Small intestine

Embryology

Primitive gut formed from the endodermal lining (yolk sac) during the fourth week of gestation
- Endodermal layer gives rise to the epithelial lining of the GIT, and the splanchnic mesoderm surrounding the endoderm gives rise to the muscular connective tissue and all the other layers of the intestine
- Splanchnic mesoderm also wraps around the gut to form the mesenteries
- Neural crest provides the origin of the neurons in the gut wall
- Duodenum derived from foregut; the rest of the small bowel from the midgut
The midgut herniates through the umbilicus in the fifth week
- Cranial limb becomes the distal duodenum, jejunum and proximal ileum
- Caudal limb becomes the distal ileum and proximal two thirds of transverse colon
- The vitelline duct connects to the yolk sac at the juncture of cranial and caudal limbs, and is normally obliterated before birth, but can persist as a Meckel diverticulum in 2% of people (see separate topic under 'small bowel')
Gut temporarily occluded by endodermal proliferation in the fifth week, but recanalises in the seventh to ninth week
Intestine returns to the abdomen in the 10th week
- 90 degree anti-clockwise rotation during herniation, and another 180 degrees during return to abdomen
- Proximal jejunum completes a 270 degree rotation (when viewed from anterior), to occupy the left side of the abdomen
- Caecum now in the right upper quadrant, but gradually descends to RLQ
- Malrotation occurs around this time
Villi begin to form at about the 9th week in the proximal intestine, then proceeding caudally to fill the remainder of the bowel
Crypt formation begins in weeks 10-12 and cells differentiate into the four main types
- Absorptive enterocytes (95%)
- Goblet cells
- Paneth cells
- Enteroendocrine cells

Gross anatomy

Entire small intestine is 4-6m
- Duodenum 25cm
- Jejunum
  - Begins at duodenojejunal angle (suspensory ligament of the fourth part of the duodenum - ligament of Treitz - a fibrous band, sometimes containing muscle fibres, which suspends the superior and left aspect of the DJ flexure to the right crus of the diaphragm)
  - Look for IMV to left of ligament of Treitz to confirm location (has to be IMV, as SMV would be to the right, involved with the root of mesentery - see Netter plate below)
  - Conventionally described as the proximal two-fifths of the small intestine
- Ileum
  - No obvious demarcation between jejunum and ileum
  - Conventionally described as the distal three-fifths of the small intestine
Small bowel mesentery - see separate topic under 'peritoneal cavity'
Differentiating jejunum and ileum

Jejunum	Ileum
Larger circumference 3-4cm	Smaller circumference 2.5-3.5cm
Thicker wall	Thinner wall
One or two arcades with long, straight vasa recta	Four or five separate arcades with shorter vasa recta
Prominent plicae circularis/valves of Kerkring	Less prominent, absent in TI
Pink	White
Mesenteric fat does not reach bowel wall	Reaches bowel wall
Less fat	More mesenteric fat - always to bowel wall

Duodenum

Structure

C-shaped tube lying in front of the IVC and aorta. Loops around head of pancreas, which is at L2 level.
Total length 25cm
First 2.5cm are contained within the peritoneum of the lesser and greater omenta, but the rest is retroperitoneal
Four parts:
- Superior (D1)
  - Proximal 2-4cm
  - Incorporating duodenal bulb
  - Lies in front of GDA, CBD, and PV
  - Lies posterior to GB/inferior surface of right lobe of liver
  - Pancreas inferomedially, but not intimately related
  - Separate blood supply to pancreas
- Descending (D2)
  - Commences at the superior duodenal angle, which is where the first circular fold is found
  - Retroperitoneal structure
  - Curves downwards over hilum of right kidney
  - HOP medially
  - Covered anteriorly with peritoneum, where the transverse mesocolon attachment crosses
  - Posteromedial wall receives common opening of CBD and main pancreatic duct
  - Contains valvulae conniventes/Kerckring's valves, which are the circular folds seen on endoscopy
  - Mobilisation
    - 'Kocher manoeuvre'
    - Incise the peritoneum along its right border
    - Elevate the duodenum anteriorly and to the left
    - Does not disrupt blood supply
- Horizontal (D3)
  - Curves forward from the right paravertebral gutter over the slope of the right psoas muscle, and passes over the forwardly projecting IVC and aorta to reach the left psoas muscle
  - Lies on commencement of IMA at inferior border
  - Posterior to base of small bowel mesentery containing SMA/SMV
  - Blood supply comes from pancreatic uncinate process
  - Hardest to mobilise because of the anterior relationships
- Ascending (D4)
  - Blood supply from branches off SMA
Blood supply
- Superior and inferior pancreaticoduodenal arteries
- First 2cm receives blood from the hepatic, GDA, supraduodenal, right gastric and right gastroepiploic arteries
  - See 'liver' for full description of GDA/hepatic
- Venous drainage to tributaries of SMV and PV

