Course Guide High Yield Flashcards
PARASITIC PROTOZOA
one celled organisms with a facultative anaerobic metabolism, free oxygen being limited in the host.
“flask-shaped” lesions
- Entamoeba histolytica* is the causative agent of amebic dysentery
- trophozoites attach and invade intestinal mucosa causing the formation of amebic ulcers in the large intestine primarily in the cecum or sigmoidorectal area, appendix and ascending colon less frequently
“ground glass” cytoplasm and a single
nucleus with central karyosome and evenly distributed chromatin
What do cysts look like?
Entamoeba histolytica
cysts are spherical with 1 to 4
nuclei, and may contain sausage
shaped chromatoid bodies.
Acanthamoeba
- free-living protozoans
- associated with improperly sterilized contact lenses
Naegleria fowleri
- free-living amoeba is found in warm fresh water
- primary amebic meningoencephalitis
most common intestinal protozoan infection in US
Giardia lamblia-a flagellate
cyst is football-shaped with 2-4 nuclei (each cyst with 2 individuals) and axonemes.
Giardia lamblia
-oval-pear-shaped trophozoites, with one nucleus
motile by four flagella, and characteristic undulating membrane
Trichomonas vaginalis- common sexually transmitted flagellate
- Oocysts are tiny (4-6 um) and round
- acid fast nature helps to identify in stained preparations.
Cryptosporidium sp.-
Cyclospora cayetanensis:
Similar to Cryptosporidium (except larger)
Also acid fast oocysts
Contaminated food (fruit) from South America, Asia
Isospora belli
In US, major problem is in AIDS patients. Diagnostic form is large, oval shaped oocyst, often with 2 embryos. Acid fast.
Balantidium coli:
- only known ciliate to cause human disease
- Major reservoir is swine
- similar to Entamoeba histolytica (dysentary), but almost never invades beyond gut wall
- Cyst is diagnostic and infectious stage
Cestodes
tapeworms
- characterized by bodies with 3 principal features. First a scolex (head) with specialized attachment organs (hooks and/or suckers),
- second, a neck or immature region giving rise to the
- third region called a strobila.
- lack of a digestive tract
Nematodes
round worms
basic body plan is a tube within a tube, the outer tube is the body wall, inner tube is the digestive system.
larvae undergo a series of molts (shedding of outer cuticle)
L1 larvae referred to as rhabditiform, L3 larvae are referred to as filariform (infective).
world’s most common parasite
Enterobium vermicularis -(pinworm)-affects mostly children
rare autosomal dominant genetic disease
(LKB1/STK11 mutation)
PEUTZ-JEGHERS SYNDROME
branching smooth muscle
fibers, proliferated complex glands and increased mucin
mucocutaneous pigmentation,
gastrointestinal hamartomatous polyps and increased risk of malignancies in organs such as colon, pancreas, breast, ovary and testis
Extra-intestinal manifestations include congenital hypertrophy of retinal pigment epithelium (CHRPE), osteomas, epidermal cysts, desmoid tumors and CNS tumors.
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
autosomal dominant germline mutation in one of
the multiple mismatch repair genes (MLH1, MSH2
HEREDITARY NON-POLYPOSIS COLON CARCINOMA
Lynch syndrome
most common malignancy of the GI tract
COLORECTAL ADENOCARCINOMA (CRC)
third most common malignancy in either gender, and second most common cause of cancer-related mortality
Name 4 drugs that Induction Immunosuppression
- Anti-lymphocyte globulin (ATGAM and Thymoglobulin)
- Alemtuzumab (Campath)
- Basiliximab (Simulect)
- Methylprednisolone
Calcineurin inhibitors
Cyclosporine
Tacrolimus
Antimetabolites
Azathioprine
Mycophenolate
mTOR inhibitors
Sirolimus
Everolimus
Alemtuzumab
(Campath®)
Humanized monoclonoal antibody against CD52
Binds to CD52 on lymphocytes, monocytes, macrophages, and natural killer cells, which causes cell lysis
Basiliximab
(Simulect®)
BASically, an IL-2 receptor-Inhibitory chimeric (XI) MAB
IL-2 Receptor Blockade - monoclonal antibodies (mAb) against the alpha subunit of IL-2.
