Gastrointestinal tract

Gastrointestinal system is composed of digestive tract and the accessory organs, salivary glands, pancreas, gallbladder, and liver. The upper gastrointestinal (GI) tract consists of buccal cavity (mouth), pharynx, esophagus, stomach, and duodenum. Duodenum can be divided in four segments: bulb, and descending, horizontal, and ascending duodenum. The lower GI tract includes the rest of the small intestine, and large intestine. The small intestine can be divided into three segments: duodenum (part of the upper intestine), jejunum, and ileum. The large intestine consists of cecum; ascending, transverse, descending, and sigmoid colon; rectum, and anal canal.

The layers of the GI tract surrounding lumen are

mucosa, containing: epithelium, lamina propria, and muscularis mucosae;
submucosa, containing: vasculature, lymphatic vessels, and Meissner's plexus;
(tunica) muscularis, containing: circular muscle, myenteric (Auerbach's) plexus, and longitudinal muscle; and
(tunica) serosa (serous layer), containing: areola connective tissue, and epithelium.

The smooth muscles of the GI tract are regulated by sympathetic and parasympathetic autonomous nervous system, and by an extensive network of intrinsic neurons of the gut, located in the submucosal plexus and in the myenteric plexus with glial cells.

Vasculature of the GI tract belongs to splanchnic circulation, which includes gastric and intestinal, and hepatic, pancreatic, and splenic circulations. Splanchnic circulation is supplied by celiac, superior mesenteric, and inferior mesenteric arteries, and is drained via portal vein to the liver. Chylomicrons (chylomicra), synthesized by enterocytes in the intestines, do not enter the splanchnic circulation and liver, but are released into the intestinal lymphatics, and enter the circulation via thoracic duct.

Most of the blood flow of GI tract is directed to the mucosa and submucosa, where perfusion can be ∼0.2-1.2 mL/(mL*min), while perfusion in outer layers is ∼0.3 mL/(mL*min) or less (Hultén et al., 1976a, 1976b, and 1977; Ivarsson et al., 1982). Perfusion in GI tract can increase substantially after a meal, and reduce during exercise and cold or heat stress. Oxygen consumption is relatively constant, as oxygen extraction changes according to perfusion changes.

Enterocytes absorb luminal contents and deliver some of that as chyle into lymphatic capillaries of the GI tract (lacteals). Lacteals connect to the submucosal lymphatic vessels, and with lymphatic vessels from the muscular layer drain into collecting lymphatic vessels, and from there to lymph nodes. Lymph nodes from the intestinal and lumbar trunks drain into a dilated sac, cisterna chyli, and from there into the thoracic duct. Chyle contains lymph, lymphocytes, immunoglobulins, albumin, and chylomicrons. Most of the lymph produced in the body is derived from the GI tract, ∼2 L/day, especially after a fat-containing meal (Alexander et al., 2010). Lymph flow is increased also during acute and chronic inflammation, partly because venous outflow may be blocked.

During a meal, glucose sensing activates sympathetic nervous system, which stimulates glucose uptake and glycogenesis in skeletal muscle, and synthesis and storage of lipids in white adipose tissue (WAT). Neuropeptides ghrelin, peptide YY (PYY), and GLP-1 are secreted from entero-endocrine cells in response to meal and nutrients in intestinal lumen. Gut hormones can directly modulate triglyceride metabolism in adipocytes; for instance, PYY inhibits lipolysis, and secretin stimulates lipolysis. All macronutrients elicit meal-associated thermogenesis. Cholecystokinin (CKK) and GLP-1 stimulate sympathetic innervation in brown adipose tissue (BAT), activating meal-associated thermogenesis. Secretin directly stimulates BAT thermogenesis (Li et al., 2018), and induces satiation via BAT-brain axis (Sun et al., 2023).

Movement, erosion, and dissolution of particles in the GI tract are important for the physiology-based pharmacokinetic modelling of drugs. Colon motility can be assessed using capsule telemetric methods (Mark et al., 2019). Colonic wall motion and fluid distribution can be studied using MRI (Hoad et al., 2016; Sulaiman et al., 2019). PET can be used to dynamically follow fluid distribution in the GI tract by giving orally a nonabsorbable radiopharmaceutical, such as [¹⁸F]deoxyfluoropoly(ethylene glycol) (Takashima et al., 2013).

