The Digestive System, gastrointestinal system - GIT

Biomolecules are organic molecules that are associated with living organisms. Four groups

1. Carbohydrates
1. Monosaccharides
1. Fructose, Glucose, Galactose
2. Disaccharides
1. Sucrose (table sugar)
1. Fructose + Glucose
2. Maltose
1. Glucose + Glucose
3. Lactose
1. Glucose + Galactose
3. Polysaccarides
1. Polymers of Disaccharides
2. Glycogen 
2. Lipids - lipid related molecules
1. Phospholipids
1. 3 carbon glycerol plus long fatty acids.
2. Phosphate group (-H2PO4)
3. saturated fatty acids - no double bonds -palmitic acid
1. monounsaturated - one double bond - oleic acid, or
1. Olive oil is healthy
2. polyunsaturated - two or more double bonds - associated with atherosclerosis
3. Trans fats - are as likely to cause atherosclerosis - OH bonds in margarines that make it solid at room temp - So it does not matter if trans fatty acid free margarine - they "all the same"
4. Triglicerides - 90% of all fats in the body
2. Steroids
1. Cholesterol is the source
2. Important component of cell membranes
3. Eicosanoids - 20 carbon fatty acids
1. Thromboxanes, leukorines, and protaglandins
3. Proteins - Proteins are composed of 20 different amino acids that can be linked in almost an infinite number of sequences. these combinations allow proteins to take on different forms, such as globular and fibrous proteins.
1. amino acids - 20
1. 9 are essential amino acids. 
2. Amino acids that do not occur in proteins:
1. Homocystine - associated with heart disease
2. GABA - neurotransmitter
3. Creatine - stores energy when binding to a phosphate group
3. Peptides
1. 2-9 amino acids - oligopeptide
2. 10 - 100 - polypeptide
3. >100 amino acids - protein
2. Globular Proteins
1. Plasma carriers of lipid soluble molecules
2. Enzymes 
3. Cell to cell communication as hormones and neurotransmitters
4. Immunoglobulins
3. Quaternary Structure - several proteins associate with one another to form a functional protein like hemoglobin.
4. NH2 - amino group and -COOH is the carboxyl group
4. Nucleotides - Transmit and store energy and information
1. DNA and RNA - Energy ATP and regulation of metabolism cAMP
2. Composed of a:
1. one or more phosphate group
2. 5 carbon sugar
1. Ribose or Deoxyribose
3. carbon-nitrogen ring called a nitrogenous base
1. Purine
1. Adenine A
2. Guanine G
2. Pyrimidine
1. Cytosine C
2. Thymine T
3. Uracil U
3. AT and GC in DNA - AU and GC in RNA

Some molecules combine carbohydrates, proteins and lipids

1. Proteins with Lipids = lipoproteins - cell membranes, and transport hydrophobic molecules like cholesterol in the blood
2. Proteins with carbohydrates = glycoproteins - cell membranes
3. Lipids with carbohydrates = glycolipids - cell membranes

Micelles are small droplets with a single layer of phopholipids arranged so that the interior of the micelle is filled with hydophobic fatty acid tails. 

