SEQ Exercise

8/12/2019 SEQ Exercise

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SEQ EXERCISE

By:Dr. Mohammad Saad Abdul-Majid


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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 infectiveendocarditis.

Q. Discuss the pathogenesis of infective endocarditis.


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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 ofosteomyelitis.

Q. Discuss the pathogenesis of Rheumatic fever.


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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.


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Q. Define the following:

A. Sepsis: a clinical syndrome that complicates severe infection and ischaracterized 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 theabsence of other known causes.

D. MODS: A state of physiologic derangements in which organ function is notcapable of maintaining homeostasis.


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Q. Discuss the pathogenicity of Enterotoxigenic E. co li

(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.


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Q. Discuss the routes of infection of liver abscess.1. Biliary tract infection (60%): secondary to biliary obstructive and

inflammatory conditions (eg, cholecystitis, choledocholithiasis, andcholangitis, especially in patients with biliary tract malignancies with biliarystents).

2. Infection from gastrointestinal or pelvic organs drained via the portalcirculation (24%): examples include appendicitis, diverticulitis, andperforated bowel.

3. Unknown (20%)

4. Hematogenous spread secondary to bacteremia (15%).

5. Blunt or penetrating trauma (3%)


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Q. Discuss the virulence factors of Samonel la typh i . 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.


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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, throughcells that overlie gut-associated lymphoid tissues.

S Typhi crosses the intestinal mucosal barrier after attachment tothe microvilli.

Organisms enter the mesenteric lymphoid system and then pass intothe bloodstream.

This primary bacteremia is usually asymptomatic, and blood cultureresults are frequently negative at this stage of the disease.

Then disseminated throughout the body (Liver, Bones andkidneys).

After a period of bacterial replication, organisms are shed backinto the blood, causing a secondary bacteremia that coincideswith the onset of clinical symptoms and marks the end of theincubation period.


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Q. List down the most common bacteria causing meningitis

in adults and state the shared features.

1. Haemophi lus in f luenzae: cocco-bacillary" gram-negative rods.

2. Neisser ia meningi t id is : Gram-negative diplococci.

3. Streptococcu s p neumon iae: Gram-positive diplococci.

These three pathogens have several virulence factors in common

including:

1. Polysaccharide capsule.

2. IgA protease.


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Q. Discuss the laboratory diagnosis of bacterial meningitis.

Specimens:

1. Cerebrospinal fluid

2. Blood cultures

3. Throat swabs4. Stool specimens (for viral culture)

Cerebrospinal fluid (Golden standard)

1. Cytology

2. Biochemical test : glucose and protein levels.

CSF glu cos e level must b e consid ered in relat ion to blo od g luco se level.Normally CSF gluco se level is 50-70% low er than the bloo d glu cos elevel.

3. Culture

4. Rapid diagnostic tests


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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.


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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).


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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.


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Q. Discuss the pathogenesis of pertussis. The first stage is colonization:

It is an upper respiratory disease with fever, malaise and coughing, whichincreases 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 onthe 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 acharacteristic inspiratory gasp (whoop).

During the second stage, B. pertussis can rarely be recovered, and antimicrobialagents have no effect on the progress of the disease, this stage is mediated by avariety of soluble toxins.


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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.


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Q. List down the virulence factors of Streptococcus

penumoniaein 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.


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Q. Compare between acute and sub-acute infective

endocarditis.

Acute

Affects normal heartvalves

Rapidly destructive

Metastatic foci

Commonly Staph.

If not treated, usually

fatal within 6 weeks

Subacute

Often affects damagedheart valves

Indolent nature

Commonly Strep.

If not treated, usuallyfatal by one year


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Q. Discuss the pathogenesis of IE


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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.


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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.


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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 sluggishpredisposing 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 thesubperiosteal 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. Anaccumulation of new bone eventually encloses it.

The old, dead bone is called a sequestrum.

The surrounding live bone is termed involucrum.


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The sequestrum:

It has NOblood 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.


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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 ofK. kingae.

Polymerase chain reaction: appears to be the most sensitive technique to detectK.

kingae.


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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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