Monday 24 December 2012

Digestive System

An Overview

Why do we eat?
Consider for a moment a Big Mac. The purpose in your eating a Big Mac, other than simple hedonism, is to assimilate the nutrients it represents and make them available to build, repair and maintain your own tissues, as well as provide energy for studying and occasional other pursuits.
You may have asked yourself - "Exactly what nutrients are present in a Big Mac that I can assimilate?" MacDonald's comes close to full disclosure in this regard, but what they don't tell you is that in order to take advantage of these nutrients, you have to provide the means to carefully break them down into much smaller molecules that can be imported into blood. Luckily, your digestive system takes care of this very complex process so efficiently that most of the time you don't even need to think about it.
At its simplest, the digestive system it is a tube running from mouth to anus. This tube is like an assembly line, or more properly, a disassembly line. Its chief goal is to break down huge macromolecules (proteins, fats and starch), which cannot be absorbed intact, into smaller molecules (amino acids, fatty acids and glucose) that can be absorbed across the wall of the tube, and into the circulatory system for dissemination around your body.
The breakdown of foodstuffs like a Big Mac is accomplished through a combination of mechanical and enzymatic processes. To accomplish this breakdown, the digestive tube requires considerable assistance from accessory digestive organs such as the salivary glands, liver and pancreas, which dump their secretions into the tube. The name "accessory" should not be taken to mean dispensable; indeed, without pancreatic enzymes you would starve to death in short order.
In many ways, the digestive system can be thought of as a well-run factory in which a large number of complex tasks are performed. The three fundamental processes that take place are:
Secretion: Delivery of enzymes, mucus, ions and the like into the lumen, and hormones into blood.
Absorption: Transport of water, ions and nutrients from the lumen, across the epithelium and into blood.
Motility: Contractions of smooth muscle in the wall of the tube that crush, mix and propel its contents.
Each part of the digestive tube performs at least some of these tasks, and different regions of the tube have unique and important specializations.
Like any well-run factory, proper function of the digestive system requires robust control systems. Control systems must facilitate communication among different sections of the digestive tract (i.e. control on the factory floor), and between the digestive tract and the brain (i.e. between workers and management). Control of digestive function is achieved through a combination of electrical and hormonal messages which originate either within the digestive system's own nervous and endocrine systems, as well as from the central nervous system and from endocrine organs such as the adrenal gland. Different parts of these systems are constantly talking to one another. The basic messages are along the lines of "I just received an extraordinary load of food, so I suggest you get prepared" (stomach to large intestine) or "For goodness sake, please slow down until I can catch up with what you've already given me" (small intestine to stomach).
Finally, a note about differences in digestive anatomy and physiology among animals. The digestive systems of humans, dogs, mice, horses, kangaroos and great white sharks are, to a first approximation, virtually identical. If you look more carefully however, it becomes apparent that each of these species has evolved certain digestive specializations that have allowed it to adapt to a particular diet.
These differences become particularly apparent when you compare a carnivore like a dog with a herbivore like a goat or a horse. Goats and horses evolved from ancestors that subsisted on plants and adapted parts of their digestive tracts into massive fermentation vats which enabled them efficiently utilize cellulose, the major carbohydrate of plants.
In contrast, dogs evolved from animals that lived on the carcasses of other animals, and have digestive systems that reflect this history - extremely small fermentation vats and essentially no ability to utilize cellulose. Bridging the gap between carnivores and herbivores are omnivores like humans and pigs, whose digestive tracts attest to a historical diet that included both plants and animals. 


Digestive Tube Anatomy
Remarkably diverse and specialized processes take place in different sections of the digestive tract, but there is a fundamental consistency in the architecture of the tubular digestive tract. From the mouth to the anus, the wall of the digestive tube is composed of four basic layers or tunics.

 

Tunica serosa is the outermost covering of the digestive tube. In most of the digestive tract (stomach and intestines) it consists of a thin layer of loose connective tissue covered by mesothelium (a type of squamous epithelium that lines body cavities); within the peritoneal cavity, this structure is also referred to as visceral peritoneum.

In the abdominal cavity, the serosa on each side of the tube fuses together to form a suspensory structure called mesentery, which houses vascular and nervous supplies to the digestive tract and is continuous with the lining of the cavity. In regions outside of the abdominal cavity where the digestive tube is essentially affixed to adjacent structures via its outer layer of connective tissue (esophagus and rectum), this tunic is referred to as tunica adventitia instead of tunica serosa.

