What Is The Basic Molecular Mechanism Of Diarrhea?

Diarrhea is a common symptom of various gastrointestinal illnesses, particularly in underdeveloped regions. It is caused by increased secretion or decreased absorption of fluids and electrolytes, with certain ion transport processes being particularly associated with diarrhea. These include chloride channels (CFTR and CLCA) and the Na+/H+ exchange isoform (NHE3) involved in Na+ absorption.

Diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both. The secretory mechanism occurs when there is a stimulation of secretion mediators by exotoxins produced by bacterial pathogens (Vibrio cholerae, enterotoxigenic). Secretory diarrhoeas are caused by certain bacterial and viral infections, inflammatory processes, drugs, and genetic disorders.

There are two principal mechanisms by which watery diarrhea occurs: (i) secretion and (ii) osmotic imbalance. Intestinal infections can cause diarrhea by drawing too much water into the bowels, such as excessive sugar or salt consumption. Osmotic diarrhea occurs when secretion of water into the intestinal lumen exceeds absorption. Many millions of people have died of secretory diarrhea associated with pathogenic bacteria and viruses, allergens, and disruptions to bile acid homeostasis.

Secretory diarrheas are common and include those induced by pathogenic bacteria and viruses, allergens, and disruptions to bile acid homeostasis. These effects can be caused by inhibition of Na+ absorption (decreasing intestinal water and electrolyte absorption) or stimulation of Cl−/HCO 3 − secretion.

The presence of unabsorbed bile acids in the colon is believed to induce diarrhea through various mechanisms, including stimulation of fluid, mucus, or sodium. Understanding the cellular and molecular mechanisms underlying diarrhea associated with different infectious agents, such as bacteria and viruses, is crucial for public health in underdeveloped regions.

What is the biochemical mechanism of diarrhea?

Diarrhoea is a condition resulting from excessive secretion and impaired absorption of fluid and electrolytes across the intestinal epithelium. The movement of fluid between the intestinal lumen and blood is driven by the active transport of ions, mainly Na+, Cl−, HCO 3−, and K+, and solutes, mainly glucose. Fluid absorption or secretion involves the coordinated activity of membrane transporters located on the apical and basolateral epithelial membranes.

In secretory diarrhoeas, both absorption and secretion can occur in the same epithelial cells, with secretory processes predominating in crypts and absorptive processes in villi. Luminal and basolateral membrane transporters and intracellular signaling mechanisms are involved in intestinal fluid absorption and secretion by enterocytes. Some bacteria secrete enterotoxins that increase intracellular cyclic nucleotides, resulting in Cl− secretion and inhibition of NHE3 and Na+ absorption. Invasive bacteria cause a tissue inflammatory response involving recruitment of immune cells and release of cytokines, resulting in intracellular Ca2+ signalling.

Fluid absorption is driven by the active transport of Na+ across the epithelium with parallel Cl− or HCO 3− absorption. The electrochemical driving force for this process is the basolateral Na+/K+ -ATPase. In the small intestine, fluid absorption is facilitated by the sodium/hydrogen exchanger 3 (NHE3), sodium/glucose cotransporter 1 (SLC5A1), and Cl−/HCO 3− exchanger (DRA (SLC26A3) and PAT1 (SLC26A6)). Electroneutral fluid absorption is carried out by the coordinated activity of NHE3 with Cl−/HCO 3− exchangers (PAT1 for HCO 3− absorption and DRA for Cl− absorption in the jejunum and colon).

In the colon, absorption is facilitated by the epithelial Na+ channel and short-chain fatty acid transporters. Intracellular messengers, including Ca 2+ and cyclic nucleotides such as cAMP and cGMP, inhibit the activity of apical Na+ transporters.

What causes diarrhea on a cellular level?

In the secretory form of diarrhea, bacterial and viral infections are the common causes. In this instance, the watery stool results from injury to the gut epithelium. Epithelial cells line the intestinal tract and facilitate water absorption, electrolytes, and other solutes. Infectious etiologies cause damage to the epithelial cells, which leads to increased intestinal permeability. The damaged epithelial cells cannot absorb water from the intestinal lumen, leading to loose stool.

History and Physical. In developed regions, acute diarrhea is almost always a benign, self-resolving condition that subsides in a few days. The duration of illness and clinical presentation vary depending on the etiology of diarrhea and the host factors. For instance, rotavirus diarrhea commonly presents with vomiting, dehydration, and more workdays lost than nonrotavirus diarrhea.

Knowledge of certain diarrhea-associated factors, such as volume, consistency, color, and frequency, helps distinguish the source. The following table outlines these characteristics that can be utilized to narrow down the list of differential diagnoses:

How does diarrhea occur at the molecular level?

Diarrhea caused by enteric infections is a significant global health issue, with an estimated 2-4 billion episodes occurring annually, particularly in infants. This review explores the cellular and molecular mechanisms associated with diarrhea, which are linked to bacteria, viruses, and parasites. Bacterial pathogens, such as Vibrio cholerae, Clostridium difficile, and Shigella species, have been used as model organisms for this review. Recent studies have focused on the alteration of epithelial ion absorption in viruses and parasites, including rotavirus, norovirus, and astrovirus infections. Parasites, on the other hand, have a greater complexity and can create molecules similar to those produced by the host, such as serotonin and PGE 2. The underlying mechanisms of infectious diarrhea include alterations in ion transport and tight junctions, as well as virulence factors that alter these processes through direct effects or indirectly through inflammation and neurotransmitters.

