gastroenterology - peskó

Gastroenterology - PeskóSEMMELWEIS UNIVERSITY Faculty of Medicine 3rd Department of Internal Medicine Director: Professor Tamás Masszi
Case I. – source NEJM
A 40 year-old man presented to the ER with a 6-week long andominal pain and diarrhea. The pain was epigastric at the begining and occured after eating. Than it became more constant and diffuse: 7/10. The diarrhea started gradually and was watery, 6-7x daily (including when the patient fasted, at night). It was 6-7x daily (including when the patient fasted, at night). It was associated with urgency and tenesmus.
The stool was partially black, there was no fress red blood, it was not oily, foul smelleing or difficult to flush in the toilet. He lost 14kgs, but not his appetite. He has no fevers, night sweats, chest pain, cough, SOB, nausea, vomiting, dysuria, oral ulcerations or rashes.
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Case I.
By definition diarrhea is defined as the passage of loose or watery stools, typically at least three times in a 24-hour period. It reflects increased water content of the stool, whether due to impaired water absorption and/or active whether due to impaired water absorption and/or active water secretion by the bowel.
Case I. –chronic diarrhea
Acute — 14 days or fewer in duration
Persistent diarrhea — more than 14 but fewer than 30 days in duration
Chronic — more than 30 days in duration
Acute diarrhea most often caused by infections.Acute diarrhea most often caused by infections.
Noninfectious etiologies become more common as the course of the diarrhea persists and becomes chronic.
In developing countries, chronic diarrhea is frequently caused by chronic bacterial, mycobacterial, and parasitic infections, although functional disorders, malabsorption, and inflammatory bowel disease are also common.
In developed countries, common causes are irritable bowel syndrome (IBS), inflammatory bowel disease, malabsorption syndromes (such as lactose intolerance and celiac disease), and chronic infections (particularly in patients who are immunocompromised).
Functional diarrhoe
The typical example is IBS: the symptom complex of chronic lower abdominal pain and altered bowel habits remains the nonspecific yet primary characteristic of IBS. (Rome IV criteria for IBS)
Rome IV criteria for IBS — According to the Rome IV criteria, IBS is defined as recurrent abdominal pain, on average, at least one day per week in the last three months, associated with two or more of the following criteria:
Related to defecation
Associated with a change in stool frequency Associated with a change in stool frequency
Associated with a change in stool form (appearance)
Most bowel movements are preceded by extreme urgency and may be followed by a feeling of incomplete evacuation
Post-infectious IBS can occur following recovery from Clostridium difficile and other bacterial infections
Large volume diarrhea, bloody stools, nocturnal diarrhea, and greasy stools are not associated with IBS
Rather organic: weight loss of more than 5kgs, nocturnal diarrhea, GI bleeding, anemia, hypalbuminemia, elevated inflammatory markers
Osmotic diarrhoe
Fecal osmotic GAP 290-2x(stoolNa+stoolK) >150msom is diagnostic
luminal substances are responsible for the induction of the fluid secretion
Typical: osmotic laxatives, sweeteners, CH/fat malabsobtion Typical: osmotic laxatives, sweeteners, CH/fat malabsobtion
most common cause of carbohydrate malabsorption is lactose intolerance
uncommon defects in carbohydrate absorption — including sucrase– isomaltase deficiency
it is essential to determine whether steatorrhea is present
Typically ceases with fasting!
endogenous substances (often referred to as “secretagogues”) induce fluid secretion that persists even when the patient is fasting
Watery voluminousus stools with narrow GAP (<50mosm) Watery voluminousus stools with narrow GAP (<50mosm)
Typical: drugs, bowel resection, neuroendocrine tumors
Helpful to assess the effect of a fast on stool output: when diarrhea ceases with fasting, a dietary nutrient is likely to be the cause; if diarrhea persists unabatedly with fasting, a dietary nutrient is not likely to be the cause.
