6de5a1ff-c9bf-453a-ad00-61ad5cd47a9c_Lecture_8_Histology_of_the_gastrointestinal_tract.pdf

🐣 Lecture 8: Histology of the gastrointestinal tract LO: General organisation - 4 key players - germ layer origins of layers The four key layers of the GI tract: Mucosa - epithelium, la...

🐣 Lecture 8: Histology of the gastrointestinal tract LO: General organisation - 4 key players - germ layer origins of layers The four key layers of the GI tract: Mucosa - epithelium, lamina propria, muscularis mucosa Submucosa Muscularis externa Serosa or adventia Mucosa Lecture 8: Histology of the gastrointestinal tract 1  Epithelium: The innermost layer lining the gut lumen, consisting of different cell types that vary across different regions of the gut. Lamina Propria: A layer of loose connective tissue beneath the epithelium, rich in capillaries and lymphatics. This tissue supports blood flow to the Lecture 8: Histology of the gastrointestinal tract 2  epithelium and facilitates the absorption of nutrients into the bloodstream. The lamina propria also contains various immune cells to protect against harmful substances and microbes in the gut, along with fibroblasts (including myofibroblasts) that help regulate the epithelium and produce connective tissue. Nerve Fibers and Glial Cells: Nerve fibers project from the submucosal and myenteric plexuses into this region, regulating epithelial function, immune responses, and blood flow. Muscularis Mucosa: This is a thin layer of smooth muscle located beneath the lamina propria, separating the mucosa from the submucosa. It can vary in prominence depending on the gut region. Submucosa Dense Connective Tissue: Unlike the loose connective tissue of the lamina propria, the submucosa is composed of denser, irregular connective tissue with more collagen fibers, providing structural strength. Lecture 8: Histology of the gastrointestinal tract 3  Blood Vessels and Lymphatics: Larger blood vessels and lymphatic vessels are found here, supplying the mucosa and supporting nutrient absorption. Submucosal Nerve Plexus: This network of nerves helps regulate gut functions. The nerve cells form clusters and connect in a way that resembles fishnet stockings, coordinating communication between the muscle, epithelium, immune cells, and blood vessels. Glands and Lymphoid Follicles: These structures, including clusters of immune cells, can extend into the submucosa, further contributing to gut immune responses. Muscularis externa Lecture 8: Histology of the gastrointestinal tract 4  Smooth Muscle Layers: Composed of two layers of smooth muscle: an inner circular layer and an outer longitudinal layer. These muscles are responsible for the peristaltic movements that propel food through the gut. Myenteric Plexus: Located between the two muscle layers, this nerve plexus helps regulate gut motility and other functions, with support from glial cells and macrophages. Serosa and Adventitia: Lecture 8: Histology of the gastrointestinal tract 5  Serosa: A thin, outer covering of the gut made of mesothelium, a type of simple squamous epithelium that secretes a lubricating fluid to prevent friction between organs. It is found around intraperitoneal organs (e.g., stomach, small intestine). The serosa is found around intraperitoneal organs. These are organs that are suspended within the peritoneal cavity and are not directly attached to the body wall. Examples include the liver, stomach, and the loops of the small intestine. These organs are essentially "held off" from the body wall by the serosa. Adventitia: A connective tissue layer that binds retroperitoneal organs (e.g., parts of the colon) to the body wall or other organs. The primary role of the adventitia is to connect organs to each other and to the body wall. It provides structural support, helping to anchor retroperitoneal organs in place. The adventitia surrounds retroperitoneal organs. These are organs that are positioned against the posterior body wall, behind the Lecture 8: Histology of the gastrointestinal tract 6  peritoneum. Parts of the colon are examples of retroperitoneal organs, where the adventitia attaches the organ to the body wall and to surrounding structures. Embryological Origins: LO: Regional histological differences - oesophagus, stomach, duodenum, jejunum, ileum, large intestine OESOPHAGUS The esophagus is lined with stratified squamous epithelium → designed for protection ^^ since it’s responsible for transporting food from the mouth to the stomach, it needs to withstand the abrasion caused by swallowing Lecture 8: Histology of the gastrointestinal tract 7  different types of food, which can sometimes be rough or bulky. There are some mucous glands in the esophagus that extend into the submucosa → secrete mucus into the lumen of the esophagus & serves to lubricate the passage of food Muscularis externa