1. Chapter 24
Digestive System

2. Digestive System Anatomy
Digestive tract: also called alimentary tract or canal
GI tract: technically refers to stomach and intestines
Accessory organs
Primarily glands, secrete fluids into tract
Regions
Mouth or oral cavity with salivary glands and tonsils
Pharynx (throat) with tubular mucous glands
Esophagus with tubular mucous glands
Stomach with many different kinds of glands that are tubular
Small intestine (duodenum, ileum, jejunum) with liver, gallbladder and pancreas as major accessory organs
Large intestine including cecum, colon, rectum and anal canal with mucous glands
Anus

3. Functions Ingestion: introduction of food into stomach
Mastication: chewing. Chemical digestion requires large surface area so breaking down large particles mechanically facilitates chemical digestion.
3. Propulsion (movement of food hours oral end to anal end)
Deglutition: swallowing (oral cavity -> esophagus) (bolus = mass of food or liquid)
Peristalsis: moves material through digestive tract . A wave of circular smooth muscle relaxation moves ahead of the bolus of food or chyme allowing the digestive tract to expand. Then a wave of contraction of the circular smooth muscles behind the bolus of food or chyme (ingested food & stomach secretions) propels it through the digestive tract.
Mass movements in large intestine (contractions that extend for larger parts of digestive tract)

4. 4. Mixing: Segmental contractions ( mixing contractions that occur
4. Mixing: Segmental contractions ( mixing contractions that occur in small intestine. -Some contractions do not propel food from one end of digestive tract to the other but, rather, move it back & forth within digestive tract to mix it with digestive secretions & help break it into smaller pieces)

5. Functions, cont. 5. Secretion: lubricate, liquefy, digest
Mucus: secreted along entire digestive tract, lubricates food and lining, coats lining and protects from mechanical digestion, from acid and from digestive enzymes.
Water: liquefaction makes food easier to digest and absorb
Bile: emulsifies fats
Enzymes: chemical digestion
6. Digestion: Mechanical and chemical
7. Absorption: Movement from tract into circulation or lymph
8. Elimination: Waste products removed from body; feces. Defecation

6. Digestive Tract Histology: The Tunics
Mucosa. Innermost layer, consisting of mucous epithelium (stratified squamous in mouth, oropharynx, esophagus and anal canal), simple columnar epithelium in the rest of the tract.
Loose connective tissue: lamina propria
Muscularis mucosae: smooth muscle
Submucosa. Thick C.T. layer with nerves, blood vessels, small glands. Parasympathetic submucosal plexus.

7. Digestive Tract Histology: The Tunics
Muscularis: 2 or 3 layers of smooth muscle, two of which are circular and longitudinal. Exception: esophagus where the upper 1/3 is striated & stomach. This layer also contains the myenteric plexus. The myenteric and submucosal plexi together are called the enteric or intramural plexus. Important in control of movement and secretion
Serosa or adventitia: Connective tissue. Where serosa is present, called visceral peritoneum. Where adventitia is present, connective tissue blends with connective tissue of surrounding structures

8. Digestive System Regulation
Nervous regulation
Local: enteric nervous system
Types of neurons: sensory, motor, interneurons
Coordinates peristalsis and regulates local reflexes
General: coordination with the CNS. May initiate reflexes because of sight, smell, or taste of food. Parasympathetic primarily (through vagas nerve). Sympathetic input inhibits muscle contraction, secretion, and decrease of blood flow to the digestive tract.
Chemical regulation
Production of hormones to be discussed later
Gastrin, secretin
Production of paracrine chemicals like histamine
Help local reflexes in ENS control the conditions of the internal environment of the digestive tract such as pH levels

9. Peritoneum and Mesenteries
Visceral: Covers organs
Parietal: Covers interior surface of body wall
Retroperitoneal: Certain organs covered by peritoneum on only one surface and are considered behind the peritoneum; (lie against abdominal wall) e.g., kidneys, pancreas, duodenum
Mesenteries: two layers of peritoneum with thin layer of loose C.T. between
Routes by which vessels and nerves pass from body wall to organs
Greater omentum: connects greater curvature of the stomach to the transverse colon (extends inferiorly from stomach over surface of small intestine).
Lesser omentum: connects lesser curvature of the stomach and the proximal part of the duodenum to the liver and diaphragm.
Transverse mesocolon, sigmoid mesocolon, mesoappendix (mesentery refers to serous membranes attached to abdominal organs).
Ligaments
Coronary: between liver and diaphragm
Falciform: between liver and anterior abdominal wall

