Transcript Ch. 24

Chapter 24
The Digestive System
Lecture Outline
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INTRODUCTION
• Food contains substances and energy the body needs to
construct all cell components. The food must be broken
down through digestion to molecular size before it can be
absorbed by the digestive system and used by the cells.
• The organs that collectively perform these functions
compose the digestive system.
• The medical professions that study the structures, functions,
and disorders of the digestive tract are gastroenterology for
the upper end of the system and proctology for the lower
end.
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Chapter 24
The Digestive System
• Structure
– Gross Anatomy
– Histology
• Function
– Mechanical
– Chemical
• Development
• Disorders
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OVERVIEW OF THE DIGESTIVE SYSTEM
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Overview of GI tract Functions
• Mouth---bite, chew, swallow
• Pharynx and esophagus----transport
• Stomach----mechanical disruption;
absorption of water & alcohol
• Small intestine--chemical &
mechanical digestion & absorption
• Large intestine----absorb electrolytes
& vitamins (B and K)
• Rectum and anus---defecation
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Organization
• The two major sections of the digestive system perform the
processes required to prepare food for use in the body
(Figure 24.1).
• The gastrointestinal tract is the tube open at both ends for
the transit of food during processing. The functional
segments of the GI tract include the mouth, esophagus,
stomach, small intestine, and large intestine.
• The accessory structures that contribute to the food
processing include the teeth, tongue, salivary glands, liver,
gallbladder, and pancreas.
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Digestion
• Digestion includes six basic processes.
• Ingestion is taking food into the mouth (eating).
• Secretion is the release, by cells within the walls of the GI tract and
accessory organs, of water, acid, buffers, and enzymes into the lumen of
the tract.
• Mixing and propulsion result from the alternating contraction and
relaxation of the smooth muscles within the walls of the GI tract.
• Digestion
• Mechanical digestion consists of movements of the GI tract that aid
chemical digestion.
• Chemical digestion is a series of catabolic (hydrolysis) reactions that
break down large carbohydrate, lipid, and protein food molecules into
smaller molecules that are usable by body cells.
• Absorption is the passage of end products of digestion from the GI tract
into blood or lymph for distribution to cells.
• Defecation is emptying of the rectum, eliminating indigestible
substances from the GI tract.
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LAYERS OF THE GI TRACT
• The basic arrangement of layers in the gastrointestinal tract
from the inside outward includes the mucosa, submucosa,
muscularis, and serosa (visceral peritoneum) (Figure 24.2).
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Layers of the GI Tract
1. Mucosal layer
2. Submucosal layer
3. Muscularis layer
4. Serosa layer
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Mucosa
• Epithelium
– stratified squamous(in mouth,esophagus & anus) = tough
– simple columnar in the rest
• secretes enzymes and absorbs nutrients
• specialized cells (goblet) secrete mucous onto cell surfaces
• enteroendocrine cells---secrete hormones controlling organ
function
• Lamina propria
– thin layer of loose connective tissue
– contains BV and lymphatic tissue
• Muscularis mucosae---thin layer of smooth muscle
– causes folds to form in mucosal layer
– increases local movements increasing absorption with exposure to
“new” nutrients
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LAYERS OF THE GI TRACT
• The submucosa consists of aerolar connective tissue. It is
highly vascular, contains a part of the submucosal plexus
(plexus of Meissner), and contains glands and lymphatic
tissue.
• The submucosal plexus is a part of the autonomic nervous
system.
• It regulates movements of the mucosa, vasoconstriction of
blood vessels, and innervates secretory cells of mucosal
glands.
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Submucosa
• Loose connective tissue
– containing BV, glands
and lymphatic tissue
• Meissner’s plexus--– parasympathetic
– innervation
• vasoconstriction
• local movement by
muscularis mucosa
smooth muscle
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Enteric Nervous System
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Muscularis
• Skeletal muscle = voluntary control
– in mouth, pharynx , upper esophagus and anus
– control over swallowing and defecation
• Smooth muscle = involuntary control
– inner circular fibers & outer longitudinal fibers
– mixes, crushes & propels food along by peristalsis
• Auerbach’s plexus (myenteric)-– both parasympathetic & sympathetic innervation of circular
and longitudinal smooth muscle layers
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Serosa
• An example of a serous membrane
• Covers all organs and walls of cavities not open to the
outside of the body
• Secretes slippery fluid
• Consists of connective tissue covered with simple
squamous epithelium
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NEURAL INNERVATION OF THE GI TRACT
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Enteric Nervous System
• ENS consists of neurons that extend from the esophagus to
the gut (Figure 24.2)
• Located in the myenteric plexus and the submucosal plexus.
• Consists of motor neurons, interneurons, and sensory
neurons (Figure 24.3)
• Myenteric neurons control gastric motility while the
submucosal neurons control the secretory cells.
• Can function independently of the CNS
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Enteric Nervous System
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Autonomic Nervous System (ANS)
• Vagus nerve (X) supplies parasympathetic fibers. These
fibers synapse with neurons in the ENS and increase their
action.
• Sympathetic nerves arise from the thoracic and upper
lumber regions of the spinal cord. These fibers also
synapse with neurons in the ENS. However, they inhibit the
ENS neurons.
• Gastrointestinal Reflex Pathways
– Regulate secretions and motility in response to stimuli
present in the lumen.
– The reflexes begin with receptors associated with
sensory neurons of the ENS.
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Peritoneum
• Peritoneum
– visceral layer covers
organs
– parietal layer lines the
walls of body cavity
• Peritoneal cavity
– potential space
containing a bit of
serous fluid
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Parts of the Peritoneum
•
•
•
•
•
Mesentery
Mesocolon
Lesser omentum
Greater omentum
Peritonitis = inflammation
– trauma
– rupture of GI tract
– appendicitis
– perforated ulcer
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Greater Omentum, Mesentery & Mesocolon
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Lesser Omentum
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Clinical Application
• Peritonitis is an acute inflammation of the peritoneum.
• Cause
– contamination by infectious microbes during surgery or
from rupture of abdominal organs
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MOUTH
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Introduction
• The mouth (oral or buccal cavity) is formed by the cheeks,
hard and soft palate, lips, and tongue (Figure 24.5).
• The vestibule of the oral cavity is bounded externally by the
cheeks and lips and internally by the gums and teeth.
• The oral cavity proper is a space that extends from the
gums and teeth to the fauces, the opening between the oral
cavity and the pharynx or throat.
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Mouth
• Lips and cheeks-----contains buccinator muscle that keeps food between
upper & lower teeth
• Vestibule---area between cheeks and teeth
• Oral cavity proper---the roof = hard, soft palate and uvula
– floor = the tongue
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Pharyngeal Arches
• Two skeletal muscles
• Palatoglossal muscle
– extends from palate to
tongue
– forms the first arch
– posterior limit of the mouth
• Palatopharyngeal muscle
– extends from palate to
pharyngeal wall
– forms the second arch
– behind the palatine tonsil
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Salivary
Glands
•
•
•
•
Parotid below your ear and over the masseter
Submandibular is under lower edge of mandible
Sublingual is deep to the tongue in floor of mouth
All have ducts that empty into the oral cavity
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Composition and Functions of Saliva
• Wet food for easier swallowing
• Dissolves food for tasting
• Bicarbonate ions buffer acidic foods
– bulemia---vomiting hurts the enamel on your teeth
• Chemical digestion of starch begins with enzyme (salivary
amylase)
• Enzyme (lysozyme) ---helps destroy bacteria
• Protects mouth from infection with its rinsing action---1 to 1
and 1/2qts/day
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Salivary Gland Cellular Structure
• Cells in acini (clusters)
• Serous cells secrete a watery fluid
• Mucous cells (pale staining) secrete a slimy, mucus secretion
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Salivation
• Increase salivation
– sight, smell, sounds, memory of food, tongue
stimulation---rock in mouth
– cerebral cortex signals the salivatory nuclei in
brainstem---(CN 7 & 9)
– parasympathetic nn. (CN 7 & 9)
• Stop salivation
– dry mouth when you are afraid
– sympathetic nerves
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Mumps
• Myxovirus that attacks the parotid gland
• Symptoms
– inflammation and enlargement of the parotid
– fever, malaise & sour throat (especially swallowing
sour foods)
– swelling on one or both sides
• Sterility rarely possible in males with testicular
involvement (only one side involved)
• Vaccine available since 1967
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Structure and Function of the Tongue
• The tongue, together with its associated muscle, forms the
floor of the oral cavity. It is composed of skeletal muscle
covered with mucous membrane.
• Extrinsic and intrinsic muscles permit the tongue to be
moved to participate in food manipulation for chewing and
swallowing and in speech.
• The lingual frenulum is a fold of mucous membrane that
attaches to the midline of the undersurface of the tongue.
• The upper surface and sides of the tongue are covered with
papillae. Some papillae contain taste buds .
• On the dorsum of the tongue are glands that secrete lingual
lipase, which initiates digestion of triglycerides.
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Structure and Function of the Tongue
• Muscle of tongue is
attached to hyoid,
mandible, hard palate
and styloid process
• Papillae are the bumps--taste buds are protected
by being on the sides of
papillae
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Structure and Function of the Teeth
• The teeth project into the mouth and are adapted for mechanical
digestion (Figure 24.7).
• A typical tooth consists of three principal portions: crown, root, and neck.
• Teeth are composed primarily of dentin, a calcified connective tissue
that gives the tooth its basic shape and rigidity; the dentin of the crown is
covered by enamel, the hardest substance in the body, which protects
the tooth from the wear of chewing.
• The dentin of the root is covered by cementum, another bone-like
substance, which attaches the root to the periodontal ligament (the
fibrous connective tissue lining of the tooth sockets in the mandible and
maxillae).
• The dentin encloses the pulp cavity in the crown and the root canals in
the root.
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Tooth Structure
•
•
•
•
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Crown
Neck
Roots
Pulp cavity
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Composition of Teeth
• Enamel
– hardest substance in
body
– calcium phosphate or
carbonate
• Dentin
– calcified connective
tissue
• Cementum
– bone-like
– periodontal ligament
penetrates it
What is the gingiva?
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Dentition
• There are two dentitions, or sets of teeth, in an individual’s
lifetime: deciduous (primary), milk teeth, or baby teeth; and
permanent (secondary) teeth (Figure 24.8 a,b).
• Primary or baby teeth
– 20 teeth that start erupting at 6 months
– 1 new pair of teeth per month
• Permanent teeth
– 32 teeth that erupt between 6 and 12 years of age
– differing structures indicate function
• incisors for biting
• canines or cuspids for tearing
• premolars & molars for crushing and grinding food
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Dentistry
• In root canal therapy all traces of pulp tissue are removed
from the pulp cavity and root canal of a badly diseased tooth
• The branch of dentistry that is concerned with the
prevention, diagnosis, and treatment of diseases that affect
the pulp, root, periodontal ligament, and alveolar bone is
known as endodontics.
