Transcript 11 Digestive Physiology

Steps in the Process of Digestion
In the oral cavity, saliva dissolves some organic
nutrients, and mechanical processing with
the teeth and tongue disrupts the physical
structure of the material and provides access
for digestive enzymes. Those enzymes begin
the digestion of complex carbohydrates
(polysaccharides) and lipids.
In the stomach, the material is further broken
down physically and chemically by stomach
acid and by enzymes that can operate at an
extremely low pH.
In the duodenum, buffers from the pancreas and
liver moderate the pH of the arriving chyme, and
various digestive enzymes are secreted by the
pancreas that catalyze the catabolism of
carbohydrates, lipids, proteins, and nucleic acids.
Nutrient absorption then occurs in the small
intestine, primarily in the jejunum, and the
nutrients enter the bloodstream.
Indigestible materials and wastes enter the large
intestine, where water is reabsorbed and bacterial
action generates both organic nutrients and
vitamins. These organic products are absorbed
before the residue is ejected at the anus.
Most of the nutrients absorbed by the digestive
tract end up in a tributary of the hepatic portal
vein that ends at the liver. The liver absorbs
nutrients as needed to maintain normal levels
in the systemic circuit.
Within peripheral tissues, cells absorb the
nutrients needed to maintain their nutrient pool
and ongoing operations.
Figure 22 Section 2
Digestion, Absorption,
Transport

Digestion

Breakdown of food molecules for absorption into
circulation
Mechanical: Breaks large food particles to small
 Chemical: Breaking of covalent bonds by digestive
enzymes


Absorption and transport

Molecules are moved out of digestive tract and into
circulation for distribution throughout body
Digestive System Regulation

Nervous regulation

Involves enteric nervous
system


Types of neurons: sensory,
motor, interneurons
Coordinates peristalsis
and regulates local
reflexes

Chemical regulation

Production of hormones


Gastrin, secretin
Production of paracrine
chemicals


Histamine
Help local reflexes in ENS
control digestive
environments as pH levels
Digestive System Anatomy

Digestive tract



Accessory organs


Alimentary tract or
canal
GI tract
Primarily glands
Regions







Mouth or oral cavity
Pharynx
Esophagus
Stomach
Small intestine
Large intestine
Anus
Peritoneum and Mesenteries

Peritoneum




Visceral: Covers organs
Parietal: Covers interior
surface of body wall
Retroperitoneal: Behind
peritoneum as kidneys,
pancreas, duodenum
Mesenteries



Routes which vessels and
nerves pass from body wall to
organs
Greater omentum
Lesser omentum
Digestive Tract Histology
Oral Cavity

Mouth or oral cavity




Lips (labia) and
cheeks
Palate: Oral cavity
roof



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

Two sets



Primary, deciduous, or
milk: Childhood
Permanent or
secondary: Adult (32)
Types

Incisors, canine,
premolar and molars
Tooth structure:
Salivary Glands

Produce saliva



Prevents bacterial
infection
Lubrication
Contains salivary
amylase


Breaks down starch
Three pairs



Parotid: Largest
Submandibular
Sublingual: Smallest
Deglutition (Swallowing)

Three phases

Voluntary


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

Esophageal

Reflex: Epiglottis is tipped posteriorly, larynx elevated
to prevent food from passing into larynx
Phases of Deglutition (Swallowing)
The process of peristalsis
Bolus of food
arrives in
digestive
system.
Food
bolus
Toward
anus
Longitudinal
muscle
Circular muscle
Circular muscles
contract behind
bolus.
Longitudinal
muscles ahead
of bolus
contract.
Contraction in
circular muscle
layer forces
bolus forward.
Stomach Anatomy:

Openings



Gastroesophageal:
To esophagus
Pyloric: To
duodenum
Regions




Cardiac
Fundus
Body
Pyloric
Stomach Anatomy cont.


