Digestion and Absorption of Food

The gastrointestinal (GI) system includes the gastrointestinal tract (mouth, pharynx, oesophagus, stomach, small intestine, large intestine) and accessory organs (salivary gland, liver, gallbladder, pancreas) that secrete substances into the tract via connecting ducts.

GI system breaks down particles of ingested food into molecular forms by enzymes (digestion) that are then transferred to the internal environment (absorption).

Functions of GI organs
The GI tract begins at the mouth, where digestion begins with chewing. Saliva containing mucus and the enzyme amylase is secreted from 3 pairs of salivary glands, located in the head. Mucus moistens the food and amylase partially digests polysaccharides (starches). Food then reaches the stomach through the pharynx and ooesophagus.

The stomach is the sac that stores and digests food macromolecules into a solution called chyme. Glands lining the stomach secrete hydrochloric acid that dissolves food particles and protein-digesting enzymes, called pepsin.

Final stages of digestion and most of the nutrient absorption occurs in next portion of the tract: the small intestine. The small intestine is divided into 3 segments - duodenum, jejunum, and ileum.
The pancreas is a gland located behind the stomach. From its exocrine portion it secretes (1) digestive enzymes and (2) a fluid rich in HCO3- ions to neutralize the acid from stomach. The liver secretes bile. Bile contains HCO3- ions and bile salts to solubilise fats. Bile reaches the gall bladder through hepatic ducts and is stored in the gall bladder between meals. During a meal, bile is secreted from the gland by smooth muscle contraction and reaches the duodenum portion of the small intestine by the common bile duct.

Monosaccharide, amino acids and mineral salts are absorbed by transporter-mediated processes while fatty acid water diffuse passively.

Undigested material is passed to large intestine, where it is temporarily stored and concentrated by reabsorption of salts and water. Finally, contractions of rectum, the last part of large intestine, expel the faeces through the anus.

Structure of GI Tract Wall
The luminar surface is covered by a single layer of epithelium containing exocrine and endocrine cells. The exocrine cells disintegrate and discharge into the lumen, releasing their enzymes. The epithelia with an underlying layer of connective tissue (lamnia propia) and muscle (muscularis mucosa) are called mucosa. Below the mucosa is a layer of inner circular and outer longitudinal smooth muscle called muscularis externa, which provides the forces for moving and mixing the GI contents. The outermost layer of the tube is made up of connective tissue called serosa. The luminar surface of the tube is highly convoluted into projections called villi and microvilli; both of which increase total surface area for absorption. The center of each villus has a single blunt-ended lymphatic vessel called lacteal. Venous drainage from the intestine transports absorbed materials to the liver for processing via the hepatic portal vein.
  
Digestion and Absorption

Carbohydrate
Digestion begins in the mouth by salivary amylase and completed in the small intestine by pancreatic amylase. Monosaccharides, such as glucose, galactose and fructose, are produced by the breakdown of polysaccharides and are transported to the intestinal epithelium by facilitated diffusion or active transport. Facilitated diffusion moves the sugars to the bloodstream.

Protein
Proteins are broken down to peptide fragments by pepsin in the stomach, and by pancreatic trypsin and chemotrypsin in the small intestine. The fragments are then digested to free amino acids by carboxypeptidase from the pancreas and aminopeptidase from the intestinal epithelium. Free amino acids enter the epithelium by secondary active transport and leave it by facilitated diffusion. Small amounts of intact proteins can enter interstitial fluid by endo- and exocytosis.

Fat
Fat digestion occurs by pancreatic lipase in small intestine. A monoglyceride and two fatty acids are produced in the digestive process. Large lipid droplets are first broken down into smaller droplets, by a process called emulsification. Emulsification is driven by mechanical disruption (by contractile activity of GI tract) and emulsifying agents (amphipathic bile salts). Pancreatic colipase binds the water-soluble lipase to the lipid substrate.

Digested products and bile salts form amphipathic micelles. These micelles keep the insoluble products in soluble aggregates from which small amounts are released and absorbed by epithelial cells via diffusion. Free fatty acids and monoglycerides then recombine into triacylglycerols at the smooth ER, are processed further in the Golgi and enter the interstitial fluid as droplets called chylomicrons, which are then taken up by the lacteals in the intestine.

Vitamins
Fat-soluble vitamins are absorbed and stored along with fats. Most water-soluble vitamins are absorbed by diffusion or mediated transport. Vitamin B12, because of its large size and charged nature, first binds to a protein, called intrinsic factor, which is secreted by the stomach epithelium, and is then absorbed by endocytosis.