• Orthodontics is a dental branch concerned with the
prevention and correction of abnormally aligned teeth.
• Periodontics is a dental branch concerned with the
treatment of abnormal conditions of tissues immediately
around the teeth.
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Primary and Secondary Dentition
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Digestion in the Mouth
• Table 24.1 summarizes digestion in the mouth.
• Mechanical digestion (mastication or chewing)
• breaks into pieces
• mixes with saliva so it forms a bolus
• Chemical digestion
– amylase
• begins starch digestion at pH of 6.5 or 7.0 found in mouth
• when bolus & enzyme hit the pH 2.5 gastric juices hydrolysis
ceases
– lingual lipase
• secreted by glands in tongue
• begins breakdown of triglycerides into fatty acids and glycerol
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PHARYNX
• The pharynx is a funnel-shaped tube that extends from the
internal nares to the esophagus posteriorly and the larynx
anteriorly (Figure 24.4).
• It is composed of skeletal muscle and lined by mucous
membrane.
• The nasopharynx functions in respiration only, whereas the
oropharynx and laryngopharynx have digestive as well as
respiratory functions.
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Pharynx
• Funnel-shaped tube extending from internal nares to the
esophagus (posteriorly) and larynx (anteriorly)
• Skeletal muscle lined by mucous membrane
• Deglutition or swallowing is facilitated by saliva and mucus
– starts when bolus is pushed into the oropharynx
– sensory nerves send signals to deglutition center in
brainstem
– soft palate is lifted to close nasopharynx
– larynx is lifted as epiglottis is bent to cover glottis
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ESOPHAGUS
• The esophagus is a collapsible, muscular tube that lies
behind the trachea and connects the pharynx to the
stomach (Figure 24.1).
• The wall of the esophagus contains mucosa, submucosa,
and muscularis layers. The outer layer is called the
adventitia rather than the serosa due to structural
differences (Figure 24.9).
• The role of the esophagus is to secrete mucus and transport
food to the stomach.
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Esophagus
•
•
•
•
•
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Collapsed muscular tube
In front of vertebrae
Posterior to trachea
Posterior to the heart
Pierces the diaphragm at
hiatus
– hiatal hernia or
diaphragmatic hernia
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Histology of the Esophagus
• Mucosa = stratified squamous
• Submucosa = large mucous
glands
• Muscularis = upper 1/3 is skeletal,
middle is mixed, lower 1/3 is
smooth
– upper & lower esophageal
sphincters are prominent
circular muscle
• Adventitia = connective tissue
blending with surrounding
connective tissue--no peritoneum
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DEGLUTITION
• Moves a bolus from the mouth to the stomach. It is facilitated by saliva
and mucus and involves the mouth, pharynx, and tongue (Figure 24.10).
– It consists of a voluntary stage, pharyngeal stage (involuntary) and
esophageal stage.
• Voluntary stage begins when the bolus is forced into the oropharynx by
tongue movement.
• Receptors in the oropharyns stimulate the deglutition center in the
medulla. This begins the pharyngeal stage which moves food from the
pharynx to the esophagus.
• The esophageal stage begins when the bolus enters the esophagus.
During this stage the peristalsis movers the bolus from the esophagus to
the stomach.
• Table 24.2 summarizes the digestion related activities of the pharynx
and esophagus.
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Physiology of the Esophagus - Swallowing
• Voluntary phase---tongue pushes food to back of oral cavity
• Involuntary phase----pharyngeal stage
– breathing stops & airways are closed
– soft palate & uvula are lifted to close off nasopharynx
– vocal cords close
– epiglottis is bent over airway as larynx is lifted
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Swallowing
• Upper sphincter relaxes when larynx is
lifted
• Peristalsis pushes food down
– circular fibers behind bolus
– longitudinal fibers in front of
bolus shorten the distance
of travel
• Travel time is 4-8 seconds for solids and 1 sec for liquids
• Lower sphincter relaxes as food approaches
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Gastroesophageal Reflex Disease
• If lower sphincter fails to open
– distension of esophagus feels like chest pain or heart attack
• If lower esophageal sphincter fails to close
– stomach acids enter esophagus & cause heartburn (GERD)
– for a weak sphincter---don't eat a large meal and lay down in
front of TV
– smoking and alcohol make the sphincter relax worsening the
situation
• Control the symptoms by avoiding
– coffee, chocolate, tomatoes, fatty foods, onions & mint
– take Tagamet HB or Pepcid AC 60 minutes before eating
– neutralize existing stomach acids with Tums
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STOMACH
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Introduction
• The stomach is a J-shaped enlargement of the GI tract that
begins at the bottom of the esophagus and ends at the
pyloric sphincter (Figure 24.11).
• It serves as a mixing and holding area for food, begins the
digestion of proteins, and continues the digestion of
triglycerides, converting a bolus to a liquid called chyme. It
can also absorb some substances.
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Anatomy of the Stomach
• The gross anatomical subdivisions of the stomach include
the cardia, fundus, body, and pyloris (Figure 24.11).
• When the stomach is empty, the mucosa lies in folds called
rugae.
• Pylorospasm and pyloric stenosis are two abnormalities of
the pyloric sphincter that can occur in newborns. Both
functionally block or partially block the exit of food from the
stomach into the duodenum and must be treated with drugs
or surgery (Clinical Application).
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Anatomy of the Stomach
• At the greater curvature, the visceral peritoneum becomes
the greater omentum.
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Anatomy of Stomach
• Which side is it on?
• Size when empty?
– large sausage
– stretches due to rugae
• Parts of stomach
– cardia
– fundus---air in x-ray
– body
– pylorus---starts to
narrow as approaches
pyloric sphincter
• Empties as small squirts of
chyme leave the stomach
through the pyloric valve
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Anatomy of Stomach
• Which side is it on?
• Size when empty?
– large sausage
– stretches due to rugae
• Parts of stomach
– cardia
– fundus---air in x-ray
– body
– pylorus---starts to
narrow as approaches
pyloric sphincter
• Empties as small squirts of
chyme leave the stomach
through the pyloric valve
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Pylorospasm and Pyloric Stenosis
• Abnormalities of the pyloric sphincter in infants
• Pylorospasm
– muscle fibers of sphincter fail to relax trapping
food in the stomach
– vomiting occurs to relieve pressure
• Pyloric stenosis
– narrowing of sphincter indicated by projectile
vomiting
– must be corrected surgically
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Histology of the Stomach
• The surface of the mucosa is a layer of simple columnar epithelial cells
called mucous surface cells (Figure 24.12a).
• Epithelial cells extend down into the lamina propria forming gastric pits
and gastric glands.
• The gastric glands consist of three types of exocrine glands: mucous
neck cells (secrete mucus), chief or zymogenic cells (secrete
pepsinogen and gastric lipase), and parietal or oxyntic cells (secrete
HCl).
• Gastric glands also contain enteroendocrine cells which are hormone
producing cells. G cells secrete the hormone gastrin into the
bloodstream.
• Zollinger-Ellison Syndrome is a syndrome in which an individual
produces too much HCl. It is caused by excessive gastrin which
stimulates the secretion of gastric juice.
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Histology of the Stomach
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Mucosa & Gastric Glands
• Hydrochloric acid converts pepsinogen
from chief cell to pepsin
• Intrinsic factor
– absorption of vitamin B12 for RBC
production
• Gastrin hormone (g cell)
– “get it out of here”
• release more gastric juice
• increase gastric motility
• relax pyloric sphincter
• constrict esophageal sphincter
preventing entry
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Mucosa of the Fundus
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Histology of the Stomach
• The submucosa is composed of areolar connective tissue.
• The muscularis has three layers of smooth muscle:
longitudinal, circular, and an inner oblique layer.
• The serosa is a part of the visceral peritoneum.
• At the lesser curvature, the visceral peritoneum becomes
the lesser omentum.
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Submucosa
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Muscularis
• Three layers of smooth
muscle--outer
longitudinal, circular &
inner oblique
• Permits greater
churning & mixing of
food with gastric juice
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Serosa
• Simple squamous epithelium over a bit of connective tissue
• Also known as visceral peritoneum
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Physiology--Mechanical Digestion
• Gentle mixing waves
– every 15 to 25 seconds
– mixes bolus with 2 quarts/day of gastric juice to
turn it into chyme (a thin liquid)
• More vigorous waves
– travel from body of stomach to pyloric region
• Intense waves near the pylorus
– open it and squirt out 1-2 teaspoons full with each
wave
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Physiology--Chemical Digestion
• Protein digestion begins
– HCl denatures (unfolds) protein molecules
– HCl transforms pepsinogen into pepsin that breaks
peptides bonds between certain amino acids
• Fat digestion continues
– gastric lipase splits the triglycerides in milk fat
• most effective at pH 5 to 6 (infant stomach)
• HCl kills microbes in food
• Mucous cells protect stomach walls from being digested
with 1-3mm thick layer of mucous
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Gastric pH
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Application
• Vomiting is the forcible expulsion of the contents of the
upper GI tract (stomach and sometimes duodenum) through
the mouth. Prolonged vomiting, especially in infants and
elderly people, can be serious because the loss of gastric
juice and fluids can lead to disturbances in fluid and acidbase balance
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PANCREAS
• The pancreas is divided into a head, body, and tail and is
connected to the duodenum via the pancreatic duct (duct of
Wirsung) and accessory duct (duct of Santorini) (Figure
24.14).
• Pancreatic islets (islets of Langerhans) secrete hormones
and acini secrete a mixture of fluid and digestive enzymes
called pancreatic juice (Figure 18.23).
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Anatomy of the
Pancreas
•
•
•
•
•
5" long by 1" thick
Head close to curve in C-shaped duodenum
Main duct joins common bile duct from liver
Sphincter of Oddi on major duodenal papilla
Opens 4" below pyloric sphincter
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Pancreatic Duct
• Main duct joins common bile
duct from liver
• Sphincter of Oddi on major
duodenal papilla
• Opens 4" below pyloric
sphincter
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Histology of the Pancreas
• Acini- dark clusters
– 99% of gland
– produce pancreatic juice
• Islets of Langerhans
– 1% of gland
– pale staining cells
– produce hormones
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Pancreas - Overview
• Pancreatic juice contains enzymes that digest starch
(pancreatic amylase), proteins (trypsin, chymotrypsin, and
carboxypeptidase), fats (pancreatic lipase), and nucleic
acids (ribonuclease and deoxyribonuclease).
• It also contains sodium bicarbonate which converts the acid
stomach contents to a slightly alkaline pH (7.1-8.2), halting
stomach pepsin activity and promoting activity of pancreatic
enzymes.
