7.09 Infective diarrhoea

Salmonella, shingella, yersinia and some helminths

Giardia lamblia, which results in more subtle injury

Particles invade mature enterocytes and cause them to desquamate. In reaponse, crypt cells (which aren't infected by virus) proliferate and cover the injured villus but fail to differentiate normally- the villus is covered with immature cells which lack the normal brush border enzymessuch as lactase and glucose-coupled Na transporter (SGLT1)- osmotic diarrhoea

It can be induced by bacterial toxins secreted in the gut lumen. E.g. Vibrio cholera and Escheria coli.

They stimulate chloride secretion from enterocytes by:
a) altering cell regulation events in enterocytes and
b) modulating enteric nerves and enteroendocrine cells which have a role in modulating secretion

Rotavirus has been shown to produce a capsid protein which stimulates enterocyte secretion by altering intracellular Ca2+ levels

Mast cell degranulation which induces profuse secretion

They release inflammatory mediators such as arachadonic acid metabolites, TNF and 5'-AMP which can induce water secretion.

Unabsorbed fat is fermented into dihydroxy fatty acids by colonic bacteria. These compounds can induce secretion in the colon but steatorrhoea is not usually a problem in infectious gastrointeritis.

It causes intestinal anaphylaxis which induces rapidly migrating peristaltic waves which move aborally, propelling contents distally. Local inflammation causes the release of mediators which directly affect smooth muscle and modulate local neural circuits (which are involved in coordinated motor activity of the gut)

Altered motillity contributes to it

9L. 2L is ingested and 7L is endogenous fluid and electrolytes (including salivary; gastric secretions, bile, pancreatic secretions and endogenous small intestinal secretion)

About 1.5 L enters the colon and 0.1-0.2 exits in stool. Diarrhoea occurs when stool volume increases by as little as 0.1L.

An epithelial sheet with crypt and/or villous compartments

Enterocytes, paneth cells, goblet cells and enteroendocrine cells

The epithelium is interdigitated with immunocytes and overlies a stroma of lymph, blood vessels, immunocytes and fibroblasts (lamina propria), myocytes (muscularis mucosae). A rich nerve supply (submucosal plexus) is linked to the central nervous system.

The intestine exhibits geographical differences in structure and ion transport characteristics in the long axis (small vs large; jejunum vs ileum) and structural and functional differences along the vertical, crypt villous axis.

The transport of water, electrolytes nutrients and other substances important for maintaining mucosal integrity (e.g. immunoglobulin A, mucus). Transport can occur in both blood to lumen and lumen to blood directions.

To facilitate vectorial transport with an apical membrane and a basolateral membrane which possesses different solute transporters. E.g. basolateral Na/K ATPase pumps Na from the cell into the extracellular space causing a concentration gradient for Na which drives an apical Na/glucose cotransporter to absorb Na and glucose from the lumen against large concentration gradients.

Water is absorbed via the paracellular pathway and transcellularly.

Ions and other small molecular weight solutes can be absorbed passively through the paracellular pathway, dissolved in the water ie solvent drag

Ions and other small molecular weight solutes can be absorbed transcellularly via specific ion transporters . Basolateral Na/K ATPase is the main basolateral transporter which creates the internal concentration and electrical gradients to facilitate vectorial transport of ions and some solutes. Other basolateral transporters are also important Na/K/2Cl cotransporter and K channels.

K is absorbed passively in the small intestine and is actively absorbed or secreted in the colon

Several nutrients e.g. glucose, galactose and amino acids. When ion transporters or Na/Solute transporters are activated water and other ions such as Cl follow passively by osmosis.

They are mainly absorbed in the small intestine but the colon has the ability to 'salvage' a small amount of dietary nutrients not absorbed by the small intestine especially carbohydrate. Undigested carbohydrate is fermented to short chain fatty acids by colonic bacteria and then absorbed coupled to Na or via anion exchangers.

Secretion is facilitated by apical secretion of Cl- via specific Cl- channels. The cellular electrical and chemical gradients necessary to facilitate Cl- secretion are maintained by the basolateral transporters. After Cl- exits into the lumen, water and other ions follow passively

Some cells contain both Na absorptive channels and Cl secretory channels in the apical membrane. In general, when Cl secretion is stimulated, Na absorption is inhibited in the same cell. The exception to this is Na coupled solute absorption (glucose, AA) which remains functional even in the presence of profuse Cl secretion. This can be observed when patients with cholera are treated with oral rehydration solutions. Ingesting the solution reverses the cholera induced secretion by stimulating Na/glucose cotransport by the glucose and Na contained in the solution.

