Transcript Journey through the GI tract

Journey through the GI tract
Barb Bancroft, RN, MSN
www.barbbancroft.com
[email protected]
Open wiiiiiiide…
• Let’s take a journey through the GI tract
with a few stops along the way…
The Teeth
• Tooth loss and heart disease
• Periodontal disease, subclinical vasculitis and
coronary plaque development
• State with the least teeth is the state with the
most heart disease
Oral bacteria and coronary artery
disease
• Specific periodontal pathogens are implicated
• Enter the bloodstream via small ulcers that develop in
the gum tissue of patients with periodontal disease
• Contribute to plaque formation via inflammation; induce
platelet aggregation and clot formation
• 4 bacteria are implicated—Tannerella forsythia,
Porphyromonas gingivalis, Actinobacillus
actinomycetemcomitans, Treponema denticola.
• Depending on the bacterial concentration, the increased
risk of heart attack in persons with one or another of
these bacteria ranges from 200-300 percent, compared
to people with no evidence of the bacteria
Floss
• “Floss only the teeth you want to keep…”
• MINUTIAE: On average, each person
uses 54 feet of dental floss every month or
about 1.5 feet of floss per day which
equals 548 feet of floss in a year.
Meth mouth
• 22 y.o. meth user; snorted and/or injected meth
x 2 years
• Denied use of any other drugs
• Drank 2-3 liters of carbonated drinks each day
because of a dry mouth
• How addicting is methamphetamine? Dopamine
and addiction
• (British Journal of Medicine 2006;333:156)
Osteoporosis and tooth loss
• Osteoporosis of the mandible and maxilla
on dental X-rays—loss of trabecular bone
• Women who do NOT take estrogen have
fewer teeth
Bites
• The bite scale. The King of the Jungle, the
African lion, has a bite force of only 940 pounds
(427 kg). Hyenas register a 1,000-pound (454
kg) bite which explains why they might get the
best of the African lion. Dusky sharks manage
only 300 pounds (136 kg) of force.
Bites
• Labrador retrievers nip at your ankles with 125
pounds (57 kg) of force, only slightly surpassed
by the infamous Mike Tyson, the heavyweight
boxer, who chomped off Evander Holyfield’s ear
with a force of 170 pounds (77 kg).
• Had we lived in the day of the dinosaur,
Tyrannosaurus Rex, the bite would have
registered 3,011 pounds (1369 kg).
• What about Petey the pit bull? Endorphins, Ltyrosine and dopamine
Other human bites
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Self-inflicted bites
Thumb-sucking
Seizures (can you swallow your tongue?)
Child abuse
Gingival hypertrophy
• Drugs—phenytoin (Dilantin), nifedipine
(Procardia), cyclosporine
• Leukemias—acute and chronic
The immunocompromised patient
• Candida albicans (inhaled steroids in
asthmatics)
• Diabetics with hyperglycemia
• Fungal infections and TNF-α antagonists
(infliximab/Remicade; adalimumab/Humira;
certolizumab/Cemzia etanercept/Enbrel)
• HSV-1, HSV-2
• Kaposi’s sarcoma
• HPV
• HIV (TB)
OPEN Wide
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Aphthous ulcers and celiac disease
Mouth clues to vitamin deficiencies
Vitamin C—gingivitis, dental erosion
Vitamin B2 (riboflavin)—stomatitis, cheilosis, geographic
tongue
• Vitamin B3 (niacin), B6 (pyridoxine), B12 (cobalamin),
folic acid (B9)—glossitis
• Calcium (hypocalcemia)—numbness and tingling around
the mouth**; tetany; Chvostek’s sign; Trusseau’s sign
Say “ah”…
• Soft palate and the uvula
• Relationship of the pharyngeal musculature with
CN IX (Glossopharyngeal) and X (Vagus)
• Stroke patients
• Swallowing
• What is the hardest thing to swallow?
Water…
• Ya’ can’t size it, ya’ can’t shape it…
Back to CN IX and X
• The gag reflex
• CN IX and X close off the nasopharynx
• Head injured patients lose their gag reflex and
have a high risk of aspiration pneumonia
• Open your mouth and pant like a dog
• “K, K, K, K, K”
• uvula midline
Causes of nasal speech
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Cleft palate (folic acid!!)
Lou Gehrig’s (ALS) disease
Glossopharyngeal nerve palsy—(viral)
Guillain-Barré syndrome with bulbar onset
(cranial nerve onset vs. ascending paralysis
beginning with the longest nerves first—ie. the
feet)
• #1 cause of Guillain-Barré
ACE inhibitors and angioedema
• The “PRILS”
• Muffled speech
• Swollen lips, pharyngeal
edema
• Hives around the mouth
• Highest risk patients?