Water
The stomach absorbs some water but most is absorbed at small intestine by diffusion.


Regulation of GI Processes
Control mechanisms of the GI system regulate conditions in the lumen of the tract. Reflexes are initiated by:
(1)   Distension of wall by volume of luminal contents
(2)   Chyme osmolarity
(3)   Chyme pH
(4)   Chyme concentrations of specific products.

Neural Regulation of the GI tract
Impulses to the GI muscles and exocrine glands are supplied by enteric nervous system, the local nervous system of GI tract, which allows local, short reflexes, independent of CNS. Long reflexes through the CNS are possible via sympathetic and parasympathetic nerves, which also innervate the GI tract.

Hormonal Regulation
Endocrine cells are scattered throughout GI epithelia and surface of these cells is exposed to the lumen. Chemical substances in the chyme stimulate them to release hormones into blood.



Phases of GI control
Each phase is named according to where the receptor for a reflex is located. These phases do not occur in temporal sequence.
1. The cephalic phase is initiated when sight, smell, taste, chewing, and emotional states stimulate receptors in the head. Reflexes mediated by sympathetic and parasympathetic fibers activate secretory and contractile activity.
2. The gastric phase is initiated by distension, acidity, and the presence of amino acids and peptides in the stomach. This phase is mediated by short and long reflexes and activates the secretion of gastrin.
3. The intestinal phase is initiated by distension, acidity, osmolarity of digestive products in intestine and is mediated by GI hormones and short and long neural reflexes.

Mouth, Pharynx, and Oesophagus
Chewing is controlled by somatic nerves to the skeletal muscles and the reflex activation of mechanoreceptors on the palate, gums and tongue.

Autonomic nerves in response to chemoreceptor’s and pressure receptors in mouth stimulate saliva secretion.

Swallowing is mediated by pressure receptors on walls of pharynx, which send impulses to the swallowing center in the medulla oblongata. The center activates muscles in the pharynx and oesophagus. Multiple responses occur in a temporal sequence. The palate is elevated to prevent food from entering the nasal cavity, respiration is inhibited and the epiglottis covers the glottis to prevent food from entering trachea (windpipe). The upper oesophageal sphincter opens and food enters the oesophagus and moves toward the stomach by muscle contractions called peristaltic waves. Food then moves to the stomach when the lower oesophageal sphincter opens. A less efficient, or faulty,  lower oesophageal sphincter results in the reflux of gastric contents into the oesophagus (gastro-oesophageal reflux), this reversal results in heartburn and over time contributes to ulceration of oesophagus.

Epithelium lining the stomach invaginates into the mucosa, forming tubular glands. Parietal (oxyntic) cells secrete acid and intrinsic factor and chief cells secrete pepsinogen. Also scattered throughout are enterochromaffin-like (ECL) cells, which secrete histamine, and other cells that secrete somatostatin. The antrum, a lower portion of the stomach,secretes gastrin.

Increased protein content in a meal stimulates release of gastrin and histamine, which in turn stimulates HCl secretion. Somatostatin inhibits acid secretion by inhibiting the release of gastrin and histamine. Enterogastones in the duodenum also inhibit gastric acid secretion.

The precursor pepsinogen, which is produced by chief cells, is converted to pepsin by the acid in the stomach.
The stomach produces peristaltic waves in response to the arrival of food. The pyloric sphincter between the stomach and duodenum opens to release small amounts of chyme into the duodenum with each wave. These waves are generated by pacemaker cells in the longitudinal smooth muscle layer and are spread out by gap junctions. Gastrin, distension of stomach etc. stimulate gastric motility while distension of duodenum inhibits it.

Pancreatic Secretions
Inactive trypsinogen is secreted by pancreas and is later converted by the intestinal enzyme enterokinase to active trypsin, which digests proteins. Pancreatic amylase and lipase are secreted in active forms. The pancreas also secretes bicarbonate ions.

Secretion of pancreatic enzymes is stimulated by cholecystokinin (CCK), the secretion of which is triggered by the detected presence of fatty acids and amino acids in the small intestine. The secretion of bicarbonate ions is stimulated by secretin, which is triggered by acidity in small intestine.

Bile Secretion
Bile contains bile salts, which solubilize fats, and bicarbonate ions, which in turn are used to neutralize stomach acids. Bile salts, secreted by hepatocytes (liver cells) enter the GI tract and are reabsorbed by transporters in the intestine and are returned to the liver via the portal vein. This recycling pathway is called the entero-hepatic circulation.
The sphincter of Oddi controls the entry of the bile duct into the duodenum. When the sphincter is closed, secreted bile is shunted into the gallbladder. The presence of fat in the intestine releases CCK, which relaxes the sphincter to discharge bile salts into the duodenum.