By second messengers which convey signals from the cell surface eg neurotransmitter or hormone and modulate transport activity by altering the transporters themselves

The luminal nutrients, toxins by internal environment eg local chemicals (paracrine factors) neurotransmitters hormones. This allows normal function during health and adaption to potentially harmful situations eg increased absorption during dehydration increased secretion during infection (secretion being a mechanism to flush out the lumen) 'first defence'.

dehydration (high serum urea and creatinine) and depleted intravascular volume (resulting in metabolic acidosis; low pH, low HCO 3 ). Depending on faecal losses and oral intake, there may be normal, low or high serum sodium. In chronic diarrhoea, potassium and magnesium levels may be low.

Excessive loss of gastric juices or of stool containing an unusually high chloride concentration (eg congenital chloridorrhoea) can result in metabolic alkalosis.

It is usually corrected with rehydration and bicarbonate therapy is rarely required.

Viral gastroenteritis is an example of mucosal damage which causes osmotic diarrhoea. Some bacterial ( Salmonella, Shigella ) and parasitic ( Giardia lamblia, Cryptosporidiosis ) infections also damage the small intestinal mucosa

Ainc and Vitamin A

It elaborates a toxin which stimulates fluid and electrolyte secretion via activation of electrogenic chloride secretion, a group of transporters present in intestinal epithelium. This is mediated by enterocyte cAMP, though recently a major component of cholera induced secretion was found to be mediated via mucosal nerves and enteroendocrine cells

It infects food and release toxins into it. When ingested the toxins stimulate secretion and alter intestinal motor function causing vomiting and diarrhoea. Symptoms develop within hours.

Colonic bacteria breakdown the fat to dihydroxy fatty acids which stimulate enterocyte secretion in the colon contributing to increased stool volume

Inadequate bile salt concentration, reduced pancreatic lipase secretion eg cystic fibrosis, damage to the mucosal surface eg coeliac disease, abnormal chylomicron formation (abeta lipoproteinaemia) or blocked intestinal lymphatics (intestinal lymphangectasia). Steatorrhoea does not usually occur in infections of the gastrointestinal tract, but may occur in the setting of severe malnutrition as the latter causes pancreatic insufficiency and may coexist with tropical enteropathy syndrome

These signs arise from colonic inflammation. The commonest in children are Campylobacter jejuni, Salmonella species, Yersinia enterocolitica, Shigella species, Escherichia coli and in some helminth infections such as Strongylides stercoralis)

Other causes of bloody diarrhoea are food allergies (particularly in infants), some viral infections (Cytomegalovirus) in immunosuppressed individuals and chronic inflammatory bowel disease. Occassionally patients with rectal inflammation complain of frequency of stooling without a large increase in stool volume.

Campylobacter jejuni

Ham ( S.aureus ), rice ( B.cereus ), undercooked eggs (Salmonella species) chicken (Salmonella species, Campylobacter jejuni )

Rotavirus ("wheel virus") in children and norwalk and related viruses in adults. Occasionally adenovirus

Non-specific immune defects (eg. Achlorhydria ) increase susceptibility to enteropathogens. Specific immune defects eg AIDS increase susceptiblity to diarrhoea caused by microbes which are ordinarily benign eg Mycobacterium avium/intracellular and Microsporidia

Enteropathogenic Escherichia coli (EPEC)) (Clostridium difficile (C.difficile) infection

Salmonella species

Even severe disease eg cholera is effectively treated with oral rehydration. (Antibiotic therapy is actually harmful in uncomplicated Salmonella diarrhoea)

With the exception of rota- and adenoviruses for which immune assays are available, identifying viral agent of diarrhoea requires electron microscopy

Identifying pathogens in prolonged diarrhoea for which there is specific, antimicrobial treatment (eg Campylobacter jejuni). Also identifing pathogens where a public health intervention may limit epidemic spread (Salmonella and Shigella species).

To absorb fluid arriving from the ileum before excretion.

Epithelial cells lining the lumen of teh large intestine absorb Na+ and Cl- which creates an osmotic force driving water from the lumen, across the epithelium to the plasma. Colonic epithelium can also secrete K+ and HCO3- into the lumen

Firstly, Na+ enters the cell via either the Na+ channel (electrogenic) or the Na+-H+ exchanger (electroneutral) and secondly Na+ leaves the cell into the interstitium via the Na+-K+-ATPase on the basolateral membrane. Electrogenic Na + absorption creates the driving force for paracellular movement of Cl - from the lumen to the serosa, whereas the electroneutral Na+ absorption via the Na+-H + exchanger is coupled with Cl - absorption and HCO3- secretion via the apical Cl-HCO3- exchanger

T.