• Don’t forget the cough…
• Drugs discovered because
of a bite—Brazilian pit viper
• Captopril (Capoten)
• Enalapril (Vasotec)
• Lisinopril (Prinivil, Zestril)
• Perindopril (Aceon)
• Moxepril (Univasc)
• Benazepril (Lotensin)
• Quinapril (Accupril)
• Trandolapril (Mavik)
• Ramipril (Altace)
• Etc…
• Diabetics, HBP, CHF, post-MI)
Hoarseness
• Vocal cords supplied by a branch of the vagus-recurrent laryngeal nerve
• Causes of hoarseness? increased vocal cord
thickness--testosterone, hypothyroidism,
acromegaly, aneurysm of the thoracic aorta, lung
cancer, and GERD—just to name a few
• Hypothyroidism, large tongue, teeth
indentations--♀ > ♂
• Amyloidosis
Salivary glands—parotid,
sublingual, submandibular
• Parotid gland—MUMPS (kids and vaccines)
• Hypertrophy of the parotid gland in women with eating
disorders (serum amylase will be elevated)
• Acetylcholine innervates the salivary glands to produce
saliva
• Drugs to boost acetylcholine for patients w/ dry
mouths—5 mg QID pilocarpine; cevimeline (Evoxac)
• Artificial saliva?
More on saliva
• Sjögren’s syndrome (sicca)—autoimmune
disease; may be primary or secondary to
another autoimmune disease such as
lupus
• Saliva as innate defense--IgA
• Taste and saliva—the elderly and
anticholinergic drugs; stop the flow of
saliva
Drugs with anti-cholinergic properties
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Amitryptyline (Elavil)
Doxepin (Sinequan)
oxybutynin (Ditropan)
Meclizine (Antivert)
Theophylline
Captopril (Capoten), nifedipine (Procardia)
Prednisolone
digoxin
dipyridamole (Persantine)
warfarin
Furosemide (Lasix)
isosorbide dinitrate (Isordil)
More anticholinergic drugs
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Codeine
Oxycodone
Fexofenadine (Allegra)
thioridazine (Mellaril)
Hydroxyzine (Atarax)
Loratadine (Claritin)
dicyclomine (Bentyl)
Cimetidine (Tagamet), ranitidine (Zantac)
benztropine (Cogentin)
trihexyphenidyl (Artane)
Diphenhydramine (Benadryl)
haloperidol (Haldol)
Sublingual
• Saliva and sublingual drugs—you need
saliva to absorb sublingual drugs
• NTG under the tongue to vasodilate the
coronary arteries in patients with anginal
chest pain
• Jaundice and soft palate/sublingual
mucosa
Speaking of saliva…
• How much saliva do you make a
day? about 1 liter of saliva per day
• How many times do you swallow in
an hour? (70/200/10)
• Swallowing is something we take
for granted…spit in a cup!
• Swappin’ saliva…chemistry? MHC
complex
Neurologic conditions
• Parkinson disease
• Low dopamine with a relative increase in
acetylcholine
• Relative increase in acetylcholine results
in excess saliva and drooling
You take swallowing for granted-until you have this sore throat…
• Say ahhhhh…
• Can you say “ouch”?
• Can you say “I have a sore throat, and I
can’t swallow…”
• Group A beta hemolytic strep
• Peritonsillar abscesses
Enlarged tonsils
• EBV infection of tonsils
• Waldeyer’s ring (tonsils and adenoids)
• Kids and sleep apnea; kids, lack of sleep
and growth hormon
• Adults and sleep apnea? (hypertension,
CAD in adults)
• Behavior disorders? ADHD? In kids?
• Non-Hodgkin’s lymphoma
Oral signs of an eating disorder
• The frequent vomiting and nutritional
deficiencies often associated with eating
disorders can severely affect health
• 89% of bulimic patients have signs of tooth
erosion; over time, loss of tooth enamel can be
considerable
• Change in color, shape, length
• Brittle, translucent, and sensitive to temperature
• Swelling of salivary glands
• Dry and cracked lips
• Chronic dry mouth
Oral cancers
• Causes? The usual suspects…
• Tobacco, smoked, chewed, pipes, cigars,
cigarettes, cigarillos
• Alcohol?
Cut back on the booze…
• Alcohol is on the list of “probable cause” for
cancers of the colon, rectum and breast;
“convincing cause” of cancers of the mouth and
pharynx, larynx, esophagus, liver, and “possible
cause” for lung cancer.
The big surprise…Oral cancers and
HPV
• HPV-16 and oral sex
• mouth/throat cancer
• Will the HPV vaccine (Gardisil) prevent
this type of cancer if given early?
Let’s move into the esophagus
• Hollow, highly distensible muscular tube that
extends from the pharynx to the
gastroesophageal junction at the level of T11 or
T12 vertebra.
