GI Tract: Tubular Gut (part 2: small intestine and large intestine)

Small intestine: Describe lymphocytes stuck in the epithelium of small intestines

-Lymphocytes wander across the BM and get stuck in diapedesis, etc. -Characteristic epithelium of most of small intestine (w/enterocytes and goblet cells)

Small intestine: What do the nerve plexuses function as?

-The plexuses are the functional controller of peristalsis in the gut -When brain is changing peristalsis in the gut, it doesn't directly control it - it just sends signals to speed up or slow down -The plexuses are the direct controllers of peristalsis

Diagram: Surface amplification in small intestine (A) - has very long organ (B) - has folds called plicae aka valve of Kerckring (C) = villi (D) = brush border (E) = microvilli

Diagram: Surface amplification in small intestine (A) - has very long organ (B) - has folds called plicae aka valve of Kerckring (C) = villi (D) = brush border (E) = microvilli

Small intestine: What is sprinkled amongst the enterocytes?

Goblet cells

Paneth cells are involved in secreting materials that help control the microbe population in the lumen of the small intestine

Paneth cells are involved in secreting materials that help control the microbe population in the lumen of the small intestine

Small intestine: What is the role of villus in transport?

-Amplifies surface area -Also, makes absorption of water more efficient

Small intestine: Describe Paneth cells of the small intestine mucosa

-At the base of glands (crypts) -Still somewhat mysterious, but their granules contain antibacterial agents (lysozyme, defensins, and other materials important for controlling bacterial growth in intestine)

Small intestine: Describe Auerbach's (myenteric) plexus

-Between inner circular and outer longitudinal layers of muscularis externa -Has smooth muscle behind it -Thicker lines in the front - ganglia and enrve connections of the Myenteric nerve plexus are very extensive

Small intestine: Describe Submucosal glands of the small intestine mucosa

-Called "Brunner's glands" -ONLY in the duodenum -Produce bicarbonate secretion that helps to neutralize acid travelling from stomach to the duodenum

Small intestine: Describe the Central lacteal

-Each villus has a single, blind-ended lymph capillary that runs down the center of it -Blind end is a tip of villus -Carries lymph towards base of the villus and joins up with the rest of lymphatic system -Called lacteal because it carries a milky-looking fluid (chylomicrons suspended in water - the fat droplets)

Small intestine: What happens to lipid breakdown products?

-Emulsified lipid breakdown products are absorbed across microvilli of enterocytes by passive diffusion and are taken up by smooth ER -Triglycerides are re-synthesized in the smooth ER, complexed with proteins in the rough ER to form chylomicrons that are transported to the basolateral membrane and released by exocytes to be picked up by lymphatics in the core of the villus

Small intestine: Where are enterocytes located along the villi?

-Enterocytes migrate along outside of the villus and slough off at the tip -These cells only last a few days -Simple columnar epithelium with a brush border

Small intestine: Describe enterocyte absorption of solutes and water

-Enterocytes on outside of villus - transport solutes from chyme into the connective tissue (get increase in connective tissue as a result) -Vasculature sets up concentration gradient from tip of the villus that helps drive absorption (movement of fluid and lipids across that wall)

Small intestine: Describe the Muscularis externa of the small intestine

-Inner and circular outer longitudinal layer of smooth muscle (both layers) -Highly innervated

Small intestine: Describe the M-cells (multifold cells) of the small intestine

-M-cells are specialized epithelial cells that exist in regions above peyer's patches in the ileum -Facilitate access of lymphocytes to luminal contents transported by endocytosis to pockets at basal cell surface into which it dumps large quantities of fluid from the lumen that it transports via endocytosis -Associated with lymphoid accumulations in the gut -Below M cells is discontinuous basolateral membrane to allow lymphocytes better access

Small intestine: Describe features of the duodenum

-Mucosa has villi sticking up -Villi sticking out are covered by epithelium -Small tubular mucosal glands underneath "crypts of Lieberkuhn" -Muscular mucosae lying underneath -Small intestine submucosa is devoid of glands except in the duodenum -Duodenum has submucosal glands, but NOT the ileum and jejunum

Small intestine: What cells make up the mucosa of the intestine? Is the mucosa of the intestine the same or does it vary throughout?

