Lucy Allen Flashcards
What does the introduction video reveal about Lucy Allen?
Last 6 months - travelling around indonesia, Phillipines and Australia
Started new job 6 weeks ago
Persistent diarrhoea for the last 10 days
Has a temperature
Mildly dehydrated
What does Lucy’s patient persona say about her?
Enjoys playing 5 a side football in the weekends
Loves to collect souvenirs from overseas trips
Loves her cactus garden
Loves to travel around the world
Finding it difficult to sleep lately
Lost 7kg since most recent trip overseas (i.e. 6 months ago)
What does Lucy Allen talk about in the case video?
Terrible diarrhoea - been there for 6 weeks, but gotten a lot worse over the weekend
Tummy pain
3-4 times a day for a month, last 2-3 days like 8x a day
Overnight too - particularly the last few days
Loose poo - brown, watery, occasionally blood on the tissue (From wiping, not actual faeces)
Indonesia and then the Philippines for 10 weeks, 2 months ago
Did not have these symptoms overseas, except once has a bout of diarrhoea for 2 days over something she ate
No nausea or vomiting
Poorer appetite
Pain comes and goes - most on left upper quadrant
Pain does not change with opening bowels
Lost about 7kg since she got back
Very tired, no energy atm
On the contraceptive pill
Adopted - no FH
Drink on weekends, drink occasionally with friends after work
Smoke 5 a day
What is diarrhoea? How is it clinically defined?
Defined as the passage of:
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 weigh greater than 200 g/day
What are the 3 types of diarrhoea based on duration?
Acute (≤14 days)
Persistent (>14 days)
Chronic (>4 weeks)
What is the basic pathophysiology of diarrhoea?
Normally approximately 10L of fluid + secretions (from the salivary glands, stomach, pancreas, bile ducts, and duodenum) enter the GI tract every day
The small intestine = major site for re-absorption
Overall, about 99% of the fluid is re-absorbed, leaving 0.1 litre to be excreted in the faeces
Diarrhoea = factors interfere with normal process = decreased reabsorption or increased secretion of fluid and electrolytes, or increase in bowel motility
What two categories can diarrhoea be divided into pathophysiologically?
Inflammatory diarrhoea
Non-inflammatory diarrhoea
What is inflammatory diarrhoea? What can it be caused by?
Inflammatory process present - can be due to bacterial, viral, or parasitic infection, or may develop early in the course of bowel ischaemia, radiation injury, or inflammatory bowel disease
May also be called infectious diarrhoea
What are the symptoms of inflammatory diarrhoea?
Associated with - mucoid and bloody stool, tenesmus, fever, and severe crampy abdominal pain
Infectious inflammatory diarrhoea = small in volume, with frequent bowel movements (so does not result in volume depletion in adults, but may do so in children or older adults)
What is the most common cause of infectious diarrhoea?
In the US = bacterial infection: mainly Campylobacter, Salmonella, Shigella, Escherichia coli, or Clostridium difficile
Viruses = more common among children who attend day care centres
Protozoa and parasites are common causes of acute diarrhoea in developing countries
What is likely to show up in the examinations, tests and histology reports in a patient with inflammatory diarrhoea?
Examination of the stool may show leukocytes, and tests for faecal occult blood may be positive
The test for faecal leukocytes is plagued by a high rate of false-negative results leading to low sensitivity, but a positive test is very informative
Histology of the GI tract is abnormal in inflammatory diarrhoea
What is non-inflammatory diarrhoea?
Watery, large-volume, frequent stool (>10 to 20 per day)
Volume depletion is possible due to high volume and frequency of bowel movements
No tenesmus (cramping rectal pain), blood in the stool, fever, or faecal leukocytes
Histologically the GI architecture is preserved
What are the 2 further subdivisions of non-inflammatory diarrhoea?
Secretory diarrhoea
Osmotic diarrhoea
What is secretory diarrhoea?
What does not alleviate secretory diarrhoea?
Altered transport of ions across the mucosa = increased secretion and decreased absorption of fluids and electrolytes from the GI tract, esp. in the small intestine.
Secretory diarrhoea tends not to decrease by fasting
What are some causes of secretory diarrhoea?
Enterotoxins = can be from infections e.g. Vibrio cholerae, Staphylococcus aureus, enterotoxigenic E coli, and possibly HIV and rotavirus
Hormonal agents = vaso-active intestinal peptide, small-cell cancer of the lung, and neuroblastoma
Laxative use, intestinal resection, bile salts, and fatty acids
It is also seen in chronic diarrhoea with coeliac sprue, collagenous colitis, hyperthyroidism, and carcinoid tumours
What is osmotic diarrhoea?
How does it differ from secretory diarrhoea in terms of alleviating factors?