has skeletal muscle in upper parts (voluntary control over swallowing) → smooth muscle near stomach. Most of the esophagus is covered by an adventitia, with only the lowest portion having a serosa as it enters the peritoneal cavity before connecting to the stomach. Most of the esophagus is retroperitoneal, meaning it lies outside the peritoneal cavity and is attached to other organs or the body wall by the adventitia. STOMACH Lecture 8: Histology of the gastrointestinal tract 8 Lecture 8: Histology of the gastrointestinal tract 9  Rugae are folds of the mucosa and submucosa that are visible when the stomach is empty. These folds allow the stomach to expand when it fills with food. As the stomach fills, the rugae flatten out to accommodate the increased volume. The mucosa is the innermost layer of the stomach The epithelium in the stomach changes from the stratified squamous epithelium (found in the esophagus) to simple columnar epithelium (crucial for secretion and absorption.) Simple columnar epithelium forms gastric pits, which are invaginations that extend down into gastric glands. The gastric glands are deep structures within the mucosa that extend to the muscularis mucosae and contain several different cell types, each with a specific function: Mucous (Neck) Cells: These cells produce mucus, which coats the stomach lining to protect it from the acidic environment. Lecture 8: Histology of the gastrointestinal tract 10  Parietal Cells: These cells secrete hydrochloric acid (HCl), which creates the acidic environment necessary for digestion and activation of enzymes. Chief Cells: These cells secrete pepsinogen, an inactive enzyme that is activated by the acidic environment to become pepsin, a proteolytic enzyme that breaks down proteins. Enteroendocrine Cells: These are hormone-secreting cells that, despite being few in number, play a critical role in regulating stomach functions by releasing hormones that act locally on other cells in the stomach. Stem Cells: These cells are responsible for the renewal of the various cell types in the mucosa. Given the harsh acidic environment, frequent renewal of the epithelium is essential to maintain the integrity of the stomach lining. Lamina propria layer - found just beneath the epithelium Contains immune cells such as lymphocytes and plasma cells, as well as lymphoid follicles. These structures provide immune protection to the stomach lining. Lecture 8: Histology of the gastrointestinal tract 11 Lecture 8: Histology of the gastrointestinal tract 12  The submucosa lies beneath the mucosa and is made up of dense irregular connective tissue. Provides structural support to the mucosa and contains blood vessels, nerves, and lymphatics that supply the stomach tissue. The muscularis externa in the stomach is unique because it consists of three layers of smooth muscle → circular, longitudinal and some oblique muscle These muscle layers work together to mix and propel the stomach contents (chyme) through the digestive tract. The oblique layer, in particular, enhances the stomach's ability to churn food and mix it with digestive juices. The outermost layer of the stomach is the serosa, which is a smooth membrane lined with mesothelium (a layer of simple squamous Lecture 8: Histology of the gastrointestinal tract 13  epithelium). The stomach is an intraperitoneal organ, meaning it is covered by the serosa and lies within the peritoneal cavity. This allows the stomach to move freely within the abdominal cavity as it expands and contracts. SMALL INTESTINE Primary site for nutrient absorption in the gastrointestinal tract & is lined with simple columnar epithelium, similar to the stomach, which is ideal for absorption The small intestine maximises its absorptive capacity through several structural adaptations that increase the surface area: Plicae Circulares: These are folds of the submucosa. These circular folds slow down the movement of food, allowing more time for nutrient absorption. Villi: Lecture 8: Histology of the gastrointestinal tract 14  Villi are finger-like projections of the mucosa that extend into the lumen of the intestine. The villi increase the surface area available for absorption significantly. Each villus contains a core of lamina propria (a layer of connective tissue) with capillaries and lymphatic vessels (lacteals) that absorb nutrients. Microvilli: Microvilli are microscopic projections on the surface of enterocytes (the absorptive cells of the small intestine). These projections form a brush border, further increasing the surface area for absorption. Microvilli contain actin filaments that support their structure, allowing them to efficiently absorb nutrients. The brush border is crucial for nutrient absorption because it contains enzymes that further break down nutrients, allowing them to be absorbed by