-Mucosa is pretty much the same throughout the intestine: Villi with absorptive cells and goblet cells; intestinal crypts with undifferentiated cells and paneth cells, and enteroendocrine cells sprinkled throughout

Large intestine: What do the cecum and colon lack? What do they have abundance of?

-No villi -No submucosal glands -No Paneth cells -Many long crypts of Lieberkuhn (a bit different than small intestine crypts)

Small intestine: Describe Meissner's plexus

-Often has a bit of nerve material running out in the connective tissue of the submucosa -Seeing ganglia is rare, but will exist

Large intestine: Describe the musclaris externa of the large intestine

-Outer, longitudinal muscle in bands called "tenia coli" -Outer longitudinal muscle layer is thickened in certain regions -Arrangement of muscle and their contractions give rise to Haustra

Small intestine: How do the enterocytes/epithelial cells function? (Na+/glucose)

-Polarization in epithelial cells allows them to function -Principle action: Na+/Glucose symporter carries the glucose into the cytoplasm; Glucose gets out of cytoplasm by facilitated carrier on the basolateral memmbrane to get into the blood. This is similar to how AAs and sugars are absorbed from lumen to the blood. Enterocytes do all the work. *Note: there is also somewhat restricted paracellular transport (lipids) going on

Large intestine: Describe Haustra

-Pouches that help hold the material in the colon so it stays longer -Allow for dehydration of feces as it's being formed

Anal margin: Describe the transition from rectum to anus

-Rectum has histologic structure very similar to rest of large intestine (has crypts of Lieberkuhn, full of goblet cells) -Internal part of anus has development of keratinized skin, as transitions to outside

Small intestine: Describe the Goblet cells of the small intestine

-Single mucous-secreting cells among the enterocytes in simple columnar epithelium of small intestine and large intestine

Small intestine: Plicae circularis in interior of intestine. Describe the structure and its relation with Peyer's patches

-Submucosa goes all the way up into the plicae -Villi project out from the surface of plicae -Peyer's patches are located in region that is the anti-mesenteric side of the ilium -Plicae are absent where Peye's patches are located (M-cells are present in these regions)

Small intestine: Describe the enteroendocrine cells of the small intestine mucosa

-There are lots of different kinds of endocrine cells in the GI tract

Small intestine: Describe epithelium over Peyer's patches or other lymphoid nodules in the gut

-These are special epithelial cells that have a space inside them (expanded basal membrane) -Allow lymphocytes to come up in this space -These cells undergo pinocytosis and bring little bits of fluid from lumen of the gut into this space where lymphocytes can sample the material and see what's in the gut -This is a continual process- immune system monitors bacterial flora and other things in gut to make sure things are ok

Small intestine: What are the 2 types of lymphatic infiltration?

1) Nodular lymphatic infiltration 2) Diffuse lymphatic infiltration

Small intestine: Describe fat absorption in enterocytes

1. Bile acids are detergent molecules important in mixing with chyme so that lipids in foodstuffs are dispersed into small droplets. If lipids are not dispersed in small droplets, the enzymes can't act on them effectively. *Note: this requires high surface area-to-volume ratio so that the lipases present in gut can break the lipids down 2. In lumen of the gut (sometimes in glycocalyx next to microvilli), lipases present in the gut can break the lipids down into glycerol, fatty acids, and monoglycerides. These are the substances absorbed across apical membrane that enter the cytoplasm of enterocytes. 3. Enterocytes take these compounds and remakes them into triglycerides, packages them in the ER, processes them through Golgi, coats them with lipoproteins, and ejects them as chylomicrons on lateral and basal sides of cell 4. Chylomicrons go through porous BM of epithelium and enter the lymph capillaries 5. Chylomicrons are taken up by lymphatic capillary in villus (central lacteal) because they can't get across wall of capillary (too big) Very extended process for fat absorption: must break fats down, bring them into cell, repackage them into triglycerides, and package them into chylomicrons (high action of Golgi and ER of enterocytes) that can float in blood.

Large intestine: What cells are found in the large intestine mucosa?

