Digestion and Absorption
All the life forms act as open system that incessantly exchange energy and matter with their surroundings to sustain the state of ‘life’. The autotrophs convert carbon dioxide into organic molecules (simple carbohydrates like glucose) by harvesting the energy of solar radiation (photoautotrophs) or chemical redox reactions (chemoautotrophs). Thus, photoautotrophs (photosynthesizing organism like plants, algae, cyanobacteria, etc.) and chemoautotrophs (methanogens, etc.) are nutritionally independent as they can produce their own food. The heterotroph, however, depends on autotrophs or other heterotrophs for its need of food. Any substance that a heterotroph can metabolize into substrates for replenishing its pool of biomolecules in its body is defined as food. The biomolecules obtained from food serve as substrates in the processes of generating cellular energy, growth and development, and reproduction, etc. Cow and other ruminants (goat, deer, giraffe, etc.) metabolize cellulose-rich grass with the help of their stomach microflora, thus grass is food for them. However, the omnivores including human and carnivores can’t metabolize grass, thus, it’s is not food for them. It’s the intrinsic properties of the digestive system of an animal that discriminates if a particular substance serves as food or not.
The digestive tract or alimentary canal is the tubular passage of food through animal body, extending from mouth (entry point of food) to anus (exit point of undigested food). It develops from the endoderm germ layer during embryogenesis. Depending on the relative position, anatomy and morphology, and roles in digestion the alimentary canal of higher animals is further subdivided into mouth, esophagus (oesophagus), stomach, small intestine, large intestine and caecum. The alimentary canal and its associated organs participating in digestion (salivary glands, liver, pancreas and gall bladder) collectively form the digestive system. The digestive system acts as an extended muscular tube that facilitates mechanical and enzymatic break down of food into constituent monomers and subsequent absorption while passage of food through it.
Mouth or buccal cavity is the anterior opening of alimentary canal. It provides a passage for ingestion of food. The buccal cavity is enclosed laterally by cheeks, at upper roof by palate and at base by buccal floor and tongue. The taste buds on tongue help perceive taste, temperature and texture of food. The strong musculature of tongue also helps in mixing of food with saliva, mechanical breakdown of food to some extent and formation of bolus during mastication and ingestion. Besides these, it also helps in speech formation. The exocrine glands in the pits around circumvallate and foliate papillae on tongue also secrete lingual lipase (an acidic lipase). The exocrine glands secreting lingual lipase are also known as Von Ebner’s glands, Ebner’s glands or gustatory glands. The enzyme has pH optima of 3.5- 4.5, thus remains inactive in the neutral pH of saliva. Once it reaches the stomach along with the bolus, it becomes catalytically active. Lingual lipase activity accounts for around one-third of total lipolytic activities during digestion.
Mastication, the process of breakdown of food into smaller particles, is mostly aided by teeth embedded in the upper (maxilla) and lower (mandibula) jaw. Dentition defines the type and number of teeth and the pattern of their development and attachment in jaws at specific age. An adult human has four types of morphologically and functionally different teeth- incisor, canine, premolar and molar, from center of jaw front to rear of jaw in each quadrant. The dentition presenting morphologically different teeth (appear different in shape and size) is termed as heterodont. The incisor teeth have flat and sharp edges like chisel and useful in biting food. The canine teeth are pointed and useful in tearing and shredding food (for example- sugarcane). This tooth is highly reduced and bit flattened in present day human, thus is sometimes also called incisiform. The canine teeth are highly developed, pointed and much longer than rest of the teeth in carnivores (dog and related animals). Unlike incisors and canine, the premolar and molar teeth have relatively broad chewing surface and bear more than one roots (the number of divisions in base of a tooth that fix it into the jaw socket) and 2-5 tooth cusp (the pointed projections on the chewing or biting surface of a tooth). Each premolar tooth bears one pair each of roots and cusps. The molar tooth may bear 4-5 cusps and two (mandibular molars) or three roots (maxillary molars). The relatively broad and cusped surface of premolar and molar teeth with multiple roots make them suit
The socket in jaw holding a tooth is called an alveolus; and the type of dentition being called thecodont (means- ‘socket-tooth’). The alveolar ligament lining alveolus firmly holds the roots of tooth. Superficially, the tooth is divided into crown (the visible part of tooth protruding above gum), neck (the line in between crown and root) and root (the portion of tooth embedded into alveolar bone of jaw). The keratinized tissue covering the alveolar bone in jaws is called gingiva or gum. The outermost layer of white to off-white tissue of the crown is called enamel. It is composed of crystalline calcium phosphate (hydroxyapatite) and the hardest material in body. The yellowish tissue underlying enamel is called dentin. It is less densely crystallized than enamel. The cavity in center of dentin is called pulp cavity. The pulp (soft tissue) in pulp cavity has blood and nerve supplies through root canal. Cementum, a white crystalline tissue, surrounds the dentine in root region.