• Inflammation of the pancreas is called pancreatitis and can
result in trypsin beginning to digest pancreatic cells.
• Pancreatic cancer is nearly always fatal and in the fourth
most common cause of cancer death in the United States.
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Composition and Functions of Pancreatic Juice
• 1 & 1/2 Quarts/day at pH of 7.1 to 8.2
• Contains water, enzymes & sodium bicarbonate
• Digestive enzymes
– pancreatic amylase, pancreatic lipase, proteases
– trypsinogen---activated by enterokinase (a brush
border enzyme)
– chymotrypsinogen----activated by trypsin
– procarboxypeptidase---activated by trypsin
– proelastase---activated by trypsin
– trypsin inhibitor---combines with any trypsin
produced inside pancreas
– ribonuclease----to digest nucleic acids
– deoxyribonuclease
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Pancreatitis
• Pancreatitis---inflammation of the pancreas occurring with
the mumps
• Acute pancreatitis---associated with heavy alcohol intake or
biliary tract obstruction
– result is patient secretes trypsin in the pancreas & starts
to digest himself
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Regulation of Pancreatic Secretions
• Secretin
– acidity in intestine
causes increased
sodium bicarbonate
release
• GIP
– fatty acids & sugar
causes increased insulin
release
• CCK
– fats and proteins cause
increased digestive
enzyme release
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LIVER AND GALLBLADDER
• The liver is the heaviest gland in the body and the second
largest organ in the body after the skin.
• Anatomy of the Liver and Gallbladder
• The liver is divisible into left and right lobes, separated by
the falciform ligament. Associated with the right lobe are the
caudate and quadrate lobes (Figure 24.14).
• The gallbladder is a sac located in a depression on the
posterior surface of the liver (Figure 24.14).
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Anatomy of the Liver and Gallbladder
• Liver
– weighs 3 lbs.
– below diaphragm
– right lobe larger
– gallbladder on right
lobe
– size causes right
kidney to be lower
than left
• Gallbladder
– fundus, body &
neck
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Histology of
the Liver Introduction
• Hepatocytes arranged in
lobules
• Sinusoids in between
hepatocytes are blood-filled
spaces
• Kupffer cells phagocytize
microbes & foreign matter
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Histology of the Liver
• The lobes of the liver are made up of lobules that contain
hepatic cells (liver cells or hepatocytes), sinusoids, stellate
reticuloendothelial (Kupffer’s) cells, and a central vein
(Figure 24.15).
• Bile is secreted by hepatocytes.
• Bile passes into bile canaliculi to bile ducts to the right and
left hepatic ducts which unite to form the common hepatic
duct (Figure 24.14).
• Common hepatic duct joins the cystic duct to form the
common bile duct which enters the hepatopancreatic
ampulla.
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Histology of the Gallbladder
•
•
•
•
Simple columnar epithelium
No submucosa
Three layers of smooth muscle
Serosa or visceral peritoneum
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Application
• Jaundice is a yellowish coloration of the sclera, skin, and
mucous membranes due to a buildup of bilirubin. The main
categories of jaundice are prehepatic, hepatic, and
enterohepatic.
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Blood Supply
• The liver receives a double supply of blood from the hepatic
artery and the hepatic portal vein. All blood eventually
leaves the liver via the hepatic vein (Figure 24.16).
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Blood Supply to the Liver • Hepatic portal vein
– nutrient rich blood
from stomach, spleen
& intestines
• Hepatic artery from
branch off the aorta
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Flow of Fluids Within the Liver
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Bile - Overview
• Hepatic cells (hepatocytes) produce bile that is transported by a duct
system to the gallbladder for concentration and temporary storage.
• Bile is partially an excretory product (containing components of worn-out
red blood cells) and partially a digestive secretion.
• Bile’s contribution to digestion is the emulsification of triglycerides.
• The fusion of individual crystals of cholesterol is the beginning of 95% of
all gallstones. Gallstones can cause obstruction to the outflow of bile in
any portion of the duct system. Treatment of gallstones consists of using
gallstone-dissolving drugs, lithotripsy, or surgery.
• The liver also functions in carbohydrate, lipid, and protein metabolism;
removal of drugs and hormones from the blood; excretion of bilirubin;
synthesis of bile salts; storage of vitamins and minerals; phagocytosis;
and activation of vitamin D.
• In a liver biopsy a sample of living liver tissue is removed to diagnose a
number of disorders.
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Pathway of Bile
Secretion
• Bile capillaries
• Hepatic ducts connect to form common hepatic duct
• Cystic duct from gallbladder & common hepatic duct join to form
common bile duct
• Common bile duct & pancreatic duct empty into duodenum
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Bile Production
• One quart of bile/day is secreted by the liver
– yellow-green in color & pH 7.6 to 8.6
• Components
– water & cholesterol
– bile salts = Na & K salts of bile acids
– bile pigments (bilirubin) from hemoglobin molecule
• globin = a reuseable protein
• heme = broken down into iron and bilirubin
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Regulation of Bile Secretion
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Liver Functions--Carbohydrate Metabolism
• Turn proteins into glucose
• Turn triglycerides into glucose
• Turn excess glucose into glycogen & store
in the liver
• Turn glycogen back into glucose as needed
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Liver Functions --Lipid Metabolism
• Synthesize cholesterol
• Synthesize lipoproteins----HDL and
LDL(used to transport fatty acids in
bloodstream)
• Stores some fat
• Breaks down some fatty acids
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Liver Functions--Protein Metabolism
• Deamination = removes NH2 (amine group) from
amino acids so can use what is left as energy source
• Converts resulting toxic ammonia (NH3) into urea for
excretion by the kidney
• Synthesizes plasma proteins utilized in the clotting
mechanism and immune system
• Convert one amino acid into another
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Other Liver Functions
• Detoxifies the blood by removing or altering drugs & hormones(thyroid &
estrogen)
• Removes the waste product--bilirubin
• Releases bile salts help digestion by emulsification
• Stores fat soluble vitamins-----A, B12, D, E, K
• Stores iron and copper
• Phagocytizes worn out blood cells & bacteria
• Activates vitamin D (the skin can also do this with 1 hr of sunlight a
week)
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Summary of Digestive Hormones
• Gastrin
– stomach, gastric & ileocecal sphincters
• Gastric inhibitory peptide--GIP
– stomach & pancreas
• Secretin
– pancreas, liver & stomach
• Cholecystokinin--CCK
– pancreas, gallbladder, sphincter of Oddi, &
stomach
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SMALL INTESTINE
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Introduction
• The major events of digestion and absorption occur in the
small intestine.
• The small intestine extends from the pyloric sphincter to the
ileocecal sphincter.
• Anatomy of the Small Intestine
• The small intestine is divided into the duodenum, jejunum,
and ileum (Figure 24.17).
• Projections called circular folds, or plicae circularies, are
permanent ridges in the mucosa that enhance absorption by
increasing surface area and causing chyme to spiral as it
passes through the small intestine (Figure 24.17).
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Anatomy of the Small Intestine
• 20 feet long----1 inch in diameter
• Large surface area for majority of absorption
• 3 parts
– duodenum---10 inches
– jejunum---8 feet
– ileum---12 feet
• ends at ileocecal valve
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• plica circularis
– permanent ½ inch tall folds that
contain part of submucosal
layer
– not found in lower ileum
– can not stretch out like rugae in
stomach
• villi
– 1 Millimeter tall
– Core is lamina propria of
mucosal layer
– Contains vascular capillaries
and lacteals(lymphatic
capillaries)
• microvilli
– cell surface feature known as
brush border
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small intestine
104
Small Intestine - Overview
• The mucosa forms fingerlike villi which increase the surface area of the
epithelium available for absorption and digestion (Figure 24.18a).
• Embedded in the villus is a lacteal (lymphatic capillary) for fat
absorption.
• The cells of the mucosal epithelium include absorptive cells, goblet cells,
enteroendocrine cells, and Paneth cells (Figure 24.18b).
• The free surface of the absorptive cells feature microvilli, which increase
the surface area (Figure 24.19d). They form the brush border which also
contains several enzymes.
• The mucosa contains many cavities lined by glandular epithelium. These
cavities form the intestinal glands (crypts of Lieberkuhn).
• The submucosa of the duodenum contains duodenal (Brunner’s) glands
which secrete an alkaline mucus that helps neutralize gastric acid in
chyme. The submucosa of the ileum contains aggregated lymphatic
nodules (Peyer’s patches) (Figure 24.19a).
• The muscularis consists of 2 layers of smooth muscles
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Histology of Small Intestine
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Functions of Microvilli
•
•
•
•
Absorption and digestion
Digestive enzymes found at cell surface on microvilli
Digestion occurs at cell surfaces
Significant cell division within intestinal glands
produces new cells that move up
• Once out of the way---rupturing and releasing their
digestive enzymes & proteins
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Cells of Intestinal Glands
• Absorptive cell
• Goblet cell
• Enteroendocrine
– secretin
– cholecystokinin
– gastric inhibitory
peptide
• Paneth cells
– secretes lysozyme
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Goblet Cells of GI epithelium
Unicellular glands
that are part of
simple columnar
epithelium
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Roles of Intestinal Juice & Brush-Border Enzymes
• Submucosal layer has duodenal glands
– secretes alkaline mucus
• Mucosal layer contains intestinal glands = Crypts of
Lieberkuhn(deep to surface)
– secretes intestinal juice
• 1-2 qt./day------ at pH 7.6
– brush border enzymes
– paneth cells secrete lysozyme kills bacteria
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Intestinal Juice and Brush Border Enzymes
• Intestinal juice provides a vehicle for absorption of
substances from chyme as they come in contact with the
villi.
• Some intestinal enzymes (brush border enzymes) break
down foods inside epithelial cells of the mucosa on the
surfaces of their microvilli.
• Some digestion also occurs in the lumen of the small
intestine.
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Mechanical Digestion in the Small Intestine
• Segmentation, the major movement of the small intestine, is
a localized contraction in areas containing food.
• Peristalsis propels the chyme onward through the intestinal
tract.
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Mechanical Digestion in the Small Intestine
• Weak peristalsis in
comparison to the
stomach---chyme remains
for 3 to 5 hours
• Segmentation---local
mixing of chyme with
intestinal juices---sloshing
back & forth
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Chemical Digestion in the Small Intestine
• Carbohydrates are broken down into monosaccharides for
absorption.
• Intestinal enzymes break down starches into maltose,
maltotriose, and alpha-dextrins (pancreatic amylase); alphadextrins into glucose (alphadestrinase); maltose to glucose
(maltase); sucrose to glucose and fructose (sucrase); and
lactose to glucose and galactose (lactase).