Inflammatory
The intestinal mucosa is distrupted by an inflammatory process
The hallmark is bloody stool (or melena) combined with systematic symptomes (abdominal pain, fever)
IBD: ulcerative colitis and Crohn disease
Invasive infectious diarrhea (bloody, fecal leukocytes, lactoferrin) Invasive infectious diarrhea (bloody, fecal leukocytes, lactoferrin)
When there is bloody diarrhea with few or no fecal leukocytes, stool should be sent for evaluation for amebiasis, which can be diagnosed on stool by microscopy, antigen testing, or molecular methods
Steatorrheic
The absorbtion of fat in the small intestine is impaired
Greasy, bulky, malodorous stool that floats in water and difficult to flush
Typical: chronic pancreatitis, bacterial overgrowth, celiac disease
Differential diagnosis of chronic diarrhea
Don’t forget: • IBS • Overflow diarrea
DDx of chronic diarrhea - bloody
Clinical exam RDV: rule out hemorrhoids and fissures
Type of diarrhea inflammatory
subtype infections IBD other
Eosiniophilic gastroenteritis, Chronic GVHD, Radiation colitis, Pleisiomonas,
Campylobacter, Yersinia, CMV, HSV, Entamoeba histolytica, Strongiloides, Giardia, Cryptosporidium, Cyclospora
Radiation colitis, Ischemic colitis, Colon Cancer, Lymphoma, Diverticular colitis
DDx of chronic diarrhea - watery
Clinical exam Continues while fasting Low osmotic gap
Normal osmotic gap Decrease while fasting High osmolar gap
Type of diarrhea Secretory diarrhea Rome IV criteria met no red flags
Osmotic diarrhea
IBS, post-infectious irritable bowel syndrome
Lactase deficiency Osmotic laxatives Non-absorbable CH-s
syndrome) Endogenous sectretagogues (NET hormones, malabsorbtion of bile acids) Exogenous sectretagogues (alcohol, stimulant laxatives – Senna, toxins) Endocrin disorders (hyperthyreodism, Addison’s, diabetic autonomic neuropathy) Microscopic colitis Chronic infections
DDx of chronic diarrhea - fatty
Clinical exam Stool elastase < 200ug
Type of diarrhea Steatorrheal diarrea
subtype
Pancreatic insuffitiency Bile-salt deficiency (hepatic disease, disease of the disease, disease of the terminal ileus) Mucosal malabsorbtion (celiac disease, bacterial overgrowth, Whipple’s disease, short gut syndrome)
Let’s see some examples for chronic diarrhoe!chronic diarrhoe!
44-year old woman who has diarrhea for several years reports fatigue
and weight loss. She got the diagnosis of osteoporosis and iron-
deficiency anemia.
F. Whipple's disease
G. Zollinger-Ellison syndome
Closed
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Celiac disease
Aberrant inflammatory response to gliadin (component of gluten)
Resolves with removal of gluten from diet
60 year-old woman with hypothyroidism has profuse watery diarrhea,
sometimes nocturnal for the past year. She lost weight. No blood or
mucus in the stool. She takes high doses if ibuprofen for osteoarthriris.
A. Bacterial owergrowth
B. Celiac disease
C. Dumping syndrome
F. Whipple disease
G. Zollinger-Ellison syndrome
Closed
Microscopic colitis
chronic, inflammatory disease of the colon that is characterized by chronic, watery diarrhea, 50% nocturnal
female predminance, with a mean age at diagnosis of 65 years
At endoscopy the mucose seems to be normal, but biopsy reveals mucosal inflammation (always get a biopsy!)
Two types: lymphocytic (intraepithelial lymphocytic infiltrate) Two types: lymphocytic (intraepithelial lymphocytic infiltrate) and collagenous (colonic subepithelial collagen band)
associated with celiac disease, autoimmune thyroiditis, type 1 diabetes mellitus, and nonerosive, oligoarticular arthritis
autoantibodies are found in approximately one-half of patients (RF, ANA, AMA, ANCA, ASCA, TPO)
should be advised to avoid nonsteroidal anti-inflammatory drugs
Th: budesonide, cholestyramine, bismuth salicylate
26-year-old mother of healthy children of kindergarden age reports
having abdominal cramps, loose stool, flatulance and weight loss for 1
month.
