Figure 22 Section 2Figure 22 Section 2
Steps in the Process of Digestion
In the oral cavity, saliva dissolves some organicnutrients, and mechanical processing withthe teeth and tongue disrupts the physicalstructure of the material and provides accessfor digestive enzymes. Those enzymes beginthe digestion of complex carbohydrates(polysaccharides) and lipids.
In the stomach, the material is further brokendown physically and chemically by stomachacid and by enzymes that can operate at anextremely low pH.
In the duodenum, buffers from the pancreas andliver moderate the pH of the arriving chyme, andvarious digestive enzymes are secreted by thepancreas that catalyze the catabolism ofcarbohydrates, lipids, proteins, and nucleic acids.
Nutrient absorption then occurs in the smallintestine, primarily in the jejunum, and thenutrients enter the bloodstream.
Indigestible materials and wastes enter the largeintestine, where water is reabsorbed and bacterialaction generates both organic nutrients andvitamins. These organic products are absorbedbefore the residue is ejected at the anus.
Most of the nutrients absorbed by the digestivetract end up in a tributary of the hepatic portalvein that ends at the liver. The liver absorbsnutrients as needed to maintain normal levelsin the systemic circuit.
Within peripheral tissues, cells absorb thenutrients needed to maintain their nutrient pooland ongoing operations.
Digestion, Absorption, Digestion, Absorption, TransportTransport
DigestionDigestion Breakdown of food molecules for Breakdown of food molecules for
absorption into circulation absorption into circulation MechanicalMechanical: Breaks large food particles to : Breaks large food particles to
smallsmall ChemicalChemical: Breaking of covalent bonds by : Breaking of covalent bonds by
digestive enzymes digestive enzymes
AbsorptionAbsorption and and transporttransport Molecules are moved out of digestive tract Molecules are moved out of digestive tract
and into circulation for distribution and into circulation for distribution throughout bodythroughout body
Digestive System Digestive System RegulationRegulation
Nervous regulationNervous regulation Involves enteric Involves enteric
nervous systemnervous system Types of neurons: Types of neurons:
sensory, motor, sensory, motor, interneuronsinterneurons
Coordinates Coordinates peristalsis and peristalsis and regulates local regulates local reflexesreflexes
Chemical regulationChemical regulation Production of Production of
hormoneshormones Gastrin, secretinGastrin, secretin
Production of Production of paracrine chemicalsparacrine chemicals
Histamine Histamine Help local reflexes in Help local reflexes in
ENS control digestive ENS control digestive environments as pH environments as pH levels levels
Digestive System Digestive System AnatomyAnatomy
Digestive tractDigestive tract Alimentary tract or Alimentary tract or
canalcanal GI tractGI tract
Accessory Accessory organsorgans Primarily glandsPrimarily glands
RegionsRegions Mouth or oral cavityMouth or oral cavity PharynxPharynx EsophagusEsophagus StomachStomach Small intestineSmall intestine Large intestineLarge intestine AnusAnus
Peritoneum and Peritoneum and MesenteriesMesenteries
PeritoneumPeritoneum VisceralVisceral: Covers organs: Covers organs ParietalParietal: Covers interior : Covers interior
surface of body wallsurface of body wall RetroperitonealRetroperitoneal: Behind : Behind
peritoneum as kidneys, peritoneum as kidneys, pancreas, duodenumpancreas, duodenum
MesenteriesMesenteries Routes which vessels Routes which vessels
and nerves pass from and nerves pass from body wall to organsbody wall to organs
Greater omentumGreater omentum Lesser omentumLesser omentum
Digestive Tract Digestive Tract HistologyHistology
Oral CavityOral Cavity Mouth or oral Mouth or oral
cavitycavity VestibuleVestibule: Space : Space
between lips or between lips or cheeks and alveolar cheeks and alveolar processesprocesses
Oral cavity properOral cavity proper Lips (labia) and Lips (labia) and
cheekscheeks PalatePalate: Oral cavity : Oral cavity
roofroof Hard and soft Hard and soft
Palatine tonsilsPalatine tonsils TongueTongue: Involved in : Involved in
speech, taste, speech, taste, mastication, mastication, swallowingswallowing
TeethTeeth
Two setsTwo sets Primary, deciduous, Primary, deciduous,
or milk: Childhoodor milk: Childhood Permanent or Permanent or
secondary: Adult secondary: Adult (32)(32)
TypesTypes Incisors, canine, Incisors, canine,
premolar and premolar and molarsmolars
Tooth structure:Tooth structure:
Salivary GlandsSalivary Glands Produce salivaProduce saliva
Prevents bacterial Prevents bacterial infectioninfection
LubricationLubrication Contains salivary Contains salivary
amylaseamylase Breaks down starchBreaks down starch
Three pairsThree pairs Parotid: LargestParotid: Largest SubmandibularSubmandibular Sublingual: Sublingual:
SmallestSmallest
Deglutition Deglutition (Swallowing)(Swallowing)
Three phasesThree phases VoluntaryVoluntary
Bolus of food moved by tongue from oral Bolus of food moved by tongue from oral cavity to pharynxcavity to pharynx
PharyngealPharyngealReflexReflex: Upper esophageal sphincter : Upper esophageal sphincter
relaxes, elevated pharynx opens the relaxes, elevated pharynx opens the esophagus, food pushed into esophagusesophagus, food pushed into esophagus
EsophagealEsophageal ReflexReflex: Epiglottis is tipped posteriorly, : Epiglottis is tipped posteriorly,
larynx elevated to prevent food from larynx elevated to prevent food from passing into larynxpassing into larynx
Phases of Deglutition Phases of Deglutition (Swallowing)(Swallowing)
The process of peristalsis
Foodbolus
Towardanus
Longitudinalmuscle
Circular muscle
Circular musclescontract behindbolus.
Bolus of foodarrives indigestivesystem.
Longitudinalmuscles aheadof boluscontract.
Contraction incircular musclelayer forcesbolus forward.
Stomach Anatomy:Stomach Anatomy:
OpeningsOpenings GastroesophaGastroesopha
geal: To geal: To esophagusesophagus
Pyloric: To Pyloric: To duodenumduodenum
RegionsRegions CardiacCardiac FundusFundus BodyBody PyloricPyloric
Stomach Anatomy Stomach Anatomy cont.cont.
Rugae: Folds in stomach when emptyRugae: Folds in stomach when empty Gastric pits: Openings for gastric glandsGastric pits: Openings for gastric glands
Contain cellsContain cells Surface mucous: MucusSurface mucous: Mucus Mucous neck: Mucus Mucous neck: Mucus Parietal: Hydrochloric acid and intrinsic factor Parietal: Hydrochloric acid and intrinsic factor Chief: Pepsinogen Chief: Pepsinogen Endocrine: Regulatory hormonesEndocrine: Regulatory hormones
The structure of the wall of the stomach
Layers of the Stomach Wall
Mucosa
Muscularis Externa
Submucosa
Serosa
Lamina propria
Muscularis mucosae
Oblique muscle
Circular muscle
Longitudinal muscle
Consists of a simple columnarepithelium that produces an alkalinecarpet of mucus that covers the interiorsurfaces of the stomach and protectsepithelial cells against the acid andenzymes in the gastric lumen
Lymphatic vessel
Artery and vein
Myenteric plexus
Figure 21.9 Figure 21.9 2 2
The structure of gastric pits and gastric glands
Gastric pit
Gastric glands
Lamina propria
Mucous epithelial cells
Neck
Cells of Gastric GlandsParietal cells(secrete HCl and intrinsic factor)
G cells(produce a varietyof hormones)
Chief cells(secrete pepsinogen)
Figure 21.9 Figure 21.9 33
The secretory activities of parietal cells
Hydrogen ions (H+) aregenerated inside a parietalcell as the enzyme carbonicanhydrase converts CO2 andH2O to carbonic acid (H2CO3),which then dissociates.