Small Intestine
The most common motion of the small intestine is stationary contraction and relaxation, called segmentation. Segmentation results in little net movement. The chyme is mixed and brought into contact with the intestine wall and then moved slowly toward the large intestine. The movements are initiated by pacemaker cells in the smooth muscle layer.

After most of the materials are absorbed, segmentation is replaced by peristaltic activity called migrating motility complex, which moves any undigested material to the large intestine. The candidate intestinal hormone, motilin, initiates migrating motility.

Large Intestine
The large intestine consists of 3 parts: the cecum, colon and rectum. The primary function is to store and concentrate fecal material for elimination.  Chyme enters the cecum through the ileocecal sphincter, which relaxes and opens as a result of the gastroileal reflex.

Na+ is absorbed along with water. K+ and HCO3- ions are secreted into the lumen. Undigested polysaccharides (fiber) are metabolized to short-chain fatty acids by the residing bacteria and these are then absorbed by diffusion. A small amount of vitamin K is also produced and absorbed. Bacterial metabolism produces a mixture of gases, called flatus.

Motility and Defecation
Regular contractions of the circular smooth muscle produce a slow rhythmic segmentation movement.  The undigested material moves slowly in order to provide resident bacteria time to grow and multiply. Following a meal, there is a wave of intense contraction, called mass movement. The internal anal sphincter is made of smooth muscle and closes the anus, while the external anal sphincter is made of skeletal muscle and is under voluntary control. Both sphincters regulate the anal opening and closing.  Mass movement of fecal material into the anus initiates the defecation reflex, which is mediated by mechanoreceptors. The two sphincters open to expel the feces. If defecation is delayed, rectal contents are driven back into colon by reverse peristalsis until the next mass movement.

Pathophysiology of the GI Tract Ulcers
Ulcers are eroded areas of gastric surface and breaks in the mucosal barrier, which expose the underlying tissue to corrosive action of acid and pepsin. Damage to underlying blood vessels may cause bleeding.

Vomiting
The vomit reflex results in the forceful expulsion of toxic gastric contents. This reflex is coordinated by the vomiting center in the medulla oblongata. Various mechano- and chemo- receptors in the stomach and elsewhere can trigger this reflex. Increased salivation, sweating, heart rate, pallor etc. accompany the reflex. Abdominal muscles contract to raise abdominal pressure while the lower esophageal sphincter opens and gastric contents are forced into the oesophagus (retching). If the upper esophageal sphincter opens, contents are then expelled from the mouth (vomiting). Excessive vomiting can lead to loss of water and salts, which will ultimately result in dehydration.

Gallstones
Excessive secretion of water insoluble cholesterol in bile results in formation of crystals, called gallstones, which can close the opening of gallbladder or the bile duct. If a stone prevents bile from entering the intestine fat digestion and absorption decreases. If a stone blocks the entry of the pancreatic duct, it prevents pancreatic enzymes from entering the intestine, thus preventing the digestion of other nutrients. A blocked bile duct inhibits further secretion of bile, resulting in accumulation of bilirubin in tissues, producing a yellowish coloration called jaundice. Jaundice is common in newborns and is rectified by sunlight exposure.

Lactose Intolerance
Lactose intolerance results from a lack of the enzyme lactase which digests lactose, the sugar in milk. The lack of lactase results in the incomplete digestion of lactose to glucose and galactose.

Constipation and Diarrhea
Constipation is the absence of defecation due to decreased motility of the large intestine. This results in excess absorption of water from feces, making it hard to expel.
Dietary fiber, which is not digested in small intestine, can produce distension and increase motility.
Diarrhea results from decreased fluid absorption, or increased fluid secretion resulting in increased luminal fluid, which in turn, causes distension and increased motility. Diarrhea results in decreased blood volume, loss of water and other nutrients.
The Human Digestive System

Digestion is the breaking down of chemicals in the body to a form that can be absorbed and used. Digestion begins, in mammals, with the saliva in the mouth.

The Mouth
This is the buccal cavity in a human and is where mechanical digestion and mastication (chewing) takes place.
Saliva in the mouth consists of mucin (binds food together), salivary amylase (digests starch to maltose) and mineral salts (regulates pH around 7, neutral).


Oesophagus
Peristalsis of the circular muscle contracts and relaxes to push food down.The upper part of the ooesophagus is under conscious control until a point when it becomes involuntary.It usually takes between 4 and 8 seconds for food to travel from mouth to stomach.

