The histology and histopathology of the colon Introduction The colon forms part of the large intestine, and is about 1.5-1.8 m long according to (Vanputte et al. 2016). It consists of four parts: ascending, transverse, descending and sigmoid as can be seen in figure 1. The food in the large intestine takes at least 18-24 hours to pass through; as a result the movements of the colon are more sluggish than that of the small intestine. Once the food has been digested and absorbed in the small intestine, it enters the colon through the ileocecal valve. This valve stops the material from flowing back into the small intestine, by separating the small intestine from the cecum.  Figure 1: Showing the large intestineThe main function of the colon is to recover the fluids and salts from faeces, and to process the waste product until voiding. For the chyme to be converted into faeces a number of steps are taken in the colon: firstly, the ascending colon must carry the faeces from the cecum to the transverse colon. There the chyme is further broken down by micro-floral metabolism.The transverse colon is inhabited by a variety of commensal bacteria; these can reproduce rapidly, forming 30% of the dry weight of faeces according to (Vanputte et al. 2016). One of the important functions of the colonic bacteria is to synthesize vitamin K, which is passively absorbed in the colon as stated by (Vanputte et al. 2016). During the fermentation process (breakdown of waste by microorganisms), as metabolic waste products acids are secreted by colonic bacteria, to maintain the pH balance a molecular pump found in the epithelial cells of the colon exchanges HCO 3 – for Cl -. Another pump exchanges sodium (Na+) for hydrogen (H +). 6-7% of water left in the lumen of the colon diffuses out through osmosis as Na+ and Cl– move into the epithelial.The descending colon (left colon) is where the final reabsorption of any remaining intraluminal fluids and the processing of waste products are done before voiding. According to (Vanputte et al. 2016) about 1500mL of chyme enters the cecum each day; however 90% of it is reabsorbed leaving 80-150mL of faeces to be defecated.Food is pushed towards the rectum by two main mechanisms: involuntary contraction of smooth muscle called peristalsis and a variety of local acting hormones some of which are secreted by neuroendocrine cells found along the gastrointestinal tract. Both of these mechanisms are controlled by the autonomic nervous system. The autonomic regulation of certain glandular secretions and smooth muscle of the gut as well as the blood vessels are all mediated by the enteric nervous system (ENT). Mass movements coordinated by local reflexes in the ENS moves the contents a considerable distance towards the anus. These strong contractions (mass movements) occur 3-4 times each day at spaced intervals. Contractions of the smooth muscle is initiated by pacemaker cells known as interstitial cells of Cajal as stated by (Young et al. 2014).This is controlled by the autonomic nervous system especially the parasympathetic nervous system. Stretch of the rectum initiates action potentials which travel up to the cerebrum where awareness of the need to defecate is realized. The muscularis externa of the colon compared to the small intestine is made up of circular (continuous) and longitudinal muscle layer. The circular muscle layer of the colon is complete, meaning it surrounds (envelopes) the large intestine, whereas the longitudinal section is incomplete.  The longitudinal muscle layer can be divided into three separate bands, called the teniae coli.The contraction of the teniae coli causes the colon to form pouches called haustra, which gives the colon the appearance of having a chain of small sacs according to (Vanputte et al. 2016). The haustra disappear during contractions of a segment and their location moves, this helps to slow the passage of the faecal material to facilitate absorption. On the outer surface of the colon, small fat filled connective tissue pouches called epipolic appendages can be found, there exact function is unknown according to (Young et al. 2014); however they are thought to aid in absorption of nutrients and act as cushions for the colon during peristalsis.The mucosal lining of the colon is made up of simple columnar epithelium cells, this epithelium does not form folds or structure like villi instead has numerous straight tubular glands called crypts. The crypts according to  are similar to the intestinal glands in that they are made up of three different cell types – absorptive, goblet and granular cells. Underneath the crypts, according to (Vanputte et al. 2016) you can find undifferentiated and endocrine cells. These stem cells found at the base of the glands continuously replace the epithelium.The lamina propria fills the space between the glands, extending into the submucosal layer; it contains numerous blood vessels into which water is absorbed as stated by (Ersoz et al. 2016). The lamina propria also contains collagen, lymphocytes and plasma cells these form part of the defence mechanism against pathogens along with the intraepithelial T lymphocytes according to (Young et al. 2014).Tall columnar absorptive cells contain microvilli, which produce digestive enzymes and absorb digested food, they also have an oval based nuclei. In contrast globular cells which produce protective mucus contain small and condensed nuclei. Granular cells help protect the intestinal epithelium from bacteria and the goblet cells produce a protective mucus.The major difference between the small and large intestine according to… is that the globular cells are dominant than the other 2 cell types. This is because there is little need for enzymatic activity in the colon, whereas mucus secreted by goblet cells is needed to stick the faecal matter together. Rhythmic contractions expulsion of mucus to prevent clogging of the glands as stated by (Young et al. 2014) Tactile stimuli (sensation of texture) and irritation of the colon wall according to (Vanputte et al. 2016) triggers local eccentric reflexes that increase mucous secretion. Parasympathetic stimulation increases the rate of secretion by goblet cells.There are many major disorders affecting the large intestine, the ones I will be addressing include Crohn’s disease, diverticulosis and carcinoma of the colon.Crohn’s diseases is an autoimmune inflammatory diseases of the intestine usually affecting the terminal ileum and colon, according to (Vanputte et al. 2016).  