case 11 - diarrhoea Flashcards
what is diarrhoea?
three or more loose or liquid stools per 24 hours
AND/OR
stools that are more frequent than what is normal for the individual lasting <14 days
AND/OR
stool weight greater than 200 g/day
what are the three classifications of diarrhoea?
acute (≤14 days)
persistent (>14 days)
chronic (>4 weeks)
what is acute diarrhoea?
lasting less than or equal to 14 days
what is persistent diarrhoea?
lasting longer than 14 days
what is chronic diarrhoea?
lasting longer than 4 weeks
how much fluid enters the GI tract every day?
approx 10 litres in one day
what are the constituents of the fluid that enters the GI tract every day?
ingested food and drink
secretions from salivary glands, stomach, pancreas, bile duct and duodenum
how much of the fluid entering the GI tract is reabsorbed and how much is excreted?
99% reabsorbed = 9.9 litres
1% excreted (in the faeces) = 0.1 litres
where does the majority of reabsorption take place in the GI tract?
small intestine
what happens in the GI tract as a result of diarrhoea?
reduced reabsorption of fluid
increased secretions of fluid and electrolytes
increased bowel motility
what are the two classifications of diarrhoea?
inflammatory and non-inflammatory diarrhoea
what are the classifications and sub-classifications of diarrhoea?
inflammatory and non-inflammatory
inflammatory = infectious OR non-infectious
non-inflammatory = secretory or osmotic
osmotic = malabsorption or maldigestion
what are some infectious causes of inflammatory diarrhoea?
bacterial, viral or parasitic infection
what are some non-infectious causes of inflammatory diarrhoea?
(inflammation due to) bowel ischaemia, radiation injury or inflammatory bowel disease
what symptoms does inflammatory diarrhoea present with?
mucoid or bloody stool
tenesmus
sever crampy abdominal pain
fever
define tenesmus
continual or recurrent inclination to empty the bowels
what is the most common cause of infectious inflammatory diarrhoea?
bacterial infection (Campylobacter, Salmonella, Shigella, E. coli C. difficile)
who is affected by viral inflammatory diarrhoea most commonly?
children who attend day care centres
who is affected by protozoa/parasitic inflammatory diarrhoea most commonly?
people in developing countries (get acute diarrhoea as a result)
what does infectious inflammatory diarrhoea usually look like?
small in volume, but frequent bowel movements
why does infectious inflammatory diarrhoea not usually result in volume depletion?
small in volume, but frequent bowel movements
can result in volume depletion in children/young adults
what will a stool test for infectious inflammatory diarrhoea show?
high leukocytes (but false-negatives common)
faecal occult blood
what does non-inflammatory diarrhoea look like?
watery, large volumes and frequent stool (10-20 per day)
why does non-inflammatory diarrhoea usually result in volume depletion?
usually larger volumes and watery so increased fluid loss
which type of diarrhoea is usually associated with volume depletion and why?
non-inflammatory diarrhoea as it is watery and large in volume whereas inflammatory diarrhoea is smaller in volume
(both have frequent bowel movements)
what are the symptoms of non-inflammatory diarrhoea?
large volumes of water stool + cramping
no tenesmus/blood in stool/fever/faecal leukocytes
compare the symptoms of inflammatory and non-inflammatory diarrhoea
inflammatory diarrhoea presents w tenesmus, mucoid and bloody stool, fever and abdominal cramps whereas non-inflammatory diarrhoea only presents w abdominal cramps
inflammatory = small volumes, frequent
non-inflammatory = large volumes, watery stool, frequent
compare the histology of the GI tract in inflammatory and non-inflammatory diarrhoea
histology of the GI tract is abnormal in inflammatory diarrhoea but is preserved in non-inflammatory diarrhoea
what are the two categories of non-inflammatory diarrhoea?
secretory and osmotic
how do the stool test results differ for the two types of diarrhoea?
blood in stool and faecal leukocytes present = inflammatory
NO blood in stool and faecal leukocytes absent = non-inflammatory
why does secretory diarrhoea occur?
altered transport of ions across the mucosa
how does secretory diarrhoea occur?