Humans get two sets of teeth at two different stage of life- the milk teeth during early childhood and the permanent teeth in late childhood and adulthood. The dentition presenting two set of teeth at different stages in an animal is called diphyodont. The first set of teeth that appears in diphyodont animals is called primary teeth, deciduous teeth, temporary teeth or milk teeth and baby teeth (in hum
The mouth is constantly kept wet by continuous secretion of saliva by salivary glands. Based on the location in the oral cavity, the salivary glands are broadly classified into intrinsic and extrinsic salivary glands. The functional unit of salivary gland that forms and secretes saliva is called salivon. Each salivon consists of several acini and their associated ducts and tubules. Numerous intrinsic glands, mostly consisting of sero-mucous cells, lie embedded in the submucosa throughout the oral cavity. These glands actively secrete saliva all the time and primarily responsible for moistening the oral cavity. The intrinsic saliva accounts less than 10% of the daily salivary secretion.
Three pairs of extrinsic salivary glands, namely parotid, submandibular and sublingual, become active on thought, smell, sight and taste of food, thus primarily participate in digestion of food. These salivary glands lie external to the oral cavity, hence called extrinsic salivary glands. The parotid salivary gland is the largest among the extrinsic salivary glands. It lies beneath the external ear (earlobe) on either lateral sides and opens opposite to second maxillary molar through duct. It consists primarily of serous cells (pyramidal in shape with central nucleus) that protein-rich saliva consisting of salivary amylase, lysozymes, secretory antibodies IgA, etc. besides water and electrolytes. Its secretions account around 20% of the daily salivary secretion. The inflammation of parotids glands as a result of viral (mumps virus) infection is called mumps. The submandibular salivary gland, intermediary sized, is present in the medial mandible body along molar region, one at each lateral side. It consists of both the serous cells and mucous cells (cuboid to columnar cell with nucleus at its base). Its secretions also contain mucin besides the serous components of saliva. It opens along lingual frenulum below the tongue. Mucin (glycoproteins) in saliva lubricate the food and protects the oral cavity from abrasion (wear and tear of epithelium dur to friction between food and oral cavity). It secretes around 65-70% of the total daily salivary secretion. Sublingual salivary glands, the smallest among extrinsic salivary glands, lie embedded in the anterior floor of the oral cavity. It also consists of serous and mucous cells. Its secretion has relatively higher mucin content. It opens in anterior floor of the oral cavity through duct. It secretes around 7-8% of the total daily salivary secretion.
Saliva consists of approximately 99% water; the remaining 1% is constituted of electrolytes, proteins and very few cells. It’s a pH of 7.0 being hypotonic with presence of very small quantities of chloride, glucose, sodium and urea. The hypotonicity of saliva helps better solvation of food particles and enhanced taste perception.
