Digestion, Absorption, Transport Digestion Digestion Breakdown of food molecules for absorption into circulation Breakdown of food molecules for absorption

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,

milk: Childhoodmilk: 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

Pharynx and EsophagusPharynx and Esophagus

PharynxPharynx NasopharynxNasopharynx Oropharynx: Oropharynx:

Transmits food Transmits food normallynormally

Laryngopharynx: Laryngopharynx: Transmits food Transmits food normallynormally

EsophagusEsophagus Transports food from Transports food from

pharynx to stomachpharynx to stomach Passes through Passes through

esophageal hiatus esophageal hiatus (opening) of (opening) of diaphragm and ends diaphragm and ends at stomachat stomach

Hiatal herniaHiatal hernia SphinctersSphincters

UpperUpper LowerLower

Phases of Deglutition Phases of Deglutition (Swallowing)(Swallowing)

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

FunctionsFunctions IngestionIngestion: Introduction of food into stomach: Introduction of food into stomach MasticationMastication: Chewing: Chewing PropulsionPropulsion

Deglutition: SwallowingDeglutition: Swallowing Peristalsis: Moves material through digestive Peristalsis: Moves material through digestive

tracttract

Stomach Anatomy:Stomach Anatomy:

OpeningsOpenings GastroesophaGastroesopha

gealgeal: To : To esophagusesophagus

PyloricPyloric: To : To duodenumduodenum

RegionsRegions CardiacCardiac FundusFundus BodyBody PyloricPyloric

Stomach Anatomy Stomach Anatomy cont.cont.

RugaeRugae: Folds in stomach when empty: Folds in stomach when empty Gastric pitsGastric pits: Openings for gastric glands: 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

Stomach Histology:Stomach Histology: LayersLayers

Serosa or visceral Serosa or visceral peritoneum: peritoneum: OutermostOutermost

Muscularis: Three Muscularis: Three layerslayers

Outer longitudinalOuter longitudinal Middle circularMiddle circular Inner oblique Inner oblique

SubmucosaSubmucosa MucosaMucosa

Phases of Gastric Activity Phases of Gastric Activity I I

Hydrochloric Acid Hydrochloric Acid ProductionProduction

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

Gastric hormones:Gastric hormones:

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

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

Movement in small Movement in small intestine:intestine:

Mixing: Segmental contraction that occurs in small Mixing: Segmental contraction that occurs in small intestineintestine

Secretion: Lubricate, liquefy, digestSecretion: Lubricate, liquefy, digest Digestion: Mechanical and chemicalDigestion: Mechanical and chemical Absorption: Movement from tract into circulation or lymphAbsorption: Movement from tract into circulation or lymph Elimination: Waste products removed from bodyElimination: Waste products removed from body

Accessory Glands and Accessory Glands and StructuresStructures

LiverLiver Gall bladderGall bladder

Exocrine PancreasExocrine Pancreas Pancreatic ductPancreatic duct

Hepatic Portal SystemHepatic Portal System

Duodenum and Duodenum and PancreasPancreas

Duct SystemDuct System

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

BileBile

Bile acidBile acid PhospholipidsPhospholipids CholesterolCholesterol BilirubinBilirubin Waste productsWaste products ElectrolytesElectrolytes MucinMucin

…each day around 600 ml of bile is produced…

Blood and Bile FlowBlood and Bile Flow

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

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

Bicarbonate Ion Bicarbonate Ion ProductionProduction

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

Large IntestineLarge Intestine

CecumCecum Blind sac, vermiform appendix attachedBlind sac, vermiform appendix attached

ColonColon Ascending, transverse, descending, sigmoidAscending, transverse, descending, sigmoid

RectumRectum Straight muscular tubeStraight muscular tube

Anal canalAnal canal Internal anal sphincter (smooth muscle) Internal anal sphincter (smooth muscle) External anal sphincter (skeletal muscle) External anal sphincter (skeletal muscle) Hemorrhoids: Vein enlargement or inflammationHemorrhoids: Vein enlargement or inflammation

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))

Histology of Large Histology of Large IntestineIntestine

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

PumpsPumps 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

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

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

Reflexes inReflexes in Colon and Colon and Rectum:Rectum:

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 nmPotentially proinflammatoryPotentially proinflammatory

9–15 nm9–15 nmPotentially 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 The exogenous pathway begins in the intestine, and commences as the dietary fats intestine, and commences as the dietary fats become packaged into lipoprotein particles become packaged into lipoprotein particles called chylomicrons. called chylomicrons.

Chylomicrons contain phospholipid, Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for cholesterol, apolipoproteins (apo), for example apo B48, apo A-1, apo 11, C –11 and example apo B48, apo A-1, apo 11, C –11 and apo-E. apo-E.

Chylomicrons contain phospholipid, Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for cholesterol, apolipoproteins (apo), for example apo B48, apo A-1, apo 11, C –11 and example apo B48, apo A-1, apo 11, C –11 and apo-E. 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 Modified LDL Taken LDL Taken

up by up by MacrophagMacrophag

eeIntimaIntima

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


Ross R. N Engl J Med 1999;340:115-126.

MCP-1MCP-1MCP-1MCP-1




MCP-1MCP-1MCP-1MCP-1AdhesionAdhesionMoleculesMolecules

The Remnants of VLDL and The Remnants of VLDL and Chylomicrons are Also Chylomicrons are Also ProinflammatoryProinflammatory

Foam CellFoam Cell

IntimaIntimaModifiedModifiedRemnantsRemnantsCytokinesCytokines

Cell ProliferationCell ProliferationMatrix DegradationMatrix Degradation

Doi H et al. Circulation 2000;102:670-676.


Remnant LipoproteinsRemnant Lipoproteins

RemnantsRemnants

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 HDL Prevent Formation of Foam CellsCells

IntimaIntimaHDL Promote Cholesterol HDL Promote Cholesterol EffluxEfflux

Foam Foam CellCell

LDLLDL

LDLLDL

Mackness MI et al. Biochem J 1993;294:829-834.






CytokinesCytokines

HDL Inhibit the Oxidative Modification of HDL Inhibit the Oxidative Modification of LDLLDL

Foam Foam CellCell

HDL Promote Cholesterol HDL Promote Cholesterol EffluxEfflux

IntimaIntima

HDL HDL InhibitInhibit

OxidationOxidationof 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 HDL Inhibit Adhesion Molecule ExpressionExpression

Foam Foam CellCell

HDL Promote Cholesterol HDL Promote Cholesterol EffluxEfflux

Macrophage Functions in Macrophage Functions in AtherogenesisAtherogenesis

Activation

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Digestion, Absorption, Transport Digestion Digestion Breakdown of food molecules for absorption into circulation Breakdown of food molecules for absorption