enterocytes. Lecture 8: Histology of the gastrointestinal tract 15  Epithelial cell types of the small intestine Enterocytes: Lecture 8: Histology of the gastrointestinal tract 16  These are the primary absorptive cells, covered with microvilli. They play a key role in absorbing nutrients across their surface. Goblet Cells: These cells secrete mucus, which lubricates the intestinal lining and protects it from the harsh digestive environment. Goblet cells are named for their goblet-like shape. Enteroendocrine Cells: Similar to those in the stomach, these cells are sparse but essential, secreting hormones that regulate various functions in the gut. Paneth Cells: Located at the base of the intestinal crypts, Paneth cells support stem cells and have a role in antimicrobial defense by secreting enzymes like lysozyme. Stem Cells: Found in the crypts of Lieberkühn (the indentations between villi), these stem cells continuously regenerate the epithelial lining of the intestine, producing new enterocytes, goblet cells, and Paneth cells. Transit Amplifying Cells: These are intermediate cells that are rapidly dividing and differentiate into various types of mature intestinal cells. They are crucial for the ongoing renewal of the intestinal lining. Regional differences in the small intestine Duodenum A unique feature of the duodenum is the presence of Brunner's glands, which are located in the submucosa → secrete an alkaline mucus that helps neutralize the acidic chyme coming from the stomach. Lecture 8: Histology of the gastrointestinal tract 17  Duodenum also contains villi, which are finger-like projections of the mucosa that increase the surface area for absorption These villi in the duodenum are of moderate length compared to those in the jejunum Jejunum Longest villi - maximises its surface area for nutrient absorption Lecture 8: Histology of the gastrointestinal tract 18  Ileum A distinguishing feature of the ileum is the presence of Peyer's patches, which are large aggregates of lymphoid follicles Extend from the submucosa up to the epithelium and are involved in monitoring and responding to antigens, bacteria, and other potentially harmful substances in the gut Villi in the ileum are generally shorter than those in the jejunum LARGE INTESTINE (COLON) Differences to small intestine: Lecture 8: Histology of the gastrointestinal tract 19  Unlike the small intestine, which has villi to increase surface area for absorption, the large intestine has crypts but no villi. Many Goblet cells Increased number of goblet cells is crucial for this lubrication process, which is more demanding in the large intestine Absorptive enterocytes Primary role here is to absorb water and electrolytes rather than nutrients Cells line the surface of the crypts and contribute to the dehydration of the intestinal contents as they become feces Stem cells, enteroendocrine cells Crypts in the large intestine also house stem cells at their base, which are crucial for renewing the epithelium There are also enteroendocrine cells, though fewer in number, which play a role in secreting hormones that influence local gut function and overall digestion No Paneth cells Thick muscularis externa Much thicker compared to that in the small intestine - responsible for the powerful contractions that move fecal material through the colon Outer longitudinal layer of the muscularis externa in the large intestine is not continuous but instead forms three distinct bands called teniae coli Lecture 8: Histology of the gastrointestinal tract 20  LO: Liver and pancreas histology Liver histology – cell types Hepatocytes - primary cell type in the liver, making up about 80% of its cell population. Functions: Synthesis of Plasma Proteins: Hepatocytes are responsible for producing various plasma proteins, including albumin, clotting factors, and proteins involved in transport and immune responses. Lecture 8: Histology of the gastrointestinal tract 21  Bile Production: These cells synthesize bile, which is crucial for the digestion and absorption of fats. The bile is secreted into bile ducts and stored in the gallbladder. Storage of Metabolites: Hepatocytes store essential energy molecules such as lipids and glycogen. Metabolic Functions: Hepatocytes are involved in gluconeogenesis, the process of producing glucose from non- carbohydrate sources, particularly during fasting. Detoxification: One of the liver's most critical roles is detoxifying harmful substances, including drugs, alcohol, and metabolic waste products. Hepatocytes modify these substances to make them less toxic or easier to excrete. Kupffer cells - a type of macrophage that reside within the liver sinusoids, which are specialised capillaries Functions: Phagocytosis, immune response Endothelial Cells of the Sinusoids - these cells line the sinusoids, which are the capillary-like