Bicarbonate, calcium, chloride, magnesium, phosphate, potassium and sodium ions are present in the electrolyte fraction. The bicarbonate ions neutralize acidic contents in food. Relatively greater content of calcium and phosphate ions in saliva has crucial roles in maintaining the enamel structure. The protein fraction consists of enzymes [salivary amylase (approx. 40-50% of total salivary proteins), DNAse, RNAse, proteinase, lipases, lysozymes, peroxidase, etc.] and non-enzyme proteins [IgA, histatine, mucins, epidermal growth factors, etc.] Salivary amylase (a Ca2+ metalloenzyme), also known as Ptyalin, hydrolyzes starch during mastication of food in the buccal cavity. Relatively longer chewing time also produces little amount of glucose from starch hydrolysis, thus provides the perception of sweet taste of starch-rich food like loaves and bread, etc. Secretory antibodies IgA binds to antigens in food and help in their neutralization. Histatine is a defense peptide with bactericidal and fungicidal activities. The lysozyme (also known as muramidase or glycoside hydrolase) in saliva kills bacteria by hydrolyzing the peptidoglycan layer in bacterial cell wall. The saliva also contains gustin (a proteins) that mediates development of taste buds. Lactoferrin in saliva binds free iron and hinder its availability to bacteria, thus, it acts as bacteriostatic agent by retarding bacterial growth. Peroxidases in saliva also act as microbicide. Haptocorrin (also known as R-protein, R-factor, cobalophin or transcobalamin-I) secreted in saliva binds is a glycoprotein that binds to dietary vitamin B12. The resultant haptocorrin-VitB12 complex protects acid labile vit B12 from gastric juice during its transport into duodenum. In duodenum at neutral pH, pancreatic proteases hydrolyze Haptocorrin resulting vitB12 set free. Free vitB12 is further complex with gastric intrinsic factor and is absorbed in ilium.
Pharynx (Throat) and Esophagus:
Pharynx is a funnel shaped (widened at superior end and narrowed at its inferior base) muscular tube that connects the buccal (oral) cavity and nasal cavity to esophagus (oesophagus) and larynx, respectively. Epiglottis covers larynx while swallowing the food, thus preventing the entry of food into the it. However, by doing so, epiglottis also unblocks the opening to esophagus that leads the bolus to stomach.
Esophagus is muscular tube (25-30 cm long) that connects the pharynx (laryngopharynx) to stomach. It opening into the stomach is called cardiac orifice as being positioned adjacent to heart. Cardiac orifice consists of circular sphincter muscles that regulates the opening of esophagus into stomach. It further ensures that the stomach content does not flows back to esophagus.
Stomach is a strong muscular sac (roughly J-shaped) that temporarily stores bolus (for around 3-4 hours) simultaneously with aiding its partially chemical and mechanical digestion. Superficially, it is divided into four regions- cardiac region (cardia; as positioned near the heart), fundus region (the dome-shaped region superior to cardia), body (corpus; largest region) and pylorus region (relatively narrower region distal to corpus). The pylorus regions is further divided into pyloric antrum (relatively broader, immediately adjacent to corpus towards distal end) and pyloric canal (relatively narrower, at distal end of stomach). Pylorus is defined as the tubular connection between the stomach and duodenum. A band of circular sphincter muscles in pylorus, called pyloric (gastro-duodenal) sphincter, regulates the unidirectional flow to stomach content into duodenum.
The outmost layer of stomach wall, constituted of squamous epithelia and areolar connective tissue is called serosa. It secretes thin, slippery serosa fluid that minimizes the friction in the peritoneum when stomach expands while food enters into it. From outermost serous layer to gastric lumen, following tissue layers are present- muscularis externa, submucosa and mucosa layer. Muscularis externa consists of (from serosa towards lumen) longitudinal muscle, circular muscle and oblique muscle layers. These smooth muscles coordinately exhibit peristalsis when stimulated by presence of food. The submucosa, underlying muscularis externa, consists of connective tissues, blood supplies (arteries and veins) and nerves. The mucus layer consists of muscularis mucosae (a thin band of smooth muscles lying beneath submucosa) and lamina propia (facing gastric lumen). Lamina propia consists of numerous gastric glands. Gastric glands are present throughout the mucus layer of the stomach presenting site specific variations in the relative abundance of the constituent cells. These glands are specifically named cardiac gastric glands (cardiac glands) and pyloric gastric glands (pyloric glands) indicating their location in cardiac and pyloric region, respectively. However, the term ‘gastric (oxyntic) gland’ specifically refer to those glands present in body (corpus) and fundus regions. The longitudinal folds in mucosa layer of an empty stomach is called ‘rugae of mucosa’ or gastric rugae. The mucosal folds extend when food enters stomach causing its volume to increase from 50 mL (approx. volume of completely empty stomach) to around 3000- 4000 mL (approx. volume of fully extended stomach).
The gastric glands (oxyntic glands, pyloric glands, cardiac glands) secrete gastric juice (pH 0.9- 3.8) that principally contains HCl, pepsinogen and intrinsic factor along with other chemicals.