Smooth Muscle 

1. Sequential waves of smooth muscle contraction move food from the mouth to the anus
2. Smooth Muscle give sustained contractions with less energy, uses less oxygen
1. Prolonged contractions without fatiguing
1. Tonically contracted sphincters of the esophagus and the urinary bladder.
2. Smooth Muscle has:
1.  more variety
2. anatomy makes studies more difficult
3. contraction is controlled by hormones and paracrines in addition to neurotransmitters
4. variable electrical properties
5. Multiple pathways influence contraction and relaxation of smooth muscle
3. Smaller than Skeletal Muscle
1.  Spindle shaped cells with a single nucleus (skeletal muscles have large multinucleated fibers)
2. Nerotransmitters are released by autonomic neuron varicosities, simple diffusion - no motor end plates and synapses
3. Single unit smooth muscle - muscles contract as a single unit - all the fibers are electrically connected to one another, an electrical current in one smooth muscle rapidly spread through gap junctions to the entire sheet.
1. The amount of Calcium that enters the cell determines the force of contraction
4. Multi-unit smooth muscle - not electrically linked - need independent innervation
1. Smooth Muscle has longer Actin and Myosin filaments
1. Greater actin to myosin ratio 10-15:1
2. has tropomycin but lacks tropinin
3. Primary Calcium release channel is IP3 - Inisitol triphosphate receptor channel. IP3 is a second messanger created in the phospholipase C pathway
2. Smooth Muscle is not arranged in sarcomeres - they become globular when they contract.
1. Actin is attached to dense bodies and they terminate in a protein attachment plaque in the cell membrane - continous line of myosin heads
2. The dense bodies are analogous to the Z-disks of sarcomeres, Smooth muscle myosin is longer, has heads the length of the filament, and has slower ATPase activity
3. Smooth Muscle actin is longer than skeletal muscle actin, and it lacks troponin
3. Protein Phosphoralation Plays an important role in Smooth Muscle contraction
1. Ca - MLCK - (ATP-ADP) - phophoralate the myosin head - move actin
1. modulated by caldesmon - unkonwn mechanism
2. RElexation  requires myosin phosphatase for relaxation - dephosphoralation of the myosin light chain. Takes a long time to release - Latch STATE.
2. Graded contractions: Calcium concentration varies contraction strength. IP3-activated receptor channel responds to signal transduction pathways that produce IP3
1. Skeletal muscle use the ryodinie receptor that opens when the action potential reaches the DHP receptor. 
2. Smooth muscle SR monitor calcium levels and open calcium channels to increase calcium uptake if store levels are low. 
3. Stretch activated Calcium Channels that open when pressure or other forces distorts the cell membrane 
1. Myogenic contraction as the contraction initiates from a property of the muscle fiber itself. 
4. Pacemaker potentials always reach their threshold and create regular rhythms of contraction. slow wave potentials are variable in magnitude and may not reach their threshold each time.  
3. Smooth Muscles have Unstable Membrane Potentials
1. Initiation phase of depolarisation phase is due to calcium (and not to sodium as per skeletal muscle and nerves). Repolarisation also allows potassium into the cell.
2. Action potential is not required to open the calcium channel - graded potentials may open a few calcium channels - allowing small amounts of Calcium into the cell - Calcium then depolarises the cell and opens additional calcium channels. 
3. Cyclic depolarisation and Repolarisation of the cells - SLOW WAVE POTENTIALS - spontaneous ion channel opening and closing
4. PACEMAKER POTENTIALS - Regular rhythms of contractions - spontaneous ion channel opening and closing
4. Smooth Muscle Activity is Regulated by Chemical Signals
1. Neurotransmitters, hormones and paracrines
2. Second massager action on actin and myosin  

GIT Diseases account for 1/10 of the money spent on health care - heartburn, indigestion, gas, and constipation

The stomach digests:

1. Meat with Hydrochloric acid and Pepsin

Digestive function and Processes:

Muscular tube with intermittent sphincters - part of the external environment

Autodigestion leads to peptic ulcer formation - balance between digestion and protection of the GIT

Diarrhoea: Mass Balance - About 9 L is secreted into the lumen of the GIT and 9 L needs to be reabsorbed. Massive fluid loss happens when in imbalance.

Keep bugs out - Largest collection 80% of all lymphoid tissue is in the GIT - Gut Associated Lymphoid Tissue - GALT

Four Basic Processes of the GIT: Digestion, Absorption, Motility and Secretion

1. Regulated and controlled based on the bodies long term requirements and cellular feedback from stores and usage requirements.

Anatomy of the Digestive System

Salivary glands - sublingual, submental and parotid glands - chewing and saliva

Chyme - soupy mixture of secretory epithelium, liver and pancreas 

Digestion takes place in the Lumen.

Digestion is the chemical and Mechanical breakdown of food into absorbable units. Digestion takes place in the GI tract lumen, which is external to the body; metabolism takes place in the body's internal environment. 

Absorption moves material from the GI Lumen into the ECF; secretion moves substances from the cells or the ECF into the lumen.

The Digestive system is a Tube.  (Contracted GIT is 4,5m long)

Esophagus - 1/3 skeletal muscle and lower 1/3 smooth muscle - with a transition zone of 1/3 with both muscle types.

Stomach - fundus, body, antrum and pylorus - limited by the pyloric valve. Intergrated signals and feedback loops regulate the amount of chyme entering the small intestine from the stomach - regulating the rate of intestinal digestion.

