Topics to Review

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Topics to Review

• Macromolecules (monomer to polymer structure)
• Membrane transport proteins (carriers, pumps,
  channels)
• Active Transport
• Diffusion
• Osmosis
• Simple epithelium
• Enzymes
• Hydrolysis
• Exocrine glands

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Digestive System

• The digestive system allows your body to obtain
  substances required to sustain life that your
  body cannot make on its own including
• monosaccharides, amino acids, nucleic acids,
  fats, vitamins, electrolytes (ions) and water
• The alimentary canal or gastrointestinal (GI)
  tract is a long muscular tube lined with
  epithelial tissue passing through the body which
  is closed off at each end by a sphincter of
  skeletal muscle
• Opens to the outside world therefore the lumen
  and its contents are part of the external
  environment
• Its primary function is to move water, nutrients
  and electrolytes from the external environment
  into the bodys internal environment

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The Digestive System

• Accessory organs and exocrine glands (teeth,
  salivary glands, pancreas and the liver) aid in
  the process of digestion in the alimentary canal
  by physical manipulation of food or through the
  secretion of substances into the GI tract

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Anatomy of the Digestive System

• Begins with the oral cavity (mouth and pharynx)
  where chewing and the secretion of saliva starts
  digestion
• Food moves through the GI tract (esophagus to
  anus)
• rings of smooth muscle act as sphincters to
  separate the tube into segments (esophagus ?
  stomach ? small intestine ? large intestine) with
  different functions
• Digestive secretions are added to the food by GI
  epithelium, liver and pancreas, turning it into a
  soupy mixture called chyme
• The products of digestion pass out of the lumen
  into the ECF where they pass into blood or lymph
  for distribution throughout the body
• Any material remaining in the lumen at the end of
  the GI tract is defecated through the anus

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Peritoneum

• 2 connective tissue membranes in the abdominal
  cavity which protect the organs in the abdominal
  cavity from damage by friction/abrasion
• Visceral peritoneum
• covers external surface of digestive organs
• Parietal peritoneum
• lines the internal wall of the abdominal cavity
• Between the 2 layers of the peritoneum is a
  peritoneal cavity which is filled with the
  peritoneal fluid secreted by the cells of each
  layer
• the fluid functions to lubricate digestive
  organs, allowing them to slide across one another
  without creating friction which would lead to
  inflammation

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4 Basic Processes of the Digestive System

• Digestion
• mechanical and chemical breakdown of food
• Motility
• movement of material along the GI tract
• Secretion
• release of substances (hydrolytic enzymes, mucus,
  acid, bicarbonate, water, ions) from salivary
  glands, GI epithelial cells, hepatocytes or
  pancreatic acinar cells into the GI tract lumen
  or ECF
• Absorption
• active or passive transfer of substances from the
  lumen of the GI tract to ECF
• Processes are regulated by the nervous and
  endocrine systems as well as paracrine signals

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4 Basic Processes of the Digestive System
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Wall of the Alimentary Canal

• 4 principle layers of the GI tract
• Mucosa (superficial)
• inner layer of epithelial, connective and
  muscular tissues that faces lumen
• Submucosa
• loose connective tissue with blood and lymph
  vessels and submucosal plexus of the Enteric
  Nervous System
• Muscularis
• 2 layers of smooth muscle (superficial circular
  and deeper longitudinal) responsible for motility
  which is innervated by the myenteric plexus of
  the Enteric Nervous System
• Serosa (deep)
• strong connective tissue membrane that maintains
  the structural integrity of the alimentary canal
  (visceral layer of the peritoneum)

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Layers of the Alimentary Canal Wall
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Mucosal Epithelium

• Simple epithelium
• absorptive cells use integral transporting
  proteins in the apical and basal membranes to
  absorb ions, water and nutrients out of the lumen
  into the body by facilitated diffusion, primary
  and secondary active transport processes
• secretory cells (endocrine and exocrine)
• exocytose digestive enzymes and mucus into lumen
  for digestion and protection against the
  autodigestion of the mucosa, respectively
• exocytose hormones and/or paracrine molecules
  into the ECF for digestive regulation
• sensory cells act as mechano- and chemoreceptors
  which detect the presence of food by the
  distension of the GI wall and by the presence of
  specific chemicals (proteins, salts, acids, fats)

