Human Gastrointestinal Tract (GIT)

The Human GIT

• The human gastrointestinal tract (GIT) is responsible for digestion in the upper section and absorption in the lower section of ingested molecules.
• Upper GIT consists of the Mouth, Oesophagus, Stomach and Duodenum.
• Lower GIT consists of the Small Intestine: Duodenum, Jejunum, Ileum and Large Intestine: Caecum, Auxiliary Colon Ascending Colon, Descending Colon &, Anus.

The GIT Wall

• Mucosa is the absorptive and secretory layer made up of simple epithelium cells and a thin connective tissue with specialized goblet cells that secrete mucus with Villi and Micro Villi.
• Sub-mucosa that is vascularised is thick, highly vascular and serves the mucosa consisting of absorbed elements that pass through the blood vessels of the sub-mucosa as well as glands and nerve plexuses.
• Muscularis is responsible for segmental contractions and peristaltic movement, made of 2 layers of muscle (inner circular and outer longitudinal layers of smooth muscle).
• This layer of muscle moves food and churns it with digestive enzymes.
• Serosa, the last layer, is the protective layer. It is composed of avascular connective tissue and simple squamous epithelium.
• Serosa secretes lubricating serous fluid, and is the visible layer on the outside of the organs.

Diarrhoea

• Defined as having three or more loose, liquid, or watery stools daily, or having more stools than normal.
• Acute diarrhoea lasts 5-10 days and chronic is over 10 days.
• Symptoms often include abdominal pains, low fever, nausea, and vomiting (Gastroenteritis).
• Approximately 3.5 million deaths are attributable to diarrhoea, as determined by the World Health Organization (WHO) per year.
• 80% of diarrhoea related deaths are children under the age of 5.
• Children are more susceptible to the complications of diarrhoea because a smaller amount of fluid loss leads to dehydration, compared to adults.

Mechanisms of Diarrhoea

• Secretory Diarrhoea is an increase in the active secretion, or there is an inhibition of absorption with little to no structural damage.
• The most common cause of secretory diarrhoea is a cholera toxin that stimulates the secretion of anions, especially chloride ions where sodium is carried, along with water, to maintain a charge balance in the lumen.
• Intestinal fluid secretion is isotonic with plasma even during fasting. Osmotic Diarrhoea occurs when too much water is drawn into the bowels.
• This can be the result of indigestion, in which the nutrients are left in the lumen to pull in water or osmotic laxatives.
• Exudative Diarrhoea occurs with blood and pus present in the stool, and in inflammatory bowel diseases.
• Crohn's disease or ulcerative colitis, and other severe infections such as E. coli or other forms of food poisoning are causes of exudative diarrhoea.
• Motility-related Diarrhoea occurs due to the rapid movement of food through the intestines (hypermotility) that does not allow enough time for absorption of sufficient nutrients and water due to diabetic neuropathy, hyperthyroidism, or Bowel removal.
• Inflammatory Diarrhoea (viral) occurs due to damage of the mucosal lining or brush border, which leads to a passive loss of protein-rich fluids, and a decreased ability to absorb fluids caused by bacterial, VIRAL, parasitic infections, autoimmune problems, and Colon cancer.
• Dysentery is where blood is visible in the stools, and is a trace of an invasion of bowel tissue caused by Shigella, Entamoeba histolytica, and Salmonella.

Complication of Diarrhoea

• Dehydration from loss of electrolytes (sodium, chloride, potassium, and bicarbonate) through liquid stools, vomit, sweat, urine, and breathing.
• Severe dehydration has at least two of the following signs: lethargy, unconsciousness, sunken eyes, unable to drink or drinks poorly.
• Severe dehydration causes the skin pinch to go back very slowly.
• Some dehydration has two or more of the following signs: restlessness, irritability, sunken eyes and drinks eagerly, thirsty.
• No dehydration does not have enough signs to classify as some or severe dehydration.

Clinical Types of Diarrhoea

• Acute watery diarrhoea [Acute Gastroenteritis (AGE)] lasts hours or days and mostly caused by viruses viruses (viral gastroenteritis).
• Some bacteria are also causing agents.

Viruses of Acute Gastroenteritis (AGE)

• Gastroenteritis: Inflammation of the lining stomach and small and large intestines.

• Viral gastroenteritis is an infection that results in vomiting or diarrhoea and called the "stomach flu", however, it is not influenza.

• Viral pathogens are the most common cause of gastroenteritis.

• AGE viruses: Reoviridae (Rotavirus), Calciviridae (Norovirus, Sapovirus), Adenoviridae (Adenovirus 40, Adenovirus 41), Astroviridae (Astrovirus).

• Other GIT viruses: Poliovirus, Coxsackie A & B, Echoviruses, Enteroviruses 68-71, Hepatitis A virus, Hepatitis E virus, Adenoviruses 1-39, Reoviruses.

• Common Symptoms of viral gastroenteritis: Nausea, Vomiting, Watery diarrhoea.

• Common Signs of dehydration due to viral gastroenteritis: Decreased urine output, Dark colored urine, Dry skin, Thirst and Dizziness.

• Other symptoms of viral gastroenteritis include Headache, Low grade fever, Chills, and Stomach-ache.

• Signs of dehydration in young children includes Dry diapers , Lack of tears, Dry mouth, Drowsiness, and Sunken fontanel.

• Viruses that cause gastroenteritis are transmitted through close contact with infected persons.

• Individuals may also become infected by eating or drinking contaminated foods or beverages via oral-faecal route.

• All ages and sexes can be affected but infants, children, and the elderly, are most at risk for dehydration.

• Immune-compromised people are at risk for dehydration with greater vomiting or diarrhoea.