The tonically contracted sphincter of Oddi keeps the pancreatic and bile fluid from entering the small intestine - except during meal time. 

Digestion is completed in the small intestine - nearly all the nutrients and fluids are absorbed here

1.5 L of chime into the large intestine - Colon absorbs water and electrolytes - faeces remain. The defication reflex propels the faeces out of the anus when the external anal sphincter relax.

GI Tract has four layers

Mucosa, Submucosa, Muscularis Externa, Serosa

Mucosa

1. Single layer of epithelial cells
2. Lamina propria - subepithelial connective tissue
3. Muscularis Mucosae - tin layer of smooth muscle
1. Entire wall is crumpled into rugae in the stomach and plicae circularis in the small intestine. Villi - fingerlike extensions increase surface area. 
2. Invaginations: Gastric glands in the stomach and crypts in the small intestine extend down into the supporting tissue. Some deep invaginations form secretory submucosal glands that open into the lumen through ducts.
3. Epithelium - Transport cells transport water and ions to the lumen and absorb water and ions and nutrients into the ECF.
1. Apical Secretory cells release enzymes, mucus and paracrines into the lumen. (no hormones here)
2. Basolateral surface secretory cells secrete hormones into the blood or paracrines into the interstitial fluid.
4. Cellular junctions have plasticity - can vary according to requirements. Stomach - tight junctions and small intestine cellular junctions are "leaky"
5. GI Stem cells are forming new cells in the gastric glands and crypts. Rapid division and turnover make it a site for colon and rectal cancer. 
6. Lamina Propria - subepithelial connective tissue contains blood vessels, lymph and nerves. Wandering immune cells - macrophages and lymphocytes. In the intestine - collections of lymphoid tissue form small nodules and larger Payers Patches - visible bumps under the mucosa. GALT - Gut Associated Lymphoid Tissue. 
7. Muscularis mucosae - seperates mucosa from submucosa - contraction alters the effective surface area  for absorption moving the villi back and forth, like waving tentacles.

Submucosa - 

1. Contains the submucosal plexus - (Meissner's plexus), larger lymph and blood vessels in connective tissue.

Muscularis Externa and Serosa

1. Inner circular layer, decreases the diameter of the lumen
2. Myentric plexus - Auerbachs Plexus - between the circular and longitudinal layer - coordinates muscular activity of the  muscularis externa
3. Longitudinal Layer - shortens the tube 
1. The Stomach has an additional oblique layer between the circular layer and the submucosa
4. Serosa - continuation of the peritonium

MOTILITY

2 Purposes - movement and mixes the food to break it into uniform small particles - increasing the surface area of the exposed particles to the digestive enzymes

1. GI Smooth Muscle Contracts Spontaneously
1. Single-unit Smooth Muscle - with groups of cells electrically connected by gap junctions to create contracting segments
1. Tonic contractions - sustained for minutes to hours in sphincters
2. Phasic Contractions - contraction relaxation cycles every few seconds - posterior region of the stomach and the small intestine
2. Slow wave potentials - spontaneous cycles of depolarisation and repolarisation - slow in rate (compared to the heart) and do not reach threshold with each cycle.
3. When Slow Waves reach threshold, voltage gated calcium channels in the muscle fiber open and  more calcium enters the cell - initiates muscle contraction.
4. Contraction is graded by the amount of calcium entering the cell. The more the action potential fires, the greater the calcium that enters the cell, the greater the contraction. Amplitude and duration is modified by neurotransmitters, hormones and paracrines.
5. Slow Waves originate in network cells called the Intestinal Cells of Cajal - ICC - between the smooth muscle layers and the intrinsic nerve plexus, act as an intermediary between the neurons and smooth muscle. 
6. Interstitial Cells of Cajal - ICC function as the pacemakers for slow wave activity in different regions of the GI tract. Just as cardiac muscle - the fastest pacemaker of the group sets the pace for the entire group. 
1. Link between ICCs and functional bowel disorders, such as irritable bowel syndrome and chronic constipation.
2.  GI Smooth Muscle Exhibits Different Patterns of Contraction
1. The "housekeeping" function every 90 minutes on an empty stomach - migrating motor complex - a series of contractions from the stomach to the anus, moves food remnants and bacteria from the upper GI tract to the large intestine
2. Peristalsis - progressive waves of contraction behind a food bolus - pushing the bolus forward to a receiving segment, where the circular muscles are relaxed. The wave than contracts the receiving segment  propelling the food forward at a rate of 2 to 25 cm/s. The esophagus is the main area of paristalsis - propelling food into the stomach. Paristalsis also mixes food.
3. Segmental contractions - responsible for mixing - the circular muscles contract and the longitudinal muscles relax. This churns the intestinal contents, mixing and keeping it in contact with the intestinal absorptive epithelium.

