Table Of ContentМИНИСТЕРСТВО ЗДРАВООХРАНЕНИЯ
РОССИЙСКОЙ ФЕДЕРАЦИИ
ВОЛГОГРАДСКИЙ ГОСУДАРСТВЕННЫЙ
МЕДИЦИНСКИЙ УНИВЕРСИТЕТ
PATHOPHYSIOLOGY
OF INFECTIOUS PROCESS
Учебно-методическое пособие
Рекомендовано Центральным методическим советом ВолгГМУ
в качестве учебно-методического пособия для студентов
медицинских ВУЗов, обучающихся по специальности
«Лечебное дело» (с частичным обучением на английском языке)
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ÈÇÄÀÒÅËÜÑÒÂÎ
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2019
УДК 616.9-092(07)
ББК 55.14+52.5я7
Р 598
Составители:
Л. Н. Рогова, В. Н. Поветкина, Т. В. Замечник
Рецензенты:
зав. кафедрой общей и клинической патологической физиологии
ФГБОУ ВО «Кубанский государственный медицинский университет»
д. м. н. профессор А. Х. Каде;
зав. кафедрой патологической физиологии
ФГБОУ ВО «Ставропольский государственный медицинский университет»
д. м. н. профессор Е. В. Щетинин
Печатается по решению ЦМС ВолгГМУ (протокол № 1 от 31.10 2018 г.)
Рогова, Л. Н.
Р 598 Pathophysiology of infectious process: учебно-методическое посо-
бие / Рогова Л.Н., Поветкина В.Н, Замечник Т.В. – Волгоград: Изд-во
ВолгГМУ, 2018. – 52 с.
Учебно-методическое пособие для студентов составлено в соответствии
с учебным планом, государственным стандартом, рабочей программой и требова-
ниями к минимуму содержания и базовому уровню подготовки по специальности
«Лечебное дело» (с частичным обучением на английском языке). Учебно-методи-
ческое пособие для студентов по проведению практических занятий по дисциплине
«Патофизиология, клиническая патофизиология» по теме «Патофизиология
инфекционного процесса» содержит современную и актуальную информацию по
вопросам клинической патофизиологии. Значительная часть пособия посвящена
решению ситуационных задач, во многом отражающих реальные проблемы и зада-
чи клинической патофизиологии.
УДК616.9-092(07)
ББК55.14+52.5я7
© Волгоградский государственный
медицинский университет, 2019
© Издательство ВолгГМУ, 2019
CONTENTS
1. GENERAL MECHANISMS
OF AN INFECTIOUS PROCESS DEVELOPMENT ....................4
1.1. Host defenses against infection......................................................5
1.2. Inflammatory response................................................................10
1.3. The role of cytokines in infectious process...................................14
1.4. Sepsis pathophysiology ................................................................19
1.5. Ways of treatment.......................................................................23
2. PATHOPHYSIOLOGY OF PRIVATE
INFECTIOUS DISEASES............................................................25
2.1. Infective Endocarditis..................................................................25
2.2. Meningitis....................................................................................28
2.3. Pneumonia ..................................................................................32
2.4. Infectious Diarrhea......................................................................35
2.5. Sepsis & Septic Shock.................................................................39
LIST OF RECOMMENDED REFERENCES ...................................44
CASE STUDIES ...............................................................................45
Case 1 ...............................................................................................45
Case 2 ...............................................................................................46
Case 3 ...............................................................................................46
Case 4 ...............................................................................................47
Case 5 ...............................................................................................48
3
1. GENERAL MECHANISMS
OF AN INFECTIOUS PROCESS
DEVELOPMENT
Infectious process in the organism is reflected in various infectious
diseases. It causes significant morbidity and mortality, especially in
individuals who are most vulnerable to illness: the very young, the elderly,
the immunocompromised, and the disenfranchised.
Fig. 1. The pathogenesis of infectious diseases is dependent
on the relationship among the human host, the infectious agent,
and the external environment
An infectious agent can be either exogenous (i.e., not normally found
on or in the body) or endogenous (i.e., one that may be routinely cultured
from a particular anatomic site but that does not normally cause disease
in the host). Infection results when an exogenous agent is introduced into
a host from the environment or when an endogenous agent overcomes
innate host immunity to cause disease. Host susceptibility plays an
4
important role in either of these settings. The environment includes vectors
(insects and other carriers that transmit infectious agents) and zoonotic
hosts or reservoirs (animals that harbor infectious agents and often act to
amplify the infectious agent).
