Transcript 11 Digestive Physiology

Digestion, Absorption,
Transport
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Digestion
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Breakdown of food molecules for absorption into
circulation
Mechanical: Breaks large food particles to small
 Chemical: Breaking of covalent bonds by digestive
enzymes
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Absorption and transport
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Molecules are moved out of digestive tract and into
circulation for distribution throughout body
Digestive System Regulation
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Nervous regulation
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Involves enteric nervous
system
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Types of neurons: sensory,
motor, interneurons
Coordinates peristalsis
and regulates local
reflexes
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Chemical regulation
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Production of hormones
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Gastrin, secretin
Production of paracrine
chemicals
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Histamine
Help local reflexes in ENS
control digestive
environments as pH levels
Digestive System Anatomy
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Digestive tract
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Accessory organs
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Alimentary tract or
canal
GI tract
Primarily glands
Regions
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Mouth or oral cavity
Pharynx
Esophagus
Stomach
Small intestine
Large intestine
Anus
Peritoneum and Mesenteries
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Peritoneum
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Visceral: Covers organs
Parietal: Covers interior
surface of body wall
Retroperitoneal: Behind
peritoneum as kidneys,
pancreas, duodenum
Mesenteries
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Routes which vessels and
nerves pass from body wall to
organs
Greater omentum
Lesser omentum
Digestive Tract Histology
Oral Cavity
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Mouth or oral cavity
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Lips (labia) and
cheeks
Palate: Oral cavity
roof
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Vestibule: Space
between lips or cheeks
and alveolar processes
Oral cavity proper
Hard and soft
Palatine tonsils
Tongue: Involved in
speech, taste,
mastication,
swallowing
Teeth
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Two sets
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Primary, deciduous,
milk: Childhood
Permanent or
secondary: Adult (32)
Types
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Incisors, canine,
premolar and molars
Tooth structure:
Salivary Glands
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Produce saliva
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Prevents bacterial
infection
Lubrication
Contains salivary
amylase
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Breaks down starch
Three pairs
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Parotid: Largest
Submandibular
Sublingual: Smallest
Pharynx and Esophagus
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Pharynx
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Nasopharynx
Oropharynx: Transmits
food normally
Laryngopharynx:
Transmits food
normally
Esophagus
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Transports food from
pharynx to stomach
Passes through esophageal
hiatus (opening) of
diaphragm and ends at
stomach
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Hiatal hernia
Sphincters
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Upper
Lower
Phases of Deglutition
(Swallowing)
Deglutition (Swallowing)
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Three phases
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Voluntary
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Bolus of food moved by tongue from oral cavity to
pharynx
Pharyngeal
Reflex: Upper esophageal sphincter relaxes, elevated
pharynx opens the esophagus, food pushed into
esophagus
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Esophageal
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Reflex: Epiglottis is tipped posteriorly, larynx elevated
to prevent food from passing into larynx
Functions
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Ingestion: Introduction of food into stomach
Mastication: Chewing
Propulsion
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Deglutition: Swallowing
Peristalsis: Moves material through digestive tract
Stomach Anatomy:
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Openings
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Gastroesophageal:
To esophagus
Pyloric: To
duodenum
Regions
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Cardiac
Fundus
Body
Pyloric
Stomach Anatomy cont.
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Rugae: Folds in stomach when empty
Gastric pits: Openings for gastric glands
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Contain cells
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Surface mucous: Mucus
Mucous neck: Mucus
Parietal: Hydrochloric acid and intrinsic factor
Chief: Pepsinogen
Endocrine: Regulatory hormones
Stomach Histology:
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Layers
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Serosa or visceral
peritoneum:
Outermost
Muscularis: Three
layers
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Outer longitudinal
Middle circular
Inner oblique
Submucosa
Mucosa
Phases of Gastric Activity I
Hydrochloric Acid Production
Phases of Gastric Activity II
Movements in Stomach
Phases of Gastric Activity III
Gastric hormones:
Small Intestine
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Site of greatest amount of
digestion and absorption
Divisions
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Modifications
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Duodenum
Jejunum
Ileum: Peyer’s patches or
lymph nodules
Circular folds or plicae
circulares, villi, lacteal,
microvilli
Cells of mucosa
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Absorptive, goblet, granular,
endocrine
Small Intestine Secretions
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Mucus
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Digestive enzymes
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Protects against digestive enzymes and stomach acids
Disaccharidases: Break down disaccharides to
monosaccharides
Peptidases: Hydrolyze peptide bonds
Nucleases: Break down nucleic acids
Duodenal glands
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Stimulated by vagus nerve, secretin, chemical or tactile