A countertransport mechanismejects the bicarbonate ions intothe interstitial fluid and importschloride ions into the cell.
The chloride ions then diffuseacross the cell and exit throughopen chloride channels into thelumen of the gastric gland.
Interstitialfluid
Tobloodstream
Carbonicanhydrase
Parietal cell
Lumen ofgastricgland
The hydrogen ions areactively transported into thelumen of the gastric gland.
KEY
Diffusion
Carrier-mediatedtransport
Active transport
Countertransport
Phases of Gastric Activity Phases of Gastric Activity I I
Phases of Gastric Activity Phases of Gastric Activity II II
Movements in StomachMovements in Stomach
Phases of Gastric Activity Phases of Gastric Activity III III
Materialarrives in
jejunum
Chyme induodenum
Food instomach
Ingestedfood
facilitates
Acid production byparietal cells
Stimulation of gastricmotility; mixing wavesincrease in intensity
Release of insulinfrom pancreas
Release of pancreaticenzymes and buffers
Bile secretion andejection of bile fromgallbladder
Dilation of intestinalcapillaries
Nutrient absorptionNUTRIENT
UTILIZATIONBY ALL TISSUES
facilitates
KEYinhibits
stimulates
Gastrin
GIP
Secretinand CCK
VIP
The pattern of hormone release and the effects of thosehormones within the digestive system
Hormone Action
Figure 21.13 Figure 21.13 22
The two central reflexes triggered by thestimulation of stretch receptors in thestomach wall
Central GastricReflexes
Gastroenteric reflex:stimulates motilityand secretion alongthe entire smallintestine
Gastroileal reflex:triggers the openingof the ileocecal valve,allowing materials topass from the smallintestine into thelarge intestine
Ileocecal valve
Small IntestineSmall Intestine Site of greatest Site of greatest
amount of digestion amount of digestion and absorptionand absorption
Divisions Divisions DuodenumDuodenum JejunumJejunum Ileum: Peyer’s patches Ileum: Peyer’s patches
or lymph nodulesor lymph nodules ModificationsModifications
Circular folds or plicae Circular folds or plicae circulares, villi, lacteal, circulares, villi, lacteal, microvillimicrovilli
Cells of mucosaCells of mucosa Absorptive, goblet, Absorptive, goblet,
granular, endocrinegranular, endocrine
Figure 21.11 Figure 21.11 22
Ileum
Duodenal glands
Duodenum
Jejunum
Serosa
Muscularisexterna
Submucosa
Mucosa
Muscularismucosae
Plicaecirculares
Villi
Aggregated lymphoid nodules
The characteristic features of each of thethree segments of the small intestine
Small Intestine Small Intestine SecretionsSecretions
MucusMucus Protects against digestive enzymes and Protects against digestive enzymes and
stomach acidsstomach acids Digestive enzymesDigestive enzymes
Disaccharidases: Break down disaccharides Disaccharidases: Break down disaccharides to monosaccharidesto monosaccharides
Peptidases: Hydrolyze peptide bondsPeptidases: Hydrolyze peptide bonds Nucleases: Break down nucleic acidsNucleases: Break down nucleic acids
Duodenal glandsDuodenal glands Stimulated by vagus nerve, secretin, chemical Stimulated by vagus nerve, secretin, chemical
or tactile irritation of duodenal mucosaor tactile irritation of duodenal mucosa
Mixing: Mixing:
Segmental contraction Segmental contraction that occurs in small that occurs in small intestineintestine
Involves contraction of Involves contraction of circular muscles onlycircular muscles only
Figure Figure 21.1021.10
Intestinal adaptations for absorbing nutrients
A plica circulares and villiin the small intestinal wall
Plica circulares
Villi
A diagrammatic sectional view of the intestinal wall showing featurescommon to all segments ofthe small intestine
Villi Submucosalartery and vein
Lacteal(lymphaticcapillary)
Intestinal gland
Muscularis mucosae
Lymphoid nodule
Submucosal plexus
Circular layer ofsmooth muscle
Myenteric plexus
Longitudinal layerof smooth muscle
Lymphatic vessel
Serosa
Muscularisexterna
Submucosa
Mucosa
Layers of theSmall Intestine
Lacteal
Columnar epithelial cell
Mucous cell
Nerve
Capillary network
Arteriole
Lymphatic vessel
Venule
Muscularis mucosae
Muscles that move the villiback and forth to exposethe epithelial surfaces to
the intestinal contents
Lamina propria
The structure of an intestinal villus
The complex internal structure ofan intestinal villus
A photomicrograph showing the brushborder of an intestinal villus
Capillaries
Mucous cells
Lacteal
Brush border
Tip of villus LM x 250
Figure 21.10 Figure 21.10 11 – – 33
Intestinal adaptations for absorbing nutrients
A plica circulares and villiin the small intestinal wall
Plica circulares
Villi
A diagrammatic sectional view of the intestinal wall showing featurescommon to all segments ofthe small intestine
Villi Submucosalartery and vein
Lacteal(lymphaticcapillary)
Intestinal gland
Muscularis mucosae
Lymphoid nodule
Submucosal plexus
Circular layer ofsmooth muscle
Myenteric plexus
Longitudinal layerof smooth muscle
Lymphatic vessel
Serosa
Muscularisexterna
Submucosa
Mucosa
Layers of theSmall Intestine
Figure 21.10 Figure 21.10 22
A plica circulares and villiin the small intestinal wall
Plica circulares
Villi
Figure 21.10 Figure 21.10 33
A diagrammatic sectional view of the intestinal wall showing featurescommon to all segments ofthe small intestine
Villi Submucosalartery and vein
Lacteal(lymphaticcapillary)
Intestinal gland
Muscularis mucosae
Lymphoid nodule
Submucosal plexus
Circular layer ofsmooth muscle
Myenteric plexus
Longitudinal layerof smooth muscle
Lymphatic vessel
Serosa
Muscularisexterna
Submucosa
Mucosa
Layers of theSmall Intestine
Figure 21.10 Figure 21.10 44 – – 55
Lacteal
Columnar epithelial cell
Mucous cell
Nerve
Capillary network
Arteriole
Lymphatic vessel
Venule
Muscularis mucosae
Muscles that move the villiback and forth to exposethe epithelial surfaces to
the intestinal contents
Lamina propria
The structure of an intestinal villus
The complex internal structure ofan intestinal villus
A photomicrograph showing the brushborder of an intestinal villus
Capillaries
Mucous cells
Lacteal
Brush border
Tip of villus LM x 250
Accessory Glands and Accessory Glands and StructuresStructures
LiverLiver Gall bladderGall bladder
Exocrine PancreasExocrine Pancreas Pancreatic ductPancreatic duct
Hepatic Portal SystemHepatic Portal System
Duct SystemDuct System
PancreasPancreas
AnatomyAnatomy EndocrineEndocrine
Pancreatic islets Pancreatic islets produce insulin and produce insulin and glucagon glucagon
ExocrineExocrine Acini produce Acini produce
digestive enzymesdigestive enzymes RegionsRegions: Head, : Head,
body, tailbody, tail
SecretionsSecretions Pancreatic juice Pancreatic juice
(exocrine)(exocrine) TrypsinTrypsin ChymotrypsinChymotrypsin CarboxypeptidaseCarboxypeptidase Pancreatic amylasePancreatic amylase Pancreatic lipasesPancreatic lipases Enzymes that Enzymes that
reduce DNA and reduce DNA and ribonucleic acidribonucleic acid
Duodenum and Duodenum and PancreasPancreas
Exocrine PancreasExocrine Pancreas – – EnzymesEnzymes
TrypsinogenTrypsinogen ChymotrysinogenChymotrysinogen CarboxypeptidasesCarboxypeptidases Pro-elastasePro-elastase PhospholipasePhospholipase pancreatic lipasepancreatic lipase Pancreatic amylasePancreatic amylase Enzymes that reduce DNA and Enzymes that reduce DNA and
ribonucleic acidribonucleic acid
GallbladderGallbladder
Bile is stored and concentratedBile is stored and concentrated Stimulated by cholecystokinin and Stimulated by cholecystokinin and
vegal stimulationvegal stimulation Dumps into small intestineDumps into small intestine Production of gallstones possibleProduction of gallstones possible
Drastic dieting with rapid weight lossDrastic dieting with rapid weight loss
LiverLiver LobesLobes
MajorMajor: Left and right: Left and right MinorMinor: Caudate and : Caudate and
quadratequadrate DuctsDucts
Common hepaticCommon hepatic CysticCystic
From gallbladderFrom gallbladder Common bileCommon bile
Joins pancreatic duct Joins pancreatic duct at hepatopancreatic at hepatopancreatic ampullaampulla
Functions of the LiverFunctions of the Liver Bile productionBile production
Salts emulsify fats, contain pigments as bilirubinSalts emulsify fats, contain pigments as bilirubin
StorageStorage Glycogen, fat, vitamins, copper and ironGlycogen, fat, vitamins, copper and iron
Nutrient interconversionNutrient interconversion DetoxificationDetoxification
Hepatocytes remove ammonia and convert to ureaHepatocytes remove ammonia and convert to urea
PhagocytosisPhagocytosis Kupffer cells phagocytize worn-out and dying red and Kupffer cells phagocytize worn-out and dying red and
white blood cells, some bacteriawhite blood cells, some bacteria
SynthesisSynthesis Albumins, fibrinogen, globulins, heparin, clotting factorsAlbumins, fibrinogen, globulins, heparin, clotting factors
Clicker Question:Clicker Question:
Which of the following enzymes is Which of the following enzymes is critical to the primary function of the critical to the primary function of the gastric parietal cells?gastric parietal cells?
