Normal histology
•
•
Layers:
Mucosa
Submucosa
Muscularis propria (externa)
Subserosa
Serosa - contains mesothelial
lining, loose connective tissue
• Lamina propria: contains loose
connective tissue, lymphocytes, plasma
cells, occasional eosinophils,
macrophages, mast cells, neutrophils
Mucosa
• contains villi with
central blood
vessels, lymphatics
• epithelium
• lamina propria
• muscularis mucosa
Mucosa
• Villi: contain microvilli;
contain primarily
columnar absorptive
cells and goblet cells
• Absorptive cells: have
microvilli on luminal
surface (brush border)
and underlying mat of
microfilaments
(terminal web)
Crypts of Lieberkuhn
• lower 20% of epithelium,
contain undifferentiated
(immature) crypt cells,
Paneth cells (have large,
apical eosinophilic granules
containing antimicrobial
proteins), scattered goblet
cells and endocrine cells
• secrete ions, water, IgA,
antimicrobial peptides into
lumen
• crypt cells take 3-8 days to
migrate to surface; allows
for rapid repair, but also
causes these cells to be
sensitive to radiation
therapy and chemotherapy
Submucosa
• contains connective
tissue, blood vessels,
lymphatics, submucosal
(Meissner’s) plexus
Muscularis propria (externa)
inner circular and
outer longitudinal
layer, with
myenteric
(Auerbach’s)
plexus between
these layers;
plexus also
contains interstitial
cell of Cajal,
ganglion cells,
fibroblasts
Auerbach’s cells
• Interstitial cell of Cajal =type
of interstitial cell found in the
gastrointestinal tract that
serves as a pacemaker which
creates the basal electrical
rhythm leading to peristalsis
• ganglion cells=special nerve
cells in the intestine that make
the muscles push; congenital
aganglionosis-Hirschsprung's
disease
• fibroblasts=produce the
extracellular matrix and
participate in the transport of
absorbet metabolites to the
blood and lymphatic apillaries
Endocrine cells
• similar to cells in pancreas,
biliary tree, lung, thyroid,
urethra
• contain fine eosinophilic
granules with secretory
proteins
• nuclei on luminal side of
granules, not basal
- Serotonine
(enterocromafine)
- Gastrine (G)
- Secretine (S)
- Enteroglucagon (EG)
DISEASES OF THE INTESTINE
Congenital anomalies
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Meckel diverticulum
Duplications
Intestinal atrezia & stenosis
Malrotation
Gastroschisis & omphalocele
Meckel diverticulum
• During early gestation,
the omphalomesenteric
or vitelline duct connects
the fetal yolk sac to the
primitive gut. By 7 to 8
weeks of gestation, this
duct is normally
completely obliterated.
• A Meckel diverticulum,
results when this
structure fails to resorb
completely.
Symptoms
• most adults remain asymptomatic
• intestinal obstruction is manifested by cramping
abdominal pain, obstipation, nausea and
vomiting
• acute Meckel's diverticulitis is characterized by
abdominal pain and tenderness typically
localized below or to the left of the umbilicus; it
is often accompanied by vomiting and is similar
to appendicitis except for location of pain.
• bleeding- typically resulting in melena rather
than frank blood.
Signs
• voluntary guarding with mild tenderness
- in the absence of strangulation, the abdomen is not
tender
- with infarction, the abdomen becomes tender and
auscultation reveals a silent abdomen or minimal
peristalsis
• hyperactive, high-pitched peristalsis with rushes
coinciding with cramps is typical
• sometimes, dilated loops of bowel are palpable
• shock and oliguria are serious signs that indicate either
late simple obstruction or strangulation
Diagnosis
• based on symptoms
• flat and upright X-rays of the abdomen (vomiting and
signs of obstruction)
• CT scan with oral contrast (for abdominal pain and
focal tenderness)
• wireless capsule
• radionuclide scan
- 99mTc pertechnetate scan may identify ectopic gastric
mucosa and hence the diverticulum (if rectal bleeding
is suspected to originate from a Meckel's diverticulum)
Barium X-ray
Axial contrast-enhanced CT scan shows blind-ending Meckel's diverticulum
with thickened mucosal folds (arrow). Pathology confirmed ectopic gastric
mucosa in Meckel's diverticulum.
Giant Meckel diverticulum in a 21-year-old
man who was referred for wireless capsule
endoscopy because of chronic abdominal
pain and anemia. Results of a small bowel
follow-through study, radionuclide
examination, and endoscopy of the upper
and lower gastrointestinal tract were
unremarkable. (a) Wireless capsule
endoscopic image shows a shallow ulcer in
one segment of the ileum (arrow). Other
images showed ulcers in an adjacent
segment and possibly in the colon. Doublecontrast barium enteroclysis was requested
to determine the extent of Crohn disease.
(b) Double-contrast air-barium enteroclysis
image shows a large saccular dilatation
(arrowheads) in a pelvic segment of the
ileum. Scattered ulcerations (arrow) are
seen adjacent to the point of attachment of
the dilatation to a normal-appearing loop of
ileum. Results of surgery confirmed the
presence of a giant Meckel diverticulum
with ulcerations. There was no evidence of
Crohn disease.
Technetium-99m pertechnetate
scan in a 12-year-old boy who
presented with intermittent dull
abdominal pain and a mild iron
deficiency anemia. On the present
occasion, the pain appeared more
severe and was associated with
occasional vomiting; thus, the
child was hospitalized.
This 90-minute delayed image
shows focal activity in the mid
abdomen. The activity is more
diffuse than is expected with
Meckel diverticulum.
At surgery, an inflamed Meckel
diverticulum containing ectopic
gastric mucosa was removed.
