Liver, Liver Glands, Gastrointestinal Tract and Glands


Gastrointestinal Tract and Glands

The epithelium of the gastrointestinal (GI) tract is simple and columnar throughout, except for the stratified squamous epithelia in regions of maximal friction (esophagus and anus). The stomach is a grinding organ with glands in the fundus and body that produce mucus (surface and neck cells), pepsinogen (chief cells), and acid and intrinsic factor (parietal cells).

Intrinsic factor binds to vitamin B12 and is required for uptake of that vitamin from the intestine. The parietal cell functions in a similar fashion to the osteoclast in using carbonic anhydrase to produce protons that are pumped into the intracellular canaliculi, which are lined by microvilli in the active parietal cell. In the inactive parietal cell, the proton pumps are sequestered in tubulovesicles in the cytosol. The small intestine is an absorptive organ with folds at several levels (plicae, villi, and microvilli) that increase surface area for more efficient absorption. The microvilli also contain specific enzymes for the breakdown of sugars (disaccharidases), lipids (lipases), and peptides (peptidases).

The major digestive processes in the small intestine occur through the action of the pancreatic juice, which contains trypsinogen, chymotrypsinogen, procarboxypeptidases, amylase, lipase, and other enzymes. Trypsinogen is activated by enterokinase found on the microvilli. Lipids are broken down to triglycerides in the small intestinal lumen which are subsequently degraded to glycerol, fatty acids, and monoglycerides that are transported into the enterocyte. Once in the cytosol of the enterocyte, the SER resynthesizes the triglycerides, which are coupled with protein to form chylomicra. The chylomicra are exocytosed into the lacteals and travel to the cisterna chyli and through the thoracic duct to the venous system. They return to the liver through the arterial system (hepatic artery). In the liver the lipid processing is similar, but reversed to form very low density lipoprotein (VLDL) from chylomicra.

Other digested materials travel through the hepatic portal vein to the liver where hepatocytes process the digested nutrients.  Cell types in the small intestine include enterocytes (absorption), Paneth cells (production of lysozyme, defensins, and cryptidins), goblet cells (mucus), and enteroendocrine cells (secretion of peptide hormones). All of those cells originate from a single stem cell in the crypt. New cells are born in the crypt, move up the villus, die by apoptosis, and are sloughed off at the tip. The primary function of the colon, which appears histologically as crypts with prominent goblet cells and no villi, is water resorption.

The major salivary glands (parotid, submandibular, and sublingual) are exocrine glands that secrete amylase and mucus, primarily regulated by the autonomic nervous system. In contrast, the pancreas has both exocrine (acinar cells) and endocrine (islet cells) components that synthesize pancreatic juice and blood sugar–regulating hormones, respectively. The exocrine pancreas is primarily regulated by the hormones cholecystokinin (CCK) and secretin, which primarily regulate acinar and ductal secretion, respectively.

The liver is also a dual-function gland whose exocrine product is bile, synthesized by hepatocytes, and transported by a duct system to the gallbladder for storage and concentration. Bile emulsifies lipids for more efficient enzymatic access. The endocrine products include glucose and major blood proteins (albumin, fibrinogen, coagulation proteins). The liver subserves numerous other functions including synthesis of cholesterol and detoxification of lipid-soluble drugs, such as phenobarbital by the SER (using the P450 enzyme system).
The liver is also a dual-function gland whose exocrine product is bile, synthesized by hepatocytes, and transported by a duct system to the gallbladder for storage and concentration. Bile emulsifies lipids for more efficient enzymatic access. The endocrine products include glucose and major blood proteins (albumin, fibrinogen, coagulation proteins). The liver subserves numerous other functions including synthesis of cholesterol and detoxification of lipid-soluble drugs, such as phenobarbital by the SER (using the P450 enzyme system).

Alcohol detoxification is one of the major processes carried out in the hepatocyte. Alcohol detoxification involves alcohol dehydrogenase (ADH), MEOS (microsomal ethanol oxidation system, P450 enzymes in the SER), and catalase in peroxisomes. The primary metabolic pathway is ADH. At higher alcohol levels the MEOS and even catalase systems are activated. The bile canaliculus is defined as apical, the junctional complexes as lateral, and the blood surface with the space of Disse and hepatic sinusoids is considered basal.

The sinusoids are lined by hepatic stellate cells, endothelial cells, and Kupffer cells. The hepatic stellate cells are affected following chronic alcohol toxicity and are converted into myofibroblasts during the onset of cirrhosis. Those cells synthesize large quantities of collagen and are responsible for the fibrotic changes observed in cirrhosis. The Kupffer cells are the antigen-presenting cells of the liver and are derived from monocytes. Hepatocytes are arranged in interlocking cords and plates so there are several ways of analyzing the histological organization of the liver. The classic lobule emphasizes the endocrine function of the liver; the portal lobule emphasizes the exocrine function of the liver, and the liver acinus focuses on actual blood supply and regeneration.

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