Human Organ Systems Test 4, Digestive Tract

  1. Mucosa
    • Composed of:
    • Epithelium and its basement membrane, which often form finger villi to maximize surface area for absorption; often made of stratified squamous (protection) or of simple columnar (absorption)
    • Underlying lamina propria, which includes blood vessels, lymphatics, glands, and mucosa-associated lymphoid tissues (MALT) in the form of nodules
    • Muscularis mucosa, which is smooth muscle that moves independently of the muscularis externa (not present in oral cavity and anal canal)
  2. Submucosa
    A region of dense irregular connective tissue that contains the blood vessels and lymphatics that supply and drain the lamina propria; also contains glands, MALT, and the submucosal (Meissner's) plexus, which containns the sympathetic and parasympathetic neurons that innervate the muscularis mucosa, neuroendocrine cells, and enzyme-secreting cells of the epithelium
  3. Muscularis externa
    • Made up of:
    • Inner circular smooth muscle layer (is partially skeletal in the oral cavity and esophagus)
    • Auerbach's (myenteric) plexus (innervates the two layers of muscle)
    • Outer longitudinal smooth muscle layer (also may be skeletal in oral cavity and esophagus; is thickened skeletal muscle to form the external anal sphincter)
  4. Serosa versus adventitia
    • Loose irregular connective tissue surrounding the outside of the gut tube
    • Serosa: Peritoneal mesothelium
    • Adventitia: The loose irregular connective tissue surrounding the gut tube in retroperitoneal spaces (there is no mesothelium)
  5. Types of oral mucosa
    • Masticatory: Keratinized/parakeratinized epithelium that withstands stresses of chewing; found on hard palate and gingiva
    • Specialized: Keratinized epithelium that contains taste buds; found on the dorsal surface of the tongue
    • Lining: Non-keratinized epithelium that allows for flexibility; found on the rest of the surfaces in the oral cavity
  6. Oral squamous cell carcinoma
    Most common in areas of lining mucosa (floor of the mouth, ventral and lateral surfaces of the tongue, and the soft palate); smoking and alcohol use are risk factors; surgery and radiation are treatments; affects 30,000 Americans each year
  7. Aphthous stomatitis
    • Canker sores
    • Occur only in lining mucosa in response to citrus fruits, physical trauma, and stress
  8. Cold sores
    • Result of HSV-1 infection that only occurs in keratinized epithelium
    • No cure and the virus remains in the body for life, causing recurrent outbreaks
  9. Tongue
    Composed of skeletal muscle fibers arranged in longitudinal, transverse, and vertical bundles; covered in specialized mucosa on dorsum and lining mucosa elsewhere
  10. Types of papillae on tongue
    • Filiform: Most numerous; thick keratin layer; no taste buds (hairy appearance)
    • Fungiform: Less numerous and irregularly shaped; lightly keratinized; have taste buds
    • Circumvallate: Only 7-12 papillae found in front of the terminal sulcus; have taste buds and serous glands of von Ebner to cleanse them
    • Foliate: Poorly developed in humans; have taste buds; found in the postero-lateral surface of the tongue
  11. Taste bud structure
    Molecules dissolved in saliva enter the taste pore and bind receptors on the gustatory microvilla; secretions from the serous glands of von Ebner wash away food particles around the taste buds; basal cells provide support of the gustatory cells
  12. How many teeth do we have as children versus adults and how are they numbered?
    • We have 32 permanent teeth and 20 deciduous teeth
    • From upper right to upper left are 1-16; from lower left to lower right are 17-32
    • Pairs: 1 wisdom; 2 molar; 2 premolar; 1 canine; 2 incisors on upper and lower
  13. Anatomy of a tooth
    • Crown: Part of tooth above gum that is covered in enamel
    • Root: Portion of the tooth within the alveolar bone; surrounded by cementum
    • Cervix: Junction of the crown and root
    • Gingiva: The gums, which are covered in masticatory mucosa
    • Pulp cavity: The space inside a tooth that is filled with soft tissue; made of a coronal chamber and a radicular canal (root canal)
    • Dentin: Calcified material surrounding the pulp cavity
    • Alveolus: Bony socket surrounding the tooth
    • Cementum: Bone-like material surrounding the root
    • Periodontal ligament: Connective tissue that join the cementum to the alveolus
  14. Enamel
    • The hardest substance in the body that is made of 98% hydroxyapatite (inorganic matrix)
    • Deposited during development by Tome's processes of ameloblasts; these cells cycle back to have a Ruffled membrane and move backwards, depositing more enamel
    • Enamel consists of very closely-packed rods that extend through the thickness of the enamel layer and cannot be regenerated
    • This layer is lost during histological preparation
  15. Dentin
    • Made of about 70% calcium hydroxyapatite (inorganic matrix); odontoblasts secrete type I collagen fibers and GAGs (organic components)
    • Odontoblasts (tall cells lining the pulp cavity) line the pulp cavity and secrete predentin from their apical surface
    • Predentin is rapidly mineralized to form dentin
    • Dentinal tubules are canals in which odontal processes extend; they run the entire thickness of dentin, because the processes lengthen as new matrix mineralizes around the processes
  16. Pulp
    • Pulp consists of mesenchye-like connective tissue beneath the odontoblast layer
    • Contains many blood vessels and nerves which enter via the apical foramina in the tooth root
    • Some unmyelinated nerve fibers extend in dentinal tubules
    • Pulp fibers are sensitive to temperature and pH which is interpreted as pain