10. Oral Cavity
Bounded by lips anteriorly, fauces (opening into pharynx) posteriorly
Vestibule: space between lip/cheeks and alveolar processes with teeth
Oral cavity proper: medial to alveolar processes
Lined with moist stratified squamous epithelium

11. Lips and Cheeks Both structures important in mastication and speech
Lips (labia): orbicularis oris muscle within. Keratinized stratified squamous exterior is thin and color of blood in dermis gives a red/pink color.
Labial frenula (mucous folds) extend from alveolar processes of maxilla and mandible to the upper and lower lips, respectively.
Many facial muscles act to move lips
Cheeks: lateral walls of oral cavity
Buccinator muscle
Buccal fat pad

12. Palate and Palatine Tonsils
Hard palate: anterior, supported by maxilla and palatine bone
Soft palate: posterior, consists of skeletal muscle and connective tissue
Uvula: projects from posterior of soft palate
Palatine tonsils: lateral walls of fauces

13. Tongue
Muscular with free anterior surface and attached posterior surface. Covered with moist stratified squamous epithelium.
Intrinsic muscles: change shape
Extrinsic muscles: protrude or retract tongue, move side to side
Lingual frenulum attaches tongue inferiorly to floor of oral cavity
Terminal sulcus: groove divides tongue into anterior 2/3; posterior 1/3
Anterior part: papillae, some of which have taste buds
Posterior part: no papillae and a few scattered taste buds. Lymphoid tissue embedded in posterior surface: lingual tonsil
Moves food in mouth, participates in speech and swallowing

14. Teeth Two sets Types Primary, deciduous, milk: Lost during childhood
Permanent or secondary: Adult (32)
Types
Incisors, canines, premolars and molars

15. Teeth Involved in mastication and speech
Anatomic crown: enamel-covered part of tooth; clinical crown is section of tooth above gum line
Neck: enameled part of tooth below gum line
Enamel: outermost layer of anatomical crown. Non-living; acellular. Protective.
Dentin: living, cellular, calcified tissue. In the root, dentin is covered by cellular bone-like structure that helps hold tooth in the socket.
Pulp cavity filled with blood vessels, nerves, and connective tissue
Periodontal ligaments: hold tooth in socket.
Gingiva: dense, fibrous C.T. covered by stratified squamous epithelium.

16. Mastication
Chewing: incisors and canines bite or cut off food; molar-type teeth grind food
Muscles involved: masseter, temporalis, medial and lateral pterygoids.
Elevate mandible (close jaw): temporalis, masseter, medial pterygoids
Depress mandible (open jaw): lateral pterygoids
Protraction (moving in anterior direction) and lateral and medial excursion (lateral = moves mandible to either right or left of midline medial = returns mandible to neutral position): pterygoids and masseter
Retraction (moves structure back to anatomical position)- temporalis
Mastication reflex: medulla oblongata, but descending pathways from cerebrum provide conscious control. Controls basic movements involved in chewing

17. Salivary Glands Three pairs of multicellular glands
Parotid: largest. Serous. Just anterior to the ear. Parotid duct crosses over masseter, penetrates buccinator, and enters the oral cavity adjacent to the 2nd upper molar
Submandibular: mixed, but more serous than mucous. Posterior half of inferior border of mandible. Duct enters oral cavity on either side of lingual frenulum
Sublingual: smallest. Mixed, but primarily mucous. Each has ducts that enter the floor of the oral cavity.
Lingual glands. Small, coiled tubular glands on surface of tongue.

18. Saliva Compound alveolar salivary glands. Produce saliva
Prevents bacterial infection
Lubrication
Contains salivary amylase that breaks down starch into disaccharides maltose and isomaltose (gives starch sweet taste in mouth).
Helps to form bolus for swallowing
Parasympathetic input causes salivary production

19. Pharynx and Esophagus Pharynx Esophagus
Posterior walls of oropharynx and laryngopharynx contains group of muscles called pharyngeal constrictors that contribute to swallowing
Esophagus
Transports food from pharynx to stomach
Passes through esophageal hiatus (opening) of diaphragm and ends at stomach
Hiatal hernia: widening of hiatus (causes ulcers, acid reflux)
Sphincters
Upper. Striated
Lower. Smooth
Mucosa is moist stratified squamous epithelium. Produces thick layer of mucus.