• 10 to 11 cm in the newborn
• 23 to 25 cm in the adult
• A 2-4 cm segment just proximal to the anatomic
esophagogastric junction, at the level of the
diaphragm, is the LES, or lower esophageal
sphincter
GERD (gastroesophageal reflux
disease)
• ACID is the bad guy
• The Lower Esophageal Sphincter (LES) pressure
• With GERD--decreased pressure in the lower
esophageal sphincter due to drugs, nicotine, alcohol,
fatty foods, peppermint, chocolate, citrus fruits and
juices, increased pressure in stomach (late evening
meal)
• So, how about a pizza, cold beer and a cigarette before
bedtime?
• What drugs? Bronchodilators, NTG, tetracycline,
quinidine, KCl, NSAIDS, Iron salts, bisphosphonates,
Viagra and other ED drugs
• Obesity
What are non-drug ways to reduce
GERD?
• Dietary changes?
• A meta-analysis in the Archives of Internal
Medicine revealed support for 2 measures:
• Weight loss and head-of-bed elevation
• Avoiding tobacco, alcohol, high-fat foods, and
carbonated beverages was NOT shown to
alleviate symptoms of GERD—even tho’ there is
substantial evidence that consumption of these
substances has an adverse impact on GERD
Pharmacology of GERD
• Classic reflux sx (heartburn, reflux) have a + predictive
value of 80%
• Empiric therapy can be started without endoscopy, but
endoscopy can only tell whether or not erosive
esophagitis is present
• PPIs (Proton Pump Inhibitors)—the “prazoles” are the
mainstay of therapy in healing erosive esophagitis and
treating symptoms of GERD
• Omeprazole (Prilosec), lansoprazole (Prevacid),
pantoprazole (Protonix), rabeprazole (Aciphex), and “the
purple pill”—esomeprazole (Nexium)
• Fastest acting—esomeprazole, rabeprazole,
omeprazole, lansoprazole, pantoprazole
Drugs to treat GERD
• MOA—Inhibition of the proton pump at the
luminal surface of the stomach…especially after a
meal—work best when taken 30-60 minutes before breakfast or
dinner
H+, Intrinsic Factor-B12
PPIs work here
Luminal surface
Parietal cell
Basilar surface
H2 receptors
H2
H2 blockers work here
H2 blockers
• Work by blocking H2 receptors on basal surface
of the parietal cell; work best when taken at night
to reduce nocturnal histamine secretion and acid
production
• Cimetidine (Tagamet)*
• Ranitidine (Zantac)
• Famotidine (Pepcid)**
• *drug interactions and side effects
• **least drug interactions and side effects and
most effective
Has your patient been on the
“prazoles” for longer than 5 years?
• Check B12 levels in your patients…
• The parietal cell that pumps acid also pumps out intrinsic
factor (IF)
• Intrinsic Factor is necessary for the absorption of B12
from food
• If you stop pumping the acid into the stomach, you also
stop pumping intrinsic factor for B12 absorption
• Combine that with a decreased absorption of B12 over
the age of 50 and you may have a B12 deficiency;
• May also be caused by an autoimmune disease with
antibodies against IF (pernicious anemia)
• No acid, no calcium (elderly and patients on PPIs need
to take calcium citrate for absorption)
• No acid, no iron (check for iron deficiency anemia)
Hematologic and neurologic
symptoms of B12 deficiency
• Hematologic—megaloblastic anemia (big,
immature RBCs)—MCV is greater than 120; also
known as a macrocytic anemia
• Neurologic—Cognitive dysfunction; Spinal cord
dysfunction; peripheral neuropathy
• The number 1 nutritional cause of dementia is
B12 deficiency—is it reversible? Yes.
• How can you supplement with B12?
B12 supplementation
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Pill
Sublingual
Nasal
Injection
• Need 6 mcg per day; take 1000 mcg by
mouth/sublingual/nasal daily (1% via passive
diffusion in stomach if you take B12 by mouth)
• 1000 mcg/month via injection
• Do not take over 3,000 mcg per day…the one
dreaded side effect is:
Barrett’s esophagus
• Complication of acid reflux (GERD)
• Metaplasia of the lower third of the esophagus
• What is metaplasia? The substitution of one adult cell for
another adult cell
• Usually a protective mechanism
• Gastric epithelial cells have replaced squamous
epithelial cells of the esophagus
• Gastric epithelial cells are “used to” acid
What do we know about Barrett’s
esophagus?
• Patients with at least weekly symptoms of GERD—315% are found to have Barrett’s
• May be a gross underestimate—autopsy findings were
20-fold higher than clinical studies
• Caucasian males greater than 55; 2:1 ratio; big bellies
contribute…Body fat increases intraabdominal pressure;
fatty foods decrease LES pressure; high dietary intake of
nitrates
• Increased insulin resistance results in high serum levels
of insulin-like growth factor-1
• Adenocarcinoma of the esophagus (10% in 1960; 50% in
2005);
• One of fastest rising cancers in U.S.