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Enteric Nervous System

• A specialized division of the nervous system
  associated only with the alimentary canal
• Connected to the CNS via the Parasympathetic NS
  (stimulates digestion) and Sympathetic NS
  (inhibits digestion)
• Composed of two major nerve plexuses (groups)
  which send both sensory and motor information
  throughout the alimentary canal to control
  digestion
• Submucosal nerve plexus (submucosa layer)
• associated with mechano- and chemoreceptors in
  the mucosa
• controls the endo- and exocrine secretion of the
  mucosa
• Myenteric nerve plexus (muscularis layer)
• controls the contraction of smooth muscle

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Chemical Digestion

• Chemical digestion occurs by the action of
  powerful enzymes that are either secreted into
  the lumen or are integral proteins of the mucosal
  epithelium hydrolyze complex macromolecules into
  molecules small enough to be absorbable
• Occurs in the mouth, stomach and small intestine

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Motility

• Contraction of the muscularis causes motility in
  2 ways
• Peristalsis is characterized by progressive waves
  of contraction that move from one section to the
  next
• moves food between 2 and 25 cm/sec
• occurs over long distances in esophagus to move
  food from the pharynx to the stomach and within
  the stomach where it contributes to the mixing of
  food
• occurs over short distances in the small
  intestine
• Segmentation is characterized by short segments
  of the small and large intestines alternately
  contracting and relaxing which mixes contents and
  keeps them in contact with absorptive epithelium

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Secretion and Absorption

• Exocrine (epithelial) cells of the salivary
  glands, pancreas and liver as well as the GI
  mucosal cells secrete as much as 7 liters of
  enzymes, mucus, electrolytes and water into the
  lumen daily
• Occurs in all segments from the mouth to the
  rectum
• The 7 liters of fluid secreted daily into the
  lumen of the GI tract must be absorbed to prevent
  dehydration
• excessive vomiting or diarrhea can be dangerous
• In addition, an average human ingests 2 liters of
  food and fluid daily that also needs to be
  absorbed
• By the time the food and secretions reach the
  rectum 98.9 will be absorbed and moved into the
  body leaving 100 mL of fluid to be defecated
• Occurs in the small and large intestines

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3 Stages of Digestion

• The processes of digestion, secretion, motility
  and absorption take place throughout the entire
  length of the GI tract in 3 overlapping stages
  named by the location of food
• Cephalic (head) phase
• thinking about, smelling, or seeing food which
  has not entered the alimentary canal
• food is in the mouth
• Gastric phase
• food is in the stomach
• Intestinal phase
• food is in the small intestine

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Cephalic phase

• This phase prepares the digestive system before
  the ingestion of food which significantly
  decreases the time required for digestion and
  absorption
• Anticipatory stimuli as well as the presence of
  food in the mouth activate Parasympathetic
  Nervous System (PNS) controlled reflexes
  coordinated by the medulla oblongata
• Action potentials from the medulla are sent to
  the stomach, small and large intestines to
  increase the secretion of the mucosal cells as
  well as stimulate the contraction of the
  muscularis to move the previously consumed food
  distally towards the rectum
• In addition, action potentials are sent to the
  salivary glands, and the pancreas to stimulate
  secretion of saliva and pancreatic juice,
  respectively

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Composition and Functions of Saliva

• Water
• Ions
• Hydrolytic enzymes
• salivary amylase
• begins the chemical digestion of carbohydrates
• lingual lipase
• begins the chemical digestion of lipids
• Mucin
• protein that aids in the lubrication of a bolus
• ball of chewed food and saliva that is swallowed
• Lysozyme
• antibacterial enzyme that reduces the risk of
  infections

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Swallowing (Deglutition)

• The tongue forces the bolus into the pharynx
  causing the epiglottis to fold over the opening
  to the airways (glottis) and diverts the bolus
  into the esophagus
• The tonically contracted upper esophageal
  sphincter which keeps the proximal esophagus
  closed, relaxes and opens momentarily while
  breathing is inhibited
• Once the bolus enters the esophagus, a strong
  peristaltic wave pushes the bolus to the stomach

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• At distal end of the esophagus, the tonically
  contracted lower esophageal sphincter (cardiac
  sphincter) momentarily relaxes and opens
  momentarily to allow the bolus to enter the
  stomach
• if the cardiac sphincter does not close properly,
  gastric juice containing acid can enter the
  esophagus causing painful irritatation (heart
  burn)

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Gastric Phase

• As food enters the stomach, the gastric phase of
  digestion begins
• The cephalic phase continues until the food has
  been completely ingested and swallowed
• The presence of food in the stomach detected by
  mechanoreceptors and chemoreceptors stimulates
  the secretion of gastric juice from the gastric
  mucosa into the lumen of the stomach to further
  hydrolyze ingested food
• The presence of food in the stomach detected by
  mechanoreceptors and chemoreceptors also
  stimulates the contraction of the muscularis
  which mixes the food with gastric juice making a
  soupy mixture called chyme