irritation of duodenal mucosa
Movement in small intestine:
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Mixing: Segmental contraction that occurs in small intestine
Secretion: Lubricate, liquefy, digest
Digestion: Mechanical and chemical
Absorption: Movement from tract into circulation or lymph
Elimination: Waste products removed from body
Accessory Glands and Structures
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Liver
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Exocrine Pancreas
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Gall bladder
Pancreatic duct
Hepatic Portal System
Duodenum and Pancreas
Duct System
Gallbladder
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Bile is stored and concentrated
Stimulated by cholecystokinin and vegal
stimulation
Dumps into small intestine
Production of gallstones possible
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Drastic dieting with rapid weight loss
Liver
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Lobes
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Major: Left and right
Minor: Caudate and
quadrate
Ducts
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Common hepatic
Cystic
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From gallbladder
Common bile
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Joins pancreatic duct at
hepatopancreatic ampulla
Functions of the Liver
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Bile production
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Storage
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Hepatocytes remove ammonia and convert to urea
Phagocytosis
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Glycogen, fat, vitamins, copper and iron
Nutrient interconversion
Detoxification
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Salts emulsify fats, contain pigments as bilirubin
Kupffer cells phagocytize worn-out and dying red and white blood cells,
some bacteria
Synthesis
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Albumins, fibrinogen, globulins, heparin, clotting factors
Bile
…each day around 600 ml of bile is produced…
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Bile acid
Phospholipids
Cholesterol
Bilirubin
Waste products
Electrolytes
Mucin
Blood and Bile Flow
Pancreas
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Anatomy
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Endocrine
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Exocrine
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Pancreatic islets produce
insulin and glucagon
Acini produce digestive
enzymes
Regions: Head, body, tail
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Secretions
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Pancreatic juice (exocrine)
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Trypsin
Chymotrypsin
Carboxypeptidase
Pancreatic amylase
Pancreatic lipases
Enzymes that reduce DNA
and ribonucleic acid
Exocrine Pancreas –
Enzymes
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Trypsinogen
Chymotrysinogen
Carboxypeptidases
Pro-elastase
Phospholipase
pancreatic lipase
Pancreatic amylase
Enzymes that reduce DNA and ribonucleic acid
Bicarbonate Ion Production
Lipoproteins
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Types
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Chylomicrons
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VLDL
LDL
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Enter lymph
Transports cholesterol
to cells
HDL
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Transports cholesterol
from cells to liver
Large Intestine
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Cecum
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Colon
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Ascending, transverse, descending, sigmoid
Rectum
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Blind sac, vermiform appendix attached
Straight muscular tube
Anal canal
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Internal anal sphincter (smooth muscle)
External anal sphincter (skeletal muscle)
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Hemorrhoids: Vein enlargement or inflammation
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Large Intestine:
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Extends from ileocecal junction to anus
Consists of cecum, colon, rectum, anal canal
Movements sluggish (18-24 hours)
Histology of Large Intestine
Transport and Secretion by Large
Intestine
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Mucus provides protection
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Parasympathetic stimulation increases rate of goblet
cell secretion
Pumps
Exchange of bicarbonate ions for chloride ions
 Exchange of sodium ions for hydrogen ions
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Bacterial actions produce gases called flatus
Water and Ions:
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Water
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Can move in either direction
across wall of small intestine
depending on osmotic
gradients
Ions
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Sodium, potassium, calcium,
magnesium, phosphate are
actively transported
Movement in Large Intestine
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Mass movements
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Local reflexes in enteric plexus
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Gastrocolic: Initiated by stomach
Duodenocolic: Initiated by duodenum
Defecation reflex
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Common after meals
Distension of the rectal wall by feces
Defecation
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Usually accompanied by voluntary movements to expel feces
through abdominal cavity pressure caused by inspiration
Reflexes in
Colon and
Rectum:
Effects of Aging
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Decrease in mucus layer, connective tissue,
muscles and secretions
Increased susceptibility to infections and toxic
agents
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Ulcerations and cancers
Atherosclerosis is an Inflammatory Disease
Vessel Lumen
Monocyte
Endothelium
Cytokines
Growth Factors
Metalloproteinases
Cell Proliferation
Matrix Degradation
Foam Cell
Ross R. N Engl J Med 1999;340:115-126.
Macrophage
Intima
Lipoprotein Classes and Inflammation
Chylomicrons,
VLDL, and
their catabolic
remnants
LDL
HDL
> 30 nm 20–22 nm 9–15 nm
Potentially proinflammatory
Potentially antiinflammatory
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-
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LDL is composed of a core of 1500
molecules of cholesterol enclosed in layers
of phospholipid and unesterified cholesterol
molecules.
