1 - Anatomy/Histology/Embryology

Question 0

Describe the cellular arrangement of the intestinal crypts.

Answer 0

1) formed by both a protruding villus and invaginating crypt
2) Villus is lines by simple columnar cells and goblet cells; internally there is highly vascular lamina propria
3) at entrance of crypt there are proliferating progenitor cells where mitotic bodies can be seen
4) in the “lower portion” of the crypt (not bottom) are the Crypt Intestinal Stem Cells which can migrate up or down as needed to replace cells
5) at the bottom of the crypts are the Enteroendocrine Cells; cells secrete hormones (serotonin, CCK, secretin) through their basal border into the vessels in the submucosa => their secretory granules can be seen in their basal border and nucleus at the apical, as opposed to the secretory cells of the villus which secrete into the lumen and are the opposite orientation
6) Also on the bottom of the cells are Paneth Cells that participate in antimicrobial host defense (alpha defensins and lysozyme); secretory granules are located apically since they release into the lumen and help in distinguishing them from ECs

Question 1

Describe the histology of the Z-Line.

Answer 1

• Z-line refers to the irregular border at the Gastro-Esophageal Junction.
• The esophageal epithelium is Non-Keratinized Stratified Squamous Epithelium
• The gastric epithelium is Simple Columnar Epithelium; goblet cells are also typically seen
• In Barrett’s Esophagus, the squamous epithelium of the esophagus is replaced with columnar (columnar metaplasia)

Question 2

Characterize the muscle types of the sphincters in the GI tract.

Answer 2

Skeletal: Upper Esophageal, External Anal
Smooth: Lower Esophageal, Internal Anal, Pyloric, Ileocecal

Question 3

Briefly describe the development of teeth.

Answer 3

1) outgrowth of the ectoderm of the oral cavity
2) it is a process of interactions between the ectoderm and mesenchyme that is conducted in a series of stages
3) Ameloblasts are derived from ectoderm and form enamel
4) Odontoblasts are derived from mesenchyme and form dentin
5) In the center of the dentin shell is a pulp cavity

Question 4

What are the types of papillae of the tongue? Where are they located?

Answer 4

1) Filiform: small, hair-like protrusions that cover the anterior 2/3 of the tongue
2) Fungiform: mushroom-like papillae that are interspersed with the filiform over the anterior 2/3 of the tongue; taste buds are located on the apical surface of the papilla
3) Folate: larger, leaf-like papillae that are located on the edge of the tongue; taste buds are located on the lateral walls within the crypts
4) Circumvallate: largest, dome-like papillae that line the v-shape of the terminal groove; taste buds located on the lateral walls and are “washed” over by serous secretion of saliva (glands of von Ebner( to allow for repeat stimulation

Question 5

Describe the basics of taste sensation.

Answer 5

1) Taste buds are located on fungiform, folate and circumvallate papilla on the surface of the tongue
2) they are composed of sensory, supporting and basal cells; all of which rest on the same basement membrane as the squamous epithelium of the tongue
3) the taste pore allows for the chemicals of the oral cavity to wash over the sensory cells and interact with sets of chemoreceptors
4) Tastes of Bitter, Sweet and Umami: binding to these receptors release a second messenger (PLC/IP3) which causes rise in Na+ (taste-specific Na+ Ch) and subsequent rise in Ca++; this in turn causes release of synaptic vesicles and nerve stimulation
5) Tastes of Sour: sour-buds contain a H+ sensitive K+ ch, which shuts when exposed to lower pH; this causes an opening of taste-specific H+ ch and a rise in intracellular H+, which opens Ca++ Ch; this causes release of synaptic vesicles and nerve stimulation
6) Tastes of Salt: Na+ Ch allow for rise in intracellular Na+, which opens Ca++ Ch, release of synaptic vesicles and nerve stimulation
7) Nerves pass through basement membrane en route to solitary nucleus via CN VII, IX, X

Question 6

Describe the form and function of a salivary gland.