F. Whipple's disease
G. Zollinger-Ellison syndrome
Closed
Giardiasis Giardia duodenalis (also known as G. lamblia or G. intestinalis) is a protozoan
parasite capable of causing sporadic or epidemic diarrheal illness
important cause of waterborne, foodborne, or fecal-oral transmissions in daycare center outbreaks, and illness in international travelers
It has two morphological forms: cysts and trophozoites:
Cysts are the infectious form of the parasite; following cyst ingestion, trophozoites are released in the proximal small intestine
Trophozoites that do not adhere to the small intestine move forward to the large intestine where they revert to the infectious cyst form; these cysts are passed intestine where they revert to the infectious cyst form; these cysts are passed back into the environment in excreted stool
Giardia can lead to acute and chronic diarrhea with malabsobtion and malaise:
half of exposed individuals clear the infection in the absence of clinical symptoms
15 percent of individuals shed cysts asymptomatically
35 to 45 percent of individuals have symptomatic infection
Acquired lactose intolerance occurs in up to 40 percent of patients
Small intestine bacterial overgrowth (SIBO)
colonic bacteria are present in increased numbers in the small intestine
can occur in association with anatomical abnormalities; motility disorders; metabolic and systemic disorders; immune disorders
May lead to diarrhea, malabsobtion, abdominal pain, bloating, weight loss in patients
Carbohydrate malabsorption results from the intraluminal degradation of sugars by enteric bacteria. This leads to the production of short-chain fatty acids, carbon dioxide, hydrogen, and methane.
Fat malabsorption results from bacterial deconjugation of bile acids and the toxic effect of free bile acids on the intestinal mucosa. Hydroxylated fatty acids and free bile acids stimulate the secretion of water and electrolytes, leading to diarrhea.
Protein malabsorption results from decreased mucosal uptake of amino acids and the intraluminal degradation of protein precursors by bacteria. SIBO may also be associated with a reversible form of protein-losing enteropathy.
Deficiency in vitamin B12 results from utilization of vitamin B12 coupled to intrinsic factor by anaerobic bacteria.
The endoscopic appearance and histopathology of the small intestine and colon is normal in most patients with SIBO
The diagnosis of SIBO should be suspected in patients with bloating, flatulence, abdominal discomfort, or diarrhea, and is established with a positive carbohydrate breath test or jejunal aspirate culture
Oral antibiotics are effective in many patients: rifaximin
Diseases causing diarrhea with skin manifestation Celiac disease: In patients with this condition,
other autoimmune disorders, cancer, or dermatitis herpetiformis may develop. This symmetric, intensely pruritic, papulovesicular eruption intensely pruritic, papulovesicular eruption appears on the elbows, knees, and trunk. The vesicles are often sparse or absent (as pictured), since patients typically scratch them off as soon as they appear, leaving excoriated remnants.
Case I.
Medical history:
Type-2 DM for 5 years
Chronic back and neck pain for 20 years Chronic back and neck pain for 20 years
One time uveitis 3 years ago treated with steroids
Nephrolithiasis
Smoked for 30 years
Meds: insulin, metformin, ibuprofen
Case II. Maybe: celiac disease, Whipple’s disease, IBD or colonoc ulcers due to
NSAIDs
Tenderness to palpation in epigastrium Tenderness to palpation in epigastrium
Hemoccult positive stool
decreased mobility of lumbar spine spondyloarthritis
Back pain in a patient younger than 45 years, with insidious onset and duration for more than 3 months, accompanied by morning stiffness and improvement with exercise inflammatory back pain = axial spondyloarthritis
Dg: sacroileitis + 1 clinical feature or HLA-B27 + 2 clinical features
Which is NOT one of the clinical features of spondyloarthritis?
