SEQ EXERCISE

By:
Dr. Mohammad Saad Abdul-Majid
Q. Discuss the pathogenesis of SIRS.
Q. Define the following:
A. Sepsis
B. Severe Sepsis
C. Septic shock
D. MODS
Q. Discuss the pathogenicity of Enterotoxigenic E. coli
(ETEC).
Q. Discuss the routes of infection of liver abscess.
Q. Discuss the virulence factors of Samonella typhi.
Q. Discuss the pathogenesis of typhoid fever.
Q. List down the most common bacteria causing meningitis
in adults and state the shared features.
Q. Discuss the laboratory diagnosis of bacterial meningitis.
Q. Discuss the pathogenesis of meningitis.
Q. Discuss the pathogenesis of gas gangrene.
Q. Discuss the pathogenesis of pertussis.
Q. Discuss the pathogenesis of pneumonia.
Q. List down the virulence factors of Streptococcus
penumoniae in causing pneumonia.
Q. Compare between acute and sub-acute infective
endocarditis.
Q. Discuss the pathogenesis of infective endocarditis.
Q. Discuss the three glass test.
Q. List down the routes of infection of osteomyelitis.
Q. Discuss the pathogenesis of osteomyelitis.
Q. Discuss the specific laboratory diagnosis of
osteomyelitis.
Q. Discuss the pathogenesis of Rheumatic fever.
Q. Discuss the pathogenesis of SIRS.
A/ Stage I
Following an insult, local cytokine is produced, thereby promoting wound repair and
recruitment of the reticular endothelial system.
Stage II
Small quantities of local cytokines are released into the circulation to improve the local
response. This leads to growth factor stimulation and the recruitment of macrophages
and platelets.
Stage III
A significant systemic reaction occurs. The cytokine release leads to destruction rather
than protection.
Activation of numerous humoral cascades
The activation of the reticular endothelial system
Loss of circulatory integrity.
Leads to end-organ dysfunction.
Q. Define the following:
A. Sepsis: a clinical syndrome that complicates severe infection and is
characterized by systemic inflammation and widespread tissue injury.
(SIRS in the presence of or as a result of suspected or proven infection).
B. Severe Sepsis: Sepsis plus cardiovascular organ dysfunction (hypotension),
ARDS, or two or more other organ dysfunction: Lactic acidosis, Oliguria, Acute mental
state changes or Hepatic dysfunction.
C. Septic shock: Septic shock is sepsis with hypotension (systolic blood pressure
< 90 mm Hg) despite adequate fluid resuscitation. Concomitant organ dysfunction or
perfusion abnormalities (e.g. lactic acidosis, oliguria, and coma) are present in the
absence of other known causes.
D. MODS: A state of physiologic derangements in which organ function is not
capable of maintaining homeostasis.
Q. Discuss the pathogenicity of Enterotoxigenic E. coli
(ETEC).
A/
Heat-labile (LT):
It consists of polypeptide subunits, A and B.
Five B subunits mediate attachment to cells via the GD1 receptor, and one A subunit then
enters the cell and activates Adenylate cyclase.
This toxin is biologically and immunologically closely related to cholera toxin.
Heat-stable (ST):
It induces hypersecretion by stimulating Guanylate cyclase synthesis.
Q. Discuss the routes of infection of liver abscess.
1. Biliary tract infection (60%): secondary to biliary obstructive and
inflammatory conditions (eg, cholecystitis, choledocholithiasis, and
cholangitis, especially in patients with biliary tract malignancies with biliary
stents).
2. Infection from gastrointestinal or pelvic organs drained via the portal
circulation (24%): examples include appendicitis, diverticulitis, and
perforated bowel.
3. Unknown (20%)
4. Hematogenous spread secondary to bacteremia (15%).
5. Blunt or penetrating trauma (3%)
Q. Discuss the virulence factors of Samonella typhi.
Lipopolysaccharide (LPS): protects the bacterial cell from the bactericidal
activity of serum, influences macrophage interactions (release TNF- and
cytokines) and functions as endotoxin.