Answer 6

1) divided into acinus and ductal sections
2) Acinus is composed of serous or mucous secreting cells based on the gland; serous is less glyconated (more water) and stains darker than mucous which has a concentration of glycoproteins
3) Ducts are responsible for modulating the volume/tonicity of the salivary excretion
4) Intercalated ducts just collect/transport secretions and have little or no ion transport
5) Striated ducts (so appeared due to high volume of mitochondria) actively reabsorb Na+ (for K+) and secrete HCO3- (for Cl-)
6) The amount of reabsorption varies based on salivary flow: at low flow, more Na+ is reabsorbed, while at high flow, lumen concentrations of Na+ and Cl- increase
7) The ducts are largely impermeable to water, making low flow secretions Hypotonic and high flow Isotonic

Question 7

How is salivary flow controlled?

Answer 7

1) based on the phases of digestion (cephalic, gastric, intestinal) there are differing signals from Para and Sympathetic innervation
2) Para: high flow, vasodilation, with reduced organic content
3) Symp: low flow, vasoconstriction, rich in organic content

Question 8

Describe the innervation of the esophagus.

Answer 8

1) CNS: there is somatic, afferent, parasympathetic and sympathetic innervation to the esophagus to control swallowing
- Somatic: N-ACh receptors from swallowing center(N. ambiguus) to upper 1/3 esophagus; travel along CN V, VII, X, XII and C1-C3
- Sensory: travels up vagus to the N. tractus solitarius/ambiguus
- Parasympathetic: excitatory ACh in myenteric plexus from the DMX
- Sympathetic: largely inhibitory NE from T5-T6 to lower 2/3, T6-T10 to LES
2) Enteric Plexus: intrinsic innervation via Submucosal and Myenteric Plexus
- Myenteric (Auerbach): located between the layers of the muscularis externus; acts to coordinated motility along the entire length of the gut (peristalsis)
- Submucosal (Meissner): located in the submucosa; acts to regulate secretions, blood flow, and absorption

Question 9

What are the stages of swallowing?

Answer 9

1) Voluntary Phase: voluntary phase during which food is moved into the pharynx
2) Pharyngeal Phase: involuntary process initiated by bolus of food entering the pharynx signaling to the brainstem (swallowing center); prevents aspiration (vocal folds close, palatopharyngeal folds close, larynx close), UES relaxes and contraction of Superior Constrictor starts the peristaltic wave
3) Esophageal Phase: continuation of the peristaltic wave that takes 5-10s; only important for solids, or both when reclined
3) Esophageal Phase:

Question 10

Distinguish primary peristalsis, secondary peristalsis, and the mechanism of rapid swallowing.

Answer 10

1) Primary peristalsis: peristaltic wave that is initiated by food bolus at the pharynx; lasts 5-10s
2) Secondary peristalsis: wave that is initiated by esophageal distention that continues until food is cleared
3) Rapid swallowing: induces refractory period that will delay peristalsis until swallowing is complete; clearing wave after swallowing

Question 11

Describe the nervous control of peristalsis.

Answer 11

1) Stimulatory via parasympathetic (ACh) and inhibitory via sympathetic (NE) transmitted via myenteric plexus
2) Skeletal muscle and longitudinal smooth muscle are stimulated in a constant manner for a Duration Response
3) Circular Smooth muscle stimulated via parasympathetics causes an initial, small “On Response” contraction, followed by a larger “Off Response” contraction;
4) The Latency Gradient causes the Off Response in the distal esophagus to come after the Off Response of the proximal and creates the “wave” of peristalsis
5) Striated muscles are activated sequentially via vagus and is suppressed by vagotomy
6) Smooth muscles activation “travels” through synsitium; this produces the Latency Gradient and therefore is not suppressed by bilateral vagotomy

Question 12

Describe the action of the Lower Esophageal Sphincter.

Answer 12

1) in the resting state, the LES is tonically contracted by intrinsic muscle activity to prevent reflux
2) LES is relaxed when stimulated by vagus (parasympathetic)
3) hormonal control of LES:
- increase pressure: gastrin, motilin, substance P, vasopressin, angiotensin II
- decrease pressure: secretin, CCK, glucagon, GIP, VIP, progesterone
4) Other influences on LES:
- increase pressure: ACh, beta adrenergic, food proteins, gastric distention, high abdominal pressure
- decrease pressure: alpha adrenergic, dopamine, fats, EtOH, chocolate

Question 13

Describe the composition of the oxyntic gland of the stomach.