Motility disorders are the most common gastrointestinal problems. Esophageal spasms and delayed gastric emptying to constipation and diarrhea. Irritable bowel syndrome is a functional disorder characterised by altered bowel function and abdominal pain.

Delayed Gastric Emptying - gastroparesis - is a significant complication of Diabetes and plagues 1/3 of all diabetics. The Migrating Motor Complex is absent and the stomach empties very slowly after meals. Patients suffer from nausea and vomiting as a result. May be as a result of the loss of function of the Interstitial cells of Cajal - pacemakers between the enteric and nervous plexus and the smooth muscle. Implanting a pacemaker to promote gastric motility in diabetic patients with severe gastroparesis.  

Some sphincters are tonically contracted to close off the GI tract from the outside world and to keep material from passing freely from one section to another.

SECRETION
The digestive System secretes Ions and Water

1. Ions are first secreted than absorbed. Water follows the osmotic gradient created by ionic transfer, and absorbed through the cells via membrane channels and between the cells - the paracellular pathway.
2. Like the renal apical and basolateral membranes
1. Sodium Potassium ATPase
2. Cotransporters include 
1. NaK-2Cl symporter - NKCC,
2. Chloride Bicarbonate exchangers
3. Sodium Hydrogen exchanger - NHE
4. Hydrogen potassium ATPase - H+K+-ATPase
3. Ion Channels
1. Sodium, Potassium and Chloride Channels
2. Defective chloride channel - cystic fibrosis transmembrane conductance regulator - or the CFTR chloride channel. Defects in the CFTR channel or function leads to cystic fibrosis. 
3. Acid Secretion - 



http://www.colorado.edu/intphys/Class/IPHY3430-200/020digestion.htm

1. Parietal Cells deep in the gastric glands secrete hydrochloric acid into the lumen of the stomach. Luminal pH as low as 1 from a intracellular pH of 7,2 - against an amazing Hydrogen gradient.
2. Hydrogen potassium ATPase pump pumps out the Hydrogen in exchange for Potassium at the apical parietal cell. The potassium recirculates through the apical Potassium ion channel. Chloride leaves through the Chloride channel - to form HCl. 
3. Chloride enters the basolateral membrane in exchange for bicarbonate -  Chloride Bicarbonate Exchanger. The bicarbonate (and hydrogen) is made from CO2 and H2O catalysed by Carbonic anhydrase. The bicarbonate creates a "alkaline tide" from the blood leaving the stomach in active digestion.
4. Bicarbonate secretion
1. Bicarbonate secretion neutralises acid entering the duodenum from the stomach. 