A) PepsinA) Pepsin B) GastrinB) Gastrin C) Carbonic AnhydraseC) Carbonic Anhydrase D) LipaseD) Lipase E) None of the aboveE) None of the above
Clicker Question:Clicker Question:
Where would you find a high Where would you find a high frequency of Peyer’s patches?frequency of Peyer’s patches?
A) StomachA) Stomach B) DuodenumB) Duodenum C) JejunumC) Jejunum D) IleumD) Ileum
Clicker Question:Clicker Question: The Plicae Circularis perform which of the following The Plicae Circularis perform which of the following
functions?functions?
A) They impart a spin to the chyme as it travels A) They impart a spin to the chyme as it travels through the through the jejunum. jejunum.
B) They act like an accordion bellows, to allow the B) They act like an accordion bellows, to allow the wall of the wall of the jejunum to stretch. jejunum to stretch.
C) They provide attachment sites for beneficial C) They provide attachment sites for beneficial bacteria.bacteria.
D) They increase the surface area of the D) They increase the surface area of the duodenum and duodenum and jejunum. jejunum.
E) None of the above.E) None of the above.
Clicker Question:Clicker Question:
Activity in the myenteric plexus is Activity in the myenteric plexus is inhibited by by:inhibited by by:
A) GastrinA) Gastrin B) CCKB) CCK C) SecretinC) Secretin D) All of the aboveD) All of the above E) B and C aboveE) B and C above
Blood and Bile FlowBlood and Bile Flow
Figure 21.19 Figure 21.19 33
The functional relationships involvedin the storage and ejection of bile
Duodenum
CCK
Lipiddroplet
Bile salt emulsifying lipiddroplet in the lumen of
the digestive tract
The liversecretes bilecontinuously—roughly 1 literper day.
As it remains inthe gallbladder,bile becomesmoreconcentrated.
The release of CCK by theduodenum triggers dilation ofthe hepatopancreatic sphincterand contraction of thegallbladder. This ejects bile intothe duodenum through theduodenal ampulla.
Liver
Start
BileBile
Bile acidBile acid PhospholipidsPhospholipids CholesterolCholesterol BilirubinBilirubin Waste productsWaste products ElectrolytesElectrolytes MucinMucin
…each day around 600 – 1000 ml of bile is produced…
Figure 24-26: A Summary of the Chemical Events in DigestionFigure 24-26: A Summary of the Chemical Events in Digestion
ORAL CAVITY
ESOPHAGUS
STOMACH
Proenzyme released: Pepsinogen by chief cells, activated to pepsin by HCl
Source: G cells of stomachHormone: Gastrin
Stimulus: Anticipation or arrival of food
SMALL INTESTINE
Enzymes released: Pancreatic amylase, pancreatic lipase, nuclease, enterokinase
Proenzymes released: Chymotrypsinogen, procar- boxypeptidase, proelastase, trypsinogen. Enterokinase activates trypsin, which activates other enzymes
Hormone: CCK
Stimulus: Arrival of chyme in duodenum
INTESTINAL MUCOSA
BLOODSTREAM
(a) (b) (c)
REGION AND HORMONALCONTROLS LIPIDS
EXOCYTOSIS
Monoglycerides,Fatty acids in
micelles
Monoglycerides,Fatty acids
Triglycerides
Chylomicrons
Chylomicrons
Lacteal
Bile salts and pancreatic lipase
Lingual lipase
DIFFUSION
PROTEINS
Polypeptides
Amino acids
FACILITATEDDIFFUSION ANDCOTRANSPORT
FACILITATEDDIFFUSION ANDCOTRANSPORT
Amino acids
CapillaryCapillary
Dipeptidases
TrypsinChymotrypsinElastaseCarboxypeptidase
Pepsin
Monosaccharides
FACILITATEDDIFFUSION
TrisaccharidesDisaccharides
TrisaccharidesDisaccharides
Monosaccharides
FACILITATEDDIFFUSION ANDCOTRANSPORT
Salivary amylase
Pancreaticalpha-amylase
CARBOHYDRATES
Maltase, SucraseLactase
Short peptides,Amino acids
Brush border
Cell body
CarbohydratesCarbohydrates
Carbohydrates are usually preferred Carbohydrates are usually preferred substrates for catabolism and ATP substrates for catabolism and ATP production when restingproduction when resting
Steps of carbohydrate digestionSteps of carbohydrate digestion In mouth, salivary amylase digests In mouth, salivary amylase digests
complex carbohydrates into disaccharides complex carbohydrates into disaccharides and trisaccharidesand trisaccharides
Enzyme active only down to pH 4.5 and Enzyme active only down to pH 4.5 and denatured in stomachdenatured in stomach
At duodenum, At duodenum, pancreatic alpha-amylasepancreatic alpha-amylase continues carbohydrate digestioncontinues carbohydrate digestion
CarbohydratesCarbohydrates
Steps of carbohydrate digestion Steps of carbohydrate digestion (continued)(continued)
In jejunum, brush border enzymes finish In jejunum, brush border enzymes finish carbohydrate digestion down to simple carbohydrate digestion down to simple sugars (monosaccharides)sugars (monosaccharides)
Maltase Maltase (digests maltose: glucose + glucose)(digests maltose: glucose + glucose) Sucrase Sucrase (digests sucrose: glucose + fructose)(digests sucrose: glucose + fructose) Lactase Lactase (digests lactose: glucose + galactose)(digests lactose: glucose + galactose)
In large intestine, remaining indigestible In large intestine, remaining indigestible carbohydrates (such as cellulose) are food carbohydrates (such as cellulose) are food source for colonic bacteriasource for colonic bacteria
Produce intestinal gas (Produce intestinal gas (flatusflatus) during ) during metabolic activitiesmetabolic activities
CarbohydratesCarbohydrates
Carbohydrate absorption and Carbohydrate absorption and transporttransport
Transported into small intestine Transported into small intestine epithelial cellsepithelial cells
Leave cells by facilitated diffusion through Leave cells by facilitated diffusion through basolateral surfacebasolateral surface
Enter cardiovascular capillaries to Enter cardiovascular capillaries to transport to liver in hepatic portal veintransport to liver in hepatic portal vein
Processed by liver to maintain glucose levels Processed by liver to maintain glucose levels (~90 mg/dL)(~90 mg/dL)
Released as glucose Released as glucose oror Stored as glycogenStored as glycogen
CarbohydratesCarbohydrates Cellular use of digested carbohydratesCellular use of digested carbohydrates
Generally preferred for catabolismGenerally preferred for catabolism Proteins and lipids more important for Proteins and lipids more important for
structural components of cells and tissuesstructural components of cells and tissues In skeletal muscle, stored as glycogenIn skeletal muscle, stored as glycogen In most tissues, transported into cell by In most tissues, transported into cell by
carrier molecule (regulated by insulin)carrier molecule (regulated by insulin) May be converted to riboseMay be converted to ribose May be converted to 2 May be converted to 2 pyruvate pyruvate molecules in molecules in
glycolysisglycolysis Produces 2 ATPProduces 2 ATP Pyruvates used by mitochondriaPyruvates used by mitochondria
Uses 3 OUses 3 O22, generates 3 CO, generates 3 CO22, 6 H, 6 H22O, 34 ATPO, 34 ATP
Citricacidcycle
Coenzymes
ATP
Electrontransport
system
CO2
H2O
O2
ATP
CO2Coenzyme A
Other simple sugars
Pyruvate(3-carbon)
Pyruvate(3-carbon)
Insulin
(6-carbon)GLUCOSE
Carbohydrates (such as glucose) are generallypreferred for catabolism because proteins andlipids are more important as structuralcomponents of cells and tissues.