What do we know about Barrett’s
esophagus?
• Progression to dysplasia is an ominous histologic finding—precursor
to invasive adenocarcinoma
• Annual risk is 0.5% per year
• 30x to 40 x greater risk of adenocarcinoma w/ Barrett’s if greater
than 2 cm of Barrett mucosa on endoscopy
• Does ultra-aggressive anti-secretory therapy have anti-proliferative
effects on intestinal metaplasia? Recent studies say yes…higher
than conventional PPI doses
• BID dosing if QD doesn’t relieve symptoms of GERD (35% of
patients are on BID dosing)
• Add H2 blocker at HS—double the OTC dose (Zantac 300 po hs)
• Nocturnal symptoms are more often associated with severe
disease—esophageal cancer, otolaryngologic and pulmonary
disorders
Esophageal candidiasis/rupture
• HIV patients—dysphagia in AIDS patients—also
consider Herpes simplex and CMV esophagitis
• Irritation and possible rupture in
postmenopausal females taking
bisphosphonates (Fosamax and friends)
• Other pills “stick”
• Lye, acids, and detergents
Esophageal dysmotility syndromes
• Achalasia--LES is too tight, lack of
peristalsis in lower third of esophagus;
LES needs to be dilated frequently
• Viagra has been used to open the LES
(nitric oxide relaxes the sphincter)
• Esophageal spasms (women and other
spastic disorders)
Esophageal varices
• How do you develop esophageal varices?
• Due to increased pressure in the portal system of the
liver
• Primarily due to cirrhosis of the liver; 90% of patients
with cirrhosis will develop varices
• Worldwide, hepatic schistosomiasis is the second most
common cause of variceal bleeding
• Beta blockers to reduce portal pressure
• 40% die with first episode, rebleeding occurs in more
than half within one year
Major causes of cirrhosis of the
liver today are…
• Hepatitis C (15% clear on own; 85% develop chronic
hepatitis; chronic hepatitis can lead to cirrhosis and
hepatocellular carcinoma)
• Hepatitis B (10% develop chronic hepatitis, 90% clear on
own as adults; opposite percentages with infants and
vertical transmission)
• Alcohol (fatty liver)
• Diabetes (fatty liver)
• Obesity (fatty liver)
• NASH (Non-alcoholic steato-hepatitis, also known as
non-alcoholic fatty liver disease--NAFLD)
Hepatitis C virus--1989
• Cirrhosis with progression to hepatocellular
cirrhosis
Hepatitis C virus—identified in
1989
HIGH RISK GROUPS—primary factors
• IV drug user (even 1 time experimental drug
use)
• Blood transfusions prior to July1992 —or organ
transplant recipients
• Persons who have ever received hemodialysis
• Hemophiliacs who received clotting factor
concentrates prior to 1987
• Children born to HCV-infected moms (screen at
age 1 or older)
Hepatitis C high risk factors
• HCW after a needle stick injury or mucosal
exposure to HCV-positive blood
• Current sexual partners of monogamous HCVinfected persons (prevalence is low, but a
negative test provides reassurance)
• How about MULTIPLE partners—how many?
• Intranasal cocaine use
• Tattoos (prison applied?)
• Body piercings
• Receipt of injection in a developing world
• The American Association of Blood Banks
requires a one-year wait between getting a
tattoo and donating blood
Treatment of Hepatitis C
• 24 weeks vs 48 weeks depending on
genotype
• Pegylated interferon + ribivirin
The stomach
• “Whoever said the way to a man’s heart is
through his stomach flunked geography…”
--anonymous
• The stomach is a saccular organ with a
volume of 1200 to 1500 ml but a capacity
of greater than 3000 ml
Gastric acid
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At maximal secretory rates, the stomach intraluminal
concentration of hydrogen ion is 3 million times greater
than that of the blood and tissues
The mucosal barrier protects the gastric mucosa from
autodigestion and is created by:
mucus secretion;
bicarbonate secretion
epithelial barrier and,
mucosal blood flow
Truly a physiological marvel, or gastric walls would
suffer the same fate as a T-bone
Peptic ulcer disease
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Usually solitary lesions less than 4 cm in diameter
Duodenum, first portion
Stomach, antrum
GE junction, in the setting of GERD
4 million people have peptic ulcers; 350,000 new cases per year,
100,000 hospitalized, 3000 die
Male/female for duodenal = 3:1; male/female for gastric = 1.5 to 2:1
Imbalance between the gastroduodenal mucosal defense
mechanisms and the damaging forces—gastric acid and pepsin
Hyperacidity is NOT a prerequisite
H. pylori is present in 100% of duodenal ulcers and about 70% of
patients with gastric ulcers
Gastric ulcers (peptic ulcer
disease)
• Helicobacter pylori—the most common infection
worldwide
• Elaborates urease and produces ammonia which buffers
gastric acid in the immediate vicinity
• Gastric ulcers
• Chronic inflammation (gastritis) and regeneration of the
antrum
• The only bacteria known to be “oncogenic”
• Is it normal flora?