altered transport of ions across the mucosa
SO increased secretion and less reabsorption of ions of fluid and electrolytes
how are the types of non-inflammatory diarrhoea affected by fasting?
secretory diarrhoea does not decrease by fasting
osmotic diarrhoea usually improves/stops on fasting
what are some causes of secretory diarrhoea?
enterotoxins (cholera, S. aureus, E. coli)
hormonal agents (neuroblastoma, small cell cancer of lung, vasoactive intestinal peptide)
laxative use
intestinal resection
bile salts, fatty acids
coeliac sprue, collagenous colitis, hyperthyroidism, carcinoid tumours (= chronic diarrhoea)
why does osmotic diarrhoea occur?
due to the presence of unabsorbed/poorly absorbed solute in the GI tract
how does osmotic diarrhoea occur?
due to the presence of unabsorbed/poorly absorbed solute in the GI tract
= increased secretion of liquids into the gut lume
what happens if you measure stool electrolytes in osmotic diarrhoea?
increased osmotic gap
but not significant as stool always isoosmotic - 260-290 mOsml/L
what are the two categories of osmotic diarrhoea?
malabsoprtion and maldigestion
what is malabsoprtion diarrhoea?
a type of non-inflammatory, osmotic diarrhoea
diarrhoea due to impaired absorption of nutrients across the gut lumen
what is maldigestion diarrhoea?
a type of non-inflammatory, osmotic diarrhoea
diarrhoea due to impaired digestion of nutrients within intestinal lumen or at the brush border membrane of mucosal epithelial cells
what are the causes of malabsorption diarrhoea?
mesenteric ischaemia, short bowel syndrome (post a bowel resection), mucosal disease (coeliac disease)
what are the causes of maldigestion diarrhoea?
pancreatic exocrine insufficiency, lastase deficiency
what are the broad causes of diarrhoea?
infection of the bowel
inflammation of the bowel
irritation of the bowel
increased bowel motility
secretion of water into the bowel
why does inflammatory diarrhoea cause mucoid stool?
layer of mucus lines and protects the inside of your colon
layer gets damaged due to inflammation so more mucus in stool
+ overactivity of mucus-secreting goblet cells
what is the function of the small intestine?
to absorb digested nutrients
to reabsorb 90 % of the water in the GI tract
what is the function of the large intestine?
to hold and prepare faeces (containing undigested food, dead
cells, dead bacteria) for egestion from the body.
to reabsorb the remaining 10% of the water in variable amounts
how does water re-enter enterocytes from the lumen?
via osmosis from an area of high water potential to an area of low water potential
via aquaporins
explain how inflammatory diarrhoea occurs
viral/bacterial infection (infectious) OR radiation injury, bowel ischaemia, IBD (non-infectious) etc
inflammatory response damages epithelial lining and impairs enterocyte function
so absorption of nutrients and WATER impaired
explain how secretory diarrhoea occurs
enterocyte functioning is impaired
instead of retaining the solutes that will allow water absorption, they secrete them into the lumen so water remains in lumen
(if sufficiently low water potential is generated, water from inside the enterocyte side also enters the lumen)
explain how osmotic diarrhoea occurs
enterocytes and their functioning is intact however due to the presence of solutes in the lumen, an sufficiently strong water potential cannot be established
explain how malabsorption diarrhoea occurs
a digested solute present in the lumen is not absorbed into the enterocyte and remains within the intestinal lumen and decreases water potential
explain how maldigestion diarrhoea occurs
enterocytes and their functioning is intact
molecules that should have been digested are not and at they cannot therefore be absorbed, they remain in the intestinal lumen and decrease water potential
how does cholera cause secretory diarrhoea?
cholera enterotoxin interferes w the transport of ions across the intestinal lumen as chloride secretion is increased and so the osmotic balance is disrupted so water remains inside the lumen
give an example of maldigestion diarrhoea
lactose intolerance (i.e. lactase deficiency)
also pancreatic exocrine insufficiency
give an example of malabsorption diarrhoea
sorbitol in prunes is not absorbed = laxative effect
which ion is specifically responsible for the ionic imbalance in secretory diarrhoea?