Tunica muscularis endows the digestive tube with an ability to be motile. In most of the digestive tube, this tunic consists of two thick layers of smooth muscle. Muscle fibers in the inner layer are aligned circularly, whereas those in the outer layer have a longitudinal orientation.

This combination of circular and longitudinal smooth muscle gives the tube an ability to perform complex movements that squeeze and propel ingesta in the lumen. Between the inner circular and outer longitudinal layers of smooth muscle is another critical component of the digestive tract's nervous system - the myenteric plexus.

Tunica submucosa, immediately beneath the mucosa, is a layer of loose to dense connective tissue containing blood and lymphatic vessels. The submucosa also contains the submucous plexus, a critical component of the digestive tract's nervous system which provides nervous control to the mucosa.

Tunica mucosa is the innermost layer of the digestive tube and lines the lumen. Among the four tunics, the mucosa is most variable in structure and function, endowing the tube with an ability to perform diverse and specialized digestive tasks along its length. Of critical importance in this regard are the epithelial cells that cover the mucosa and are thus in direct contact with the lumen.

This epithelial cell sheet (lamina epithelialis) is distinctly different in different regions of the tract. Indeed, in most of the tract, several different cell types contribute to the epithelium, including cells dedicated to secretion, absorption or production of hormones.

These distinctive differences in architecture of the epithelium can be seen below in the micrographs of mouse digestive tube. The magnification of all four images is identical and the epithelial layer is oriented toward the top.

Beneath the epithelium, but still within the tunica mucosa is a layer - the lamina propria - of loose connective tissue through which course blood vessels and lymphatics that supply the epithelium. This layer also contains lymphatic nodules important to immune functions of the digestive tract. Finally, beneath the lamina propropria is a thin layer of smooth muscle ( lamina muscularis mucosae) which permits the mucosa to dynamically move and fold.

The Digestive System (notes)



Organs of digestion

          Gastrointestinal tract (alimentary canal)
        mouth
        pharynx
        esophagus
        stomach
        small intestine
        large intestine
          Accessory structures of digestive system
        teeth
        tongue
        salivary glands
        liver
        gallbladder
        pancreas



Digestive processes
          Ingestion
        Taking of food and liquid into the mouth (eating)
          Secretion
        Cells secrete ~7 litres of fluids per day
          Mixing and Propulsion
        Mixing and movement of material along GI tract is termed motility
          Digestion
        Mechanical
        Chemical
          Absorption
          Defecation
        Indigestible material eliminated as feces during defacation


Layers of GI tract
          Mucosa
        Epithelium
          cells firmly sealed by tight junctions
          secretes mucus, digestive enzymes and hormones
          Absorption
        Lamina propria
          Contains mucosa-associated lymphatic tissue
        Muscularis mucosae
          causes folds which increase surface area
          Submucosa
        Blood and lymphatic vessels
        Glands
        Submucosal plexus
          Regulates movement of mucosa and vasoconstriction of blood vessels
          Muscularis
        Mouth, pharynx, upper esophagus  and external anal sphincter contain skeletal muscle
        Rest of GI tract contains smooth muscle
          inner circular and outer longitudinal layers
          Myenteric plexus between layers
          Controls motility
          serosa (visceral peritoneum)
        Forms portion of peritoneum


          Peritoneum
          Largest serous membrane in body
        Parietal layer
»        Lines wall of abdomino-pelvic cavity
        Visceral layer
»        Covers some organs in cavity
        Peritoneal cavity
»        Contains serous fluid
          Folds bind organs to each other and to walls of abdominal cavity

Mouth - Salivary glands
          Mucous membranes of mouth and tongue secrete small amount of saliva
          Most saliva secreted by major salivary glands which lie outside the mouth
        Parotid
        Submandibular
        Sublingual


Mouth - composition and functions of saliva
          Saliva is ~99.5% water
        contains:
          IgA
          Lysozyme
          Salivary amylase
          Various solutes, organic substances, etc
          Saliva functions to:
        keep mucous membranes of mouth and pharynx moist
        cleanse mouth and teeth
        dissolve food
        begin chemical digestion of carbohydrates (salivary amylase)
Mouth - control of salivation
          Salivation under nervous control
        salivary nuclei in brain stem
          Receive input from cortex, taste buds, olfactory apparatus
        Parasympathetic output increases salivation
        Sympathetic output reduces salivation (dry mouth when stressed)



