infection 2006 dr. nasser rizk. infection invasion and multiplication of microorganisms inside body...

Infection

2006Dr. Nasser Rizk

Infection

• Invasion and multiplication of microorganisms inside body producing S&S and immune response.

• Severity of infection depends on : 1- Pathogenicity 2- number 3- host defenses

• Transmission of infection needs:1- Causative agent 2- reservoir 3-port of transmission

4-susceptible host

Risk Factors

• 1-Weak defense mechanisms• 2- Enviromemental factors• 3- Developmental factors• -----------------------• Weak Defense mechanisms:1. Immunodeficiency or Immunocompromise2. Impaired WBCs and low level of T and B cells

(immunodeficiency)3. May be congenital (before or at birth) or

acquired (after birth)4. body’s ability to recognize and fight pathogens

is impaired

Risk Factors (continued)

• Conditions which suppress immune Response:

1-Diabetes mellitus 2 –Renal failure 3- Liver cirrhosis 4- Steroids 5-Immunosuppresive drugs (transplantation) 6- Chemotherapy.Acquired immune suppression in: stress malnutrition infections pregnancy

2 -Enviromemental factors• Conditions weaken a

person immune defense are:

1- Poor hygiene 2- Malnutrition 3- Inadequate barriers 4- Stressors 5- Chronic diseases 6- Inadequate treatment 7-Inadeqaute immunization Dust facilities transport of

pathogens, e.g., Aspergillus, (lung)

conditions

Poor hygiene

Chronic diseases

Inadequate immunization

Treatment

stressors

Inadequate barrier

3 -Developmental factors• Children and old age at high risk.• Children : immune system is not fully

developed (6 months)• most common: respiratory infections• Exposure to communicable diseases is

high in care- centers and schools.

• Old age: decline in immune system• DM and atherosclerosis: weak delivery of

nutrients by impaired blood flow to organs

Components of the chain of infection

• Agents: • Bacteria, Viruses, • Fungi, Parasites,

Mycoplasma, • Ricketessia, Chlamydia

• Reservoir:• Microbes can survive• E.g., humans, animals , etc

6 components

Causative agents

Reservoir

Portal of Exit

Mode of Transmission

Portal of Entry

Susceptible host

Components (continued)

• Portal of exit (entry): • infectious agent leave (enter)

the organism• Respiratory, genitourinary,

GIT, skin, Mucus membranes, and placenta.

• Secretions as : blood, sputum, emesis, stools, urine, wound drainage and genital secretions act as portal.

Mode of transmissionMeans from portal of exit to host4 modes: chart 3Vector- born: flea, mosquito

(tropical)

Mode of transmission

Contact Droplet Airborne Enteric

Chart 3

Stages of infection• 1- Incubation: replication, transmission.• 2-Prodromal stage: vague complaint, transmission.• 3- Acute illness: microbes destroy host cells, affecting

systems.• 4- Convalescent stage: body defense take over the microbe,

healing.

Pathophysiologic changes• Characteristic changes:Prodromal stage1- Fever2- Muscle aches3- Headache4- LethargyAcute stages:Moe specific symptoms

Inflammation• A major reactive defense mechanism

against infective agents. • It may result from: 1- tissue injury 2- infection 3- allergy• Stages:• 1- Vascular 2- CellularVascular: arterioles constrict then dilate--------edemaCellular: inflamm. Cells release histamine---edemaWhich dilute microbes

Signs and Symptoms of Inflammation

• Redness

• Heat

• Pain

• Edema

• Loss of function

Five classic local signs of acute inflammation

These were known– Heat– Redness– Swelling– Pain– Loss of function

by the Romans– Calor– Rubor– Tumor– Dolor– Functio laesa

Added Later

Five classic local signs of acute inflammation

• The major components responsible for these local signs are – Heat - vasodilatation– Redness - vasodilatation– Swelling - vascular permeability– Pain - mediator release/pmn’s– Loss of function - mediator release/pmn’s

Alerts!!

• 1- Localized infections:

• produce rapid inflammatory response

• Obvious symptoms and signs

• 2- Disseminated infections:

• Slow inflammatory response

• Long time for treatment

• Acute - minutes to days– Characterized by fluid and protein – PMN’s

• Chronic - weeks to years– Lymphocytes and macrophages

• ACUTE Inf - PMN’s (Polymorphonuclear Cells)

• CHRONIC Inf - Mononuclear Cells

Inflammation

EXUDATE

Fever

• After introduction of infectious agent

• Elevated temperature helps to fight infection

• Many organisms can’t survive

• Diaphoresis is the method of cooling down

• Improve immune system rspone.

