Action potential

Vitamins

-not substrates

-serve catalytic role as enzyme cofactors or prosthetic groups

-must be included in diet b/c they cannot be synthesized in the body

-fat-soluble vitamins require bile acids for solubilization and absorption

-excess fat-soluble vitamins are stored in adipose tissue

-water-soluble - excess is secreted in urine by kidneys

Gastrointestinal (GI) Tract

-is a long, muscular tube extending from the mouth to the anus-derived from the cavity produced by gastrulation during embryogenesis

-anus is derived from the blastopore

-other names for GI tract: digestive tract, alimentary canal or gut

GI Lumen

-inside of the gut-continuous with the space outside the body

-where usable foodstuffs are extracted, while wastes are left to be excreted as feces

-innermost lining of the lumen is composed of epithelial cells b/c its exposed to substances from the outside world

Basement Membrane

-epithelial cells are attached by definition to BMApical Surface

-apex: top

-surface of epithelial cells which faces into the lumen

Microvilli

-outward folds of plasma membrane

-in the small intestine, the apical surfaces of these cells have these folds

-to increase surface areaTight Junctions

-apical surface is separated by the remainder of the cell surface by tight junctions

-bands running all the way around the sides of epithelial cells, creating a barrier that separates body fluids from the extracellular environment

Basolateral Surface

-sides and bottom of the epithelial cell form the surface opposite of the lumen, the basolateral surface

Smooth Muscle Lining the Gut

-longitudinal layer - runs along the gut lengthwise

-circular layer - encircles it

GI Motility

-refers to the rhythmic contraction of GI smooth muscle

-determine by complex of five factors:

(1) GI smooth muscle exhibits automaticity

(2) is a functional syncytium

(3) contains its own nervous system, known as enteric nervous system, plays a major role in controlling GI motility

(4) Affected by hormonal input

(5) parasympathetic nervous system stimulates motility and causes sphincters to relax --> allowing the passage of food through the gut (sympathetic nervous system does opposite)

serves two purposes: (1) mixing of food (2) movement of food down the gut

Automaticity

-contracts periodically without external stimulation due to spontaneous depolarization

Functional Syncytium

-when one cell has action potential and contracts, the impulse spreads to neighboring cellsPeristalsis

-movement of food down the GI tract is accomplished by an orderly form of contraction-contraction of circular smooth muscle at point A prevents food located at point B from moving backward-then longitudinal muscles at point B contract, with the result being shortening of the gut so that it is pulled up over the food like a rock --> food moves toward point C

-then circular muscles at point B contract to prevent the food from moving backward and longitudinal muscles at point C contract --> being movement of food past point C

Bolus

-a ball of food moving through the GI tract

GI Secretion

-stimulated by food in the gut-stimulated by the parasympathetic nervous system

-inhibited by sympathetic stimulation

-two types of secretion: exocrine and endocrine

Exocrine Glands

-composed of specialized epithelial cells, organized into sacs called acini

-release enzymes into ducts that ultimately empty into the GI lumen

-digestive organs involved are liver, gallbladder, and pancreas

-some exocrine secretion is performed by specialized individual epithelial cells in the wall of the gut itself (miniature exocrine glands) releasing secretions directly into the gut lumen

Acini

-sacs of specialized epithelial cells that make up the exocrine glands

-acinar cells secrete products which pass into ducts

Goblet Cells

-specialized mucus-secreting cells

-found along the entire GI tract

-mucus is a slimy liquid which protects and lubricates the gut

-mucous membrane - any body surface covered with mucusGastric Glands

-in the stomach-secrete acid

-pepsinogen a protease zymogen

Endocrine

-endocrine secretion is also accomplished by both specialized organs and by cells in the wall of the gut

-do not empty into duct but instead are picked up by nearby capillaries

-when an organ has both endocrine and exocrine activities, these functions are accomplished by separate cells

Pancreatic Acinar Cells

-exocrine cells of the pancreas

Islets of Langerhans

-endocrine cells of the pancreas that are clumped together in groupsAccessory Organs

-liver, gallbladder, pancreas and the large salivary glands found outside the mouth-play a role in digestion but are not part of alimentary canal

-gallbladder is not essential, but can be infected, obstructed or cancerous and thus medically important-pancreas and liver are essential for GI function