• How do you “catch” it?
• How do you treat it?
• Is H. pylori a good thing?
Gastric ulcer caused by NSAIDS
• 2.74 RR of any GI complication
• If over 50, RR is 5.57
• RR 12.7 with NSAIDS and warfarin; 4.76
with NSAIDS and steroids
• PPIs decrease ulcer/ bleed by 4-fold
Gastric cancer
• In 1930, gastric cancer was the most common cause of
cancer death in the U.S.
• Annual mortality rate in the US has dropped from 38 to 7
per 100,000 in men and from 28 to 4 per 100,000 in
women.
• Causes 2.5% of all cancer deaths in U.S. and is the
leading cause of deaths from cancer worldwide
• H. pylori and diet play a major role
• N-nitroso compounds and nitrates, benzopyrene
• Consumption of preserved, smoked, and cured and
salted foods
• Water contamination with nitrates
Bariatric surgery—BMI ≥ 30
• Swedish study—2010 patients; 74% followed for
10 years; 0 relapsed into obesity; found that the
most effective therapy was the gastric bypass—
removing most of the lower part of the stomach
and attaching to a loop of small bowel
• Stapling only half as effective
• Lap-banding
• Risk? Only about ¼ of 1 percent mortality rate
• Long-term effects? malabsorption
• Cure for type 2 diabetes? Duodenal exclusion
surgery
The small intestine—duodenum,
ileum, jejunum
• Small intestine is ~6-7 meters (18 to 22 feet) in
length; large intestine is ~1.5 meters in length
• First 25 cm (12 inches) is duodenum
• Normal renewal of the epithelial lining of the
small intestine every 4 to 6 days; colonic
turnover every 3 to 8 days
• Remarkable capacity for repair, but it also
renders the intestine particularly vulnerable to
agents that interfere with cell replication, such as
radiation and chemotherapy
The small intestine and grapefruit
juice
• Metabolizing enzymes to break drugs are
located in the small intestine
• CYP3A4 metabolized 40-60% of all drugs
(11000)
• Grapefruit juice/grapefruit inhibits this
enzyme; drugs metabolized by this
enzyme enter the system in a higher
bioavailability—hence, drug toxicity
Grapefruit juice interactions increase
bioavailability and increase the risk for
toxicity
• Amiodarone HCl—increased absorption with GFJ
increasing risk of adverse effects and toxicities:
pulmonary toxicity, hypotension, and cardiac
arrhythmias, (TSH). Avoid using Amiodarone in patients
who may not understand the toxic potential of this
interaction.
• Felodipine (Plendil), nisoldipine (Sular), nicardipine HCl
(Cardene), nifedipine (Procardia), isradipine (Dynacirc)—
increased toxicity with headaches and peripheral edema
• Simvastatin (Zocor)—300% increase in bioavailability
with grapefruit vs. atorvastatin (Lipitor) 25% increase;
rosuvastatin (Crestor)—no interaction
Grapefruit juice/grapefruit
• Avoid grapefruit juice and grapefruit with
antibiotics
• One interaction is especially dangerous
• Interaction between grapefruit juice and
erythromycin
• Accumulates and may cause tachycardia
• Prolongs QT interval and may cause death from
“torsades de points”
Fluids and the small intestine
• A typical adult imbibes 2 liters of fluid per day, to
which is added 1-1.5 liters of saliva; 2 liters of
gastric juice; 1 liter of bile; 2 liters of pancreatic
juice, and 1 liter of intestinal secretions
• Of these 9 liters presented to the intestine, less
than 200 gm of stool are excreted per day, of
which 65 to 85% is water.
• Jejunal absorption is 3 to 5 liters/day; ileal
absorption is 2 to 4 liters per day; colon absorbs
1 to 2 liters per day but is capable of absorbing
almost 6 liters per day.