  17. Periodontium
    • Consists of the structures that maintain the teeth in the maxilla and the mandible
    • Cementum: Similar composition to bone; keeps teeth in close contact with socket by resorbing/secreting of cementocytes (found in periodontal ligament); covers dentin of the root and is thickest at the apical region
    • Periodontal ligament: Thick layer of connective tissue that attaches the cementum to the alveolar bone of the tooth socket; allows limited movement of tooth in socket to allow for stresses of mastication; made of type I collagen and has a high turnover
    • Alveolar bone: Appearance of primary (immature) bone; containing osteocytes within lacunae
    • Gingiva: Gums covered in masticatory mucosa
  18. Scruvy
    • Caused by a lack of vitamin C in diet
    • Vitamin C allows for collagen synthesis
    • Lack of collagen synthesis affects the periodontal ligament where there is a high rate of collagen turnover and renewal
    • Teeth can become loose in sockets or fall out
  19. Tooth development
    • Starts in 6-week embryo and takes about 14 months to develop a tooth
    • Bud stage: Oral mucosa over dental arches thickens to form dental lamina (proliferating oral epithelium; ectoderm) and dental bud (formed by ingrowth of dental lamina into mesoderm)
    • Cap stage: Dental bud invaginates and engulfs a region of ecto-mesenchyme called the dentl papilla; the dental follicle/sac is the entire cap of the dental bud and the dental papilla
    • Bell stage: Dental bud continues to invaginate; the enamel organ are the layers surrounding the dental papilla and include the inner enamel epithelium (overlays the papilla and will form ameloblasts through reciprocal induction), stellate reticulum (core of loosely woven tissue), and outer enamel epithelium (outer cells of dental lamina); cells of dental papilla differentiate to form odontoblasts and pulp (derived from remaining cells of dental papilla)
  20. Reciprocal induction
    • Formation of enamel and dentin in the crown
    • The enamel organ induces the dental papilla to form odontoblasts that produce dentin
    • The dentin induces the enamel organ to form ameloblasts that secrete enamel
  21. Root formation
    • Begins after the crown is completed
    • Involves reciprocal induction between a downgrowth of the enamel organ (Hertwig's epithelial root sheath) and the dental follicle
  22. Embryonic folding to form the digestive tract
    • Head and tail folds form along with lateral body folds
    • After folding, the digestive tract forms the foregut (esophagus, stomach and proximal duodenum), midgut (distal duodenum, ileum, jejunum, proximal colon, and accessory organs of digestion), and hindgut (distal colon, rectum, and anal canal)
  23. Characteristics of esophagus
    • Epithelium: Non-keratinized stratified squamous epithelium
    • Lamina propria: Contains esophageal cardiac glands that secrete mucous in the moist distal region of the esophagus near the stomach and lymphoid aggregates
    • Muscularis mucosa
    • Submucosa: Contains esophageal glands that produce mucous to lubricate the epithelium
    • Muscularis externa: Contains an inner circular layer and an outer longitudinal layer; the upper third is skeletal muscle, the middle third is mixed, and the distal third is smooth only
    • Adventitia/serosa: The esophagus has a loose irregular connective tissue adventitia, but the distal portion becomes covered with serosa as it passes through the diaphragm at T10
  24. Characteristics of the stomach
    • Epithelium: Contains simple columnar cells that produce neutral mucous that protects the lining cells against self-digesion; gastric pits and gastric glands are also present; they receive acid and enzyme secretions from branched tubular glands
    • Lamina propria: The gastric pits/glands extend into this layer
    • Muscularis mucosa
    • Submucosa
    • Muscularis externa: Has an inner oblique smooth muscle (to aid in churning during digestion), a middle circular (which thickens to form the pyloric sphincter), and an outer longitudinal smooth muscle
    • Serosa: Since the stomach is peritonized in the abdomen and covered by a messothelium, we call this a serosa
  25. Structure and function of a principal gastric gland
    • Gastric pit: The initial infolding of the epithelium that is made up of surface mucous cells
    • Gastric gland neck: Contains neck mucous cells that secrete mucous to protect the somach from self-digestion and parietal (oxyntic) cells [fried egg appearance] that secrete hydrochloric acid and intrinsic factor
    • Gastric gland base: Contains chief (zymogenic) cells [basophilic appearance] that secrete pepsinogen and rennin/chymosin and enteroendocrine cells that release a variety of hormones into the blood vessels of the lamina propria
  26. Hydrochloric acid
    • Carbonic acid is made by carbonic anhydrase from carbon dioxide and water
    • Carbonic acid dissociates to form bicarbonate
    • Bicarbonate is exchanged for chloride (chloride goes into cell through basal side)
    • Chloride diffuses out the apical side and forms HCl with H, that was pumped into the canaliculus with exchange for K
    • Functions: Destroys bacteria, denatures protein, and converts pepsinogen into pepsin
  27. Intrinsic factor
    • A glycoprotein required for the uptake of vitamin B12 in the gut
    • Made by parietal cells found in the neck of a gastric gland
  28. Helicobacter pylori
    • A gram-negative bacterium found in the stomach of patients with gastric ulcers
    • It dives into the mucous lining with its helical shape and flagellum
    • Once in the mucous, it produces large amounts of teh enzyme urease, that breaks down urea to surround itself in a cloud of its alkali byproducts (bicarbonate and ammonium)