channels within the liver Functions: Fenestration: The endothelial cells are highly fenestrated, meaning they have large pores or openings. This allows for efficient exchange between the blood and the hepatocytes, facilitating the liver's functions in metabolism, detoxification, and nutrient storage Epithelial Cells of the Bile Ducts - cells form the lining of the bile ducts, which transport bile from the liver to the gallbladder and intestines Functions: Cuboidal or Columnar Shape: Unlike the squamous (flat) cells lining blood vessels, the epithelial cells of the bile ducts are typically cuboidal (cube-shaped) or columnar (taller than they are wide), reflecting their role in the active transport of bile. Lecture 8: Histology of the gastrointestinal tract 22  Liver organisation The liver receives venous blood AND arterial blood Venous blood: 70% of the blood supply comes from the portal vein. This blood is rich in nutrients absorbed from the intestines, making the liver the first stop for processing these nutrients. Arterial blood: 30% of the blood supply comes from the hepatic artery, providing oxygenated blood necessary for the metabolic activities of the liver cells (hepatocytes). Portal hepatis - a deep fissure or gateway on the underside (visceral surface) of the liver / hilum of the liver ⇒ the “gateway” where the portal vein, hepatic artery, bile duct enter or leave the liver Lecture 8: Histology of the gastrointestinal tract 23 Lecture 8: Histology of the gastrointestinal tract 24  Three vessels form a structure known as a portal triad. Portal vein: Carries nutrient-rich blood from the intestines. Hepatic artery: Supplies oxygenated blood to the liver. Bile duct: Transports bile produced by hepatocytes out of the liver. The liver is mostly filled (~80%) with cords of hepatocytes. These hepatocytes are arranged in a radiating pattern from a central vein, creating a lobular structure. Sinusoids are the spaces between the cords of hepatocytes. They are specialized capillaries that allow blood to flow between the hepatocytes, exposing them to nutrients and oxygen. The sinusoids are lined with a Lecture 8: Histology of the gastrointestinal tract 25  discontinuous simple squamous epithelium, making them highly permeable, which is crucial for the hepatocytes' role in processing blood. Liver histology - blood & bile flow in the liver: Blood Supply: The liver receives blood from two sources: Portal vein: Carries nutrient-rich but oxygen-poor blood from the intestines to the liver. Hepatic artery: Supplies oxygenated blood to the liver. Lecture 8: Histology of the gastrointestinal tract 26  These two types of blood mix in the liver's small blood vessels called sinusoids. The blood flows from the portal triad toward the central vein of each liver lobule. The liver cells (hepatocytes) are exposed to this blood as it flows through the sinusoids, allowing them to absorb nutrients and detoxify substances. Bile Production and Flow: Hepatocytes produce bile, a digestive fluid that helps break down fats. Bile flows in the opposite direction to blood, starting in tiny channels called bile canaliculi located between hepatocytes. These canaliculi empty into larger ducts that eventually lead to the bile ducts in the portal triad, which then transport bile out of the liver to the gallbladder and intestines. Space of Disse: There is a small space between the endothelial cells lining the sinusoids and the hepatocytes, called the Space of Disse (also known as the perisinusoidal space). This space allows the blood to easily exchange substances with hepatocytes, ensuring efficient detoxification and nutrient processing. Kupffer Cells: Kupffer cells are specialized macrophages (immune cells) that reside in the sinusoids. They play a critical role in filtering the blood by engulfing and breaking down old or damaged red blood cells and other debris. Lecture 8: Histology of the gastrointestinal tract 27  Structural/functional organisation of the liver The liver's structural and functional organisation can be understood in three different ways, each providing a unique perspective on how the liver operates. 1) Classic liver lobule Shape and Arrangement: The classic liver lobule is described as a hexagonal structure. At each corner of the hexagon, there is a portal triad. Components of Portal Triad: Each portal triad consists of a branch of the portal vein, hepatic artery, and bile duct. Blood Flow: Blood from the portal triads flows towards the central vein, which is located at the center of the lobule. This arrangement emphasizes the direction of blood flow from the periphery (portal triads) to the center (central vein). Lecture 8: Histology of the gastrointestinal tract 28  2) Portal lobule (triangular) Shape and Arrangement: The portal lobule is conceptualized as a triangular structure, with the portal triad at the center and central veins at the corners. Focus on Bile Production: This model focuses on the flow of bile. Bile is produced by hepatocytes and flows from the hepatocytes toward the central portal triad where the bile duct is located. Bile Flow: The bile flows in the opposite direction of blood, moving towards the bile duct in the portal triad at the center of the triangle. 