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Gross Anatomy of the Stomach

• The stomach is divided into the 3 regions the
  fundus, the body and the antrum and is able to
  hold up to 2 liters of food and fluid when
  completely filled

• When the stomach is empty, the mucosa folds into
  rugae
• when filled, the expanded wall of the stomach
  causes these folds to disappear (flatten)

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The Stomach Wall

• Tubular invaginations (depressions) of the
  surface epithelium called gastric glands extend
  down into the supporting connective tissue

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• Chief cells and parietal cells of gastric glands
  secrete substances into the lumen of the stomach
  which combine to make gastric juice

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Gastric Juice

• Chief cells
• secrete the inactive enzyme (zymogen) pepsinogen
• Begins the chemical hydrolysis of proteins when
  pepsinogen is converted to pepsin (active)
• secrete gastric lipase
• continues the chemical hydrolysis of lipids
• Parietal cells
• secrete HCl (hydrochloric acid) to lower pH to
  2.0 (optimal for chemical digestion in the
  stomach)
• denatures swallowed proteins, kills bacteria and
  activates pepsin
• secrete intrinsic factor which forms complexes
  with vitamin B12 and is essential for its
  absorption in the intestine
• lack of intrinsic factor results in pernicious
  anemia which is a reduction of red blood cell
  synthesis due to a vitamin B12 deficiency

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Protection of the Stomach Mucosa

• Mucous cells secrete a combination of mucus
  (superficial physical barrier) and bicarbonate
  (chemical buffer barrier under mucus) to protect
  the mucosa from autodigestion by HCl

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Hormonal Control of Gastric Function

• The food that enters the stomach dilutes the HCl
  component of gastric juice which causes the pH to
  increase above 2
• in response, (G cells) of the gastric glands
  secrete the hormone gastrin
• gastrin stimulates the parietal cells to secrete
  additional HCl to return the pH to 2
• During the intestinal phase (while food is slowly
  leaving the stomach), the intestinal hormones
  secretin and cholecystokinin (CCK) inhibit HCl
  secretion from parietal cells and inhibit the
  muscularis of the stomach thus limiting the rate
  of acidic chyme movement into the small intestine

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Gastric Motility

• As food particles are reduced to a more uniform
  texture, each peristaltic wave forces a
  contracted pyloric sphincter open which allows
  only a small amount of chyme to move into the
  small intestine

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Small Intestine 3 Segments

• The 3 segments of the small intestine include
  the duodenum (proximal 25 cm), the jejunum
  (middle 250 cm) and the ileum (distal 360 cm)
• Here digestion is completed by intestinal enzymes
  aided by the secretions of the liver and pancreas
• hepatic and pancreatic secretions (bile and
  pancreatic juice) enter the lumen of the small
  intestine at the duodenum through a duct which is
  guarded by the contracted sphincter of Oddi to
  keep these fluids from entering the small
  intestine except during the intestinal phase of
  digestion
• The presence of food in the small intestine
  detected by mechanoreceptors stimulates a
  combination of segmental and peristaltic
  contractions which mixes the chyme with
  pancreatic juice and bile and moves it toward the
  large intestine

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Small Intestine
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Pancreas

• A triangular gland located behind the stomach
  which has both exocrine and endocrine functions
• Acinar (epithelial) cells secrete pancreatic
  juice into a duct that empties through the
  sphincter of Oddi at the duodenum
• Pancreatic islets (islets of Langerhans) secrete
  the hormones insulin and glucagon to control
  blood glucose levels

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Pancreatic Juice

• Acinar cells exocytose pancreatic juice into the
  pancreatic duct which flows into the duodenum
• Pancreatic juice contains
• pancreatic amylase hydrolyzes carbohydrates
• pancreatic proteases hydrolyze proteins
• secreted as zymogens
• pancreatic lipase hydrolyzes lipids
• pancreatic nucleases hydrolyze nucleic acids
• bicarbonate (HCO3-)
• a buffer secreted by duct cells that neutralizes
  the gastric acid, raising the pH to 8.0 (optimal
  for both pancreatic and intestinal enzymes)

