effects of LPS on the liver?

Lipopolysaccharide (LPS), a type of bacterial product, can compromise liver homeostasis and trigger inflammation when it enters the liver. Signup and view all the answers

What is the primary function of the GPBAR1 receptor?

The GPBAR1 receptor is a G protein-coupled bile acid receptor. Signup and view all the answers

Describe the effect of GPBAR1 activation on vascular inflammation.

Activation of GPBAR1 has been shown to attenuate (reduce) vascular inflammation. Signup and view all the answers

Based on the provided information, what is the relationship between NAFLD and cardiovascular disease?

NAFLD, or Non-Alcoholic Fatty Liver Disease, has been linked to cardiovascular disease. Signup and view all the answers

How does GPBAR1 activation affect atherosclerosis in an animal model?

Activation of GPBAR1 reduces the severity of atherosclerosis in a mouse model of NAFLD-related cardiovascular disease. Signup and view all the answers

Explain the role of macrophages in atherosclerosis.

Macrophages, a type of immune cell, contribute to atherosclerosis by driving vascular inflammation and influencing the stability of the plaque. Signup and view all the answers

What is the effect of GPBAR1 activation on the ratio of IL-10+ to IL-6+ macrophages?

Activation of GPBAR1 increases the ratio of IL-10+ to IL-6+ macrophages, indicating a shift toward an anti-inflammatory phenotype. Signup and view all the answers

What are the two liver-related components of the disease being investigated in the study?

The study investigates the effects of GPBAR1 activation on liver steatosis and liver fibrosis. Signup and view all the answers

What type of diet was used in the study to induce liver steatosis and fibrosis in the ApoE-/- mice?

The study used a high-fat diet (HFD-F) to induce liver steatosis and fibrosis in the ApoE-/- mice. Signup and view all the answers

What is the primary product of β-oxidation of fatty acids in the liver?

Acetyl-CoA Signup and view all the answers

How much bile is typically produced by hepatocytes daily?

800–1000 mL Signup and view all the answers

What type of cells in the liver are responsible for the phagocytosis of particulate materials?

Kupffer Cells Signup and view all the answers

What are the five general reactions that manifest liver damage?

Degeneration, necrosis, inflammation, regeneration, and fibrosis. Signup and view all the answers

Name one major disease associated with infectious hepatitis.

Viral hepatitis Signup and view all the answers

What is one mode through which drug-induced liver damage can occur?

Direct hepatocyte damage. Signup and view all the answers

What enzyme complex plays a significant role in the drug-metabolizing enzymatic system in the liver?

Cytochrome P450 Signup and view all the answers

What liver condition is characterized by the accumulation of fat within liver cells?

Non-Alcoholic Fatty Liver Disease (NAFLD) Signup and view all the answers

What are the two types of adverse drug reactions and how do they differ?

The two types are predictable (intrinsic) and unpredictable (idiosyncratic). Predictable reactions are dose-dependent and known toxic effects, while idiosyncratic reactions are rare, not dose-related, and often linked to individual susceptibility. Signup and view all the answers

At what therapeutic dose is paracetamol considered safe, and what is the threshold for potential liver damage?

Paracetamol is safe at a therapeutic dose of 1 to 4 grams per day, but doses exceeding 7–10 grams can result in liver damage. Signup and view all the answers

What factors can increase the risk of paracetamol-induced liver toxicity?

Factors include moderate overdoses in habitual alcohol consumers, fasting or malnourished individuals, or those taking medications that interact with paracetamol metabolism. Signup and view all the answers

What are the guidelines for moderate alcohol intake for men and women?

Men should consume no more than 2–3 alcohol units (36 grams) per day, while women should limit intake to 1–2 units (24 grams) per day. Signup and view all the answers

What is the primary metabolic pathway for ethanol in the liver?

Ethanol is primarily metabolized by alcohol dehydrogenase (ADH) to acetaldehyde in hepatocytes. Signup and view all the answers

What percentage of individuals have severe liver damage untreated in cases of paracetamol poisoning?

Severe liver damage occurs in about 20% of individuals untreated for paracetamol poisoning. Signup and view all the answers

What is considered an Alcohol Unit (AU) and what beverages typically contain this amount?

One Alcohol Unit (AU) is approximately 12 grams of ethanol, found in a small glass of wine (125 mL), a can of beer (330 mL), or a standard bar serving of spirits (40 mL). Signup and view all the answers

What is the risk of mortality associated with acute alcoholic hepatitis?

Acute alcoholic hepatitis has a mortality risk of 10–20%. Signup and view all the answers

Study Notes

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.

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Description

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.