Lecture 23: Diarrhoea and acute GI illness Flashcards
Define gastroenteritis, diarrhoea and acute, persistent & chronic:
Gasteroenteritis: Sydnrome diarrhoea and/or vomiting
Diarrhoea: 3+ loose stools in 24 hrs
Acute: <14 days
Persistent: 14-30 days
Chronic: >30 days
Write some brief notes on anatomy and function of GI tract:
Fluid and nutrient absorption!
- Villi + Microvilli
- Crypts
- Mucous layer
Describe the innate immunity features of the GI tract:
- Intestinal motility -> Helps clear bacteria out (loperamide stops gut motility)
- Intestinal microflora
- Gastric acidity (Norovirus and guradia are resistant tho)
- Changes in Na/glucose/fat absorption can result in loose stools / osmotic diarrhoea (think toxins)
- M Cells aid dendritic cells sampling in payers patches continuously
Describe the role of the human microbiome in GI health:
7 features
- Protects against pathogens
- Synthesis of vitamins
- Immune system development
- Promotion of intestinal angiogenesis
- Promotion of fat storage
- SCFA production by fermentation of dietary fibre
- Modulation of central nervous system
Give an overview of the mechanisms of infectious diarrhoea:
- Essentially an altered movement of ions and water (Water following the osmotic gradient)
- Enteric pathogens alter the balance towards net secretion -> Diarrhoea
- Occurs either through:
Direct modulation of ion process and function (Non-inflammatory diarrhoea)
Indirectly through inflammation, neuropeptides or loss of absorptive surface (Inflammatory diarrhoea)
What is distinct about non-inflammatory diarrhoea and what causes it?
- Watery diarrhoea WITHOUT blood or pus.
- Mucosal disruption affecting absorption/secretory processess without causing acute inflammation or mucosal destruction
Causes include:
- Enterotoxin ingestion
- Enterotoxin producing organisms
- Viruses that adhere to mucosa
Describe the mechanisms of inflammatory diarrhoea:
- Predominantly target large bowl (Esp. distal ileum and colon)
- Acute mucosal inflammation with various degrees of mucosal ulceration
- Blood, mucus and WCC in stool, pain and fever
Causes include:
- Secretions of cytotoxins
- Invasion of intestinal epithelium causing acute inflammatory reaction (Shigella, Campylobacter, salmonella)
What are the diagnostics for diarrhoea?
Trying to identify a pathogen within normal flora (Vs sterile i.e CSF)
- Microscopy
- Culture
- Antigen testing
- Molecular (PCR/multiplex PCR)
Write some notes on using culture for diagnosis:
- Stool: Non-sterile, dont want to grow non-pathogenic bacterial (selective media)
- Need to grow pathogenic bacteria that may be present in small numbers relative to other bacteria
- Need to be able to differentiate pathogenic bacteria from non-pathogenic bacteria easily.
Whats the function of chromogenic agar?
- Target specific pathogenic species based on enzyme activity
- Generally target organism grow as coloured colonies due to metabolism of one or more chromogenic enzyme substrates
- Reduces the number of colonies that require further identification
Write some notes on syndromic panel molecular testing:
- Utilise multiplex PCR testing to perform molecular testing for variety of viral/bacterial/parasitic pathogens
- Single sample, single test - multiple different pathogens
- Rapid and easy to use
- Only detect what primers bind to
- No organism for susceptibility testing (Individual and public health implications)
- Can be difficult to interpret (Detecting DNA not viable organism, remain positive after resolution/treatment) i.e rotavirus post vaccine
Whats the general management of diarrhoea?
- Symptomatic relief
- Rehydration
- Prevent transmission
- Identify those at risk of severe disease which requires treatment i.e those with severe/prolonged diarrhea, invasive disease or risk factors for complications
What aspects of history are you looking for in a patient with diarrhea?
- Assessment of dehydration (Oral vs IV)
- Co-morbidities and risk factors for severe disease
- Transmission and public health risk (impact on work)
- Specific treatment
What are some examples of diarrhea and their causes?
Non-inflammatory / small bowel infection
- > Food poisoning
- > Viral gastroenteritis
Inflammatory diarrhea / colitis
- > Campylobacter
- > Shigella
- > Salmonella
Giardia (Parasite)
Metronidazole
Write some notes on food poisoning: and an example:
- Acute vomiting (Some forms have diarrhea also)
- Toxin ingestion (Bacteria multiply outside host, toxins consumed)
Staphylococci Spp or B cereus
- Multiply at range of temps.