Rugae: Folds in stomach when empty
Gastric pits: Openings for gastric glands

Contain cells





Surface mucous: Mucus
Mucous neck: Mucus
Parietal: Hydrochloric acid and intrinsic factor
Chief: Pepsinogen
Endocrine: Regulatory hormones
The structure of the wall of the stomach
Layers of the Stomach Wall
Mucosa
Consists of a simple columnar
epithelium that produces an alkaline
carpet of mucus that covers the interior
surfaces of the stomach and protects
epithelial cells against the acid and
enzymes in the gastric lumen
Lamina propria
Lymphatic vessel
Muscularis mucosae
Artery and vein
Submucosa
Muscularis Externa
Oblique muscle
Circular muscle
Longitudinal muscle
Serosa
Myenteric plexus
The structure of gastric pits and gastric glands
Lamina propria
Mucous epithelial cells
Gastric pit
Neck
Cells of Gastric Glands
Parietal cells
(secrete HCl and
intrinsic factor)
G cells
(produce a variety
of hormones)
Gastric glands
Chief cells
(secrete pepsinogen)
Figure 21.9
2
The secretory activities of parietal cells
Hydrogen ions (H+) are
generated inside a parietal
cell as the enzyme carbonic
anhydrase converts CO2 and
H2O to carbonic acid (H2CO3),
which then dissociates.
Diffusion
Carbonic
anhydrase
A countertransport mechanism
ejects the bicarbonate ions into
the interstitial fluid and imports
chloride ions into the cell.
Interstitial
fluid
To
bloodstream
KEY
Parietal cell
The chloride ions then diffuse
across the cell and exit through
open chloride channels into the
lumen of the gastric gland.
Carrier-mediated
transport
The hydrogen ions are
actively transported into the
lumen of the gastric gland.
Active transport
Countertransport
Lumen of
gastric
gland
Figure 21.9
3
Phases of Gastric Activity I
Phases of Gastric Activity II
Movements in Stomach
Phases of Gastric Activity III
Ingested
food
The pattern of hormone release and the effects of those
hormones within the digestive system
Hormone
Action
KEY
Food in
stomach
inhibits
Acid production by
parietal cells
stimulates
Gastrin
Stimulation of gastric
motility; mixing waves
increase in intensity
GIP
Chyme in
duodenum
Release of insulin
from pancreas
Release of pancreatic
enzymes and buffers
Secretin
and CCK
VIP
Bile secretion and
ejection of bile from
gallbladder
facilitates
Dilation of intestinal
capillaries
facilitates
Material
arrives in
jejunum
Nutrient absorption
NUTRIENT
UTILIZATION
BY ALL TISSUES
The two central reflexes triggered by the
stimulation of stretch receptors in the
stomach wall
Central Gastric
Reflexes
Gastroenteric reflex:
stimulates motility
and secretion along
the entire small
intestine
Gastroileal reflex:
triggers the opening
of the ileocecal valve,
allowing materials to
pass from the small
intestine into the
large intestine
Ileocecal valve
Figure 21.13 2
Small Intestine


Site of greatest amount of
digestion and absorption
Divisions




Modifications


Duodenum
Jejunum
Ileum: Peyer’s patches or
lymph nodules
Circular folds or plicae
circulares, villi, lacteal,
microvilli
Cells of mucosa

Absorptive, goblet, granular,
endocrine
The characteristic features of each of the
three segments of the small intestine
Jejunum
Serosa
Duodenum
Muscularis
externa
Duodenal glands
Plicae
circulares
Villi
Submucosa
Mucosa
Muscularis
mucosae
Ileum
Aggregated lymphoid nodules
Figure 21.11 2
Small Intestine Secretions

Mucus


Digestive enzymes




Protects against digestive enzymes and stomach acids
Disaccharidases: Break down disaccharides to
monosaccharides
Peptidases: Hydrolyze peptide bonds
Nucleases: Break down nucleic acids
Duodenal glands

Stimulated by vagus nerve, secretin, chemical or tactile
irritation of duodenal mucosa
Mixing:
Segmental contraction
that occurs in small
intestine
Involves contraction of
circular muscles only
Intestinal adaptations for absorbing nutrients
A photomicrograph showing the brush
border of an intestinal villus
The structure of an intestinal villus
Plica circulares
Capillaries
The complex internal structure of
an intestinal villus
Villi
Mucous cells
A plica circulares and villi
in the small intestinal wall
Lacteal
Brush border
Tip of villus
A diagrammatic sectional view of the intestinal wall showing features
common to all segments of
Villi
Submucosal
Lacteal
the small intestine
artery and vein
(lymphatic
Columnar epithelial cell
Mucous cell
capillary)
Lacteal
Nerve
Layers of the
Small Intestine
Intestinal gland
Capillary network
Mucosa
Arteriole
Muscularis mucosae
Lymphatic vessel
Lamina propria
Venule
Lymphoid nodule
Submucosa
Submucosal plexus
Circular layer of
smooth muscle
Muscularis
externa
Myenteric plexus
Serosa
Longitudinal layer
of smooth muscle
Lymphatic vessel
Muscles that move the villi
back and forth to expose
the epithelial surfaces to
the intestinal contents
Muscularis mucosae
Figure 21.10
LM x 250
Intestinal adaptations for absorbing nutrients
Plica circulares
Villi
A plica circulares and villi
in the small intestinal wall
A diagrammatic sectional view of the intestinal wall showing features
common to all segments of
Lacteal
Submucosal
Villi
the small intestine
(lymphatic
artery and vein
capillary)
Layers of the
Small Intestine
Intestinal gland
Mucosa
Muscularis mucosae
Lymphoid nodule
Submucosa
Submucosal plexus
Circular layer of
smooth muscle
Muscularis
externa
Myenteric plexus
Serosa
Longitudinal layer
of smooth muscle
Lymphatic vessel
Figure 21.10 1
–
3
Plica circulares
Villi
A plica circulares and villi
in the small intestinal wall
Figure 21.10 2
A diagrammatic sectional view of the intestinal wall showing features
common to all segments of
Lacteal
Submucosal
Villi
(lymphatic
the small intestine
artery and vein
capillary)
Layers of the
Small Intestine
Intestinal gland
Mucosa
Muscularis mucosae
Lymphoid nodule
Submucosa
Submucosal plexus
Circular layer of
smooth muscle
Muscularis
externa
Myenteric plexus
Serosa
Longitudinal layer
of smooth muscle
Lymphatic vessel
Figure 21.10 3
A photomicrograph showing the brush
border of an intestinal villus
The structure of an intestinal villus
Capillaries
The complex internal structure of
an intestinal villus
Mucous cells
Lacteal
Brush border
Tip of villus
LM x 250
Columnar epithelial cell
Mucous cell
Lacteal
Nerve
Capillary network
Arteriole
Lymphatic vessel
Lamina propria
Venule
Muscles that move the villi
back and forth to expose
the epithelial surfaces to
the intestinal contents
Muscularis mucosae
Figure 21.10 4
–
5
Accessory Glands and Structures