The superficial portion of the gastric gland facing the lumen is called ‘gastric pit’. It forms a depression in the mucosal surface through which the gastric secretion is released into lumen. The columnar epithelial cells that constitute gastric pit are named surface mucus cells. These cells also thoroughly line the gastric mucosal surface. The isthmus consists of regenerative (stem) cells that replenish all the cellular components of the gland. The neck cells (mucus neck cells) and surface mucus cells incessantly secrete large amount of thick, alkaline (due to presence of bicarbonate ions, HCO3–) mucus. The mucus forms a protective mucous gel layer on the mucosal surface and acts as an impermeable barrier to HCl and enzymes present in lumen. Bicarbonate (HCO3–) ions present in protective layer also neutralizes HCl that slowly diffuses into it. Moreover, the tight junctions between adjacent mucosal epithelial cells hinders the entry of proteolytic enzymes deep into mucosa by making the intercellular space an impermeable barrier. As a result, luminal HCl and enzymes do not reach the mucosal epithelium. Thus, the tissue layers of stomach remain unharmed by gastric juice. The base of gastric gland consists of the two glandular epithelial cells (chief cell and parietal cell) and several types of enteroendocrine (neuroendocrine) cells whose secretions altogether forms the gastric juice. Chief cell (zymogen or peptic cell) are the most abundant cells of the oxyntic (gastric) glands characterized by the presence of zymogen granules (stores pepsinogen). These cells secrete pepsinogen and gastric lipase. Pepsinogen is a zymogen (proenzyme), the inactive precursor of a proteolytic enzyme pepsin. Low pH of gastric juice autocatalyzes catalytically inactive pepsinogen into active pepsin. Pepsin is an aspartic protease with pH optima of 1.8- 3.5, gets inactivated (reversible) at pH 6.5 and denatured (irreversible) above pH 8.0. The enzyme hydrolyzes a small fraction (» 20%) of proteins is stomach. Gastric lipase (an acidic lipase similar to lingual lipase) has pH optima of 3.0– 6.0. Together, lingual and gastric lipase hydrolyze around 30% lipid contents of food. Parietal (Oxyntic or Delomorphous cell) cell secretes H+ (mediated by H+-K+ ATPase), Cl– (mediated by Cl– / HCO3– antiport) ions and intrinsic factor. High concentration of H+ and Cl– ions in gastric juice lowers the pH to 0.8 to 3.8. The low pH serves as an excellent acidic medium to kill most of the microbes ingested along with the food. The intrinsic factor is a glycoprotein that binds to dietary vitamin B12 and promotes its absorption later in small intestine.
The disruption of protective mucous gel layer of stomach is called gastric ulcer (observed as ruptured gastric mucosa). It may occur due to over production of HCl and pepsinogen in the gastric juice, invasion of gastric mucosa by Helicobacter pylori (an acid-resistant bacteria), consumption of nonsteroidal anti-inflammatory drugs like aspirin (NSAID inhibits production of prostaglandin- a compound that stimulates mucus and HCO3– production) or worsening of gastritis (inflammation and irritation of gastric mucosa; observed as red, swollen spot on gastric mucosa). It may also be caused by a Zollinger–Ellison syndrome (ZES)- a rare condition of gastrin- secreting gastrinomas of duodenum and pancreas. ZES triggers over-production of HCl by parietal cells, thus leading to HCl- mediated corrosion of gastric mucosa and gastric ulcers.
Enteroendocrine or neuroendocrine cells constitute a group of cells that secrete hormones and other chemical signaling molecules to regulate the overall process of digestion.
The stomach of an adult human produces around 2.5 L gastric juice (pH 0.9 – 3.8) each day. It consists of around 0.5 % solids dissolved in aqueous system. When stimulated, the smooth muscles of stomach wall exhibit peristalsis (peristaltic movement). The unidirectional wave-like, radially symmetric contractions and subsequent relaxations of smooth muscles of the alimentary canal is called peristalsis or peristaltic movement. Peristalsis causes mechanical breakdown of food particles (mechanical digestion) and subsequent mixing of bolus with gastric juice forming a semi-fluid slurry, called the chyme. Formation of chyme maximizes the interactions among food particles and enzymes (pepsin, gastric lipase) to enhances chemical digestion of food.