A. enthesitis
B. uveitis
C. dactylitis
D. fever
Closed
Case I. What is the diagnosis that gonna explain it all?
chronic, secretory, inflammatory diarrhea (bloody)
weight lossweight loss
nephrolithiasis
Given the patient's diagnosis of ulcerative colitis, which one of the
following conditions do not endanger him?
A. Hepatocellular carcinoma
Closed
Diseases causing diarrhea with skin manifestation Ulcerative colitis: The classic presentation of pyoderma gangrenosum is an
undermined leg ulcer, but the ulcer may occur anywhere on the body. Lesions may appear in response to trauma and are often located near stomas or surgical wounds. Pyoderma gangrenosum occurs in Crohn’s disease but is more common in ulcerative colitis. Other causes include rheumatoid arthritis and myeloproliferative disorders. Lesions respond to local or systemic myeloproliferative disorders. Lesions respond to local or systemic glucocorticoids
Erythema nodosum is also a skin manifestation of the disease:
Case II. acute diarrhea
A 43-years-old man seeks help at the doctor’s office:
Past medical history: HTN, tonsillectomia
Meds: ACEi+amlodipine
No medical allergies. No tobacco. No alcohol.No medical allergies. No tobacco. No alcohol.
Present illness: diarrhea started yesterday: 5-6x small amount watery (nonbloody, nonblack), it waked the patient up; nausea but no vomitus; fever+chills (over 38.5Celisus); cramping abdominal pain; no xanthema; others have not developed diarrhea
Acute diarrhea
diarrheal diseases represent one of the five leading causes of death worldwide
most cases of acute diarrhea in adults are of infectious etiology
dilemmas in assessing patients with acute diarrhea is deciding dilemmas in assessing patients with acute diarrhea is deciding when to perform stool testing and if and when to initiate therapy
most cases of acute diarrhea are due to infections and are self- limited
most cases of acute infectious diarrhea are likely viral, as indicated by the observation that stool cultures are positive in only 1.5 to 5.6
Among those with severe diarrhea, however, bacterial causes are responsible for most cases
Try to guess the patogen Characteristics (small or large bowel)
small bowel origin is typically watery, of large volume, and associated with abdominal cramping, bloating, and gas, fever is rare, occult blood/inflammatory cells/lactoferrin is rare
large intestinal origin often presents with frequent, regular, small volume, and often painful bowel movements, fever and bloody or mucoid stools are common, red blood cells and inflammatory cells can be seen routinely
inflammatory signs associated with large bowel infection (fever, bloody or mucoid stools) suggest invasive bacteria bloody or mucoid stools) suggest invasive bacteria (Salmonella, Shigella, Campylobacter), enteric viruses (cytomegalovirus [CMV], adenovirus), Entamoeba histolytica, cytotoxic organism such as C. difficile
Visibly bloody acute diarrhea is relatively uncommon, raises the possibility of enterohemorrhagic E. coli (EHEC) (eg, E. coli O157:H7) infection. Other bacterial causes of visibly bloody diarrhea are Shigella, Campylobacter, and Salmonella (sometimes Yersinia) species. Bloody diarrhea can also reflect noninfectious etiologies such as IBD or ischemic colitis
syndromes that begin with diarrhea but progress to fever and systemic complaints, such as headache and muscle aches: typhoidal illness, infection with Listeria monocytogenes
Try to guess the patogen
Food history: it is often difficult to know which food exposure was the potential source, the timing of symptom onset following exposure to the suspected offending food can be an important clue to the diagnosis
Exposure to animals (poultry, turtles, petting zoos) has been associated with Salmonella infectionbeen associated with Salmonella infection
Occupation in daycare centers has been associated with infections with Shigella, Cryptosporidium, and Giardia
Medical history: recent antibiotic use (C. difficile infection), other medications (such as proton pump inhibitors), past medical history (immunocompromised host or the possibility of nosocomial infection)
pregnancy increases the risk of listeriosis
cirrhosis has been associated with Vibrio infection
Patogenic mechanism
Organisms that make a toxin in the food before the food is consumed. Consumption of the toxin-contaminated food will usually lead to the rapid onset of symptoms (6 to 12 hours) that are predominantly upper intestinal. (Staphylococcus aureus, Bacillus cereus emetic toxin, botulism)
Pathogens that make toxin once they have been ingested. This usually takes longer (approximately 24 hours or longer), causes diarrhea that may be watery longer (approximately 24 hours or longer), causes diarrhea that may be watery (Vibrio cholerae or Enterotoxigenic E. coli) or bloody (Shiga toxin-producing E.