Liver


Exocrine Pancreas


Gall bladder
Pancreatic duct
Hepatic Portal System
Duct System
Pancreas

Anatomy

Endocrine


Exocrine


Pancreatic islets produce
insulin and glucagon
Acini produce digestive
enzymes
Regions: Head, body, tail

Secretions

Pancreatic juice (exocrine)






Trypsin
Chymotrypsin
Carboxypeptidase
Pancreatic amylase
Pancreatic lipases
Enzymes that reduce DNA
and ribonucleic acid
Duodenum and Pancreas
Exocrine Pancreas –
Enzymes








Trypsinogen
Chymotrysinogen
Carboxypeptidases
Pro-elastase
Phospholipase
pancreatic lipase
Pancreatic amylase
Enzymes that reduce DNA and ribonucleic acid
Gallbladder




Bile is stored and concentrated
Stimulated by cholecystokinin and vegal
stimulation
Dumps into small intestine
Production of gallstones possible

Drastic dieting with rapid weight loss
Liver

Lobes



Major: Left and right
Minor: Caudate and
quadrate
Ducts


Common hepatic
Cystic


From gallbladder
Common bile

Joins pancreatic duct at
hepatopancreatic ampulla
Functions of the Liver

Bile production


Storage



Hepatocytes remove ammonia and convert to urea
Phagocytosis


Glycogen, fat, vitamins, copper and iron
Nutrient interconversion
Detoxification


Salts emulsify fats, contain pigments as bilirubin
Kupffer cells phagocytize worn-out and dying red and white blood cells,
some bacteria
Synthesis

Albumins, fibrinogen, globulins, heparin, clotting factors
Clicker Question:

Which of the following enzymes is critical to the
primary function of the gastric parietal cells?
A) Pepsin
 B) Gastrin
 C) Carbonic Anhydrase
 D) Lipase
 E) None of the above

Clicker Question:

Where would you find a high frequency of
Peyer’s patches?
A) Stomach
 B) Duodenum
 C) Jejunum
 D) Ileum

Clicker Question:

The Plicae Circularis perform which of the following functions?





A) They impart a spin to the chyme as it travels through the
jejunum.
B) They act like an accordion bellows, to allow the wall of the
jejunum to stretch.
C) They provide attachment sites for beneficial bacteria.
D) They increase the surface area of the duodenum and
jejunum.
E) None of the above.
Clicker Question:

Activity in the myenteric plexus is inhibited by
by:
A) Gastrin
 B) CCK
 C) Secretin
 D) All of the above
 E) B and C above

Blood and Bile Flow
Start
As it remains in
the gallbladder,
bile becomes
more
concentrated.
The liver
secretes bile
continuously
—roughly 1 liter
per day.
Liver
The functional relationships involved
in the storage and ejection of bile
Duodenum
CCK
Bile salt emulsifying lipid
droplet in the lumen of
the digestive tract
Lipid
droplet
The release of CCK by the
duodenum triggers dilation of
the hepatopancreatic sphincter
and contraction of the
gallbladder. This ejects bile into
the duodenum through the
duodenal ampulla.
Figure 21.19 3
Bile
…each day around 600 – 1000 ml of bile is produced…