Inside the cell, the glucose may be converted toanother simple sugar, such as ribose, used tobuild glycoproteins, other structural materials,or nucleic acids. They may also be converted toglycerol for the synthesis of glycerides.
If needed to provide energy, the 6-carbon glucosemolecule is broken down into two 3-carbonmolecules of pyruvate. This anaerobic process,called glycolysis, yields a net gain of 2 ATP forevery glucose molecule broken down.
For each molecule of pyruvate processed bymitochondria, the cell gains 17 ATP, consumes3 molecules of O2, and generates 3 molecules ofCO2 and 6 molecules of water. Thus for each pairof pyruvate molecules catabolized, the cell gains34 ATP.
Each pyruvate molecule can then be used bymitochondria, after conversion to acetyl-CoA.
In most tissues, thetransport of glucose into thecell is dependent on thepresence of a carrier proteinstimulated by insulin.
The events in carbohydrate catabolism and ATP production from glucose
Acetyl-CoA(2-carbon)
Figure 24-26: A Summary of the Chemical Events in DigestionFigure 24-26: A Summary of the Chemical Events in Digestion
ORAL CAVITY
ESOPHAGUS
STOMACH
Proenzyme released: Pepsinogen by chief cells, activated to pepsin by HCl
Source: G cells of stomachHormone: Gastrin
Stimulus: Anticipation or arrival of food
SMALL INTESTINE
Enzymes released: Pancreatic amylase, pancreatic lipase, nuclease, enterokinase
Proenzymes released: Chymotrypsinogen, procar- boxypeptidase, proelastase, trypsinogen. Enterokinase activates trypsin, which activates other enzymes
Hormone: CCK
Stimulus: Arrival of chyme in duodenum
INTESTINAL MUCOSA
BLOODSTREAM
(a) (b) (c)
REGION AND HORMONALCONTROLS LIPIDS
EXOCYTOSIS
Monoglycerides,Fatty acids in
micelles
Monoglycerides,Fatty acids
Triglycerides
Chylomicrons
Chylomicrons
Lacteal
Bile salts and pancreatic lipase
Lingual lipase
DIFFUSION
PROTEINS
Polypeptides
Amino acids
FACILITATEDDIFFUSION ANDCOTRANSPORT
FACILITATEDDIFFUSION ANDCOTRANSPORT
Amino acids
CapillaryCapillary
Dipeptidases
TrypsinChymotrypsinElastaseCarboxypeptidase
Pepsin
Monosaccharides
FACILITATEDDIFFUSION
TrisaccharidesDisaccharides
TrisaccharidesDisaccharides
Monosaccharides
FACILITATEDDIFFUSION ANDCOTRANSPORT
Salivary amylase
Pancreaticalpha-amylase
CARBOHYDRATES
Maltase, SucraseLactase
Short peptides,Amino acids
Brush border
Cell body
Protein digestion and amino Protein digestion and amino acid metabolismacid metabolism
Steps of protein digestionSteps of protein digestion In mouth, mechanical processing occursIn mouth, mechanical processing occurs In stomach:In stomach:
Mechanical processing due to churningMechanical processing due to churning Stomach acid denatures protein secondary Stomach acid denatures protein secondary
and tertiary structuresand tertiary structures PepsinPepsin (from parietal cells) attacks certain (from parietal cells) attacks certain
peptide bondspeptide bonds Digests proteins to polypeptide and peptide Digests proteins to polypeptide and peptide
chainschains
Protein digestion and amino Protein digestion and amino acid metabolismacid metabolism
Steps of protein digestion (continued)Steps of protein digestion (continued) In duodenum:In duodenum:
Enteropeptidase Enteropeptidase (from duodenal epithelium) (from duodenal epithelium) converts trypsinogen (pancreatic proenzyme) converts trypsinogen (pancreatic proenzyme) to to trypsintrypsin
Trypsin Trypsin activates other pancreatic activates other pancreatic proenzymesproenzymes
Chymotrypsin, carboxypeptidase, Chymotrypsin, carboxypeptidase, and and elastaseelastase Activated pancreatic enzymes digest specific Activated pancreatic enzymes digest specific
peptide bonds producing short peptides and peptide bonds producing short peptides and amino acidsamino acids
Protein digestion and amino Protein digestion and amino acid metabolismacid metabolism
Digested protein absorption and transportDigested protein absorption and transport Epithelial brush border enzymes (Epithelial brush border enzymes (peptidasespeptidases) )
finish protein digestionfinish protein digestion Amino acids absorbed through:Amino acids absorbed through:
Facilitated diffusionFacilitated diffusion CotransportCotransport
Released from epithelial cell basal surface Released from epithelial cell basal surface through same cell transport mechanismsthrough same cell transport mechanisms
Amino acids transported to liver through Amino acids transported to liver through intestinal capillaries to hepatic portal veinintestinal capillaries to hepatic portal vein
Protein digestion and amino Protein digestion and amino acid metabolismacid metabolism
Amino acid processing in liverAmino acid processing in liver Control of plasma amino acid levels is Control of plasma amino acid levels is
less precise than glucoseless precise than glucose Normal range: 35–65 mg/dLNormal range: 35–65 mg/dL Can increase after protein-rich mealCan increase after protein-rich meal
Liver amino acid useLiver amino acid use Synthesize plasma proteinsSynthesize plasma proteins Create 3-carbon molecules for Create 3-carbon molecules for
gluconeogenesisgluconeogenesis
Protein digestion and amino Protein digestion and amino acid metabolismacid metabolism
Amino acid processing in liver Amino acid processing in liver (continued)(continued)
Amino acid catabolismAmino acid catabolism Deamination Deamination (removal of amino group)(removal of amino group)
Ammonium ions released are toxicAmmonium ions released are toxic Liver enzymes convert to Liver enzymes convert to urea urea excreted excreted
into urineinto urine = = Urea cycleUrea cycle
Figure 22.7Figure 22.7
Organic acid 1 Organic acid 2 TyrosineGlutamic acid
Transaminase
Amino Acid Synthesis
In a transamination, the amino group of one amino acid gets transferredto another molecule, yielding a different amino acid. The remaining carbonchain can then be broken down or used in other ways.