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Chemical Digestion in Small Intestine
• Chart page 853--groups enzymes by region where they are
found
• Need to trace breakdown of nutrients
– carbohydrates
– proteins
– lipids
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Review: Digestion of Carbohydrates
•
•
•
•
Mouth---salivary amylase
Esophagus & stomach---nothing happens
Duodenum----pancreatic amylase
Brush border enzymes (maltase, sucrase & lactase)
act on disaccharides
– produces monosaccharides--fructose, glucose &
galactose
– lactose intolerance (no enzyme; bacteria ferment
sugar)--gas & diarrhea
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Lactose Intolerance
• Mucosal cells of small intestine fail to produce lactase
– essential for digestion of lactose sugar in milk
– undigested lactose retains fluid in the feces
– bacterial fermentation produces gases
• Symptoms
– diarrhea, gas, bloating & abdominal cramps
• Dietary supplements are helpful
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Review: Digestion of Proteins
• Stomach
– HCl denatures or unfolds proteins
– pepsin turns proteins into peptides
• Pancreas
– digestive enzymes---split peptide bonds between different
amino acids
– brush border enzymes-----aminopeptidase or dipeptidase
• enzymes break peptide bonds that attach terminal amino
acids to carboxyl ends of peptides (carboxypeptidases)
• enzymes break peptide bonds that attach terminal amino
acids to amino ends of peptides (aminopeptidases)
– enzymes split dipeptides to amino acids (dipeptidase)
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Review: Digestion of Lipids
• Mouth----lingual lipase
• Most lipid digestion, in an adult, occurs in the
small intestine.
– emulsification by bile of globules of
triglycerides
– pancreatic lipase---splits triglycerides into fatty
acids & monoglycerides
– no enzymes in brush border
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Digestion of Nucleic Acids
• Nucleic acids are broken down into nucleotides for absorption.
• Pancreatic juice contains 2 nucleases
– ribonuclease which digests RNA
– deoxyribonuclease which digests DNA
• Nucleotides produced are further digested by brush border
enzymes (nucleosidease and phosphatase)
– pentose, phosphate & nitrogenous bases
• Absorbed by active transport
A summary of digestive enzymes in terms of source,
substrate acted on, and product is presented in Table
24.5.
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Regulation of Secretion & Motility
• Enteric reflexes that respond to presence of chyme
– increase intestinal motility
– VIP (vasoactive intestinal polypeptide) stimulates
the production of intestinal juice
– segmentation depends on distention which sends
impulses to the enteric plexus & CNS
• distention produces more vigorous peristalsis
• 10 cm per second
• Sympathetic impulses decrease motility
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Regulation of Secretion & Motility
• Enteric reflexes that respond to presence of chyme
– increase intestinal motility
– VIP (vasoactive intestinal polypeptide) stimulates
the production of intestinal juice
– segmentation depends on distention which sends
impulses to the enteric plexus & CNS
• distention produces more vigorous peristalsis
• 10 cm per second
• Sympathetic impulses decrease motility
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Absorption in the Small Intestine
• Absorption is the passage of the end products of digestion
from the GI tract into blood or lymph and occurs by diffusion,
facilitated diffusion, osmosis, and active transport.
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Absorption in Small Intestine
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Where will the absorbed nutrients go?
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Absorption of Monosaccharides
• Essentially all carbohydrates are absorbed as
monosaccharides.
• They are absorbed into blood capillaries (Figure 24.19 a,b).
• Absorption of Amino Acids, Dipeptides, and Tripeptides
• Most proteins are absorbed as amino acids by active
transport processes.
• They are absorbed into the blood capillaries in the villus
(Figure 24.22a,b).
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Absorption of Monosaccharides
• Absorption into epithelial cell
– glucose & galactose----sodium symporter(active transport)
– fructose-----facilitated diffusion
• Movement out of epithelial cell into bloodstream
– by facilitated diffusion
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Absorption of Amino Acids & Dipeptides
• Absorption into epithelial cell
– active transport with Na+ or H+ ions (symporters)
• Movement out of epithelial cell into blood
– diffusion
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Absorption of Lipids - Overview
• Dietary lipids are all absorbed by simple diffusion.
• Long-chain fatty acids and monoglycerides are absorbed as part of
micelles, resynthesized to triglycerides, and formed into protein-coated
spherical masses called chylomicrons.
• Chylomicrons are taken up by the lacteal of a villus.
• From the lacteal they enter the lymphatic system and then pass into the
cardiovascular system, finally reaching the liver or adipose tissue
(Figure 24.23, 24.22a).
• The plasma lipids - fatty acids, triglycerides, cholesterol - are insoluble in
water and body fluids.
• In order to be transported in blood and utilized by body cells, the lipids
must be combined with protein transporters called lipoproteins to make
them soluble.
• The combination of lipid and protein is referred to as a lipoprotein.
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Absorption of Lipids
•
•
•
•
•
Small fatty acids enter cells & then blood by simple diffusion
Larger lipids exist only within micelles (bile salts coating)
Lipids enter cells by simple diffusion leaving bile salts behind in gut
Bile salts reabsorbed into blood & reformed into bile in the liver
Fat-soluble vitamins are enter cells since were within micelles
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Absorption of Lipids
• Inside epithelial cells fats are rebuilt and coated with protein to form
chylomicrons
•
Chylomicrons leave intestinal cells by exocytosis into a lacteal
– travel in lymphatic system to reach veins near the heart
– removed from the blood by the liver and fat tissue
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Absorption of Electrolytes
• Many of the electrolytes absorbed by the small intestine come
from gastrointestinal secretions and some are part of digested
foods and liquids.
• Enter epithelial cells by diffusion & secondary active transport
– sodium & potassium move = Na+/K+ pumps (active transport)
– chloride, iodide and nitrate = passively follow
– iron, magnesium & phosphate ions = active transport
• Intestinal Ca+ absorption requires vitamin D & parathyroid
hormone
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Absorption of Vitamins
• Fat-soluble vitamins (A, D, E, and K) are included along
with ingested dietary lipids
– travel in micelles & are absorbed by simple diffusion
• Water-soluble vitamins (B and C)
– absorbed by diffusion
• B12 combines with intrinsic factor before it is transported
into the cells
– receptor mediated endocytosis
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Absorption of Water
• Figure 24.24 reviews the fluid input to the GI tract.
• All water absorption in the GI tract occurs by osmosis from
the lumen of the intestines through epithelial cells and into
blood capillaries.
• The absorption of water depends on the absorption of
electrolytes and nutrients to maintain an osmotic balance
with the blood.
• Table 24.5 summarizes the digestive and absorptive
activities of the small intestine and associated accessory
structures.
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Absorption of Water
• 9 liters of fluid dumped into GI
tract each day
• Small intestine reabsorbs 8 liters
• Large intestine reabsorbs 90% of
that last liter
• Absorption is by osmosis through
cell walls into vascular capillaries
inside villi
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LARGE INTESTINE
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Anatomy of the Large Intestine (Figure 24.25b)
• The large intestine (colon) extends from the ileocecal
sphincter to the anus.
• Its subdivisions include the cecum, colon, rectum, and anal
canal (Figure 24.25a).
• Hanging inferior to the cecum is the appendix.
– Inflammation of the appendix is called appendicitis.
– A ruptured appendix can result in gangrene or peritonitis,
which can be life-threatening conditions.
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Anatomy of
Large Intestine
•
•
•
•
5 feet long by 2½ inches in diameter
Ascending & descending colon are retroperitoneal
Cecum & appendix
Rectum = last 8 inches of GI tract anterior to the sacrum &
coccyx
• Anal canal = last 1 inch of GI tract
– internal sphincter----smooth muscle & involuntary
– external sphincter----skeletal muscle & voluntary control
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Appendicitis
• Inflammation of the appendix due to blockage of the
lumen by chyme, foreign body, carcinoma, stenosis, or
kinking
• Symptoms
– high fever, elevated WBC count, neutrophil count
above 75%
– referred pain, anorexia, nausea and vomiting
– pain localizes in right lower quadrant
• Infection may progress to gangrene and perforation
within 24 to 36 hours
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Histology of the Large Intestine
• The mucosa of the large intestine has no villi or permanent
circular folds. It does have a simple columnar epithelium
with numerous globlet cells (Figure 24.26).
• The muscularis contains specialized portions of the
longitudinal muscles called taeniae coli, which contract and
gather the colon into a series of pouches called haustra
(Figure 24.25a).
• Polyps in the colon are generally slow growing and benign.
They should be removed because they may become
cancerous.
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Histology of
Large
Intestine
• Mucosa
– smooth tube -----no villi or plica
– intestinal glands fill the the mucosa
– simple columnar cells absorb water &
goblet cells secrete mucus
• Submucosal & mucosa contain lymphatic
nodules
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Histology of Large Intestine
• Muscular layer
– internal circular layer is
normal
– outer longitudinal muscle
• taeniae coli = shorter
bands
• haustra (pouches)
formed
• epiploic appendages
• Serosa = visceral peritoneum
• Appendix
– contains large amounts of
lymphatic tissue
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Mechanical Digestion in Large Intestine
• Mechanical movements of the large intestine include
haustral churning, peristalsis, and mass peristalsis.
• Peristaltic waves (3 to 12 contractions/minute)
– haustral churning----relaxed pouches are filled from
below by muscular contractions (elevator)
– gastroilial reflex = when stomach is full, gastrin hormone
relaxes ileocecal sphincter so small intestine will empty
and make room
– gastrocolic reflex = when stomach fills, a strong
peristaltic wave moves contents of transverse colon into
rectum
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Chemical Digestion in Large Intestine
• No enzymes are secreted only mucous
• Bacteria ferment
– undigested carbohydrates into carbon dioxide &
methane gas
– undigested proteins into simpler substances
(indoles)----odor
– turn bilirubin into simpler substances that produce
color
• Bacteria produce vitamin K and B in colon
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Absorption & Feces Formation in the Large
Intestine
• Some electrolytes---Na+ and Cl• After 3 to 10 hours, 90% of H2O has been removed from
chyme
• Feces are semisolid by time reaches transverse colon
• Feces = dead epithelial cells, undigested food such as
cellulose, bacteria (live & dead)
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Absorption and Feces Formation in the Large
Intestine
• The large intestine absorbs water, electrolytes, and some
vitamins.
• Feces consist of water, inorganic salts, sloughed-off
epithelial cells, bacteria, products of bacterial
decomposition, and undigested parts of food.
• Although most water absorption occurs in the small
intestine, the large intestine absorbs enough to make it an
important organ in maintaining the body’s water balance.
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Defecation Reflex
• The elimination of feces from the rectum is called
defecation.
• Defecation is a reflex action aided by voluntary contractions
of the diaphragm and abdominal muscles. The external anal
sphincter can be voluntarily controlled (except in infants) to
allow or postpone defecation.