Bile acid
Phospholipids
Cholesterol
Bilirubin
Waste products
Electrolytes
Mucin
Figure 24-26: A Summary of the Chemical Events in Digestion
REGION AND HORMONAL
CONTROLS
CARBOHYDRATES
ORAL CAVITY
LIPIDS
Salivary
amylase
PROTEINS
Lingual
lipase
ESOPHAGUS
STOMACH
Pepsin
Stimulus: Anticipation or
arrival of food
Hormone: Gastrin
Source: G cells of stomach
Disaccharides
Trisaccharides
Polypeptides
Proenzyme released:
Pepsinogen by chief cells,
activated to pepsin by HCl
SMALL INTESTINE
Bile salts
and
pancreatic
lipase
Stimulus: Arrival of chyme
in duodenum
Pancreatic
alpha-amylase
Hormone: CCK
Proenzymes released:
Chymotrypsinogen, procarboxypeptidase, proelastase,
trypsinogen. Enterokinase
activates trypsin, which
activates other enzymes
Disaccharides
Trisaccharides
Monoglycerides,
Fatty acids in
micelles
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase
Short peptides,
Amino acids
Enzymes released: Pancreatic
amylase, pancreatic lipase,
nuclease, enterokinase
INTESTINAL MUCOSA
Brush border
Cell body
Maltase, Sucrase
Lactase
DIFFUSION
Dipeptidases
FACILITATED
DIFFUSION AND
COTRANSPORT
Monoglycerides,
Fatty acids
FACILITATED
DIFFUSION AND
COTRANSPORT
Monosaccharides
Triglycerides
Amino acids
Chylomicrons
FACILITATED
DIFFUSION
EXOCYTOSIS
FACILITATED
DIFFUSION AND
COTRANSPORT
Monosaccharides
Chylomicrons
Amino acids
BLOODSTREAM
Capillary
(a)
Lacteal
(b)
Capillary
(c)
Carbohydrates


Carbohydrates are usually preferred substrates for
catabolism and ATP production when resting
Steps of carbohydrate digestion

In mouth, salivary amylase digests complex
carbohydrates into disaccharides and trisaccharides


Enzyme active only down to pH 4.5 and denatured in
stomach
At duodenum, pancreatic alpha-amylase continues
carbohydrate digestion
Carbohydrates

Steps of carbohydrate digestion (continued)

In jejunum, brush border enzymes finish carbohydrate
digestion down to simple sugars (monosaccharides)




Maltase (digests maltose: glucose + glucose)
Sucrase (digests sucrose: glucose + fructose)
Lactase (digests lactose: glucose + galactose)
In large intestine, remaining indigestible carbohydrates
(such as cellulose) are food source for colonic bacteria

Produce intestinal gas (flatus) during metabolic activities
Carbohydrates

Carbohydrate absorption and transport

Transported into small intestine epithelial cells


Leave cells by facilitated diffusion through basolateral
surface
Enter cardiovascular capillaries to transport to liver in
hepatic portal vein

Processed by liver to maintain glucose levels (~90 mg/dL)


Released as glucose or
Stored as glycogen
Carbohydrates

Cellular use of digested carbohydrates

Generally preferred for catabolism



Proteins and lipids more important for structural components
of cells and tissues
In skeletal muscle, stored as glycogen
In most tissues, transported into cell by carrier molecule
(regulated by insulin)


May be converted to ribose
May be converted to 2 pyruvate molecules in glycolysis