http://www.colorado.edu/intphys/Class/IPHY3430-200/020digestion.htm

1. Small amount is secreted by the deodenal cells, 
2. Pancreas secretes most in the form of NaHCO3 - sodium bicarbonate- from the duct cells, or the non exocrine part of the pancreas. The Acini secrete digestive enzymes.
1. Bicarbonate produced is secreted by the bicarbonate chloride exchanger. 
1. The Chloride enters the basolateral membrane NKCC and leaves the apical membrane by the CFTR. The Chloride is recirculated by the bicarbonate chloride exchanger. 
2. Sodium enters the cell with the Sodium hydrogen exchanger, the NKCC and is pumpted out with the NK-ATPase - on the basolateral membrane. 
3. There is a large amount of Carbonic anhydrase - like in renal tubules and RBC's. 
4. Hydrogen pumped out helps regulate the HCO3 from the parietal basolateral membrane when producing hydrogen.
2. The net movement of negative ion into the lumen attracts Sodium and Water which move passively through leaky junctions down the electrochemical gradient. The secretion of Sodium and Bicarbonate into the lumen, creates a osmotic gradient and water follows by osmosis. The net result is a watery sodium bicarbonate secretion. 
3. Cystic fibrosis, an inherited defect in or absence of the cystic fibrosis transmembrane conductance regulator - or the CFTR chloride channel - results in secretion of fluid ceasing. The goblet cells still secrete mucus - that cannot be thinned. This blocks the pancreatic ducts and pancreatic digestive enzymes. In the lungs there is a failure of the muco-cilliary escalator leading to recurrent lung infections.
1. NaCl Secretion
1. Intestinal and colonic crypt cells secrete Chloride. Chloride enters the basolateral membrane by the NKCC transporter and is excreted by the apical membrane by the CFTR channel. Potassium then leaves by facilitated diffusion through the basolateral membrane by the potassium ion channel and sodium is actively pumped out by the NK-ATPase pump. There is a electrochemical gradient gradient created by the negative chloride excreted into the lumen, Sodium follows with water along the paracellular pathway = isotonic saline solution in the lumen.
2. Digestive Enzymes are Secreted into the Lumen
1. Digestive enzymes:
1.  are secreted by:
1.  exocrine glands - salivery glands and the pancreas, or 
2. by endothelial cells in in the mucosa of the stomach and the small intestine
2. Enzymes are proteins
1. Proteins are synthesised in the Ribosome's of the RER, packed by the Golgi Complex into secretory vesicles, then stored in the cell until needed. They are excreted on demand.  
3. Enzymes are not freely released into the lumen, but are bound to the intestinal apical membranes by transmembrane "stalks" and lipid anchors.
2. Inactive Proenzymes aka Zymogens - are secreted and activated in the lumen. This allows the secretory cells to stockpile these digestive enzymes without damaging themselves. 
3. Stimulated by parasympathetic vagus neuron, hormones and paracrine glands.
3. Specialised Cells secrete Mucus
1. Mucus is made from mucins, which are glycoproteins. Mucus forms a protective coating over the GI mucosa and lubricates the contents of the gut. Mucus is made by mucus cells in the stomach and goblet cells in the intestine. Salivary glands have specialised mucus secretory cells. 
2. Parasympathetic innervation,  cytokines from immune system. Parasitic infections and inflammatory processes in the gut also cause a substantial increase in mucus output as the body attempts to fortify its protective barrier. 
4. Saliva is an Exocrine Function
1. Acidic saliva is hyposmotic fluid - containing water, ions, mucus and proteins - enzymes and immunoglobulins. 
2. Excocrine secretion initially is like ECF, but before the fluid reaches the oral cavity sodium is exchanged for potassium and then looks like intracellular fluid - water does not follow the sodium as the cells have a low water permeability (High Potassium and Low Sodium).
3. Parasympathetic innervation. Sympathetic inhibition - drys the saliva in emotional distress.
5. The Liver Secretes Bile
1. Bile is a nonenzymatic solution secreted by from hepatocytes. 
1. bile salts - which facilitate enzymatic fat digestion, are made from steroid bile acids combined with amino acids. They act as detergents to solubilise fats during digestion. 
2. bile pigments - billirubin from hemoglobin degeneration
3. Cholesterol - secreted in the faeces

REGULATION OF GI Function

• Long reflexes integrate in the CNS 
• CNS integration = long reflexes, 
• Feed forward cephalic reflexes,  sight, smell, sound and thought, stimulates digestion
• Emotions influence the GI responses
• Parasympathetic - Vagus is stimulatory and sympathetic is inhibitory for the GI tract
• Short Relexes integrate the entric nervous system
• Complete independent integration and response within the GIT - Enteric Nervous system. Process of motility, secretion and growth. The submucosal plexus receives sensory stimuli from the lumen - the ENS integrates info and  initiates a response through - submucosal plexus or changes in motility of the myenteric neurons.  
• Reflexes involving GI peptides
• GI peptides may act as hormones secreted in the blood, or as paracrins - acting locally. 
• Influence Motility or Secretion. 
• Ghrelin is secreted by the stomach, and acts on the brain to increase food intake.
• CCK  - Cholecystokinine - found to enhance satiety, the feeling that hunger was satisfied. Also an neurotransmitter in the brain. 