20. Swallowing (Deglutition)
Three phases
Voluntary: bolus of food moved by tongue from oral cavity to pharynx.
Pharyngeal: reflex. Controlled by swallowing center in medulla oblongata. Soft palate elevates, upper esophageal sphincter relaxes, elevated pharynx opens the esophagus, food pushed into esophagus by pharyngeal constrictors’ successive contraction from superior to inferior. Epiglottis is tipped posteriorly due to pressure of the bolus, larynx elevated to prevent food from passing into larynx.
Esophageal: reflex. Stretching of esophagus causes enteric NS to initiate peristalsis of muscles in the esophagus.

21. Three Phases of Swallowing

22. Stomach Anatomy Openings
Gastroesophageal (cardiac): to esophagus
Pyloric: to duodenum
Parts
Cardiac
Fundus
Body
Pyloric: antrum and canal
Greater and lesser curvatures: attachment sites for omenta
Sphincters
Cardiac (lower esophageal)
Pyloric

23. Stomach Histology Layers
Serosa or visceral peritoneum
Muscularis: three layers
Outer longitudinal
Middle circular
Inner oblique (Having a slanting or sloping direction)
Submucosa
Mucosa
Rugae: folds in stomach when empty. Mucosa and submucosa.

24. Stomach Histology
Gastric pits: openings for gastric glands. Lined with simple columnar epithelium
Cells of gastric pits
Surface mucus: mucus that protects stomach lining from acid and digestive enzymes
Mucous neck: mucus
Parietal: hydrochloric acid and intrinsic factor
Chief: pepsinogen
Endocrine: regulatory hormones
Enterochromaffin-like cells: secretes histamine that stimulates acid secretion
Gastrin-containing cells: secrete gastrin (a hormone that stimulates acid secretion)
Somatostatin-containing cells: secrete somatostatin that inhibits gastrin and insulin secretion

25. Secretions of the Stomach
Chyme: ingested food plus stomach secretions
Mucus: surface and neck mucous cells
Viscous and alkaline
Protects from acidic chyme and enzyme pepsin
Irritation of stomach mucosa causes greater mucus
Intrinsic factor: parietal cells. Binds with vitamin B12 and helps it to be absorbed in the ileum. B12 necessary for DNA synthesis and RBC production (lack of B12 absorption leads to pernicious anemia)
HCl: parietal cells
Kills bacteria (found in ingested food)
Stops carbohydrate digestion by inactivating salivary amylase
Denatures proteins
Helps convert pepsinogen to pepsin (optimal activity at pH 3 or less)
Pepsinogen: packaged in zymogen granules released by exocytosis. Pepsin catalyzes breaking of covalent bonds in proteins (breaks them into smaller peptide chains)

26. Hydrochloric Acid Production

27. Cephalic Phase
The taste or smell of food, tactile sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata.
Parasympathetic action potentials are carried by the vagus nerves to the stomach, where enteric plexus neurons are activated.
Postganglionic neurons stimulate secretion by parietal and chief cells (HCl and pepsin) and stimulate the secretion of the hormone gastrin and histamine.
Gastrin is carried through the circulation back to the stomach where it and histamine stimulate further secretion of HCl and pepsin.

28. Gastric Phase
Distention of the stomach activates a parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata.
Medulla oblongata stimulates further secretions of the stomach.
Distention also stimulates local reflexes that amplify stomach secretions.

29. Intestinal Phase
Chyme in the duodenum with a pH less than 2 or containing lipids inhibits gastric secretions by three mechanisms
Sensory input to the medulla from the duodenum inhibits the motor input from the medulla to the stomach. Stops secretion of pepsin and HCl.
Local reflexes inhibit gastric secretion
Secretin, and cholecystokinin produced by the duodenum decrease gastric secretions in the stomach.

30. Movements in Stomach
Combination of mixing waves (80%) and peristaltic waves (20%)
Both esophageal and pyloric sphincters are closed.