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Defecation
• Gastrocolic reflex moves feces into
rectum
• Stretch receptors signal sacral
spinal cord
• Parasympathetic nerves contract
muscles of rectum & relax internal
anal sphincter
• External sphincter is voluntarily
controlled
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Defecation Problems
• Diarrhea = chyme passes too quickly through intestine
– H20 not reabsorbed
• Constipation--decreased intestinal motility
– too much water is reabsorbed
– remedy = fiber, exercise and water
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Applications
• Dietary fiber may be classified as insoluble (does not dissolve in water)
and soluble (dissolves in water).
– Both types affect the speed of food passage through the GI tract
• Insoluble fiber
– woody parts of plants (wheat bran, veggie skins)
– may help protect against colon cancer
• Soluble fiber
– gel-like consistency = beans, oats, citrus white parts, apples
– lowers blood cholesterol by preventing reabsorption of bile
salts so liver has to use cholesterol to make more
• Colonoscoy is the visual examination of the lining of the colon using an
elongated, flexible, fiberoptic endoscope.
• Occult blood test is to screen for colorectal cancer.
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Review
• Table 24.6 summarizes the digestive activities in the large
intestine while Table 24.7 summarizes the organs of the
digestive system and their functions.
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PHASES OF DIGESTION
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Regulation of Gastric Secretion and Motility
• Cephalic phase
• Gastric phase
• Intestinal phase
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Gastric Secretion and Motility
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Cephalic phase
• The cephalic phases is initiated by sensory receptors in the
head; prepares the mouth and stomach for food that is
about to be eaten.
• Cerebral cortex =sight, smell, taste & thought
– stimulate parasympathetic nervous system
• The facial and glossopharyngeal nerves stimulate the
salivary glands.
• Vagus nerve increases stomach muscle and glandular
activity
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Gastric Phase = “Stomach Working”
• Nervous control keeps stomach active
– stretch receptors & chemoreceptors provide information
– vigorous peristalsis and glandular secretions continue
– chyme is released into the duodenum
• Endocrine influences over stomach activity
– distention and presence of caffeine or protein cause G
cells secretion of gastrin into bloodstream
– gastrin hormone increases stomach glandular secretion
– gastrin hormone increases stomach churning and
sphincter relaxation
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Intestinal phase
• The intestinal phase begins when food enters the small intestine.
• Stretch receptors, fatty acids or sugar signals medulla
– sympathetic nerves slow stomach activity & increase intestinal
activity
– The enterogastric reflex inhibits gastric motility and increases the
contraction of the pyloric sphincter to decrease gastric emptying.
• Hormonal influences
– secretin stimulates the flow of pancreatic juice rich in bicarbonate,
and inhibits the secretion of gastric juice.
– cholecystokinin(CCK) decreases stomach emptying and stimulates
the secretion of pancreatic juice rich in digestive enzymes, and
increase the flow of bile
– gastric inhibitory peptide(GIP) decreases stomach secretions,
motility & emptying
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Absorption of Nutrients by the Stomach
•
•
•
•
Water especially if it is cold
Electrolytes
Some drugs (especially aspirin) & alcohol
Fat content in the stomach slows the passage of alcohol to the intestine
where absorption is more rapid
• Gastric mucosal cells contain alcohol dehydrogenase that converts some
alcohol to acetaldehyde-----more of this enzyme found in males than
females
• Females have less total body fluid that same size male so end up with
higher blood alcohol levels with same intake of alcohol
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Regulation of Gastric
Emptying - Review
• Release of chyme is regulated by neural and
hormonal reflexes
• Distention & stomach contents increase
secretion of gastrin hormone & vagal nerve
impulses
– stimulate contraction of esophageal
sphincter and stomach and relaxation of
pyloric sphincter
• Enterogastric reflex regulates amount
released into intestines
– distension of duodenum & contents of
chyme
– sensory impulses sent to the medulla
inhibit parasympathetic stimulation of the
stomach but increase secretion of
cholecystokinin and stimulate sympathetic
impulses
– inhibition of gastric emptying
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Vomiting (emesis)
• Forceful expulsion of contents of stomach & duodenum through
the mouth
• Cause
– irritation or distension of stomach
– unpleasant sights, general anesthesia, dizziness & certain
drugs
• Sensory input from medulla cause stomach contraction &
complete sphincter relaxation
• Contents of stomach squeezed between abdominal muscles
and diaphragm and forced through open mouth
• Serious because loss of acidic gastric juice can lead to alkalosis
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Other hormones
• Other hormones that have effects on the GI tract are motilin,
substance P, bombesin, vasoactive intestinal polypeptide
(VIP), gastrin-releasing peptide, and somatostatin.
• Table 24.8 summarizes the major hormones that control
digestion.
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DEVELOPMENT OF THE DIGESTIVE SYSTEM
• The endoderm of the primitive gut forms the epithelium and
glands of most of the gastrointestinal tract (Figure 24.12).
• The mesoderm of the primitive gut forms the smooth muscle
and connective tissue of the GI tract.
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Development of the Digestive System
• Endoderm forms primitive gut with help from the splanchnic mesoderm --resulting tube is made up of epithelial, glandular, muscle & connective
tissue
• Differentiates into foregut, midgut & hindgut
• Endoderm grows into the mesoderm to form salivary glands, liver,
gallbladder & pancreas
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Development of the Digestive System
• Stomodeum develops
into oral cavity
– oral membrane
ruptures
• Proctodeum develops
into anus
– cloacal membrane
ruptures
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Aging and the Digestive System
• Changes that occur
– decreased secretory mechanisms
– decreased motility
– loss of strength & tone of muscular tissue
– changes in neurosensory feedback
– diminished response to pain & internal stimuli
• Symptoms
– sores, loss of taste, peridontal disease, difficulty swallowing, hernia,
gastritis, ulcers, malabsorption, jaundice, cirrhosis, pancreatitis,
hemorrhoids and constipation
• Cancer of the colon or rectum is common
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Diseases of the GI Tract
•
•
•
•
•
•
Dental caries and periodontal disease
Peptic Ulcers
Diverticulitis
Colorectal cancer
Hepatitis
Anorexia nervosa
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DISORDERS: HOMEOSTATIC IMBALANCES
• Dental caries, or tooth decay, is started by acid-producing
bacteria that reside in dental plaque, act on sugars, and
demineralize tooth enamel and dentin with acid.
• Periodontal diseases are characterized by inflammation and
degeneration of the gingivae (gums), alveolar bone,
periodontal ligament, and cementum.
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DISORDERS: HOMEOSTATIC IMBALANCES
• Peptic ulcers are crater-like lesions that develop in the
mucous membrane of the GI tract in areas exposed to
gastric juice. The most common complication of peptic
ulcers is bleeding, which can lead to anemia if blood loss is
serious. The three well-defined causes of peptic ulcer
disease (PUD) are the bacterium Helicobacter pylori;
nonsteroidal anti-inflammatory drugs, such as aspirin; and
hypersecretion of HCl.
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DISORDERS: HOMEOSTATIC IMBALANCES
• Diverticula are saclike outpouchings of the wall of the colon
in places where the muscularis has become weak. The
development of diverticula is called diverticulosis.
Inflammation within the diverticula, known as diverticulitis,
may cause pain, nausea, vomiting, and either constipation
or an increased frequency of defecation. High fiber diets
help relieve the symptoms.
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DISORDERS: HOMEOSTATIC IMBALANCES
• Hepatitis is an inflammation of the liver and can be caused
by viruses, drugs, and chemicals, including alcohol.
• Hepatitis A (infectious hepatitis) is caused by hepatitis A
virus and is spread by fecal contamination. It does not
cause lasting liver damage.
• Hepatitis B is caused by hepatitis B virus and is spread
primarily by sexual contact and contaminated syringes and
transfusion equipment. It can produce cirrhosis and possibly
cancer of the liver. Vaccines are available to prevent
hepatitis B infection.
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DISORDERS: HOMEOSTATIC IMBALANCES
• Hepatitis C is caused by the hepatitis C virus. It is clinically
similar to hepatitis B and is often spread by blood
transfusions. It can cause cirrhosis and possibly liver
cancer.
• Hepatitis D is caused by hepatitis D virus. It is transmitted
like hepatitis B and, in fact, a person must be co-infected
with hepatitis B before contracting hepatitis D. It results in
severe liver damage and has a high fatality rate.
• Hepatitis E is caused by hepatitis E virus and is spread like
hepatitis A. It is responsible for a very high mortality rate in
pregnant women.
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DISORDERS: HOMEOSTATIC IMBALANCES
• Anorexia nervosa is a chronic disorder characterized by
self-induced weight loss, body-image and other perceptual
disturbances, and physiologic changes that result from
nutritional depletion. The disorder is found predominantly in
young, single females and may be inherited. Individuals may
become emaciated and may ultimately die of starvation or
one of its complications. Treatment consists of
psychotherapy and dietary regulation.
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end
Principles of Human Anatomy and Physiology, 11e
173
Chapter 25
Metabolism and Nutrition
Suggested Lecture Outline
INTRODUCTION
• The food we eat is our only source of energy for performing
biological work.
• There are three major metabolic destinations for the
principle nutrients. They will be used for energy for active
processes, synthesized into structural or functional
molecules, or synthesized as fat or glycogen for later use as
energy.
METABOLIC REACTIONS
• Metabolism refers to all the chemical reactions in the body.
• Catabolism includes all chemical reactions that break down
complex organic molecules while anabolism refers to
chemical reactions that combine simple molecules to form
complex molecules.
• The chemical reactions of living systems depend on transfer
of manageable amounts of energy from one molecule to
another. This transfer is usually performed by ATP (Figure
25.1).
ENERGY TRANSFER
• All molecules (nutrient molecules included) have energy
stored in the bonds between their atoms.
Oxidation-Reduction Reactions
• Oxidation is the removal of electrons from a molecule and
results in a decrease in the energy content of the molecule.
Because most biological oxidations involve the loss of
hydrogen atoms, they are called dehydrogenation reactions.
• When a substance is oxidized, the liberated hydrogen atoms
do not remain free in the cell but are transferred immediately
by coenzymes to another compound.
• Reduction is the opposite of oxidation, that is, the addition of
electrons to a molecule and results in an increase in the
energy content of the molecule.
Coenzymes
• Two coenzymes are commonly used by living cells to carry
hydrogen atoms: nicotinamide adenine dinucleotide (NAD)
and flavin adenine dinucleotide (FAD).
• An important point to remember about oxidation-reduction
reactions is that oxidation is usually an energy-releasing
reaction.