Leukocytosis• Body’s response to introduction of pathogens;

WBCs increases• Neutrophils count increases, with increase

immature cells “bands”, but not function• Neutrophils, monocytes, and macrophages

begin phagocytosis of dead tissues and bacteria

• They identify the foreign antigen and kill the microbe

• Elevated count of WBCs is common; N in acute stages and Monocytes during resolution or chronic stages

Chronic inflammation

• Infection longer than 2 weeks

• May occur after acute Inflammation

• Permanganate scarring and loss of function may occur

• E.g., Mycobacterium tuberculosis

Diagnosis• Medical history• Examination• Investigations-tests• WBCs and CBC (first test)• ESR: increased, inflammatory response• Gram stain, silver stains• Culture- sensitivity tests• MRI to locate infection sites• Chest X-ray (lung)• Gallium scan for abscess detection

TreatmentTreatment• Vary widely

• Use vaccines----1ry immune response

• Drugs when appropriate

• Supportive therapy

• Antibiotics, antiviral, antifungal-----

• Overuse of medication----resistance

• Proper prevention of epidemic and pandemic transmission.

Acute inflammation

• The immediate and early response to injury

• The point? Get the pmn’s to the site as fast as possible

• Vasodilatation

• Endothelial permeability

• Extravasation of pmn’s

Acute inflammation major components

• Vasodilatation

• Endothelial permeability

• Extravasation of pmn’s

Vascular changes you need to know this

• Vasodilation (forget the few seconds of vasoconstriction)

• Exudation of protein rich fluid

• Blood stasis

• Margination

• Emigration/Transmigration

Vascular changes you need to know this

• Vasodilation (forget the few seconds of vasoconstriction)

• Exudation of protein rich fluid

• Blood stasis

• Margination

• Emigration/Transmigration

Fig 2.1 Graphic of

Acute Inflammation

Vascular permeability

• Vasodilation, increased blood flow

• Increased intravascular hydrostatic pressure

• Transudate - ultrafiltrate blood plasma (contains little protein)– Again, this is very transient and just gets the

process started. Think Acute Inflammation, think EXUDATE

• Increased vascular permeability

Vascular permeability

• Exudate - (protein-rich with pmn’s)– Exudate is the characteristic fluid of acute

inflammation

• Intravascular osmotic pressure decreases

• Osmotic pressure of interstitial fluid increases

• Outflow of water and ions - edema

Fig 2.2 Graphic

of Vascular Changes

How do endothelial cellsbecome leaky?

• Endothelial cell contraction

• Junctional retraction

• Direct endothelial injury (immediate sustained response)

• Leukocyte-dependent endothelial injury

• Increased transcytosis of fluid

Direct endothelial injury (immediate sustained response)

• Endothelial cell necrosis and detachment• Result of severe injury or burn• Occurs immediately and lasts until vessel

repaired

• Occurs at sites of leukocyte accumulation

• Due to leukocyte activation which releases proteolytic enzymes and toxic oxygen

Leukocyte-dependent endothelial injury

Leukocyte Cellular Events

• Margination and Rolling

• Adhesion and Transmigration

• Migration into interstitial tissue

Fig 2.4

Margination

• Normal flow - RBC’s and WBC’s flow in the center of the vessel

• A cell poor plasma is flowing adjacent to endothelium

• As blood flow slows, WBC’s collect along the endothelium

• This is “Margination”

Endothelial Activation

• The underlying stimulus causes release of mediators which activate the endothelium causing selectins and other mediators to be moved quickly to the surface

Selectins

• Selectins bind selected sugars – Selected + Lectins (sugars) = Selectins

• Some selectins are present on endothelial cells (E-Selectin)

• Some selectins are present on leukocytes (L-Selectin)• Some selectins are present on platelets (P-Selectin)

Chemotaxis

• Movement toward the site of injury along a chemical gradient– Chemotactic Factors include

• Complement components• Arachadonic Acid (AA) metabolites• Soluble bacterial products• Chemokines

Leukocyte Activation

• Chemokines also “activate” PMN’s– AA metabolite production– Degranulation and Secretion of lysosomal

enzymes– Oxidative burst– Modulation of adhesion molecules

Phagocytosis & Degranulation

• Phagocytosis (to eat and destroy)– Attach– Engulf– Kill

• Degranulation and the oxidative burst destroy the engulfed particle

Leukocyte-induced tissue injury

• Lysosomal enzymes are released into the extracellular space during phagocytosis causing cell injury and matrix degradation

• Activated leukocytes release reactive oxygen species and products of arachidonic acid metabolism which can injure tissue and endothelial cells

• These events underlie many human diseases (e.g. Rheumatoid arthritis)

Normal Lung

Pneumonia

Pneumonia

Another picture of the same thing…At a higher power!