1. Columnar absorptive cells (brush border is low and difficult to see) 2. Goblet cell (many in epithelium of colon and in crypts) 3. Undifferentiated cells (deep in crypts) give rise to enterocytes and goblet cells, which migrate up the gland and, in the small intestine, to the tips of villi

Small intestine: What are modes of surface amplification of the small intestine?

1. Length: 12-24 feet - so long because it's the main organ by which food is absorbed 2. Plicae circulares - aka "valves of Kerckring": folds of mucosa analogous to rugae of the stomach, except rugae are longitudinally-arranged - Valves of Kerckring are circularly arranged, run transversely to the length, and form a ring around the internal part of the intestine 3. Villi: leaf- or finger- like evaginations of the mucosa; villi are covered with enterocytes, which has a brush border 4. Microvilli: On the absorptive cells (increases the surface amplification even further)

Small intestine: What are the 2 nerve plexuses that control which muscle will contract at which time (peristalsis in the gut)?

1. Meissner's plexus (submucosa) 2. Auerbach's (myenteric) plexus

A = gland B = lacteal C = lamina propria D = goblet cell E = enterocyte -Villus sticking out in the middle. At the top (circular structure), villus cut across the section -Purple epithelial border - the enterocytes (E - can see their brush border)

A = gland B = lacteal C = lamina propria D = goblet cell E = enterocyte -Villus sticking out in the middle. At the top (circular structure), villus cut across the section -Purple epithelial border - the enterocytes (E - can see their brush border)

Appendix image: -See crypts and mucosal glands -Has same structure as rest of large intestine, except has lots of lymphoid nodules associated with it

Appendix image: -See crypts and mucosal glands -Has same structure as rest of large intestine, except has lots of lymphoid nodules associated with it

Small intestine: Describe the "vasculature gradient aiding with absorption" process

Because of the structure of the villus, blood comes in and out of the same region. This means that blood coming in will give up its water to the more concentrated blood coming out of the villus. Blood coming out of the villus will give up its solute to the less concentrated blood coming into the villus. This causes trapping of solute in the villus. [solute] in the villus is higher than [solute] in the rest of the body. In each villus, there's a microscopic region of higher concentration that helps pull water from the chyme into the connective tissue to get it into the blood. So, the structure of the villus is more than surface area; it also plays a role in transporting solutes (especially water) into the blood.

Colon: A = muscularis mucosae D = lamina propria C = Crypts of Lieberkuhn - glands -Lots of lymphocytes -Lots of goblet cells

Colon: A = muscularis mucosae D = lamina propria C = Crypts of Lieberkuhn - glands -Lots of lymphocytes -Lots of goblet cells

Small intestine: Describe the mucosal glands (crypts of Lieberkuhn) of small intestine mucosa

Crypts of Lieberkuhn are intestinal crypts at the base of villi but not completely surrounding it -Simple tubular glands in the mucosa of small intestine and also in the large intestine -Site of proliferative activity and undifferentiated cells undergoing division and crawling out over to replace enterocytes and goblet cells that get sloughed off at ends of villi -Extend down into lamina propria of mucosa

Diagram of colon: Colon is a flat surface with lots of crypts; no villi

Diagram of colon: Colon is a flat surface with lots of crypts; no villi

Diagram of single villus covered with enterocytes

Diagram of single villus covered with enterocytes

Diagram: Plicae circularis in the interior of intestine

Diagram: Plicae circularis in the interior of intestine

Duodenum: D = Villi (contain enterocytes and goblet cells B = Crypts (empty out into the lumen) C & E = lymphocytes A = Brunner's glands (only in duodenum)

Duodenum: D = Villi (contain enterocytes and goblet cells B = Crypts (empty out into the lumen) C & E = lymphocytes A = Brunner's glands (only in duodenum)

EM of Secretory granules (unusual appearance with a dual-phase interior)

EM of Secretory granules (unusual appearance with a dual-phase interior)

Endoscopic view of ileum: -See plicae/rings of Kerckring -Peyer's patches are located in region that is the anti-mesenteric side of ileum -Plicae are absent where Peyer's patches are located -M-cells are present in these regions

Endoscopic view of ileum: -See plicae/rings of Kerckring -Peyer's patches are located in region that is the anti-mesenteric side of ileum -Plicae are absent where Peyer's patches are located -M-cells are present in these regions

Small intestine: What do enterocytes transport?

