Pathophysiology
. Mechanisms of diseases
.the physiology of abnormal states or diseases
. Pathophysiology can also mean the functional
changes associated with or resulting from disease or
injury.
. Another definition is the functional changes that
accompany a particular disease
1
PATHOPHYSIOLOGY OF
INFECTIOUS DISEASES
Mehtap KAÇAR MD. PhD Assist. Prof.
Pathophysiologist
Yeditepe University, Faculty of Medicine
Department of Physiology
2
Learning Objectives:
1- Describe the relationships between humans and
infectious agents,
2- Describe the mechanisms of infection and
cellular injury by bacteria, viruses, and fungi,
3- Describe the clinical manifestations of
infectious diseases.
4- Describe the septic shock.
3
Infectious Agents



Infectious diseases are the number one
cause of death world-wide.
Dense populations in developing countries
with poor sanitation are victims of plaque,
cholera, malaria, tuberculosis, leprosy and
schistosomiasis.
Only smallpox has been eradicated from the
world by vaccination.
4
5
Microorganisms and Humans: A
Dynamic Relationship




Many microorganisms find human bodies
to be hospitable sites in which to grow and
flourish; there they are provided with
nutrients and the appropriate conditions of
temperature and humudity.
These microorganisms are called the
“normal flora”.
They are found in different parts of body,
including the skin, mouth, gastrointestinal
tract, respiratory tract and genital tract.
6

The many relationships between humans
and organisms: (box 9-1)
7
Stages of infection:





Four separate stages are associated with
pathologic infection:
colonization,
invasion,
multiplication,
Spread. (Table 9-3)
8
9
Infection by a pathogen is influenced by several
factors as listed below:







a- mechanism of action,
b- infectivity,
c- pathogenity,
d- virulence,
e- immunogenicity,
f- toxigenicity,
g- portal of entry.
10
a- Mechanism of action:

Direct damage of cells, interference with
cellular metabolism and rendering a cell
dysfunctional because of the accumulation
of pathogenic substances and toxin
production.
11
b- Infectivity

ability of the pathogen to invade and multiply
in the host.

For example, coagulase, an enzymatic product
of some pathogens that causes coagulation
and allows some microorganism, such as
staphylococci, to clot and form a sticky layer
around themselves, protects the pathogens
against host defenses.
12
c- Pathogenicity

Ability of an agent to produce disease – success
depends on speed of pathogen reproduction,
extent of tissue damage, and production of
toxins.
13
d- Virulence


Potency of a pathogen meausered in terms
of the number of microorganisms or
micrograms of toxin required to kill a host.
For example, measles virus is low virulence;
rabies virus is highly virulent.
14
e- Immunogenicity

Ability of pathogens to induce an immune
response.
15
f- Toxigenicity


A factor important in determining a pathogen’s
degree of virulence, that is, the ability to
produce disease by production of a soluble
toxin, such as hemolysin, leukocidin, other
exotoxins and endotoxins.
For example: hemolysin destroys erythrocytes
and leukocidin destroys leukocytes; both are
products of streptococci and staphylococci.
16
g- Portal of entry





Route by which a pathogenic microorganism
infects the host:
direct contact,
inhalation,
ingestion,
bites of an animal or insect.
17
Classes of infectious microorganisms


Infectious disease can be caused by
microorganisms that range in size from 20
nm (poliovirus) to 10 m (tapeworm).
Table 9-4
18
19
Infection compartments
Pathogens cause damage to the host in
three main ways:



1- They may cause direct tissue injury to cells
they enter or contact, either mechanically or
chemically, or by interfering with normal
cellular metabolism.
2- microbial products may be toxic to host
cells. (exotoxins, endotoxins)
3- pathogens may cause the host immune
system to damage host tissue
(immunopathogenesis)
21
Direct Mechanisms of Pathogen-induced tissue Damage
Indirect Mechanisms of Pathogen-induced tissue Damage
Defense Mechanisms:
1. External defense
2. Internal Defense
3. Immune Defense
24
Protective Immunity To Microorganisms
Defense against microbes is mediated by:
Innate immunity
and
acquired immunity
Humoral immunity (antibodies)
Through both
Cell mediated immunity (CMI)
25
Overview of Immune System Responses
innate host defense mechanisms