Rotavirus - Reoviridae

• Reoviridae are Respiratory-Enteric-Orphan Viruses with Genus Orthoreovirus, Orbivirus, Rotavirus, Coltivirus.
• Shape & size: naked, icosahedral symmetry, diameter = 70-80 nm, double shelled.
• Genome: 10-12 segmented dsRNA where Re-assortment of gene segments creates hybrid viruses.
• Rota is the Latin word for wheel, and there are 9 species.
• Species A (>90% of human rotavirus infections); B, C, D, E (found in pigs), F, G, H, I, J.
• Transmission: faecal-oral spread, close contact and by fomites (toys, environmental surfaces contaminated by stool), and respiratory droplets.
• Antigen detection in stool sample by ELISA or immunochromatography and molecular detection of viral genome (PCR) are used for diagnosis.
• 3 classified Serogroups of HRV are key.
• Treatment & Prevention: supportive, 3 oral RV vaccines are licensed.
• Ecology: very stable and may remain viable in the environment for weeks or months if not disinfected.
• Very stable and may remain viable in the environment for weeks or months if not disinfected and moderately resistant to heat, organic solvents and non – ionic detergents.
• Rotavirus is stable at a wide range of pH, infecting many species of mammals (cows and monkeys) with Animal strains that are antigenically distinct from human strains.
• Virus is ingested via the faeco-oral route and VP4 spike protein binds to receptors on the small intestinal epithelial cells (enterocytes), enhancing viral entry.
• The virus enters the cell via endocytosis and uncoats inside the cytoplasm and replication occurs in viral factories called viroplasms.
• NSP4 acts as an enterotoxin, stimulating chloride and water secretion, leading to secretory diarrhoea.
• NSP4 also triggers neural reflexes, increasing gut motility and further exacerbating fluid loss.
• Villous Atrophy and Malabsorption occurs when infected enterocytes are destroyed, leading to villous blunting and loss of absorptive surface area, resulting in malabsorption of nutrients and fluids.
• Major cause of severe diarrhea worldwide among children aged <5 years including Elderly and immuno-compromised also at risk and found in the GIT & stool of infected humans.
• Rotavirus is in GIT & stool of infected humans which is spread worldwide. Harmattan and Winter.
• Estimated to have caused the death of 185 390 children 5 years of age every year and has a mortality rate of 66.9/100,000 population <5 years old compared with a global rate of 20.3/100 000 population.

Caliciviridae (Norovirus & Sapovirus)

• Human Noroviruses (HuNoVs) are estimated to be responsible for 60 to 80% of all human gastroenteritis.
• Infections have become an increasing problem in healthcare institutions such as nursing homes and hospitals because outbreaks often result in closed wards:
• Causes are Small (27-40nm), non-enveloped, icosahedral viruses that possess a linear, +ve sense, ssRNA genome.
• Diagnosis: Differential, RT-PCR, ELISA, Immunochromatography (possibility)
• Treatment: Oral fluid and electrolyte replacement therapy, buscopan (for abdominal cramps) are key.
• Transmission: Person to person, food, water, and contaminated surface
• Previously estimated to be as high as 212,000 deaths per year in children under 5 in developing countries.
• Norovirus enters the body via ingestion and resists gastric acid and bile salts, and binds to histo-blood group antigens (HBGAs) on epithelial cells of the small intestine.
• Infects the small intestinal enterocytes in the cytoplasm, and it replicates positive-sense single-stranded RNA genome. Newly synthesized virions are released and spread within the gastrointestinal tract.
• Epidemiology in persons under 18, but outbreaks occur more in temperate countries during the winter.

Sapovirus

• Formerly known as Sapporo-like viruses where the virion contains approximately 7,500 nucleotides. of ssRNA (+). Genetically classified into 5 genotypes (GI-V).
• Family: Caliciviridae that causes gastroenteritis in humans and swine caused by Genotypes I, II, IV, and V and Genotype III being a porcine pathogen.
• Diagnosis: ELISA, RT-PCR
• Sapovirus have been implicated in acute sporadic gastroenteritis and in gastroenteritis outbreaks primarily children with Genotypes I and II being implicated as cause of greatest outbreaks.

Adenovirus

• Family: Adenoviridae with name origin.
• The Adenoid cells have capsids medium-sized (90-100 nm), non-enveloped and icosahedral symmetry.
• dsDNA Genome categorized in 7 species (A-G) with 52 serotypes in total.
• Diagnosis: Antigen detection, PCR, virus isolation and serology where testing is completed by hemagglutination-inhibition and/or neutralization with type-specific antisera or by molecular methods.
• Most common Adenovirus are Adenovirus 40 and Adenovirus 41 via fecal-oral spread, close contact, fomites, contaminated food and water and respiratory droplets.
• Treatment: supportive, with no available vaccine.
• Adenoviruses are relatively resistant to chemical and physical agents/adverse pH conditions and can live for a long time outside the body.

Astrovirus

• Virology: Non-enveloped, star-like (under EM), icosahedral viruses; with +ve sense, ssRNA genome.
• 2nd most common cause of diarrhoea in young children and was discovered in 1975 and is transmitted through the fecal-oral route.
• The virus is resistant to acidic pH and bile salts, enabling survival in the stomach and passage into the small intestine where it it binds to specific receptors on enterocytes, facilitating viral entry.
• Infects and replicates in mature enterocytes of the intestinal villi, mainly in the jejunum and ileum does not cause severe enterocyte destruction, but it still disrupts intestinal function.
• limited to the small intestine – mature epithelial cells near the villi tip; that is more extensive in the jejunum than the duodenum.
• Cases are treated with self-limiting, oral or IV fluid resuscitation and immunoglobulin.