Bowel motion and movement of gas during the PET study, and between transmission and PET scan, can cause image artifacts (Nakamoto et al., 2004; Lodge et al., 2010). Image registration may also be hampered by the physiological motion (Nakamoto et al., 2003). Combined PET/CT still improves the overall accuracy of diagnostic studies (Kamel et al., 2004).

Metabolism

Metabolism in intestinal and colon tissue can be studied with PET: [¹⁸F]FDG has been used to assess glucose uptake, and [¹⁵O]H₂O has been used to measure perfusion. [¹⁸F]FTHA has been administered orally to study organ-specific dietary fatty-acid uptake (Labbé et al., 2011). Intravenous administration of [¹⁸F]FTHA has been used to study the FFA uptake rate in intestine (duodenum and jejunum) and colon (Motiani et al., 2017; Koffert et al., 2018).

Gut microbiota

Gut microbiota is metabolically active; it constitutes at least 1% of an adult human's body mass, and ∼7.5% of total caloric flux (Riedl et al., 2021). High [¹⁸F]FDG uptake in colon is related to low bacterial diversity, and vice versa (Boursi et al., 2018; Svetkovic et al., 2021). Faecal transplantation can be studied with in vitro labelled bacteria (Wang et al., 2020).

Inflammation

[¹⁸F]FDG has been used in imaging of inflammatory bowel disease (IBD) (Perlman et al., 2013), including the staging, treatment planning, and follow-up of Crohn's disease (Palatka et al., 2018). FAPI PET have been found to correlate with markers of Crohn's disease and to detect lesions in all intestinal segments (Chen et al., 2023). Oral ⁶⁷Ga-citrate can be used to assess inflammatory activity in Crohn's disease (Tajra et al., 2020). In small animals models of IBD VAP-1 radioligand [⁶⁸Ga]DOTA-Siglec-9 has shown promising results (Bhowmik et al., 2023). Also TSPO radioligand [¹¹C]PBR28 has been used in small animals, but colitis was not detected with PET because of insufficient resolution (Kurtys et al., 2017). The same issue was noticed with [¹⁸F]FDG unless urinary bladder was continuously flushed during imaging (Deleye et al., 2014).

Peritoneum and peritoneal cavity

The peritoneum is a large, normally <1 mm thick, serous membrane that consists of two continuous layers, parietal and visceral peritoneum. Peritoneum is covered by mesothelial monolayer which is just 10µm thick, but protected by glycocalyx. Basement membrane under the mesothelial cells covers less dense connective tissue layer containing blood vessels and lymphatic vessels and adipocytes (Kastelein et al., 2019). The parietal peritoneum is attached to abdominal wall and it lines the surface of the abdominal and pelvic cavity. The visceral peritoneum covers the internal organs (viscera). (Terawaki, 2018). Peritoneal cavity is a minimal fluid-filled thin space between the membrane layers, normally containing only ∼5-100 mL fluid, functioning as lubricant to minimize the friction between intra-abdominal organs. Infections, trauma, bowel perforation, and malignancies can marked thickening of peritoneal membranes, or increased fluid volume or appearance of gas, blood, or urine in the peritoneal cavity (Patel & Planche, 2013). Peritoneal cavity can be anatomically divided into greater and lesser sac, which are connected. Mesothelial cells of the peritoneum regulate the transport of interstitial fluid into the cavity and back (van Baal et al., 2017; Krediet et al., 2018; Isaza-Restrepo et al., 2018; Kastelein et al., 2019). Mesothelial cells produce components of the fluid. Lymphatic system resorbs some of the fluid as it enters subperitoneal lymphatic lacunae. Stomata are lymphatic portals between mesothelial cells, directly connected to the lymphatic system. Approximately 1 L of peritoneal fluid is produced and absorbed daily (van Baal et al., 2017). Diaphragmatic movement and bowel peristalsis circulate the fluid inside the peritoneal cavity. Peritoneal dialysis, in treatment of patients with CKD, is based on inserting catheter into the peritoneal cavity, increasing the fluid volume, enhancing the peritoneal circulation; the very large surface are of the peritoneum ensures the purification of blood. Additionally, mesothelial cells are covered by microvilli (Terawaki, 2018). Fluid removal rate is affected by hydrostatic pressure against the diaphragm and, thus, posture (Barrett et al., 1997).

Intraperitoneal organs (liver, stomach, spleen, intestines) are not inside peritoneal cavity, because they are too surrounded by the visceral peritoneum. Extra- and retroperitoneal organs (duodenum, pancreas, kidneys) only partially touch the peritoneum (Patel & Planche, 2013).