31. Small Intestine
Site of greatest amount of digestion and absorption of nutrients and water
Divisions
Duodenum- first 25 cm beyond the pyloric sphincter.
Jejunum- 2.5 m
Ileum- 3.5 m. Peyer’s patches or lymph nodules

32. Duodenum Curves to the left; head of pancreas in the curve
Major and minor duodenal papillae: openings to ducts from liver and/or pancreas.

33. Modifications to Increase Surface Area
Increase surface area 600 fold
Plicae circulares (circular folds)
Villi that contain capillaries and lacteals. Folds of the mucosa
Microvilli: folds of cell membranes of absorptive cells

34. Mucosa and Submucosa of the Duodenum
Cells and glands of the mucosa
Absorptive cells: cells with microvilli, produce digestive enzymes and absorb digested food
Goblet cells: produce protective mucus
Endocrine cells: produce regulatory hormones (Secretin, and cholecystokinin)
Granular cells (paneth cells): may help protect from bacteria (contain lysozymes)
Intestinal glands (crypts of Lieberkühn): tubular glands in mucosa at bases of villi [secrete sucrase ,maltase, trypsin, chymotrypsin, and pepsin (endopeptidases and exopeptidases) ]
Duodenal glands (Brunner’s glands): tubular mucous glands of the submucosa. Open into intestinal glands [produce a mucus-rich alkaline secretion (containing bicarbonate)

35. Jejunum and Ileum
Gradual decrease in diameter, thickness of intestinal wall, number of circular fold, and number of villi the farther away from the stomach
Major site of nutrient absorption
Peyer’s patches: lymphatic nodules numerous in mucosa and submucosa
Ileocecal junction: where ileum meets large intestine. Ileocecal sphincter (ring of smooth muscle) and ileocecal valve (one-way valve)

36. Small Intestine Secretions
Fluid primarily composed of water, electrolytes and mucus.
Mucus
Protects against digestive enzymes and stomach acids
Digestive enzymes: bound to the membranes of the absorptive cells
Disaccharidases: Break down disaccharides to monosaccharides
Peptidases: Hydrolyze peptide bonds
Nucleases: Break down nucleic acids
Duodenal glands
Stimulated by vagus nerve, secretin, chemical or tactile irritation of duodenal mucosa

37. Movement in Small Intestine
Mixing and propulsion over short distances
Segmental contractions mix
Peristalsis propels
Ileocecal sphincter remains slightly contracted until peristaltic waves reach it; it relaxes, allowing chyme to move into cecum
Cecal distention causes local reflex and ileocecal valve constricts
Prevents more chyme from entering cecum
Increases digestion and absorption in small intestine by slowing progress of chyme
Prevents backflow

38. Liver
Lobes
Major: Left and right
Minor: Caudate and quadrate
Porta: on inferior surface. Vessels, ducts, nerves, exit/enter liver
Hepatic portal vein, hepatic artery, hepatic nerve plexus enter
Lymphatic vessels, two hepatic ducts exit
Ducts
Right and left hepatics (which transport bile out of liver) unite to form
Common hepatic
Cystic: from gallbladder
Common bile: union of cystic duct and common hepatic duct (common bile joins the pancreatic duct at the hepatopancreatic ampulla------ampulla empties into duodenum at major duodenum papilla)

39. Liver, Gallbladder, Pancreas and Ducts

40. Histology of the Liver
Connective tissue septa branch from the porta into the interior
Divides liver into lobules
Nerves, vessels and ducts follow the septa
Lobules: portal triad at each corner
Three vessels: hepatic portal vein, hepatic artery, hepatic duct
Central vein in center of lobule
Central veins unite to form hepatic veins that exit liver and empty into inferior vena cava

41. Liver Histology
Hepatic cords: radiate out from central vein. Composed of hepatocytes
Hepatic sinusoids: between cords, lined with endothelial cells and hepatic phagocytic (Kupffer) cells
Bile canaliculus: between cells within cords
Hepatocyte functions
Bile production
Storage
Interconversion of nutrients
Detoxification
Phagocytosis
Synthesis of blood components