The gastro-intestinal tract has a significant capacity to absorb fluid and electrolytes, but enteric pathogens can alter this balance, leading to diarrheal disease. Some transporters, such as sodium-dependent glucose transporter (SGLT1), Na+/H+ exchanger isoform 3 (NHE3), and the apicalCl −/HCO 3 − exchanger, are tightly coupled with water movement. The classical secretory diarrhea caused by cholera toxin is due to cAMP-dependent activation of the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl-channel. Changes in Ca 2+ levels can also increase the activity of the calcium activated chloride channel (CLCA).

What is the physiological basis of diarrhea?

Diarrhea Secondary to Altered Mucosal Transport or Secretory Dysfunction. Along the small bowel both absorption and secretion of fluid and electrolytes occur; normally there is net absorption. Diarrhea can result when either decreased absorption or increased secretion occurs.

Classic secretory diarrhea is caused most commonly by toxins produced by various bacterial pathogens such as Staphylococcus, Escherichia coli, and Vibrio cholerae. Certain hormones, when produced in excess, such as vasoactive intestinal peptide (VIP) and gastrin produced by pancreatic tumors, and calcitonin produced by medullary cancer of the thyroid, can also stimulate excessive mucosal secretion, leading to diarrhea.

In the case of cholera and VIP tumors, this loss of net absorption across the intestinal mucosa is thought to be mediated by an increased concentration of certain mucosal cell cyclic nucleotides. Experimental evidence suggests that elevated levels of cyclic AMP can stimulate net anion secretion, thus causing diarrhea.

Secretory diarrhea occurs independent of dietary intake and does not subside with fasting. In addition, there is no significant stool osmotic gap, defined as:

What is the mechanism that causes diarrhea?

Pathophysiology. Diarrhea results from reduced water absorption by the bowel or increased water secretion. Most acute diarrheal cases have an infectious etiology. Chronic diarrhea is commonly categorized into 3 groups: watery, fatty (malabsorption), or infectious. Another way of classifying the pathophysiology of diarrhea is into secretory and osmotic forms.

Lactose intolerance causes watery diarrhea, which causes increased water secretion into the intestinal lumen. Patients typically have symptoms of bloating and flatulence along with watery diarrhea. The enzyme lactase breaks down lactose in the intestine. The byproducts are readily absorbed by the epithelial cells. When lactase is decreased or absent, lactose cannot be absorbed and remains in the gut lumen. Lactose is osmotically active, and it retains and attracts water, leading to watery diarrhea.

Common causes of fatty diarrhea include celiac disease and chronic pancreatitis. The pancreas releases enzymes that are necessary for the breakdown of food. Enzymes are released from the pancreas and aid in the digestion of fats, carbohydrates, and proteins. Once broken down, the products are available for uptake in the gut. Patients with chronic pancreatitis have insufficient enzyme release, leading to malabsorption. Symptoms often include upper abdominal pain, flatulence, and foul-smelling, bulky, pale stools due to malabsorption of fats.

How does diarrhea happen biologically?

In the latter stages of human digestion, ingested materials are inundated with water and digestive fluids such as gastric acid, bile, and digestive enzymes in order to break them down into their nutrient components, which are then absorbed into the bloodstream via the intestinal tract in the small intestine. Prior to defecation, the large intestine reabsorbs the water and other digestive solvents in the waste product in order to maintain proper hydration and overall equilibrium. Diarrhea occurs when the large intestine is prevented, for any number of reasons, from sufficiently absorbing the water or other digestive fluids from fecal matter, resulting in a liquid, or “loose”, bowel movement.

Acute diarrhea is most commonly due to viral gastroenteritis with rotavirus, which accounts for 40% of cases in children under five. In travelers, however, bacterial infections predominate. Various toxins such as mushroom poisoning and drugs can also cause acute diarrhea.

Chronic diarrhea can be the part of the presentations of a number of chronic medical conditions affecting the intestine. Common causes include ulcerative colitis, Crohn’s disease, microscopic colitis, celiac disease, irritable bowel syndrome, and bile acid malabsorption.

What are the biological factors of diarrhea?

CausesViruses. Viruses that can cause diarrhea include Norwalk virus, also known as norovirus, enteric adenoviruses, astrovirus, cytomegalovirus and viruses that cause hepatitis. … Bacteria and parasites. … Medicines. … Lactose intolerance. … Fructose. … Artificial sweeteners. … Surgery. … Other digestive disorders.

Diarrhea — loose, watery and possibly more-frequent passage of stool — is a common problem. Sometimes, it’s the only symptom of a condition. At other times, it may be associated with other symptoms, such as nausea, vomiting, abdominal pain or weight loss.