chloride ions (secreted into the lumen)
why is volume depletion a medical emergency?
larger volumes of water are lost causing dehydration which impairs the preservation of blood volume and blood pressure risking hypoperfusion
how is volume depletion managed?
oral rehydration therapy
why is it important to preserve blood volume?
sufficient volume = sufficient pressure to perfuse the organs effectively = prevent circulatory collapse and shock
what is oral rehydration solution?
oral rehydration salts (sodium chloride, potassium chloride, sugars etc) dissolved in water
how does oral rehydration solution work?
using the SGLT1 transport protein found on the brush border of enterocytes
high enough concentrations of sodium and glucose will activate SGLT1 so two sodium molecules and one glucose are transported into the enterocyte
solutes transported into te blood via transport proteins, decreasing water potential of blood
water follows solute movement into blood, down the water potential gradient, via aquaporins
name five cell types present in the gut epithelium
enterocytes goblet cells Paneth cells enteroendocrine cells stem cells
what is the function of enterocytes?
absorption of solutes and water
what is the function of goblet cells?
mucus secretion to facilitate passage of material through bowel
what is the function of Paneth cells?
secretion of antimicrobial peptides and immunomodulating proteins
what is the function of enteroendocrine cells?
secrete hormones to influence gut motility
what is the function of stem cells in the gut epithelium?
continuously replenish the surface epithelium
why does secretory diarrhoea not improve with fasting?
pumps will secrete solutes into the intestinal lumen and so pathogenesis is not affected by food you eat
why does osmotic diarrhoea improve with fasting?
digestion of solutes is impaired and so osmotic imbalance increases and can worsen based on the foods you eat (more solutes are being taken into GI tract)
differentiate between IBS and IBD
IBS = disorder of the gastrointestinal (GI) tract
IBD = inflammation or destruction of the bowel wall = can lead to sores and narrowing of the intestines.
which symptoms overlap between IBS and IBD?
abdominal pain, faecal urgency and fatigue
which features are exclusive to IBS and do not appear in IBD?
alternating constipation and diarrhoea, mucoid stool, abdominal bloating
what is important to remember about an IBS diagnosis?
IBS is a diagnosis of exclusion - rule out majority of possible causes before diagnosing IBS
(i.e. patients suspected of having IBS should be check for UC or CD first)
which features are exclusive to IBD and do not appear in IBS?
weight loss, fever, blood in stool
what are the top differentials for patients that present with chronic diarrhoea?
Crohn’s disease OR ulcerative colitis (IBD)
list some basic investigations to carry out on a patient that presents with chronic diarrhoea
blood tests = FBC, CRP, ESR, LFTs, ferritin, TFTs, vitamin B12 anf folate, U+E
stool tests = faecal calprotectin, serology (microbiology, culture, ova and cysts)
why is a FBC done to investigate chronic diarrhoea?
to look for anaemia (of chronic disease) and signs of inflammation/infection
why are CRP and ESR done to investigate chronic diarrhoea?
markers of inflammation
CRP = non-specific marker of inflammation
why are U+E done to investigate chronic diarrhoea?
to check renal function and electrolyte status
why are LFTs done to investigate chronic diarrhoea?
liver responds to inflammation by causing hypoalbuminaemia = acute inflammation
+ surrogate marker for malnutrition (frequently seen in IBD patients)
why is a ferritin test done to investigate chronic diarrhoea?
liver responds to inflammation by sequestering iron from the bloodstream that can further cell damage during inflammation (by partaking in free-radical driven reactions)
so inflammation = high stored iron = high ferritin
why is a faecal calprotectin test done to investigate chronic diarrhoea?
surrogate marker of inflammation specifically in the bowel
indicative of migration of neutrophils to the intestinal mucosa
why are serological investigations (microbiology, ova/cysts) done to investigate chronic diarrhoea?
to check for coeliac disease and infective causes
coeliac serology - will present with tissue glutaminase antibody
microbiology - bacterial infection
ova, cysts - parasitic infection
why are TFTs done to investigate chronic diarrhoea?
hyperthyroidism can also cause diarrhoea (increased gut motility)
- also caused by hypothyroidism -
why are vitamin B12 and folate tests done to investigate chronic diarrhoea?