Enterocytes act to transport the solutes in the chyme across the wall of the epithelium, into the interior, where nutrients are carried away in blood and lymph.

Small intestine: What are the main cells of the small intestine?

Enterocytes: -Absorptive cells -Have a brush border (for maximal usage of apical membrane for absorption of nutrients) -Have microvilli, further increasing surface amplification -Simple columnar epithelium with a brush border -Function: absorption of solutes and water, fat absorption (*Note: there is a different mechanism for fat and water/solute absorption)

Figure: Intestine in which outer longitudinal layer of smooth muscle has been removed: Myenteric (aka Auerbach's) plexus with smooth muscle behind it. All of strands in the back are smooth muscle fibers. Thicker lines in front - ganglia and nerve connections of Myenteric/Auerbach's nerve plexus; very extensive

Figure: Intestine in which outer longitudinal layer of smooth muscle has been removed: Myenteric (aka Auerbach's) plexus with smooth muscle behind it. All of strands in the back are smooth muscle fibers. Thicker lines in front - ganglia and nerve connections of Myenteric/Auerbach's nerve plexus; very extensive

Small intestine: Where does mitotic activity occur? What else happens here?

Glands at the base of the villi is where mitotic activity occurs and where cells undergo differentiation to different cell types

Image of colon: -Smooth surface, has a fold, but much simpler in structure -Lots of long, tubular glands - crypts of Lieberkuhn -Musclaris mucosae - the thin dark line beneath all the crypts outlining the folds over submucosa

Image of colon: -Smooth surface, has a fold, but much simpler in structure -Lots of long, tubular glands - crypts of Lieberkuhn -Musclaris mucosae - the thin dark line beneath all the crypts outlining the folds over submucosa

Image: Left = base of intestinal crypts of small intestine A = Paneth cells Right = higher power; can see secretory granules B = Muscularis mucosae (can see inner circular (I) and outer longitudinal (O) layer) C = lamina propria

Image: Left = base of intestinal crypts of small intestine A = Paneth cells Right = higher power; can see secretory granules B = Muscularis mucosae (can see inner circular (I) and outer longitudinal (O) layer) C = lamina propria

Image: Base of crypt of Lieberkuhn: Paneth cells = produce lysozymes and defensins -Large, easy-to-see eosinophilic granules at apical surface (usually brightly staining)

Image: Base of crypt of Lieberkuhn: Paneth cells = produce lysozymes and defensins -Large, easy-to-see eosinophilic granules at apical surface (usually brightly staining)

Image: Mucous secreted out of glands into the lumen

Image: Mucous secreted out of glands into the lumen

Slide of duodenum submucosa and muscularis externa

Note that the submucosa (Sm), occupied by glands of Brunner (GB), is a vascular structure (BV) and also houses Meissner's submucosal plexus. The submucosa extends to the muscularis externa (ME), composed of an inner circular (IC) and outer longitudinal (OL) smooth muscle layer. Note the presence of Auerbach's myenteric plexus (AP) between these two muscle layers. The duodenum, in part, is covered by a serosa (Se), whose mesothelium provides this organ with a smooth, moist surface

Slide of Ileum of small intestine (zoom-in of previous slide)

Note that the villi (V) are covered by a simple columnar epithelium, whose cellular constituents include numerous goblet cells (GC). The core of the villus displays blood vessels (BV) as well as a large lymphatic vessel known as a lacteal (l). The crypts of Lieberkühn (CL) open into the intervillar spaces (arrow). The group of lymphatic nodules of the ileum are known as Peyer's patches (PP). Inset a. Crypt of Lieberkühn. l.s. Monkey. Plastic section. ×540. The crypts of Lieberkühn also possess DNES cells (APD), recognizable by their clear appearance and usually basally oriented fine granules.