Pancreas is a tadpole-shaped gland (15 cm x 2.5 cm). It is divided into head (portion adjacent to duodenum), body (mid portion) and tail (tapered distal end). It acts as both exocrine and endocrine gland. The endocrine cells (glandular epithelial cells) are present as clusters mostly in the tail portion. The cluster of endocrine cells is called pancreatic islets or ‘islets of Langerhans’. These cells synthesize insulin, glucagon and somatostatin hormones and release them directly into the blood circulation. The exocrine glands constitute most of pancreatic tissue (around 99%) and secrete around 1.2- 1.5L alkaline pancreatic juice in a day. The acinar cell, characterized by the presence of extensive network of endoplasmic reticulum and zymogen granules, secretes zymogens and hydrolytic enzymes. The duct cell secretes sodium bicarbonate (NaHCO3) that neutralizes the acidic chyme in duodenum.
Numerous exocrine glands release their secretions into pancreatic duct (duct of Wirsung) that opens into duodenum. In the head regions, the common biliary duct opens into pancreatic duct. The junction of pancreatic and biliary duct, called hepatopancreatic ampulla (ampulla of Vater), appears relatively expanded (broader) than adjacent duct portions. The opening of ampulla into duodenum is called major duodenal papilla which opening and closure is regulated by hepatopancreatic sphincter (sphincter of Oddi). An accessory pancreatic duct branching off the main pancreatic duct opens into duodenum at minor duodenal papilla. The duct lacks sphincter muscle. Moreover, the duct does not join the biliary duct, thus releases only pancreatic juice, but not bile juice, into duodenum.
Pancreatic secretion has most significant roles in digestion in terms that it can hydrolyze all the four classes of biomolecules (protein, carbohydrate, lipid, nucleic acid). The secretion consists of NaHCO3, zymogens (trypsinogen, chymotrypsinogen, procarboxypeptidase A, procarboxypeptidase B, procolipase, proelastase, prophosphatase A2), hydrolytic enzymes (pancreatic amylase, pancreatic lipase, deoxyribonuclease and ribonuclease). The zymogens become active enzyme only after they reach duodenum. In duodenal content neutralized by NaHCO3, trypsinogen is converted into active trypsin by enteropeptidase (also known as enterokinase, secreted by duodenal mucosa). The resultant trypsin also acts on trypsinogen converting it into trypsin. The conversion of trypsinogen into trypsin by enteropeptidase or trypsin is called trypsinogen autoactivation. Trypsin further converts rest of the zymogens into their respective active forms. Altogether the active proteolytic enzymes and other hydrolytic enzymes chemically digest various types of proteins, carbohydrates, lipids and nucleic acids.
Gall Bladder and Bile Juice
Gall bladder is a pear-shaped organ that stores and concentrates bile. Bile is synthesized in liver and released through common hepatic duct. The gall bladder connects to common hepatic duct through cystic duct at its neck region. This ducts provides a route of entry of bile juice into gall bladder for storage and concentration and subsequent release during digestion. When need, concentrated bile juice is released into common biliary duct (biliary duct), an extension of common hepatic duct. It later joins the pancreatic duct at hepatopancreatic ampulla and released in duodenum through major duodenal papilla.
Bile juice (around 97% water by mass) is alkaline, dark green to brownish- yellow colored. It consists of bile salts (bile acids), bile pigments, lipids (cholesterol, fatty acids, lecithin, etc.), and various electrolytes (HCO3–, Na+, K+, Ca2+, Cl– etc.). Both the primary bile acids (cholic acid, chenodeoxycholic acid) and secondary bile acids (deoxycholic acid, lithocholic acid) are amphipathic molecules and act as surfactant and emulsifying agent. They micellize fats in intestine. Formation of micelle increases the accessibility of lipases to lipids, helps in hydrolysis of lipids and its subsequent absorption. Around 90-95% bile acids are absorbed in small intestine and transported back to liver for recycling. Bile pigments bilirubin (orange to yellow colored) and biliverdin (green colored) provide the characteristic brown color of the stool.