can be due to OR can cause the diarrhoea
how are ova and cysts tested for in suspected chronic diarrhoea?
three specimens two days apart
as ova and cysts are shed intermittently
what are some shared features of CD and UC?
chronic inflammation of the GI tract
in genetically predisposed patients
triggered by dysbiosis
symptoms - diarrhoea, tiredness (inflammation is energy consumptive), weight loss (poor absorption of nutrients)
define dysbiosis
dysregulation of the gut flora
what is Crohn’s disease?
a chronic inflammatory disease characterised by transmural granulomatous inflammation affecting any part of the GI tract
what causes Crohn’s disease?
inappropriate immune response against the normal gut flora in a genetically susceptible individual
what two factors can exacerbate Crohn’s disease?
smoking increases risk of CD
NSAIDs can exacerbate CD
what are examples of some NSAIDs?
don’t give NSAIDs to Crohn’s patients
ibuprofen, neproxene, diclofenac, indomethacin, high dose aspirin
what is ulcerative colitis and what causes it?
aberrant immune response in which antibodies are formed against colonic epithelial proteins
what are the layers of the GI tract?
mucosa, submucosa, muscularis propia, serosa
compare the gut layers affected in CD and UC
in CD = transmural (all gut layers affected)
in UC = limited to mucosa (rarely, submucosa can be affected)
compare the regions affected in CD and UC
in CD = entire GI tract affected, in patches
in UC = limited to colon, but always includes rectum
compare the pattern of disease in CD and UC
in CD = patchy, ‘skip’ lesions
in UC = continuous (in colon)
compare the macroscopic findings in CD and UC
in CD = cobblestone appearance, strictures, fat creeping (increased risk of fistulas)
in UC = pseudopolyps
compare the microscopic findings in CD and UC
in CD = non-caseating granulomas, increased goblet cell
in UC = crypt abscesses, decreased goblet cells
what causes the patchy ‘skip’ lesions in CD?
in CD, the patches of inflammation (i.e. granulomas in specific areas) are interspersed between bits of completely normal mucosa
what causes the cobblestone appearance in CD?
the patches of inflammation are interspersed between bits of completely normal mucosa = cobblestone appearance
(i.e. granulomas form only in specific areas)
what causes the fat creeping in CD?
form as a mechanical plug for transmural ulcers to prevent pathogenic bacteria exiting the lumen
(but unclear why the fat continues to advance after this)
what causes the strictures in CD?
due to repeating cycles of inflammation in isolated sections of bowel
what causes the formation of pseudopolyps in UC?
benign complication of active colitis - due to mucosal loss
what are non-caseating granulomas?
granulomas that are not typically cheese-like
cluster of white blood cells that will enclose the pathogenic material separating it from the healthy tissue
what are crypt abscesses and why do they form?
commonly seen in UC
when crypt structure is affected causing crypt atrophy, crypt loss or crypt branching = impaired ability to remove pathogens that get stuck in this region = abscess formation
differentiate between pseudopolyps and polyps
polyps have an increased cancer risk associated w them (hyperplasia of mucous membrane causing growth of tissue)
pseudopolyps are a benign overgrowth of
compare the flare pattern of CD and UC
in CD = continuous symptoms
in UC = relapsing-remitting symptoms
what is a functional disorder?
cannot detect any abnormalities on blood tests or imaging but symptoms are present
how is Crohn’s disease treated acutely?
corticosteroids - to induce remission and settle the symptoms
how is Crohn’s disease treated in the long term medically?
azithroprine - targets purine needed for replication of immune cells
biologics - infliximab works on TNF-alpha to dampen down the immune response and counter granuloma formation
surgery - NOT a cure but treats fistulas and strictures that form
(smoking cessation + avoiding trigger foods = non-medical treatment)
how does azithroprine work?
targets the purine needed for replication of immune cells
how does infliximab work?
works on TNF-alpha to dampen the immune response and counter granuloma formation
how does smoking affect CD as opposed to UC?
in CD = increases risk
in UC = apparent protective effect?
what is one extraintestinal manifestation of CD?
aphthous ulcers