Slide of colon

Note the absence of surface modifications such as pits and villi, which indicate that this section is not of the stomach or small intestines. The epithelium (Ep) lining the lumen (L) is simple columnar with numerous goblet cells (GC). The straight tubular glands are crypts of Lieberkühn (CL), which extend down to the muscularis mucosae (MM). The inner circular (IC) and outer longitudinal (OL) layers of smooth muscle comprising this region of the mucosa are evident. The submucosa (Sm) is very vascular (BV) and houses numerous fat cells (FC).

PAS stain: Left = brush border surface of colonic absorptive cells A = run down into the crypts B = many goblet cells Right = cross section of crypts; made up of colonic absorptive cells and goblet cells

PAS stain: Left = brush border surface of colonic absorptive cells A = run down into the crypts B = many goblet cells Right = cross section of crypts; made up of colonic absorptive cells and goblet cells

PAS stain: stain of mucin granules in apical surface of goblet cell and staining of brush border of enterocytes

PAS stain: stain of mucin granules in apical surface of goblet cell and staining of brush border of enterocytes

SEM: Villi with small crypts/glands that empty into the regions between the villi. This is where undifferentiated cells undergo division and crawl out over to replace enterocytes and goblet cells that get sloughed off the ends of villi

SEM: Villi with small crypts/glands that empty into the regions between the villi. This is where undifferentiated cells undergo division and crawl out over to replace enterocytes and goblet cells that get sloughed off the ends of villi

Slide of Auerbach's plexus: -White area in the center of the image (nerve = B)

Slide of Auerbach's plexus: -White area in the center of the image (nerve = B)

Slide of anal margin: Transition of rectum (C) to anus (D) -Rectum = histologic structure very similar to rest of large intestine -Internal part of anus (development of keratinized skin (B) as transitions to outside)

Slide of anal margin: Transition of rectum (C) to anus (D) -Rectum = histologic structure very similar to rest of large intestine -Internal part of anus (development of keratinized skin (B) as transitions to outside)

Slide of duodenum: -Can distinguish inner circular and outer longitudinal layer (G & F( -See Brunner's glands in the submucosa (C) -Villi and crypts present in the mucosa

Slide of duodenum: -Can distinguish inner circular and outer longitudinal layer (G & F( -See Brunner's glands in the submucosa (C) -Villi and crypts present in the mucosa

What is the cell turnover rate in the GI tract?

Small intestine: 3-6 days Large intestine: 4-8 days -Not all cells turnover at the same rate - surface absorptive cells have a much faster rate of turnover than the enteroendocrine cells

Slide of anorectal juntion

The anorectal junction presents a superficial similarity to the esophagogastric junction because of the abrupt epithelial transition. The simple columnar epithelium (CE) of the rectum is replaced by the stratified squamous epithelium of the anal canal (AC). The crypts of Lieberkühn (CL) of the anal canal are shorter than those of the colon. The lamina propria (LP) is infiltrated by lymphoid cells (LC).

Slide of the base of the crypt of Lierberkuhn

The base of the crypt of Lieberkühn displays the several types of cells that compose this gland. Paneth's cells (Pc) are readily recognizable due to the large granules in their apical cytoplasm. DNES cells (APD) are clear cells with fine granules usually located basally. Goblet cells (GC), columnar cells (Cc), and stem cells (Sc) constitute the remaining cell population.

Slide of colon (zoom-in of previous slide)

The cell population of the crypts of Lieberkühn (CL) is composed of numerous goblet cells (GC), which deliver their mucus into the lumen (L) of the crypt. Surface epithelial cells (SEC) as well as undifferentiated stem cells are also present. The latter undergo mitosis (arrow) to repopulate the epithelial lining. DNES cells (APD) constitute a small percentage of the cell population. Note that Paneth's cells are not present in the colon. The lamina propria (LP) is very cellular, housing many lymphoid cells (LC). The inner circular (IC) and outer longitudinal (OL) smooth muscle layers of the muscularis mucosae (MM) are evident.

Slide of Appendix

The cross section of the appendix displays a lumen (L) that frequently contains debris (arrow). The lumen is lined by a simple columnar epithelium (Ep), consisting of many goblet cells (GC). Crypts of Lieberkühn (CL) are relatively shallow in comparison with those of the colon. The lamina propria (LP) is highly infiltrated with lymphoid cells (LC), derived from lymphatic nodules (LN) of the submucosa (Sm) and lamina propria. The muscularis mucosae (MM) delineates the border between the lamina propria and the submucosa.