Produces 2 ATP
Pyruvates used by mitochondria

Uses 3 O2, generates 3 CO2, 6 H2O, 34 ATP
The events in carbohydrate catabolism and ATP production from glucose
GLUCOSE
In most tissues, the
transport of glucose into the
cell is dependent on the
presence of a carrier protein
stimulated by insulin.
(6-carbon)
Insulin
Other simple sugars
ATP
Inside the cell, the glucose may be converted to
another simple sugar, such as ribose, used to
build glycoproteins, other structural materials,
or nucleic acids. They may also be converted to
glycerol for the synthesis of glycerides.
If needed to provide energy, the 6-carbon glucose
molecule is broken down into two 3-carbon
molecules of pyruvate. This anaerobic process,
called glycolysis, yields a net gain of 2 ATP for
every glucose molecule broken down.
Pyruvate
(3-carbon)
Pyruvate
(3-carbon)
Carbohydrates (such as glucose) are generally
preferred for catabolism because proteins and
lipids are more important as structural
components of cells and tissues.
CO2
Coenzyme A
Each pyruvate molecule can then be used by
mitochondria, after conversion to acetyl-CoA.
Acetyl-CoA
(2-carbon)
Citric
acid
cycle
ATP
Coenzymes
Electron
transport
system
O2
H2O
CO2
For each molecule of pyruvate processed by
mitochondria, the cell gains 17 ATP, consumes
3 molecules of O2, and generates 3 molecules of
CO2 and 6 molecules of water. Thus for each pair
of pyruvate molecules catabolized, the cell gains
34 ATP.
Figure 24-26: A Summary of the Chemical Events in Digestion
REGION AND HORMONAL
CONTROLS
CARBOHYDRATES
ORAL CAVITY
LIPIDS
Salivary
amylase
PROTEINS
Lingual
lipase
ESOPHAGUS
STOMACH
Pepsin
Stimulus: Anticipation or
arrival of food
Hormone: Gastrin
Source: G cells of stomach
Disaccharides
Trisaccharides
Polypeptides
Proenzyme released:
Pepsinogen by chief cells,
activated to pepsin by HCl
SMALL INTESTINE
Bile salts
and
pancreatic
lipase
Stimulus: Arrival of chyme
in duodenum
Pancreatic
alpha-amylase
Hormone: CCK
Proenzymes released:
Chymotrypsinogen, procarboxypeptidase, proelastase,
trypsinogen. Enterokinase
activates trypsin, which
activates other enzymes
Disaccharides
Trisaccharides
Monoglycerides,
Fatty acids in
micelles
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase
Short peptides,
Amino acids
Enzymes released: Pancreatic
amylase, pancreatic lipase,
nuclease, enterokinase
INTESTINAL MUCOSA
Brush border
Cell body
Maltase, Sucrase
Lactase
DIFFUSION
Dipeptidases
FACILITATED
DIFFUSION AND
COTRANSPORT
Monoglycerides,
Fatty acids
FACILITATED
DIFFUSION AND
COTRANSPORT
Monosaccharides
Triglycerides
Amino acids
Chylomicrons
FACILITATED
DIFFUSION
EXOCYTOSIS
FACILITATED
DIFFUSION AND
COTRANSPORT
Monosaccharides
Chylomicrons
Amino acids
BLOODSTREAM
Capillary
(a)
Lacteal
(b)
Capillary
(c)
Protein digestion and amino acid
metabolism

Steps of protein digestion


In mouth, mechanical processing occurs
In stomach:



Mechanical processing due to churning
Stomach acid denatures protein secondary and tertiary
structures
Pepsin (from parietal cells) attacks certain peptide bonds

Digests proteins to polypeptide and peptide chains
Protein digestion and amino acid
metabolism

Steps of protein digestion (continued)

In duodenum:


Enteropeptidase (from duodenal epithelium) converts
trypsinogen (pancreatic proenzyme) to trypsin
Trypsin activates other pancreatic proenzymes


Chymotrypsin, carboxypeptidase, and elastase
Activated pancreatic enzymes digest specific peptide bonds
producing short peptides and amino acids
Protein digestion and amino acid
metabolism

Digested protein absorption and transport

Epithelial brush border enzymes (peptidases) finish protein
digestion

Amino acids absorbed through:

Facilitated diffusion

Cotransport

Released from epithelial cell basal surface through same cell
transport mechanisms

Amino acids transported to liver through intestinal capillaries
to hepatic portal vein
Protein digestion and amino acid
metabolism

Amino acid processing in liver

Control of plasma amino acid levels is less precise
than glucose



Normal range: 35–65 mg/dL
Can increase after protein-rich meal
Liver amino acid use


Synthesize plasma proteins
Create 3-carbon molecules for gluconeogenesis
Protein digestion and amino acid
metabolism

Amino acid processing in liver (continued)

Amino acid catabolism

Deamination (removal of amino group)

