The Gastro-intestinal System 1-3 PDF

**The Gastro-intestinal System 1-3** **Outline of Lectures** - The main functions of the GI or Digestive System - Organisation & functional anatomy of the gastro-intestinal (digestive) system - Digestive processes in the mouth & stomach - Digestive processes in the small intestine...

**The Gastro-intestinal System 1-3** **Outline of Lectures** - The main functions of the GI or Digestive System - Organisation & functional anatomy of the gastro-intestinal (digestive) system - Digestive processes in the mouth & stomach - Digestive processes in the small intestine - Digestive processes in the large intestine **Learning Outcomes** - Describe the basic anatomy & main functions of the gastro-intestinal (digestive) system - Explain the digestive processes that take place in the major parts of the digestive tract - Describe the neural & chemical control of the gastro-intestinal (digestive) system - Discuss the major sites of absorption in the gastro-intestinal (digestive) system **The Gastro-intestinal System (1)** **The GI System** - A group of organs that work together to breakdown ingested food into smaller, absorbable nutrient molecules that can then be absorbed into blood for distribution to all the cells in the body - Main functions - **Digests** or biochemically **breaks down** ingested food into small, simple nutrient molecules - **Absorbs** & **transfers** the nutrient molecules, electrolytes & water derived from the ingested food into systemic circulation - **Makes** the preformed organic nutrient molecules in ingested food available to body cells to be used as a. **Sources of fuel or energy** b. **Building blocks** - Performs 5 basic digestive processes - **Motility** - **Secretion** - **Digestion** - **Absorption** - **Storage & elimination of indigestible food** **Motility** - Muscular contractions that mix & move the contents of the digestive tract forward - Two types of digestive motility 1. Propulsive movements a. **Propel or push contents forward through the digestive tract** move the foods 2. Mixing movements a. **Mix food with digestive juices & promote digestion** b. **Facilitate absorption of digested food** **Secretion** plays central role in digestive process - Several digestive juices secreted in GI tract in response to specific neural or hormonal stimulation - Consist of water, electrolytes & specific organic constituents (enzymes, mucus, etc) - Include both exocrine & endocrine secretions distinguish differences between them! 1. Exocrine -- **secreted into the lumen of GI tract** outside of the body? a. **H2O, HCl, HCO3-, bile, lipase, pepsin, amylase, trypsin & histamine** 2. Endocrine -- **secreted into the blood stream** a. **Gastrin, secretin, CCK, VIP & somatostatin** **Digestion** - Biochemical breakdown of complex foodstuffs into smaller, absorbable units **(chemical digestion)** - Accomplished by **enzyme-mediated hydrolysis** - Complex foodstuffs & their absorbable units a. **Carbohydrates** (starch) **→** (disaccharides) **monosaccharides** b. **Proteins → amino acids** c. **Fats → glycerol & fatty acids** **Absorption** - Transfer of small digested units, along with water, vitamins & electrolytes, from the GI tract into blood or lymph - Occurs largely & most completely in the small intestine **Functional Anatomy of The Gastro-intestinal (Digestive) System**  A list of medical information Description automatically generated - **Gross Structure & Organisation** - Also called the **Gastro-intestinal (GI) tract** - Comprises 2 main components 1. The alimentary canal a. **Long, continuous hollow tube stretching from the mouth to the anus (\~30 feet long)** 2. Accessory organs & glands a. **Salivary glands** b. **Liver & Pancreas** **\ ** - **Alimentary canal** -- continuous from mouth to anus; consists of 1. 2. Mouth 3. Pharynx 4. Oesophagus 5. Stomach 6. Small intestine a. Duodenum b. Jejunum c. Ileum 7. Large intestine a. Caecum b. Appendix c. Colon d. Rectum 8. Anus - - **Accessory digestive organs** 1. Salivary glands 2. Exocrine pancreas 3. Biliary system a. Liver b. Gallbladder **The GI System --** **The Alimentary Canal** - Gross Functional Organisation - Divided into 3 main parts 1. Upper part a. **The mouth, oesophagus & stomach** **⇒ serves as food intake source & receptacle** **⇒ site of initial digestive processes** 2. Middle part a. **The small intestine -- duodenum, jejunum & ileum** **⇒ site of main digestive & absorptive processes** 3. Lower part a. **The large intestine -- caecum, colon & rectum** **⇒ serves as the storage channel for efficient elimination of waste** (form of faeces) **Wall Structure of Alimentary Canal** A diagram of the structure of the human body Description automatically generated **Wall Structure of Alimentary Canal -- Comprises 4 layers** - **Mucosa** 1st - Innermost, moist, folded -- increase the surface area available to maximize nutrient/water/electrolyte absorption lining of epithelial cells, connective tissue & smooth muscle cells - Lines the luminal surface of the digestive tract -- divided into **three** layers 1. **Mucous membrane** - An inner epithelial layer serves as a protective surface - Modified in particular areas for secretion & absorption - Contains ***a) exocrine gland cells*** for **secretion** of digestive juices/ ***b) endocrine gland cells*** for **secretion** of blood-borne GI hormones, and ***c) epithelial cells*** specialised for **absorbing** digested nutrients 2. **Lamina propria** - A thin middle layer of connective tissue on which the epithelium 상피(조직) rests - Houses the **gut-associated lymphoid tissue (GALT)** -- important in **defence** against disease -- causing intestinal bacteria 3. **Muscularis mucosa** - A sparse thinly dispersed **outermost** mucosal layer of smooth muscle - **Main functions (summary)** a. **Protective barrier against pathogens, etc** b. **Secretes mucus, digestive enzymes & hormones** c. **Absorbs digested nutrients into the blood** **⇒ undergoes rapid cell division & regeneration** as very acidic hostile environment - **Submucosa** 2nd - Dense connective tissue layer containing the larger blood and lymphatic vessels send branches inward to the mucosal layer/outward to surrounding thick muscle layer, lymphoid follicles & nerve fibres - Contains the ***submucosal nerve plexus*** network ***of Meissner*** GI own local nervous system -- **enteric nervous system (ENS)** - Main functions a. **Provides the digestive tract with distensibility and elasticity** b. **Glands secrete digestive enzymes** c. **Nerve plexus helps regulate gut motility** - **Muscularis externa** 3rd - Consists of **two** layers: 1. ***inner*** layer of **[circular]** smooth muscle contraction -- ↓ the diameter of lumen -- constricting the tube 2. ***outer*** layer of **[longitudinal]** smooth muscle contraction -- shorten the tube - ***Myenteric plexus of Auerbach*** lies in between myo; muscle, enteric; intestine - Main functions a. **Contractions facilitate mixing & movement of food contents (peristalsis & segmentation)** b. **Myenteric plexus (with submucosal) helps regulate gut motility** & local gut activity - **Serosa** 4th - Outer connective tissue & epithelial covering of the digestive tract - Continuous with the **mesentery** suspends the digestive organs from inner wall of the abdominal cavity ㄴprovides relative **fixation**(organs in proper position)/ allows **freedom** for mixing & propulsive movements - Main functions a. **Secretes a watery, slippery serous fluid** **⇒ lubrication and ↓ friction between digestive organs & surrounding viscera** 내장 **Complex Extrinsic & Intrinsic Regulation of Digestive Function** - Mediated *via* - **Interstitial cells of** **Cajal** (ICCs; pacemaker cells) located throughout the layers of the muscularis externa ⇒ **slow-wave potentials** (basic electrical rhythm **BER**) ⇒ spontaneous rhythmic electrical activity -- ileum contracts (observable) due to cajal - Intrinsic nerve plexuses (ENS) ⇒ GI muscle contraction or relaxation - Extrinsic nerves (from ANS) ⇒ increase or decrease GI contraction & secretion 위에 두개 GI unique mechanism! Intrinsic -- relaxation / Extrinsic -- promotion & activation - Gastro-intestinal hormones ⇒ increase or decrease GI contraction & secretion - Local sensory receptors -- **chemo**receptors, **mechano**receptors & **osmo**receptors  Diagram of a nervous system Description automatically generated **Functions of the Digestive System** +-----------------------------------+-----------------------------------+ | **Organ** | **Functions** | +===================================+===================================+ | Oral cavity | - **Ingestion**; Solid food and | | | fluids are taken into the | | | digestive tract through the | | | oral cavity. | | | | | | - **Taste**; Tastants dissolve | | | in saliva stimulate taste | | | buds in the tongue. | | | | | | - **Mastication**; Movement of | | | the mandible by the muscles | | | of mastication causes the | | | teeth to break food into | | | smaller pieces. The tongue | | | and cheeks help place the | | | food between the teeth. | | | | | | - **Digestion**; Amylase in | | | saliva begins carbohydrate | | | (starch) digestion. | | | | | | - **Swallowing**; The tongue | | | forms food into a bolus and | | | pushes the bolus into the | | | pharynx. | | | | | | - **Protection**; Mucin and | | | water in saliva provide | | | lubrication, and lysozyme (an | | | enzyme that lyses cells) | | | kills microorganisms. | | | Nonkeratinized stratified | | | squamous epithelium prevents | | | abrasion. | +-----------------------------------+-----------------------------------+ |.Pharynx | - **Swallowing**; The | | | involuntary phase of | | | swallowing moves the bolus | | | from the oral cavity to the | | | oesophagus. Materials are | | | prevented from entering the | | | nasal cavity by the soft | | | palate and kept out of the | | | lower respiratory tract by | | | the epiglottis and vestibular | | | folds. | | | | | | - **Breathing**; Air passes | | | from the nasal or oral cavity | | | through the pharynx to the | | | lower respiratory tract. | | | | | | - **Protection**; Mucus | | | provides lubrication. | | | Nonkeratinized stratified | | | squamous epithelium prevents | | | abrasion. | +-----------------------------------+-----------------------------------+ | Oesophagus | - **Propulsion**; Peristaltic | | | contractions move the bolus | | | from the pharynx to the | | | stomach. The lower | | | oesophageal sphincter limits | | | reflux of the stomach | | | contents into the oesophagus. | | | | | | - **Protection**; Glands | | | produce mucus, which provides | | | lubrication and protects the | | | inferior oesophagus from | | | stomach acid. | +-----------------------------------+-----------------------------------+ | Stomach | - **Storage**; Rugae allow the | | | stomach to expand and hold | | | food until it can be | | | digested. | | | | | | - **Digestion**; Protein | | | digestion begins as a result | | | of the actions of | | | hydrochloric acid and pepsin. | | | | | | - **Absorption**; Absorption of | | | a few substances (e.g. water, | | | alcohol, aspirin) takes place | | | in the stomach. | | | | | | - **Mixing and Propulsion**; | | | Mixing waves churn stir | | | ingested materials and | | | stomach secretions into | | | chyme. Peristaltic waves move | | | the chyme into the small | | | intestine. | | | | | | - **Protection**; Mucus | | | provides lubrication and | | | prevents digestion of the | | | stomach wall. Stomach acid | | | kills most microorganisms. | +-----------------------------------+-----------------------------------+ | Small intestine | - **Neutralization**; | | | Bicarbonate ions from the | | | pancreas and bile from the | | | liver neutralize stomach acid | | | to form a pH environment | | | suitable for pancreatic and | | | intestinal enzymes. | | | | | | - **Digestion**; Enzymes from | | | the pancreas and the lining | | | of the small intestine | | | complete the breakdown of | | | food molecules. Bile salts | | | from the liver emulsify | | | lipids. | | | | | | - **Absorption**; The circular | | | folds, villi, and microvilli | | | increase surface area. Most | | | nutrients are actively or | | | passively absorbed. Most of | | | the ingested water or the | | | water in digestive tract | | | secretions is absorbed. | | | | | | - **Mixing and Propulsion**; | | | Segmental contractions mix | | | the chyme, and peristaltic | | | contractions move the chyme | | | into the large intestine. | | | | | | - **Excretion**; Bile from the | | | liver contains bilirubin and | | | excess cholesterol. | | | | | | - **Protection**; Mucus | | | provides lubrication, | | | prevents digestion of the | | | intestinal wall, and protects | | | the small intestine from | | | stomach acid. Peyer patches | | | protect against | | | microorganisms. | +-----------------------------------+-----------------------------------+ | Large intestine | - **Absorption**; The proximal | | | half of the colon absorbs | | | salts (e.g. sodium chloride), | | | water, and vitamins (e.g. K) | | | produced by bacteria. | | | | | | - **Storage**; The distal half | | | of the colon holds faeces | | | until they are eliminated | | | | | | - **Mixing and Propulsion**; | | | Slight segmental mixing | | | occurs. Mass movements propel | | | faeces toward the anus, and | | | defecation eliminates the | | | faeces. | | | | | | - **Protection**; Mucus | | | provides lubrication; mucus | | | and bicarbonate ions protect | | | against acids produced by | | | bacteria. | +-----------------------------------+-----------------------------------+ **GLOSSARY** **Propulsion** -- the movement of food from one end of the digestive tract to the other. The total time it takes food to travel the length of the digestive tract is usually about 24-36 hours. Each segment of the digestive tract is specialised to assist in moving its contents from the oral end to the anal end: a. **Swallowing** b. **Peristalsis**; propel material through most of the digestive tract (peristaltic waves -- muscular contractions) c. **Mass movements** **Digestive Processes from Mouth to Stomach** - **Mastication** (chewing) - Aids in mechanical breakdown of larger food units - Mixes food with saliva which contains salivary amylase ⇒ partial digestion of starch - Saliva