Mechanisms of ATP Generation
• Phosphorylation is
– bond attaching 3rd phosphate group contains
stored energy
• Mechanisms of phosphorylation
– within animals
• substrate-level phosphorylation in cytosol
• oxidative phosphorylation in mitochondria
– in chlorophyll-containing plants or bacteria
• photophosphorylation.
Phosphorylation in Animal Cells
• In cytoplasm (1)
• In mitochondria (2, 3 & 4)
CARBOHYDRATE METABOLISM
• During digestion, polysaccharides and disaccharides are
converted to monosaccharides (primarily glucose)
– absorbed through capillaries in villi
– transported to the liver via the hepatic portal vein
• Liver cells convert much of the remaining fructose and
practically all of the galactose to glucose
– carbohydrate metabolism is primarily concerned with
glucose metabolism.
Carbohydrate Review
• In GI tract
– polysaccharides broken down into simple sugars
– absorption of simple sugars (glucose, fructose &
galactose)
• In liver
– fructose & galactose transformed into glucose
– storage of glycogen (also in muscle)
• In body cells --functions of glucose
– oxidized to produce energy
– conversion into something else
– storage energy as triglyceride in fat
Fate of Glucose
• Since glucose is the body’s preferred source for
synthesizing ATP, the fate of absorbed glucose depends on
the energy needs of body cells.
• If the cells require immediate energy, glucose is oxidized by
the cells to produce ATP.
Fate of Glucose
• Glucose can be used to form amino acids, which then can
be incorporated into proteins.
• Excess glucose can be stored by the liver and skeletal
muscles as glycogen, a process called glycogenesis.
• If glycogen storage areas are filled up, liver cells and fat
cells can convert glucose to glycerol and fatty acids that can
be used for synthesis of triglycerides (neutral fats) in the
process of lipogenesis.
Glucose Movement into Cells
• Glucose absorption in the GI tract is accomplished by
secondary active transport (Na+ - glucose symporters).
• Glucose movement from blood into most other body cells
occurs via facilitated diffusion transporters (Glu-T
molecules). Insulin increases the insertion of Glu-T4
molecules into the plasma membranes except neurons and
hepatocytes, thus increasing the rate of facilitated diffusion
of glucose.
• Glucose is trapped in the cell when it becomes
phosphorylated.
– Concentration gradient remains favorable for more
glucose to enter
Glucose Movement
into Cells
• In GI tract and kidney tubules
– Na+/glucose symporters
• Most other cells
– GluT facilitated diffusion
transporters
– insulin increases the insertion
of GluT transporters in the
membrane of most cells
– in liver & brain, always lots of
GluT transporters
• Glucose 6-phosphate forms
immediately inside cell (requires
ATP) thus, glucose is “hidden”
when it is in the cell.
– Concentration gradient
remains favorable for more
glucose to enter.
Glucose
Catabolism
Glucose
Oxidation
• Cellular respiration
– 4 steps are involved
– glucose + O2 produces
H2O + energy + CO2
• Anaerobic respiration
– called glycolysis (1)
– formation of acetyl CoA (2)
is transitional step to Krebs cycle
• Aerobic respiration
– Krebs cycle (3) and electron transport chain (4)
Glycolysis
• Glycolysis refers to the
breakdown of the six-carbon
molecule, glucose, into two
three-carbon molecules of
pyruvic acid.
– 10 step process occurring in
cell cytosol
– use two ATP molecules, but
produce four, a net gain of
two (Figure 25.3).
Glycolysis in Ten Steps
Glycolysis of Glucose & Fate of Pyruvic Acid
• Breakdown of six-carbon
glucose molecule into 2
three-carbon molecules of
pyruvic acid
– Pyruvic acid is
converted to acetylCoA,
which enters the Kreb’s
Cycle.
– The Kreb’s Cycle will
require NAD+
• NAD+ will be
reduced to the highenergy intermediate
NADH.
Glycolysis of Glucose &
Fate of Pyruvic Acid
When O2 falls short in a cell
– pyruvic acid is reduced
to lactic acid
• coupled to oxidation
of NADH to NAD+
• NAD+ is then
available for further
glycolysis
– lactic acid rapidly
diffuses out of cell to
blood
– liver cells remove lactic
acid from blood &
convert it back to
pyruvic acid
Pyruvic Acid
• The fate of pyruvic acid depends on the availability of O2.
Formation of Acetyl
Coenzyme A
• Pyruvic acid enters the
mitochondria with help
of transporter protein
• Decarboxylation
– pyruvate
dehydrogenase
converts 3 carbon
pyruvic acid to 2
carbon fragment
acetyle group plus
CO2.
Formation of Acetyl Coenzyme A
• 2 carbon fragment (acetyl
group) is attached to
Coenzyme A to form Acetyl
coenzyme A, which enter Krebs
cycle
– coenzyme A is derived from
pantothenic acid (B vitamin).
Krebs Cycle
• The Krebs cycle is also called
the citric acid cycle, or the
tricarboxylic acid (TCA) cycle.
It is a series of biochemical
reactions that occur in the
matrix of mitochondria (Figure
25.6).
Krebs Cycle
Krebs Cycle
• The large amount of chemical potential energy stored in
intermediate substances derived from pyruvic acid is
released step by step.
• The Krebs cycle involves decarboxylations and oxidations
and reductions of various organic acids.
• For every two molecules of acetyl CoA that enter the Krebs
cycle, 6 NADH, 6 H+, and 2 FADH2 are produced by
oxidation-reduction reactions, and two molecules of ATP are
generated by substrate-level phosphorylation (Figure 25.6).
• The energy originally in glucose and then pyruvic acid is
primarily in the reduced coenzymes NADH + H+ and FADH2.
Krebs Cycle (Citric Acid Cycle)
• The oxidation-reduction
& decarboxylation
reactions occur in matrix
of mitochondria.
– acetyl CoA (2C)
enters at top &
combines with a 4C
compound
– 2 decarboxylation
reactions peel 2
carbons off again
when CO2 is formed
• Potential energy (of chemical bonds) is released step by
step to reduce the coenzymes (NAD+NADH &
FADFADH2) that store the energy
Review:
Krebs Cycle
• Glucose 2 acetyl CoA molecules
• each Acetyl CoA
molecule that enters the Krebs
cycle produces
– 2 molecules of C02
– 3 molecules of NADH + H+
– one molecule of ATP
– one molecule of FADH2
Review
• Figure 25.7
summarizes the
eight reactions
of the Krebs
cycle.
Electron Transport Chain
• The electron transport chain involves a sequence of electron
carrier molecules on the inner mitochondrial membrane,
capable of a series of oxidation-reduction reactions.
• As electrons are passed through the chain, there is a
stepwise release of energy from the electrons for the
generation of ATP.
• In aerobic cellular respiration, the last electron receptor of
the chain is molecular oxygen (O2). This final oxidation is
irreversible.
• The process involves a series of oxidation-reduction
reactions in which the energy in NADH + H+ and FADH2 is
liberated and transferred to ATP for storage.
Electron
Transport Chain
• Pumping of
hydrogen is linked
to the movement of
electrons passage
along the electron
transport chain.
• It is called
chemiosmosis
(Figure 25.8.)
• Note location.
Chemiosmosis
• H+ ions are
pumped from matrix
into space between
inner & outer
membrane
• High concentration
of H+ is maintained
outside of inner
membrane
• ATP synthesis
occurs as H+
diffuses through a
special H+ channels
in the inner
membrane
Electron Transport Chain
• The carrier molecules involved include flavin
mononucleotide, cytochromes, iron-sulfur centers, copper
atoms, and ubiquinones (also coenzyme Q).
Electron Carriers
• Flavin mononucleotide (FMN) is derived from
riboflavin (vitamin B2)
• Cytochromes are proteins with heme group (iron)
existing either in reduced form (Fe+2) or oxidized
form (Fe+3)
• Iron-sulfur centers contain 2 or 4 iron atoms bound to
sulfur within a protein
• Copper (Cu) atoms bound to protein
• Coenzyme Q is nonprotein carrier mobile in the lipid
bilayer of the inner membrane
Steps in Electron Transport
• Carriers of electron transport chain are clustered into 3 complexes that
each act as a proton pump (expelling H+)
• Mobile shuttles (CoQ and Cyt c) pass electrons between complexes.
• The last complex passes its electrons (2H+) to oxygen to form a water
molecule (H2O)
Proton Motive Force & Chemiosmosis
• Buildup of H+ outside the inner membrane creates + charge
– The potential energy of the electrochemical gradient is called the proton
motive force.
• ATP synthase enzymes within H+ channels use the proton motive force to
synthesize ATP from ADP and P
Summary of Aerobic Cellular Respiration
• The complete oxidation of glucose can be represented as
follows:
• C6H12O6 + 6O2 => 36 or 38ATP + 6CO2 +6H2O
• During aerobic respiration, 36 or 38 ATPs can be generated
from one molecule of glucose.
– Two of those ATPs come from substrate-level
phosphorylation in glycolysis.
– Two come from substrate-level phosphorylation in the
Krebs cycle.
Review
• Table 25.1 summarizes the ATP
yield during aerobic respiration.
• Figure 25.8 summarizes the sites
of the principal events of the
various stages of cellular
respiration.
Glycogenesis &
Glycogenolysis
• Glycogenesis
– glucose storage as
glycogen
– 4 steps to glycogen
formation in liver or
skeletal muscle
– stimulated by insulin
• Glycogenolysis
– glucose release
Glycogenesis &
Glycogenolysis
• Glycogenesis
– glucose storage as glycogen
• Glycogenolysis
– glucose release
– not a simple reversal of
steps
– Phosphorylase enzyme is
activated by glucagon
(pancreas) & epinephrine
(adrenal gland)
– Glucose-6-phosphatase
enzyme is only in
hepatocytes so muscle can
not release glucose into the
serum.
Carbohydrate Loading
• Long-term athletic events (marathons) can exhaust
glycogen stored in liver and skeletal muscles
• Eating large amounts of complex carbohydrates (pasta
& potatoes) for 3 days before a marathon maximizes
glycogen available for ATP production
• Useful for athletic events lasting for more than an hour.
Gluconeogenesis
• Gluconeogenesis is the conversion of protein or fat
molecules into glucose (Figure 25.12).
Gluconeogenesis
• Glycerol (from fats) may be converted to glyceraldehyde-3phosphate and some amino acids may be converted to
pyruvic acid. Both of these compounds may enter the Krebs
cycle to provide energy.
• Gluconeogenesis is stimulated by cortisol, thyroid hormone,
epinephrine, glucagon, and human growth hormone.
Transport of Lipids by Lipoproteins
• Most lipids are
transported in the blood
in combination with
proteins as lipoproteins
(Figure 25.13).
Transport of Lipids by Lipoproteins
• Four classes of
lipoproteins are
chylomicrons, very lowdensity lipoproteins
(VLDLs), low-density
lipoproteins (LDLs),
and high-density
lipoproteins (HDLs).