Ammonium ions released are toxic

Liver enzymes convert to urea excreted into urine

= Urea cycle
The liver does not control circulating levels
of amino acids as precisely as it does
glucose concentrations. Plasma amino acid
levels normally range between 35 and 65
mg/dL, but they may become elevated after
a protein-rich meal. The liver itself uses
many amino acids for synthesizing plasma
proteins, and it has all of the enzymes
needed to synthesize, convert, or catabolize
amino acids. In addition, amino acids that
can be broken down to 3-carbon molecules
can be used for gluconeogenesis when
other sources of glucose are unavailable.
Amino Acid Synthesis
Liver cells and other body cells can readily synthesize the carbon
frameworks of roughly half of the amino acids needed to synthesize proteins.
There are 10 essential amino acids that the body either cannot synthesize
or that cannot be produced in amounts sufficient for growing children.
In an amination
reaction, an ammonium
ion (NH4+) is used to
form an amino group
that is attached to a
molecule, yielding an
amino acid.
NH4+
H2O
H+
α–Ketoglutarate
Glutamic acid
In a transamination, the amino group of one amino acid gets transferred
to another molecule, yielding a different amino acid. The remaining carbon
chain can then be broken down or used in other ways.
Transaminase
Glutamic acid
Organic acid 1
Organic acid 2
Tyrosine
Figure 22.7
Figure 24-26: A Summary of the Chemical Events in Digestion
REGION AND HORMONAL
CONTROLS
CARBOHYDRATES
ORAL CAVITY
LIPIDS
Salivary
amylase
PROTEINS
Lingual
lipase
ESOPHAGUS
STOMACH
Pepsin
Stimulus: Anticipation or
arrival of food
Hormone: Gastrin
Source: G cells of stomach
Disaccharides
Trisaccharides
Polypeptides
Proenzyme released:
Pepsinogen by chief cells,
activated to pepsin by HCl
SMALL INTESTINE
Bile salts
and
pancreatic
lipase
Stimulus: Arrival of chyme
in duodenum
Pancreatic
alpha-amylase
Hormone: CCK
Proenzymes released:
Chymotrypsinogen, procarboxypeptidase, proelastase,
trypsinogen. Enterokinase
activates trypsin, which
activates other enzymes
Disaccharides
Trisaccharides
Monoglycerides,
Fatty acids in
micelles
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase
Short peptides,
Amino acids
Enzymes released: Pancreatic
amylase, pancreatic lipase,
nuclease, enterokinase
INTESTINAL MUCOSA
Brush border
Cell body
Maltase, Sucrase
Lactase
DIFFUSION
Dipeptidases
FACILITATED
DIFFUSION AND
COTRANSPORT
Monoglycerides,
Fatty acids
FACILITATED
DIFFUSION AND
COTRANSPORT
Monosaccharides
Triglycerides
Amino acids
Chylomicrons
FACILITATED
DIFFUSION
EXOCYTOSIS
FACILITATED
DIFFUSION AND
COTRANSPORT
Monosaccharides
Chylomicrons
Amino acids
BLOODSTREAM
Capillary
(a)
Lacteal
(b)
Capillary
(c)
Lipids

Steps of lipid digestion



In mouth, mechanical processing and chemical
digestion by lingual lipase
In stomach, lingual lipase continues to function but
can only access surface of lipid drops that have formed
In duodenum


Bile salts break up lipid drops into smaller droplets (=
emulsification)
Pancreatic lipase digests triglycerides into fatty acids,
monoglycerides, and glycerol

Forms micelles (lipid–bile salt complexes)
Lipoproteins

Types

Chylomicrons



VLDL
LDL


Enter lymph
Transports cholesterol
to cells
HDL

Transports cholesterol
from cells to liver
Lipids

Absorption and transport of digested lipids




Lipids diffuse from micelle into intestinal epithelial cell
Intracellular anabolic reactions synthesize new triglycerides from
digested lipids
New triglycerides packaged in chylomicrons (chylos, milky lymph,
mikros, small) and released via exocytosis
Chylomicrons diffuse into intestinal lacteals due to their size


Transported through lymphatic vessels (including thoracic duct) to
bloodstream
Enzyme in capillaries (lipoprotein lipase) breaks down chylomicron
and releases digested lipids to tissues
Lipids

Digested lipid distribution and processing

Tissues that use or process digested lipids

Skeletal muscles


Adipose tissue


Use fatty acids to generate ATP for contraction and to convert
glucose to glycogen
Uses fatty acids and monoglycerides to synthesize triglycerides for
storage
Liver

Absorbs intact chylomicrons and extracts triglycerides and
cholesterol from chylomicron
Lipids

Cholesterol distribution


Released from liver attached to low-density lipoproteins (LDL) for
distribution to peripheral tissues
LDLs absorbed and broken down by lysosomes in cells



High-density lipoproteins (HDL) (plasma proteins from liver)
absorb peripheral cholesterol and return to liver


Cholesterol extracted and used
Unused cholesterol released into bloodstream
Cholesterol released again with LDLs or excreted in bile
Ratio of LDL/HDL and total cholesterol used diagnostically for
cardiovascular problems
Thoracic
duct
The chylomicrons
enter the bloodstream
at the left subclavian
vein, then pass
through the
pulmonary circuit
before entering the
systemic circuit.
Resting skeletal muscles absorb fatty
acids and break them down, using the
ATP provided both to power the
contractions that maintain muscle
tone and to convert
glucose to glycogen.
Capillary walls contain the
enzyme lipoprotein lipase,
which breaks down the
chylomicrons and releases
fatty acids and monoglycerides that can diffuse into the
interstitial fluid.
Adipocytes absorb
the monoglycerides
and fatty acids,
and use them to
synthesize triglycerides for storage.
Lipoproteins and Lipid Transport and Distribution
The liver absorbs chylomicrons, removes the
triglycerides, combines the cholesterol from the
chylomicron with synthesized or recycled
cholesterol, and alters the surface proteins. It then
releases low-density lipoproteins (LDLs) into
the circulation, which deliver cholesterol to
peripheral tissues. Some of the cholesterol is used
by the liver to synthesize bile salts; excess
cholesterol is excreted in the bile.
The HDLs return
the cholesterol to
the liver, where it
is extracted and
packaged in new
LDLs or excreted
with bile salts in
bile.
From the lacteals,
the chylomicrons
proceed along the
lymphatic vessels
and into the
thoracic duct.
Chylomicrons
Triglycerides
removed
LDL
The LDLs released by the
liver leave the bloodstream
through capillary pores or
cross the endothelium by
vesicular transport.
Cholesterol
extracted
Excess
cholesterol is
excreted with
HDL the bile salts
HDL
High
cholesterol
Once in peripheral tissues,
the LDLs are absorbed.
LDL
Low
cholesterol
Lysosomal
breakdown
HDL
Cholesterol
release
Used in synthesis
of membranes,
hormones,
other material
Figure 22.5
Clicker Question:

The Respiratory Rhythmicity Centre (RRC) in
the medulla contains:
A) The apneustic centre
 B) The dorsal respiratory group
 C) The pneumotaxic centre
 D) The limbic system
 E) The cardioregulatory centre

Clicker Question:

The neurones of the dorsal regulatory group:
A) Stimulate the muscles of expiration.
 B) Directly inhibit the muscles of expiration
 C) Stimulate the muscles of inspiration
 D) Inhibit activity in the apneustic centre

Clicker Question:

The anatomic dead space:
A) Consists of all the conducting zone airways,
including the upper tract
 B) Consists of the trachea, bronchi, and bronchiole
down to, and including, the respiratory bronchiole
 C) The pharyngeal region
 D) None of the above

Clicker Question:

In order to do well on the final exam, Students
need to:
A) Party hard
 B) Study hard
 C) Bribe the lecturer
 D) Ask questions about processes they don’t
understand
 E) B and D above

Large Intestine:



Extends from ileocecal junction to anus
Consists of cecum, colon, rectum, anal canal
Movements sluggish (18-24 hours)
The wall of the large intestine
Aggregated
lymphoid
nodule
Simple columnar
epithelium
Intestinal gland
Mucous cells
Muscularis mucosae
Submucosa
Muscularis Externa
Circular layer
Longitudinal
layer (taenia coli)
Figure 21.15 1
Large intestine

General characteristics of the large intestine



Also known as large bowel
Length is ~1.5 m (4.9 ft) and width is 7.5 cm (3 in.)
Major functions during mass movement (peristalsis)
1.
2.
3.

Reabsorption of water and compaction of contents into
feces
Absorption of important vitamins liberated by bacterial
action
Storage of feces prior to defecation
Three segments: cecum, colon, rectum
Large intestine

Large intestine segments and structures

Cecum (expanded pouch beginning colon)



Begins compaction (compression into feces)
Contains ileocecal valve
Has attached appendix



~9 cm (3.6 in.) in length
Contains numerous lymphoid nodules
Appendicitis (inflammation)
Large intestine

Large intestine segments and structures (continued)

Colon

Ascending


Transverse


Across abdomen from right colic flexure to left colic flexure
Descending


Along right margin of peritoneal cavity from cecum to right colic
flexure
Along left margin of peritoneal cavity from left colic flexure to
sigmoid flexure
Sigmoid

S-shaped last segment empties into rectum
Large intestine

Large intestine segments and structures (continued)

Rectum



Forms last 15 cm (6 in.) of digestive tract
Expandable for temporary feces storage
Fecal material within rectum triggers defecation urge
The characteristic features of the rectum
Rectum
Anal canal
Anal columns
Internal anal sphincter
External anal sphincter
Rectum
Anus
Rectum, sectioned
Figure 21.15 2
Large intestine

Other large intestine structures

Taeniae coli

Three longitudinal muscle bands along outer colon surface


Haustra



Corresponds to muscularis externa
Pouches along colon wall
Allow for expansion and elongation of colon
Fatty appendices

Teardrop-shaped fat sacs attached to serosa
Movement in Large Intestine

Mass movements


Local reflexes in enteric plexus



Gastrocolic: Initiated by stomach
Duodenocolic: Initiated by duodenum
Defecation reflex


Common after meals
Distension of the rectal wall by feces
Defecation

Usually accompanied by voluntary movements to expel feces
through abdominal cavity pressure caused by inspiration
Transport and Secretion by Large
Intestine

Mucus provides protection


Parasympathetic stimulation increases rate of goblet
cell secretion
Ion Pumps
Exchange of bicarbonate ions for chloride ions
 Exchange of sodium ions for hydrogen ions


Bacterial actions produce gases called flatus
Production and elimination of feces

