A/45-49 GENERAL PATHOLOGY OF INFECTIOUS DISEASES (Tamer) Flashcards
Name the main taxonomic categories of infectious agents
“President Putin Has Very Few Badass Competitors”
- *P**rions
- *P**rotozoa
- *H**elminths
- *V**iruses
- *F**ungi
- *B**acteria
- *C**hlamydia , rickettsias, mycoplasmas
AND
Ectoparasites
prions are infectious agents that cause transmissible diseases.
what are they composed of ? where are they found ? describe their mechanism of action
- composed entirely of a protein material (PrP) found in high levels in neurons.
- cause transmissible spongiform encephalopathies
- Prp (Prion protein) undergoes conformational change and becomes Protease resistant. this resistant Prp causes Sensitive Prp’s to become protease resistant as well . that’s what makes them transmissible.
Name few features of Viruses
- Obligate intracellular, uses Host cells
- 20-300 nm
- usually seen in EM but may aggregate in infected cell and form inclusion bodies seen by LM
-consist of nucleic acid surrounded by capsid
(protein coat) and sometimes a lipid membrane (from host)
-Transient (C.C ,influenza )OR Persistent that may replicate (chronic EBV) or may not (latent infection by herpes zoster)
Some Viruses can transform host cell into … ?
neoplastic cells.
Examples :
-Adenovirus
- upper/lower RTI’s
- conjunctivits
- diarrhea
-Rotavirus
- childhood diarrhea
- EBV
- infectious mononucleosis
give the general characteristics of Bacteria
- Prokaryotes, have cell membrane and Wall ,some have flagella/pilli ,different locations (intra/extra)
- classfied GRAM +/- according to thickness of peptidoglycan in cell wall , shape, form of respiration
- synthesize DNA,RNA, use host for nutrition
- some are considered normal flora
- Strep.Mutans (teeth)
- Staph. Epidermidis (skin)
- GI
Chlamydia, Rickettsia and Mycoplasma are considered Atypical Microorganisms. HAWCUMDIS ?
-similar to bacteria but lack structures/metabolic capabilities
-Chlamydia (Obli.Intra) - can’t synthesize ATP
,cause female infertility , blindness
-Rickettsia (Obli.Intra) -transmitted by lice,ticks,mites
cause hemorrhagic vasculitis , pneumonia , hepatitis ,CNS injuries, DEATH
-Mycoplasma - tiniest , lack cell wall
cause atypical pneumonia
Pathogenic Fungi Have shit-load of properties.
mention few of them.
- Eukaryotes
- Chitin in cell wall and ergosterol in cell membrane
- grow as
- budding yeast
- hyphae (septate/aseptate)
-thermal dimorphism :
- hyphae at room temp
- yeast at body temp
-sexual/ asexual spores
there are 2 types of infection caused by fungi. what are these ?
1) superficial infections: skin,hair,nails can cause abscesses/granulomas in subcutaneous tissue
2) deep infections that are dormant and spread in immunocompromised individuals e.g. candida, aspergillus,cryptococcus
Protozoa are …
- Single cell Eukaryotes
- replicate
-
intra-celluary (malaria in RBC)
OR - extra-cellularly (UG system ,intestine,blood)
-major cause of morbidity/mortality in developing countries
name the features of helminth
- highly differentiated multicellular parasitic worms
- generate eggs/larvae
- disease proportional with number of organisms and usually due to inflammatory responses against egg/larvae
- reproduction
- sexual multiplication -in definitive host
- asexual multiplication- in intermediate host/vector
Name the 3 classes of Helminths.
**_1) Roundwarms_** collagenous tegument (cover), non-segmented structure
2) Flatworms
gutless , head and ribbon of flat segments , absorptive tegument
3) Flukes
leaf-like , primitive ,syncytial integument
what are Ectoparasites ?
Insects - lice, bedbugs, fleas
OR
Arachnids- mites, ticks, spiders
- Cause disease by biting /attaching to and living on or in the skin
- arthopods can cause direct/indirect (vector for infectious agent) damage
mention few possible routes of infection
- inhalation
- ingestion (fecal-oral)
- sexual transmission
- bites (vectors)
- zoonotic
- injection
the skin and mucosal surface are the 1st line of defence against infectious agents. explain how they do so .
- skin kertainized layer has low pH (5.5) and fatty acids prevent the growth of microbes. skin sheds and renews.
- humid skin is more penetrable as well as breaks in skin e.g. cuts , wounds , burns , few microbes penetrate unbroken skin (schistosoma)
- intravenous catheters ,needles ,bites can also cause infections
Name few agents that impair the mucociliary clearance
- smoking -metaplasia
- intubation
- Cystic Fibrosis -hyperviscous mucus
- B.pertussis -toxin mediated Cilliostasis
- Influenza - lower mucus viscosity ,loss of ciliated epithelium
- TB-escape phagocytosis
- immunosupression
- gastric acid aspiration
Most of intestinal tract pathogens are transmitted by …
food and drink contaminated with fecal material
what are some of the defense mechanisms of the GI tract ?