Luckily, diarrhea is usually short-lived, lasting no more than a few days. But when diarrhea lasts beyond a few days, it is usually a clue to another problem — such as medicine side effects, changes in diet, irritable bowel syndrome (IBS), or a more serious disorder, including ongoing infection, celiac disease or inflammatory bowel disease (IBD).

Symptoms. Symptoms associated with loose, watery stools, also called diarrhea, may include:

What are the cellular and molecular mechanisms by which cholera causes diarrhoea?

Cholera is characterized by severe watery diarrhea due to changes in ion secretion and absorption. Both CLCA and CFTR-dependent Cl− secretion are activated, the first by Ace and the second by cholera toxin and NAG heat-stabile toxin. Increased cAMP levels also block sodium absorption through NHE2 and NHE3.

What cells cause diarrhea?

Inflammatory bowel disease (IBD) is linked to mucosal T cell activation and diarrhea. A study found that T cell activation with anti-CD3 mAb induces profound diarrhea in mice. Diarrhea was quantified by intestinal weight-to-length ratios, mucosal Na+/K+-ATPase activity, and ion transport changes in Ussing chambers. Anti-CD3 mAb increased jejunal wt/l ratios by more than 50 at 3 hours, returning to base line after 6 hours. Fluid accumulation was significantly reduced in TNF receptor-1 (TNFR-1 –/–) mice, but not IFN-γ knockout mice. Anti-CD3 mAb decreased mucosal Na+/K+-ATPase activity, which was blocked by anti-TNF mAb and occurred to a lesser degree in TNFR-1 –/– mice. Neither α nor β subunits of Na+/K+-ATPase decreased in abundance at 3 hours. Intestinal tissue from anti-CD3–treated mice exhibited increased permeability to mannitol at 1 hour and decreases in electroneutral Na+ absorption, Na +-dependent glucose absorption, and cAMP-stimulated anion secretion at 3 hours. Enteral fluid accumulation was observed in CFTR –/– mice, indicating a minor role of active anion secretion. These data suggest that diarrhea in IBD is due to TNF-mediated malabsorption rather than to secretory processes. Clinical trials indicate that blockade of the inflammatory mediator TNF effectively reduces disease parameters, including diarrhea, in patients with Crohn disease. TNF is detected at high levels in tissues in several disorders characterized by mucosal inflammation and diarrhea, including Crohn disease, graft-versus-host disease, small-bowel allograft rejection, and celiac sprue. Relatively high levels of TNF have been detected in the stool of patients with diarrheal illnesses due to enteric infections.

What causes diarrhea chemically?

Diarrhea is a common and serious health issue that can be caused by various secretory stimuli, including bacterial enterotoxins, hormones, dihydroxy bile acids, hydroxylated fatty acids, and inflammatory mediators. It is a major cause of death worldwide, with millions of lives lost annually, primarily among infants. Poverty, crowding, and contaminated water supplies contribute to the disease. Diarrhea is one of the two most common reasons for pediatric emergency department visits and is also common among institutionalized elderly. Chronic diarrheas present diagnostic dilemmas and can be difficult to manage.

Physiology of the intestine from duodenum to distal colon involves mechanisms for both absorbing and secreting water and electrolytes. Over the last half-century, two key observations have energized research in this area: the discovery in the 1960s that sugars and amino acids are absorbed across the small-intestinal brush border membrane via carriers that couple their movements to that of Na+. This allows the organic solute to move uphill, moving downhill from enterocyte to blood via basolateral membrane carriers. Some oligopeptides are also absorbed intact across the intestinal brush border by a proton-coupled mechanism, indirectly coupled to Na+ transport.

The Na+ gradient is the driving force for amino acid, oligopeptide, and sugar absorption. As these organic solutes are absorbed, salt is absorbed with them, and water follows osmotically. The coupled transport of Na+ and organic solute is the theoretical basis for oral rehydration therapy in severe diarrhea.

What is the scientific basis for diarrhea?

Introduction. The normal water content value in stools is approximately 10 mL/kg/day in infants and young children or 200 g/day in teenagers and adults. Diarrhea is the augmentation of water content in stools because of an imbalance in the normal functioning of physiologic processes of the small and large intestine responsible for the absorption of various ions, other substrates, and, consequently, water.

Acute diarrhea is the onset of 3 or more loose or watery stools a day lasting 14 days or less. However, chronic or persistent diarrhea is labeled when an episode lasts beyond 14 days. Infection commonly causes acute diarrhea. Noninfectious etiologies become more common as the duration of diarrhea becomes chronic. This distinction is important because treatment and management are based on the duration and specific etiology. Rehydration therapy is an important aspect of managing any patient with diarrhea. Prevention of infectious diarrhea includes proper handwashing to prevent the spread of infection.

The term “acute gastroenteritis” is synonymously used with “acute diarrhea”; however, the former is a misnomer. The term gastroenteritis signifies both gastric and small intestinal involvement, whereas, practically, it is rarely seen in acute diarrhea, even if it is the infective form of diarrhea. Additionally, enteritis is also not always present. Examples of infectious diarrhea without enteritis include cholera and shigellosis. Hence, using the term acute diarrhea instead of acute gastroenteritis is more clinically appropriate.