Stomach
Acidic conditions (pH1/2, enzyme optimum pH). Mechanical digestion takes place here (churning of the stomach makes food break down in size giving it a larger surface area).While food is in the stomach it mixes with gastric juice by churning. Food in the stomach stimulates stomach wall to produce gastrin (transported in the blood).With a fatty meal enterogasterone is produced to slow churning, it also weakens the acidic pH of the stomach.

The gastric juices produced consist of:
Pepsinogen – made inactive to prevent autolysis and when added to HCl become active and is then called pepsin and is used to convert proteins.
Pro-rennin – when added to HCl forms rennin used to coagulate caseinogen and increasing surface area allowing a chance to digest.
Hydrochloric acid (HCl)
Mucus
Pro-rennin is only found in babies though, used for the digestion of the mothers milk.
Mucus is used for the protection from excess stomach acid and most of all autolysis. It also acts as a lubricant, reducing friction.

The stomach wall contains oxyntic cells which secrete hydrochloric acid (HCl), goblet cells which secrete mucus and peptic cells which secrete pepsin.
Chyme is the word we use to describe the semi-liquid food which is now all mixed together.

Duodenum (early small intestine)
This is the first 20cm of small intestine and receives secretions from the liver and pancreas.
Further digestion takes place.
Input of pancreatic juices.
Lipids broken down into fatty acids.
Protein broken down into amino acids.
Large surface area due to a large number of villi (villus).
The digestion of carbohydrates takes place inside cells.
.
Liver
Produces bile (stored in gall bladder, transported by the bile duct).
Bile made from bile salts and mineral salts.
Bile salts help with the digestion of fats by breaking them down from large globules to smaller globules, lowering surface tension and making a larger surface area.
Mineral salts neutralise the stomach acid (HCl) to around 7/8 pH in the small intestine.

Pancreas
Produces pancreatic juices which contain pancreatic amylase, pancreatic lipase and trypsinogen (or trypsin in its active form).
Pancreatic amylase converts the remaining amylose (starch) into maltose.
Pancreatic lipase converts lipids into fatty acids and glycerol
Trypsinogen, upon meeting with the enzyme enterokinase, is activated and is called trypsin. Trypsin then continues to break down proteins in digestion.

Brunner’s gland
Located in the wall of the duodenum.
Secretes alkaline juices (which help maintain the correct pH) and mucus (for lubrication and protection).



Ileum
·         This is the longest part of the small intestine.
·         Secretes endopeptidases and exopeptidases.
·         Endopeptidases break proteins into small polypeptides by breaking the bonds in the middle.
·         Exopeptidases also break down protein but by taking single amino acids of the end. Both work together to break down the proteins into small amino acids.
·         Sucrose is hydrolysed into fructose and glucose by sucrase.
·         Maltose is also hydrolysed into two glucose by maltase.
·         Contains crypts of Lieberkuhn which secrete maltase, sucrase, endopeptidases and exopeptidases.

Small Intestine in General
Glucose and amino acids are absorbed over the epithelium of the villi by diffusion and active transport into the capillaries of the villi.Once absorbed from the small intestine and into the capillaries, the products travel through the venules and the hepatic portal vein into the liver. Here in the liver toxins like alcohol, drugs, spent hormones and other toxins get converted into a non-toxic form. When they’re safe and non-toxic they can be transported to the kidney in the form of urea.
The absorption of fatty acids and glycerol don’t enter straight into the capillaries instead entering the lacteal of the villi and then into the lymphatic system and then via the thoracic duct into the blood system.

Products from digestion do one of three things, they either get stored (assimilation), used or converted (deamination). An example of assimilation is excess glucose being stored in the liver as glycogen. Deamination only occurs with excess of amino acids, they then get converted into urea by the removal of the amino group (NH2) which combines with CO2 to form CONH2 (urea). The remaining organic molecule can be broken down and respired.

The final products of digestion, carbohydrates in the form of monosaccharides, proteins in the form of amino acids and lipids in the form of fatty acids and glycerol.

Large Intestine
The large intestine absorbs water (by osmosis), minerals and vitamins.
Chyme at the start of the large intestine consists of water, bile, mucus, dead cells, bacteria and undigested food.
The large intestine has a larger lumen, is smaller in length and has a thinner wall than the small intestine.
**Faeces is stored in the rectum and then egested through the sphincter muscle called the anus.
**Diarrhoea causes dehydration because of the lack of absorption. Pernicious Anemia is another disease and is caused by not absorbing enough vitamin B and can be a side effect of diarrhoea.


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