    • The immune response results in inflammation and the area becomes prone to acid and enzyme damage resulting in the gastric ulcer
  29. Pernicious anemia
    • A megaloblastic anemia that is the result of impaired DNA synthesis in RBCs during hematopoiesis due to lack of intrinsic factor
    • Intrinsic factor binds vitamin B12 for uptake
    • Parietal cells produce intrinsic factor, and they can be destroyed by atrophic gastritis (chronic inflammation of the stomach mucosa)
  30. Pepsinogen
    • A zymogen found in the chief cells of the gastric gland base
    • It becomes activated to pepsin outside of the cells in the lumen of the stomach due to cleavage of the amino acid chain by hydrochloric acid
  31. Rennin/chymosin
    • Chymosin is made in the chief cells of the basal gastric gland when we are infants; it coagulate milk in order to maximize its time in the stomach
    • Rennin is the same enzyme found in infant calves, and is used to produce cheese
  32. G-cells
    • Release gastrin in response to the presence of protein in the stomach
    • Gastrin increases the secretions from parietal cells and chief cells and influences contraction of the muscularis externa to increase gastric motility
    • These cells are found in the body and pylorus (antrum) of the stomach
  33. D-cells
    • Release somatostatin in response to increased levels of acid in the stomach
    • Somatostatin targets G-cells to inhibit the release of gastrin
    • These cells are found in the pylorus of the stomach
  34. Ghrelin cells
    • Release ghrelin in response to fasting conditions when glucose levels ecrease
    • Ghrelin targets the hypothalamus to increase appetite
    • These cells are found in the body of the stomach
  35. Cardiac gastric glands
    • Function: Protect the mucosa from acid/enzyme damage and lubricate it for passage of food
    • Cell type: Mainly mucous-secreting cells
    • Appearance: Short gastric pits with long and coiled gastric glands
  36. Principal gastric glands
    • Function: Protect the mucosa in the fundus and the body
    • Cell type: Mucous-sereting cells and neuroendocrine cells (release ghrelin and gastrin)
    • Appearance: Short gastric pits with long and branched gastric glands
  37. Pyloric gastric glands
    • Function: Protection of the mucosa from acid/enzyme damage and lubrication en route to the duodenum
    • Cell type: Mucous-secreting cells and neuroendocrine cells (release gastrin and somatostatin)
    • Appearance: Long gastric pits with short and coiled gastric glands
  38. Barrett's esophagus
    • Metaplasia, or replacement of the stratified squamous epithelium by columnar epithelium, of the inferior aspect of the esophagus (may appear similar tot he gastro-esophageal junction)
    • Pre-malignant condition that is the result of an adaptive change from the chronic exposure to stomach acids and enzymes during reflux esophagitis
  39. Maximization of surface area (SA) for absorption in the midgut is obtained by:
    • Plicae circulares: Semicircular folds of teh mucosa and submocosa; increase SA 3x and slow the flow of chyme; most pronounced in the jejunum
    • Villi: Finger-like projections of the epithelium and lamina propria; increase SA 10x; within each villus there is an artery, vein, and lacteal (lymphatic vessel)
    • Microvilli: Finger-like projections of the plasma membranes; increase surface area 20X and are the surface across which absorption occurs
  40. Characteristics of the small intestine wall
    • Epithelium: Has enterocytes/absorptive cells that are simple columnar with microvilli, mucous goblet cells that are single-cell exocrine glands that secrete mucous (the number of goblet cells increases as we move distally), and crypts of Lieberkuhn (intestinal glands) that are simple tubular infolding of the epithelium that extend into the lamina propria
    • Lamina propria: Contains capillaries and lacteal (important for chylomicron transport of fatty acids to the thoracic duct)
    • Muscularis mucosa
    • Submucosa: The duodenum contains large mucous glands called Brunner's glands
    • Muscularis externa: Contains an inner circular layer and an outer longitudinal layer
    • Adventitia/serosa: Mostly is serosa, but is adventitia in the retroperitoneal duodenum
  41. Crypts of Lieberkuhn
    • Found within the small and large intestine, and become deeper as the tube gets closer to the large intestine; contains the following cells
    • Enterocytes/absorptive cells: Columnar cells with microvilli extending into the crypts
    • Mucous goblet cells
    • Stem cells: Source of the epithelial cells that line the crypt and intestinal villi; found in and just above the base of the crypt
    • Paneth cells: Found in the base of the crypts in only the small intestine; secrete lysozyme (breaks up peptidoglycan of gram-(+) bacteria) and alpha-defensin (breaks up lipid component of bacterial wall of gram-(-) bacteria)
    • Enteroendocrine cells: Include S-cells, I-cells, and enterochromaffin cells
  42. S-cells
    • Found in crypts of the duodenum
    • Release secretin in response to low pH
    • Secretin targets parietal cells in the stomach to decrease the amount of acid they release, targets the centroacinar cells of the pancreas to increase their alkaline secretions (bicarbonate), and causes decreased gastric motility
  43. I-cells
    • Located in the crypts of the duodenum and jejunum
    • Release cholecystokinin in response to fat- and protein-rich chyme entering the duodenum
    • Cholecystokinin targets the pancreatic acinar cells to increase their levels of trypsinogen secretion