42. Functions of the Liver
Bile production: mL/day. Bile salts, bilirubin (bile pigment that results from breakdown of hemoglobin), cholesterol, fats, fat-soluble hormones, lecithin
Neutralizes and dilutes stomach acid (neutralizes chyme so that pancreatic enzymes can function)
Bile salts emulsify fats. Most are reabsorbed in the ileum. (90% bile salts reabsorbed in the ileum & carried back to liver)
Secretin (from the duodenum) stimulates bile secretions, increasing water and bicarbonate ion content of the bile
Storage
Glycogen, fat, vitamins (A, B12, D, E, and K), copper and iron. Hepatic portal blood comes to liver from small intestine (nutrients are stored and secreted back into circulation when needed)
Synthesis
Blood proteins: Albumins, fibrinogen, globulins, heparin, clotting factors (liver produces its own new compounds)

43. Functions of the Liver Nutrient interconversion
Amino acids to energy producing compounds (ex: person on a excessively high protein diet and low fat & carb diet an oversupply of amino acids & an undersupply of lipids & carbs are delivered to the liver. The hepatocytes break down the amino acids and cycle them through metabolic pathways so they can be used to produce adenosine triphosphate, lipids, and glucose)
Hydroxylation of vitamin D. Vitamin D then travels to kidney where it is hydroxylated again into its active form
Hepatocytes also transform substances that cannot be used by most cells into usable sunstances. (ex: ingested fats combined with choline {nutrient in B vitamin family} & phosphorous in liver to produce phospholipids, which are imp. for cell membranes)
Detoxification
Hepatocytes remove ammonia (by-product of amino acid metabolism) which is toxic & not readily removed by kidneys. Hepatocytes convert it to urea which is less toxic and easily eliminated by kidneys.
Phagocytosis
Kupffer cells phagocytize worn-out and dying red and white blood cells, some bacteria

44. Blood and Bile Flow Through the Liver

45. Gallbladder
Sac lined with mucosa folded into rugae, inner muscularis, outer serosa
Bile arrives constantly from liver is stored and concentrated
Stimulated by cholecystokinin (from the intestine) and vagal stimulation
Bile exits through cystic duct then into common bile duct
Gallstones: precipitated cholesterol (occurs when excess cholesterol in bile due to high-cholesterol diet and not enough bile salts to keep it in solution)
Can block cystic duct
If gallstone moves far down the duct, it can block pancreatic duct, resulting in pancreatitis.
Can occur because of drastic dieting (as the body metabolizes fat during prolonged fasting and rapid weight loss—such as “crash diets”—the liver secretes extra cholesterol into bile, which can cause gallstones.)

46. Control of Bile Secretion and Release

47. Pancreas Pancreas both endocrine and exocrine Head, body and tail
Endocrine: pancreatic islets. Produce insulin, glucagon, and somatostatin
Exocrine: groups acini (grape-like cluster) form lobules separated by septa.
Intercalated ducts lead to intralobular ducts lead to interlobular ducts lead to the pancreatic duct.
Pancreatic duct joins common bile duct and enters duodenum at the hepatopancreatic ampulla controlled by the hepatopancreatic ampullar sphincter

48. Pancreatic Secretions: Pancreatic Juice
Aqueous. Produced by columnar epithelium lining smaller ducts. Na+, K+, HCO3-, water. Bicarbonate lowers pH inhibiting pepsin and providing proper pH for enzymes
Enzymatic portion: (without the enzymes produced by pancreas, lipids, proteins, & carbs not adequately digested)
Trypsinogen- active form is trypsin proteolytic enzyme
Chymotrypsinogen- active form is chymotrypsin proteolytic enzyme
Procarboxypeptidase- active form is carboxypeptidase proteolytic enzyme
Pancreatic amylase- continues digestion of starch.
Pancreatic lipases- lipid digesting enzyme
Deoxyribonucleases and ribonucleases- reduce DNA & RNA to their nucleotide
Interaction of duodenal and pancreatic enzymes
Enterokinase is a proteolytic enzyme from the duodenal mucosa and it activates trypsinogen to trypsin.
Trypsin activates chymotrypsinogen to chymotrypsin.
Trypsin activates procarboxypeptidase to carboxypeptidase.