The ascending colon transports Na + mainly by electroneutral pathways whereas Na + transport by the descending colon is mainly electrogenic

It increases Na+ absorption in the colon by increasing number of the apical amiloride-sensitive Na+ channel in the brush border membrane. Other extrinsic factors such as vasoactive intestinal peptide (VIP), histamine, serotonin and autonomic stimulation act via the intracellular secondary messengers such as cAMP or Ca 2+ , which in turn influence transepithelial ion transport activity of the colonic epithelium.

The child is very wasted, has lost almost all the subcutaneous fat and a lot of muscle. The protein loss is mostly from skeletal muscle. Marasmus is diagnosed by a child's weight less than 60% of the WHO standard for age and mild to moderate protein-energy malnutrition by weight for age to 60% to 80% of WHO standard

The child has oedema, characteristic pigmented scaly skin lesions, changed hair colour, is miserable and won ' t eat. Internally there is fatty liver and hypoalbuminaemia. The protein depletion is visceral (liver and gut) rather than somatic and the liver fails to produce plasma albumin and low density lipoproteins. Kwashiorkor is less common than marasmus. In the classical theory it is due to a diet of very low protein with some carbohydrate, though there are other theories about the aetiology.

First resuscitation, second refeeding and third, rehabilitation.

Most can be managed at home. Encourage normal diet and fluids ad libitum (continue breast milk).
Consider admission if high risk of dehydration (very young, diagnosis in doubt, large losses)

Some can be managed at home with OR solution. Some require observation during OR therapy and, if OR therapy not tolerated or large ongoing losses occur, may require NG or IV fluids for rehydration over 4-6 h.
Normal diet when tolerated.

Check acid base status, urea, electrolytes before IV fluids.
If shock present, first resuscitate with IV bolus.
Rehydrate intravenously (enteral fluids have been used) over 4-6 h with regular clinical and biochemical review.

Solution with water containing a precisely determined mixture of sodium, potassium, chloride and a base (e.g. citrate) in addition to glucose. It is designed to stimulate the sodium-coupled glucose transporter, which when activated induces water flow and passive absorption of other electrolytes

Sweet drinks (juice, soft drink, cordial) diluted to at least 1 part drink:3 parts water can be used in non-dehydrated children with mild symptoms. Many of the drinks above have a high sugar content (osmolality) which may worsen diarrhoea by causing osmolar diarrhoea. These drinks do not contain Na and are therefore poor stimulators of sodium-coupled glucose transport and offer no K to replace losses.

Initially when the child is shocked.

YES!

Rapid rehydration of these patients may be accompanied by a rapid fall in serum sodium may cause cerebral oedema due to fluid shift

Lowering of blood pressure is a late sign of dehydration and therefore monitoring of pulse rate is a more reliable and sensitive measure of the effectiveness of rehydration therapy

No. Starvation/malnutrition exacerbates gut damage and delays weight gain

Secondary lactose intolerance may occur but is usually transient.

Anti-motility, anti-secretory, stool binding and anti-vomiting agents are not recommended for routine use in children with gastroenteritis. They do not alleviate the loss of extracellular fluid and dehydration. They may cause serious side effects in children, including death. Newer medications e.g. Ondansetron may prove useful for control of vomiting but are not currently recommended for routine use.

They are not routinely recommended except for bacterial septicaemia and Shigella, Giardia lamblia and helminth infestations. They are of no proven benefit in most cases of bacterial gastroenteritis, in some circumstances prolong the carrier state, and may alter gut motility and increase diarrhoea.

Promotion of breast feeding, hand washing, food hygiene (one day vaccination)

Until the 2nd or 3rd year of life

he internal sphincter is a continuation of the circular smooth muscle of the rectal wall and is under involuntary control by the autonomic nervous system: parasympathetic supply from S2,3,4 and sympathetic L2,3,4. It provides the majority of resting anal tone.

The external sphincter is a striated muscle which does not play a major part in maintaining resting tone, but which is essential for voluntary anal squeeze pressure. External sphincter is supplied by branches of the pudendal nerve. Maximal voluntary contraction of the anal sphincter can only be maintained for about 1 minute.

The average length of the high pressure zone in the anal canal is about 4 cm in adults. In people who are incontinent, the anal canal is likely to be shorter, but there is quite a wide variation in the length of the canal in those with normal continence.

This is the angle between the axis of the anal canal and the rectum. It may play a role in maintenance of continence at times when the intra-abdominal pressure is increased, such as when sneezing. The angle varies widely, but tends to be more obtuse in those who are incontinent.

Normally, the rectum is able to accommodate by distension in response to a faecal bolus. This allows the pressure in the rectum to fall to a normal level, relieving the urge to defaecate. If the rectum is 'stiff' and less compliant than usual, it's ability to distend is reduced. This can be a cause of incontinence in conditions such as ulcerative proctitis or radiation proctitis.