Topics to Review

1
Topics to Review

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

2
Topics to Review

• 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
3
-Its primary function is to move water, nutrients
and electrolytes from the external environment
into the bodys internal environment
4
(No Transcript)
5
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
6
4 Basic Processes of the Digestive System

• Processes are regulated by the nervous and
  endocrine systems as well as paracrine signals

• 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 GI
  epithelial cells, hepatocytes or pancreatic
  acinar cells into the lumen GI tract lumen or ECF

• Absorption
• active or passive transfer of substances from the
  lumen of the GI tract to ECF

7
4 Basic Processes of the Digestive System
8
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

9

• Any material remaining in the lumen at the end of
  the GI tract is defecated through the anus

10
Peritoneum
-2 membranes in the abdominal cavity made of
connective tissue 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
11
Wall of the GI Tract
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
  longitudinal and deeper circular) responsible for
  motility which is innervated by the myenteric
  plexus of the Enteric Nervous System

12

• Serosa (deep)
• strong connective tissue membrane that maintains
  the structural integrity of the alimentary canal
  (visceral layer of the peritoneum)

13
Anatomy of the Alimentary Canal
Diaphragm
Myenteric Nerve Plexus
Submucosal Nerve Plexus
Serosa
Mucosa
Submucosa
Muscularis
Blood vessels
Exocrine gland
14
Mucosa
Structural modifications of the mucosa increase
the amount of surface area for digestion and
absorption

• When the GI tract is empty, the mucosa is folded
• rugae in the stomach
• plicae in the small intestine

-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
• gastric glands in the stomach
• crypts in the intestines

15
Sectional View of Small Intestine
16
Sectional View of Stomach
17
Mucosa
Simple epithelium

• transporting cells move ions and water into lumen
  as well as absorb ions water and nutrients into
  ECF

• secretory cells (endocrine and exocrine)
• at apical surface exocytose enzymes and mucus
  into lumen for digestion and protection
• at basal surface release hormones or paracrine
  molecules into the ECF for digestive regulation
• also serve as mechano- and chemoreceptors which
  detect the presence of food in the GI tract by
  distension or the presence of molecules

• Lamina propria
• connective tissue holds epithelium in place
• contains nerve fibers of the submucosal plexus
  that innervate epithelium as well as small blood
  and lymph vessels

18

• Muscularis mucosae
• thin layer of smooth muscle

19
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

20
Digestion

• Chemical digestion occurs by the action of
  powerful enzymes that hydrolyze complex
  macromolecules into molecules small enough to be
  absorbable

• enzymes are either secreted into the lumen or are
  integral proteins in the microvilli of the
  mucosal epithelium

• Secretion of mucus into the GI lumen protects
  against autodigestion of the mucosa to prevent
  peptic ulcers

21
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 intestines alternately contracting and
  relaxing which mixes contents and keeps them in
  contact with absorptive epithelium

22
(No Transcript)
23
Absorption

• The 7 liters of fluid secreted daily into the
  lumen of the GI tract must be absorbed to prevent
  dehydration

• In addition, an average human ingests 2 liters of
  food and fluid daily that also is to be absorbed

• Only 100 mL of fluid remains in the GI tract and
  is lost in feces

-vomiting and diarrhea can be life
threatening if ECF volume is
significantly depleted
-Absorption of nutrients, ions and water across
the GI epithelium uses membrane transporting
proteins in the apical and basal membranes
24
Regulation of Digestion
-The control and coordination of the digestive
process throughout the GI tract and accessory
organs of digestion occurs from nervous signals
of the CNS and ENS as well as from hormonal and
paracrine signals

• Stimuli such as thinking of, smelling and tasting
  food as well as the presence of food within the
  GI tract initiate reflexes (homeostatic control
  mechanisms) that promote the digestion, motility
  and secretion

25
(No Transcript)
26
3 Stages of Digestion

• The entire digestive process takes place in 3
  overlapping stages which are named by the
  location of food within the alimentary canal

• 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

27
Cephalic phase

• This phase prepares the digestive system before
  the ingestion of food

-Anticipatory stimuli and the stimulus of food in
the oral cavity activate Parasympathetic Nervous
System (PNS) neurons in the medulla oblongata

• The medulla sends action potentials through
  nerves to salivary glands and through the Vagus
  nerve to the ENS which increases the secretion
  and motility of the stomach (growling),
  intestines and pancreas
• decreases the time required for overall digestion

28
Salivary Glands

• 3 exocrine glands
• parotid, submandibular and sublingual

29
Composition and Functions of Saliva

• Water
• Ions
• Digestive enzymes

• salivary amylase
• begins the chemical digestion of carbohydrates
• high concentration

• lingual lipase
• begins the chemical digestion of lipids
• low concentration

• Mucin
• protein that aids in the lubrication of a bolus
• ball of chewed food and saliva that is swallowed

• Lysozyme
• antibacterial salivary enzyme

30
Swallowing (Deglutition)

• The tongue forces the bolus into the pharynx
  causing the epiglottis to fold over the opening
  to the airways (glottis). This diverts the bolus
  into the esophagus as the tonically contracted
  upper esophageal sphincter relaxes momentarily as
  respiration is inhibited

31
Gastric Phase

• Digestive processes in the stomach are initiated
  by cephalic reflexes before food enters the
  stomach
• these processes are continued by the presence of
  food beginning the gastric phase of digestion