Slide of Jejunum of small intestine (zoom-in of previous slide)

The crypts of Lieberkühn are composed of several cell types, some of which are evident in this figure. Goblet cells (GC) that manufacture mucus may be noted in various degrees of mucus production. Narrow stem cells (Sc) undergo mitotic activity (arrowhead), and newly formed cells reconstitute the cell population of the crypt and villus. Paneth's cells (PC) are located at the base of crypts and may be recognized by their large granules. DNES cells (APD) appear as clear cells, with fine granules usually basally located. The lamina propria displays numerous plasma cells (PlC).

Slide of Ileum of small intestine

The entire wall of the ileum is presented, displaying spiral folds of the submucosa that partially encircle the lumen. These folds, known as plicae circulares (Pci), increase the surface area of the small intestines. Note that the lamina propria is clearly delineated from the submucosa (Sm) by the muscularis mucosae. The lamina propria forms numerous villi (V) that protrude into the lumen (L); glands known as crypts of Lieberkühn (CL) deliver their secretions into the intervillar spaces. The submucosa abuts the inner circular (IC) layer of smooth muscle that, in turn, is surrounded by the outer longitudinal (OL) smooth muscle layer of the muscularis externa. Observe the serosa (Se) investing the ileum.

Slide of the duodenum:

The lamina propria of the duodenum possesses finger-like evaginations known as villi (V), which project into the lumen (L). The villi are covered by surface absorptive cells (SA), a simple columnar type of epithelium with a brush border. Interspersed among these surface absorptive cells are goblet cells (GC) as well as occasional APUD cells. The connective tissue (CT) core (lamina propria) of the villus is composed of lymphoid and other cellular elements whose nuclei stain very intensely. Blood vessels also abound in the lamina propria, as do large, blindly ending lymphatic channels known as lacteals (l), recognizable by their large size and lack of red blood cells. Frequently, these lacteals are collapsed. The deeper aspect of the lamina propria houses glands, the crypts of Lieberkühn (CL). These simple tubular glands deliver their secretions into the intervillar spaces. The bases of these crypts reach the muscularis mucosae (MM), composed of inner circular and outer longitudinal layers of smooth muscle. Deep to this muscle layer is the submucosa, which, in the duodenum, is occupied by compound tubular glands of Brunner (GB). These glands deliver their mucous secretion via ducts (D), which pierce the muscularis mucosae, into the crypts of Lieberkühn.

Slide of Jejunum of small intestine

The mucosa (M) and submucosa (Sm) of the jejunum are presented in this photomicrograph. The villi (V) of this region possess more goblet cells (GC) than those of the duodenum. Observe that the crypts of Lieberkühn (CL) open into the intervillar spaces (arrow) and that the lamina propria displays numerous dense nuclei, evidence of lymphatic infiltration. The flimsy muscularis mucosae (MM) separates the lamina propria from the submucosa. Large blood vessels (BV) occupy the submucosa, which is composed of a loose type of collagenous connective tissue. The inner circular (IC) layer of the muscularis externa is evident at the bottom of the photomicrograph.

Slide: Magnification of epithelium and part of connective tissue core of a villus

This higher magnification of a region similar to the boxed area presents the epithelium and part of the connective tissue core of a villus. Note that the surface absorptive cells (SA) display a brush border (BB), terminal bars (arrow), and goblet cells (GC). Although APUD cells are also present, they constitute only a small percentage of the cell population. The lamina propria (LP) core of the villus is highly cellular, housing lymphoid cells (LC), smooth muscle cells (SM), mast cells, macrophages (Ma), and fibroblasts, among others.

Trichome stain of colon: -Surface epithelium = columnar absorptive cells -Crypts of Lieberkuhn (C) are everywhere, cut in different ways -Lots of goblet cells and some columnar epithelial cells

Trichome stain of colon: -Surface epithelium = columnar absorptive cells -Crypts of Lieberkuhn (C) are everywhere, cut in different ways -Lots of goblet cells and some columnar epithelial cells