Large intestine characteristics associated with fecal production
 Diameter is larger and wall is thinner than small intestine
 Lack of villi
 Abundance of mucous cells
 Many intestinal glands dominated by mucous glands
 Mucus provides lubrication for drier and more compact fecal
material
 No digestive enzymes produced
Production and elimination of feces

Rectum and anal structure

Anal canal (distal portion of rectum)



Contains longitudinal folds (= anal columns)
Epithelium transitions from columnar to stratified squamous epithelium
Large network of veins contained within wall




Enlarged veins = hemorrhoids
Internal anal sphincter (inner circular smooth muscle layer)
External anal sphincter (outer skeletal muscle layer)
Anus (exit of anal canal)

Stratified epithelium becomes keratinized
Production and elimination of feces

Defecation reflex
Begins with distension of rectum wall after arrival of
feces
 Involves two positive feedback loops

1.
Long reflex


2.
Coordinated by sacral parasympathetic system
Stimulates mass movements in feces toward rectum from
descending and sigmoid colon
Short reflex

Stimulation of myenteric plexus to move feces in sigmoid colon
and rectum
Water and Ions:

Water


Can move in either direction
across wall of small intestine
depending on osmotic
gradients
Ions

Sodium, potassium, calcium,
magnesium, phosphate are
actively transported
The events in the defecation reflex,
which includes two positive feedback loops
Stimulation of
somatic motor
neurons
stimulates
Stimulation of
parasympathetic
motor neurons
in sacral spinal
cord
Stimulation of
myenteric plexus in
sigmoid colon and
rectum
Long Reflex
Short Reflex
The first loop is a
short reflex that
triggers a series
of peristaltic
contractions in the
rectum that move
feces toward the anus.
Increased
peristalsis
throughout large
intestine
Stimulation of
stretch
receptors
Start
Increased local
peristalsis
inhibits
The long reflex is
coordinated by the sacral
parasympathetic system.
This reflex stimulates mass
movements that push feces
toward the rectum from the
descending colon and
sigmoid colon.
DISTENSION
OF RECTUM
Relaxation of internal
anal sphincter; feces
move into anal canal
Voluntary relaxation of the
external sphincter can
override the contraction
directed by somatic motor
neurons (L2a).
Involuntary contraction
of external anal
sphincter
If external sphincter is voluntarily relaxed,
DEFECATION OCCURS
Figure 21.15 4
Appetite regulation

Appetite is controlled by two areas of
hypothalamus
1.
2.
Feeding center
Satiety center


Causes inhibition of feeding center
Regulation of appetite can occur on two levels
1.
2.
Short-term regulation
Long-term regulation
Appetite regulation

Short-term regulation of appetite

Stimulation of satiety center
Elevation of blood glucose levels
 Hormones of digestive tract (like CCK)
 Digestive tract wall stretching


Stimulation of feeding center

Neurotransmitters


Example: neuropeptide Y or NPY from hypothalamus
Ghrelin

Hormone secreted by gastric mucosa when stomach is empty
Appetite regulation

Long-term regulation of appetite

Leptin



Peptide hormone secreted by adipocytes
Stimulates satiety center and suppresses appetite
Effects are gradual
Short-Term Regulation of Appetite
Stimulation of Satiety Center
Hypothalamus
Satiety center
Elevated blood glucose levels depress
appetite, and low blood glucose
stimulates appetite. The likely
mechanism is glucose entry stimulating
the neurons of the satiety center.
Several hormones of the digestive tract,
including CCK, suppress appetite
during the absorptive state.
Feeding center
Stimulation of stretch receptors along
the digestive tract, especially in the
stomach, causes a sense of satiation
and suppresses appetite.
Long-Term Regulation of Appetite
Stimulation of Feeding Center
Several neurotransmitters have
been linked to appetite regulation.
Neuropeptide Y (NPY), for example,
is a hypothalamic neurotransmitter that
(among other effects) stimulates the
feeding center and increases appetite.
The hormone ghrelin (GREL-in),
secreted by the gastric mucosa,
stimulates appetite. Ghrelin levels are
high when the stomach is empty, and
decline as the stomach fills.
When appetite outpaces energy usage,
excess calories are stored as fat in
adipose tissue. Leptin is a peptide
hormone released by adipose tissues
as they synthesize triglycerides. In the
CNS it stimulates the satiety center
and suppresses appetite. The effects
are gradual, and it is probably involved
in long-term regulation of food intake.
Mechanisms in the control
of appetite
Figure 22.12
Effects of Aging


Decrease in mucus layer, connective tissue,
muscles and secretions
Increased susceptibility to infections and toxic
agents

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
> 30 nm
LDL
20–22 nm
Potentially proinflammatory
HDL
9–15 nm
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;15:1987-1994.



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.

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
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
Monocyte
LDL Vessel Lumen
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