Mesentery is the part of peritoneum that suspends the small and large intestine from the posterior abdominal wall. Greater and lesser omentum are parts of peritoneum that connect the stomach, duodenum, colon, and liver. Splenorenal and gastrosplenic ligament are peritoneal parts that connect spleen to kidney and stomach to spleen. Peritoneal ligaments also support pelvic organs and structures, including ureters, uterus and ovaries. Peritoneum and especially the mesentery supports attached vascular and lymphatic vessels, and nerves for the internal organs (Patel & Planche, 2013). These supportive peritoneal ligaments are generally fatty structures, with variable microvasculature. Total effective blood flow to the peritoneum is 60-100 mL/min, that is, 1-2% of cardiac output. Veins attached to the peritoneum drain into the portal vein, directing ∼1L blood per min into the liver (Solass et al., 2016).

Gastrointestinal symptoms are common in rheumatologic diseases, such as fibromyalgia and rheumatoid arthritis (Schatz & Moshiree, 2018). Intra-abdominal sepsis often develops in the peritoneal cavity. Peritoneum is active in abdominal infections and inflammation, and it contributes to fibrotic adhesion formation after infection or surgery. Metastases from many epithelial malignancies, including ovarian, colon, and gastric cancer, localize to peritoneum (van Baal et al., 2017).

[¹⁸F]FDG PET can be used in imaging of peritoneal cavity carcinomas (Prassopoulos et al., 2018).

Peritoneal endometriosis

Endometriosis is a common disorder, affecting ∼10% of women, causing chronic pelvic pain. it is characterized by presence and growth of endometrial-like tissue outside of the uterine cavity, most commonly in the ovaries and peritoneal ligaments. Pathogenesis includes chronic inflammation and cell proliferation (van Baal et al., 2017; Foti et al., 2018; Silveira et al., 2018).

Clinical utility of [¹⁸F]FDG PET and somatostatin tracer [⁶⁸Ga]DOTATATE in localizing endometriosis is poor (Fastrez et al., 2011 and 2017; Setubal et al., 2011). Numerous case reports show that endometriosis can mimic malignant tumours, even in the lungs. Estradiol stimulation could help in endometriosis imaging with [¹⁸F]FDG (Arsenault & Turcotte, 2016).

[¹⁸F]fluorocholine has shown some uptake in rat model, but uptake was increased also in sham-operated animals (Silveira et al., 2018).

Estrogen receptor (ER) is a promising target for detecting ER-positive tumours and endometriosis. 3-Aminoethyl estradiol (EDL) -based PET radiopharmaceuticals have increased specific uptake in animal models of endometriosis (Takahashi et al., 2007). In human studies, 16α-[¹⁸F]fluoro-17β-estradiol ([¹⁸F]FES) has shown better accuracy than MRI in diagnosis of deep infiltrating endometriosis (Cosma et al., 2016).

Literature

Debas HT: Gastrointestinal Surgery - Pathophysiology and Management. Springer, 2004. ISBN 0-387-00721-0. doi: 10.1007/b97293.

diZerega GS, Rodgers KE: The Peritoneum. Springer, 1992. doi: 10.1007/978-1-4613-9235-4.

Du Y (ed.): PET/CT in Colorectal Cancer. Springer, 2017. doi: 10.1007/978-3-319-54837-1.

Hodler J, Kubik-Huch RA, von Schulthess GK (eds.): Diseases of the Abdomen and Pelvis 2018-2021: Diagnostic Imaging - IDKD Book. Springer, 2018. Open Access. doi: 10.1007/978-3-319-75019-4.

Michailova KN, Usunoff KG: Serosal Membranes (Pleura, Pericardium, Peritoneum): Normal Structure, Development and Experimental Pathology. Springer, 2006. ISBN 978-3-540-28044-6. doi: 10.1007/3-540-28045-6.

Szyszko TA (ed.): PET/CT in Oesophageal and Gastric Cancer. Springer, 2016. doi: 10.1007/978-3-319-29240-3.

Welcome MO: Gastrointestinal Physiology - Development, Principles and Mechanisms of Regulation. Springer, 2018. ISBN 978-3-319-91056-7. doi: 10.1007/978-3-319-91056-7.

Tags: Intestine, Portal vein, Bile acids, Lymphatic system, Lipoproteins

Updated at: 2024-01-15
Created at: 2018-09-04
Written by: Vesa Oikonen