Mouth: Roles

three roles in the digestion of foodstuffs:

(1) fragmentation - accomplished by mastication (chewing)

incisors - front teeth; for cutting

cuspids - canine teeth; for tearing

molars - for grinding

(2) lubrication - saliva

(3) some enzymatic digestion

Saliva

-viscous fluid secreted by salivary glands

-contains salivary amylase (ptyalin) - hydrolyzes starch breaking it into fragments

-smallest fragment yielded by salivary amylase is the disaccharide-digestion to monosaccharide only occurs at the intestinal brush border

-saliva contains a small amount of lingual lipase for fat digestion-no digestion of proteins occur in the mouth

-saliva contains lysozyme - attacks bacterial cell walls (mouths role in innate immunity)

Bolus

-chewed food into a smooth lump which can be swallowed

-mouth

-a bolus of food passes through the pharynx, over the epiglottis and into the esophagus where it is conveyed to the stomach by peristalsisPharynx

-what we commonly call the throat

-contains the opening to two tubes: trachea and esophagus

Trachea

-is a cartilage-lined tube at the front of the neck which conveys air to and from the lungsEsophagus

-a muscular tube behind the trachea which conveys food and drink from the pharynx to the stomach

Epiglottis

-flat cartilaginous flap that excludes solids and liquids from the trachea during swallowing

Upper Esophageal Sphincter

-is near the top of the esophagus

Lower Esophageal Sphincter

-also known as cardiac sphincter-found near the heart

-at the end of the esophagus, at the entrance of the stomach

-purpose is to prevent reflux

Stomach

-hollow muscular organ

-three purposes: (1) partial digestion of food (2) regulated release of food into the small intestine (3) destruction of microorganisms -gastric - related to the stomach

-secretion of inactive precursor is common theme in the GI tractGastric Acidicity

-pH is 2 due to secretion of HCL by parietal cells located in the gastric mucosa

-effects: (1) destruction of microorganisms (2) acid-catalyzed hydrolysis of many dietary proteins (3) conversion of pepsinogen to pepsin

Pepsin

-enzyme secreted by chief cells in the stomach wall-catalyzes proteolysis (protein breakdown)

-pepsin is secreted as pepsinogen, inactive precursor that must be converted to the active form; conversion is catalyzed by gastric acidity-activated by acidic proteolysis (autocleavage) instead of proteolytic cleavage by another enzyme

Zymogen

-inactive form of an enzyme

-most are activated by proteolysis (cleavage of protein at a specific site that activates it

Chyme

-food mixed with gastric secretions

Pyloric Sphincter

-prevents the passage of food from the stomach into the duodenum

-opening of pyloric sphincter (stomach emptying) is inhibited by the small intestine, when the small intestine already has a large load of chyme

-stretching/excess acidicity in the duodenum inhibits further stomach emptying by causing the pyloric sphincter to contract

-this effect is mediated by both by nerves connecting the duodenum and stomach and by hormones (specifically cholecystokinin)Cholecystokinin (CCK)

-secreted by epithelial cells in the wall of the duodenum

-main hormone responsible for the inhibition of stomach emptying when stretching/excess acidicity in the duodenum exists

-is secreted in response to fats in the duodenum

-causes pancreas to secrete digestive enzymes (exocrine pancreas)-stimulates gallbladder contraction (bile release)

-decreases gastric motility

-the above three processes cooperate to deal with fats in the duodenum, by digesting them and preventing further stomach emptyingGastrin

-hormone secreted by cells in the stomach known as G cells-stimulates acid and pepsin secretion and gastric motility

-stimulated by food in the stomach and by parasympathetic stimulation

Histamine

-small molecule that binds to parietal cells to stimulate acid release

-which is secreted in response both to stomach stretching and to gastrin

Small Intestine

-divided into three segments: duodenum, jejunum and ileum-digestion is completed in the duodenum and jejunum-key feature that allows SI to accomplish absorption is its large surface area, is the result of: (1) length

(2) villi - macroscopic (multicellular); projections in the wall of the SI

(3) microvilli - microscopic foldings of the cell membranes of individual intestinal epithelial cells

-lumenal surface of the SI is brush border due to appearance of brush-like microvilli

Duodenum

-digestion is completed here and the jejunum

-absorption begins in the duodenum and continues throughout the small intestine

-key anatomical feature is it empties into two ducts: pancreatic duct and common bile duct