    • Cholecystokinin also targets smooth muscle in the gallbladder causing it to contract and push bile out, where bile can emulsify the lipid in the chyme, and causes decreased stomach contractility
    • In addition, it targets the hypothalamus to decrease appetite
  44. Enterochromaffin cells
    • Found throughout the small intestine
    • Release serotonin in response to presence of food in the intestine
    • Serotonin targets the smooth muscle of the gut to promote peristalsis
  45. Differences in regions of the small intestine
    • Duodenum: Contains large branched tubular mucous Brunner's glands in the submucosa that release alkaline secretions that neutralize acid chyme
    • Jejunum: Lack of special features; do have tall villi
    • Ileum: Contain Peyer's patches in the lamina propria and submucosa; also contain M-cells (microfold cells) that are found above Peyer's patches and induce antigen-specific immune responses in the gut
  46. Characteristics of the large intestine
    • Epithelium: Have enterocytes/absorptive cells that are in a simple columnar epithelium with microvilli; many mucous goblet cells; contain crypts of Lieberkuhn with many goblet cells and few Paneth cells
    • Lamina propria: Contains capillaries and many lymph nodes
    • Muscularis mucosae
    • Submucosa
    • Muscularis externa: Has inner circular smooth muscle and taeniae coli, which is outer longitudinal smooth muscle organized into three bands
    • Serosa
  47. Characteristics of the appendix
    Similar to the colon but without taeniae coli and with prominent lymph nodules in the lamina propria and submucosa
  48. Appendicitis
    Rupture of the thin wall of the appendix occurs following inflammation and results in leakage of intestinal contents into the peritoneal cavity
  49. The three major salivary glands and their amounts
    • Submandibular gland: 600mls/day
    • Parotid gland: 300mls/day
    • Sublingual gland: 50mls/day
    • Minor glands: 50mls/day (includes buccal, palatine, and labial glands)
  50. Functions of saliva
    • Moisten and lubricate food for the esophagus, since there are few mucous glands present there (mucus)
    • Begin digestion of carbohydrates (amylase)
    • Destroy bacteria (antibacterial enzymes)
    • Reaborb sodium and secrete potassium (ducts)
  51. General structure of salivary glands
    • Stroma: A connective tissue capsule that divides the gland into lobes and lobules with septa
    • Parenchyma: Contains the functional tissue made of serous cells, mucous cells, and myoepithelial cells
    • Duct system: Secretory units into intercalated ducts and striated ducts (both interlobar ducts), that go into interlobar ducts, then the main excretory duct and finally the oral cavity
  52. Appearance of serous cells versus mucous cells
    • Serous: They are pyramidal-shaped cells with a large circular nucleus, a basophilic cytoplasm, and many granules; formed into acini
    • Mucous: Have a basally-located flat nucleus and a pale-staining cytoplasm with foamy-looking mucin vesicles; formed into tubules
    • Myoepithelial cells: These cells may surround the secretory units and intercalated ducts; they contract to squeeze out secretions
  53. Types of ducts
    • Intercalated: Numerous ducts that have low cuboidal epithelial cells and produce lysozyme and lactoferrin (antibacterial agents)
    • Striated: These ducts are only found in serous-secreting glands; they are lined by columnar epithelial cells and appear striated around their base due to many infoldings with mitochondria; these basal membranes also contain many Na-K and Cl-HCO3 pumps for HCO3 and K secretion and Na and Cl reabsorption; causes hypotonic saliva
    • Interlobar (excretory) ducts: Found in the connective tissue septa draining the lobules and are made of simple columnar or pseudostratified epithelial cells
    • Main excretory duct: The duct that empties saliva into the oral cavity
  54. Parotid gland
    • 100% serous
    • Contains striated intralobular ducts and a main excretory duct (Stensen's)
    • Made of branched acinar serous glands
    • Secrete α-amalase for breakdown of carbohydrates and proline-rich proteins that are antimicrobial and bind Ca to maintain tooth enamel
  55. Submandibular gland
    • Mixed with lots of serous and a few mucous
    • Contains striated intralobar ducts and a main excretory duct (Wharton's)
    • Made of branched tubulo-acinar glands and occasional serous demilunes (half-moon shaped mucous tubules capped with serous cells)
    • Secrete α-amylase, proline-rich proteins, and lysozyme (another antibacterial)
  56. Sublingual gland
    • Mixed with loads of mucous
    • Duct system does not contain striated intralobular ducts, but the main excretory duct is Bartholin's
    • Made of branched tubulo-acinar glands and occasional serous demilunes
  57. Exocrine component of the pancreas
    • Contains serous acini (similar to the parotid gland) packed full of secretory granules
    • The ducts run from the acini as centro-acinar cells (duct cells found in the acini that secrete bicarbonate) into intercalated ducts, then non-striated interlobar ducts, then to the main pancreatic ducts and out the duodenal papillae
    • Secretes:
    • 1: Trypsinogen, which is converted into trypsin by the duodenal enzyme enteropeptidase
    • 2: Chymotrypsinogen, which is converted into chymotrypsin by trypsin
    • 3: α-amylase, which digests carbohydrates and polysaccharides
    • 4: Lipase, that breaks down dietary fat molecules
    • 5: Ribonuclease and deoxyribonuclease that degrade nucleoproteins
    • Control of Secretions:
    • Secretin is made by S-cells in the glands of the duodenum, and stimulates centro-acinar to produce bicrbonate in order to neutralize acidic gastric products