Stool volume is relatively small (compared with secretory diarrhoea), and diarrhoea improves or stops with fasting
Results from presence of unabsorbed / poorly absorbed solute (magnesium, sorbitol, and mannitol) in the GI tract that causes an increased secretion of liquids into the gut lumen
What test may be done to see if a patient has osmotic diarrhoea?
Why is this test limited in a practical setting?
Measuring stool electrolytes shows an increased osmotic gap (>50), but the test has very limited practical value
Stool (normal or diarrhoea) is always isosmotic (260 to 290 mOsml/L)
What are the 2 subdivisions of osmotic diarrhoea?
Maldigestion and Malabsorption
What are the characteristics of maldigestion and malabsorption?
Maldigestion = impaired digestion of nutrients within the intestinal lumen or at the brush border membrane of mucosal epithelial cells; can be seen in pancreatic exocrine insufficiency and lactase deficiency
Issue with the breakdown of the nutrients in the lumen for it to be absorbed (e.g. lactose intolerance)
Malabsorption = impaired absorption of nutrients; can be seen in small bowel bacterial overgrowth, in mesenteric ischaemia, post bowel resection (short bowel syndrome), and in mucosal disease (coeliac disease)
Issue with the movement of the nutrient from the lumen to the enterocytes
Are the fluids that enter the digestive system only the ones we drink?
How much fluid is lost in the faeces?
What happens to the fluid that is not excreted?
1-2 litres = fluids we drink/ day
6-7 litres = entering via secretions/ day
So overall 10 - 11 L fluids go through our digestive tract a day
And 0.1L lost in faeces
Gets absorbed via the walls of the small and large intestine
How are fluids reabsorbed in the lumen of the digestive tract?
Enterocytes and permeable molecules can travel across the lumen into the enterocyte
First the permeable nutrients travel into the enterocytes
The nutrients are pushed in the bloodstream in exchange for solutes using a pump
The solutes accumulate in the enterocyte
This creates an osmotic gradient allowing water to follow into the enterocyte to be reabsorbed
This is how 99% of the fluids are reabsorbed
[look up bio notes]
So what happens in diarrhoea?
Issue with membrane that prevents uptake of the nutrients (and so fluids) into the enterocytes
Or
Increased fluid secretion into the lumen
What are the issues between the lumen and the enterocyte for each type of diarrhoea?
Inflammatory Diarrhoea
- exodation of serum and blood
- inflammation damages the enterocyte membrane, nutrients are lost to the lumen (affects osmotic gradient) = fluid left in the lumen
Non-inflammatory Diarrhoea:
Secretory diarrhoea
- Error with the ion channels, whilst solutes are supposed to only stay on the enterocyte side, but now the
- Cl channel activated in cholera = solute in the lumen = fluid held by the solutes in the lumen
Osmotic diarrhoea:
Maldigestion
- Lack of digestion of nutrients = nutrients remain in the lumen = fluid held in the lumen
Malabsorption
- Solutes not absorbed by enterocytes e.g. prunes, sorbitol (sugar alcohol) = water is retained in lumen
What happens in inflammatory diarrhoea (enterocytes)?
Destruction of the epithelium due to inflammation
Enterocytes cannot absorb fluids
Excess fluid in lumen
What happens in secretory diarrhoea (enterocytes)?
Ion channels become wrongly activated so solutes moves into the lumen
E.g. Cholera - chloride channel on enterocyte membrane becomes activates
Fluid follows the chloride
What happens in maldigestion diarrhoea (enterocytes)?
Solutes are not able to digest
Products remain in lumen - high solute concentration
Fluid moves to lumen
E.g. lactose intolerance
What happens in malabsorption diarrhoea (enterocytes)?
Solutes not absorbed by enterocytes
E.g. prunes
Sorbitol is not absorbed by enterocytes
Water is retained
What drug could help inflammatory?
Anti-cytokines e.g. Anti-TNF
What drug could help secretory?
Block dysregulated channel
What drug could help maldigestion?
Enzyme replacement to facilitate reabsorption
What drug would you design for each type of diarrhoea?
Inflammatory = something that reduces inflammation e.g. steroids
Secretory = antagonist to fight the molecule that is activating the ion channels
Maldigestion = give the enzyme that is missing
Malabsorption = a drug that kills the parasite
What is the treatment for diarrhoea in the short term (acutely)?
ORS - oral rehydration salts
Sodium glucose linked transporter 1 channel (SGLT1)
ORS gives a ratio of 1 glucose to 2 Na+
SGLT1 pick up the Na+ ions into the enterocytes, solute is now inside the enterocyte so fluid moves down the osmotic gradient into the enterocytes as well
Why does diarrhoea kill?