49. Bicarbonate Ion Production in Pancreas

50. Control of Pancreatic Secretion

51. Large Intestine Extends from ileocecal junction to anus
Consists of cecum, colon, rectum, anal canal
Movements sluggish (18-24 hours); chyme converted to feces.
Absorption of water and salts, secretion of mucus, extensive action of microorganisms are involved in the formation of feces.
1500 mL chyme enter the cecum, 90% of volume reabsorbed yielding mL of feces

52. Anatomy of Large Intestine
Cecum
Blind sac, vermiform appendix attached. Appendix walls contain numerous lymph nodules
Colon
Ascending, transverse, descending, sigmoid
Circular muscle layer complete; longitudinal incomplete (three bands called teniae coli). Contractions of teniae form pouches called haustra. Small fat-filled pouches called epiploic appendages
Mucosa has numerous straight tubular glands called crypts. Goblet cells predominate, but there are also absorptive and granular cells as in the small intestine

53. Anatomy of Large Intestine
Rectum
Straight muscular tube, thick muscular tunic
Anal canal- superior epithelium is simple columnar; inferior epithelium is stratified squamous
Internal anal sphincter (smooth muscle)
External anal sphincter (skeletal muscle)
Hemorrhoids: Vein enlargement or inflammation

54. Secretions of Large Intestine
Mucus provides protection
Parasympathetic stimulation increases rate of goblet cell secretion
Pumps: bacteria produce acid and the following remove acid from the epithelial cells that line the large intestine
Exchange of bicarbonate ions for chloride ions
Exchange of sodium ions for hydrogen ions
Bacterial actions produce gases (flatus) from particular kinds of carbohydrates found in legumes and in artificial sugars like sorbitol
Bacteria produce vitamin K which is then absorbed
Feces consists of water, undigested food (cellulose), microorganisms, sloughed-off epithelial cells

55. Movement in Large Intestine
Mass movements (strong contractions)
Common after meals
Integrated by the enteric plexus
Local reflexes instigated by the presence of food in the stomach and duodenum
Gastrocolic: initiated by stomach
Duodenocolic: initiated by duodenum
Defecation
Defecation reflex: distension of the rectal wall by feces
Parasympathetic stimulation
Usually accompanied by voluntary movements to expel feces. Abdominal cavity pressure caused by inspiration and by contraction of muscles of abdominal wall.

56. Digestion, Absorption, Transport
Breakdown of food molecules for absorption into circulation
Mechanical: breaks large food particles to small
Chemical: breaking of covalent bonds by digestive enzymes
Absorption and transport
Molecules are moved out of digestive tract and into circulation for distribution throughout body

58. Carbohydrates: Hydrolyzed into Monosaccharides
Glucose is transported to cells requiring energy; insulin influences rate of transport

59. Transport of Lipids Across Intestinal Epithelium

60. Lipids
Include triglycerides, phospholipids, steroids, fat-soluble vitamins
Bile salts surround fatty acid and glycerol to form micelles
Chylomicrons are 90% triglyceride, 5% cholesterol, 4% phospholipid, 1% protein.
Chylomicrons enter blood stream and travel to adipose tissue. In blood, triglycerides converted back into fatty acids and glycerol where they are transported into the adipose cells, then converted back into triglycerides.

61. Lipoproteins
All lipids carried in the blood are done so in combination with protein to make them soluble in plasma.
Cholesterol: 15% ingested; 85% manufactured in liver and intestinal mucosa
Lipids are lower density than water; proteins are higher density than water
Chylomicrons: 99% lipid and 1% protein (extremely low density); enter lymph
VLDL: 92% lipid, 8% protein
Form in which lipids leave the liver
Triglycerides removed from VLDL and stored in adipose cells. VLDL has been converted to LDL.
LDL: 75% lipid, 25% protein
Transports cholesterol to cells
Cells have LDL receptors
# of LDL receptors become less once cell’s lipid/cholesterol needs are met.
HDL: 55% lipid, 45% protein
Transports excess cholesterol from cells to liver

62. Transport of LDL into Cells

63. Amino Acid Transport

64. Proteins Pepsin breaks proteins into smaller polypeptide chains
Proteolytic enzymes produce small peptide chains
Dipeptides, tripeptides, amino acids
After absorption, amino acids are carried through the hepatic portal vein to the liver.

65. Water and Ions
Water: can move in either direction across wall of small intestine depending on osmotic gradients
Ions: sodium, potassium, calcium, magnesium, phosphate are actively transported

66. Effects of Aging
Decrease in mucus layer, connective tissue, muscles and secretions
Increased susceptibility to infections and toxic agents, increase in incidences of ulcerations and cancers