    • Cholecystokinin is made by I-cells in the intestinal glands of the duodenum, and stimulates pancreatic acinar cells to release zymogen granules and gallbladder to release bile
  58. Endocrine component of the pancreas
    The pale-staining islets of Langerhans secrete glucagon and insulin
  59. Structure of the liver
    • Porta hepatis: The inferior surface of the liver where the hepatic portal vein (70-80% of blood flow), the hepatic artery, common hepatic duct, and lymphatics (to the thoracic duct); however, the hepatic vein exit the liver at the postero-superior aspect of the liver
    • Stroma: Glisson's capsule is made of connective tissue and surrounds the liver and extends inward to form lobes; the connective tissue eventually gives way to thin reticular fibers that support the liver cells and sinusoids
    • Parenchyma: Hepatocytes contain glycogen granules and are rich in rough endoplasmic reticulum; they are organized into functional units called lobules
  60. Structure of a classic liver lobule
    • Portal triads: Contain a venule, arteriole, and bile duct (cuboidal epithelium) arranged in a hexagonal pattern around a central vein
    • Sinusoids: Large capillaries that carry a mixture of arterial and venous blood through the lobule from the periphery to the central vein; are lined by a layer of  fenestrated endothelial cells on top of a discontinuous basal lamina
    • Kupffer cells: Macrophages that are located between sinusoid endothelial cells and within sinusoids; they remove bacteria and debris and breakdown aged RBCs to recycle the heme
    • Space of Disse: A space between hepatocytes and sinusoids that contain hepatocyte microvilli; blood passes through this space and bathes the microvilli, allowing for exchange of nutrients and metabolites
    • Bile canaliculi: Tubular spaces that are surrounded by the plasma membranes of two adjacent hepatocytes; these cells secrete bile that flows centrifugally toward peripherally-located bile ducts in the portal spaces; these ducts have a cuboidal epithelium
  61. Biliary tract
    • Lined with simple cuboidal epithelium
    • Sphincter of Oddi is a smooth muscle thickening in the wall of the duodenum around the major duodenal papilla that controls the flow of bile and pancreatic juice into the duodenum
    • The ampulla of Vater is an enlarged area of the duct before the sphincter of Oddi
  62. Gallbladder function and structure
    • Function: Stores and concentrates bile by reabsorbing water; adds mucous to bile; cholecystokinin causes contraction of smooth muscle in the gallbladder wall
    • Structure: Simple columnar epithelium with microvilli and an underlying lamina propria that is folded to form rugae; has smooth muscle muscularis that contracts to expel bile and is surrounded by a serosa of simple squamous epithelium on the outside; submucousa is almost absent
  63. What percentage of blood is supplied to the liver by the portal vein and what might that blood contain?
    • 60-80% of the hepatic blood flow is provided by the portal vein
    • It is a low-pressure system that has lower oxygen content that arterial blood, but is rich in nutrients, hormones (especially from the pancreatic venous drainage), gut-derived ntigens, bacteria, bacterial products, cells that are ultimately cleared by the liver, and drugs/toxins
  64. Acinar model of the liver
    • The portal triad is placed in the center of the acinus, with the "central" veins around the periphery
    • Focuses on the area from which blood enters the liver parenchyma
  65. Portal hypertension (types, causes, treatment)
    • Caused by capillarization (deposition of ECM proteins in the space of Disse) and decreased diameter of sinusoids
    • Portal blood is diverted into collateral vessels (aka varices) because of increased resistance to flow through the liver
    • Cirrhosis: The most common cause of sinusoidal portal hypertension in this part of the world; the increased resistance to portal flow occurs due to structural alterations of the liver and increased local production of vasoconstrictors (endothelin) and decreased production of vasodilators (nitric oxide)
    • Remeber that Pressure = Resistance x Flow
    • Portal flow also increases as a consequence of splanchnic vasodilation (decreased arteriolar resistance due to local nitric oxide production)
    • Schistosomiasis: Causes presinusoidal portal hypertension when the eggs of this organism lodge in the small portal vein branches of the portal triads
    • Damage to terminal hepatic venules: Chemotherapy or radiation can result in post-sinusoidal portal hypertension
    • Portal vein thrombosis: A clot in the portal vein can cause pre-hepatic portal hypertension
    • Congestive heart failure: High right-sided filling pressures in the heart can cause post-hepatic portal hypertension
    • Treatment: Transjugular intrahepatic portosystemic shunt (TIPS) is when a direct communication is created between a hepatic vein branch and a portal vein branch, shunting blood through a stent placed within the liver
  66. Energy metabolism in the liver
    • Glucose homeostasis: Glycogenesis, glycogenolysis, and gluconeogenesis (liver damage such as acetaminophen overdose can cause hypoglycemia)
    • Lipid metabolism: Major site of synthesis of cholesterol and lipoproteins; trafficks lipoprotein particles; oxidizes, synthesizes, stores, and transports triglycerides
    • Metabolism of amino acids: Transamination, de novo synthesis, deamination, and conversion of ammonia to urea (urea cycle); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are expressed relatively exclusively by hepatocytes and are used as an indicator of liver damage; in cirrhosis, impaired detoxification of ammonia occurs and contributes to development of hepatic encephalopathy