1. The Enteric Nervous System Can Act Independently
1. Intrinsic neurons - of the two nerve plexus
2. Neurotransmitters and Neuromodulators - serotonin, vasoactive intestinal peptide, and nitric oxide
3. Glial support cells - similar to astrocytes
4. Diffusion barrier - capillaries that surround the ganglia in the ENS is not permeable and create a diffusion barrier - like the blood brain barrier.
5. Integrating centre - 
6. It appears that there are taste receptors in the endothelial cells of the gut - express the same G Protein GUSDUCIN as tastebuds.
2. GI Peptides Include Hormones, Neuropeptides and Cytokines
1. The Gastrin family - including gastrin and Cholecystokinin - bind to the CCKB receptor on parietal cells
2. The Secretin Family - includes Secretin, vasoactive Intestinal Peptide, and GIP - Gastric Inhibitory Peptide. Glucagon-like peptide I (GLP-1) important in glucose homeostasis. 
3. Motilin - stimulates the migrating motor complex 

DIGESTION AND ABSORPTION

1. Breaks down macromolecules into smaller absorbable units mechanically and with enzymes.
2. Most absorption takes place in the small intestine
3. Small intestine surface area is expended with crypts AND intestinal villi with their associated brush boarder. Nutrients enter capillaries, but fats are absorbed by lymph vessels called lacteals.
4. Digestion is controlled indirectly by motility and secretion.
5. CARBOHYDRATES ARE ABSORBED AS MONOSACCHARIDES
1. Amylase - breaks complex starch and glycogen into Disaccharides - Maltose (GG), Sucrose (GF) and Lactose (GGal). The disaccharides are broken down into the primary monosaccharides - glucose, galactose and fructose with disaccharidase.
2. Absorbed by:
1.  the apical - SGLUT symporter
2. the basolateral GLUT2 transporter
3. Entrocytes do not use glucose as their primary energy source - they use amino acids glutamine. 
6. PROTEINS ARE DIGESTED INTO PEPTIDES AND AMINO ACIDS
1. All proteins are not equally digestible - plant proteins least and egg the most.
2. Endopeptadases: commonly called proteases, break the peptide bonds, breaking the long peptide chain into smaller fragments. Secreted as prohormones that are activated in the lumen.
1. pepsin - secreted in the stomach, and 
2. trypsin and chymotrypsin - secreted by the pancreas 
3. Exopeptadases: release single amino acids from peptides by chopping them off at their ends, one at a time.
1. Carboxypeptidases - secreted by the pancreas
2. Aminopeptidases - play a lesser role in digestion.
4. Product of digestion is amino acids, dipeptides and tripeptides - all are absorbable 
5. Transport at the apical membrane
1. Free amino acid - Sodium dependent cotransport - 
2.  Di and Tripeptide cotransport with hydrogen - the oligopeptide transporter PepT1
6. Transport at the Basolateral Membrane
1. Oligopeptides are transported with the hydrogen dependent transporter
2. Amino Acids are transported with the Sodium amino acid counter transporter
7. Small peptides are carried intact across the cell by transcytosis
1. Peptides act as antigens - food allergies
2. Newborns have immature Villi - and the crypts are exposed to luminal contents. Peptide absorption takes place mainly in crypts. As the Villi grow there is less peptide absorption. Parents should delay feeding allergy inducing peptides, the gut has a chance to mature and lessen the likelihood of antibody formation
3. Gluten, a component of wheat, is one of the most common childhood allergies - the allergies have reduced since parents were advised not to feed children gluten-based cereals.
4. Drugs like vasopressin can be given orally rather then by ingestion.
7. BILE SALTS FACILITATE FAT DIGESTION
1. Enzymatic fat digestion is carried out by:
1.  lipases, enzymes that remove two fatty acids from each triglyceride molecule. The resultant monoglyceride plus 2 fatty acids.
2. Phospholipids are digested by pancreatic phospholipase. 
3. Free Cholesterol need not be digested to be absorbed
2. Bile salts break down the non-soluble the coarse emulsion into stable molecules - increasing the surface area for fat absorption
3. Bile Salts are amphipathic
4. Lipase and colipase break down fats into moglycerides and fatty acid stores in micelles.
5. Cholesterol - although expected to be diffusing across the cell membrane by simple diffusion - now it is known has a specific transporter blocked, NPC1L1 receptor,  by drug EZETIMIBE. 
6. Monoglicerides are reconstituted to form triglicerides in the cells SER. The TG and Cholestrol and Protein then form Chylomicron - packed in the Golgi apparatus and released to the lymphatic system - lacteals.
8. NUCLEIC ACIDS ARE DIGESTED INTO BASES AND MONOSACCHARIDES
1. Pancreatic and intestinal enzymes digest nucleic acids into nitrogenous bases and monosaccharides. Bases are absorbed by active transport.
9. THE INTESTINE ABSORBS VITAMINS AND MINERALS
1. ADEK
2. Vitamin B12 - cobalamin is only absorbed in the distal illium when complexed with a protein, Intrinsic Factor from the stomach.
3. Mineral transport is active - Iron and Calcium are specifically regulated
1. Iron
1. Iron is ingested as Heme iron in meat and ionised iron in some plants
2. Heme is absorbed by endocytosis
3. Ionised Iron is actively absorbed by cotransport with Hydrogen - divalent metal cotransporter DMT1. 
4. Inside cells: heme iron is converted to Fe2+,
5. Pools of iron leave the cell on ferroportin.
6. Iron uptake is regulated by hepcin. 
2. Calcium
1. most calcium absorption is passive in the paracellular pathways
2. Hormonally transcellular calcium absorption occurs in the duodenum - 
1. active transport - Calcium ATPase or the Sodium Calcium Antiporter
10. The Intestine Absorbs Ions and Water
1. Sodium Chloride reabsorption in the small intestine