The Meckel diverticulum had
intussuscepted into the terminal
small bowel.
Differential diagnosis
•
•
•
•
•
•
•
•
•
appendicitis
intestinal polyposis syndromes
colitis
intussusception
colonic vascular malformations
juvenile polyps
necrotizing enterocolitis
Crohn disease
ulcerative colitis
Complications
• The risk for complications dramatically decreases
with age, and most adults with a Meckel
diverticulum remain asymptomatic.
• Complications develop in approximately 2% of all
adults with a Meckel diverticulum:
- bleeding
- intestinal obstruction
- diverticulitis
- perforation
- carcinoma
Obstruction is caused by:
• intussusception of the diverticulum into
adjacent bowel
• volvulus around or herniation into a fibrous
band
• entrapment in inguinal, femoral or umbilical
hernia sacs (Littré hernia)
• inflammation and scarring leading to blockage
around the diverticular neck and adjacent
ileum
Structural anomalies
•
•
•
•
Volvulus
Intussusception
Lymphangiectasia
Celiac artery compression
Volvulus
• abnormal twisting of the intestine around the
axis of its own mesentery, resulting in
obstruction of the more proximal bowel
• twisting of the mesentery may involve the
mesenteric vessels and so make the involved
loop particularly susceptible to strangulation
and gangrene, with resulting perforation,
peritonitis and sepsis
Symptoms
• often has an abrupt onset
- abdominal pain continuous, sometimes
with superimposed waves
of colicky pain
- obstipation
- nausea
- vomiting
- marked abdominal
distention
Signs
•
•
•
•
•
abdominal distention
rebound
guarding
rigidity
a palpable abdominal
mass (occasionally)
Complications
• SURGICAL EMERGENCY!
•
•
•
•
•
strangulation of the twisted bowel loop
loss of blood supply
deterioration
perforation
fatal peritonitis when the bowel material
infects the abdominal cavity
Investigations
• abdominal and chest X-rays may show the
obstruction and abnormal air-fluid levels in
the bowels
• barium enema X-ray shows typical volvulus
shapes
• CT
• white blood cell count will be higher than
normal
Radiological investigations
• Plain abdominal radiographs taken in supine and
upright positions may demonstrate distended
bowel with air-fluid levels, consistent with
obstruction.
• Perforation may be indicated by the presence of
free air.
• A typical corkscrew-like appearance of the
barium in the distorted duodenum and jejunum
is diagnostic.
• Angiography may reveal twisting of the branches
of the superior mesenteric artery.
X-ray
Small-Bowel Obstruction (Supine)
Small-Bowel Obstruction (Upright)
Dysmotility
• Chronic small intestine pseudoobstruction
- it may be secondary to neuropathy or
myopathy
- abnormalities of small bowel ICCs
- there is some evidence of a genetic
association
- it can occur in conjunction with Kawasaki
disease or Parkinson's disease
Dysmotility-causes
Primary
Secondary
• Familial visceral myopathies
• Mithocondrial DNA and
myopathies
• Familial visceral neuropathies
• Congenital neuropathic
motility disorders
• MEN type 2B
• Non-familial visceral
myopathies
• Idiopatic non-familial visceral
neuropathies
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Scleroderma
Dermatomyositis and polymyositis
Systemic lupus erythematosus
Mixed connective tissue disease
Diabete mellitus
Parkinson disease
Neurofibromatosis
Spinal cord injury
Paraneoplastic visceral neuropathy
Myotonic distrophy
Amiloidosis
Thyroid disease
Hypoparathyroidism
Drug-induced changes in small intestine
motility
Celiac disease
Irradiation
Clinical findings
• Isolated severe small intestinal dysmotility is
very unusual; small intestinal dysmotility is
generally associated with dysmotility in other
parts of the digestive tract.
• asymptomatic
• recurrent symptoms and signs of small
intestinal obstruction = chronic small
intestinal pseudoobstruction
Symptoms
• Between those two ends of the spectrum, the patient may have
recurrent symptoms
- postprandial cramping
- periumbilical and epigastric abdominal pain
- abdominal bloating
- easy satiety
- anorexia
- weight loss
- nausea
- vomiting
• symptoms are usually related to eating.
• diarrhea can occur in patients with bacterial overgrowth and
malabsorption.
• in severe cases, the patients have episodes of chronic intestinal
pseudoobstruction syndrome
Signs
• cachectic and malnourished
• the abdomen may be distended and mildly tender
• the bowel sounds are inactive and infrequent in
patients with smooth muscle dysfunction, but they are
hyperactive and high-pitched in those with myenteric
plexus dysfunction
• in those with chronic intestinal pseudoobstruction,
during an obstructive episode, the abdominal
examination findings may be indistinguishable from
those of true mechanical obstruction
• symptoms and signs of multiple-organ dysmotility
Complications
• malnutrition
• bacterial overgrowth
• pneumatosis cystoides intestinalis - rare condition
characterized by multiple, gas-filled cysts in the wall of the
small and large intestine. Pneumoperitoneum may occur.
Investigations
•
•
•
•
•
•
Blood tests
Plain abdominal X-ray
Enteroclysis
Whole-gut transit with radiopaque markers
Radioactive isotope transit by scintigraphy
Small intestinal manometry
Blood tests
• Blood cell count: anemia and macrocytosis
• Blood chemistries: malnutrition,
malabsorption
Plain abdominal X-ray
• during exacerbations, show multiple air-fluid
levels and dilation of the small intestine
Enteroclysis
Spot radiograph of small intestine from enteroclysis
shows marked dilation of the mid small intestine.
The luminal diameter is 9 cm (double arrow).
