Figure 22 Section 2 Steps in the Process of Digestion In the oral cavity, saliva dissolves some organic nutrients, and mechanical processing with the

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


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


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


Plica circulares

Villi




Intestinal gland

Muscularis mucosae

Lymphoid nodule

Submucosal plexus


Myenteric plexus


Lymphatic vessel

Serosa

Muscularisexterna

Submucosa

Mucosa




Plica circulares

Villi





Intestinal gland

Muscularis mucosae

Lymphoid nodule

Submucosal plexus


Myenteric plexus


Lymphatic vessel

Serosa

Muscularisexterna

Submucosa

Mucosa


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


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.


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


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


Amino acids

CapillaryCapillary

Dipeptidases

TrypsinChymotrypsinElastaseCarboxypeptidase

Pepsin

Monosaccharides

FACILITATEDDIFFUSION

TrisaccharidesDisaccharides


Monosaccharides


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


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


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)


ORAL CAVITY

ESOPHAGUS

STOMACH




SMALL INTESTINE



Hormone: CCK


INTESTINAL MUCOSA

BLOODSTREAM

(a) (b) (c)


EXOCYTOSIS


micelles


Triglycerides

Chylomicrons

Chylomicrons

Lacteal


Lingual lipase

DIFFUSION

PROTEINS

Polypeptides

Amino acids



Amino acids

CapillaryCapillary

Dipeptidases


Pepsin

Monosaccharides




Monosaccharides


Salivary amylase


CARBOHYDRATES



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


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


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


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


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


ORAL CAVITY

ESOPHAGUS

STOMACH




SMALL INTESTINE



Hormone: CCK


INTESTINAL MUCOSA

BLOODSTREAM

(a) (b) (c)


EXOCYTOSIS


micelles


Triglycerides

Chylomicrons

Chylomicrons

Lacteal


Lingual lipase

DIFFUSION

PROTEINS

Polypeptides

Amino acids



Amino acids

CapillaryCapillary

Dipeptidases


Pepsin

Monosaccharides




Monosaccharides


Salivary amylase


CARBOHYDRATES



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


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


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


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


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))


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 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 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 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


The characteristic features of the rectumRectum

Anal canal

Anal columns

Internal anal sphincter

External anal sphincter

Anus

Rectum, sectioned

Rectum


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


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


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


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.


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.



IntimaIntima

MonocyteMonocyte


MCP-1MCP-1

LDLLDL

LDLLDL

Differentiation of Monocytes into Differentiation of Monocytes into MacrophagesMacrophages




IntimaIntima

MonocyteMonocyte


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.


Vessel LumenVessel LumenMonocyteMonocyte



MCP-1MCP-1

AdhesionAdhesionMoleculesMolecules

CytokinesCytokines

IntimaIntima

LDLLDL

LDLLDLEndotheliumEndothelium



MCP-1MCP-1



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




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.





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.






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.






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

Documents

Figure 22 Section 2 Steps in the Process of Digestion In the oral cavity, saliva dissolves some organic nutrients, and mechanical processing with the