Glutamic acidα–Ketoglutarate
In an aminationreaction, an ammoniumion (NH4
+) is used toform an amino groupthat is attached to amolecule, yielding anamino acid.
Liver cells and other body cells can readily synthesize the carbonframeworks of roughly half of the amino acids needed to synthesize proteins.There are 10 essential amino acids that the body either cannot synthesizeor that cannot be produced in amounts sufficient for growing children.
The liver does not control circulating levelsof amino acids as precisely as it doesglucose concentrations. Plasma amino acidlevels normally range between 35 and 65mg/dL, but they may become elevated aftera protein-rich meal. The liver itself usesmany amino acids for synthesizing plasmaproteins, and it has all of the enzymesneeded to synthesize, convert, or catabolizeamino acids. In addition, amino acids thatcan be broken down to 3-carbon moleculescan be used for gluconeogenesis whenother sources of glucose are unavailable.
NH4+
H+
H2O
Figure 24-26: A Summary of the Chemical Events in DigestionFigure 24-26: A Summary of the Chemical Events in Digestion
ORAL CAVITY
ESOPHAGUS
STOMACH
Proenzyme released: Pepsinogen by chief cells, activated to pepsin by HCl
Source: G cells of stomachHormone: Gastrin
Stimulus: Anticipation or arrival of food
SMALL INTESTINE
Enzymes released: Pancreatic amylase, pancreatic lipase, nuclease, enterokinase
Proenzymes released: Chymotrypsinogen, procar- boxypeptidase, proelastase, trypsinogen. Enterokinase activates trypsin, which activates other enzymes
Hormone: CCK
Stimulus: Arrival of chyme in duodenum
INTESTINAL MUCOSA
BLOODSTREAM
(a) (b) (c)
REGION AND HORMONALCONTROLS LIPIDS
EXOCYTOSIS
Monoglycerides,Fatty acids in
micelles
Monoglycerides,Fatty acids
Triglycerides
Chylomicrons
Chylomicrons
Lacteal
Bile salts and pancreatic lipase
Lingual lipase
DIFFUSION
PROTEINS
Polypeptides
Amino acids
FACILITATEDDIFFUSION ANDCOTRANSPORT
FACILITATEDDIFFUSION ANDCOTRANSPORT
Amino acids
CapillaryCapillary
Dipeptidases
TrypsinChymotrypsinElastaseCarboxypeptidase
Pepsin
Monosaccharides
FACILITATEDDIFFUSION
TrisaccharidesDisaccharides
TrisaccharidesDisaccharides
Monosaccharides
FACILITATEDDIFFUSION ANDCOTRANSPORT
Salivary amylase
Pancreaticalpha-amylase
CARBOHYDRATES
Maltase, SucraseLactase
Short peptides,Amino acids
Brush border
Cell body
Lipids Lipids
Steps of lipid digestionSteps of lipid digestion In mouth, mechanical processing and In mouth, mechanical processing and
chemical digestion by chemical digestion by lingual lipaselingual lipase In stomach, lingual lipase continues to In stomach, lingual lipase continues to
function but can only access surface of function but can only access surface of lipid drops that have formedlipid drops that have formed
In duodenumIn duodenum Bile salts Bile salts break up lipid drops into smaller break up lipid drops into smaller
droplets (= droplets (= emulsificationemulsification) ) Pancreatic lipasePancreatic lipase digests triglycerides into digests triglycerides into
fatty acids, monoglycerides, and glycerolfatty acids, monoglycerides, and glycerol Forms Forms micelles micelles (lipid–bile salt complexes)(lipid–bile salt complexes)
LipoproteinsLipoproteins
TypesTypes ChylomicronsChylomicrons
Enter lymphEnter lymph VLDLVLDL LDLLDL
Transports Transports cholesterol to cellscholesterol to cells
HDLHDL Transports Transports
cholesterol from cholesterol from cells to livercells to liver
LipidsLipids
Absorption and transport of digested lipidsAbsorption and transport of digested lipids Lipids diffuse from micelle into intestinal epithelial Lipids diffuse from micelle into intestinal epithelial
cellcell Intracellular anabolic reactions synthesize new Intracellular anabolic reactions synthesize new
triglycerides from digested lipidstriglycerides from digested lipids New triglycerides packaged in New triglycerides packaged in chylomicrons chylomicrons ((chylos, chylos,
milky lymph, milky lymph, mikros, mikros, small) and released via small) and released via exocytosis exocytosis
Chylomicrons diffuse into intestinal lacteals due to Chylomicrons diffuse into intestinal lacteals due to their sizetheir size
Transported through lymphatic vessels (including Transported through lymphatic vessels (including thoracic duct) to bloodstreamthoracic duct) to bloodstream
Enzyme in capillaries (Enzyme in capillaries (lipoprotein lipaselipoprotein lipase) breaks ) breaks down chylomicron and releases digested lipids to down chylomicron and releases digested lipids to tissuestissues
LipidsLipids
Digested lipid distribution and Digested lipid distribution and processingprocessing
Tissues that use or process digested Tissues that use or process digested lipidslipids
Skeletal musclesSkeletal muscles Use fatty acids to generate ATP for contraction Use fatty acids to generate ATP for contraction
and to convert glucose to glycogenand to convert glucose to glycogen Adipose tissueAdipose tissue
Uses fatty acids and monoglycerides to synthesize Uses fatty acids and monoglycerides to synthesize triglycerides for storagetriglycerides for storage
Liver Liver Absorbs intact chylomicrons and extracts Absorbs intact chylomicrons and extracts
triglycerides and cholesterol from chylomicrontriglycerides and cholesterol from chylomicron
LipidsLipids
Cholesterol distributionCholesterol distribution Released from liver attached to Released from liver attached to low-density low-density
lipoproteins (LDL) lipoproteins (LDL) for distribution to peripheral for distribution to peripheral tissuestissues
LDLs absorbed and broken down by lysosomes in LDLs absorbed and broken down by lysosomes in cellscells
Cholesterol extracted and usedCholesterol extracted and used Unused cholesterol released into bloodstreamUnused cholesterol released into bloodstream
High-density lipoproteins (HDL)High-density lipoproteins (HDL) (plasma proteins (plasma proteins from liver) absorb peripheral cholesterol and return from liver) absorb peripheral cholesterol and return to liverto liver
Cholesterol released again with LDLs or excreted in Cholesterol released again with LDLs or excreted in bilebile
Ratio of LDL/HDL and total cholesterol used Ratio of LDL/HDL and total cholesterol used diagnostically for cardiovascular problemsdiagnostically for cardiovascular problems
Figure 22.5Figure 22.5
From the lacteals,the chylomicronsproceed along thelymphatic vesselsand into thethoracic duct.
The chylomicronsenter the bloodstreamat the left subclavianvein, then passthrough thepulmonary circuitbefore entering thesystemic circuit.
Capillary walls contain theenzyme lipoprotein lipase,which breaks down thechylomicrons and releasesfatty acids and monoglycer-ides that can diffuse into theinterstitial fluid.