1) Acidic pH , Viscous mucus
2) Lytic pancreatic enzymes , bile
3) defensins, IgA
4) Normal Flora
How do infections occur in the GI ?
- when defense mechanisms are either supressed (fungi) /organism developes resistance against them(protozoa) .
(e. g. non-enveloped virus may be resistant to defense mechanisms)
pathogens cause disease by :
- entero/exo-toxins
- invade and cause hemorrhage (shigella,salmonella)
- invade and travel through layers into blood stream
- *-**protozoa travel in cyst resistant to stomach acid
the Urogenital tract is usually sterile because its flushed many times per day . how do infections occur then ?
- by pathogens that adhere to urothelium
- more frequent in women - shorter urethra
- catheters increase risk
if a Urogenital Tract infectious agent travels to the kidney it may lead to …
Chronic pyelonephritis
spreading of microorganisms can be
locally
OR
spread to other areas via blood,lymphatics ,nerves
-invasion to blood is rapidly supressed (tooth brushing)
but if sustained causes fever, hypotension ,sepsis
-If reached blood either :
- travel freely -EBV,poliovirus
- intracellularly -herpes in wbc’s , HIV
name the few possible routes in which pathogens exit the host
1) skin shedding
2) coughing
3) sneezing
4) urination
5) defecation
6) placentofetal/vertical transmission
7) insect vectors
-following (second) transmission depends on badassness of the microbe
- bacteria form spores
- protozoa travel in cyts
- helminths make eggs
Steps in microbial pathogenesis
- Attachment to host cell , colonisation
- invasion
- local/wide spread , multiplication
- cell/tissue damage
describe the general mechanism by which viruses cause injury
viruses directly damage cells by replicating inside them at the host’s expense . they enter cell , replicate and translate genome, into viral proteins that interfere with cell normal function.
how can Viral Poteins cause injury ?
1) lyis of host cell due to interfering replicaiton
2) immune cell-mediated killing
infected cells are recognized and attacked by cytotoxic t-cells
3) alteration of apoptosis by viral proteins
- adenovirus induce cell apoptosis -microbe elimination (good)
- some release anti-apoptotic proteins - viral replication (not good)
4) transformaiton of infected cell resulting in cancer
- EBV
- HBV
- HCV
- HPV
5) inhibition of host’s DNA,RNA, protein synthesis
6) insert into plasma membrane causing it’s damage
7) secondary infections
the ability of bacteria to cause disease depends on …
1) **adherence to host molecules
- ** adhesins aid bacteria to bind host cells
-on gram +(bind fibronectin,prevent phagocytosis)
- fimbria
- lipoteichoic acid
- M protein
- F protein
- on gram -
- fimbria/pilli for adhesion
2) virulence of intracellular bacteria
ability to enter the cell by opsonization and endocytosis
ability to survive by inhibition of ,escape from ,resistance to phagolysosomes and lysosmal products
3) bacterial toxins
-Endotoxin
LPS (lipid-A) of gram - bacteria promote cell activation and inflammatory repsonse involving IL-1, TNF, kinins ,septic shock
-Exotoxin
- Enzymes
- A-B toxins -alter intracellular signaling/regulatory pathways
- Superantigens-massive stimulation of T-cells leading to SIRS, toxic shock syndrome
- Neurotoxins - inhibit release of NT’s , paralysis
- Enterotoxins-nausea , vomting
host-mediated immune injury is …
- tissue injury caused by host’s own immune response against tissue injury.
e. g. - TB causes GRANULOMATOUS reaction that prevents spread of bacilli, but on the other hand tissue damage and fibrosis.
- antibodies against bacterial M protein can also attack cardiac proteins leading to rheumatic fever
what are the techniques used for diagnosis of infectious agents ?
1) Culture
2) Serological tests
3) Stain in direct smear/sliders
4) PCR, QR-PCR - gonorrhea , Chlamydia, TB
5) In situ hybridization - CMV, EBV
6) Immunohistochemistry on slides /smears
7) EM: EBV, Helico.B , Herpes ,
Gram stain is used for …
most bacteria
Acid fast stain is used for …
Mycobacteria , Nocardiae
Silver stain is used for …
Fungi , Legionella , Pneumocystis
PAS is used for …
Fungi ,Amebae
Giemsa staining is used for …
Campylobacter, protozoa
Define Bacteremia
bacteria present in blood , confirmed by culture , may be transient
what are the steps leading to a septic shock ?