Small intestine is around 3.0 m long with a luminal diameter of 2.5 cm. It is divided into three regions namely duodenum, jejunum and ilium. The intestinal epithelium exhibits circular folds (rugae or plicae), villi and microvilli. Villi are finger-like or tongue-shaped projections (approx. 0.5– 1.0 mm high) of the intestinal mucosa into lumen. It has rich supply of blood and lymphatic vessels that are crucial for absorption of nutrients and their subsequent transportation to liver. Microvilli are hair-like cytoplasmic projections of the enterocytes of mucosal epithelial at the luminal face. The folds and projections of the mucosal surface forms a functional surface area of around 30 m2 (compared to theoretical value of 0.047 m2). Between the villi in both the small and large intestine lies numerous pits, called crypts of Lieberkuhn or intestinal crypts. These are tubular intestinal glands similar to gastric glands. These glands are composed of several types of cells, namely enterocyte (has extensive luminal brush border, present throughout mucosal epithelium of the intestine), neuroendocrine cell (ex- argentaffin cell, at the base of gland; secretes hormones), goblet cell (secretes mucus), tuft cell (senses chemical stimuli in lumen), microfold cell (M cell, provides passive immunity in MALT and GALT, Payer’s patch), Paneth cell (at the base of gland; provides passive immunity, secretes lysozymes, defensins and other antimicrobial chemicals; absent in large intestine), stem cells (tissue regeneration) and cup cells (function unknown). The relative abundance of different cell types varies depending on the regions of the intestine. Peyer patches, small cluster of lymphatic nodules, are visible with naked eyes in ilium and post-ilium intestine.
Besides secreting mucus, the enterocyte also synthesizes several digestive enzymes. It includes glycosidases (glucoamylase, lactase, maltase, isomaltase, sucrase, trehlase, etc.), peptidases (aminopeptidases, dipeptidases, enteropeptidase, endopeptidases, carboxypeptidases, g-glutamyl transferase, etc.), and phosphatases, etc. Interestingly, these enzymes are retained at the brush-border with help of specific peptides (thus, called brush border enzymes), but not released into secretions. So, these enzymes hydrolyze their substrates only when the luminal content is in direct contact with the brush border.
Duodenum (means- length equal to 12 fingers) is the first and smallest part. Duodenal submucosa has duodenal glands (Bruner’s gland; secretes alkaline mucus) that releases its secretions to the base of intestinal glands. The neutralization and subsequent digestion of acidic chyme entering duodenum is facilitated by pancreatic, bile and intestinal juice combinedly. Intestinal juice or succus entericus is the overall secretion of intestinal mucosa.
Increase in pH (near 7.0) inactivates gastric enzymes (pepsin, gastric lipase). Pancreatic enzymes further hydrolyze partially digested molecules into oligomers and monomers. Jejunum is the second part of small intestine having rich blood supply. Most of final digestion (hydrolysis yielding monomers) is carried out by the brush border enzymes in jejunum. Moreover, it’s also the region where most of the nutrients are absorbed.
Lingual and gastric lipase are acidic lipase, i.e. they catalyze lipid hydrolysis only under acidic conditions of the stomach. Moreover, these enzymes also exhibit higher hydrophobicity and tend to form random aggregates. Owing to their hydrophobicity, these enzymes can directly associate with lipid droplets (hydrophobic) in emulsions (milk, gastric juice, etc.) without requiring the presence of bile salts. The resultant enzyme-lipid association provides the medium for enzyme catalysis as both the enzyme and substrates share the same hydrophobic phase. The enzymes work on medium and long chain triacylglycerides. The remove only one fatty acid chain from triacylglycerides producing one free fatty acid chain and a diacylglycerol. Altogether, the acidic lipases digest around 30% fats (lipids) in stomach within first 20 minutes of ingestion. In contrast to the acidic lipases, the pancreatic lipase (pancreatic triacylglycerol lipase) is an alkali lipase, exhibits catalysis in neutral pH and is hydrophilic (soluble in aqueous medium). It requires the lipid droplets to be emulsified into an aqueous medium with the help of bile salts. Pancreatic lipase in association with its cofactor colipase acts on the emulsified micelles to hydrolyze triacylglycerides. It removes two fatty acid chain from triacylglycerides producing two free fatty acid chains and a 2-monoacylglyceride (fatty acid chain at C2 of glycerol).