  67. Synthesis of plasma proteins in the liver
    • Albumin: Regulates oncotic pressure; carries many ligands
    • α1-antitrypsin: A protease inhibitor
    • Angiotensinogen: Precursor to angiotensin II
    • Antithrombin-III: Inhibitor of intrinsic coagulation system
    • Apolipoprotein B: Assembly of lipoprotein particles
    • C-reactive protein: Unknown; involved in tissue inflammation
    • Ceruloplasmin: Copper transporter
    • Coagulation factors (II, VII, IX, X): Blood clotting
    • Fibrinogen: Fibrin precursor
    • Haptoglobin: Binds and transport cell-free hemoglobin
    • Steroid hormone-binding globulin: Carrier for steroids in the bloodstream
    • Thyroxine-binding globulin: Carrier for thyroid hormone in the bloodstream
    • Transferrin: Iron transporter
  68. Drug metabolism in the liver
    • Xenobiotics are drugs and use many of the same enzyme systems involved in the synthesis of cholesterol, steroid hormones, and bile acids
    • In general, go from lipophilic substrates to more polar compounds via biotransformation reactions (increase solubility)
    • Phase I reactions: Cytochromes P450 (mixed function oxidase system) are in the endoplasmic reticulum and include NADPH-cytochrome P450 reductase and heme-containing enzymes; these reactions produce more reactive intermediates than the parent compounds
    • Phase II reactions: These reactions conjugate the compound to a group that increases water solubility (glucuronidation, acetylation, sulfation, methylation, conjugation to glycine or glutathione)
  69. Acetaminophen overdose
    • In a healthy person, most (95%) of acetaminophen is metabolized by glucuronidation and sulfation with the remainder converted by cytochrome P450 and then detoxified by conjugation with glutathione
    • In an overdose, the glucuronidation and sulfation pathways get saturated and metabolism shifts to the P450 pathway, causing quicker depletion of the glutathione stores and subsequent liver damage
    • Chronic alcohol ingestion can induce the P450 pathway, allowing acetominophen toxicity to occur at lower doses of the drug
    • N-acetylcysteine, a precursor of cysteine, the limiting amino acid for glutathione synthesis, is an effective treatment for acetaminophen overdose
  70. Bile
    • Made of water, electrolytes, bile acids, cholesterol, phospholipids, and bilirubin
    • Bile acids are made by hepatocytes by breakdown of cholesterol and conjugation to amino acids
    • They are reabsorbed in the terminal ileum and returned to the liver
    • Cholestasis is a failure to secrete bile
    • Function 1: Bile emulsifies dietary fat and aids in absorption of fat-soluble vitamins
    • Function 2: It is also important in elimination of cholesterol (precipitation of cholesterol out of bile contributes to gall stones)
    • Function 3: Bile allows secretion of bilirubin, which is made from the porphyrin (heme) after iron has been recycled; bilirubin is conjugated in the liver and metabolized by bacteria in the gut (calcium bilirubinate gallstones can occur in patients with hemolytic anemias)
  71. Clinical implications of bile acid reabsorption
    • If cholesterol levels are too high, can increase the bile acid fecal excretion by preventing entry back into hepatic circulation by bile acid-binding resins such as cholestyramine
    • The inability to reabsorb bile acids can cause diarrhea in patients who have had extensive ileal resections, and cholestyramine can be helpful (?)
  72. Pathological diagnosis of cirrhosis
    • Fibrosis: An increase in scar tissue characterized by an increase in the content of ECM proteins; hepatic stellate cells, portal myofibroblasts, some bone marrow-derived fibroblasts, and epithelial-to-mesenchymal transitional cells may all be responsible for fibrosis
    • Nodular regeneration: Nodules of hepatocytes circumscribed by scar
  73. Alcoholic liver injury
    • Can cause firbrosis through damage to the hepatocytes around terminal hepatic venules, resulting in pericentral fibrosis
    • This occurs due to chronic ethanol exposure inducing the cytochrome p450 system
  74. Hepatic venous pressure gradient (HVPG)
    • Obtained by threading a balloon-tipped catheter connected to a pressure transducer into a hepatic vein branch using a regrograde approach
    • FHVP: The free pressure, determined by a deflated balloon in the hepatic vein branch
    • WHVP: The wedged pressure, determined by inflating the balloon to occlude the vessel; our measurements are usually slightly lower than the actual pressure because the sinusoids dissipate some of the pressure
    • HVPG = WHVP - FVHP
    • HVPG equals 1 to 5 mmHg
    • Cirrhosis: The WHVP is increased (and so is the HVPG); varices are at high risk of rupture and ascites is likely to form when HVPG > 12mmHg
    • Congestive heart failure: This post-hepatic portal hypertension will result in an elevation of both FHVP and WHVP with a normal HVPG
  75. Hyperdynamic circulation
    • A characteristic of cirrhosis (and portal hypertension) that includes increased heart rate, increased cardiac output, and decreased systemic vascular resistance (due to arterial vasodilation from production of vasodilators like nitric oxide)
    • Since there is an overproduction of vasodilators, cirrhotic patients are hyporesponsive to vasoconstrictors
    • This vasodilation causes the splangchnic vascular bed to be dilated and this causes a perceived decrease in effective arterial blood volume
    • Retention of sodium and water and ultimaltey, volume overload, occurs
    • Result: Patient has enormous volume overload with kidneys that "think" he or she is dehydrated and retain sodium (and water), causing ascites and edema