Answer 13

1) The surface of the stomach is dominated by rugae, as opposed to the plica of the intestine
2) The top invagination is the pit: cells are enterocytes(simple columnar) and mucous cells
3) The neck is at the base of the pit where it splits into two separate invaginations; there are also enterocytes and mucous cells at the neck, though these are thicker, more cuboidal in form
4) Below the neck is the glandular section: Parietel (Chief) Cells which secrete HCL, Intrinsic Factor and water; these stain deeply pink
5) At the base of the crypts are Entero-Chromaffin (Peptic) Cells which secrete pepsinogen; these stain pale with round nuclei at the apical surface

Question 14

How do parietal cells make/secrete HCl?

Answer 14

1) two separate paths produce the Cl- and H+ for HCl secretion
2) Cl-: H2O is absorbed from the lumen and HCO3- is formed by the action of carbonic anhydrase; this HCO3- is then exchanged for Cl- across the basal membrane and then into the lumen
3) H+: K+ is actively exchanged w/ Na+ at the basal membrane; the K+ then diffuses into the lumen via an open channel; the raised K+ concentrations in the lumen is then actively exchanged for H+ on the lumen border w/ the excess K+ diffusing out the basement membrane via a dedicated antiport
4) This provides a net flow of H+/Cl- into the lumen, HCO3- out the basement membrane; there is also passive H2O and Na+/K+ movement into the lumen

Question 15

What are the Trefoil Factor Family?

Answer 15

• TFF are proteins present in mucous glands
• appear to be motogenic and support migration of mucous cells across injured (ulcer) areas
• also seem to have tumor suppressor properties
• there are different (3) groups of TFFs based on location in the GI tract

Question 16

How is gastric secretion regulated?

Answer 16

1) Gastric secretion (HCl from Parietal Cells) is regulated by several pathways: endogenous peptides, endocrine hormones, and nervous stimulation
2) Excitatory: Gastrin, ACh, Histamine, Ghrelin
- Gastrin is secreted from G Cells in the antrum of the stomach in response to stomach contents (amino acids, Ca++, peptides), vagal stimulation (via Gastric Releasing Protein), or gastric distention
- Vagal stimulation can affect Parietel cells directly via ACh or via release of Gastrin (GRP at G Cells)
- EnteroChromaffin Cells (ECL) secrete histamine when stimulated by Gastrin or vagal stimulation (ACh)
3) Inhibitory: Low pH, prostaglandins, Gastrin Inhibitory Peptide, somatostatin
- Low pH due the lack of food to act as a buffer or from excess secretion directly inhibits parietal cells and causes the release of Secretin from S Cells in the duodenum which inhibit acid production
- FA, AA and glucose in the duodenum also stimulates secretion of GIP from K Cells in the duodenum, which inhibits further acid production
* * Vagal stimulation (ACh) and Gastrin use a Gq/IP3 protein to raise Ca++ concentration BUT histamine, somatostatin and prostaglandins affect the concentrations of cAMP => by using different pathways multiple inputs can potentiate each other (the affect of multiple inputs is greater than their sum)

Question 17

Describe the phases of gastric secretion.

Answer 17

1) Interdigestive: basal stimulus w/ 15% total secretion
2) Cephalic: stimulated by “thinking” about food, sight, smell and taste -> raise in secretion to 30% primarily via Enteric stimulation of G cells to release gastrin and Vagal stimulation of Parietal and ECL cells (histamine)
3) Gastric: stimulated by chemical and physical properties of food in the stomach -> raise secretion to 50% via the same nervous stimulation as present in the Cephalic phase, however the G cells are now directly stimulated by food; as the pH falls there are inhibitor signals from inhibition of G cells and stimulation somatostatin releasing D cells
4) Intestinal: digestive products in the duodenum -> lowers secretion to 5% due to inhibitory signals from S cells (secretin), and CCK, G cells are inhibited by lower pH of stomach

Question 18

What are the distinguishing characteristics of the histology of the three portions of the intenstine?

Answer 18

1) all of them contain four cellular layers: mucosa (epithelium, lamina propria, and muscularis mucosa), submucosa, musclularis externus (longitudinal and circular) and serosa(w/membrane)/adventitia(w/o membrane)
2) Duodenum: Brunner Glands in submucosa, no pleyer’s patches
3) Jejunum: no brunner glands or pleyer’s patches, though there may be some lymphatic nodules in the submucosa
4) Ilium: Pleyer’s Patches in submucosa, no brunner glands

Question 19

How are carbohydrates digested and absorbed?