Despite the marked luminal dilation, the valvulae
conniventes are tightly packed. The folds are
smooth and of normal caliber
Scleroderma (Small Bowel)
Differential diagnosis between chronic intestinal
pseudoobstruction and mechanical obstruction
• Partial small bowel obstruction from adhesions,
tumors, intussusception or stricture can mimic
chronic intestinal pseudoobstruction.
• Enteroclysis or careful small bowel radiography
with fluoroscopy is probably the most helpful way
to differentiate chronic intestinal
pseudoobstruction from mechanical obstruction.
• In most cases, exploratory laparoscopy may be
necessary to rule out an obstructing lesion.
Infections
Acute
• Common bacteria
• Viral pathogens
• Traveller’s diarrhea
Chronic
• Whipple disease
• Tropical sprue
• Tuberculosis
• Mycotic infections
Pathophysiology
Host factors
Microbial factors
• Normal intestinal flora
• Control mechanisms
• Intestinal immunity
• number of organisms
• enterotoxins
• adherence to gut mucosa
• invasion of enterocytes
Clinical manifestations
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Diarrhea
Nausea and vomiting
Loss of appetite
Fever
Headaches
Abnormal flatulence
Abdominal pain
Bloody stools (dysentery - suggesting infection by
amoeba, Campylobacter, Salmonella, Shigella or
some pathogenic strains of Escherichia coli)
Diagnosis
• diagnosing gastroenteritis is mainly an exclusion procedure
• in rare cases when the symptoms are not enough to
diagnose gastroenteritis, several tests may be performed in
order to rule out other gastrointestinal disorders.
- rectal examinations
- complete blood count
- electrolytes
- kidney function tests
• when the symptoms are conclusive, no tests
apart from the stool tests are required
Diarrhea - the most common manifestation of
intestinal tract infections
• Young children and the elderly are at greatest risk for more
severe disease and complications.
• The presence of underlying medical conditions, especially
those that compromise immunity, greatly enhances the risk of
acquiring an infection and its ultimate severity.
• Poor sanitation, inadequate water supplies and increasing
globalization of food transport systems all predispose to the
development of large epidemics of food- and water-borne
outbreaks of gastrointestinal disease.
• Seasonal or cyclic weather variations also influence the
epidemiology of diarrhoeal disease and food poisoning.
Is just a little case of diarrhea…
• Second leading causes of all death worldwide
• Most common cause of morbidity and mortality
in children worldwide
• Accounts for 9% of hospitalizations in children <5
years old in the United States
• You will likely suffer from diarrhea in the near
future!
Definition
• >3 feces/day, > 200 g/day
• acute/chronic
• Physiology:
– in gastrointestinal tract 9-10 l fluids (2l ingestion,
the rest secretions);
– Na - co-transport with Cl and glucose in small
bowel and biliary salts in terminal ileum; cotransport with H - HCO3; K absorbed with H or Ca.
– parasimpatic is stimulating the peristalsis and
electrolyte secretion; simpatic nerves are doing
the opposite.
– enteric nervous system
Figure 4.1 - Water fluxes through the intestine
©Copyright Science Press Internet Services
Functional design of small intestine
Acute diarrhea - definition
• Stool weight in excess of 200 g/day
• 3 or more loose or watery stools/day
• Alteration in normal bowel movement
characterized by decreased consistency and
increased frequency
• Less than 14 days in duration
Etiology
• Viral: 70-80% of infectious diarrhea in
developed countries
• Bacterial: 10-20% of infectious diarrhea but
responsible for most cases of severe diarrhea
• Protozoars: less than 10%
Epidemiology
• 1.2-1.9 episodes per person annually in the
general population
• 2.4 episodes per child <3 years old annually
• 5 episodes per year for children <3 years old
and in daycare
• Seasonal peak in the winter
Viral Diarrhea
• Rotavirus
• Norovirus (Norwalk-like)
• Enteric Adenovirus
• Astrovirus
Rotavirus
• Leading cause of hospitalization for diarrhea in
children
• Most prevalent during winter season
• Fecal-oral transmission: viral shedding can persist
for 21 days
• Acute onset of fever followed by watery diarrhea
(10-20 BM/day) and can persist for up to a week
Mechanism
Norovirus
• Most common cause of diarrheal
outbreaks/epidemics
• Multiple modes of fecal-oral transmission
• Acute onset of nausea and vomiting, watery
diarrhea with abdominal cramps and can
persist for 1-3 days
Enteric adenovirus
• Primarily affects children < 4 years old
• Fecal-oral transmission
• Clinical picture similar to rotavirus (fever and
watery diarrhea)
Astrovirus
• Primarily affects children < 4 years old and
immunocompromised
• Seasonal peak in the winter
• Fecal-oral transmission: viral shedding can occur
for several weeks
• Fever, nausea and vomiting, abdominal pain and
diarrhea lasting up to a week
Symptoms of viral enteritis
• low grade fever
• nausea
• vomiting
• abdominal cramps
• watery diarrhea lasting up to 1 week
• Viral shedding can occur for weeks after
symptoms resolve
Bacterial diarrhea
• Campylobacter
• Salmonella
• Shigella
• Enterohemorrhagic Escherichia coli
Campylobacter
• Most common bacterial
pathogen
• Transmitted through
ingestion of
contaminated food or
by direct contact with
fecal material
• diarrhea (+/- blood),
abdominal cramps (can
be severe), malaise,
fever
• Usually self-limited and
does not require
antibiotics
Salmonella
• Most common in children <4 years old and a peak
in the first few months of life
• Transmitted via ingestion of contaminated food
and contact with infected animals
• fever, diarrhea and abdominal cramping
• Antimicrobial therapy can prolong fecal shedding
Mechanism
Shigella
• Fecal-oral transmission
• fever, abdominal cramps, tenesmus, and
mucoid stools with or without blood
• Can lead to serious complications
• Antimicrobial treatment shortens duration of
illness and limits fecal shedding
Mechanism
E. Coli O157:H7
• Transmission via contaminated food and water
• bloody diarrhea, severe abdominal pain, and
sometimes fever
• Can lead to serious complications
• Antibiotics have no proven benefit and may
increase the risk of complications
Symptoms of bacterial enteritis
• Can affect all age groups
• Fecal-oral transmission, often through
contaminated food
• bloody diarrhea, severe cramping and malaise
• Antibiotic treatment not always necessary
History and Physical Exam
• 3 main goals
– Estimate the level of dehydration
– Identify likely causes on the basis of history and
clinical findings
– Determine if additional studies and/or
medications are necessary
History
• Onset, frequency, quantity, and character of
diarrhea
• Associated symptoms: nausea, vomiting,
fever, abdominal pain, tenesmus, malaise
• Recent oral intake
• Signs and symptoms of dehydration
Tenesmus
• Tenesmus is the feeling that you constantly
need to pass stools, even though your bowels
are already empty.