Jejunum/ileum

Endoscopic anatomy
- Jejunum is characterised by thinner but more frequent circular folds than the duodenum, and the mucosa is smoother
- Ileal mucosa has a fine, granular appearance, with visible villi underwater. Lymphoid follicles are also seen.
Arterial supply
- Branches of SMA - see separate topic under 'great vessels'
- Abundant collateral provided by vascular arcades
- In the mesentery, each branch divides into superior and inferior branches, which anastomoses with its fellow above and below to form arcades. Usually only one or two arcades in proximal small bowel, but progressively increases as you move distally to mid-small bowel up to 5 or 6, then comes down again around TI to 1-2.
- Vasa rectae (arteriae rectae) arise from the arcade farthest from the SMA and pass straight to bowel wall - essentially end arteries
- Not much intramural plexus when compared to stomach or oesophagus; only able to sustain 2-4cm of devascularised small bowel without a colour change being observed.
Venous drainage
- Into SMV, which joins the splenic vein behind the neck of the pancreas to form the portal vein
- Artery and vein do not always lie close together
- See full description under 'colon'
Innervation
- PNS
  - Derived from vagus nerve, traversing the coeliac ganglion
  - Influences secretion, motility and other bowel activity
  - Vagal afferent fibres are present but do not carry pain
- SNS
  - Three sets of splanchnic nerves - ganglions usually located in a plexus around the base of the SMA
  - Motor impulses affect blood vessel motility and probably gut secretion and motility
  - Pain is transmitted through general visceral afferent fibres of the sympathetic system
Lymphatics
- Seen as Peyer patches in the distal small bowel
- Drainage proceeds from the mucosa through the wall of the bowel to a set of nodes adjacent to the bowel in the mesentery
- Then to a group of regional nodes adjacent to the mesenteric arterial arcades
- Then to a group at the base of the superior mesenteric vessels
- Then into the cisterna chyli and up the thoracic duct

Microscopic anatomy (from external to internal)

Serosa
- Visceral peritoneum
- Jejunoileum - a single layer of encircling flattened mesoepithelial cells
- Duodenum - anterior surface of the duodenum
Muscularis propria
- Outer longitudinal layer - thin
- Intervening ganglion cells from the myenteric (Auerbach) plexus, which connect the two layers
- Inner circular layer - thick
Submucosa
- A layer of fibroelastic connective tissue containing blood vessels and nerves
- Strongest component of the intestinal wall - must be included in the anastomosis
- Elaborate lymphatic networks, arterioles, venules and the Meissner plexus (connected to Auerbach plexus)
- Lax, allows considerable movement between mucosa and muscle
Mucosa
- Muscularis mucosae
  - Thin layer of muscle, separating mucosa from submucosa
- Lamina propria
  - Connective tissue
  - Contains plasma cells, lymphocytes, mast cells, eosinophils, macrophages, fibroblasts, smooth muscle cells, non-cellular connective tissue
  - Performs a protective role due to its rich supply of immune cells
- Epithelium
  - Continual sheet of epithelial cells covering the villi and lining the crypts
  - Main functions of the crypt epithelium are cell renewal, exocrine, endocrine, water and ion secretion
  - Main functions of villous epithelium are digestion and absorption
    - Tallest in distal duodenum and proximal jejunum; shortest in TI
  - Four main cell types:
    - Absorptive enterocytes (main cell type)
      - Luminal surface covered by microvilli, increasing the absorptive capacity 30-fold
      - Microvilli covered by a fuzzy glycoprotein called glycocalyx to further increase absorption
    - Goblet cells (secrete mucus)
    - Paneth cells (secrete lysozyme, TNF and cryptdins)
    - Enteroendocrine cells (produce gastrointestinal hormones)

Physiology

Digestion and absorption

- Carbohydrates
  - In general, dietary starches are almost totally converted to maltose and other small glucose molecules before they reach the duodenum. The remainder of carbohydrate absorption occurs as a result of brush border enzymes of the luminal surface.
  - Brush borders contain lactase, maltase, sucrase-isomaltase, and trehalase - which split the disaccharides as well as other small glucose polymers into the constituent glucose monomers
  - Carbohydrates are absorbed as monosaccharides - mainly via three active transport membrane carrier systems (SLGT-1, GLUT-5, and GLUT-2)
- Protein
  - Begins in the stomach, where gastric acid denatures proteins
  - Pancreatic proteases (trypsin, chymotrypsin and elastase) continue the process in the duodenum
  - Complex proteins are split into dipeptides, tripeptides and some larger proteins, which are absorbed from the lumen by a sodium-mediated active transport mechanism and digested further by enzymes in the brush border and cytoplasm