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Pancreatic Zymogens

• The pancreatic zymogens include
• trypsinogen
• chymotrypsinogen
• procarboxypeptidase
• The zymogens are converted to their active form
  by a series of biochemical reactions initially
  catalyzed by the duodenal brush-border enzyme
  enterokinase
• enzymatically hydrolyzes trypsinogen to trypsin
• trypsin then activates the other 2 zymogens
• chymotrypsinogen to chymotrypsin
• procarboxypeptidase to carboxypeptidase

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Activation of Pancreatic Zymogens
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Liver and Gallbladder

• Hepatocytes of the liver secrete bile into the
  hepatic ducts leading to the gallbladder
• composed of bile acids and phospholipids
• a detergent which causes fat emulsification
• increases the surface area of fat globules
• increases of lipid hydrolysis by lipase
• Gallbladder
• a muscular sac that stores bile secreted from the
  liver when the sphincter of Oddi is closed

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Hormonal Control of Intestinal Phase

• The presence of acidic chyme in the small
  intestine causes the secretion of the intestinal
  hormone secretin
• stimulates the secretion of pancreatic
  bicarbonate
• The presence of fatty acids and peptides in the
  chyme in the small intestine causes the secretion
  of the intestinal hormone CCK
• stimulates the secretion of pancreatic enzymes
• stimulates the contraction of the gallbladder to
  squeeze the bile into the bile duct
• relaxes (opens) the sphincter of Oddi, allowing
  the entry of pancreatic juice and bile into
  duodenum
• Both secretin and CCK inhibit HCl secretion from
  parietal cells and inhibit the muscularis of the
  stomach thus limiting the rate of acidic chyme
  movement into the small intestine

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pH lt 8
fats and proteins
distension
inhibits peristalsis and HCl secretion
secretin
CCK
stimulates muscularis
stimulates enzyme secretion
stimulates contraction
causes relaxation
stimulates HCO3- secretion
slow gastric emptying
increase pH in the small intestine
expel bile
chemically digest chyme
bile and pancreatic juice flows into duodenum
segmentation and peristalsis
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Small Intestinal Mucosa

• Structural modifications of the mucosa increase
  the amount of surface area for digestion and
  absorption
• When the small intestine is empty, the mucosa is
  folded into structures called plicae or circular
  folds
• when filled, the expanded wall of the small
  intestine causes these folds to disappear
  (flatten)
• Intestinal mucosa also projects into the lumen in
  small fingerlike structures called villi
• Tubular invaginations (depressions) of the
  surface epithelium that extend down into the
  supporting connective tissue of the small
  intestine are called crypts

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Sectional View of Small Intestine
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• Individual epithelial cells of the small
  intestinal mucosa have a highly folded apical
  cell membrane
• each fold is called a microvilli and increase the
  number of integral membrane proteins for
  digestion (enzymes) and absorption (transporters)
  that can be exposed to the lumen
• aka the brush border for its bristle-like
  appearance

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Summary of Chemical Digestion in the GI Tract

• Carbohydrates
• salivary amylase (minor) in the mouth
• pancreatic amylase (major) in the small intestine
• Proteins
• pepsin (minor) in the stomach
• pancreatic proteases (major) in the small
  intestine
• Lipids
• lingual lipase (minor) in the mouth
• gastric lipase (minor) in the stomach
• pancreatic lipase (major) in the small intestine
• bile significantly increases the rate of
  hydrolysis
• Nucleic acids
• pancreatic nucleases (deoxyribonucleases and
  ribonucleases) in the small intestine
• Brush-border enzymes of the small intestine
  complete the final hydrolysis of carbohydrates,
  proteins and nucleotides prior to their absorption

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Absorption of Polar Substances

• Absorption begins as the molecules cross the
  apical cell membrane of an absorptive cell of a
  villus and diffuse to the basal side of the cell
• Absorption is completed as the molecules cross
  the basal cell membrane of an absorptive cell and
  is moved into a blood vessel (polar molecules) or
  a lymph lacteal (nonpolar molecules) in the
  submucosa of a villus
• Most polar molecules (amino acids, nucleotides,
  monosaccharides) cross the apical cell membrane
  by secondary active transport, using the Na
  gradient generated by the Na, K-ATPase across
  the cell membrane
• 95 of ingested and secreted (salivary, gastric,
  pancreatic, hepatic, and intestinal) water is
  absorbed in the small intestines by osmosis
• molecules of water follow the absorption of
  solute molecules through aquaporins

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Absorption of Nonpolar Substances