• It may involve straining, pain, and cramping.
• Usually occurs with inflammatory diseases of
the bowels.
• It can also occur with motility disorders.
Malaise
• Malaise is a generalized feeling of discomfort,
illness or lack of well-being.
• Malaise is a symptom that can occur with almost
any significant health condition.
• It may start slowly or quickly, depending on the
type of disease.
• Fatigue occurs with malaise in many common
diseases. Mailaise can be accompanied by a
feeling of not having enough energy to
accomplish usual activities.
Physical Exam
• Vitals, vitals, vitals!
• Abdominal exam
• Presence of occult blood
• Signs of dehydration
Dehydration
• particularly dangerous in children, older adults and people with
weakened immune systems
• must be treated promptly to avoid serious health problems, such as
organ damage, shock or coma
•
•
•
•
thirst
less frequent urination than usual
dark-colored urine
dry skin, does not flatten back to normal right away after being
gently pinched and released
• fatigue
• dizziness
• light-headedness
Laboratory evaluation
• Unnecessary for patients who present within 1
day from onset of diarrhea
• Warning signs/symptoms: bloody diarrhea, high
fever, severe abd pain, dehydration or comorbid
condition
• Fecal leukocytes followed by bacterial culture,
ova & parasites, viral antigens
• CBC, chemistries
TRAVELER’S DIARRHEA
• substantial risk (~40%) for diarrheal disease
• To some degree, the specific agents that cause
traveler’s diarrhea vary by geographic region and
season.
• Giardia and Cryptosporidium appear to be common
causes of diarrheal disease in visitors to Russia
• Aeromonas spp appear to be very common causes of
traveler’s diarrhea in visitors to Thailand
• toxigenic E coli is somewhat more frequently
encountered during the warmer summer months
• Campylobacter jejuni appears to occur more frequently
in the winter months
Clinical features
• Traveler’s diarrhea usually occurs within the first 14 days of
travel.
• It can also occur within a week or more after return from a
foreign country.
• The diarrhea is usually characterized as watery, with the
passage of three to ten bowel movements a day for 2 to 5
days.
• Abdominal cramps and pain often accompany the illness.
• Fewer patients experience fever, chills, vomiting and
dysentery-like symptoms.
• Fewer than 10% of patients have an illness that lasts longer
than a week and about 2% of patients have illness lasting a
month or more
Diagnosis
• Rarely is diagnosis required or available in the
setting of acute watery traveler’s diarrhea.
• For cases of dysentery, a diagnosis, if available, is
more useful.
• Given that traveler’s diarrhea occurs in the
traveling patient, it is almost always reasonable
to initiate treatment without an etiologic
diagnosis.
• Stool examination for parasites is warranted only
in cases of prolonged illness.
Chronic diarrhea - definition
• >3 weeks duration
• usually means three or more loose stools per
day
• average fecal daily weight in normal person is
100-200grams/day
Approach to patient
• Patient should be questioned about the onset,
duration, pattern, aggravates (especially
diet), relieving factors and stool
characteristics
• Presence or absence of fecal incontinence,
fever, weight loss, pain, certain exposurestravel, medications, contacts with diarrhea
should be noted
Approach to patient
• On physical exam, check for thyroid mass,
wheezing on lung exam, heart murmurs,
edema, hepatomegaly, abdominal mass, LAD,
perianal fistula or anal sphincter laxity.
• If diagnosis is still unclear after initial
encounter, further testing is required
• secretory vs. osmotic diarrhea vs.
malabsorption vs. inflammatory
Tests
• Stool culture - a sample of stool is analyzed in a
laboratory to check for bacteria, parasites, or
other signs of disease and infection.
• Blood tests - can be helpful in ruling out certain
diseases.
• Fasting tests - to find out if a food intolerance or
allergy is causing the diarrhea, the doctor may
ask a person to avoid foods with lactose,
carbohydrates, wheat, or other ingredients to see
whether the diarrhea responds to a change in
diet.
Complications
•
•
•
•
Dehydration
Malnutrition
Electrolytes (minerals) deficiencies
Finally, there may be irritation of the anus due
to the frequent passage of watery stool
containing irritating substances
Malabsorptive diarrhea
• Malabsorption suspected in patients with weight
loss, greasy stools, glossitis, anemia and
hypoalbumenima
• If malabsorption suspected, a 72 hr stool specimen
should be sent for fecal fat determination, if +
=>suspect malabsorption
• Causes of malabsorption include pancreatic
insufficiency (confirmed by CT/pancreatic function
tests) and disease of small intestine--Whipple’s
disease, tropical sprue, intestinal lymphoma (small
bowel biopsies by EGD)
Malabsorptive Diarrhea-Mucosal
Malabsorbtion
• Celiac sprue - hypersensitivity to gluten
• Tropical sprue - infectious disease of unknown
origin, seen in Indian subcontinent, Asia, West
Indies, North & South America, central and
southern Africa, and Central America
Mucosal Malabsorptive
• Whipple’s ->infection form Treponemawhippelii.