Vi antigen (polysaccharide): inhibits phagocytosis and masks the O
antigen, reducing the infective dose of the organism.
Many strains have developed plasmid-mediated multidrug resistance to all
3 of the primary antimicrobials:
A. Ampicillin.
B. Chloramphenicol.
C. Trimethoprim-sulfamethoxazole.
Q. Discuss the pathogenesis of typhoid fever.
Ingestion of the organism. (street foods and water reservoirs)
Infective dose is about 105-109 organisms.
Organisms invade the gut mucosa in the terminal ileum, through M
cells that overlie gut-associated lymphoid tissues.
S. Typhi crosses the intestinal mucosal barrier after attachment to
the microvilli.
Organisms enter the mesenteric lymphoid system and then pass into
the bloodstream.
This primary bacteremia is usually asymptomatic, and blood culture
results are frequently negative at this stage of the disease.
Then disseminated throughout the body (Liver, Bones and
kidneys).
After a period of bacterial replication, organisms are shed back
into the blood, causing a secondary bacteremia that coincides
with the onset of clinical symptoms and marks the end of the
incubation period.
Q. List down the most common bacteria causing meningitis
in adults and state the shared features.
1. Haemophilus influenzae: cocco-bacillary" gram-negative rods.
2. Neisseria meningitidis: Gram-negative diplococci.
3. Streptococcus pneumoniae: Gram-positive diplococci.
These three pathogens have several virulence factors in common
including:
1. Polysaccharide capsule.
2. IgA protease.
Q. Discuss the laboratory diagnosis of bacterial meningitis.
Specimens:
1. Cerebrospinal fluid
2. Blood cultures
3. Throat swabs
4. Stool specimens (for viral culture)
Cerebrospinal fluid (Golden standard)
1. Cytology
2. Biochemical test : glucose and protein levels.
CSF glucose level must be considered in relation to blood glucose level.
Normally CSF glucose level is 50-70% lower than the blood glucose
level.
3. Culture
4. Rapid diagnostic tests
Rapid diagnostic tests:
Gram-stain of centrifuged deposit
Special stains
Ziehl-Neelsen stain (for acid-fast organisms).
Latex agglutination tests:
- Neisseria meningitidis A, C, W135, Y
- Streptococcus pneumoniae
- Haemophilus influenzae serotype b
Polymerase Chain Reaction (PCR):
Mycobacterium tuberculosis.
Neisseria meningitidis.
Streptococcus pneumoniae.
Q. Discuss the pathogenesis of meningitis.
1. Initially, an infectious agent establishes a localized infection in the
host(skin, nasopharynx, respiratory tract).
2. The organism invades the sub-mucosa by evading host defenses
and reaching the CNS.
3. Increasing numbers of inflammatory cells.
4. Cytokine-induced disruptions in membrane transport, and
increased vascular and membrane permeability account for the
characteristic changes in CSF.
5. Increase vascular permeability leads to cerebral edema (Increased
ICP).
Q. Discuss the pathogenesis of gas gangrene.
The toxin involved in gas gangrene is known as -toxin,
which increases the permeability of the plasma membrane
of cells leading to disrupt normal cellular function.
Q. Discuss the pathogenesis of pertussis.
The first stage is colonization:
It is an upper respiratory disease with fever, malaise and coughing, which
increases in intensity over about a 10-day period.
During this stage the organism can be recovered in large numbers from
pharyngeal cultures.
Adherence mechanisms of B. pertussis involve:
1. A "filamentous hemagglutinin" (FHA), which is a fimbrial-like structure on
the bacterial surface.
2. Cell-bound pertussis toxin (PTx).
The second or toxemic stage:
It begins gradually with prolonged and paroxysmal coughing that often ends in a
characteristic inspiratory gasp (whoop).
During the second stage, B. pertussis can rarely be recovered, and antimicrobial
agents have no effect on the progress of the disease, this stage is mediated by a
variety of soluble toxins.
Q. Discuss the pathogenesis of pneumonia.
Pneumonia is an infection of the alveolar or gas-exchanging portions of the lung.
pneumonia produces an intense inflammatory response within the alveoli that leads to
filling of the air space with:
1. Organisms.
2. Exudate.
3. white blood cells.