3) Hepatic Acinus Shape and Arrangement: The hepatic acinus is a more functionally oriented model and is diamond-shaped. The central feature here is the portal tract, which is where blood flows through and connective tissue surrounds it. Zones of Hepatocyte Exposure: The acinus is divided into three zones: Zone 1: Closest to the portal tract, where hepatocytes have the highest exposure to oxygenated blood, nutrients, and potential toxins. Zone 2: Intermediate exposure. Zone 3: Farthest from the portal tract, with the least exposure as the blood has already passed through other hepatocytes. Lecture 8: Histology of the gastrointestinal tract 29  Gall bladder Function: Bile Collection and Concentration: The gallbladder's main role is to collect bile produced by the liver, concentrate it by absorbing water, and store it until it is needed for digestion. When required, the bile is released into the duodenum (the first part of the small intestine) to aid in the digestion of fats. Structure: Tissue Origins: The gallbladder is derived from the endoderm and mesoderm during embryonic development, similar to the rest of the gastrointestinal (GI) tract. Differences from the GI Tract: While it shares some structural similarities with the GI tract, the gallbladder is simpler in its organization. Notably: No Muscularis Mucosa or Submucosa: Unlike most of the GI tract, the gallbladder lacks these layers. Layers of the Gallbladder: Epithelium: The innermost layer is a simple columnar epithelium with microvilli on the surface, which increase the surface area for Lecture 8: Histology of the gastrointestinal tract 30  absorbing water to concentrate the bile. Lamina Propria: This layer of connective tissue lies just beneath the epithelium, providing structural support. Muscularis Externa: This outer layer consists of smooth muscle, which helps contract the gallbladder to release bile into the duodenum. Lecture 8: Histology of the gastrointestinal tract 31  Pancreas Structure & position: No Distinct Capsule: The pancreas doesn’t have a strong, defined outer layer (capsule). Instead, it is surrounded by a loose layer of connective tissue (adventitia). Retroperitoneal Position: The pancreas is located behind the peritoneum, which is the lining of the abdominal cavity. Most of the pancreas is "secondarily retroperitoneal”, the tail is intraperitoneal Two Main Components of the Pancreas: 1) Exocrine component - produces >1L of pancreatic juice daily Lecture 8: Histology of the gastrointestinal tract 32  Function: produces digestive enzymes, which help break down food in the small intestine. Structure: Acini: The exocrine part is made up of clusters of cells called acini (singular: acinus). These acini produce digestive enzymes that are stored in small granules within the cells called zymogen granules. Zymogen Granules: These granules contain inactive forms of digestive enzymes (zymogens), which are activated when they reach the small intestine. Duct System: The enzymes produced by the acini are collected by small ducts lined with low cuboidal epithelial cells. These small ducts join to form larger ducts, eventually leading to the main pancreatic duct, which empties the pancreatic juice into the duodenum (the first part of the small intestine). Lecture 8: Histology of the gastrointestinal tract 33  Histology for pancreatic acinar cell Lecture 8: Histology of the gastrointestinal tract 34  Basal Cytoplasm: This part of the cell contains the nucleus and rough endoplasmic reticulum (RER), which are involved in protein production. It stains purple due to its acidic nature. Apical Cytoplasm: This part contains the zymogen granules and stains pale pink because of the protein content. 2) Endocrine component - ~1-2% of the pancreas, consists of islands of Langerhans Function: endocrine part of the pancreas is much smaller and consists of clusters of cells called the islets of Langerhans, producing hormones like insulin (70%) and glucagon (20%) Structure: Islets of Langerhans: These are small groups of hormone- producing cells scattered throughout the pancreas. Although they make up only 1-2% of the pancreas, they are crucial for regulating blood sugar levels. Blood Supply: The islets are surrounded by many capillaries (tiny blood vessels), allowing the hormones they produce to Lecture 8: Histology of the gastrointestinal tract 35  enter the bloodstream quickly. Lecture 8: Histology of the gastrointestinal tract 36