  76. What percent of the body's immune system is found in the gut?
  77. What layer of the gut contains the immune cells?
    The lamina propria, which is part of the mucosa
  78. Enterochromaffin-like cells (ECL cells)
    Release histamine in order to stimulate gastric acid production by neighboring parietal cells (paracrine control)
  79. Enteric neurons release what neurotransmitter?
    • Acetylcholine (in general, causes secretion)
    • However, they also release a variety of other signaling molecules (transmitters) in a paracrine fashion to influence the behavior of non-neural cells
  80. Motilin
    A hormone that causes increased GI motility
  81. Vasoactive intestinal polypeptide (VIP)
    A paracrine peptide that increases bicarbonate secretion and smooth muscle relaxation
  82. Substance P
    A non-peptide transmitter that causes increased motility and histamine release (acid secretion)
  83. Norepinephrine
    A paracrine non-peptide transmitter that causes inhibition in the gut
  84. Enteric nervous system
    • A major division of the autonomic nervous system that contains about 100 million neurons in Meissener's and Auerbach's plexes, allowing the gut to function almost autonomously via internal reflexes
    • Secretomotor neurons: Stimulate or inhibit smooth muscle cells and regulate epithelial cell secretion/absorption, vasoconstriction/dilation, and release of gut hormones by enteric endocrine cells
    • Sensory neurons: Respond to mechanical stretching, changes in osmolarity, pH, concentration of specific nutrients, and other chemical stimuli
  85. Parasympathetic innervation of the gut
    • Pelvic nerves supply the distal third of the colon
    • Cranial nerves V, IX, X, and XII supply the pharynx
    • The vagus nerve provides innervation for the rest of the gut
    • Function: Increased motility and secretion
    • Neurotransmitter: Mostly ACh, but others are also used
    • Sensory fibers: Go from the gut to the autonomic centers in the medulla carrying information from gut chemoreceptors, osmoreceptors, and mechanoreceptors; these form the afferent portion of reflex loops mediated by the autonomic centers of the brain
  86. Sympathetic innervation of the gut
    • Postganglionic fibers from prevertebral sympathetic ganglia directly innervate effector cells or interact with neurons of the enteric nervous system
    • Function: Slow down motility and secretion
  87. Characteristics of gastrointestinal smooth muscle
    • Form a syncytium with intimate contact between myocytes and low-resistance gap junctions that allow for entire layers of muscle to be activated simultaneously
    • Depolarization occurs when voltage-dependent calcium channels allow influx of calcium, resulting in release of calcium from internal stores via G-protein activation
    • Longitudinal fibers shorten and dilate the bowel and circular fibers constrict the lumen (the muscularis mucosae plays little role in intestinal motility), propelling food through peristalsis
    • Action potentials move in an aboral direction (toward the anus) via slow-wave activity of the enteric nervous system
  88. Peristalsis
    Stretchign of the gut wall causes contraction of circular smooth muscle above the stretch and relaxatino of circular muscle below the stretch, moving the bolus forward and propagating the stretch/contraction reflex downstream
  89. Sphincters
    • Upper esophageal sphincter
    • Lower esophageal sphincter
    • Pylorus
    • Ileocecal valve
    • Internal anal sphincter
    • External anal sphincter
    • Functions: Prevent or reduce retrograde flow and provide a reservoir function in the upstream bowel
    • They interrupt flow by tonic contrction; stimuli above cause relaxation and stimuli below cause contraction
  90. Fasting motility of the small bowel
    • In between meals, these three phases occur and are known as the interdigestive motor complex or the migrating motor complex (MMC)
    • Phase 1: A period of complete quiescence with no measurable muscle activity
    • Phase 2: A period of brief, intermittent contractions; some are propagated downstream (propulsive) and others are not (mixing/churning)
    • Phase 3: A brief period of regular, high-amplitude contractions that propagate downstream
  91. Fed motility of the small bowel
    Feeding interrupts the cyclic pattern of the MMC and initiates a period of strong, irregular contractions that resemble phase 2 of the MMC (brief, intermittent contractions that may or may not propagate)
  92. Function of the colon
    • Fluid and electrolyte absorption: occurs mostly in the proximal colon and converts the liquid chyme into a formed stool
    • Absorption of short-chain fatty acids: Fermentation of carbohydrates that escaped absorption occurs in the colon, yielding shorthain fatty acids (lactate, butyrate, proprionate, tec) and are readily absorbed by the colon
    • Reservoir: Stores stool
    • Defecation
  93. High-amplitude propagating contractions (HAPCs)
    Mass peristalsis that occurs several times per day, pushing stool into the empty rectum and is stimulated by food in the stomach (gastrocolic reflex)
  94. Defecation (rectosphincteric reflex)