The CEPHALIC PHASE

1. saliva - 
1. dissolves food so you can taste it
2. chemical digestion with salivary amylase - breaks starch into maltose
3. Lysozyme -antibacterial salivary enzyme
4. Salivary Immunoglobulins
2. Mastication - mechanical digestion. 
3. Swallowing (diglutition) 
1. Medulla Oblongata
2. Epiglottis closes and Respiration is inhibited
3. Upper esophagus sphincter relaxes
4. the lower esophagus relaxes
1. Subatmospheric pressure of inspiration relaxes the LES and and can suck acid contents - GORD

GASTRIC PHASE
The result of the gastric phase is the digestion of proteins in the stomach by pepsin; the formation of chyme by action of pepsin, acid, and paristaltic contractions.

1. Storage 
1. Relaxes and expends
2. receptive relaxation
1. Failure = "dumping syndrome"
2. Digestion

1. The Stomach Secretes Acid and Enzymes. 
1. Acid - parietal cells secrete HCl
1. Denatures proteins 
2. Carbohydrates - breakdown by salivary amylase stops as salivary amalyse is inhibited by HCl. 
3. Parietal cells -  Intrinsic Factor - complexes with vitamin B12 to permit absorption 
1. Pernicious anaemia
2. Enzyme Secretion
1. Chief cells - secrete inactive pepsinogen - effective in digesting collagen and therefore important in meat digestion
2. Gastric lipase - co-secreted with pepsin but <10% of fat absorption takes place in the stomach.
3. Paracrine Sectretion
1. Enterochromaffin-like  (ECL) cells - histamine release that promotes acid secretion by the parietal cells
2. D cells - release somatostatin - inhibits acid secretion directly and indirectly inhibits pepsinogen secretion
4. Hormone Secretion
1. G Cells found deep in the gastric glands - Gastrin that stimulates acid secretion. Stimulated by amino acids and peptides and by gastrin-releasing peptide. COFFEE ALSO STIMULATES GASTRIN RELEASE- ONE REASON WHY YOU SHOULD AVOID COFFEE IF YOU HAVE INCREASED ACID SECRETION SYNDROMES.
3. Protection 
1. The Stomach Balances Digestion and Protection
1. Mucous Cells protect the gastric mucosa with a Mucus-Bicarbonate Barrier






Zollinger–Ellison syndrome
Classification and external resources
Endoscopy image of multiple small ulcers in the distal duodenum in a patient with Zollinger–Ellison syndrome
ICD-10	E16.4

Classification and external resources


Endoscopy image of multiple small ulcers in the distal duodenum in a patient with Zollinger–Ellison syndrome