Q. List down the virulence factors of Streptococcus
penumoniae in causing pneumonia.
1. Capsular polysaccharide.
2. Cell wall (C) polysaccharide.
3. Toxins: pneumolysin, neuraminidase.
4. Surface protein A.
5. Immunoglobulin A protease.
6. Hyaluronidase and enolase.
Q. Compare between acute and sub-acute infective
endocarditis.
Acute
Affects normal heart
valves
Rapidly destructive
Metastatic foci
Commonly Staph.
If not treated, usually
fatal within 6 weeks
Subacute
Often affects damaged
heart valves
Indolent nature
Commonly Strep.
If not treated, usually
fatal by one year
Q. Discuss the pathogenesis of IE
Q. Discuss the three glass test.
First container: when the flow is established: contains debris, cells and
organisms from the urethra and often contains strands of mucus if urethritis is
present.
Second container: the mid-stream urine (MSU) contains bladder urine.
A normal specimen appears clear and transparent, while cloudiness indicates
the presence of cells, bacteria or crystals.
Third container: contains the last millilitres of the urine flow (terminal urine).
The final sample contains:
1. Matter from the clefts of the trigone.
2. From the prostate.
3. From glands adjacent to the pelvic urethra.
4. Mucus strands are often seen in cases with prostatitis.
5. Schistosome ova from the bladder wall may be recovered from terminal
urine.
Q. List down the routes of infection of osteomyelitis.
1. Haematogenous spread: it is caused by bacterial seeding from the blood. This
condition primarily occurs in children. The most common site is the rapidly
growing and highly vascular metaphysis of growing bones.
2. Extension from an adjacent infected joint.
3. Direct invasion as a result of trauma.
4. Extension of infection from an overlying soft-tissue infection or deep ulcer.
Q. Discuss the pathogenesis of osteomyelitis.
Metaphysis: its arteries branch into non-anastomosing capillaries under the physis,
which make a sharp loop before entering venous sinusoids draining into the marrow.
Blood flow in this area is sluggish predisposing to bacterial invasion.
Once a bacterial focus is established, phagocytes migrate to the site and produce an
inflammatory exudate (metaphyseal abscess).
As the inflammatory exudate progresses, pressure increases spread through the
porous metaphyseal space via the haversian system and Volkmann canals into the
subperiosteal space.
Salmonella osteomyelitis affects the bones of individuals with sickle cell disease,
possibly because of stagnant bone circulation following sickling crises.
Formation of sequestra and involucra: (Chronic osteomyelitis)
If treatment is delayed, an infected area of bone may undergo necrosis. An
accumulation of new bone eventually encloses it.
The old, dead bone is called a sequestrum.
The surrounding live bone is termed involucrum.
The sequestrum:
It has NO blood supply, and is inaccessible to antibiotics and
immunological processes.
As with implanted foreign materials, it can become a site of
persisting infection that prevents the healing of the
osteomyelitis.
Q. Discuss the specific laboratory diagnosis of
osteomyelitis.
Blood cultures: should be performed in all suspected cases.
Aspiration or biopsy of bone or subperiosteal abscess for Gram stain, culture, and
possibly bone histology.
Direct inoculation of clinical specimens into aerobic blood culture bottles can
improve the recovery of K. kingae.
Polymerase chain reaction: appears to be the most sensitive technique to detect K.
kingae.
Q. Discuss the pathogenesis of Rheumatic fever.
Rheumatic Fever Results from antibodies cross-reacting (Type II
hypersensitivity) with tissues in the heart, joints, skin, and central
nervous system at the level of B and T lymphocytes.
Group A streptococci falls into two main classes based on differences in the C repeat
regions of the M protein:
A. GAS strains cause pharyngitis.
B. GAS strains cause impetigo.
The strains that cause pharyngitis are implicated in RF.
None of the strains cause skin infections leads to RF.
The role of GAS superantigens (pyrogenic exotoxins) in the pathogenesis of acute
rheumatic fever has been proposed.
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