Mouth – digestion
          Mechanical and chemical digestion occur in the mouth
        Mechanical digestion results from mastication
        Chemical digestion begins
          Salivary amylase
        Initiates breakdown of starch
          Lingual lipase
        Hydrolyses triglycerides into fatty acids and glycerol
        Secreted in inactive form by glands in tongue
        Becomes activated in acid environment of stomach


Pharynx – deglutition
          Swallowing occurs in 3 stages:
        Voluntary stage
          Bolus passed into oropharynx by tongue
        Pharyngeal stage
          Bolus stimulates stretch receptors in oropharynx
        Send impulses to deglutition centre in brain stem
          Involuntary passage of bolus into esophagus
        Esophageal stage
          Involuntary passage of bolus through esophagus into stomach



Esophagus
          Collapsible muscular tube behind trachea
        Secretes mucus and transports food into stomach
          Passes through mediastinum
          Pierces diaphragm through esophageal hiatus
          Upper and lower sphincters
        lower sphincter is physiological sphincter
        Diaphragm helps keep lower sphincter closed when not swallowing
          Food moves via peristalsis
        Controlled by neurons in medulla oblongata


Stomach
        acts as a mixing chamber and holding reservoir
        Starch digestion continues
        protein and triglyceride digestion begins
          Muscularis has 3 layers
        Additional oblique layer

          Columns of secretory cells form gastric glands which line gastric pits
        Mucous cells
          Secrete mucus
        Parietal cells secrete:
          hydrochloric acid
          Intrinsic factor
          Required for absorption of vitamin B12
        Chief cells secrete:
          Pepsinogen
          Gastric lipase
        G cells
          Secrete gastrin

          Mechanical digestion
        After food enters stomach mixing waves occur every 15-25 sec
          Aid in mechanical digestion to form chyme
          Forces chyme into duodenum (start of small intestine)
          Chemical digestion
        HCL
           denatures proteins
        Pepsinogen converted to pepsin in presence of HCL and other pepsin molecules
          Hydrolyses peptide bonds
        Gastric lipase hydrolyses triglycerides


Regulation of gastric secretion and motility
          Cephalic phase
        Sight, smell, taste or thought of food  recognised by cerebral cortex or feeding centre in hypothalamus
          Nerve impulses sent to medulla oblongata
        Sends impulses to submucosal plexus (in submucosa)
»         Increases secretion from gastric glands and stomach motility (via gastrin secretion)
          Gastric phase
        when food reaches stomach stimulates
          Stretch receptors
          Chemoreceptors (monitor pH)
        Stimulate secretion of Gastrin (by G cells)
»        Maintains gastric secretion and motility
          Intestinal phase
        Stimulation of intestinal receptors as food enters small intestine stimulates secretion of
          Secretin – reduces gastric secretion
          CCK-inhibits gastric emptying
         Slows exit of chyme from stomach into duodenum



Pancreas
          Pancreas connected to duodenum
        Secretes pancreatic juice into duodenum
          99% of cells arranged in clusters called acini
        Exocrine portion of gland
          Secrete pancreatic juice



Pancreas – pancreatic juice
          Pancreatic juice contains:
        Water
        Salts
        Sodium bicarbonate
        Several enzymes which digest:
          carbohydrates
        Pancreatic amylase
          Proteins
        Trypsin - secreted in inactive form and activated by brush-border enzyme called enterokinase
        Chymotrypsin – secreted in inactive form and activated by trypsin
        Cartboxypeptidase – secreted in inactive form and activated by trypsin
        Elastase – secreted in inactive form and activated by trypsin
          Triglycerides
        Pancreatic lipase
          Nucleic acids
        Ribonuclease
        Deoxyribonuclease
Liver
          Heaviest gland in body
          Two lobes
        Large right lobe
        Smaller left lobe
          Lobes made up of functional units called lobules
        Six-sided structure with hepatocytes arranged around central vein
        Blood from hepatic artery and hepatic portal circulation passes through sinusoids and drains into central veins
        Bile enters bile canaliculi and moves to gallbladder





    Blood supply
          Hepatic artery
        delivers oxygenated blood
          Hepatic portal circulation
        delivers nutrient rich blood from intestines