The first lines of defense against infectious
microorganisms are external barriers,
including the skin and mucous membranes
and the cells and biochemicals of innate
immunity. (Figure 9-1)
27
28
Cells of innate immunity express Toll-like
receptors that recognize pathogens and
activate inflammation and adaptive
immunity, the second and third lines of
defense.
 Once a microorganisms penetrates the first
lines of defense and invades the body the
inflammatory response is initiated,
especially the phagocytes. (figure 9-2)

29
30
Non-Specific Host Defense Mechanisms
1. First line of defense:
a. Intact skin and intact mucous membranes as
physical or mechanical barriers.
b. Cellular and chemical factors.
such as digestive enzymes, acidity of stomach
(PH 1.5)and alkalinity of the intestine, acidity of
vagina.
c. Microbial antagonism by indigenous microflora;
and overall nutritional status and state of health
31
2. Second line of defense:
a. Transferrin and lactoferrin, are tie up iron, thereby
preventing pathogens access to this essential mineral.
b. Fever, that augments host defense by stimulating
leukocytes to deploy and destroy invaders, reducing
available free plasma iron, and inducing the production
of IL-1, which causes proliferation, maturation, and
activation of lymphocytes in the immunologic
response.
Elevated body temperature also slow down the rate of
growth of certain pathogens and can even kill some
especially fastidious pathogens.
32
c. Interferons, are small , antiviral proteins that prevent
viral multiplication in virus- infected cells and serve to
limit viral infections.
d. Inflammation, localized an infection prevent the
spread of microbial invaders, neutralizes toxins, and
aid in the repair of damaged tissue.
e. Phagocytosis.
33
f. Complement system, involves approximately 30
different blood proteins that interact in a step-wise
manner known as the complement cascade.
Consequence of activation of the complement
system: -- Initiation and amplification of
inflammation.
- Attraction and activation of leukocytes.
- Lysis of bacteria and other foreign cells.
- Increased phagocytosis by phagocytic cells.
34
3. Specific Host Defense Mechanisms
(third line of defense)
Immunology is the scientific study of
the immune system and immune
responses.
 The immune system is the third line of
defense against pathogens; it is a
specific host defense mechanism.
 Types of Acquired Immunity:
1. Active acquired immunity.
2. Passive acquired immunity.

35
Cells of the Immune System
36
Cells of the Innate (Non-specific) Immune
System
Phagocytes
 Monocytes/Macrophages
 PMNs
 NK cells
 Basophils and Mast cells
 Eosinophils
 Platelets

Used with permission: Dr. Peter Darben,
Queensland University of Technology
37
Phagocytic Cell Functional Responses





Adhesion (localization)
Chemotaxis (migration)
Phagocytosis
NADPH oxidase activation
Lysosomal granule fusion: degranulation
38
Mechanism of Phagocytosis
Macrophage
Cells that Link the Innate and Adaptive
Immune Systems

Antigen Presenting Cells (APCs) are a
heterogenous population of leukocytes that play
and important role in:
Innate immunity
 Activation of helper T cells (Th cells)


APCs are rich in class II MHC molecules
Dendritic cells
 Macrophages
 B cells (not part of the innate immune system)
 Other cells (not part of the innate immune system)

40
Cells of the Adaptive (Specific) Immune
System

Lymphocytes

B cells


Plasma cells
T cells


Cytotoxic (Tc)
Helper (Th)
 Th1
 Th2
Used with permission: Dr. Peter Darben,
Queensland University of Technology
41
Role of antibodies and complement
system

Antibodies are
the primary
defense against
extracellular
pathogens

Neutralization
42

Antibodies are
the primary
defense against
extracellular
pathogens
Neutralization
 Opsonization

43

Antibodies are
the primary
defense against
extracellular
pathogens
Neutralization
 Opsonization
 Complement
activation

44



The complement system, through the
alternative and lectin pathways produces
C3b, which attaches itself to the surface of
the bacterium with carbohydrate capsules.
The C5b-C9 membrane lytic complex kills
bacteria.
C3b functions as a highly effective opsonin
that allows adherence between the
bacterium and C3b receptors on the
phagocyte’s surface, thus facilitating
phagocytosis.
45
46
Pathogenic defense mechanisms



True pathogens have devised means to
circumvent the host’s defenses.
Examples of these adaptations include
surface coats that inhibit phagocytosis,
surface receptors that bind to host cells, and
toxins that damage cells or alter their
function.
If the immune system is compromised,
infections cannot be regulated.
47
48
Bacterial virulence and infectivity



Bacteria injure cells by producing
desturictive enzymes (exotoxins) or
endotoxins.
Exotoxins can damage the plasma
membranes of host cells or prevent
phagocytosis.
Endotoxins activate the inflammatory
response and produce fever.
49
Exotoxins….