Binds to the alpha unit of the IL-2 receptor inhibiting binding of IL- 2 thereby preventing activation of lymphocytes
Similar to Daclizumab
Methylprednisolone
(Solu-Medrol®)
Corticosteriods - Blocks cytokine gene expression resulting in a decreased immune response
Tacrolimus (Prograf®, TAC, FK 506)
MOA
Major TOX
- blocking calcineurin - Binds to FKBP and inhibits calcineurin (same mechanism as cyclosporin)
-
Along with Cyclosporine, belongs to NIH
- NEPHROTOXICITY
- Neurotoxic
- Increased cholelithiasis in children
- Hyperglycemic
Cyclosporine
(Neoral®,
Sandimmune®, CsA)
Major TOX
Calcineurin Inhibitor - prevents bindig to transcription factor NF-AT.
This cycle belongs to the NIH
- Nephrotoxicity
- Increased cholelithiasis in children
- Hypertension, hyperglycemia
Mycophenolate
Mofetil (Cellcept®,MMF)
Mycophenolate
Sodium
(Myfortic®,MPA)
MOA
TOX
Metabolized to mycophenolic acid in liver. It Acts within B and T lymphocytes to inhibit inosine monophosphate dehydrogenase, involved in GMP synthesis in the de novo pathway of purine synthesis - Decreases DNA synthesis in B and T cells - cellular proliferation is decreased.
Clinical use - Immunosuppresant in transplant patients; autoimmune disorders.
GI intolerance, bone
marrow suppression
Azathioprine
Major TOX
(Imuran®, AZA)
Anti-Metabolites Inhibits proliferation of T and B cells by preventing RNA and DNA synthesis
GI intolerance, bone
marrow suppression,
_elevated liver
transaminases_
Sirolimus
TOX
(Rapamune®)
mTOR Inhibitors - Binds to FKBP-12 forming a complex that inhibits the target of rapamycin which proliferation of T and B-cells
- Anemia
- impaired wound
- healing
- proteinuria
Everolimus
TOX
(Zortress®)
mTOR Inhibitors - Binds to FKBP-12 forming a complex that inhibits the target of rapamycin which proliferation of T and B-cells
- Anemia
- impaired wound healing
Glycopyrrolate MOA
Anti muscarinic - Block direct muscarinic stimulation of parietal cells, decreasing acid
Sucralfate (Carafate)
Cytoprotective - Polymerizes into a protective gel to protect against gastric acid
Gel inhibits back diffusion of H+ and reduces pepsin activity
Cisapride MOA
Prokinetic - facilitates ACh release
2 Approved treatments for H. Pylori
2 approved treatments
- Bismuth subsalicylate (Pepto Bismol), metronidazole and tetracycline (2 antibiotics) for 14 days
- Omeprazole and clarithromycin for 14 days
Metoclopramide
cholinomimetic agent and a D2 receptor blocker
Promotes the release of acetylcholine from
myenteric neurons - Increases LES pressure and relaxes pyloric sphincter
Use: Diabetic gastroparisis and GERD
Under restricted use due to association with torsades de pointes
Cisapride
– Facilitates acetylcholine release from myenteric plexus
- Mg citrate
- Sodium Phosphate
Osmotic/ (Saline)
Docusate
Surfactant - Sm & large Intestines, Detergent: facilitates mixture of fat and water to soften stool
For painful hemorrhoids
Used to prevent constipation,
only a weak stimulant
Commonly given to
hospitalized pts to minimize
straining
Bisacodyl
Stimulant - Colon, Stimulate smooth Ms peristalsis.
Diphenoxylate (with Atropine-Lomotil)
Antidiarrheal
meperidine (related piperidine opioid)Acts at mu receptors on enteric neurons
Loperamide (Imodium)
Does not cross the BBB
Increase transit time, antidiarrheal
Bismuth Subsalicylate (Pepto Bismol)
Salicylate is involved in anti-motility, anti-secretory, anti inflammatory effects
salicylate so Reyes’ syndrome warnings also apply
hepatitis shows greater predisposition to hepatocellular
carcinoma with or without cirrhosis.
ground glass hepatocytes
containing HBsAg) may be seen
Chronic HBV
Family that HBV belongs to
Hepadnavirus
% Adults with HBV that don’t resolve?
10% persistent infection
90% Resolve
% of newborn HBV infections that don’t resolve
30-90% of newborn infections (from exposure to infectious maternal blood) result in chronic infection
- immune system is not fully formed
- vaccination at birth can prevent infection
used as marker for active replication in HBV
HBeAg (e antigen) - soluble, not associated with virion
DNA genome of HBV
partially double stranded in the virion.
3.2 kb DNA; smallest DNA virus genome
HDV Genome
- Genome is small, single strand RNA, circular
- Genome contains a ribozyme (RNA) sequence that cleaves the long RNA into unit length pieces and ligates the ends to recreate a circle.