The liver absorbs chylomicrons, removes thetriglycerides, combines the cholesterol from thechylomicron with synthesized or recycledcholesterol, and alters the surface proteins. It thenreleases low-density lipoproteins (LDLs) intothe circulation, which deliver cholesterol toperipheral tissues. Some of the cholesterol is usedby the liver to synthesize bile salts; excesscholesterol is excreted in the bile.
Lipoproteins and Lipid Transport and Distribution
The HDLs returnthe cholesterol tothe liver, where itis extracted andpackaged in newLDLs or excretedwith bile salts inbile.
Resting skeletal muscles absorb fattyacids and break them down, using theATP provided both to power thecontractions that maintain muscle tone and to convert glucose to glycogen.
Adipocytes absorbthe monoglyceridesand fatty acids,and use them tosynthesize triglycer-ides for storage.
The LDLs released by theliver leave the bloodstreamthrough capillary pores orcross the endothelium byvesicular transport.
Once in peripheral tissues,the LDLs are absorbed.
Chylomicrons
Excesscholesterol isexcreted withthe bile salts
LDL
Cholesterolrelease
Lysosomalbreakdown
Used in synthesisof membranes,hormones,other material
LDL
Triglyceridesremoved
Cholesterolextracted
Lowcholesterol
Highcholesterol
HDL
HDL
HDL
Thoracicduct
Clicker Question:Clicker Question:
The The Respiratory Rhythmicity Centre Respiratory Rhythmicity Centre (RRC) in the medulla contains:(RRC) in the medulla contains:
A) The apneustic centreA) The apneustic centre B) The dorsal respiratory groupB) The dorsal respiratory group C) The pneumotaxic centreC) The pneumotaxic centre D) The limbic systemD) The limbic system E) The cardioregulatory centreE) The cardioregulatory centre
Clicker Question:Clicker Question:
The neurones of the dorsal The neurones of the dorsal regulatory group:regulatory group:
A) Stimulate the muscles of expiration.A) Stimulate the muscles of expiration. B) Directly inhibit the muscles of B) Directly inhibit the muscles of
expirationexpiration C) Stimulate the muscles of inspirationC) Stimulate the muscles of inspiration D) Inhibit activity in the apneustic D) Inhibit activity in the apneustic
centrecentre
Clicker Question:Clicker Question:
The anatomic dead space:The anatomic dead space:
A) Consists of all the conducting zone A) Consists of all the conducting zone airways, including the upper tractairways, including the upper tract
B) Consists of the trachea, bronchi, and B) Consists of the trachea, bronchi, and bronchiole down to, and including, the bronchiole down to, and including, the respiratory bronchiolerespiratory bronchiole
C) The pharyngeal regionC) The pharyngeal region D) None of the aboveD) None of the above
Clicker Question:Clicker Question:
In order to do well on the final exam, In order to do well on the final exam, Students need to:Students need to:
A) Party hardA) Party hard B) Study hardB) Study hard C) Bribe the lecturerC) Bribe the lecturer D) Ask questions about processes they D) Ask questions about processes they
don’t understanddon’t understand E) B and D aboveE) B and D above
Large Intestine:Large Intestine:
Extends from ileocecal junction to anusExtends from ileocecal junction to anus Consists of cecum, colon, rectum, anal canalConsists of cecum, colon, rectum, anal canal Movements sluggish (Movements sluggish (18-24 hours18-24 hours))
Figure 21.15 Figure 21.15 11
The wall of the large intestine
Aggregatedlymphoidnodule Simple columnar
epithelium
Intestinal gland
Mucous cells
Muscularis mucosae
Submucosa
Muscularis Externa
Circular layer
Longitudinallayer (taenia coli)
Large intestineLarge intestine
General characteristics of the large General characteristics of the large intestineintestine
Also known as large bowelAlso known as large bowel Length is ~1.5 m (4.9 ft) and width is 7.5 cm (3 Length is ~1.5 m (4.9 ft) and width is 7.5 cm (3
in.)in.) Major functions during Major functions during mass movement mass movement
(peristalsis)(peristalsis)1.1. Reabsorption of water and Reabsorption of water and compactioncompaction of contents of contents
into fecesinto feces
2.2. Absorption of important vitamins liberated by Absorption of important vitamins liberated by bacterial actionbacterial action
3.3. Storage of feces prior to defecationStorage of feces prior to defecation Three segments: cecum, colon, rectumThree segments: cecum, colon, rectum
Large intestineLarge intestine
Large intestine segments and Large intestine segments and structuresstructures
Cecum Cecum (expanded pouch beginning (expanded pouch beginning colon)colon)
Begins Begins compaction compaction (compression into (compression into feces)feces)
Contains Contains ileocecal valveileocecal valve Has attached Has attached appendixappendix
~9 cm (3.6 in.) in length~9 cm (3.6 in.) in length Contains numerous lymphoid nodulesContains numerous lymphoid nodules Appendicitis Appendicitis (inflammation)(inflammation)
Large intestineLarge intestine
Large intestine segments and Large intestine segments and structures (continued)structures (continued)
ColonColon AscendingAscending
Along right margin of peritoneal cavity from cecum Along right margin of peritoneal cavity from cecum to to right colic flexureright colic flexure
TransverseTransverse Across abdomen from right colic flexure to Across abdomen from right colic flexure to left colic left colic
flexureflexure Descending Descending
Along left margin of peritoneal cavity from left colic Along left margin of peritoneal cavity from left colic flexure to flexure to sigmoid flexuresigmoid flexure
Sigmoid Sigmoid S-shaped last segment empties into rectumS-shaped last segment empties into rectum
Large intestineLarge intestine
Large intestine segments and Large intestine segments and structures (continued)structures (continued)
RectumRectum Forms last 15 cm (6 in.) of digestive tractForms last 15 cm (6 in.) of digestive tract Expandable for temporary feces storageExpandable for temporary feces storage Fecal material within rectum triggers Fecal material within rectum triggers
defecation urgedefecation urge
Figure 21.15 Figure 21.15 22
The characteristic features of the rectumRectum
Anal canal
Anal columns
Internal anal sphincter
External anal sphincter
Anus
Rectum, sectioned
Rectum
Large intestineLarge intestine
Other large intestine structuresOther large intestine structures Taeniae coliTaeniae coli
Three longitudinal muscle bands along outer Three longitudinal muscle bands along outer colon surfacecolon surface
Corresponds to muscularis externaCorresponds to muscularis externa
HaustraHaustra Pouches along colon wallPouches along colon wall Allow for expansion and elongation of colonAllow for expansion and elongation of colon
Fatty appendicesFatty appendices Teardrop-shaped fat sacs attached to serosaTeardrop-shaped fat sacs attached to serosa
Movement in Large Movement in Large IntestineIntestine
Mass movementsMass movements Common after mealsCommon after meals
Local reflexesLocal reflexes in enteric plexus in enteric plexus GastrocolicGastrocolic: Initiated by stomach: Initiated by stomach DuodenocolicDuodenocolic: Initiated by duodenum: Initiated by duodenum
Defecation reflexDefecation reflex Distension of the rectal wall by fecesDistension of the rectal wall by feces
DefecationDefecation Usually accompanied by voluntary movements to Usually accompanied by voluntary movements to
expel feces through abdominal cavity pressure expel feces through abdominal cavity pressure caused by inspirationcaused by inspiration
Transport and Secretion Transport and Secretion by Large Intestineby Large Intestine
Mucus provides protectionMucus provides protection Parasympathetic stimulation increases rate Parasympathetic stimulation increases rate
of goblet cell secretionof goblet cell secretion
Ion PumpsIon Pumps Exchange of bicarbonate ions for chloride Exchange of bicarbonate ions for chloride
ionsions Exchange of sodium ions for hydrogen ionsExchange of sodium ions for hydrogen ions
Bacterial actions produce gases called Bacterial actions produce gases called flatusflatus