Villi

-a finger-like projection of the wall of the gut into the lumen

-has three important structures:

(1) contain capillaries which absorb dietary monosaccharides and amino acids

(2) contain small lymphatic vessels called lacteals which absorb dietary fats

(3) Peyer's patches are part of the immune system; are a collection of lymphocytes dotting the villi that monitor GI contents and thus confer immunity to gut pathogens and toxins

Hepatic Portal Vein

-formed from the merger of veins

-transports blood containing amino acid and carbohydrate nutrients from the gut to the liverLacteals

-which absorb dietary fats-merge to form large lymphatic vessels which transport dietary fats to the thoracic duct, which empties into the bloodstreamPeyer's Patches

-are part of the immune system-are a collection of lymphocytes dotting the villi -monitor GI contents thus confer immunity to gut pathogens and toxinsPancreatic Duct

-delivers exocrine secretions of the pancreas (digestive enzymes and bicarbonate)

Common Bile Duct

-delivers bile

Bile

-ingredients are bile acids, cholesterol and bilirubin (from RBC breakdown)-bile acids, (bile salts) made from cholesterol in the liver & are normally absorbed & recycled

-bile is either directly secreted into the duodenum or it is stored in the gallbladder -bile has two functions:

(1) vehicle for the disposal (excretion) of waste products by the liver

(2) essential for the digestion of fats: (a) bile emulsifies large fat particles in the duodenum, creating smaller clusters of fat particles called micelles; micelles have greater surface area --> easier digestion than large particles (b) bile helps fatty particles diffuse across the intestinal mucosal membraneGallbladder

-stores bile for later use

-bile stored in gallbladder is concentrated & released when fatty meal is eaten-has no secretory activity

-bile release is dictated by both endocrine system and nervous system

-CCK and parasympathetic nervous system stimulate contraction of the gallbladder wall

Sphincter of Oddi

-bile duct and pancreatic duct empty into the duodenum via the same orificeDuodenal Enzymes

-some duodenal epithelial cells secrete enzymes

-enterokinase - activates pancreatic zymogen trypsinogen to trypsin-brush border enzymes - other duodenal enzymes that are peculiar in that they are not truly secreted, but rather do their work inside or on the surface of the brush border epithelial cell-role of brush border enzymes is to hydrolyze the smallest carbohydrate and proteins (like disaccharides and dipeptides) into monosaccharides and amino acids

Duodenal Hormones

-other duodenal epithelial cells secrete hormones

-three main duodenal hormones are:

(1) cholecystokinin (CCK)

(2) secretin

(3) enterogastroneSecretin

-is released in response to acid in the duodenum

-causes the pancreas (exocrine pancreas) to release large amounts of high-pH aqueous buffer (namely HCO3- in water) --> neutralizes HCL released by the stomach

-duodenal pH must be kept at neutral or even slightly basic for pancreatic digestive enzymes to function

Enterogastrone

-decreases stomach emptying

Jejunum and Ileum

-substances not absorbed in duodenum must be absorbed in lower segments of SI-lower SI performs special absorptive processes

-absorption of Vitamin B12 only occurs in ileum (and only when Vitamin B12 is complexed with intrinsic factor, a glycoprotein secreted by parietal cells of the stomach)

Ileocecal Valve

-separates the ileum from the cecum, first part of the large intestineColon

-muscular tube; part of large intestine

-roles is to absorb water and minerals and to form and store feces until defecation

-abnormalities in colon formation --> poor fluid absorption and diarrhea, can cause dehydration and death

-cecum - first part of the colon

-entrance of chyme into cecum is controlled by ileocecal valve

-rectum - last portion of the colon

-exit of feces thru the anus-contains bacteria (many are facultative or obligate anaerobes)

Appendix

-finger-like appendage of the cecum

-composed primarily of lymphatic tissue

Anal Sphincter

-has internal and external portion

-internal anal sphincter consists of smooth muscle, which is under autonomic control

-external anal sphincter consists of skeletal muscle and is under voluntary control (note: same arrangement as urinary sphincters)Colonic Bacteria

-located in the colon

-important for two reasons:

(1) the presence of large numbers of normal bacteria helps keeps dangerous bacteria from proliferating due to competition for space and nutrients