It can affect different parts of the gastrointestinal tract (GIT).The microscopic appearance of Crohn’s disease varies according to the stage of the disease as stated by (Stevens et al. 2009). In early stages of the disease the affected part of the intestine shows marked thickening of sub-mucosa and mucosa layer, which leads to a loss of normal transverse folds and small ulcerations form which overtime develop into fissures as stated by… There is also a loss of crypt and the mucosal layers get all distorted as can be seen in figure 2.Figure 2: Image showing Crohn’s disease in the gastrointestinal tract. Crypt absence, mucosal ulceration, structures of the mucosal layers all distorted.The disease is not continuous, normal tissue may be present between the disease segments. Adipose alteration can also be seen the serosal layer surface of the colon can become enveloped in mesenteric adipose tissue (creeping fat).  The exact cause of the disease is unknown however studies have shown these factors to play a role in its development infectious, autoimmune and hereditary for example siblings of affected individuals have been found to be at a higher risk.To identify Crohn’s disease, some of the advanced techniques used include colonoscopy or capsule endoscopy, both of these tests give a full view of the entire colon, with colonoscopy a sample of tissue may also be taken to help confirm diagnosis. Clusters of inflammatory cells called granulomas, as can be seen in figure 2 if present help confirm the diagnosis.Diverticulosis is a disease in which small pouches of mucosa or sub-mucosa form in the colon that bulges outwards as can be seen in figure 4. The exact cause of the disease is unknown however several studies according to … have suggested a low diet in fibre, (obesity) patients with a large waist circumference and smokers have an increased chance of catching the disease. Treatment of diverticulosis involves taking antibiotics and having a diet high in fibre according to … A recent study has proposed a treatment for primary and secondary preventation of AD, by the use of refaximin and mesalazine  according to (Carabotti and Annibale 2018).Carcinoma of the colon also known as bowel cancer, are malignant tumours which arise in glandular epithelium. According to … intensive research has shown a number of risk factors to be involved in the development of colon carcinoma such as long standing ulcerative colitis (form of inflammatory disease affecting the colon), Gardner syndrome (a genetic abnormality leading to numerous  benign tumours (adenomas) in the bowel) and a diet low in fibre.Figure 3, shows a classic example of adenocarcinoma in the colon. The epithelial cells form disorganised abnormal glands that penetrate into the adjacent tissues. Tumour which has not spread far and wide can usually be treated by surgery, whereas if the tumour has metastasised spread far and wide there could possibly be no treatment.To aid in the diagnosis of diseases of the colon, and advanced techniques such as colonoscopy mentioned above staining is used as stated by (Trivedi and Braden 2013). To identify specific epithelial changes and in the mucosal layer; the four most common staining methods used are vital staining, contrast staining, reactive staining (e.g. Congo red) and tattooing as stated by… Figure 3: Image taken from (Young et al. 2014) showing adenocarcinoma of the colon. In the image malignant glands (G) has invaded into the muscularis propria. Mu (smooth muscle) / N (dead tissue).Vital staining, this method involves colouring of living tissues/cells, in this case for the colon Alcian blue or methylene blue is used, the mucins contain sulphated and carboxyl ester groups which get stained by the Alcian blue as can be seen in figure 4. The staining can be restricted by digestion of hyaluronic acid. This can assist in the identification of the primary cause of disease as stated by (Trivedi and Braden 2013).Cresyl violet can be combined with methylene blue to detect early malignant changes in the colon. It can also be used as an intra-vital stain for the detection and characterization of early upper gastrointestinal cancers according to (Trivedi and Braden 2013).Figure 4 Showing the histology of the colon stained with Alcian blue, image taken at 10X magnification.As part of cancer diagnosis, contrast staining, usually H&E is often used, as it displays a range of nuclear, cytoplasmic, and extracellular matrix features; which can be very useful when studying the morphological changes, which may form as part of the disease as stated by (Fisher et al. 2008). Haematoxylin has a blue-purple colour and stains nucleic acids as blue, whereas eosin stains the cytoplasm and extracellular matrix as pink which can have varying degrees of pink staining as can be seen in figure 5.Figure 5 Cross section of the colon showing the outer surface and inner surface of the colon stained with H&E, image taken at 10X magnification.References:Carabotti, M. and Annibale, B., 2018. Treatment of diverticular disease: an update on latest evidence and clinical implications [online]. Available via: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866096/ [Accessed 16 November 2018]Ersoz, F., et al., 2016. Colonic mucosal pseudolipomatosis: Are we aware of it? [online], 32 (2), 90-92. Available via: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942168/ [Accessed 16 November 2018] Fisher, A.H., et al., 2008. Hematoxylin and eosin staining of tissue and cell sections [online]. Available via: https://www.ncbi.nlm.nih.gov/pubmed/21356829 [Accessed 16 November 2018]Stevens, A. et al., 2009. Core pathology. 3rd ed. Edinburgh: Mosby Elsevier.Trivedi, P.J and Braden, B., 2013. Monthly Journal of the Association of physicians. Indication, stains and techniques in chromoendoscopy [online], 106 (2), 117-131. Available via: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550597/ [Accesses 16 November 2018]VanPutte, C.L. et al., 2016. Seeley’s anatomy & physiology. 11th ed. New York: McGraw-Hill.Young, B. et al., 2014. Wheater’s functional histology: a text and colour atlas. 6th ed. Philadelphia: Churchill Livingstone.