          Functions of liver:
        CHO metabolism
          glycogenolysis
          gluconeogenesis
          glycogenesis
        Lipid metabolism
          Synthesise lipoproteins and cholesterol
          Store triglycerides
          b-oxidation
        Protein metabolism
          Deaminate amino acids
          Synthesise plasma proteins
        Bile production
          Detergent-like acidic buffer
        Emulsifies lipids
        Process drugs and hormones
        Excrete bilirubin
          Derived from heme of worn out RBC (secreted into bile)
        Store vitamins and minerals
        Phagocytosis of RBC, WBC and bacteria (Kupffer’s cells)
        Activation of vitamin D



Gall bladder
          Bile production signalled by
          parasympathetic activity
          secretin - released when acidity in duodenum (secretin also inhibits gastric secretion)
          Bile stored and concentrated in gallbladder
        released when fatty acids and amino acids enter duodenum
          signalled by CCK (also inhibits gastric emptying)





Small intestine
          Extends from pyloric sphincter to ileocecal valve
          3 parts:
        duodenum
        jejunum
        ileum

          Most digestion and absorption of nutrients occurs in SI
          Length gives large surface area (3m in living person)
        Surface area increased by:
          circular folds (plicae circulares) - mix chyme
          villi - capillaries and lacteals
          microvilli

          Mechanical digestion
        Segmentation mixes chyme
        Peristalsis (migrating motility complex) occurs once absorption complete
          Slowly migrates along SI over 90-120 min period
        Chyme remains in SI for 3-5 hours
          Chemical digestion
        CHO
          Pancreatic amylase splits starch into smaller fragments
          Brush border enzyme (a -dextrinase) then breaks down to glucose
          Disaccharides (sucrose, lactose and maltose) broken down by brush border enzymes
        Proteins
          Trypsin, chymotrypsin, carboxypeptidase and elastase break protein down into peptides
          Each breaks different peptide bonds
          Brush border enzymes aminopeptidase and dipeptidase break peptides into amino acids
        Lipids
          Bile salts emulsify triglycerides into small droplets
          Pancreatic lipase hydrolyses triglycerides
        Nucleic acids
          Ribonuclease and deoxyribonuclease break nucleic acids into nucleotides
          Brush border enzymes (nucleosidases and phosphatases) break nucleotides into pentoses, phosphates and nitrogenous bases


Absorption
Absorption
          Monosaccharides
        Secondary active transport with sodium
         facilitated diffusion (fructose)
          Amino acids, dipeptides, tripeptides
        amino acids primary or secondary active transport
        di- and tripeptides secondary active transport
          All move into capillaries in villus
          Lipids
        Absorbed via simple diffusion
          Short-chain fatty acids move into capillaries in villus
          Others move into lacteals
        bile combines with long-chain fatty acids and monoglycerides to form micelles
          micelles contact epithelial cell membrane
          lipids diffuse through membrane
          resynthesised to triglycerides inside epithelial cells
          coated with proteins to form chylomicrons
          chylomicrons too large to move into capillaries and move into lacteals

          Large molecules (eg complete proteins) not absorbed
        How then can foods containing functional proteins exert their effects?
          eg bovine colostrum


Large intestine
          Approx 1.5 m long
          Extends from ileocecal sphincter to anus
          Tonic contraction of three longitudinal muscles (teniae coli) form pouches (haustra 
          4 divisions:
        cecum
        colon
        rectum
        anal canal
          internal sphincter - smooth muscle
          external sphincter - skeletal muscle
          No villi or circular folds in mucosa
          Epithelium contains mostly absorptive cells (water absorption) and goblet cells (secrete mucus)
        Located mostly in intestinal glands

 
          Mechanical digestion
        Movements of large intestine  begin when substances pass iliocecal sphincter
          Haustral churning
          distention of haustra as chyme enters LI initiates haustral churning
          Peristalsis occurs at slower rate than in SI
          Mass peristalsis
          Strong peristaltic wave that begins at mid-transverse colon drives contents into rectum
          Occurs  during or immediately after meal when food enters stomach
          Chemical digestion
        Final stage of digestion occurs in LI through activity of bacteria
          Produces gases and other by-products
          Eg vitamins
 