• Diagnosed by + biopsy for PAS macrophages
• Associated symptoms include
hypersomnolescence, arthralgias, fever,
hypotension and LAD
Intraluminal Malabsorbtion
• Most commonly results from pancreatic exocrine
insufficiency when >90% of pancreatic secretory
function is lost
• ethanol abuse
• cystic fibrosis
• pancreatic duct obstruction
Secretory vs Osmotic
• check stool osmotic gap
• 290-2x[Na stool + K stool]
• If < 50, diarrhea falls under secretory category
TYPICAL FEATURES OF SECRETORY DIARRHEA
TABLE 4-5. TYPICAL FEATURES OF SECRETORY DIARRHEA
Voluminous, watery stools
Little or no fecal osmotic gap, stool pH near 7.0
Usually persists during fasting
Usually no pus, blood, or excess fat in stools
Secretory Diarrhea
• Characterized by watery, large-volume fecal
outputs that are typically painless and persist
with fasting - one may do a 24 hr stool quant.
-should exceed one liter and not
decrease with fasting
• Usually stool pH is neutral and fecal fat test is
negative
TABLE 4-6. M ECHANISMS AND CAUS ES OF S ECRETORY DI ARRHEA
Reduction in mucosal surface area
Postresection diarrhea
Short-bowel syndrome
Extensive mucosal disease and Inflammation
Viral gastroenteritis
Celiac disease
Whipple`s disease
Crohn`s disease
Lymphoma
Absence of ion transport mechanism
Congenital chloridorrhea
Bacterial toxins
Cholera
Enterotoxigenic Escherichia coli
Shigella
Staphylococcus
Clostridium perfringens
Luminal secretagogues
Bile acids
Fatty acids, hydroxy-fatty acids
Phenolphthalein, ricinoleic acid, bisacodyl
Circulating secretagogues
Gastrin (Zollinger-Ellison syndrome)
Vasoactive intestinal polypeptide (VIPoma, ganglioneuroma, neuroblas toma, pheochromocytoma)
Calcitonin, prostaglandins (medullary carcinoma of the thyroid)
Somatostatin (somatostatinoma)
Glucagon (glucagonoma)
Serotonin, kinins (carcinoid tumor)
Thyro xine (hyperthyroidism)
Histamine (mastocytosis)
Secretory diarrhea - investigations
• If secretory diarrhea confirmed, recommend
checking serum should be sent for:
• Gastrin (gastrinoma), VIP(VIPOMA), glucagon
(glucogonoma), serotonin (carcinoid), calcitonin,
histamine, and prostaglandins
• -if overproduction of one of these mediators is
documented  abdominal CT scan is recommended
Carcinoid Syndrome and Secretory
Diarrhea
• Carcinod present with watery diarrhea,
flushing, skin changes, bronchospasm and
cardiac murmurs which are all symptoms
caused by secretion of serotonin, histamine,
catecholamines, kinins and prostaglandins by
the tumor masses
• 1/3 pts with carcinoid present with diarrhea
alone
Sectretory diarrhea – differential
diagnosis
• Other conditions to consider include:
• Diseases like Crohn’s ileitis or resection of
<100cm of terminal ileum (dihydroxy bile
acids may escape absorption and stimulate
colonic secretion)
Osmotic Diarrhea
• Most common cause is lactase deficiency
• Magnesium ingestion or factitious laxative
abuse
• Intraluminal maldigestion is also seen in
cirrhotics and bile duct obstruction-there is
impaired delivery of bile salts to small
intestine, leads to poor micelle formation with
ingested fats
CHRONIC DIARRHEA -Investigation• Blood tests: ESR; hemo leucograme (anemia,
inflammation); proteinograme (hyposerinemia)
• Rectosigmoidoscopy, Colonoscopy with/without
biopsy/ UGI endoscopy ( differential diagnosis )
• Rx: small bowel/barium enema
• Chronic diarrhea: Abdominal X-Ray, US/ CT
Celiac disease
• Coeliac disease is an inflammatory disorder of the small
intestine induced by the prolamins of certain cereals, namely
the gliadins of wheat, hordeins of barley and secalins of rye.
• The inflammation is associated with loss of villous height and
crypt hypertrophy and leads to malabsorption.
(a) Dissecting microscopic
appearance of a normal jejunal
biopsy. (b) Dissecting microscopic
appearance of coeliac disease.
Pathogenesis
• There are two clear facts about the
etiopathogenesis of coeliac disease.
1. The first is that fractions of gliadin, the alcoholsoluble component of gluten, are the toxic
dietary constituent, together with similar
fractions of rye and barley prolamins.
2. The second is that there is a genetic
susceptibility to gluten intolerance because of
the close association with the HLA haplotype B8DR3-DQ2 in northern Europeans and with B8DR5/7-DQ2 in southern Europeans.
Clinical findings
• Coeliac disease in infants classically presents
soon after weaning at the point that cereals
are introduced.
• In adults, the most common presentations are
anaemia and variable abdominal symptoms of
discomfort, bloating, excess wind and an
altered bowel habit (diarrhea). Mouth ulcers
are also frequent and can be the presenting
symptom.