moistens ingested food, lubricates & exerts antibacterial effect 음식 안 들어가게 막아주는 천장 -- palate / Uvula -- gate - **Deglutition** (swallowing) - **Oropharyngeal stage** - **Oesophageal stage**  A diagram of the esophagus stage Description automatically generated **The Gastro-intestinal System (2)** **The Stomach** - J-shaped sac-like chamber lying between oesophagus and the small intestine - The most distensible 팽창가능한 part of GI tract no food -- volume ↓ up to 15ml/large meal -- volume ↑ - **Main functions** - Stores ingested food until emptied into the SI at a rate appropriate for optimal digestion/absorption - Secretes gastric juice (**hydrochloric acid (HCL), mucus & intrinsic factor, digestive enzymes -- pepsin** (salivary amylase)**, lipase)** begin the protein digestion - Mixes food with gastric juice movement of contraction → ingested food -- pulverised/mixed with gastric secretions → produce a thick liquid mixture known as **chyme** (duodenum넘어가기 전에 chyme으로 꼭 변환 필요) a. **Initiates digestion of proteins & fat** b. **Kills bacteria** acid in the stomach - Moves the partially digested food (**chyme**) at controlled & steady rate into the duodenum Divided into **three** sections: 1. **Fundus** - Lies above the oesophageal opening 2. **Body** - Middle or main part of the stomach 3. **Antrum** -- lower part - Has heavier musculature than F & B Difference in muscle thickness ⇒ plays an important role in **gastric motility** in these 2 regions **+** **Pyloric sphincter** 유문 괄약근; terminal portion of the stomach/acts as a barrier between the stomach and the upper part of the small intestine (duodenum) **Gastric Emptying and Mixing** as a result of antral peristaltic contractions A diagram of a gastric contraception Description automatically generated **Structure of Gastric Gland** A diagram of the stomach and gastric glands Description automatically generated **Three** types of gastric exocrine secretory cells: - **Mucous cells** - Line the gastric pits/entrance of the glands - Secrete a thin, watery ***mucus*** - **Chief cells** - Line the deeper parts of the gastric glands with parietal cells - Secrete the enzyme precursor ***pepsinogen*** - **Parietal (oxyntic) cells** - Secrete ***HCl*** and ***intrinsic factor*** **Gastric Secretory Products** **Product** **Source** **Functions** ------------------------------------- ---------------------- ----------------------------------- **Hydrochloric acid** Parietal cell Hydrolysis; sterilization of meal **Intrinsic factor** Parietal cell Vitamin B12 absorption **Pepsinogen** Chief cell Protein digestion **Mucus, bicarbonate** Surface mucous cells Gastroprotection **Trefoil factors** Surface mucous cells **Histamine** ECL cells Regulation of gastric secretion **Gastrin releasing peptide (GRP)** Nerves **Acetylcholine (ACh)** Nerves **Somatostatin** D cells **Mechanism of Gastric HCl Secretion**  1. The stomach's parietal cells actively secrete [*H*^+^]{.math.inline} and [Cl^−^]{.math.inline} by the actions of two separate pumps 2. [*H*^+^]{.math.inline} is secreted into the lumen by **a primary** [**H**^**+**^**−K**^**+**^ ]{.math.inline}**ATPase active-transport pump** (luminal membrane) / also pumps [*K*^+^]{.math.inline} into the cell from the lumen -- passively leaks back into the lumen through **luminal** [**K**^**+**^]{.math.inline} **channels** 3. [HCO~3~^−^]{.math.inline} *is formed within the parietal cell from* -- the [OH^−^]{.math.inline} (generated by the breakdown of [*H*~2~*O*]{.math.inline}*) combines with* [CO~2~]{.math.inline} (either has been produced within the cell by metabolic processes or has diffused in from the blood) in a reaction catalysed by **the enzyme carbonic anhydrase (ca)** 4. [Cl^−^]{.math.inline} is secreted by **secondary active transport** 5. The generated [HCO~3~^−^]{.math.inline} *is moved into the plasma by **a*** [Cl^**−**^**−**HCO~**3**~^**−**^]{.math.inline} ***antiporter** in the basolateral membrane of the cell* 6. Driven by the [HCO~3~^−^]{.math.inline} *conc. gradient, **a*** [Cl^**−**^**−**HCO~**3**~^**−**^]{.math.inline} ***antiporter** transports* [HCO~3~^−^]{.math.inline} *down its concentration gradient into the plasma/simultaneously transports* [Cl^−^]{.math.inline} from the plasma into the parietal cell against its conc. gradient 7. [Cl^−^]{.math.inline} secretion is completed as the [Cl^−^]{.math.inline} that entered from the plasma diffuses out of the cell down its electrochemical gra**dient through a luminal** [Cl^**−**^]{.math.inline} **channel** into the lumen **Pepsinogen Activation in the Stomach** A diagram of a structure Description automatically generated - **Pepsinogen** -- an inactive enzymatic molecule produced by the chief cells -- activated to the enzyme **pepsin** / begins protein digestion 1. **Pepsinogen** is