Answer 19

• Carbs: digestion begins in the mouth where salivary amylase breaks polysaccharides down into oligosaccharides; stopped in the stomach due to low pH, but digestion continues in the the duodenum via pancreatic amylase; the oligosaccharides are then further broken down into monosaccharides via sucrase, glucoamylase and lactase, present on the brush border
• Glucose and Galactose are transported across the lumen border via SGLT1 which is a Na+ cotransporter, where the Na+ concentration is maintained by an Na/K ATPase
• Fructose is transported via GLUT5
• Glucose, Fructose, and Galactose are transported across the basal border via GLUT2

Question 20

How are proteins digested and absorbed?

Answer 20

1) Digestion begins in the stomach via pepsin which is released from Chief (Pepsin) Cells as pepsinogen and activated by enterokinase
2) Pepsin breaks the protein into smaller polypeptides and proteases, but also activates pancreatic pro-enzymes -> trypsin, chymotrypsin, carbosypolypeptidase, and proetastase
3) the pancreatic enzymes break down the polypeptides further into smaller polypeptides and amino acids
4) Peptidases on the brush border (also activated by pepsin) break the remaining polypeptides into di/tripeptides which can be absorbed
5) Several membrane Na+ dependent cotransporters (>5) carry specific amino acids across the lumenal border
6) Di/Tripeptides are carried across via a H+ dependent cotransporter, utilizing a H+ gradient generated by a Na+/H+ exchanger, which itself uses the Na+ gradient from the Na/K ATPase
7) the remaining di/tripeptides are broken down to AA via cytoplasmic peptidases
8) all AA are carried over the basal border by a series of AA transporters

Question 21

How are lipids digested and absorbed?

Answer 21

1) Lipid digestion begins in the oral cavity via lingual lipase, but the majority occurs within the intestine
2) Lipids are emulsified by bile salts and “labeled” by lecithin to increase the surface area and provide a water/lipid interface for pancreatic lipases
3) micelles of lipids diffuse across the enterocyte membrane
4) the monoglycerides and FA are re-esterified to for TG, which are then combined with ApoB-100 protein to form a Chylomicron
5) Chylomicrons then enter the mesenteric lymphatics (lacteals) and travel to the blood stream via the thoracic duct; after leaving the cell ApoE is bound to the surface and the chylomicron is now “mature”
6) In the blood, Chylomicrons bind to adipocytes via Lipoprotein Lipase (LPL) which breaks the TG into FA and Glycerol, transports the FA across the membrane where it is recombined with Glycerol derived from blood glucose to for TG for storage
7) The remnant chylomicron is returned to the blood and travels to the liver for recycling

Question 22

What is the role of the large colon in digestion?

Answer 22

1) digestion primarily occurs in the small intestine, while the large colon participates in absorption of water and elimination of wastes
2) Carbs: bacteria fermentation allow for digestions of short-chain FA (plant starches); this produces H+, CO2, and CH3+ -> flatulance
3) Lipids: bacterial lipases helps stimulate fluid secretion
4) Proteins: none
5) Water: water is reabsorbed throughout the intestine via secondary transport w/ Na+; overall 95% of water is reabsorbed in the intestine (50% in jejunum, 25% in ilium, 20% in colon)
- water also passes through pores in the intercellular junctions and apical border or the small intestine, but in that colon there is no passive transport

Question 23

What is BER? Where is it present?

Answer 23

• BER = Basal Electrical Rhythm -> frequency of smooth muscle slow waves
• contractions only occur when the slow wave peaks exceed threshold
• BER is set by Intestinal Cells of Cajal (ICC) which act as pacemaker cells of the GI tract
• when excited, the Ca/Na ch open on ICC to great AP; since they are slow, the AP is longer than seen in nerve signals and requires extracellular Ca (since there is no sarcoplasmic reticulum)
• • excitation does NOT affect BER/frequency, but changes the peak hight -> contractions
• Excitatory: stretch, ACh, Substance P, Parasympathetics, GI hormones
• Inhibitory: NE/Epi, NO, VIP, Sympathetics
• BER present in Distal Stomach, Small Intestine, and Colon
• NO BER in Esophagus, Proximal Stomach and most sphincters

Question 24

Describe the types of GI contraction.