coli)
Microbes that cause pathology by either damaging the epithelial cell surface or by actually invading across the intestinal epithelial cell barrier. Wide spectrum of clinical presentations: watery diarrhea (Cryptosporidium parvum, enteric viruses) to inflammatory diarrhea (Salmonella, Campylobacter, Shigella) or systemic disease (L. monocytogenes)
Foodborne? one in five episodes of diarrhea is likely to be due to a
foodborne disease
patient presents with gastrointestinal symptoms including nausea, vomiting, abdominal pain, diarrhea and fever HOWEVER
patients with foodborne illness may present initially with other complaints such as neurologic symptoms (eg, headaches,
The incidence of laboratory-confirmed cases per 100,000 persons in 2014 was as follows (USA):
Salmonella – 15.45
Campylobacter – 13.45
Shigella – 5.81
Cryptosporidium – 2.44
Shiga-toxin producing E. coli, O157 complaints such as neurologic symptoms (eg, headaches, paralysis or tingling), hepatitis, and renal failure
What are the probable microbial causes of foodborne disease?
How do time course and types of symptoms serve as clues?
How can a food history help to narrow the diagnosis?
Listeriosis, Shiga toxin producing Escherichia coli, and nontyphoidal Salmonella are particularly associated with severe morbidity
Foodborne disease outbreak: 1. Norovirus (associated with leafy vegetables) 2. Salmonella (associated with poultry and beef)
Shiga-toxin producing E. coli, O157 – 0.92
Shiga-toxin producing E. coli, non- O157 – 1.43
Vibrio – 0.45
Yersinia – 0.28
Listeria – 0.24
Cyclospora – 0.05
VOMITING AS THE MAJOR PRESENTING SYMPTOM Sudden onset of nausea and vomiting is likely due to the ingestion of a preformed toxin - there is no risk of person-to-person spread.
Staphylococcus aureus – enterotoxin: symptoms usually begin within one to six hours of ingestion with nausea, vomiting and abdominal cramps
toxin is heat-stable and is often associated with the consumption of foods prepared by a food handler such as dairy, produce, meats, eggs, and salads; the food handler usually contaminates the product [clinical dg.]
Bacillus cereus: capable of producing a heat-stable emetic enterotoxin in starchy foods such as rice Bacillus cereus: capable of producing a heat-stable emetic enterotoxin in starchy foods such as rice
rapid (within one to six hours) onset of nausea and profuse vomiting; self-limited [clinical dg.]
Noroviruses (Norwalk-like viruses): major foodborne diseases that typically cause vomiting as the predominant symptom
most common foodborne diseases and the most frequent cause of acute gastroenteritis
low infectious dose (around 10 particles); transmitted from the vomitus and the stool of an infected person; usually transmitted from a food handler via food (salads, sandwiches, fruit)
illness usually lasts for 48 to 72 hours with a rapid and full recovery but without long- lasting immunity
diagnosis of several viruses (rotavirus, enteric adenovirus) can be made
WATERY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Many foodborne microbes cause watery diarrhea, the presence of this symptom alone is of little help in the differential diagnosis. Organisms that produce toxins once ingested typically have an incubation period of 24 to 48 hours.