Diagnosis
• The crucial test to establish the diagnosis is a
small-intestinal biopsy.
• Several serological tests have been developed
as screening tests
- antibodies to gliadin (IgA or IgG isotype)
- IgA antibodies to reticulin
- IgA antibodies to endomysium
Diagnosis
• Assessment of malabsorption
• Full blood count (hemoglobin level may be low, folate
deficiency, vitamine B12 - concentrations
• are only low in patients with extensive involvement of the
small intestine and so are usually normal)
• Biochemistry – hypokalaemia, hypomagnesiemia,
hypocalcaemia, serum albumin is often low, as is the
concentration of zinc; faecal fat excretion
• Immunological tests
• Radiology
• Small-intestinal biopsy
Small intestinal biopsy
• This has traditionally been taken from the
duodenal–jejunal junction (the ligament of
Treitz) using a Crosby capsule.
• a distal duodenal biopsy taken at
endoscopy is being used increasingly to
make the diagnosis and comparative
studies with a true jejunal biopsy have
justified its use.
Differential diagnosis
•
•
•
•
•
Giardia
common-variable hypogammaglobulinaemia
Lymphoma
Crohn's disease
small-intestinal diseases such (radiation,
enteritis, amyloid, Whipple's disease)
• Dermatitis herpetiformis is commonly
associated with an abnormal mucosal biopsy
Associated diseases
• There is an increased prevalence of autoimmune
diseases in patients with coeliac disease:
• diabetes
• thyroid disease
• Addison's disease
• fibrosing alveolitis
• systemic lupus erythematosus
• polyarteritis
Short bowell syndrome
• Large resections of the small bowel may
cause multiple nutritional and other medical
abnormalities, now commonly termed the
'short bowel syndrome'.
• thrombosis or embolus
• multiple surgical resections of the small bowel
in patients with Crohn's disease (regional
ileitis)
Clinical findings
• Intractable (cholerheic) diarrhoea
• Steatorrhoea
• Consequential metabolic abnormalities including
vitamin B 12 deficiency
• Many patients undergoing resections will be
malnourished preoperatively and energy
consumption increases in the immediate
postoperative period.
• If not appropriately managed, long-term proteinenergy malnutrition, as well as life-threatening
mineral and vitamin deficiencies develop.
Adaptation
• The residual bowel undergoes mucosal
hyperplasia and its capacity to absorb fluids
and nutrients increases over a period of weeks
or months.
• The molecular events that underly these
changes are unclear but may include
circulating trophic factors and growth factors
present in pancreatic juice or secreted into the
intestinal lumen.
CONSTIPATION
1.
2.
3.
4.
5.
Definition
Pathogenesis
Risk factors
Diagnosis and differential diagnosis
Treatment approaches
Definition: usually refers to persistent, difficult, infrequent or seemingly
incomplete defecation
The patient’s view:
The following perceptions,
• Need for straining (52%)
•Hard pellet-like stools (44%)
•Inability to defecate when desired (34%)
•Infrequent defecation (33%)
The clinical view: ROME-CRITERIA (at least 2 in any 12week period);
•< 3 bowel movements (BM) per week
•Hard stools in > 25% of BM’s
•Sense of incomplete evacuation in >25% of BM’s
•Excessive straining in >25% of BM’s
•The necessity of digital manipulation
2. Causes
•Extrinsic
•Inadequate dietary fiber, fluid
•Ignoring urge to defecate
•Structural
•Colorectal: neoplasm,stricture,ischemia,volvulus,diverticular disease
•Anorectal: inflammation, prolapse, rectocele,fissure, stricture
•Systemic
•Hypokalemia
•Hypercalcemia
•Hyperparathyroidism
•Hypothyroidism
•Diabetes mellitus
•Addison’s disease
•Pregnancy
•Uremia
•Neurological
•CNS: Parkinson's disease, Multiple sclerosis, trauma, ischemia, tumor
•Sacral nerves: trauma, tumor
•Autonomic neuropathy
•Aganglionosis ( Hirschsprung’s disease )
•Drugs
•Analgesics
•Anticholinergics
•Anticonvulsants
•Antihistamines
•Antihypertensive
•Chemotherapeutic agents
•Diuretics
•Metal ions
•Uncertain Pathophysiology
Irritable bowel syndrome, Slow transit constipation (STC)
3. Risk factors
Risk situations, groups and factors:
•Infants and children
•People older than 55 yrs
•Recent abdominal or perianal/pelvic surgery
•Late pregnancy
•Limited mobility
•Inadequate diet (fluid or fiber)
•Medications especially in the elderly
•Laxative abuse
•Terminal care patients
•Travel
•History of chronic constipation
4. Diagnosis and differential diagnosis
•History taking
•Physical examination
•Diagnostic techniques
•History taking
•Check for age of onset ( sudden or long term)
•Check for ROME- II criteria
•Check for neurological disorders
•Check for psychiatric conditions
•Check for family history of constipation?
•Physical examination
•Palpation of abdomen ( tumour )
•Percussion ( check for gases)
•Rectal palpation
•Consistency/impaction
•Presence of non-fecal masses or abnormalities (tumors, hemorrhoid,
fissures)
•Presence of blood
•Sphincter tone
Major alarm symptoms especially in patients >50yrs
•New onset constipation
•Anemia
•Weight loss
•Anal blood loss
•Positive occult blood test
•Sudden changes in defecation pattern and
appearance of stool
•Diagnostic techniques
•Stool analysis
•Weighing 3 days; < 100g avg means constipation
•Abdominal x-rays
•Radiological or endoscopic investigation
•Colon tumour, stenosis
•Abdominal echography
• Tumour mass
•Anorectal function tests
•Manometry
•Electromyography
•Rectal mucosal biopsy
•Colonic transit time (radiopaque marker)
Barium proctography in a healthy subject (A)
Barium proctography in a healthy subject (B)
Barium proctography in a healthy subject (C)
Barium proctography in a healthy subject (D)
DEFECOGRAFIA
-
Distal bowel in Hirschsprung`s disease
©Copyright Science Press Internet Services
There is fecal material in the right and left colon
(arrows).
