pathogenesis of infectious
diseases. sepsis
By Mirakhmedova Dildora 301a group
Definitions
• Path- means disease.
• Pathogenesis
The steps or mechanisms involved in the development of a
disease.
• Infection
The presence and colonization of a pathogen in human body.
• Infectious Disease
Is a disease caused by a pathogen (microorganism).
• Not all pathogens entering human body will cause disease
because humans are protected by normal flora and the
immune system.
Course of an Infectious Disease
There are 4 phases or periods in any infectious disease:
1. The incubation period:
The time between entry of the pathogen and the onset of
symptoms.
2. The prodromal period:
The time when the person feels abnormal and week.
3. The period of illness:
The time when the person feels typical symptoms associated
with that specific disease.
4. The convalescent period:
The time when the person recovers from the infection but
may develop permanent damage to the area of infection.
Localized vs. Systemic Infection
Localized Infection
The pathogen is only present at the original
site of infection (eg. Pimples or abscesses)
Systemic Infection (Generalized)
The pathogen is carried to other parts of the
body by blood, lymph,..
Acute, Subacute, and Chronic Disease
Acute Disease
Rapid onset of disease and rapid recovery.
e.g. Influenza, measles,..
Chronic Disease
Slow onset of disease and last a long time.
e.g. Tb, syphilis,..
Subacute Disease
The disease with onset less than acute but
more than chronic. e.g. bacterial endocarditis.
Signs vs. Symptoms
A Sign of a Disease
Evidence of disease found or seen by the
doctor e.g. abnormal heart or breath sounds,
blood pressure, LAB results, radiology,..
A Symptom of a Disease
Evidence of disease felt and explained by the
patient e.g. headache, stomachache, pain,
nausea, itching,..
Latent Infections
•
infectious disease may go from symptomatic to
asymptomatic, and then some time later go back
to being symptomatic again. Eg. Herpes virus
infections
Virulence ( virulent )
• Is the degree of pathogenicity of an organism, i.e.
the relative ability of a pathogen to cause disease.
• See page 242 , chapter 14
Steps in the Pathogenesis of
Infectious Diseases
1.
2.
3.
4.
5.
6.
Entry.
Attachment.
Colonization.
Invasion.
Immune response Inhibitors.
Damage to the host.
1. Entry
• Penetration of skin Skin is very difficult to penetrate,
most microorganism gain entry via trauma.
•
•
•
•
•
Introduction of pathogen by an arthropod.
Inhalation (respiratory tract)
Ingestion (gastrointestinal tract)
Through genitourinary tract.
Introduction of the pathogen directly into the
blood (eg. Blood transfusion, use of shared
needles)
II. Attachment (Adhesion)
• Microorganisms have macromolecules (proteins or
carbohydrates) that promote attachment to tissue surfaces.
• Viruses and many bacteria must first bind to host cell
surfaces.
• Prevents early clearance.
• Pathogens often bind host tissues via surface receptors. e.g.
pili in bacteria.
2. Attachment (=Adherence)
• It is a necessary first step in the establishment of
infection.
• Once they have attached themselves to host
cells, they then multiply to high enough numbers
to produce toxin or invade host tissue or both.
• Bacteria use adhesions to attach themselves to
host cells (can be found on capsules cell wall
proteins or tips of pili).
2. Attachment (=Adherence)
• The surface receptors on animal cells to which the
bacteria attach are usually glycoproteins or glycolipids.
• Binding of an adhesion to surface receptor is highly
specific, dictating the type of cells to which the
bacterium can attach.
• Example: E.coli strains that cause (UTI) urinary tract
infections generally produce a type of pili that attach to
bladder cells. While E.coli strains that cause watery
diarrhea produce a type of pili that attach specifically to
cells of small intestine.
2. Attachment (=Adherence)
• Eg. E.coli strains that cause urinary tract infections generally produce
a type of pili that attach to bladder cells. While E.coli strains that
cause watery diarrhea produce a type of pili that attach specifically to
cells of small intestine.
III. Colonization
• Some virulent bacteria produce special proteins that allow
them to colonize parts of the host body.
• Pathogens start multiplication and maintenance.
• Pathogens compete with normal flora for residence.
• Pathogens will resist body reactions e.g. Bile, stomach acid,
skin secretions, IgA (mucosal antibodies).