- Similarities to plant viroids
- Needs HBsAg coat to make infectious particles
Hepatitis A virus:
Family
Genome
Picornaviridae
ssRNA (+)
Hepatitis B virus
Family
Genome
Hepadnaviridae (DNA)
partially ds DNA
Hepatitis C virus
Family
Genome
Flaviviridae
ssRNA (+)
Hepatitis D virus
Family
Genome
Viroid (depends on HBV)
circular ssRNA (-)
Hepatitis E virus
Family
Genome
Hepevirideae
ssRNA (+)
Hepatitis viruses that have a ssRNA(+) Genome
“ACE in the ssReally Positive”
Causes chronic hepatitis (85% of infections)
Hepatitis C virus
Can progress to cirrhosis, then to liver failure, or carcinoma
HCV was THE major cause of post-transfusion hepatitis after HBV was removed from the
blood supply
What was done to solve this problem?
HCV antigen is now used to detect anti-HCV antibodies in blood supply:
has eliminated HCV contaminated blood and most post-transfusion hepatitis
Treatment for HCV
alpha-interferon for 6 months
40% of patients: ALT levels decrease to normal during therapy
10% to 30% have long-term response/resolve the infection
Many side effects
Interferon + ribovirin: allows lower dose of interferon, fewer side-effects
mortality in pregnancy, up to 25% (3rd trimester infections)
Hepatitis E virus
PARTIAL MUCOSAL INVASION
Organisms
Clinical illness
Ingested organisms divide and attach to mucosa. Cause
mucosal ulcerations but invade no deeper.
Shigella, Campylobacter jejuni, Clostridium difficile, invasive E.
coli, Entamoeba histolytica
Incubation period is 2-4 days. Dysentery with blood and pus in stools. Of all infectious diarrheas, these are most associated with grossly bloody stools
TOXIN MEDIATED DIARRHEA
Organisms
Clinical Illness
Toxin produced by organism, organism does not invade
and may not even be ingested
Vibrio cholera, enterotoxigenic E. coli, Staphylococcus aureus, Bacillus cereus, Clostridium perfringens
Acute, short incubation (2-24 hours), watery diarrhea. Minimal local inflammatory response (0 or few RBCs/WBCs in stool) and usually no fever. Typically, last 2-5 days. Major risk is dehydration.
COMPLETE MUCOSAL INVASION
Most often site?
Organisms?
Ingested organism attaches and invades full thickness of
bowel, into regional lymphatics, and occasionally into bloodstream
Site - Colon
- Salmonella typhi, Yersinia*
Viral agents that cause viral diarrhea
Norwalk virus
Norovirus
Rotavirus
Adenoviruses
Reoviridae
Shape?
Gemone
Important members
- icosahedral, double capsid, no envelope
- double-stranded RNA, segmented (10, 11, or 12)
- ROTAVIRUS
Rotavirus
- Transmission*
- Highest incidence*
- Incubation*
- Symptoms*
- Important for recovery?*
- Major cause of gastroenteritis in infants and a significant cause of mortality of infants in developing countries (1 million fatalities/yr). Age <2 yr, usually.
- Fecal-oral transmission
- Highest incidence in fall and winter (November – April)
- Incubation period: 24-72 hours
- Symptoms: vomiting, diarrhea, fever, dehydration.
- IgA is important in recovery, prevention
Therapy - rehydration, the diarrhea usually resolves in 2-7 days. Failure to rehydrate may lead to death, especially in infants. Live attenuated oral vaccine recently approved, now recommended for all infants.
Adenovirideae
- Important serotypes*
- Structure*
- Genome*
- Disease*
Adenovirus serotypes 40, 41, 42 [Serogroup F]
Icosahedral, No envelope
Linear, double-stranded DNA genome
Serotypes 40, 41, and 42 cause acute viral gastroenteritis (fecal-oral spread) in infants
(usually under 1 yr old), often associated with a concurrent respiratory tract infection.
Caliciviridae
- Shape*
- Genome*
- Transmission*
- Disease*
- Incubation*
Norovirus
no envelope - icosahedral
Positive single strand RNA genome
Food-borne/Fecal-oral
Causes nonbacterial gastroenteritis in school-age children and adults
Incubation period: short – 6-24 hours
How are viral gastroenteridites different from invasive bacterial GI infections?
All viral gastroenteridities cause watery diarrhea without blood or WBCs in the stool. Invasive bacterial GI infections (Campylobacter, Salmonella, Shigella) are characterized by GI inflammation, with blood and pus (WBCs) in stool (at least in serious cases) and always fever. Fever may be absent in viral diarrheas.