stored in the chief cells' cytoplasm within secretory vesicles known as **zymogen** **granules** released by exocytosis on appropriate stimulation 2. When **pepsinogen** is secreted into the gastric lumen, HCl a) cleaves off a small fragment of the molecule, 2) converting it to the active form of **pepsin** 3. Once formed, **pepsin** acts on other **pepsinogen** molecules to produce more **pepsin** -- a mechanism called an **autocatalytic** self-activating **process** - **Pepsin** initiates **protein digestion** by splitting certain amino acid linkages in proteins to yield peptide fragments (small amino acid chains) - Works most effectively in the **acid environment** provided by HCl - Must be stored and secreted in an inactive form because pepsin can digest protein → it does not digest the proteins of the cells in which it is formed ⇒ **Pepsin** is maintained in the inactive form of **pepsinogen** until it reaches the gastric lumen where it is activated by HCl secreted into the lumen by a different cell type **Parietal Cell -- Receptor Activation of the Proton Pump** A diagram of a secretion Description automatically generated **RECEPTOR ACTIVATION OF PROTON PUMP**  **Regulatory factors** - **G cells** - Found in the gastric pits only in the PGA - Secrete the **hormone *gastrin*** into the blood - **Enterochromaffin-like (ECL) cells** - Dispersed among the parietal and chief cells in the gastric glands of the oxyntic mucosa - Secrete the **paracrine *histamine*** - **D cells** - Scattered in gastric glands near the pylorus, more in the duodenum - Secrete the **paracrine somatostatin** **Chemical messengers** - **ACh** - Neurotransmitter released from the intrinsic nerve plexuses - In response to both short local reflexes and vagal stimulation - Stimulates the parietal and chief cells, G cells and ECL cells 그냥 다 자극하세요. - **Hormone Gastrin** - Secreted by the G cells into the blood - In response to ACh - Directly stimulates the parietal and chief cells, promoting secretion of a highly acidic gastric juice - Indirectly promotes HCl secretion by stimulating the ECL cells to release histamine -- which also stimulates the parietal cells - Main factor that brings about increased HCl secretion during meal digestion - Trophic (growth promoting) to the mucosa of the stomach and small intestine, thereby maintaining their secretory capabilities - **Histamine (paracrine)** - Released from the ECL cells - In response to ACh and gastrin - Acts locally on nearby parietal cells to **1) speed up** HCl secretion and **2) potentiates** (makes stronger) the actions of ACh and gastrin - **Histamine** - Released from the D cells - In response to acid - Acts locally as a paracrine in negative-feedback fashion to **inhibit secretion** by the parietal cells, G cells, and ECL cells ⇒ turning off the HCl-secreting cells and their most potent stimulatory pathway **\ ** **Control of Gastric Secretion** - The **3** phases of Gastric Secretion 1. 2. **Cephalic ("head") phase** increased secretion of HCl and pepsinogen - **Triggered by factors arising *[before]* food enters the stomach** -- thought, smell, sight or taste of food controlled by the factors in head (neurological signals) increases gastric secretion via vagal stimulation in **two** ways a. Vagal stimulation of the intrinsic plexuses promotes **increased secretion of ACh**, which leads to **increased secretion of HCl and pepsinogen** by the secretory cells b. Direct vagal stimulation of **the G cells causes gastrin release**, which in turn further **enhances secretion of HCl and pepsinogen**, with the effect on HCl being potentiated by gastrin promoting the release of histamine 3. **Gastric phase** most of gastric juice secretion happens/proteins/food also contributes - **Triggered by factors resulting from the presence of food in the stomach** - Stimuli acting on the stomach -- namely protein, distension, caffeine, and alcohol -- increase gastric secretion by overlapping efferent outwards pathways - Protein most potent stimulus a. Stimulates **chemoreceptors** -- activate intrinsic-plexus pathways that induce gastric secretion b. Brings about **activation of the extrinsic vagal fibres** to the stomach -- vagal activity further enhances intrinsic nerve stimulation of the secretory cells and triggers the release of gastrin c. Directly stimulates the release of **gastrin** a powerful stimulus for further HCl and pepsinogen secretion ⇒ Through these synergistic and overlapping pathways, protein **induces secretion of a highly acidic, pepsin-rich gastric juice**, which continues digestion of the protein 4. **Intestinal phase** helping shut off the flow of gastric juices as chyme begins to be emptied into the SI - **Triggered by factors resulting from movement of food from stomach into