• Following the digestion of triglycerides, the
  fatty acids and monoglycerides assemble with
  cholesterol, lipid soluble vitamins and bile into
  a micelle
• The nonpolar micelle diffuses across the apical
  cell membrane of the absorptive cell into the
  Golgi apparatus
• Once inside Golgi apparatus, the lipids are
  packaged with proteins (required for transport
  around the body) forming a chylomicron
• The chylomicrons are packed into vesicles that
  are exocytosed out of the basal membrane
• Chylomicrons, which are too large to enter a
  blood vessel, enter lymph lacteals which are
  large enough to accommodate the entry of
  chylomicrons

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Distribution of Absorbed Substances

• The polar molecules are absorbed into the blood
  vessels flow directly to the liver via the
  hepatic portal vein
• connects the blood supply of the gastrointestinal
  system and liver
• The liver uptake (transport) some of the
  nutrients into the hepatocytes (liver cells) to
  store a portion of the absorbed nutrients, the
  remainder is distributed to all other cells of
  the body
• Chylomicrons move through lymphatic vessels until
  these vessels merge with the heart where they
  enter the circulatory system to be distributed to
  all cells of the body

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Absorptive and Postabsorptive States

• The absorptive state is the period of time when
  the alimentary canal is absorbing nutrients into
  the body increasing their levels (most
  importantly glucose)
• The postabsorptive state is the period of time
  between absorptive states (when the alimentary
  canal is NOT absorbing nutrients into the body)
• nutrient levels decrease during this time as they
  are constantly used
• 2 antagonistic hormones from 2 different cell
  types of the pancreatic islets of Langerhans are
  secreted during the absorptive or the
  postabsorptive state in order to control the
  levels of circulating glucose (blood sugar)
• Alpha (?) cells secrete glucagon
• Beta (?) cells secrete insulin

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Pancreatic Islet
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Insulin

• A peptide hormone that is synthesized first in
  beta cells as proinsulin (inactive)
• proinsulin is then converted to active insulin in
  the Golgi apparatus
• Secreted into circulation during the absorptive
  state in response to an increase in the blood
  glucose level
• Insulin causes a decrease in the blood glucose
  level returning it to the set point
• stimulates the uptake of glucose out of the blood
  into skeletal muscle cells
• stimulates the uptake of glucose out of the blood
  into adipose cells and its subsequent conversion
  to glycerol which is stored in adipose as
  triglycerides
• stimulates the enzymatic conversion of glucose
  into glycogen (glycogenesis)

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Glucagon

• A peptide hormone that is secreted into
  circulation during the postabsorptive state in
  response to a decrease in the blood glucose level
• Glucagon causes an increase in the blood glucose
  level returning it to the set point
• stimulates lipolysis of triglycerides in adipose
  cells and the release of fatty acids into
  circulation
• stimulates the enzymatic hydrolysis of glycogen
  (glycogenolysis) in the liver
• stimulates gluconeogenesis in the liver
• The glucose that is synthesized by the liver is
  transported out of the liver into the blood
  increasing the blood glucose level

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Insulin vs. Glucagon

• Insulin decreases blood glucose levels
• hypersecretion causes hypoglycemia
• low blood sugar
• hyposecretion causes hyperglycemia
• high blood sugar
• can lead to diabetes mellitus
• Glucagon increases blood glucose levels
• hypersecretion causes hyperglycemia
• hyposecretion causes hypoglycemia

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Diabetes Mellitus

• A metabolic condition caused by inability of
  insulin to function properly
• The 5 symptoms of diabetes mellitus are
• Hyperglycemia
• Glycosuria
• glucose found in urine
• Polyuria
• large urine output
• Polydipsia
• large thirst
• due to dehydration caused by polyuria
• Polyphagia
• large hunger and food consumption

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Diabetes Mellitus

• Type I
• insulin dependent diabetes mellitus (IDDM) or
  juvenile onset diabetes
• caused by the loss of insulin synthesis by beta
  cells and require insulin injections to control
  blood sugar
• Type II
• non-insulin dependent diabetes mellitus (NIDDM)
  or adult onset diabetes
• mainly caused by a defect/reduction in the
  insulin receptor on target cells
• these individuals produce insulin, therefore
  insulin injections are ineffective
• exhibit insulin insensitivity
• The types can be differentially diagnosed in part
  by a glucose tolerance test

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Large Intestine

• Any food in the small intestine that could not be
  chemically digested is moved into the large
  intestine where most of the remaining water and
  ions are absorbed and the remaining material
  removed by defecation
• Subdivided into 3 anatomical segments
• the colon
• ascending colon
• transverse colon
• descending colon
• sigmoid colon
• rectum
• anal canal

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Large Intestine