Answer 24

1) Phasic: Segmental and Peristaltic
A) Segmental: contraction of circular muscle, limited in rate by the BER of the muscle; sured for mixing of GI contents and for net movement of material along tract; movement based on BER gradient throughout the tract
B) Peristaltic: coordinated contraction of the longitudinal and circular muscles that provide propulsive movement
2) Tonic: a constant contraction of varying degrees in areas of the GI that lack a BER(fundus, body, smooth muscle sphincters); intensity of contraction is affected by nervous and hormonal signaling

Question 25

Describe gastric reflexes.

Answer 25

1) Short: communicate entirely within the Enteric Nervous System and are used to control mixing and perstalsis
2) Long: reflexes that travel to the perivertebral chain/ganglia(enterogastric) or CNS (vagovagal) and return to the gut control emptying and secretions

Question 26

What hormones affect GI motility?

Answer 26

1) CCK - released from I Cells in the duodenum when stimulated by fats, peptides, and amino acids; inhibits gastric emptying, promotes secretion of bile salts/pancreatic enzymes and inhibits HCl production
2) Secretin - released from S Cells in duodenum when stimulated by low pH; inhibits gastric emptying, stimulates pancreatic and biliary HCO3-, and stimulates bile release
3) Gastric Inhibitory Peptide: released from K cells in the duodenum and jejunum when stimulated by amino acids, fatty acids, and glucose; stimulates insulin, inhibits HCl and thus slows gastric motility
4) Motilin: secreted by ECL cells in the duodenum and jejunum stimulated by the absence of food for >2hr; stimulates MMC in the stomach and small intestine and production of pepsin

Question 27

What is the Ileal Break?

Answer 27

• gastric emptying and intestinal transit is slowed when ilium is exposed to fat
• allows more time for absorption

Question 28

What are the components and function of the ileocecal junction?

Answer 28

1) composed of a sphincter and valve that slows the flow of chyme to allow for better absorbtion
2) the sphincter is held tonically contracted unless relaxed by gastroileal reflex
3) when the pre-junction ilium is distended, the sphincter relaxes and allows flow of chyme into the terminal ilium
4) when the post-junction cecum is distended or irritated, the sphincter is contracted and the terminal ilium is relaxed
5) when there is back pressure on the valve, the valve is closed to prevent reflux into the pre-junction ileum

Question 29

Describe the motility of the colon.

Answer 29

1) The motility of the colon maximizes absorption of water and nutrients from chyme
2) In the cecum and ascending colon there is a slight REVERSE BER gradient (the distal portion is faster than the proximal)
3) In the transverse and descending colon there is NO BER gradient
4) Mixing Movements: a coordinated contraction of neighboring circular muscles to push chyme back and forth between haustra (haustration) - most common
5) Haustral Migration: similar to Mixing, but the chyme can progress several segments; provides a peristaltic-like movement with some net movement
6) Mass Movement: occurs only a couple of times a day to prepare the feces for defecation; constrictive ring formed in response to distention or irritation and “pushes” feces to rectum by 30 sec of contractions of increasing intensity; this is followed by 2-3m of relaxation and then another mass movement; continues for 10-30m

Question 30

Describe the process of defacation.

Answer 30

1) Feces enter the rectum and distention activates the Rectoschincteric Reflex
2) The internal sphincter is typically tonically contracted and innervated by autonomics (Para = relax, Symp = contract)
3) The external sphincter is typically tonically contracted and innervated by somatic, unconscious innervation
4) when activated by the Rectosphicteric Reflex, the internal sphincter relaxes, the external sphincter contracts, and there is a conscious “urge” to defecate
5) defecation can be delayed by consciously contracting the external sphincter; this causes rectum relaxation and accomadation, which in turn allows the internal sphincter to contract; once the internal is contracted, the external sphincter can be relaxed

Question 31

What cells make up the Islets of La ngerhans?

Answer 31

1) Alpha Cells: secretes glucagon; located around the periphery
2) Beta Cells: secretes insulin; most common
3) Delta Cells: secretes somatostatin; few in number
4) F (PP) Cells: secrete pancreatic polypeptide which act on gastric chief cells and bile secretions; rare

Question 32

Describe the mechanism of pancreatic exocrine secretion.