The duodenum (12 fingerbreadths),
—the organ of nausea
• 5-HT3 (serotonin) receptors)
• Serotonin release causes nausea--Makes ya’
sick to your duodenum
• 5-HT3 blockers--The “setrons”—ondansetron
(Zofran), granisetron (Kytril), doasetron
(Anzemet), palonosetron
• Adding ondansetron to oral rehydration in kids
reduces nausea and vomiting and decreases the
need for IV fluids by greater than 50%
Celiac disease and the duodenum
• 1 in 250 in U.S.; greater prevalence in 1st and 2nd degree relatives;
?duration of breast feeding; age at which a person ingests gluten;
cigarette smoking
• Autoimmune disease—HLA-DQ2; HLA-DQ8
• Ingested gluten crosslinks with tissue transglutaminase released in
the lamina propria and epithelium of the small intestine
• Ingested gluten crosslinks with tissue transglutaminase released in
the lamina propria and epithelium of the intestine
• Leads to the deamidation of the gluten peptides
• CD4 cells become stimulated; cytokines IF-γ and IL-4 which damage
villi; flattened villi and malabsorption
• Anti-transglutaminase antibodies
Celiac disease
• Classic symptomatic presentation characterized
by diarrhea, abdominal pain, weight loss,
flatulence, and nutritional deficiencies
• Atypical presentation characterized by gait
ataxia, seizures, peripheral neuropathy,
aphthous stomatitis, arthritis, migraine
headaches
• Associated with other autoimmune diseases—
Type 1 diabetes, autoimmune myocarditis,
primary biliary cirrhosis
• Gluten-free diets and the improvement of
symptoms
Celiac disease
• Absorption problems result in anemias—iron
deficiency (growth problems in kids); folate
deficiency; calcium absorption problems
(osteopenia)
• Always check for osteopenia and osteoporosis in
your long-term patients with celiac disease!
• aphthous ulcers are both strongly associated w/
celiac disease (This Week in Medicine,
MDConsult, 1/31/07)
Gastroenteritis…
• Umbilicus (belly button)—embryologic origins with colon
(Homer and Dr. Colón)
Word o’ the day…
Omphaloskepsis (om-fuh-lo-SKEP-sis); noun
• Definition: Contemplation of one’s navel. (From Geek
omphalos (navel) + skepsis (act of looking, examination)
• Peri-umbilical pain
• Causes of gastroenteritis—food poisoning, viral
infections, bacterial infections
Gastroenteritis
• Infectious gastroenteritis—causes more than
12,000 deaths per day from dehydration among
children in developing countries and constituting
one half of all deaths worldwide before age 5
• Attack rates of one to two illnesses per person
per year in U.S.—results in an estimated 99
million acute cases of either vomiting or diarrhea
per year—approximately 40% of the population
Viral gastroenteritis
• Rotavirus—140 million cases and 1 million
deaths worldwide per year; 6 to 24 months of
age; shed 1,000,000,000,000 (10¹² particles)/ml
of stool (the minimum infective inoculum is only
10 particles, hence the rampant outbreaks in
daycare and pediatric populations in hospitals)
• Norwalk virus (norovirus)—rare in young kids;
incubation period of 1 to 2 days followed by 12
to 60 hours of “shuking”
Noroviruses
• Responsible for majority of nonbacterial food-borne
epidemic gastroenteritis in older children and adults;
• Salad bars (cold foods, raw shellfish), person-toperson,water on cruise ships
• Has also been found in the community and in nursing
homes
• Vicious cycle of vomiting and diarrhea for an average of
23 hours—known as “shuking”
• start shedding virus before symptoms occur and shed
virus for 4 days after symptoms subside (hence, the
rapid spread of infection); can shed virus up to 4 to 8
weeks after illness
Bacterial entercolitis
• Ingestion of preformed toxin in food—
Staphylococcus aureus, Vibrio species,
Clostridium perfringens
• Infection by toxigenic organisms, which
proliferate in the gut lumen and elaborate an
enterotoxin (Cholera toxin is the prototype
secretagogue)
• Infection by enteroinvasive organisms, which
proliferate, invade, and destroy mucosal
epithelial cells (Salmonella, Yersinia
enterocolitica)
Acute appendicitis
• Acute appendicitis presents initially with
peri-umbilical pain and subsequently
localizes to the right lower quadrant (RLQ)
• High risk occupation for acute
appendicitis?
• Pig farmers
Salmonella in raw or undercooked
eggs and chicken
• Pasteurized eggs for “seizure” salad
(Caesar salad), eggnog, and guacamole
• Salmonella in chicken
• No more sunny-side up, especially for
high-risk patients (unless the eggs are
pasteurized)
Campylobacter jejuni
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Undercooked chicken
180º whole chicken
170º white meat
180º dark meat
E. Coli 0157:H7—the “burger” bug
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3rd most deadly toxin in the world
10-100 pathogens to make you ill or kill you
Very young, very old, very immunocompromised
Acute Renal Failure in Kids—hemolytic uremic syndrome
Swimming pools, petting zoos
Mickey D’s—30 outbreaks per year
Supportive Treatment
Prevent—cook burgers to 160º F
Produce is the biggest offender for E.Coli O157:H7
Crohn’s disease—inflammatory
bowel disease
• Primarily small bowel, but can include
anywhere from the esophagus to the
rectum
• Skip lesions; fistulas; strictures
• Cause? Bacteria? Mycobacterium
paratuberculosis?