- Often reproduce in food that is left to cool slowly at room temp
Rapid onset but resolves quickly
What are the five major causes of small bowel / viral gastroenteritis
Five major causes
- Rotavirus
- Norovirus
- Enteric adenovirus
Sapovirus and astrovirus (significance unclear)
Whats the pathogenesis of small bowel / viral gastroenteritis:
- Infection of small intestine, enterocyte epithelium
- > Adherence of mucosa and disruption of absorption/secretory processes WITHOUT acute inflammation or mucosal destruction
- > Viral replication leading to epithelial cells becoming necrotic - loss of enzymes that break down CHO and proteins -> Primary malabsorption
- Localized responses causing ischemia of villi and villous atrophy -> reduced absorptive capacity
- Autonomic dysfunction (i.e vomiting), increased motility of small intestine
How does norovirus cause disease?
- 1/5th of all gastro
- Transmission is feacal-oral, human-human or environmental
- Short incubation
- Low infectious dose = spreads rapidly
- Delayed gastric emptying common therefore vomiting a feature
= Strict hand hygiene
= Doesnt culture therefore PCR needed
Write some notes on rotavirus:
- Mostly children
- Severe disease in 3 months to two years
- Fever and vomiting followed by diarrhoea
- Now have oral vaccine 6 weeks and 3 months.
What sort of diarrhoea does shigella cause?
Inflammatory diarrhoea
How is shigella transmitted and describe its pathogenesis:
- Feacal oral and sexual transmission
- Can withstand low pH and low infectious dose.
- Invasion of large intestine mucosa causing ulceration and inflammation however usually only superficial not penetrating beyond lamina propria
- Incubation 1-4 days, shed for weeks after illness
Describe shigella presentation and treatment:
Presentation:
- Watery diarrhoea with fever and abdo pain followed diarrhoea with blood, mucus and pus.
Treatment
- Antimicrobials useful for reducing shedding
- Usually self limiting but antibiotics shorten duration, transmission and severity
- Widespread and increasing antibiotic resistance
Describe the spread of campylobacter jejuni:
Feacal oral spread predominantly through contaminated food/water or contact with animals although human-human sprad can occur
Susceptible to gastric acid, drying, freezing, pasteurization or chlorination
Describe how campylobacter jejuni causes disease:
- Causes inflammatory colitis of D,J,I
- Bacteria enter intestinal epithelium through M-cells and spread to adjacent cells -> Local inflammatory response and toxin induced cell damage -> Inflammatory diarrhoea
Describe the treatment of campylobacter jejuni:
- Generally self limiting
- Antibiotics reduce duration of symptoms by <2 days and do eradicate stool carriage. Person-person spread is rare
- Use antibiotics in those with severe or prolonged symptoms, high risk complications or high risk transmission
Write some notes on salmonella pathogenesis:
- Disease in ilium and to a lesser extent colon
- Low infectious dose, long and variable incubation period.
- Person-person spread or via contaminated food and water
Describe salmonella resistance to antibiotics
- Intrinsically resistant to first and second gen cephalosporins and aminoglycosides
- Increasing resistant due to plasmids
What are the two syndromes seen with salmonella:
- Typhoid salmonella generally presenting with high fever and headache typically without diarrhoea, with bacteremia; require antibiotic treatment
- Non-typhoidal salmonella causing intestinal infection presenting with fever and diarrhoea and occasionally extraintestinal infections including bacteraemia, osteomyelitis and endovascular infection
Describe treatment for salmonella:
Adults - Antibiotics unnecessary and may prolong excretion
- Consider in those with severe disease, immunocompromised, or with prosthetic vascular grafts
- Infants <3months usually require treatment
How can giardia be transmitted?
- Feacal oral via ingestion of cysts in contaminated food or water
- Low infectious doses
Describe giardia:
Non invasive: Trophozoites (Active form) adhere to the epithelium of upper small intestine and damage mucosal brush border without invasion
How doe giardia cause disase?
Loos of brush border -> Loss of absorptive surface and diffuse shortening of villi
Often slow onset can be present for months and cause acute/chronic diarrhoea, abdo pain and malabsorption
How is giardia diagnosed and treated?
- Diagnosis via stool examination for cysts/trophozoites and increasingly antigen detection or PCR
- Treatment with metronidazole
Write some notes on the function of metronidazole:
- Inert - antimicrobial activity depends on activation after entering the organisms cell via passive diffusion (Aerobic bacteria cant activate prodrugs, thus inefective)
- Activated drugs inhibits DNA synthesis and induces DNA damage -> DNA degradation and cell death
- Near 100% bioavail
- LOw protein binding = large VoD
- Well tolerated, peripheral neuropathy with prolonged use tho
- If alcohol also used then can cause nausea, diarrhoea etc
Describe the differential approach to diarrhoea:
- Intra-abdo infection or systemic infection
- Non-infectious causes of diarrhoea
- > Inflammatory bowel disease
- > Coeliac disease
- > Meds
- > IBS