MALABSORPTION
MALABSORPTION – definition
Clinical term that encompasses defects occurring during the
digestion and absorption of food nutrients by the
gastrointestinal tract.
•
The digestion or absorption of a single nutrient component
may be impaired, as in lactose intolerance in lactase
deficiency.
•
When a diffuse disorder such as celiac disease affects the
intestine, the absorption of almost all elements is impaired.
Pathophysiology:
3 major phases of digestion and absorption of food
materials.
• Luminal phase: dietary fats, proteins, and carbohydrates
are hydrolyzed and solubilized by secreted digestive
enzymes and bile.
• Mucosal phase: relies on the integrity of the brush-border
membrane of intestinal epithelial cells to transport
digested products from the lumen into the cells.
• Post absorptive phase: reassembled lipids and other key
nutrients are transported via lymphatic and portal
circulation from epithelial cells to other parts of the body.
Pathophysiology of bacterial overgrowth
©Copyright Science Press Internet Services
Pathophysiology of lactase deficiency
©Copyright Science Press Internet Services
Symptoms
• Diarrhea
– Diarrhea is the most common symptomatic complaint.
– Diarrhea frequently is watery, reflecting the osmotic load received by
the intestine.
– Bacterial action producing hydroxy fatty acids from undigested fat also
can increase net fluid secretion from the intestine, further worsening
the diarrhea.
• Steatorrhea
– Steatorrhea is the result of fat malabsorption.
– The hallmark of steatorrhea is the passage of pale, bulky, and
malodorous stools.
– Such stools often float on top of the toilet water and are difficult to
flush. Also, patients find floating oil droplets in the toilet following
defecation.
Symptoms
• Weight loss and fatigue
– Weight loss is common and may be pronounced; however, patients
may compensate by increasing their caloric consumption, masking
weight loss from malabsorption.
– The chance of weight loss increases in diffuse diseases involving the
intestine, such as celiac disease and Whipple disease.
• Flatulence and abdominal distension
– Bacterial fermentation of unabsorbed food substances releases
gaseous products, such as hydrogen and methane, causing flatulence.
– Flatulence often causes uncomfortable abdominal distention and
cramps.
Symptoms
• Edema
– Hypoalbuminemia from chronic protein malabsorption or from loss of
protein into the intestinal lumen causes peripheral edema.
– Extensive obstruction of the lymphatic system, as seen in intestinal
lymphangiectasia, can cause protein loss.
– With severe protein depletion, ascites may develop.
• Anemia
– Depending on the cause, anemia resulting from malabsorption can be
either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency).
– Iron deficiency anemia often is a manifestation of celiac disease.
– Ileal involvement in Crohn disease or ileal resection can cause
megaloblastic anemia due to vitamin B-12 deficiency.
• Bleeding disorders
– Bleeding usually is a consequence of vitamin K malabsorption and
subsequent hypoprothrombinemia.
– Ecchymosis usually is the manifesting symptom, although occasionally,
melena and hematuria occur.
Symptoms
• Metabolic defects of bones
– Vitamin D deficiency can cause bone disorders such as osteopenia or
osteomalacia.
– Bone pain and pathological fractures may be observed.
– Malabsorption of calcium can lead to secondary hyperparathyroidism.
• Neurological manifestations
– Electrolyte disturbances such as hypocalcemia and hypomagnesemia
can lead to tetany, manifesting as the Trousseau sign and the Chvostek
sign.
– Vitamin malabsorption can cause generalized motor weakness
(pantothenic acid, vitamin D) or peripheral neuropathy (thiamine), a
sense of loss for vibration and position (cobalamin), night blindness
(vitamin A), and seizures (biotin).
Physical findings
• General
– Patients may have orthostatic hypotension.
– Fatigue
– Signs of weight loss, muscle wasting, or both may be
present.
– Patients may have signs of loss of subcutaneous fat.
• Abdominal examination
– The abdomen may be distended, and bowel sounds may
be hyperactive.
– Ascites may be present in severe hypoproteinemia.
• Dermatological manifestations
– Pale skin may reveal anemia.
– Ecchymosis due to vitamin K deficiency may be
present.
– Dermatitis herpetiformis, erythema nodosum, and
pyoderma gangrenosum may be present.
– Pellagra, alopecia, or seborrheic dermatitis
• Neurological examination
– Motor weakness, peripheral neuropathy, or ataxia may
be present.
– The Chvostek or Trousseau sign may be evident due to
hypocalcemia or hypomagnesemia.