(2) colonic bacteria supply us with Vitamin K, essential for blood clotting

Vitamin K

-essential for blood clotting

-produced by colonic bacteria

Exocrine Pancreas

-pancreatic enzymes released into the duodenum are essential for digestion

-pancreatic amylase - hydrolyzes polysaccharides to disaccharides

-pancreatic lipase - hydrolyzes triglycerides at the surface of micelle

-nucleases - hydrolyze dietary DNA and RNA

-several different pancreatic proteases are responsible for hydrolyzing polypeptides to di- and tripeptides

-pancreatic proteases are secreted in zymogen form and must be activated by removal of portion of PP chain-two hormones control pancreatic secretion: CCK and secretin

-parasympathetic NS activation increases pancreas secretion

-sympathetic NS activation decreases pancreas secretion

Trypsinogen

-pancreatic enzyme-zymogen which converted to active form, trypsin, by enterokinase, an intestinal enzyme-other pancreatic enzymes are activated by trypsin which include: chymotrypsinogen, procarboxypeptidase (active: carboxypeptidase) and procollagenaseEndocrine Pancreas

-islets of Langerhans; three type of cells in the islets

(1) cells secrete glucagon

(2) cells secrete insulin

(3) cells secrete somatostatinBlood Glucose

(1) Lowering blood glucose - insulin causes glucose to be removed from the bloodstream and stored; excess glucose directly destroys many physiological systems at the cellular level, including neurons, blood vessels and the kidneys(2) Raising blood glucose - three hormones can raise blood glucose: glucagon, epinephrine, and cortisol

-makes sense to have so many ways to increase blood glucose b/c low blood glucose can be fatal while elevated blood glucose is harmless in the short term

Liver

-receives blood from two places (1) oxygenated blood from the hepatic arteries (2) venous blood draining the stomach and intestines through hepatic portal vein (hepatic - "relating to the liver")-as blood percolates thru the liver, nutrients are extracted by hepatocytes

-both liver and skeletal muscles cells are capable of storing glycogen-only the liver is able to release free glucose to the bloodstream (because it is the only one that contains the enzyme glucose-6-phosphatase which dephosphorylates G6P, the product of glycogen breakdown)

-regulates nitrogenous waste products from protein catabolism; NH3 is transported to the liver where it is converted to urea --> blood-assists in lipid metabolism

-makes many important plasma proteins and secretes into plasma-major center for drug & toxin detoxification of the body

Hepatocytes

-liver cells

-hepatocytes monitor the blood and make changes to the body's physiology based on what is and is not present

-chylomicrons are degraded by lipases into triglycerides, glycerol and cholesterol rich chylomicron remnants-chylomicron remnants are taken up by hepatocytes and combined with proteins to make lipoproteins (HDL, LDL, etc.)

-these lipoproteins --> blood and are source of cholesterol and triglycerides for the other tissues of the body

-drug detoxification: smooth ER in hepatocytes contains enzyme pathways that breakdown drugs and toxins into other forms less toxic and more readily excreted by renal and gastrointestinal systems

-sometimes these enzyme pathways are used to convert some drugs to their active formLipoprotein Lipase

-adipose and liver tissue contain the enzyme

-hydrolyzes chylomicron triglycerides into monoglycerides and free fatty acids --> diffuse into adipocytes and liver cells and are remade into triglycerides and then stored

List of Vitamins & Function(Note: A-K are fat-soluble)

-A (retinol) a visual pigment which changes conformation in response to light

-D - stimulates Ca2+ absorption from the gut; helps control Ca2+deposition in bones

-E - prevents oxidation of unsaturated fats

-K - necessary for formation of coagulation factors

water-soluble

-B1 (thiamine) - needed for enzymatic decarboxylations

-B2 (riboflavin) - made into FAD, electron transporter-B3 (niacin) - made into NAD+, electron transporter-B6 (pyridoxine) - coenzyme involved in protein and AA metabolism-B12 (cobalamin) - coenzyme involved in the reduction of nucleotides to deoxynucleo.-C (ascorbic acid) - necessary for collagen formation; deficiency results in scurvy

-biotin - prosthetic group essential for transport of CO2 groups-folate - enzyme cofactor used in the transport of methylene groups; synthesis of purines and thymine; required for normal level of fetal nervous system developmentPAGE 4