Lipoproteins
• Chylomicrons form in small intestinal mucosal cells and
contain exogenous (dietary) lipids. They enter villi lacteals,
are carried into the systemic circulation into adipose tissue
where their triglyceride fatty acids are released and stored in
the adipocytes and used by muscle cells for ATP
production.
• VLDLs contain endogenous triglycerides. They are transport
vehicles that carry triglycerides synthesized in hepatocytes
to adipocytes for storage. VLDLs are converted to LDLs.
• LDLs carry about 75% of total blood cholesterol and deliver
it to cells throughout the body. When present in excessive
numbers, LDLs deposit cholesterol in and around smooth
muscle fibers in arteries.
• HDLs remove excess cholesterol from body cells and
transport it to the liver for elimination.
Classes of
Lipoproteins
• Chylomicrons (2 % protein)
– form in intestinal mucosal cells
– transport exogenous (dietary) fat
• apo C-2 activates enzyme that releases the fatty acids
from the chylomicron for absorption by adipose &
muscle cells; liver processes what is left
• VLDLs (10% protein)
– transport endogenous triglycerides (from liver) to fat cells
– converted to LDLs
• LDLs (25% protein) --- “bad cholesterol”
– carry 75% of blood cholesterol to body cells
– apo B100 is docking protein for receptor-mediated
endocytosis of the LDL into a body cell
• HDLs (40% protein) --- “good cholesterol”
– carry cholesterol from cells to liver for elimination
Cholesterol
• There are two sources of cholesterol in the body: food we
eat and liver synthesis.
• For adults, desirable levels of blood cholesterol are
– TC (total cholesterol) under 200 mg/dl
– LDL under 130 mg/dl
– HDL over 40 mg/dl.
– Normally, triglycerides are in the range of 10-190 mg/dl.
• Among the therapies used to reduce blood cholesterol level
– Exercise
– Diet
– Drugs that inhibit the synthesis of cholesterol
Fate of Lipids,
• Some lipids may be oxidized to produce ATP.
• Some lipids are stored in adipose tissue.
• Other lipids are used as structural molecules or to
synthesize essential molecules. Examples include
– phospholipids of plasma membranes
– lipoproteins that transport cholesterol
– thromboplastin for blood clotting
– myelin sheaths to speed up nerve conduction
– cholesterol used to synthesize bile salts and steroid
hormones.
Review
• The various functions of lipids in the body may be reviewed
in Table 2.7.
Triglyceride Storage
• Triglycerides are stored in adipose tissue, mostly in the
subcutaneous layer.
• Adipose cells contain lipases that catalyze the deposition of
fats from chylomicrons and hydrolyze neutral fats into fatty
acids and glycerol.
– 50% subcutaneous, 12% near kidneys, 15% in omenta,
15% in genital area, 8% between muscles
• Fats in adipose tissue are not inert. They are catabolized
and mobilized constantly throughout the body.
Lipid Catabolism: Lipolysis
• Triglycerides are split into fatty acids and glycerol (a process
called lipolysis) under the influence of hormones such as
epinephrine, norepinephrine, and glucocorticoids and
released from fat deposits. Glycerol and fatty acids are then
catabolized separately (Figure 25.14).
Lipid Catabolism: Lipolysis
• Glycerol can be converted into glucose by conversion into
glyceraldehyde-3-phosphate.
• In beta oxidation, carbon atoms are removed in pairs from
fatty acid chains. The resulting molecules of acetyl
coenzyme A enter the Krebs cycle.
Lipid Catabolism: Ketogenesis
• As a part of normal fatty acid catabolism two acetyl CoA
molecules can form acetoacetic acid which can then be
converted to beta-hydroxybutyric acid and acetone.
• These three substances are known as ketone bodies and
their formation is called ketogenesis (Figure 25.14).
– heart muscle & kidney cortex prefer to use acetoacetic
acid for ATP production
Lipid Anabolism: Lipogenesis
• The conversion of glucose or amino acids into lipids is
called lipogenesis. The process is stimulated by insulin
(Figure 25.14).
• The intermediary links in lipogenesis are glyceraldehyde-3phosphate and acetyl coenzyme A.
Clinical Application
• Blood ketone levels are usually very low
– many tissues use ketone for ATP production
– An excess of ketone bodies, called ketosis, may cause
acidosis or abnormally low blood pH.
• Fasting, starving or high fat meal with few carbohydrates
results in excessive beta oxidation & ketone production
– acidosis (ketoacidosis) is abnormally low blood pH
– sweet smell of ketone body acetone on breath
– occurs in diabetic since triglycerides are used for ATP
production instead of glucose & insulin inhibits lipolysis
PROTEIN METABOLISM
• During digestion, proteins are hydrolyzed into amino acids.
Amino acids are absorbed by the capillaries of villi and enter
the liver via the hepatic portal vein.
Fate of Proteins
• Amino acids, under the influence of human growth hormone
and insulin, enter body cells by active transport.
• Inside cells, amino acids are synthesized into proteins that
function as enzymes, transport molecules, antibodies,
clotting chemicals, hormones, contractile elements in
muscle fibers, and structural elements. They may also be
stored as fat or glycogen or used for energy. (Table 2.8)
Protein Catabolism
• Amino acids can be
converted to
substances that can
enter the Krebs
cycle.
– Deamination
– Decarboxylation
– Hydrogenation
– (Figure 25.13).
• Amino acids can be
converted into
– Glucose
– fatty acids
– ketone bodies
Protein Catabolism
• Liver cells convert
amino acids into
substances that can
enter the Krebs cycle
– deamination
removes the amino
group (NH2)
• converts it to
ammonia (NH3)
& then urea
• urea is excreted
in the urine
• Converted substances
enter the Krebs cycle
to produce ATP.
Protein Anabolism
– involves the
formation of peptide
bonds between
amino acids to
produce new
proteins.
– stimulated by human
growth hormone,
thyroxine, and insulin.
– carried out on the
ribosomes of almost
every cell in the body,
directed by the cells’
DNA and RNA.
Amino Acids
• Of the 20 amino acids in your body, 10 are referred to as
essential amino acids. These amino acids cannot be
synthesized by the human body from molecules present
within the body. They are synthesized by plants or bacteria.
Food containing these amino acids are “essential” for
human growth and must be a part of the diet.
• Nonessential amino acids can be synthesized by body cells
by a process called transamination. Once the appropriate
essential and nonessential amino acids are present in cells,
protein synthesis occurs rapidly.
Clinical Application: PKU
• Phenylketonuria (PKU) is a genetic error of protein
metabolism characterized by elevated blood and urine
levels of the amino acid phenylalanine.
– caused by a mutation in the gene that codes for the
enzyme phenylalanine hydrolylase.
– This enzyme is needed to convert phenylalanine to
tyrosine.
– Tyrosine can enter the Krebs cycle
• PKU causes vomiting, seizures & mental retardation
– Screening of newborns prevents retardation.
– Requires a restricted diet to avoid elevated phenylalanine
– avoid Nutrasweet which contains phenylalanine
KEY MOLECULES AT METABOLIC CROSSROADS
• Although there are thousands of different chemicals in your
cells, three molecules play key roles in metabolism
– glucose-6-phosphate
– pyruvic acid
– acetyl CoA
– (Figure 25.16).
Key Molecules at Metabolic Crossroads
• Glucose 6-phosphate, pyruvic
acid and acetyl coenzyme A
play pivotal roles in
metabolism
• Different reactions occur
because of nutritional status or
level of physical activity
Role of Glucose 6-Phosphate
•
Glucose is converted to glucose 6-phosphate just after
entering the cell
• Possible fates of glucose 6-phosphate
– used to synthesize glycogen when glucose is
abundant
– if glucose 6-phosphatase enzyme is present, glucose
can be re-released from the cell
– precursor of a five-carbon sugar used to make RNA
& DNA (ribose-5-phosphate)
– converted to pyruvic acid during glycolysis in most
cells of the body
Role of Pyruvic Acid
• 3-carbon molecule formed when glucose undergoes
glycolysis
• If oxygen is available, cellular respiration proceeds (pyruvic
acid  AcetylCoA
• If oxygen is not available, only anaerobic reactions can
occur
– pyruvic acid  lactic acid to regenerate NAD+
• Conversions
– amino acid alanine produced from pyruvic acid
– to oxaloacetic acid of Krebs cycle
Role of Acetyl coenzyme A
• Can be used to synthesize fatty acids, ketone bodies, or
cholesterol
• Can not be converted to pyruvic acid so can not be used to
reform glucose
Review
• Table 25.2 summarizes carbohydrate, lipid, and protein
metabolism.
METABOLIC ADAPTATIONS
• Your metabolic reactions depends on how recently you have
eaten. During the absorptive state, which alternates with the
postabsorptive state, ingested nutrients enter the blood and
lymph from the GI tract, and glucose is readily available for
ATP production.
• An average meal requires about 4 hours for complete
absorption, and given three meals a day, the body spends
about 12 hours of each day in the absorptive state. (The
other 12 hours, during late morning, late afternoon, and
most of the evening, are spent in the postabsorptive state.)
• Hormones are the major regulators of reactions during each
state.
Metabolism During the Absorptive State
• Several things typically happen during the absorptive state
(Figure 25.17).
• Most body cells produce ATP by oxidizing glucose to carbon
dioxide and water.
• Glucose transported to the liver is converted to glycogen or
triglycerides. Little is oxidized for energy.
• Most dietary lipids are stored in adipose tissue.
• Amino acids in liver cells are converted to carbohydrates,
fats, and proteins.
Absorptive State
Points where
insulin
stimulation
occurs.
Regulation of Metabolism During the Absorptive State
• Gastric inhibitory peptide and the rise in blood glucose
concentration stimulate insulin release from pancreatic beta
cells.
• Insulin’s functions
– increases anabolism & synthesis of storage molecules
– decreases catabolic or breakdown reactions
– promotes entry of glucose & amino acids into cells
– stimulates phosphorylation of glucose
– enhances synthesis of triglycerides
– stimulates protein synthesis along with thyroid & growth
hormone
• Table 25.3 summarizes the hormonal regulation of
metabolism in the absorptive state.
Metabolism During the Postabsorptive State
• The major concern of the body during the postabsorptive
state is to maintain normal blood glucose level (70 to 110
mg/100 ml of blood).
– glucose enters blood from 3 major sources
• glycogen breakdown in liver produces glucose
• glycerol from adipose converted by liver into glucose
• gluconeogenesis using amino acids produces glucose
– alternative fuel sources are
• fatty acids from fat tissue fed into Krebs as acetyl CoA
• lactic acid produced anaerobically during exercise
• oxidation of ketone bodies by heart & kidney
Homeostasis of blood glucose concentration is
especially important for the nervous system and red
blood cells.