• The stomach continues digestion begun in the
  mouth by mixing food with gastric juice
  (secretions of the stomach mucosa) creating chyme

32
Gross Anatomy of the Stomach
-The stomach is divided into the upper fundus,
the middle body and the lower antrum and is able
to hold up to 2 liters of food and fluid when
completely filled
-Chyme enters the small intestine in small
amounts by passing through the pyloric sphincter
(pylorus) and enters the small intestine
33
Stomach Functions

• Storage of food

• when food arrives in the stomach distension of
  the wall initiates a neurally controlled reflex
  (receptive relaxation) which causes the upper
  half of the stomach to relax and expand to hold
  the food

• in the lower half, peristaltic waves push the
  food towards the pylorus mixing it with gastric
  juice

• as food particles are reduced to a more uniform
  texture, each peristaltic wave squirts a small
  amount of chyme into the small intestine

34
Gastric Motility

• During the intestinal phase, 2 hormones released
  from the small intestine epithelium secretin and
  cholecystokinin (CCK) reduce gastric motility
  thus limiting the rate of chyme movement into the
  small intestine

35
Stomach Functions

• Digestion of food
• chemical digestion of food occurs by the
  secretion of gastric juice by the mucosal
  epithelium
• mechanical digestion of food occurs by the
  churning of the chyme by peristaltic waves

-Gastric juice is the collective exocrine
secretions of chief cells and parietal cells of
gastric glands
36
(No Transcript)
37
Gastric Juice

• Chief cells
• secrete the inactive enzyme (zymogen) pepsinogen
  (ogen means enzyme is not activated)
• the chemical digestion of proteins begins when
  pepsinogen is converted to pepsin (active)
• secrete gastric lipase (low concentration)
• continues the chemical digestion 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

38

• lack of intrinsic factor results in pernicious
  anemia which is a reduction of red blood cell
  synthesis due to a vitamin B12 deficiency

39
Hormonal Control of HCl Secretion

• 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, secretin and
  cholecystokinin (CCK) inhibit HCl secretion from
  parietal cells

40
Stomach Functions

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

41
Small Intestine 3 Segments

• Most of the digestion and absorption occurs
  within the 3 segments of the small intestine
  duodenum (proximal 25 cm), jejunum (middle 250
  cm) and ileum (distal 360 cm) during the
  intestinal phase

• Here digestion is carried out 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 sphincter of Oddi to keep these
  fluids from entering the small intestine except
  during a meal

42
Small Intestine
43
(No Transcript)
44
-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
45
Digestion and Absorption at the Brush Border
small intestinal lumen
blood vessel
Maltose
Glucose
Glucose
Glucose
Glucose
Na
Na
K
K
Na
H2O
H2O
46
Intestinal Phase
-The presence of chyme triggers a series of
reflexes which further regulates the delivery of
chyme from the stomach as well as reflexes that
promote digestion and motility of the chyme in
the small intestine
-Distention of the intestinal wall by chyme
stimulates a combination of segmental and
peristaltic contractions

• mixes chyme with enzymes and exposes digested
  nutrients to the mucosa for absorption
• movement of chyme through the small intestine
  must be slow enough to allow for digestion and
  absorption to go to completion

47

• The presence of acidic chyme causes duodenal
  mucosal cells to secrete the hormone secretin

-The presence of fatty acids and peptides in the
chyme causes duodenal mucosal cells to secrete
the hormone CCK
48
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

49
Pancreatic Juice
-Acinar cells exocytose pancreatic juice into the
pancreatic duct which flows into the duodenum

• Pancreatic juice contains
• enzymes stimulated by the hormone CCK
• pancreatic amylase hydrolyzes carbohydrates
• pancreatic proteases hydrolyze proteins
• secreted as zymogens
• pancreatic lipase hydrolyzes lipids
• pancreatic nucleases hydrolyze nucleic acids

• bicarbonate (HCO3-) stimulated by the hormone
  secretin
• a buffer secreted by duct cells that neutralizes
  the gastric acid, raising the pH to 8.0 (optimal
  for both pancreatic and intestinal enzymes)

50
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

51
Activation of Pancreatic Zymogens
52
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
• contracts during the intestinal phase in response
  to CCK to squeeze the bile into the bile duct

53
Sphincter of Oddi

• The sphincter of Oddi (hepatopancreatic
  sphincter) opens and closes depending upon the
  presence or absence of chyme in the small
  intestine

• when chyme containing fatty acids and peptides is
  delivered into the small intestine, duodenal
  cells secrete the hormone CCK
• CCK causes the sphincter to open, allowing the
  entry of pancreatic juice and bile into duodenum

54
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
55
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

56

• Brush-border enzymes of the small intestine
  complete the final hydrolysis of carbohydrates,
  proteins and nucleotides prior to their
  absorption

57
Absorption of Macromolecules

• 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

58

• 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

59
(No Transcript)
60
Absorption of Lipids
-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

61
Fate of Absorbed of 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

62
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

• Subdivided into 3 anatomical segments
• the colon
• ascending colon
• transverse colon
• descending colon
• sigmoid colon

• rectum
• fecal material is stored until defecation occurs

• anal canal

63
Large Intestine
64
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

65
Pancreatic Islet
66
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
67

• stimulates the enzymatic conversion of glucose
  into glycogen (glycogenesis)

68
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

69
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

70
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

71
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