Dehydration
ORS essential especially in children
Lucy has presented with chronic diarrhoea
What are the 2 causes for chronic diarrhoea?
Functional = e.g. IBS
Organic = everything else (all other causes) e.g. IBD = structural change that can be seen and measured
What is IBS?
Functional cause of diarrhoea
No known structural changes
Symptoms are unexplained
Non-progressive and will not kill patient
Divide the following the symptoms in terms of functional and organic causes?
Functional (e.g. IBS):
Mucus in stool
Abdominal bloating
Alternating constipation and diarrhoea
Organic (e.g. IBD):
Fever
Blood in stool
Weight loss
Both:
Fatigue
Abdominal pain
Faecal urgency
How can blood on stool be divided into 2 separate symptoms and what do they indicate?
Blood on the toilet paper VS blood actually mixed into the stool
Blood on toilet paper = more benign causes e.g. haemorrhoids
Blood in actual stool = symptom of IBD
Looking at the Venn diagram, what is the likely cause of Lucy’s chronic diarrhoea?
Organic cause
e.g. IBD, coeliac disease, lactose intolerance, bowel cancer etc.
What was found upon Lucy’s abdo examination?
Soft abdomen
Tenderness particulary in LLQ
No masses
What investigations would you do next to determine the exact organic cause of Lucy’s chronic diarrhoea and why?
- FBC - look for signs of infection / inflammation and anaemia
- Urea and electrolytes - check renal function and electrolyte status
- CRP - look for infection/inflammation
- Stool sample test - check for parasites, bacteria (microbiology, ova and cysts)
- Antibody assay - for coeliac disease
- LFT - liver function tests, also get albumin levels in this so low albumin = low something or malnourishment
- Thyroid function test - hyperthyroidism = diarrhoea esp. autoimmune thyroid conditions common in young females
- Blood test for ferritin / Vit B12, folate
- Stool test - for faecal calproctectin = surrogate marker for inflammation in the bowel = indicator of migration of neutrophils int he intestinal mucosa (cannot tell you source or cause of inflammation - raised in IBD, colon cancer, etc.)
x
x
x
x
Why bother with a stool sample if the GP has already checked?`
Need 3 samples 2 days apart as ova and cysts shed intermittently
So could have been none present in the sample given to the GP
All investigations normal except - raised WCC, raised CRP and elevated faecal calprotectin
What are the top differentials for Lucy Allen?
Investigation results suggest inflammation
Differentials narrow to IBD or colon cancer
In a young women, IBD most likely
What should be done next?
Refer to gastro unit
Here colonoscopy can take place - conducted by a specialist
The colonoscopy and histopathology report shows:
Non continuous areas of linear ulcers with cobblestone appearance are seen extending from the caecum through to the splenic flexure. When examined under a microscope, changes are seen in the mucosa, submucosa and muscularis propria. Numerous non caseating granulomas and increased goblet cells noted
What is Ms Allen’s diagnosis and why?
IBD - likely Crohn’s
Due to:
Non-continuous areas of abnormality / inflammation
Caecum –> splenic flexure = location
Non-caseating granulomas - collections of neutrophils
Deep ulcerations
Cobblestone appearance
Changes in the mucosa, submucosa and muscularis propria
How do UC and Crohn’s differ?
IBD = non-continuous and can affect any part of the GI tract from the mouth to the anus; non-caseating granulomas; cobblestone appearance due to long ulcers that go deep into the bowel; affects all layers of the bowel - transmural disease; deep transmural affect = fistula (hollow tube)
Ulcerative colitis (UC) = continuous, starting from the rectum and does NOT extend beyond the large bowel (although in severe cases is may affect small bowel due to backwash); pseudopolyps (raised areas give the appearance of polyps) due to cycle of inflammation and scarring; changes confined to mucosa (and in severe cases = submucosa); lack of fistulas but higher predisposition to colon cancer due to affecting only mucosa and submucosa
What treatments can be offered for Crohn’s disease for Lucy Allen?
Conservative
Medical
Surgical
Conservative:
Smoothies - replace malnutrition
Diet
Psychological therapies - mental support for socially embarrassing symptoms (difficult to fit into social life)
Patient support groups - meet others with same condition as them
Smoking cessation
Medical:
Acute phase = corticosteroids to induce remission of disease (settle symptoms)
Steroids are not prescribed for life due to long term side effects
Long-term = azothiprine or biologics
Biological medications - synthesised antibodies, interleukins, etc. e.g. infliximab
Surgical:
Resection of the affected areas - most patients with Crohn’s require this due to fistulas
Why does smoking worsen Crohn’s but help ulcerative colitis?
Causes small areas of infarction in the gut in Crohn’s
Dampen down immune response in UC
Does UC and Crohn’s have the same treatment?