A large protein called apoprotein B-100 is
embedded in this hydrophilic layer.
LDL is generated by the bodies fat-transport
system via two mechanisms; the exogenous
and the endogenous pathways.
Structure of LDL
Surface
Monolayer of
Phospholipids
and Free
Cholesterol
apoB
Hydrophobic Core
of Triglyceride
and Cholesteryl
Esters
Murphy HC et al. Biochemistry 2000;39:9763-970.
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The exogenous pathway begins in the
intestine, and commences as the dietary fats
become packaged into lipoprotein particles
called chylomicrons.
Chylomicrons contain phospholipid,
cholesterol, apolipoproteins (apo), for
example apo B48, apo A-1, apo 11, C –11
and apo-E.
Chylomicrons contain phospholipid,
cholesterol, apolipoproteins (apo), for
example apo B48, apo A-1, apo 11, C –11
and apo-E.
Role of LDL in Inflammation
LDL Readily Enter the Artery Wall Where They May be Modified
Vessel Lumen
LDL
Endothelium
Oxidation of Lipids
and ApoB
Aggregation
LDL
Hydrolysis of Phosphatidylcholine
to Lysophosphatidylcholine
Other Chemical Modifications
Modified LDL
Modified LDL are Proinflammatory
Steinberg D et al. N Engl J Med 1989;320:915-924.
Intima
Modified LDL Stimulate Expression of MCP-1
in Endothelial Cells
Vessel Lumen
Monocyte
LDL
MCP-1 LDL
Endothelium
Modified LDL
Monocyte chemotactic protein-1
Navab M et al. J Clin Invest 1991;88:2039-2046.
Intima
Differentiation of Monocytes into Macrophages
Vessel Lumen
Monocyte
LDL
MCP-1
Endothelium
LDL
Intima
Modified LDL
Macrophage
Steinberg D et al. N Engl J Med 1989;320:915-924.
Modified LDL Promote
Differentiation of
Monocytes into
Macrophages
Modified LDL Induces Macrophages to Release Cytokines That
Stimulate Adhesion Molecule Expression in Endothelial Cells
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
MCP-1
Cytokines
Endothelium
LDL
Modified LDL
Macrophage
Nathan CF. J Clin Invest 1987;79:319-326.
Intima
Macrophages Express Receptors That Take up
Modified LDL
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
MCP-1
Endothelium
LDL
Modified
LDL Taken
up by
Macrophage
Foam Cell
Macrophage
Steinberg D et al. N Engl J Med 1989;320:915-924.
Intima
Macrophages and Foam Cells Express Growth
Factors and Proteinases
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
Cytokines
Macrophage
MCP-1
LDL
Modified
LDL
Foam Cell
Ross R. N Engl J Med 1999;340:115-126.
Endothelium
Intima
Growth Factors
Metalloproteinases
Cell Proliferation
Matrix Degradation
The Remnants of VLDL and
Chylomicrons are Also
Proinflammatory
Monocyte
Vessel Lumen
Remnant Lipoproteins
Adhesion
Molecules
Cytokines
Macrophage
Endothelium
MCP-1
Remnants
Modified
Remnants
Foam Cell
Doi H et al. Circulation 2000;102:670-676.
Intima
Growth Factors
Metalloproteinases
Cell Proliferation
Matrix Degradation
Structure of HDL
apoA-I
apoA-II
Rye KA et al. Atherosclerosis 1999;145:227-238.
Surface
Monolayer of
Phospholipids
and Free
Cholesterol
Hydrophobic Core
of Triglyceride
and Cholesteryl
Esters
HDL Prevent Formation of Foam Cells
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
MCP-1
Endothelium
LDL
Modified LDL
Cytokines
Macrophage
Foam
Cell
HDL Promote Cholesterol
Efflux
Miyazaki A et al. Biochim Biophys Acta 1992;1126:73-80.
Intima
HDL Inhibit the Oxidative Modification of
LDL
Vessel Lumen
Monocyte
LDL
Adhesion
Molecules
MCP-1
Endothelium
LDL
Modified LDL
Cytokines
Macrophage
Foam
Cell
HDL Promote Cholesterol
Efflux
Mackness MI et al. Biochem J 1993;294:829-834.
HDL
Inhibit
Oxidation
of LDL
Intima
Inhibition of Adhesion Molecules
HDL Inhibit Adhesion Molecule
Expression
LDL Vessel Lumen
Monocyte
Adhesion
Molecules
MCP-1
Endothelium
LDL
Modified LDL
Cytokines
Macrophage
HDL Inhibit
Oxidation
of LDL
Foam
Cell
HDL Promote Cholesterol
Efflux
Intima
Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.
Macrophage Functions in Atherogenesis
Activation