duodenum** **Control of Gastric Secretion -- Excitatory Cephalic & Gastric Phases** A diagram of excitatory mechanism for enhancing gastrointestinal tract Description automatically generated **Control of Gastric Secretion -- Inhibitory Duodenal Mechanisms**  **Control of Gastric Secretion**  **Digestion & Absorption in the Stomach** very little digestion occurs - Carbohydrate digestion by salivary **amylase** continues - **Partial inhibition of amylase by acidity** strongly acidic environment - Proteins are partially digested by pepsin in the antrum - Only ethyl alcohol lipid soluble -- diffuse through the lipid memb./enter BS through submucosal capillaries & aspirin weak acid are absorbed **The Gastric Mucosal Barrier**  - **Protects Stomach from Damage** - Cell membranes of gastric mucosal cells are impermeable to HCl / H+ on the luminal side - Lateral edges of these cells are joined near their luminal borders by tight junctions -- Tight junctions between adjacent gastric mucosal (epithelial) cells are impermeable to HCl acid cannot diffuse between the cells from the lumen into the submucosa - The HCO3- rich mucus serves both as protective physical barrier & as chemical barrier that neutralizes acid close to gastric mucosa - Rapid rate of cell division cells are usually replaced before they are exposed -- entire stomach lining replaced in 3 days so that the protective mechanisms are further enhanced by this replacement - Prostaglandins inhibit acid secretion & promote alkaline mucus secretion **Digestive Processes from Small Intestine to Large Intestine** **The Small Intestine** - **Digestive & Absorptive Functions** - Main site for digestion & absorption of ingested food - Secretes aqueous salt & mucus solution for lubrication & protection - Utilizes segmentation & peristaltic contractions to mix & propel chyme, and facilitate absorption - Digestion occurs *via* action of bile, pancreatic enzymes & intestinal (brush-border) enzymes - Absorption occurs along the entire length -- but largely in the duodenum & jejunum - **Structure-function Relationships** - Mucosal surface thrown into permanent circular folds ⇒ 3-fold ↑ in surface area - Microscopic finger-like projections **(villi)** project from circular folds ⇒ 10-fold ↑ in surface area - Villi are covered by epithelial cells - Epithelial cells have numerous smaller, hair-like projections, called **microvilli** or **brush border** ⇒ 20-fold ↑ in surface area - 3 types of digestive enzymes are expressed on the membranes of microvilli or brush border -- **enteropeptidase** activates the pancreatic proteolytic enzyme trypsinogen**, disaccharidases** (maltase, sucrase-isomaltase, lactase) **& aminopeptidases** hydrolyse most of the peptide → amino acid/complete the protein digestion **Intestinal Circular Folds, Villi & Microvilli** A diagram of a human body Description automatically generated **The Structure of Intestinal Villi** A close-up of a text Description automatically generated **The Gastro-intestinal System (3)** **The Small Intestine** - **Three Main Subdivisions** 1. Duodenum first part of the SI & Hepatopancreatic organs 2. Jejunum 3. Ileum terminal part connected with colon **The Duodenum & Hepatopancreatic Region**  **The Duodenum** - **The first 10 inches of small intestine** - First site of intensive digestion & absorption - Receives bile & pancreatic juice *via* the common bile duct & main pancreatic duct - Arrival of chyme stimulates release of hepatic & pancreatic secretions **→ fatty chyme in the duodenum ⇒ release of CCK ⇒ release of bile & pancreatic enzymes** **→ acid in chyme ⇒ release of secretin ⇒ release of pancreatic bicarbonate ⇒ neutralizes the acidity** - - **Structure of the Pancreas** A diagram of a pancreas Description automatically generated - **Functional Anatomy of Pancreas** - Exocrine a. Duct cells - **Secrete aqueous bicarbonate solution** release under the control b. Acinar cells - **Secrete pancreatic juice** -- proteases, amylase, lipase breakdown fats - Endocrine a. **β-cells -- secrete insulin** b. **α-cells -- secrete glucagon** - - **Secretions of the Pancreas**  - **Activation of Pancreatic Enzymes** A diagram of a human stomach Description automatically generated - - The ***pancreas*** -- elongated gland that lies behind and below the stomach, above the first loop of the duodenum / contains both exocrine and endocrine tissue (Table below) +-----------------------------------+-----------------------------------+ | **EXOCRINE** | **ENDOCRINE** | +===================================+===================================+ | - Predominant | - Smaller | | | | | - consists of grape-like | - Consists of isolated | | clusters of secretory cells | endocrine tissue -- ***islets | | that form sacs known as | of Langerhans*** which are | | ***acini*** -- connect to | dispersed throughout the | | ducts that eventually empty | pancreas | | into the duodenum | | | | - Secretes insulin + glucagon | +-----------------------------------+-----------------------------------+ ㄴ derived from different tissues during embryonic development & share only their location in common - The **exocrine pancreas** secretes a pancreatic juice consisting of **two** components: 1. **Pancreatic enzymes** actively secreted by acinar cells / like pepsinogen a. Proteolytic enzymes - protein digestion i. Trypsinogen ⇒ Trypsin active form (a) ㄴtrypsinogen remain inactive -- prevent digesting protein of the cells ii. Chymotrypsinogen ⇒ Chymotrypsin (a) iii. Procarboxypeptidase ⇒ Carboxypeptidase (a) / ii랑 iii 얘네는 trypsin에 의해서 activate됨! **Mucus** -- secreted by the intestinal cells to **protect** against digestion of **the SI wall** by (a) enzymes b. Pancreatic amylase - carbohydrate digestion / like salivary amylase - Carbohydrate digestion by converting dietary starches (amylose/amylopectin) -- disaccharide maltose/branched polysaccharide α-limit dextrins - Amylase -- secreted in an active form since it does not endanger the secretory cells = 얘네 do not contain any polysaccharide c. Pancreatic lipase -- only enzyme secreted to digest fat throughout the entire digestive system - Lipase is secreted in the saliva lingual lipase and gastric juice gastric lipase - Hydrolyses dietary triglycerides into monoglycerides and free fatty acids absorbable - Secreted in its active form (no risk of pancreatic self-digestion) = triglycerides are not a structural component of pancreatic cells 2. **Aqueous alkaline solution** actively secreted by duct cells / rich in sodium bicarbonate (NaHCO3) a. Pancreatic enzymes work optimally in a **neutral** or **slightly alkaline** environment, yet the highly acidic gastric contents acidic chyme empty into the duodenum ㄴmust be neutralised to **1) allow** optimal functioning of the pancreatic enzymes & **2) prevent** acid damage to the duodenal mucosa b. The alkaline NaHCO3 rich fluid secreted by the pancreatic duct cells into the duodenum to neutralise the acidic chyme empties into the duodenum from the stomach c. **Mechanism of NaHCO3 secretion** i. Most of the to-be-secreted HCO3- enters the pancreatic duct cell by means of a Na+-HCO3- symporter in the basolateral membrane active step in NaHCO3 secretion ii. HCO3- is secreted from the pancreatic duct cell into the pancreatic duct lumen by **two** means: via (1) Cl- -- HCO3- antiporter and (2) a CFTR cystic fibrosis transmembrane conductance regulator channel both in the luminal membrane iii. Na+ diffuses down its electrochemical gradient via paracellular transport through "leaky" tight junctions between the pancreatic duct cells to complete NaHCO3 secretion - **Hormonal Control of Pancreatic Exocrine Secretion** A diagram of a diagram Description automatically generated - **NaHCO₃ Secretion**: - Acid in the duodenum triggers **secretin** release from duodenal mucosa - Secretin is carried by the blood to pancreatic duct cells - Duct cells secrete a NaHCO₃-rich aqueous solution into the duodenum to neutralize acid - **Pancreatic Digestive Enzyme Secretion**: - Fat and protein products in the duodenum stimulate **CCK** release from duodenal mucosa. - CCK is carried by the blood to pancreatic acinar cells - Acinar cells secrete digestive enzymes (e.g., lipase, proteolytic enzymes) into the duodenum to digest fats and proteins **The Liver & Hepatic Portal Circulation** **The Liver** - The largest gland in the body - Composed of 'plates' of liver cells (hepatocytes) - Main digestive function is the production of bile - Synthesis of bile produce bile -- key role ! - A fat emulsifier - A yellow-green, alkaline solution - Contains bile salts, bile pigments, cholesterol, neutral fats, phospholipids & electrolytes - Stored & released from gallbladder A diagram of the internal organs Description automatically generated - **Blood Sources to the Liver**: a. **Hepatic Artery**: Delivers oxygenated arterial blood with blood-borne metabolites for hepatic processing b. **Hepatic Portal Vein**: Brings venous blood rich in absorbed nutrients from the digestive tract - **Blood Flow Through the Liver**: - Blood enters liver sinusoids, allowing exchange with hepatocytes - Blood exits the liver through the hepatic vein into the inferior vena cava **Enterohepatic Circulation of Bile Salts** - **Bile Salt Recycling**: - Bile salts secreted into the duodenum consist of 95% recycled and 5% newly synthesized bile salts - After aiding in fat digestion and absorption, 95% of bile salts are reabsorbed by active transport in the terminal ileum - Reabsorbed bile salts are returned to the liver via the hepatic portal vein and re-secreted