Metabolism During the Postabsorptive State
• Most body tissue switch to utilizing fatty acids, except brain
still need glucose.
– fatty acids are unable to pass the blood-brain barrier.
• Red blood cells
– derive all of their ATP from glycolysis of glucose because
they lack mitochondria (and thus lack the Krebs cycle
and electron transport chain.)
Postabsorptive State Reactions
• Reactions that produce glucose are the breakdown of liver
glycogen, gluconeogenesis using lactic acid, and
gluconeogenesis using amino acids (Figure 25.18).
• Reactions that produce ATP without using glucose are
oxidation of fatty acids, oxidation of lactic acid, oxidation of
amino acids, oxidation of ketone bodies, and breakdown of
muscle glycogen.
Postabsorptive State
Regulation of Metabolism During the Postabsorptive
State
• The hormones that stimulate metabolism in the
postabsorptive counter the insulin effects that dominate the
absorptive state. The most important anti-insulin hormone is
glucagon.
– released from pancreatic alpha cells
– stimulates gluconeogenesis & glycogenolysis within the
liver
• Hypothalamus detects low blood sugar
– sympathetic neurons release norepinephrine and adrenal
medulla releases norepinephrine & epinephrine
• stimulates glycogen breakdown & lipolysis
• raises glucose & free fatty acid blood levels
Review
• Table 25.4 summarizes hormonal regulation of metabolism
in the postabsorptive state.
Metabolism During Fasting and Starvation
• Fasting means going without food for many hours or a few
days whereas starvation implies weeks or months of food
deprivation or inadequate food intake.
• Catabolism of stored triglycerides and structural proteins
can provide energy for several weeks.
• The amount of adipose tissue determines the lifespan
possible without food.
• During fasting and starvation, nervous tissue and red blood
cells continue to use glucose for ATP production.
Prolonged Fasting
• During prolonged fasting, large amounts of amino acids
from tissue protein breakdown (primarily from skeletal
muscle) are released to be converted to glucose in the liver
by gluconeogenesis.
• The most dramatic metabolic change that occurs with
fasting and starvation is the increase in formation of ketone
bodies by hepatocytes.
• Ketogenesis increases as catabolism of fatty acids rises.
• The presence of ketones actually reduces the use of
glucose for ATP production, which in turn decreases the
demand for gluconeogenesis and slows the catabolism of
muscle proteins.
Absorption of Alcohol
• Absorption begins in the stomach but is absorbed more
quickly in the small intestine
– fat rich foods keep the alcohol from leaving the
stomach and prevent a rapid rise in blood alcohol
– a gastric mucosa enzyme breaks down some of the
alcohol to acetaldehyde
• Females develop higher blood alcohols
– have a smaller blood volume
– have less gastric alcohol dehydrogenase activity
Heat
• Heat is a form of kinetic energy that can be measured as
temperature and expressed in units called calories.
• A calorie, spelled with a little c, is the amount of heat energy
required to raise the temperature of 1 gram of water from
140C to 150C.
• A kilocalorie or Calorie, spelled with a capital C, is equal to
1000 calories.
Metabolic Rate
• The overall rate at which heat is produced is termed the
metabolic rate.
• Measurement of the metabolic rate under basal conditions is
called the basal metabolic rate (BMR).
• BMR is a measure of the rate body breaks down nutrients to
liberate energy
– made under specific conditions
– quiet, resting, fasting
• BMR is also a measure of how much thyroxine the thyroid
gland is producing, since thyroxine regulates the rate of ATP
use and is not a controllable factor under basal conditions.
Metabolic Rate and Heat Production
• Factors that affect metabolic rate and thus the production
of body heat
– exercise increases metabolic rate as much as 15 times
– hormones regulate basal metabolic rate
• thyroid, insulin, growth hormone & testosterone
increase BMR
– sympathetic nervous system’s release of epinephrine &
norepinephrine increases BMR
– higher body temperature raises BMR
– ingestion of food raises BMR 10-20%
– children’s BMR is double that of an elderly person
– gender, climate, sleep, and malnutrition
Hypothalmic
Thermostat
•
•
•
•
The hypothalmic thermostat is the
preoptic area.
Nerve impulses from the preoptic
area propagate to other parts of
the hypothalamus known as the
heat-losing center and the heatpromoting center.
Several negative feedback loops
work to raise body temperature
when it drops too low or raises
too high (Figure 25.19).
Heat conservation mechanisms
– Vasoconstriction
– sympathetic stimulation
– skeletal muscle contraction
(shivering)
– thyroid hormone production
Body Temperature Homeostasis
• If the amount of heat production equals the amount of heat
loss, one maintains a constant core temperature near 370C
(98.60F).
• Core temperature refers to the body’s temperature in body
structures below the skin and subcutaneous tissue.
• Shell temperature refers to the body’s temperature at the
surface, that is, the skin and subcutaneous tissue.
– shell temperature is usually 1 to 6 degrees lower
• Too high a core temperature kills
– denaturing body proteins
• Too low a core temperature kills
– cardiac arrhythmias
Energy Loss
• Heat is lost from the body by radiation, evaporation,
conduction, and convection.
• Radiation is the transfer of heat from a warmer object to a
cooler object without physical contact.
• Evaporation is the conversion of a liquid to a vapor. Water
evaporating from the skin takes with it a great deal of heat.
The rate of evaporation is inversely related to relative
humidity.
• Conduction is the transfer of body heat to a substance or
object in contact with the body, such as chairs, clothing,
jewelry, air, or water.
• Convection is the transfer of body heat by a liquid or gas
between areas of different temperature.
Clinical Application
• Hypothermia refers to a lowering of body temperature to
350C (950F) or below. It may be caused by an overwhelming
cold stress, metabolic disease, drugs, burns, malnutrition,
transection of the cervical spinal cord, and lowering of body
temperature for surgery.
Energy Homeostasis and Regulation of Food Intake
• Energy homeostasis occurs when energy intake is matched
to energy expenditure
• Energy intake depends on the amount of food consumed
• Energy expenditure depends on basal metabolic rate
(BMR), nonexercise thermogenesis (NEAT), and food
induced thermogenesis.
Energy Homeostasis and Regulation of Food Intake
• Two centers in the hypothalamus related to regulation of
food intake are the feeding (hunger) center and satiety
center. The feeding center is constantly active but may be
inhibited by the satiety center (Figure 14.10).
• The hormone leptin acts on the hypothalamus to inhibit
ciruits that stimulate eating and to activate circuits that
increase enerby expenditure.
• Other stimuli that affect the feeding and satiety centers are
glucose, amino acids, lipids, body temperature, distention of
the GI tract, and choleocystokinin.
Clinical Application
• Eating is response to emotions is called emotional eating.
Problems arise when emotional eating becomes so
excessive that it interferes with health.
NUTRITION
• Guidelines for healthy eating include eating a variety of
foods; maintaining healthy weight; choosing foods low in fat,
saturated fat, and cholesterol; eating plenty of vegetables,
fruits, and grain products; using sugar only in moderation;
using salt and sodium only in moderation; and drinking
alcohol only in moderation or not at all.
• The Food Guide Pyramid (Figure 25.20) shows how many
servings of the five major food groups to eat each day.
Food Guide Pyramid 2002
Food Guide Pyramid
• Foods high in complex carbohydrates serve as the base of
the pyramid since they should be consumed in largest
quantity.
• Minerals are inorganic substances that help regulate body
processes.
• Minerals known to perform essential functions include
calcium, phosphorus, sodium, chlorine, potassium,
magnesium, iron, sulfur, iodine, manganese, cobalt, copper,
zinc, selenium, and chromium.
• Their functions are summarized in Table 25.5.
Minerals
• Inorganic substances = 4% body weight
• Functions
– calcium & phosphorus form part of the matrix of bone
– help regulate enzymatic reactions
• calcium, iron, magnesium & manganese
– magnesium is catalyst for conversion of ADP to ATP
– form buffer systems
– regulate osmosis of water
– generation of nerve impulses
Vitamins
• Vitamins are organic nutrients that maintain growth and
normal metabolism. Many function in enzyme systems as
coenzymes.
• Most vitamins cannot be synthesized by the body. No single
food contains all of the required vitamins – one of the best
reasons for eating a varied diet.
• Based on solubility, vitamins fall into two main groups: fatsoluble and water-soluble.
Vitamins
• Fat-soluble vitamins are emulsified into micelles and
absorbed along with ingested dietary fats by the small
intestine. They are stored in cells (particularly liver cells) and
include vitamins A, D, E, and K.
• Water-soluble vitamins are absorbed along with water in the
GI tract and dissolve in the body fluids. Excess quantities of
these vitamins are excreted in the urine. The body does not
store water-soluble vitamins well. They include the B
vitamins and vitamin C.
Antioxidant Vitamins
• C, E and beta-carotene (a provitamin)
• Inactivate oxygen free radicals
– highly reactive particles that carry an unpaired
electron
• damage cell membranes, DNA, and contribute
to atherosclerotic plaques
• arise naturally or from environmental hazards
such as tobacco or radiation
• May protect against cancer, aging, cataract
formation, and atherosclerotic plaque
Vitamin and Mineral Supplements
• Eat a balanced diet rather than taking supplements
• Exceptions
– iron for women with heavy menstrual bleeding
– iron & calcium for pregnant or nursing women
– folic acid if trying to become pregnant
• reduce risk of fetal neural tube defects
– calcium for all adults
– B12 for strict vegetarians
– antioxidants C and E recommended by some
Clinical Application: Vitamin-related Disorders
• The sources, functions, and related deficiency disorders of
the principal vitamins are listed in Table 25.6.
• Most physicians do not recommend taking vitamin or
mineral supplements except in special circumstances, and
instead suggest being sure to eat a balanced diet that
includes a variety of food.
DISORDERS: HOMEOSTATIC IMBALANCES
• Obesity is defined as a body weight more than 20% above
desirable standard as the result of excessive accumulation
of fat.
• Even moderate obesity is hazardous to health.
• Risk factor in many diseases
– cardiovascular disease, hypertension, pulmonary
disease,
– non-insulin dependent diabetes mellitus
– arthritis, certain cancers (breast, uterus, and colon),
– varicose veins, and gallbladder disease.
Fever
• Fever is an elevation of body temperature that is due to
resetting of the hypothalamic thermostat. The most
common cause of fever is a viral or bacterial infection
– toxins from bacterial or viral infection = pyrogens
– heart attacks or tumors
– tissue destruction by x-rays, surgery, or trauma
– reactions to vaccines
• Beneficial in fighting infection & increasing rate of tissue
repair during the course of a disease
• Complications--dehydration, acidosis, & brain damage.