• Cheilosis, glossitis, or aphthous ulcers of the
mouth
• Peripheral edema
TABLE 5-33. SELECTED SYMPTOMS AND SIGNS OF NUTRIENT DEFICIENCIES
Symptoms or sign
Possible nutrient deficiency
Weakness, weight loss, muscle
Protein, calorie
wasting
Pallor
Folate, iron, vitamin B12
Follicular hyperkeratosis
Vitamin A, vitamin C
Perifollicular petechiae
Vitamin C
Protein, calorie, niacin, riboflavin, zinc,
Dermatitis
vitamin A, essential fatty acids
Bruising, purpura
Easily plucked, alopecia
Vitamin C, vitamin K
Corkscrew hairs, coiled hair
Protein, zinc, biotin
Night blindness, keratomalacia,
photophobia
Conjunctival inflammation
Glossitis
Bleeding or receding gums, mouth
ulcers
Decreased taste
Burning or sore mouth and tongue
Angular stomatitis or cheilosis
Tetany
Paresthesias
Loss of reflexes, wrist drop, foot drop,
loss of vibratory and position sense
Dementia, disorientation
Ophthalmoplegia
Depression
Vitamin C, vitamin A
Vitamin A
Vitamin A, riboflavin
Riboflavin, niacin, folate, vitamin B12,
protein
Vitamin A, vitamin C, vitamin K, folate
Zinc, vitamin A
Vitamin B12, vitamin C, niacin, folate,
iron
Riboflavin, niacin, pyridoxine, iron
Calcium, magnesium
Thiamine, pyridoxine
Vitamin B12, vitamin E
Niacin, vitamin B12
Vitamin E, thiamine
Biotin, folate, vitamin B12
TABLE 5-1. CLASSIFICATION OF DISEASES THAT CAUSE
INTESTINAL MALABSORPTION
Premucosal
Mucosal
Postmucosal
Pancreatic
insufficiency
Celiac sprue
Congenital
lymphangiectasia
Hepatobiliary
disease
Tropical sprue
Secondary
lymphangiectasia
Bacterial
overgrowth
Whipple`s disease
Rapid intestinal
transit
Eosinophilic enteritis
Gastrectomy
Brush border enzyme
deficiency
Lymphoma
Short-bowel syndrome
Prolonged malnutrition
Radiation enteritis
Parasitic infection
Mesenteric ischemia
Massive small-bowel resection can cause significant
malabsorption
TABLE 5-16. PREDI CTED NUTRITIONAL OUTCOME IN PATIENTS WHO HAVE HAD MASSIVE
INTESTI NAL RESECTION
Remaining Jejunal length, cm
0-50
51-100
101-150
151-200
>200
©Copyright Science Press Internet Services
Colon
Nutritional outcome
-
TPN
+
TPN
-
IVFM/TPN
+
Modified oral diet
-
Regular or modified oral diet
+
Regular diet
-
Modified oral diet
+
Regular diet
- or +
Regular diet
Differentials:
• Zollinger-Ellison Syndrome
Other Problems to be Considered:
– Amino acid deficiencies (cystinuria)
– Cystic fibrosis
– Hartnup disease
– Tropical jejunitis
– Whipple disease
Workup :
TABLE 5-32. INITIAL EVALUATION OF PATIENT WITH POSSIBLE
MALABSORPTION
History and Physical Examination
Initial blood tests
Follow-up laboratory tests
Complete blood count
Serum iron
Prothrombin time
Serum folate
Standard electrolytes
Serum vitamin B12
Calcium
Serum vitamin A
Magnesium
Plasma 25-hydroxy vitamin D
Blood urea nitrogen
Urinary oxalate excretion
Creatinine
Stool for Sudan stain
Alkaline phosphatase
Stool for ova and parasites
Cholesterol
Total protein and albumin
Imaging studies
– Small bowel barium studies.
– CT-scan of the abdomen.
– Endoscopic retrograde cholangiopancreatogram
– Plain abdominal X-ray film.
– Endoscopy
Endoscopy
Upper endoscopy with small bowel mucosal biopsy
• Establishing a definitive diagnosis of
malabsorption of the mucosal phase often can
be achieved by histological examination of
biopsied mucosal specimens obtained during
routine upper endoscopy.
• Examples of conditions that can be diagnosed
this way include celiac sprue, giardiasis, Crohn
disease, Whipple disease, amyloidosis,
abetalipoproteinemia, and lymphoma.
Endoscopic image of scalloping seen in celiac disease and other mucosal
disorders including giardiasis
Other studies
– Tests of fat malabsorption.
– D-xylose test.
– Test of carbohydrate absorption.
– Test of bile salt absorption.
– Schilling test.
URINARY D-XYLOSE TEST
• The urinary D-xylose test for carbohydrate absorption
provides an assessment of proximal small-intestinal
mucosal function. D-Xylose, a pentose, is absorbed almost
exclusively in the proximal small intestine.
• The D-xylose test is usually performed by giving 25 g Dxylose and collecting urine for 5 h.
• An abnormal test (4.5 g excretion) primarily reflects the
presence of duodenal/jejunal mucosal disease.
• The D-xylose test can also be abnormal in patients with
blind loop syndrome (as a consequence primarily of
abnormal intestinal mucosa) and, as a false-positive study,
in patients with large collections of fluid in a third space
(i.e., ascites, pleural fluid).
The Schilling test
• Is performed by administering 58Co-labeled cobalamin and
collecting urine for 24 h and is dependent on normal renal
and bladder function.
• Urinary excretion of cobalamin will reflect cobalamin
absorption provided that intrahepatic binding sites for
cobalamin are fully occupied.
• To ensure saturation of hepatic cobalamin binding sites so
that all absorbed radiolabeled cobalamin will be excreted in
urine, 1 mg cobalamin is administered intramuscularly 1 h
following ingestion of the radiolabeled cobalamin.
• The Schilling test may be abnormal (usually defined as 10%
excretion in 24 h) in pernicious anemia, chronic
pancreatitis, blind loop syndrome and ileal disease.
Histologic Findings
Depending on the cause, the histologic features of
malabsorption vary.
– A frequently encountered histologic finding is villous
atrophy, which is seen in celiac disease, tropical sprue,
viral gastroenteritis, bacterial overgrowth, inflammatory
bowel disease, immunodeficiency syndromes, lymphoma
and radiation enteritis.
Caption: Small intestine. Fluorescence confocal light