The infectious diseases study requires understanding
of pathogenesis at the level of:
•the population (e.g., the spread of tuberculosis in the community is
related to the social interactions of an infectious human host);
•the individual (e.g., tuberculosis results from inhalation of respiratory
droplets containing airborne tubercle bacilli);
•the cell (e.g., these bacilli activate T cells, which play a critical role
in containing the infection. Individuals with an impaired T-cell response
(eg, those infected with HIV) are at particularly high risk for primary
tuberculosis at the time of the initial infection or for reactivation of latent
tuberculosis as their immunity wanes);
•the gene (e.g., individuals with specific polymorphisms in
a macrophage protein gene may be at significantly higher risk for pulmonary
tuberculosis).
When one person transmits an infection to another, then the time
that elapses between onset of symptoms in the primary case and onset
of symptoms of the secondary case is called «generation time»,
referring to the time it takes for the first group of patients to «generate»
the next group.
1.1. Host defenses against infection
The human body has the ability to control infection through a number
of different mechanisms.
Physical barriers impede the entry of bacteria from the external
environment and from normally colonized sites in the body into sterile
anatomic areas.
When these physical defenses are breached, the immune system is
activated.
Constitutive or innate immunity, provided by preformed proteins
(eg, complement) and immune cells (eg, phagocytes) that are activated by
nonspecific foreign proteins, allows an immediate response to foreign
material.
5
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Fig. 2. Phases of the host response to infectionage of initial infection, nonspecific mediators (complement, phagocytes) ntibody, stimulation of lymphocytes) requires clonal expansion after reconce immunity toward a specific agent is induced, the immune response reso that the response to reinfection is much more rapid
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6
Induced or adaptive immunity includes both early and late adaptive
responses activated by specific antigenic proteins (eg, production of antibodies
active against the specific strains of Streptococcus pneumoniae contained
in the pneumococcal vaccine in a previously vaccinated individual).
Induction of these specific immune receptor cells may take several
days in the immunologically naive host.
Protective immunity, which occurs after initial exposure (infection or
vaccination) through generation of memory lymphocytes and pathogen-
specific antibody, allows a much more rapid response to reinfection.
During infectious process, a cascade of events is initiated by
microorganisms and their derived products called «pathogen-associated
molecular patterns» (PAMPs).
These molecules are common to pathogenic, non-pathogenic, and
commensal bacteria, making «microbial-associated molecular patterns»
(MAMPs) a more appropriate term than PAMPs.
They include surface molecules such as endotoxin
(e.g. lipopolysaccharide, LPS; lipoproteins; outer-membrane proteins;
flagellin; fimbriae; peptidoglycan, PGN; peptidoglycan-associated lipoprotein;
and lipoteichoic acid, LTA), and internal motifs released following bacterial
lysis (e.g. heat-shock proteins, HSP; DNA fragments).
Pattern-recognition receptors (PRRs) may be divided into:
•Soluble circulating molecules: components of complement system,
acute phase proteins (C-reactive protein, serum amyloid P et al.); collectins
(mannose-binding lectin et al.);
•Cell membrane receptors expressed on the cell membrane or
phagolysosomes membrane-binding receptors (Toll-like receptors, TLR);
•The intracellular cytoplasmic receptors that recognize pathogen-
associated molecular patterns of pathogens when they enter the cytoplasm
of cells (nucleotide-binding domain leucine-rich repeat containing receptors,
NLR et al.).
In the host, Toll-like receptors (TLR) and cytoplasmic PRRs
(e.g. NOD1 and NOD2) act as sensors of the MAMPs (microbial-
associated molecular patterns), recognized as exogenous danger signals.
Within tissues, cells are exposed to more than one single signal, and
multiple stimuli act in synergy leading to an enhanced production
of inflammatory cytokines.
7
Thus, all organisms have the scheme: pathogen-associated molecular
structures interact with the pattern-recognition receptors, which leads to
the synthesis of pro-inflammatory cytokines that trigger an inflammation.
Induced or adaptive immunity includes both early and late adaptive
responses activated by specific antigenic proteins (eg, production of antibodies
active against the specific strains of Streptococcus pneumoniae contained
in the pneumococcal vaccine in a previously vaccinated individual).