Single amino acids then pass through the epithelial cell membrane and into the portal venous system
Absorption of protein is usually 80-90% complete in the jejunum

Fats
- Almost all occurs in the small intestine, mostly in the proximal part.
- Emulsifying agents from the liver (bile - containing bile salts and lecithin) assist to break down fat globules into smaller sizes. The globules are fragmented more and more through intestinal agitation.
- Lipase can now split triglycerides into free fatty acids and 2-monoglycerides
- Micelles are formed out of 20-40 molecules of bile salts with a sterol nucleus (fat soluble centre, hydrophilic outer). The micelles are carried to the brush borders, and absorbed.
- Micelles diffuse into the interior of the cell because they're so lipid-soluble. Bile salts remain in the intestinal lumen to repeat the process.
- Fatty acids and monoglycerides reform into triglycerides inside the cell (involves coenzyme A-activated fatty acids)
- Reconstituted triglycerides then combine with cholesterol, phospholipids, and apoproteins to form chylomicrons, which pass from the epithelial cells into the lacteals and then through the lymphatics into the venous system
- 80-90% of all absorbed fat is transported to the blood by way of the thoracic lymph. Short quantities of short to medium chain fatty acids may be absorbed directly into the portal blood since they are more water-soluble.
- Total bile acid pool (approximately 2-3g) recirculates about six times every 24 hours through the enterohepatic circulation. Almost all the bile salts are reabsorbed with only about 0.5g lost in the stool every day - this loss is replaced by newly synthesised bile acids from cholesterol.
Water
- 8-10L of water enters the small bowel every day, and all but 500mL is reabsorbed before leaving into the colon
- Mostly simple diffusion, but can also be drawn in by the process of osmotic pressure, after sodium, glucose or amino acids have been absorbed into cells
Electrolytes
- Sodium - absorbed by active transport through the basolateral membrane
- Chloride - absorbed in the upper part of the small intestine passively
- Bicarb - needs to be reabsorbed in large quantities. Indirectly reabsorbed as carbon dioxide, after combining with H+ ions secreted into the lumen
- Calcium - absorbed in duodenum and jejunum by active transport, which is facilitated by an acidic environment and enhanced by vitamin D and parathyroid hormone
- Iron - absorbed as haem or non-haem in the duodenum by an active process, then either deposited within the cell as ferritin or transferred to the plasma bound to transferrin
Vitamins
- Fat-soluble (ADEK)
  - Carried in micelles and transported in the chylomicrons of the lymph through the thoracic duct
- Water-soluble
  - Ascorbic acid (vitamin C) - active transport with a sodium-coupled receptor
  - Biotin
  - Nicotinic acid
  - Folic acid
  - Riboflavin (B2) - facilitated transport in the upper intestine
  - Thiamine (B1) - rapidly absorbed in the jejunum by a sodium-coupled active process
  - Pyridoxine (B6) - rapidly absorbed by simple diffusion into the proximal jejunum
  - Cobalamin (B12) - absorbed in TI with the assistance of intrinsic factor

Motility

- Peristalsis - intestinal contractions passing aborally at 1-2cm/sec - acts to move chyme through the intestine
- Motility patterns vary greatly between the fed and fasted states
- Fed - duodenum initiates pacesetter potentials
- Fasting - cyclical contractions moving aborally along the intestine every 75-100 minutes. Initiated by the migrating myoelectric complex, which is under the control of neural and humoral pathways. PNS (vagal) activity stimulates motility and SNS inhibits.
- Motilin is an intestinal peptide which seems to stimulate motility

Endocrine function

- Small bowel is the largest endocrine organ in the body

Immune function

- Gut-associated lymphoid tissue is in four areas:
  - Peyer patches
    - Unencapsulated lymphoid nodules
    - Recognise antigens through a specialised sampling mechanism
    - Antigens gaining access to Peyer patches will activate and prime B and T cells in that site
    - Activated lymphocytes then migrate into afferent lymphatics that drain into mesenteric lymph nodes, and some migrate into the lamina propria to generate the mucosal immune response
  - Lamina propria lymphoid cells
    - 60% T cells, 40% B cells
  - Paneth cells
    - Line the base of crypts and release antimicrobial factors to protect adjacent stem cells
  - Intra-epithelial lymphocytes