SIRS –> SEPSIS –> SEVERE SEPSIS –>SEPTIC SHOCK
SIRS (systemic inflammatory response syndrome)
response to a wide variety of clinical insults which can be infectious as in sepsis or non-infectious (burns,pancreatitis)
Sepsis. WASSMEANDAT ?
clinical evidence of infection and systemic response including two or more of the following conditions :
1) Temperature > 38 C , 36 C
2) HR > 90 BPM
3) Respiratory rate > 20 breaths/min , PaCO2 < 32 mmHg
4) WBC > 12,000 cells/mm3
or
WBC < 4000 cells mm3
or
WBC > 10% immature forms
Severe sepsis is
Sepsis + organ dysfunction that results in
- hypotension
- lactic acidosis
- oliguria
- confusion
- hepatic dysfunction
Septic shock is …
Severe sepsis + hypotension depsite fluid resuscitation
Refractory septic is …
septic shock that lasts >1 hour , with no response to fluid adminstration,medication
Name the risk factor for sepsis
- weak host defense
- type and duration of hospitalization (higher rate in ICU)
- operative procedure
- indwelling urinary catheters , intravascular devices
GRAM - are responsible for …
35% of sepsis incidents
include :
- E.coli
- Pseudomonas
- Klebsiella
GRAM + are responsible for …
39% of sepsis incidents
include :
- S.aureus
- S.epidermidis
- Enterococci
- Pneumococci
21% of sepsis incidents are caused by ..
a mix of microorganisms (gram +/- etc…)
Fungi ,Anaerobes and Mycobacteria are responsible for …
5% of sepsis incidents
what are the bacterial components taking part in the pathogenesis of septic shock ?
- Endotoxin (LPS, lipid -A) - all GRAM -
- Peptidoglycan - all bacteria
- Lipoteichoic acid - Gram +
- Pore-forming exotoxins - a-hemolysin , streptolysin-o
- Superantigens -TSST1 , enterotoxins A-F
- Enzymes -PLC , IL-1B cnonvertase
LPS effects the following components …
- complement system
- monocytes
- endothelial cells
- neutrophils
- factor XII
Monocytes ,macrophages and Neutrophils Secrete the following proinflammatory mediators …
TNF-α , IL-1
these further stimulate IL-6 producing cells
Endothelial cells secrete …
- NO
- TF
Upon Endothelial damage the microcircular leak unit is initiated and is composed of the following mediators …
-NO
- Vasodilation
- Regional Vasoconstriction
- Capillary shunting
- Tissue Factor
- coagulopathies ,microthrombi
- TNF-α
- reduced stroke volume
- reduced Ejection Fraction
After endothelial damage have occured the release of NO, TF, TNF-α leads to …
microvascular insufficiency
- dramatic fall in systemic vascular resistance
- severe myocardial depression
- severe hypotension
-all of these changes lead to Tissue hypoxia and finally Multi-Organ Failure
describe the changes in peripheral vasculature , myocardium and lungs during multiorgan failure in septic shock
1) Peripheral vasculature - NO and TF lead to
- vasodilation ,
- Coagulopathy (DIC) ,
- Refractory hypotension ,
- shunting
2) Myocardium -altered Ca+2 influx and decreased contractility lead to
- myocardial depression
- arrhythmias
3) Lung - due to increased endothel permability and neutrophils activation/migration
-
ARDS
*
describe the changes in the kidney , liver and gut during multiorgan failure in septic shock
- Kidney - due to renal hypoperfusion
- Acute tubular Necrosis
-Liver - due to hypoperfusion and acidosis
- Zonal necrosis
- hepatic failure
- jaundice
-Gut - due to hypoperfusion and acidosis
- Breach of endothelial integrity
-
describe the changes in the brain during multiorgan failure in septic shock
Encephalopathy due to hypoperfusion and acidosis
Managment of septic shock includes …
- treating the underlying non-infective disease
- preserve vital organ perfusion and tissue oxygenation
- treat underlying infection
- avoid complications
Perinatal infection may be acquired in two ways , namely …
- Transcervically (ascending infections)
- Transplancentally (hematogenic infections)
Transcervical perinatal infections occurs when …
- infection spreads from cervicovaginal canal (inhaled by fetus) or during birth (when passing through birth canal)
- mostly bacterial infection that lead to inflammation of placental membrane and umbilical cord
- later gives rise to pneumonia , meningitidis, sepsis
Transplacental perinatal infections enter fetal blood stream via … ?
-direct tranfusion from Chorionic villi during delivery
leads to “TORCH”
- *T**oxoplasma
- *O**ther
- *R**ubella virus
- *C**ytomegallovirus
- *H**erpesvirus
- Early in gestation: growth restriction, mental retardation, cardiac abnormalities
-
Later: inflammatory tissue injury
(pneumonia, myocarditis)