• Autoimmune response
Signs and symptoms
• Usually begins with intermittent attacks of
relatively mild diarrhea, fever, and abdominal
pain, spaced by asymptomatic periods lasting for
weeks to many months
• 1/5th of patients with abrupt onset, with acute
RLQ pain, fever, and diarrhea
• Diff dx suggesting acute appendicitis or acute
bowel perforation
• Chronic disease with fibrosing strictures, marked
loss of albumin, generalized malabsorption, B12
malabsorption, or malabsorption of bile salts
leading to steatorrhea
Treatment
• Methotrexate to reduce the immune
response
• Inflammation via TNF-alpha
• Drugs that block TNF-alpha include
infliximab (Remicade), adalimumab
(Humira), etanercept (Enbrel)
• Certolizumab pegol (Cemzia)
Antibiotic-associated diarrhea
• “the usual, run-of-the-mill diarrhea” vs.
• Clostridium difficile diarrhea (new strain)—
the “floxacins” and Clindamycin are the
biggest offenders for C. difficile
Clostridium difficile
• Clostridium difficile (difficult to culture, hence,
difficile) and soap and water kill spores better
than alcohol-based gels
• New strain (2003) produces more toxin and
causes more severe outbreaks—produces 16x
more toxin A and 23 times more toxin B;
characterized by the deletion of a gene that
downregulates the production of both toxins
• Major risk factor? Use of the fluoroquinolones;
Other antibiotics? Amox/Ampicillin, 2nd/3rd
generation cephalosporins
A few more notes on C. diff
• Has your patient had dental work with prescribed
antibiotics?
• Treatment—vancomycin, metronidazole
• Stool transplants in chronic C. diff
• High risk of recurrence in patients over 65, patients with
severe underlying disease, and additional antibiotic use
after discontinuing therapy for C. diff.
• Surawicz CM. Reining in recurrent Clostridium difficile
infection—Who’s at risk? Gastroenterology 2009
Apr;136:1152.
Necrotizing entercolitis (NEC) of
the newborn
• Acute, necrotizing inflammation of the small and
large intestine and is the most common acquired
gastrointestinal emergency of neonates,
particularly those who are premature or of low
birth weight
• Any time in the first 3 months, peak around time
infants are started on oral foods (2 to 4 days old)
• Another cause: Maternal cocaine use can
compromise intestinal blood flow, too
The sheep
• You wanna do WHAT with my intestines?
• Clinical uses of a sheep’s cecum
Movin’ right along …to the large
bowel
• What are the functions of the large bowel?
Functions of the large bowel
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Defense against bacteria--normal flora
Production of Vitamin K
Peristalsis and movement of feces
Acetylcholine triggers peristalsis
(anticholinergic drugs)
• Nicotine
• Serotonin also triggers peristalsis
• SSRIs and diarrhea
Functions of the large bowel
• Net absorption of water and salts/net
secretion of K+--diarrhea and potassium
depletion
Constipation
• “If you need time to think, ask older patients to
describe their bowel habits”.
--Clifton Meador, M.D
• The scope of the problem? 15% of the
population suffers from chronic constipation, and
over $1 billion is spent on laxatives annually
• Normal number of bowel movements?
• 3 per day to 3 per week or fewer than seven
bowel movements over a 2-week period with no
medication usage as a precipitating cause
Constipation
• + Rome III criteria w/ 5 other signs other than
stool frequency: straining, lumpy or hard stools,
incomplete evacuation, sensation of obstruction,
need for manual maneuvers to facilitate
evacuation
• If 2 or more of these 6 criteria are present for at
least 12 weeks during the previous 12 months, a
diagnosis of functional constipation can be made
Constipation—causes?
• Drugs—anticholinergic, opiods (codeine,
oxycodone)
• reduced fluid and fiber intake
• laxative abuse— “prune abuse”
• dementia—the “neglect of the call to stool”
• cancer of the colon
• decreased activity
• The infamous “other” category
New drug for opiate-induced
constipation
• Relistor (REL-i-store). It’s almost impossible to not get
constipated from opiods because of their effects on
motility. Relistor (methlynaltrexone) is an opiod
antagonist. Hmmmm…if it antagonizes opiods then how
do the opiods manage the pain. Here’s the beauty of
Relistor. Once the “methyl group” is added to naltrexone,
it prevents the antagonist from entering the brain and
reducing the opiods effects in the brain. Relistor just
blocks the opiod effect in the bowels. Almost 50% of the
patients will find relief within just 4 hours of taking
Relistor—hallelujah! It’s an injection by the way—subQ
and it’s primarily approved for palliative care patients that
are not getting relief from any other regimen.
Treatment for diarrhea
• Lomotil for diarrhea (atropine sulfate +
diphenoxylate HCl)
• Loperamide (Imodium)
• Undiarrhea (Taiwan)
• Stopit (Israel)
• “Lomotil is so good, it will…”
Colon cancer—98%
adenocarcinomas (large intestine)
• The numbers…
• Peak incidence for colorectal carcinoma is 60 to
79 years; fewer than 20% of cases occur before
the age of 50
• Cecum and ascending colon, 38%; transverse
colon, 18%; descending colon, 8%; sigmoid,
35%; multiple sites at presentation, 1%
• Risk factors?