Induction of these specific immune receptor cells may take several
days in the immunologically naive host.
Protective immunity, which occurs after initial exposure (infection or
vaccination) through generation of memory lymphocytes and pathogen-
specific antibody, allows a much more rapid response to reinfection.
During infectious process, a cascade of events is initiated by
microorganisms and their derived products called «pathogen-associated
molecular patterns» (PAMPs).
These molecules are common to pathogenic, non-pathogenic, and
commensal bacteria, making «microbial-associated molecular patterns»
(MAMPs) a more appropriate term than PAMPs.
They include surface molecules such as endotoxin (e.g.
lipopolysaccharide, LPS; lipoproteins; outer-membrane proteins; flagellin;
fimbriae; peptidoglycan, PGN; peptidoglycan-associated lipoprotein; and
lipoteichoic acid, LTA), and internal motifs released following bacterial lysis
(e.g. heat-shock proteins, HSP; DNA fragments).
Pattern-recognition receptors (PRRs) may be divided into:
•Soluble circulating molecules: components of complement system,
acute phase proteins (C-reactive protein, serum amyloid P et al.); collectins
(mannose-binding lectin et al.);
•Cell membrane receptors expressed on the cell membrane or
phagolysosomes membrane-binding receptors (Toll-like receptors, TLR);
•The intracellular cytoplasmic receptors that recognize pathogen-associated
molecular patterns of pathogens when they enter the cytoplasm of cells (nucleotide-
binding domain leucine-rich repeat containing receptors, NLR et al.).
In the host, Toll-like receptors (TLR) and cytoplasmic PRRs
(e.g. NOD1 and NOD2) act as sensors of the MAMPs (microbial-
associated molecular patterns), recognized as exogenous danger signals.
8
Within tissues, cells are exposed to more than one single signal, and
multiple stimuli act in synergy leading to an enhanced production of
inflammatory cytokines.
Thus, all organisms have the scheme: pathogen-associated molecular
structures interact with the pattern-recognition receptors, which leads to
the synthesis of pro-inflammatory cytokines that trigger an inflammation.
Fig. 3. Initiation of the immune response following infection
Immune cells of the innate immune system recognize invading
pathogens via Toll-like receptors (TLRs). The binding of pathogen-associated
molecular patterns (PAMPs), such as peptidoglycan, lipopolysaccharide
(LPS), or flagellin, to TLRs initiates signal transduction cascades that lead
to the activation of nuclear factor кB (NF-кB). NF-кB is subsequently
translocated into the nucleus where it induces the expression of cytokines
and chemokines.
9
1.2. Inflammatory response
Сlinically, signs of inflammation (heat, erythema, pain, and swelling,
loss of function) are the characteristic features of localized infection,
secondary tissue injury, and the body’s response to this injury.
Blood supply to the affected area increases in response to vasodilation,
and the capillaries become more permeable, allowing antibodies,
complement, and white blood cells to cross the endothelium and reach
the site of injury.
The increased blood flow to the area allows continued recruitment
of inflammatory cells as well as the necessary components for tissue repair
and recovery.
An important consequence of inflammation is that the pH of
the inflamed tissues is lowered, creating an inhospitable environment for
the microbe.
When a microorganism enters host tissue, it activates the complement
system and components of the coagulation cascade and induces the release
of chemical mediators of the inflammatory response.
Three pathways of complement activation have been recognized
(Fig. 5):
• The classic pathway is activated by antigen-antibody complexes or
antibody-coated particles.
• The alternative pathway is activated by mechanisms independent
of antibodies, usually by interaction with bacterial surface components.
• The lectin pathway, as the name suggests, is triggered by lectins
(which are the proteins that recognize and bind to specific carbohydrate
targets). The mannose-binding lectin (MBL) is a large serum protein that
binds to nonreduced mannose, fructose, and glucosamine on bacterial and
other cell surfaces with mannose-containing polysaccharides (mannans).
Most of the biologically significant effects of the complement system:
• the anaphylatoxins C3a, C4a, and C5a, produced by the activation
of complement, stimulate the release of histamine from mast cells (histamine
dilates the blood vessels and further increases their permeability;
bradykinin is also released, increasing vascular permeability);
• complement facilitates phagocytosis through proteins called
opsonins, which coat invading microorganisms, making them susceptible
to engulfment and destruction by neutrophils and macrophages;
10