Production and elimination of Production and elimination of fecesfeces
Large intestine characteristics associated with fecal Large intestine characteristics associated with fecal productionproduction Diameter is larger and wall is thinner than small Diameter is larger and wall is thinner than small
intestineintestine Lack of villiLack of villi Abundance of mucous cellsAbundance of mucous cells Many intestinal glands dominated by mucous glandsMany intestinal glands dominated by mucous glands
Mucus provides lubrication for drier and more Mucus provides lubrication for drier and more compact fecal materialcompact fecal material
No digestive enzymes producedNo digestive enzymes produced
Production and elimination Production and elimination of fecesof feces
Rectum and anal structureRectum and anal structure Anal canal Anal canal (distal portion of rectum)(distal portion of rectum)
Contains longitudinal folds (= Contains longitudinal folds (= anal columnsanal columns)) Epithelium transitions from columnar to stratified Epithelium transitions from columnar to stratified
squamous epitheliumsquamous epithelium Large network of veins contained within wallLarge network of veins contained within wall
Enlarged veins = Enlarged veins = hemorrhoidshemorrhoids Internal anal sphincter Internal anal sphincter (inner circular smooth muscle (inner circular smooth muscle
layer)layer) External anal sphincter External anal sphincter (outer skeletal muscle layer)(outer skeletal muscle layer) Anus Anus (exit of anal canal)(exit of anal canal)
Stratified epithelium becomes keratinizedStratified epithelium becomes keratinized
Production and elimination of Production and elimination of fecesfeces
Defecation reflexDefecation reflex Begins with distension of rectum wall Begins with distension of rectum wall
after arrival of fecesafter arrival of feces Involves two positive feedback loopsInvolves two positive feedback loops
1.1. Long reflexLong reflex Coordinated by sacral parasympathetic systemCoordinated by sacral parasympathetic system Stimulates mass movements in feces toward Stimulates mass movements in feces toward
rectum from descending and sigmoid colonrectum from descending and sigmoid colon
2.2. Short reflexShort reflex Stimulation of myenteric plexus to move feces in Stimulation of myenteric plexus to move feces in
sigmoid colon and rectumsigmoid colon and rectum
Water and Ions:Water and Ions:
WaterWater Can move in either Can move in either
direction across wall direction across wall of small intestine of small intestine depending on osmotic depending on osmotic gradientsgradients
IonsIons Sodium, potassium, Sodium, potassium,
calcium, magnesium, calcium, magnesium, phosphate are actively phosphate are actively transportedtransported
Figure 21.15 Figure 21.15 44
Voluntary relaxation of theexternal sphincter canoverride the contractiondirected by somatic motorneurons (L2a).
The first loop is ashort reflex thattriggers a seriesof peristalticcontractions in therectum that movefeces toward the anus.
Short Reflex
Long Reflex
If external sphincter is voluntarily relaxed,DEFECATION OCCURS
Involuntary contractionof external anal
sphincter
Relaxation of internalanal sphincter; fecesmove into anal canal
DISTENSIONOF RECTUM
Increased localperistalsis
Stimulation ofstretchreceptors
Start
Stimulation ofmyenteric plexus insigmoid colon andrectum
The long reflex iscoordinated by the sacralparasympathetic system.This reflex stimulates massmovements that push fecestoward the rectum from thedescending colon andsigmoid colon.
Increasedperistalsisthroughout largeintestine
Stimulation ofparasympatheticmotor neuronsin sacral spinalcord
Stimulation ofsomatic motorneurons
stimulates
inhibits
The events in the defecation reflex,which includes two positive feedback loops
Appetite regulationAppetite regulation
Appetite is controlled by two areas of Appetite is controlled by two areas of hypothalamushypothalamus1.1. Feeding centerFeeding center
2.2. Satiety centerSatiety center Causes inhibition of feeding centerCauses inhibition of feeding center
Regulation of appetite can occur on Regulation of appetite can occur on two levelstwo levels
1.1. Short-term regulationShort-term regulation
2.2. Long-term regulationLong-term regulation
Appetite regulationAppetite regulation
Short-term regulation of appetiteShort-term regulation of appetite Stimulation of satiety centerStimulation of satiety center
Elevation of blood glucose levelsElevation of blood glucose levels Hormones of digestive tract (like CCK)Hormones of digestive tract (like CCK) Digestive tract wall stretchingDigestive tract wall stretching
Stimulation of feeding centerStimulation of feeding center Neurotransmitters Neurotransmitters
Example: Example: neuropeptide Y or NPY neuropeptide Y or NPY from from hypothalamushypothalamus
GhrelinGhrelin Hormone secreted by gastric mucosa when stomach Hormone secreted by gastric mucosa when stomach
is emptyis empty
Appetite regulationAppetite regulation
Long-term regulation of appetiteLong-term regulation of appetite LeptinLeptin
Peptide hormone secreted by adipocytesPeptide hormone secreted by adipocytes Stimulates satiety center and suppresses Stimulates satiety center and suppresses
appetiteappetite Effects are gradualEffects are gradual
Figure Figure 22.1222.12
Short-Term Regulation of Appetite
Stimulation of Satiety Center
Elevated blood glucose levels depressappetite, and low blood glucosestimulates appetite. The likelymechanism is glucose entry stimulatingthe neurons of the satiety center.
Several hormones of the digestive tract,including CCK, suppress appetiteduring the absorptive state.
Stimulation of stretch receptors alongthe digestive tract, especially in thestomach, causes a sense of satiationand suppresses appetite.
Stimulation of Feeding Center
Several neurotransmitters havebeen linked to appetite regulation.Neuropeptide Y (NPY), for example,is a hypothalamic neurotransmitter that(among other effects) stimulates thefeeding center and increases appetite.
The hormone ghrelin (GREL-in),secreted by the gastric mucosa,stimulates appetite. Ghrelin levels arehigh when the stomach is empty, anddecline as the stomach fills.
Mechanisms in the controlof appetite
Hypothalamus
Satiety center
Feeding center
Long-Term Regulation of Appetite
When appetite outpaces energy usage,excess calories are stored as fat inadipose tissue. Leptin is a peptidehormone released by adipose tissuesas they synthesize triglycerides. In theCNS it stimulates the satiety centerand suppresses appetite. The effectsare gradual, and it is probably involvedin long-term regulation of food intake.
Effects of AgingEffects of Aging
Decrease in mucus layer, connective Decrease in mucus layer, connective tissue, muscles and secretionstissue, muscles and secretions
Increased susceptibility to infections Increased susceptibility to infections and toxic agentsand toxic agents Ulcerations and cancersUlcerations and cancers
Atherosclerosis is an Inflammatory Atherosclerosis is an Inflammatory DiseaseDisease
Ross R. N Engl J Med 1999;340:115-126.
EndotheliumEndothelium
Vessel LumenVessel Lumen
IntimaIntimaFoam CellFoam Cell
MonocyteMonocyte
CytokinesCytokines
Growth FactorsGrowth FactorsMetalloproteinasesMetalloproteinases
Cell ProliferationCell ProliferationMatrix DegradationMatrix Degradation MacrophageMacrophage
Lipoprotein Classes and Lipoprotein Classes and InflammationInflammation
Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000;149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.
HDLHDLLDLLDLChylomicrons,Chylomicrons,VLDL, and VLDL, and
their catabolic their catabolic remnantsremnants
> 30 nm> 30 nm 20–22 nm20–22 nm
Potentially proinflammatoryPotentially proinflammatory
9–15 nm9–15 nm
Potentially anti- Potentially anti- inflammatoryinflammatory
LDL is composed of a core of 1500 LDL is composed of a core of 1500 molecules of cholesterol enclosed in layers of molecules of cholesterol enclosed in layers of phospholipid and unesterified cholesterol phospholipid and unesterified cholesterol molecules. molecules.