    • Rectal stretching by stool results in reflex relaxation of the internal anal sphincter and sensation of the need to defecate
    • Defecation is initiated by voluntary relaxation of the external anal sphincter and contraction of the muscles of the pelvic floor
  95. Hirschsprung's disease
    • Caused by failure of ganglion cells to migrate into distal bowel during development
    • Peristalsis is absent in the affected bowel because no ganglion cells are present in Auerbach's and Meissener's plexes
    • Lack of ganglion cells also prevents reflexive relaxation of internal anal sphincter
  96. Crohn's disease
    A type of inflammatory bowel disease caused by the immune system targeting microbial antigens in the gut
  97. Process of chewing and swallowing
    • Voluntary phase: Taking up food, chewing, and swallow initiation
    • Autonomic phase: Soft palate seals off nasopharynx, pharyngeal folds contract, larynx is pulled upwards, epiglottis and vocal cords close, the upper esophageal sphincter relaxes, and pharynx contracts (swallowing center in medulla and CN V, IX, X, and XII)
  98. Primary versus secondary esophageal peristalsis
    • Primary: Initiated by swallowing
    • Secondary: Initiated by stretching of the esophagus (retained food or gastric reflux)
  99. Esophageal peristalsis
    • The UES relaxes for food to enter by swallowing
    • The UES closes and the LES opens and peristalsis begins
    • Controlled by the vagus nerve and by intrinsic plexuses in the wall of the esophagus
  100. Major segments of the stomach and the types of glands they contain
    • Cardia: 1-2 cm region below the esophagus
    • Body: The major portion of the stomach; the dome-like upper portion is the fundus; has many parietal (acid) cells, mucus cells, chief (pepsinogen) cells, and enterochromaffin-like (ECL; histamine) cells
    • Antrum: The funnel-shaped distal region of the stomach; has mucus cells, chief cells, endocrine cells, and G (gastrin) cells; does not have parietal cells
  101. Functions of the stomach
    • Food accommodation: Storage
    • Mechanical breakdown: Grinding of food by contractions and acid to make chyme
    • Secretion: Gastric glands produce around 2 liters of acid, fluid, and electrolytes; when it is not secreting, Na is dominant, but when it is, H is dominant
    • Digestion: Gastric pepsins start protein digestion at low pH
  102. Function of gastric acid
    • Creates a low pH needed for optimum pepsin function, is bactericidal, and helps break down food
    • It is NOT essential to digestion
  103. Mechanism of acid secretion
    • Parietal cells have H-K ATPase, which is made of a catalytic "a" subunit and a delivery "b" subunit that ensures it gets moved to the apical membrane
    • Unstimulated cells have the proton pump in intracellular tubulovesicles
    • Stimulated cells have fusion of these vesicles with the apical membrane, allowing the H to reach the lumen and K to be exchanged
  104. Potassium homeostasis during acid secretion
    • Excess K accumulation from the H-K ATPase is avoided by K channels that allow K to cross back outside of the apical membrane
    • Electroneutrality is maintained by excretion of Cl through a passive chloride channel
    • Water follows the HCl passively into the lumen
  105. Source of protons
    • CO2 and H2O are made into HCO3 and H by carbonic anhydrase
    • A Cl-HCO3 exchanger causes secretion of HCO3 into the blood and intake of Cl for maintenance of the electroneutrality of K
    • when the stomach is secreting acid, it is also secreting HCO3 into the blood, resulting in an alkaline tide of the venous outflow
  106. Regulation of gastric acid production
    • Three secretagogues stimulate acid production by parietal cells
    • Histamine: Directly causes secretion of acid by binding the H2 receptor; made by enterochromaffin-like (ECL) cells
    • Gastrin: Acts directly on parietal cells, but mostly acts by stimulating histamine release from ECL cells; made by G cells in the antrum of the stomach and the duodenum in 2 forms (little and big); also causes epithelial cells to proliferate in the stomach, small intestine, and colon
    • ACh: Also works mostly indirectly on acid secretion by causing ECL cells to release histamine (does work directly on parietal cells too)
    • Inhibition: Arrival of food, fat, acid, and hyperosmolar solutions in the duodenum inhibits gastric acid secretion (FAT IS THE MOST POTENT INHIBITOR); secretin, CCK, vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP), neurotensin, and peptide YY also inhibit (SECRETIN IS MOST POTENT HORMONAL ACID INHIBITOR by causing somatostatin production and inhibiting H secretion directly and antral gastrin release)
  107. Stimulation of gastrin secretion
    • Remember, gastrin is secreted by G cells and causes release of histamine, and ultimately secretion of acid into the stomach
    • Distention of the stomach causes reflex activation of G cells
    • G cells can also be directly stimulated to secrete gastrin by peptides and amino acids
Card Set
Human Organ Systems Test 4, Digestive Tract
Flashcards over Dr. Swailes's digestive tract material for the 4th HOS test