Gut overview




Gut functions – movement/motility, secretion, digestion, absorption
          Digestion and absorption of:
        Carbohydrates
        Protein
        Fat
Gut functions
          Movement/motility, secretion, digestion absorption
Movement
          Propulsion of gut contents from mouth to anus
          Churning and mixing:
        Hastens dissolving
        Emulsification
        Hastens digestion and absorption
Propulsive movements
          Rhythmic peristaltic waves along gut
          Constriction of circular muscles behind food
          Relaxation in front and contraction of longitudinal muscles
Sphincters
          Barriers to movement between parts of the gut:
        Cardiac – oesophagus to stomach
        Pyloric – stomach to duodenum
        Ileocaecal – small to large intestine
        Internal anal – smooth muscle (reflex)
        External anal – striated muscle (voluntary control)
Gut secretions
          Mucous – protects and lubricates whole gut
          Saliva, Gastric juice, Bile, Pancreatic juice & Intestinal juice
          Total 7L/day
Functions gut secretions
          Dissolve food – allows taste, makes digestible
          Emulsifies fat
          Enzymes to digest food
          Regulates pH and osmolarity
          Excretion (bile)
          Fluid, salts and bile salts all largely reabsorbed
          Protein of enzymes – digested and absorbed
Control of gut secretion
          Cephalic – sight, smell, taste – secretion via nerve stimulation
          Receptors in gut (mechanical, chemical or osmotic) via local nerve plexuses or autonomic reflexes stimulate or inhibit glands
          Endocrine cells in gut respond to stimuli release hormone into blood which inhibits or stimulates exocrine glands
Digestion
          Enzymes in gut secretions break down:
        Starch and disaccharides to monosaccharides (only these are absorbed)
        Protein to amino acids, di&tripeptides (also absorbed along with tiny amount intact protein)
        Fat (triacylglycerol) monoacylglycerol and fatty acids
        DNA & RNA to free mononucleotides
Absorption
          Large surface area of small intestine – 600X that of smooth tube
          Agitation of gut contents speeds absorption
          Most absorption in duodenum & jejunum

Carbohydrate digestion
          In the diet:
        Sucrose and lactose (disaccharides)
        Amylose (α1-4 links only)
        Amylopectin (α1-4 and α1-6 links gives very branched chain and makes up most of starch)
        Other links e.g. β1-4 in cellulose not broken by digestive enzymes but….
          α-amylase in saliva & pancreatic juice:
        Glucose, sucrose, lactose, maltose, maltotriose and isomaltose
          On brush border are specific enzymes maltase, sucrase, lactase and isomaltase
Carbohydrate absorption
          Glucose and galactose actively absorbed – this is a carrier-mediated process and is sodium dependent (linked to Na+ pump)
          Fructose is carrier mediated but not active. Facilitated diffusion so relatively slow (also things like sorbitol)
Protein digestion
          Endopeptidases break bonds within protein chain:
        Stomach – pepsin
        Intestine –trypsin  and chymotrypsin
          Exopeptidases break of terminal amino acid:
        Carboxypeptidase in pancreatic juice
        Aminopeptidases on brush border
          A range of di&tripeptidases on brush border
Protein absorption
          Several active carrier mediated processes, some are Na+ dependent
          Some di- & tri-peptides absorbed and digested within mucosal cells
          Some intact protein absorbed especially in newborn by pinocytosis – protein toxins, antibodies and passive immunity
Fat digestion/absorption
          What is fat – triacylglycerol (TAG)?
          Actions of lipase in vivo – TAG to monoacylglycerol and 2 fatty acids
          Fat insoluble in water but pancreatic lipase is a water soluble enzyme
          Fat is emulsified by bile salts and phospholipids
          Products of fat digestion also low water solubility
          Formation of micelles – minute aggregates bile salts and fat digestion products
          Absorption by diffusion
          TAG re-assembled with mucosal cells
          Chylomicrons formed and enter lymphatic system then blood (protein coated fat droplets)
          Chylomicrons lipoprotein lipase in tissue capillaries breaks fat down to allow absorption and then re-synthesis of TAG within cells



The GI Immune System


The digestive system is a potential pathogen portal. Large number of bacteria inhabit the gut 1x10^13. The largest immune 'organ' in the body (GI tract) with specialized structures Gut Associated Lymphoid Tissue (GALT). 80% of all lymphocytes are found in the GALT.

Immune cells in Preyers Patches
Immune cells concentrated in


Special epithelial cells called Microfold (M) cells sample the contents of the gut
The GI Protective Responses:
    If the immune system is activated then immune cells secrete cytokines. Cytokines trigger inflammatory response and increase Cl-, fluid and mucus secretion.
Diarrhea: immune responses can lead to diarrhea which is an attempt to expel the pathogen. Can lead to dehydration
Vomiting: A protective reflex. Reverse peristalsis along with strong muscular contractions


 Crohn's Disease

1 comment:

  1. Great blog! Thank you for sharing.
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