Answer 32

1) Acinar cells are stimulated via hormones (CCK) and nerves (ACh)
2) CCK/ACh bind to basolateral receptors to initiate signaling cascade via cAMP and Ca++ to cause vesicle fusion and protein release
3) Secretions include water (1-1.5L/d), ions (HCO3-, Na+, K+, Cl-), hydrolases and digestive enzymes
4) The fluid volume is primarily controlled by the ductal epithelium;
while the acinar cells control the protein content
5) **Trypsin Inhibitor prevents any pre-maturely activated trypsin from causing cellular damage
6) as flow rates increase HCO3- concentrations increase and Cl- fall; Na and K remain largely unchanged

Question 33

How is pancreatic secretion regulated?

Answer 33

1) Hormonal: enteroendocrine cells in the small intestine
- Secretin: acts primarily on the ducts to increase HCO3- rich fluid
- CCk: acts primarily on the acinar cells to release the digestive enzymes
2) Neuronal: vagal stimulation of the acinar cells
- ACh stimulates release of secretin and VIP (which has secretin-like properties)
- Sympathetics (NE) inhibits vagal/secretin induced secretion AND through vasoconstriction reduces secretion\

Question 34

Classify the endothelium present in the sinusoids of the liver.

Answer 34

• fenestrated, discontinuous capillaries
• allows for passage of foodstuffs from the blood into the Space of Disse
• This is the initial form of lymph drainage in the liver

Question 35

Describe regenerative capacity of the liver.

Answer 35

1) oval cells are the stem cells of the liver; reside in the periportal region
2) ~1% of the liver is replaced every day
3) Ito Cells are specialized fibroblasts that produce reticular fibers and store Vit A

Question 36

Describe the composition/formation of bile acid.

Answer 36

1) the majority (80%) of bile acids are recycled from the intestine; unconjugated acids can be reabsorbed throughout the intenstine, but 90-95% occurs in the terminal ileum via Na dependent exchange
2) the recycled acids are returned to the liver via the enterohepatic circulation, are transported into the hepatocytes w/ Na and then excreted into the bile canuliculi
3) Bilirubin is carried in the blood on serum albumin, is conjugated by the hepatocytes onto glucuronic acid and excreted w/ bile
4) FA are secreted into bile as lecithins (glycophosphotidylcholine)
5) Cholesterol is only present in small amounts in micelles
** if the cholesterol concentration is too high, it can become supersaturated and precipitate as cholesterol crystals
Regulation
7) Bile Acid-Dependent Flow: the acid/salt content of bile is only influenced by the amount of bile the hepatocytes reabsorb (no hormonal or neuronal control)
8) Bile Acid-Independent Flow: the fluid volume of the bile is controlled by the ductal epithelium; high flow is stimulated by secretin influence

Question 37

What are the phases of gallbladder function?

Answer 37

1) Interdigestive: concentrates the bile 5-15x via absorption of Na+, Cl-, HCO3- and water
2) Cephalic: gall bladder contraction and relaxation of sphincter of Oddi in anticipation of food via vagal stimulation
3) Gastric: vagovagl reflex causes increased contraction
4) Intestinal: highest rate of emptying due to stimulation by CCK

Question 38

Describe the development of the GI tract.

Answer 38

1) 4th wk: embryonic foldings (cephalic, lateral and caudal) for the primitive gut tube
- Endoderm forms epithelium and glands; Mesothelium forms the CT, muscle and wall of intestine; Migrating neural crest cells will form the autonomic innervation
2) 6th wk: the cranial portion of the midgut loop (proximal to SMA) grows rapidly and herniates out the umbilicus
3) 10th wk: the abdominal cavity expands and the herniated midgut returns; it undergoes a CCW rotation of 270deg
4) The Cephalic foldings for the forgut: oral cavity to the duodenum proximal to the ampul of vater; liver, pancreas, bile ducts and gallbladder
5) Lateral Foldings form the midgut: tract from ampul of vater to 2/3 of transverse colon
6) Caudal Foldings form the hindgut: distal 1/3 of transverse colon to the proximal portion of the anal canal