Genetics
• Who’s yo’ daddy?
• When should you start screening family
members with a history of early-onset
cancer?
• Dad with colon cancer at diagnosed at 42?
And yo’ momma?
• Patients with a family history of 2 seconddegree relatives w/ colorectal cancer
should also start screening at age 40
Risk factors--polyps
• Three types
• Tubular adenomas—cancer is rare in tubular adenomas
smaller than 1 cm in diameter
• Villous adenomas—tend to be large and sessile; risk of
cancer is high (approaching 40%) in sessile villous
adenomas greater than 4 cm in diameter
• Tubulovillous adenoma—mixture of the two
Aspirin and polyps--38% of those taking an 81.5
mg (low-dose aspirin) had a new polyp
compared to 47% in the placebo group. This is a
risk reduction of 9%. Now, this isn’t a jawdropping difference however, IF colon cancer is
a high risk in your family or in a specific patient
population, a low-dose aspirin might give you an
edge against the disease. (April 2001, American
Association of Cancer Research meeting, San
Francisco)
Risk factors
• Constipation
• “Gosh, I remember when happy hour was
something other than a good bowel movement!”
Hereditary colon cancers
• What about the use of COX-2 inhibitors for the
prevention of colon cancer in patients with
familial adenomatous polyposis (FAP)—
absolutely
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• Screening should start as young as 20 in FAP
patients
Ulcerative colitis—inflammatory
bowel disease
• Limited to the colon and affects only the mucosa
and submucosa; extends in a continuous
fashion proximally from the rectum
• Peak onset between 20 and 25 years of age
• Risk for colon cancer—risk is highest in patients
with pancolitis of 10 or more years duration; 30%
@ 35 years after dx
• Dysplasia (distortion of the normal orientation
and architecture of cells)—low-grade dysplasia
vs. high-grade dysplasia and ulcerative colitis
Colon Cancer
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Get it in and get it out!
GI transit time…less than 72 hours
How can you tell? Eat corn tonight…
Floaters vs. sinkers
Other dietary risks—obesity; high content
of refined carbohydrates; intake of red
meat; decreased fiber
Don’t forget your colonoscopies!
Every 10 years after 50
• Or sigmoidoscopy every 5 years
• Don’t forget to ask about a change in
bowel habits.
• Exit time for colonoscopies should be at
least 8 minutes to increase the detection
of polyps
Dietary prevention of colon cancer?
• Fiber decreases proliferation
• Decreases insulin release from pancreas
(growth hormone)
• Decreases ILGF-1
• Calcium and vitamin D?
• Decreased red meat?
Speaking of gas…
• What is the BFR (basal flatal rate)?
• How often do we pass gas per day?
• The PPFR (post-prandial flatal rate)?
The PPFR after a meal comprised of 51%
baked beans?
• Gender differences?
Diverticular disease
• A diverticulum is a blind pouch communicating with the
lumen of the gut
• Rare under 30; over age 60 the incidence approaches
50%
• Usually multiple diverticula = diverticulosis
• 2 factors are important in their genesis
a) focal weakness in the colonic wall
b) increased intraluminal pressure
• 20% w/ diverticula exhibit symptoms; lower abdominal
discomfort, constipation, distention, sensation of never
being able to empty the rectum completely
The rectum—a portal of entry…
• Comments from patients during rectal exams: (Dr.
James Ralph)
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“Find Amelia Earhart yet?”
“Can you hear me NOW?”
“Hey, now I know how a muppet feels…”
“How long have you been in politics?”
“Remind me never to become an altar boy.”
“Could you write me a note for my wife, saying that my
head is not, in fact, up there?”
The rectum
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Rectal foreign objects
HPV and rectal warts
Herpes
Other STIs
Rectal cancer—squamous carcinoma of
the rectum (HPV)
The end.
• Barb Bancroft, RN, MSN, PNP
• CPP Associates, Inc.
• www.barbbancroft.com
• [email protected]
Bibliography
• Bariatric Surgery—Journal of the American Medical
Association (292:1724, 2004); Emergency Medicine
(37#7;31, 2005); British Medical Journal (331:128, 2005)
• Celiac disease—Patient Care (March 2005; 16-20);
Nutrition in Clinical Care (8#2; 55, 2005)
• Ondansetron and oral rehydration—N Engl J Med
(354;1698, 2006 April)
• Proton pump inhibitors and C. difficile colitis– JAMA
2005; 294:2989-2995.
• Probiotics. Canani RB et al. Probiotics for treatment of
acute diarrheal illness in children: Randomised clinical
trial of five different preparations. BJM 2007 Aug 18:335340.