It is the largest glandular organ divided into four lobes of unequal size and shape. It lies on the right side of abdominal cavity beneath the diaphragm. An exocrine gland secretes the bile juice into the intestine for digestion of fats. The main function of the liver is to produce substance that break down fats, convert glucose to glycogen, make certain amino acids, filter harmful substance from the blood and maintain proper level of glucose in blood.
Cigarette smoke encounter liver, it indirectly affects it. The chemicals in cigarette live hydrocarbons and vinyl chloride are carcinogens, which causes cancer. They also cause oxidative stress and it leads to the damage to the liver cells and fibrosis. The chemicals prevent the liver from performing its main function. Over time, the organ becomes less efficient in removing the toxins from the body.
The main type of cancer caused due to smoking is Hepatic cell carcinoma, which is due to the accumulation of excess iron in the hepatocytes. This induces fibrosis and favors the development of the cancer.
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The liver is bound by a connective tissue capsule, which is then extended as highly branched septae. The liver is divided into four lobes based on surface features. It is divided into right anatomical and left anatomical lobe by the falciform ligament. The other two lobes are the caudate lobe and quadrate lobe. These lobes are further divided as lobules the structural unit of liver. The lobules are hexagonal in shape, with portal triads at the vertices and central vein in the middle.
The parenchyma cells of the liver are known as hepatocytes. They are polygonal in shape and are arranged as hepatic chords, which are separated by vascular sinusoids. Special cells called Kupffer cells are associated with the sinusoids, which act as liver macrophages to effectively kill the bacteria that enter through blood. The space between the endothelium and the hepatocytes is called the Space of Disse, which collects lymph and transports it to the lymphatic capillaries.
The hepatocytes produce the bile and it is collected in channels called canaliculi. These secretions flow to the periphery of lobules and then to the bile ductules and interlobular bile ducts, ultimately into the hepatic duct which is present outside the liver. The hepatic duct then continues with the common bile duct, that delivers bile into the duodenum or temporarily stored in the gallbladder through the cystic duct.
Fig.1. Liver histology
Smoking causes cytotoxic effects by the release of certain chemicals. They cause oxidative stress, which in turn leads to the activation of satellite cells and hence leading to fibrosis. The production of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha are increased by smoking which in turn causes liver cell injury in the form of necroinflammation, apoptosis and excess iron deposition. Excess iron deposition in the hepatocytes causes oxidative stress and lipid perocidation. Tobacco smoking is also associated with reduction of Tp53, which is a tumour suppressor protein.
Heavy smoking is associated with increased carboxyhaemoglabin and decreased oxygen carry capacity of red blood cells. It happens due to present of PAH (Poly aromatic hydrocarbon). Hypoxia stimulates erythropoietin production, a hormone produced by the kidney that promotes the formation of red blood in the bone marrow, which induces hyperplasia, indicates proliferation of cells within organ or tissue, of the bone marrow. It enhances the development of secondary polycythemia, is a disorder that causes too many red blood cells are produced, and increases red blood cells abnormally. This increases catabolic iron derived from both senescent red blood cells and iron derived from increased destruction of red cells associated with polycythemia. After that erythropoietin enhances the absorption of iron from the intestine. The absorption of excess catabolic iron leads to its accumulation in macrophage and in hepatocytes over time promotes oxidative stress to the cells. Increased red cells mass with increased purine catabolism, promotes excessive production of uric acid. It increases liver cell injury and enhances liver cancer.
Hepatocellular carcinoma is also known as primary liver cancer or hepatoma. This is the third most common cancer in the world. This cancer usually arises from liver cirrhosis, which arises due to smoking. Liver cirrhosis is a condition in which the liver slowly deteriorates and malfunctions due to chronic injury.
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The carcinogens present in tobacco can cross the placenta and reaches the fetal liver cells causing hepatocellular carcinoma. The alpha-fetoprotein (AFP) is synthesized by immature liver cells in the fetus and its concentration decreases after the one tear of birth. The unusual high concentration of the protein is associated with the development of hepatocellular carcinoma. Thus, this protein acts as a biomarker to estimate the birth defects.
Fig.2. Hepatocellular carcinoma
Genetic level understanding
IL-1 proteins are involved in the inflammatory
response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and
collagenase from synovial cells.
IL-1beta TaqI and IL-1Ra gene polymorphisms
Chr 2 q13
This gene encodes a cytokine that functions in inflammation and the maturation of B cells. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional
inflammatory response through interleukin 6 receptor, alpha.
G 174 C
Chr 7 p15.3
This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumour necrosis factor (TNF)
Superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors
TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological
processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation
Chr 6 p21.31
Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes
GSST1 (deletion polymorphism)
proteins that catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds
functions in the detoxification of electrophilic compounds, including carcinogens,therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione
This gene encodes tumour protein P53, which responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism.
G 249 T
Chr 17 p13.1
encodes cytochrome P450 proteins which catalyze reactions like drug metabolism and synthesis of cholestrol
Zayadi: Heavy smoking and liver. World Journal of Gastroenterology. 12(38). pp (6098-6101). 2006.