Clostridium perfringens: spores of C. perfringens can germinate in foods such as meats, poultry or gravy (large quantity needed); toxin is produced in the host GI tract
psychiatric inpatient facilities: impaired intestinal motility caused by antipsychotic medications
C. perfringens type C produces a beta toxin, which can cause enteritis necroticans (pigbel)
Enteric viruses: norovirus, rotavirus, enteric adenoviruses, and astroviruses
Enterotoxigenic Escherichia coli: common cause of traveler's diarrhea [no specific test]
both transmitted via fecal contamination of food or water from an infected person Prepared food is therefore at the top of the list of likely sources for these pathogens
WATERY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Cryptosporidium parvum: 10 percent is foodborne
persistent chronic diarrhea in immunocompromised patients
endemic in cattle; acquired from contaminated water, fresh produce, unpasteurized milk or person-to-person spread
Incubation period 7-28 days; dg: acid-fast staining of stools, immunofluorescence microscopy, Incubation period 7-28 days; dg: acid-fast staining of stools, immunofluorescence microscopy, enzyme immunoassay
no current reliable therapy
Cyclospora cayetanensis : 90 percent is foodborne
fecally contaminated water, berries, fresh basil
diagnosis of C. cayetanensis is important because it is readily treatable with trimethoprim/sulfamethoxazole
Intestinal tapeworms: Taenia saginata, Taenia solium, Diphyllobothrium latum
consumption of undercooked beef, pork and fish
INFLAMMATORY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Presence of inflammatory cells or a marker of inflammatory cells, such as fecal lactoferrin, defines an inflammatory diarrhea
Clinical clues: diarrhea with blood or mucus, severe abdominal pain, fever
Statistically the most likely pathogens in patients with inflammatory diarrhea are Salmonella or Campylobacter
Salmonella: divided into two broad categories: those that cause typhoid and enteric fever and those that primarily induce gastroenteritisthose that primarily induce gastroenteritis
typhoidal Salmonella, such as S. typhi or S. paratyphi primarily colonize humans, are transmitted via the consumption of fecally contaminated food or water, and cause a systemic illness usually with little or no diarrhea
nontyphoidal Salmonella are found in the intestines of other animals and are acquired from the consumption of products that have become contaminated with animal feces. Associated withraw meat, poultry; foods such as fresh produce (sprouts, hot peppers, tomatoes, lettuce, melons); spices such as black and white pepper, peanut butter, chocolate and dried milk; egg
incubation period for non-typhoidal Salmonella is usually one to three days, and the diagnosis is undertaken with routine stool cultures
INFLAMMATORY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Campylobacter: Campylobacter jejuni accounts for the vast majority of foodborne campylobacteriosis, with Campylobacter coli responsible for most of the remainder
incubation period usually ranges from two to five days, and poultry is a frequent source of the organism
diagnosed using routine microbiologic techniques on selective plates
Shiga toxin producing E. coli (also known as enterohemorrhagic E. coli (EHEC)): most Shiga toxin producing E. coli (also known as enterohemorrhagic E. coli (EHEC)): most frequent cause of acute renal failure in children in the United States.
associated with diarrheal disease as well as the hemolytic uremic syndrome (HUS)
found in ground beef, unpasteurized juice, raw fruits and vegetables
incubation period ranges from approximately one day up to a week, usually begins with watery diarrhea that becomes bloody
STEC can be diagnosed using Shiga toxin based assaysimportant therapeutic implications, since data indicate that antibiotic treatment of STEC-infected patients may increase the risk of developing HUS
INFLAMMATORY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Shigella: only colonize humans and some nonhuman primates; therefore, transmission of Shigella in food or water is most likely from either fecal contamination or direct contamination from a food handler
foods have been implicated in the spread of Shigella, including salads , raw vegetables, milk and dairy products and poultry, as well as common-source water supplieswater supplies
isolated routinely in clinical microbiology laboratories
Vibrio: raw shellfish in the proceeding 48 hours and develop diarrhea should be cultured for Vibriospp. Most likely organism is V. parahaemolyticus
laboratories do not routinely culture for any Vibrio spp
Yersinia: unusual cause of foodborne disease that will cause an inflammatory diarrhea is Yersinia enterocolitica
consumption of undercooked pork, unpasteurized milk, or fecally contaminated water

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