• e.g.
Helicobacter pylori is able to survive in the acidic environment
of the human stomach by producing the enzyme urease.
4. Invasion
Some virulent bacteria produce proteins that either:
a. Disrupt host cell membranes or
b. Stimulate endocytosis into host cells
• Endocytosis
is the process by which cells absorb material (molecules
such as proteins) from outside the cell by engulfing it with
their cell membrane
• Eg. Mycobacterium tuberculosis produces surface proteins
that facilitate their uptake by the alveolar macrophages.
And so the macrophage is not activated and the organism
can live in it.
5. Immune Response Inhibitors
• Many bacteria produce virulence factors that
inhibit the host's immune system defenses.
Example:
The polysaccharide capsule of Streptococcus
pneumoniae inhibits phagocytosis of the
bacterium by host immune cells.
Some bacteria can hide inside the host cells
away from phygocytosis, complement or Ab’s.
6. Damage to the Host
Bacterial Toxins
Exotoxins
Endotoxins
•It is a lipopolysaccharide, which is the
• Secreted by the bactrium or leak after
lysis of bacterial cell
•Secreted by both gram -ve and gram +ve
bacteria.
•Generally inactivated by heat.
•Generally very potent; some are among
the most potent toxins known.
•Eg. Corynebacterium diphtheriae.
component of the outer membrane of the
gram negative cell wall.
•It is found only in gram-negative
organism.
•Heat stable.
•Small amount in localized area lead to an
appropriate response that helps clear an
infection, but systemic distribution can be
deadly.
Normal Response to Infection
• Local infection
• Non-specific inflammatory response
• 3 phases
– Vasodilation - increased blood flow to site, infusion of
antibodies and cells to fight infection
– Vessel permeability - antibodies and cells exit
bloodstream and enter infected tissue
– Once infection is controlled, tissue repairs itself
Pathogenic mechanisms of viral
disease include
- implantation of virus at the portal
of entry,
- local replication,
- spread to target organs (disease
sites),
- spread to sites of shedding of
virus into the environment.
• “Sepsis is caused when the body’s immune system
becomes overactive in response to an
infection, causing inflammation which can affect how
well other tissues and organs work.”
Sepsis is a syndrome
• A group of body dysfunctions found
together
• Dysfunctions that progress together in a
predictable way
• High mortality rate, variable clinical
presentations
Pathophysiology of Sepsis
• Uncontrolled, exaggerated immune response
• Endothelium damage, cell mediator activation, disruption of
coagulation system homeostasis
• Vasodilation and capillary permeability
• Systemic inflammatory response
• End-organ damage, death
Risk Factors for Sepsis
• Extremes of age (old and young)
– Can’t communicate, need careful assessment
– Patients with developmental delay
– Cerebral Palsy
• Recent surgery, invasive procedure, illness,
childbirth/pregnancy termination/miscarriage
• Reduced immunity
• DIABETES, DIABETES, DIABETES
• Liver cirrhosis
• Autoimmune diseases (lupus, rheumatoid arthritis)
Increased Risk
for Sepsis
• HIV/AIDS
• Para/quadriplegics
• Sickle cell disease
• Splenectomy patients
• Compromised skin (chronic wounds, burns, ulcers)
•
Chemotherapy
•
Post-organ transplant (bone marrow, solid organ)
•
Chronic steroid use
•
Recent antibiotic use
•
Indwelling catheters of any kind (dialysis, Foley, IV, PICC, PEG tubes, etc)
Signs/Symptoms of Sepsis
• Symptoms of sepsis are often nonspecific and include the
following:
– Fever = most common (elderly patients often do NOT
mount a febrile response)
– Flu-like symptoms
– Chills/shaking (mistaken for seizure)
– Nausea/vomiting
– Mental status changes/fatigue/lethargy
Patient often does NOT
appear acutely ill
Multiple Organ System Dysfunction
CNS
Altered mental status
Respiratory
Tachypnea
Hypoxia
Hepatic
Jaundice
Liver inflammation
Coagulopathy
Metabolic
Lactic acidosis
Cardiovascular
Tachycardia
Hypotension
Renal
Oliguria
Anuria
Renal failure
Hematologic
Consumptive coagulopathy
Petechiae
Purpura