A large protein called apoprotein B-100 is A large protein called apoprotein B-100 is embedded in this hydrophilic layer.embedded in this hydrophilic layer.
LDL is generated by the bodies fat-transport LDL is generated by the bodies fat-transport system via two mechanisms; the exogenous system via two mechanisms; the exogenous and the endogenous pathways. and the endogenous pathways.
Structure of LDLStructure of LDL
Murphy HC et al. Biochemistry 2000;39:9763-970.
Hydrophobic CoreHydrophobic Core of Triglyceride of Triglyceride and Cholesteryl and Cholesteryl EstersEsters
apoBapoB
Surface Surface Monolayer of Monolayer of Phospholipids Phospholipids and Free and Free CholesterolCholesterol
The exogenous pathway begins in the intestine, The exogenous pathway begins in the intestine, and commences as the dietary fats become and commences as the dietary fats become packaged into lipoprotein particles called packaged into lipoprotein particles called chylomicrons. chylomicrons.
Chylomicrons contain phospholipid, cholesterol, Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for example apo B48, apo apolipoproteins (apo), for example apo B48, apo A-1, apo 11, C –11 and apo-E. A-1, apo 11, C –11 and apo-E.
Chylomicrons contain phospholipid, cholesterol, Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for example apo B48, apo apolipoproteins (apo), for example apo B48, apo A-1, apo 11, C –11 and apo-E. A-1, apo 11, C –11 and apo-E.
Role of LDL in InflammationRole of LDL in Inflammation
Steinberg D et al. N Engl J Med 1989;320:915-924.
EndotheliumEndothelium
Vessel LumenVessel LumenLDLLDL
LDL Readily Enter the Artery Wall Where They May be ModifiedLDL Readily Enter the Artery Wall Where They May be Modified
LDLLDL
IntimaIntima
Modified LDLModified LDL
Modified LDL are ProinflammatoryModified LDL are Proinflammatory
Hydrolysis of PhosphatidylcholineHydrolysis of Phosphatidylcholineto Lysophosphatidylcholineto Lysophosphatidylcholine
Other Chemical ModificationsOther Chemical Modifications
Oxidation of LipidsOxidation of Lipidsand ApoBand ApoB
AggregationAggregation
Monocyte chemotactic protein-1
LDLLDL
LDLLDL
Modified LDL Stimulate Expression Modified LDL Stimulate Expression of MCP-1 in Endothelial Cellsof MCP-1 in Endothelial Cells
Navab M et al. J Clin Invest 1991;88:2039-2046.
EndotheliumEndothelium
Vessel LumenVessel Lumen
IntimaIntima
MonocyteMonocyte
Modified LDLModified LDL
MCP-1MCP-1
LDLLDL
LDLLDL
Differentiation of Monocytes into Differentiation of Monocytes into MacrophagesMacrophages
Steinberg D et al. N Engl J Med 1989;320:915-924.
EndotheliumEndothelium
Vessel LumenVessel Lumen
IntimaIntima
MonocyteMonocyte
Modified LDLModified LDL
Modified LDL PromoteModified LDL PromoteDifferentiation ofDifferentiation ofMonocytes intoMonocytes intoMacrophagesMacrophages
MCP-1MCP-1
MacrophageMacrophage
LDLLDL
LDLLDL
Modified LDL Induces Macrophages to Release Modified LDL Induces Macrophages to Release Cytokines That Stimulate Adhesion Molecule Cytokines That Stimulate Adhesion Molecule
Expression in Endothelial CellsExpression in Endothelial Cells
Nathan CF. J Clin Invest 1987;79:319-326.
EndotheliumEndothelium
Vessel LumenVessel LumenMonocyteMonocyte
Modified LDLModified LDL
MacrophageMacrophage
MCP-1MCP-1
AdhesionAdhesionMoleculesMolecules
CytokinesCytokines
IntimaIntima
LDLLDL
LDLLDLEndotheliumEndothelium
Vessel LumenVessel LumenMonocyteMonocyte
MacrophageMacrophage
MCP-1MCP-1
AdhesionAdhesionMoleculesMolecules
Steinberg D et al. N Engl J Med 1989;320:915-924.
Macrophages Express Receptors Macrophages Express Receptors That Take up Modified LDLThat Take up Modified LDL
Foam CellFoam Cell
Modified LDL Modified LDL Taken up by Taken up by MacrophageMacrophage
IntimaIntima
LDLLDL
LDLLDLEndotheliumEndothelium
Vessel LumenVessel LumenMonocyteMonocyte
MacrophageMacrophage
AdhesionAdhesionMoleculesMolecules
Macrophages and Foam Cells Macrophages and Foam Cells Express Growth Factors and Express Growth Factors and
ProteinasesProteinases
Foam CellFoam Cell
IntimaIntimaModified Modified
LDLLDLCytokinesCytokines
Cell ProliferationCell ProliferationMatrix DegradationMatrix Degradation
Growth FactorsGrowth FactorsMetalloproteinasesMetalloproteinases
Ross R. N Engl J Med 1999;340:115-126.
MCP-1MCP-1MCP-1MCP-1
Structure of HDLStructure of HDL
Rye KA et al. Atherosclerosis 1999;145:227-238.
Hydrophobic CoreHydrophobic Core of Triglyceride of Triglyceride and Cholesteryl and Cholesteryl EstersEsters
apoA-IIapoA-II
Surface Surface Monolayer of Monolayer of Phospholipids Phospholipids and Free and Free CholesterolCholesterol
apoA-IapoA-I
LDLLDL
LDLLDL
Miyazaki A et al. Biochim Biophys Acta 1992;1126:73-80.
EndotheliumEndothelium
Vessel LumenVessel LumenMonocyteMonocyte
Modified LDLModified LDL
MacrophageMacrophage
MCP-1MCP-1AdhesionAdhesionMoleculesMolecules
CytokinesCytokines
HDL Prevent Formation of Foam CellsHDL Prevent Formation of Foam Cells
IntimaIntimaHDL Promote Cholesterol EffluxHDL Promote Cholesterol Efflux
Foam Foam CellCell
LDLLDL
LDLLDL
Mackness MI et al. Biochem J 1993;294:829-834.
EndotheliumEndothelium
Vessel LumenVessel LumenMonocyteMonocyte
Modified LDLModified LDL
MacrophageMacrophage
MCP-1MCP-1AdhesionAdhesionMoleculesMolecules
CytokinesCytokines
HDL Inhibit the Oxidative Modification of LDLHDL Inhibit the Oxidative Modification of LDL
Foam Foam CellCell
HDL Promote Cholesterol EffluxHDL Promote Cholesterol EffluxIntimaIntima
HDL InhibitHDL InhibitOxidationOxidation
of LDLof LDL
LDLLDL
LDLLDL
Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.
EndotheliumEndothelium
Vessel LumenVessel LumenMonocyteMonocyte
Modified LDLModified LDL
MacrophageMacrophage
MCP-1MCP-1AdhesionAdhesionMoleculesMolecules
CytokinesCytokines
Inhibition of Adhesion MoleculesInhibition of Adhesion Molecules
IntimaIntima
HDL InhibitHDL InhibitOxidationOxidation
of LDLof LDL
HDL Inhibit Adhesion Molecule ExpressionHDL Inhibit Adhesion Molecule Expression
Foam Foam CellCell
HDL Promote Cholesterol EffluxHDL Promote Cholesterol Efflux
Macrophage Functions in Macrophage Functions in AtherogenesisAtherogenesis
Activation