No, because for UC, inflammation always starts at rectum and proceeds in a continuous fashion - so UC patients can be given local treatments rather than systemic (rectal ointments / medications)
What are some complications of UC?
High predisposition to Colon Cancer
At what age does Crohn’s present?
How does Crohn’s present clinically?
Affects people of all ages - symptoms usually start in childhood or early adulthood.
The main symptoms are:
diarrhoea
stomach aches and cramps
blood in your poo
tiredness (fatigue)
weight loss
Symptoms may be constant, or come and go (‘come’ = flare up)
When should you see the GP regarding Crohn’s?
Blood in your poo
Diarrhoea for more than 7 days
Frequent stomach aches or cramps
Lost weight for no reason, or your child’s not growing as fast as you’d expect
What are the main treatments for Crohn’s?
Medicines to reduce inflammation in the digestive system – usually steroid tablets
Medicines to stop the inflammation coming back – either tablets or injections
Surgery to remove a small part of the digestive system – sometimes this may be a better treatment option than medicines
Where can you get support for living with Crohn’s?
CoNtrolled symptoms = normal life
Unpredictability of flare ups can affect social life
Support is available from your care team and organisations like Crohn’s and Colitis UK if you need it
What causes Crohn’s disease?
your genes – you’re more likely to get it if a close family member has it
a problem with the immune system
smoking
a previous stomach bug
an abnormal balance of gut bacteria
What are the other symptoms of Crohn’s?
a high temperature feeling and being sick joint pains sore, red eyes patches of painful, red and swollen skin – usually on the legs mouth ulcers children grow more slow than usual
What would your GP ask you about?
your symptoms
your diet
if you’ve been abroad recently – you might have an infection
any medicines you’re taking
if you have a family history of Crohn’s disease
What investigations might your GP do?
feel and examine your tummy
take a sample of blood
ask you to provide a poo (stool) sample
What investigations might a specialist do?
Colonoscopy
Biopsy
MRI/CT Scan
How can steroids help with Crohn’s?
can relieve symptoms by reducing inflammation in your digestive system – they usually start to work in a few days or weeks
are usually taken as tablets once a day – sometimes they’re given as injections
may be needed for a couple of months – do not stop taking them without getting medical advice
What are the side effects of steroids?
weight gain indigestion problems sleeping an increased risk of infections slower growth in children
What can be helpful in children and young adults?
Liquid diet
Drinks containing all the nutrients
Avoids the risk of slower growth that happens with steroids
What is a liquid diet?
liquid diet (enteral nutrition)
involves having special drinks that contain all the nutrients you need, instead of your usual diet, for a few weeks
What are the side effects of enteral nutrition?
Diarrhoea
Constipation
Nausea
What immunosuppressants might be taken with Crohn’s?
azathioprine, mercaptopurine and methotrexate
What can immunosuppressants do in Crohn’s?
can relieve symptoms if steroids on their own are not working
can be used as a long-term treatment to help stop symptoms coming back
are usually taken as a tablet once a day, but sometimes they’re given as injections
may be needed for several months or years
What are the side effects of Immunosuppressants?
feeling and being sick, increased risk of infections and liver problems
What biological medicines are used in Crohn’s?
adalimumab, infliximab, vedolizumab and ustekinumab
What can biological medicines do in Crohn’s?
can relieve symptoms if other medicines are not working
can be used as a long-term treatment to help stop symptoms coming back
are given by injection or a drip into a vein every 2 to 8 weeks
may be needed for several months or years
What are the side effects of biological medications?
increased risk of infections and a reaction to the medicine leading to itching, joint pain and a high temperature
When might surgery be recommended?
the benefits outweigh the risks or that medicines are unlikely to work
What does a resection involve?
- Making small cuts in your tummy (keyhole surgery).
- Removing a small inflamed section of bowel.
- Stitching the healthy parts of bowel together
What might you need to careful about with Crohn’s?
Triggers
e.g. certain foods
pharmacy medicines
What’s the deal with Crohn’s and vaccinations?
Flub jab yearly
Avoid live vaccines e.g. MMR
What might be more difficult during a flare up?
Getting pregnant
What might not work as well when you have Crohn’s?
Some contraceptives
e.g. the Pill
What are possible complications of Crohn’s?
Damage to bowel e.g. scarring, narrowing, ulcers, fistulas
Difficulty absorbing nutrients - osteoporosis, iron deficiency anaemia
Bowel cancer
How does the risk of bowel cancer change with Crohn’s?
after 10 years the risk is about 1 in 50
after 20 years the risk is about 1 in 10
after 30 years the risk is about 1 in 5
What should people with Crohn’s do?
Have regular colonoscopies