into bile - **Bile Secretion Regulation**: - Recycled bile salts stimulate further bile secretion during meals - Only 5% of bile salts are lost in faeces and replaced by new synthesis **\ ** **Fat Emulsification by Bile Salts** - **Structure of Bile Salts**: - Bile salts have a lipid-soluble part derived from cholesterol and a negatively charged, water-soluble part - **Emulsification Process**: - Large fat globules are broken into smaller droplets by intestinal mixing - Bile salts adsorb on the droplet surface, forming a negatively charged shell that prevents recoalescence - Emulsification increases the surface area available for pancreatic lipase activity - **Role of Colipase**: - Pancreatic colipase displaces some bile salts, anchoring lipase to fat droplets for efficient digestion - **Micelle Structure**: - Core: Hydrophobic (lipid-soluble) substances like cholesterol, bile salts, lecithin, and fat digestion products - Shell: Hydrophilic (water-soluble) portions of bile salts and lecithin - **Role in Fat Absorption**: - Micelles transport lipid-soluble substances through watery intestinal contents to absorptive surfaces - Without micelles, lipid-soluble nutrients would float on chyme and fail to reach the absorptive surface **Control of Bile Release** A diagram of the human body Description automatically generated **Digestion & Absorption in the Small Intestine** **Absorption in Small Intestine** - **Duodenum and jejunum** - Main site of absorption - *Freely* absorb all products of carbohydrate, protein & fat digestion - *Freely* absorb most ingested electrolytes, vitamins & water - Absorption of calcium & iron is adjusted to the body's needs - **Ileum** - Absorbs bile salts vitamin B12, electrolytes & water **Carbohydrate, Protein & Fat Digestion**  **Carbohydrate Digestion** - - **Polysaccharide Digestion** - Starch and glycogen are broken down by **salivary** **amylase** and **pancreatic** **amylase** into maltose. - **Disaccharide** **Digestion** - Maltose, sucrose, and lactose are converted to monosaccharides (glucose, galactose, and fructose) by the brush-border enzymes: a. **Maltase** → Glucose b. **Sucrase** → Glucose and fructose c. **Lactase** → Glucose and galactose - **Absorption Mechanisms** - **Glucose** and **Galactose**: Absorbed by Na+-dependent secondary active transport using the **SGLT symporter** at the luminal membrane - Fructose: Absorbed by facilitated diffusion via **GLUT-5** - **Monosaccharide** **Exit** - All monosaccharides exit the cell at the basal membrane by facilitated diffusion via **GLUT-2** and enter the blood **Carbohydrate Absorption**  **Protein Digestion** 1. **Protein** **Digestion** - Dietary and endogenous proteins are hydrolysed into amino acids and small peptides by: a. **Pepsin** in the stomach b. **Pancreatic** **proteolytic** **enzymes** in the small intestine 2. **Brush Border Processing** - Small peptides are broken into amino acids by **aminopeptidases** located in the brush border 3. **Absorption Mechanisms** - **Amino** **acids**: Absorbed by Na+- and energy-dependent secondary active transport using specific symporters - **Small** **peptides**: Absorbed via H+-driven tertiary active transport 4. **Intracellular Peptide Processing** - Most absorbed small peptides are broken down into amino acids by **intracellular** **peptidases** 5. **Amino Acid Exit** - Amino acids exit the epithelial cells through facilitated diffusion and enter the blood **Protein Absorption**  **\ ** **Fat Digestion and Absorption** **Iron Absorption**  **\ ** **The Large Intestine** - Consists of the colon, caecum, appendix & rectum - Primarily a drying & storage organ - Minor absorptive function - **Absorbs water, electrolytes, several vitamin B complexes. Vitamin K & folic acid** - Contains many beneficial bacteria (\~ 500-1000 *sp*) - **Produce vitamin K & folic acid** - **Ferment indigestible molecules to produce short-chain fatty acids** - **Major Sections** - **Cecum**: A pouch below the junction of the small and large intestines; contains the **appendix**, a lymphoid structure - **Colon**: Divided into **four** parts: a. **Ascending colon** b. **Transverse colon** c. **Descending colon** d. **Sigmoid colon**: S-shaped section leading to the rectum - **Rectum**: Straight portion leading to the anal canal - **Sphincters** - **Internal anal sphincter**: Smooth muscle; involuntary control - **External anal sphincter**: Skeletal muscle; voluntary control - **Functions of the Large Intestine** - Receives **500 mL of chyme** daily - Extracts water and salts, forming solid faeces for storage and elimination - Stores faeces until defecation - **Special Features** - **Haustra**: Small pouches giving the colon a segmented appearance - **Taeniae coli**: Longitudinal muscle bands aiding in motility