E16.4

1. Rx with Aspirin or Alcohol - increases stomach irritation and Mucus-Bicarbonate release (initially)
2. Zollinger-Ellison Syndrome - Excessive amount of gatrin from a gastrin secreting tumour in the pancreas. Hyperacidity from the high levels of Gastrin - creates Ulcers. 
2. Dyspepsia is treated with antacids. H2 receptor antagonist - (cimetadine and ranitadine) and Proton Pump Inhibitors that block the NK-ATPase (Sodium Potassium ATPase) of parietal cells.
4. Stimulated before digestion by the long Vagal reflex - cephalic phase

INTESTINAL PHASE

1. Chyme in the intestine slows gastric motility and secretion. 
1. 3 hormones augment the short gastric signal - 
1. Secretin,
1. Stimulated by acid chyme in the duodenum
2.  Inhibits gastric acid production and gastric motility - slowing gastric emptying. Pancreatic secretion of HCO3- 
2. Cholecystokinin, and 
1. Stimulated by a fatty meal
2. CCK Slows gastric emptying motility and acid secretion
3. Gastric Inhibitory Peptide. 
1. Stimulated by carbohydrate meal - the incretin hormones GIP and glucagon-like peptide 1(GLP-1) are released
2. GIP - feedforward to promote insulin release from the endocrine pancreas - preparing for glucose to be absorbed
3. GIP decreases gastric motility and acid secretion. 
4. the digested food in chyme is hyperosmotic solution. Osmoreceptors in the intestine wall - inhibit gastric emptying - unknown reflex.
2. Bicarbonate Neutralises Gastric Acid
1. Stimulated by Neural Stimuli and Secretin - from the pancreas
2. Intestinal goblet cells secrete mucus for protection and lubrication
3. Bile - released into the intestine - when contraction of the gall bladder is stimulated by CCK following ingestion of FATS. Bile salts are not altered and are reabsorbed in the terminal ileum. Here they encounter cells that transport them back to the circulation. Return to the Liver and taken back into the hepatocytes and resecreted
4. Digestive enzymes - from the exocrine pancreas and the brush boarder of the intestine
1. Intestinal enzymes include peptidases, disaccharidases, and a protease called enteropeptidase - anchored to the intestinal luminal entrocyte  cell membrane
3. Most Fluid is Absorbed in the Small Intestine
1. hepatic portal system
2. cytochrome p450 system -  metabolises drugs and xenobiotics before they reach the systemic circulation
4. Most Digestion occurs in the small Intestine
1. Protein digestion starts in the stomach - pancreatic protease and 17 brush boarder proteases and peptidases digest proteins
2. Carbohydrates convert digestable polysaccharides and disaccharides into monosaccharides that can be absorbed. Pancreatic Amalyse convert starch into maltose. Maltose and disaccharides are converted by brush boarder disaccharidase to absorbable Glucose, Galactose  and Fructose
3. Fats enter the small intestine to form a coarse emulsion. Bile Salts stabilise the fats and they are carried out by pancreatic lipase.
5. Large Intestine Concentrates Waste
1. The Ileocecal Valve relaxes when Chyme reaches it and and when food leaves the stomach as part of the GastoIleal Reflex.
2. Motility in the Large Intestine
1. Unique colonic contraction - MASS MOVEMENT - 3 to 4 x per day - stimulated by the GASTROCOLIC REFLEX.
2. DEFECATION REFLEX - against a closed glottis
3. Constipation 
1. Treated by Glycerine suppositories
3. Digestion and Absorption in the Large Intestine
1. Breakdown through bacterial fermentation of undigested carbohydrates and proteins. 
2. Colonic bacteria produce Vitamin K
4. Diarrhea can cause dehydration
1. Intestinal secretion is greater than intestinal absorption
2. Osmotic Diarrhea - 
1. Stimulated by lactose and sorbitol - a sugar alcohol from plants
3. Secretory Diarrhea -
1. Bacterial toxins like the cholera toxin from Vibrio cholera and EColi enterotoxin enhance colonic Chloride secretion 

IMMUNE FUNCTIONS OF THE GI TRACT

1. GALT - must protect the GIT
2. M Cells Sample Gut Contents
1. Apical membrane Clathrin coated pits - with embedded membrane receptors
2. Transcytosis
3. Basolateral membrane - released into the interstitial fluid for waiting macrophages and lymphocytes
3. Vomiting is Protective
1. Excessive - Metabolic alkalosis
2. Vomitting centre in the Medulla 
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2. http://samedical.blogspot.com