They are proteins released during bacterial
growth.
They are usually enzymes including;
-cytotoxins,
- neurotoxins,
- pneumotoxins,
- enterotoxins,
- hemolysins.
50





Exotoxins can;
- damage cell membranes,
- activate second messengers,
- inhibit protein synthesis.
Exotoxins are immunogenic and elicit the
production of antibodies known as
antitoxins.
51
Endotoxins….

Endotoxins are lipopolysaccharides (LPSs)
contained in the cell walls of gramnegative bacteria and released during lysis
of bacteria.
52
53

Bacteria that produce endotoxins are called
“pyrogenic bacteria”, because they activate
the inflammatory process and produce fever.

Inflammation is the body’s initial response
to the presence of the bacteria.

Vascular permeability is increased allowing
blood-borne substances (i.e. Complement
system).
54

Endotoxins increase capillary permeability
further by activating the anaphylotoxins (C5a
and C3a) of the complement cascade.
(Hypotension, shock)

Endotoxins also can activate the coagulation
cascade, leading to the syndrome of DIC.
55
Antibacterial Immunity
I) Immunity to extracellular bacteria:
1- The innate immunity:
a- Complement activation
b- Phagocytosis
c- The inflammatory response
2- The acquired immune responses:
i-The humoral mechanisms (antibodies) “main role”
ii- Cell mediated immune response
“less role”
56
i- the humoral immune mechanisms:
i- Antibodies induce immunity through:
a- Neutralization of bacterial toxins
b- Antibodies attach to the surface of bacteria and;
- Act as opsonins, enhance phagocytosis
(Opsonization)
- Prevent adherence of bacteria to their target cells
e.g. IgA on mucosal surfaces
- Activation the complement leading to bacterial
lysis
- Agglutinate bacteria, preventing their spread and
facilitating phagocytosis
57
ii- Cell mediated immune mechanisms:
* Microbes are internalized by APCs and presented to TH
* TH cells are activated and release cytokines which;
- activate phagocytosis their microbicidal functions
- Stimulate antibody production
- Induce local inflammation
58
II- Immunity To Intracellular Bacteria
1) Innate immunity
It is mainly by natural killer (NK) cells
- They kill infected cells and secrete IFN-γ
- IFN-γ activate phagocytosis to kill intracellular microbe
E.g. tuberculosis, leprosy, listeriosos
2) Acquired immunity is mainly by CMI
- Activation of macrophages to kill intracellular microbes
- Lysis of infected cells by cytotoxic cells (CTLs)
- Most of these organisms are resistant to phagocytosis, cause
chronic infection and granuloma formation
59
CHARACTERISTIC FEATURES OF
INTRACELLULAR BACTERIAL INFECTIONS
Pathogen:
- intracellular living
- low toxicity for the host
Immune response:
- T-cell dependent
- antibody independent
-granulomatous tissue reaction
- delayed type hypersensitivity
60

The ability to produce immunologic
hypersensitivity reactions is an important
pathogenic mechanism of bacterial toxins.

Tissue lesions of many chronic infections are
related to the induction of hypersensitivity to
the toxin or cell wall components. (for
example; mycobacterium tuberculosis causes
inflammatory chronic lesions known as
granulomas)
61
Viral infection and injury

Viruses enter host cells and use the metabolic
processes of host cells to proliferate.
62


Infection begins when a virion
binds to receptors on the
plasma membrane of a host cell
(attachment). The specifity of
the virus for these receptors and
the distirubition of receptors
throughout the host’s tissues
dictate the range of host cells
that a particular virus can
infect.
Once bound the virion
penetrates the plasma
membrane by receptor
mediated endocytosis, by
envelope fusion with the plasma
membrane or by directly
crossing the plasma membrane.
63
Cellular effects of viruses:
Once inside the host cell, viruses have
many harmful effects including the
following:
 -inhibition of host cell DNA, RNA or
protein synthesis,
 - disruption of lysosomal membranes
resulting in release of “digestive”
lysosomal enzymes that can kill the cell,

64
Cellular effects of viruses:

- promotion of apoptosis of host cells,

- fusion of infected, adjacent host cells,
thereby producing multinucleated giant
cells,

- alteration of the antigenic properties or
“identity” of the host cell, causing the
host’s immune system to attack the cell as if
it were foreign,
65
Cellular effects of viruses:

- transformation of host cells into
cancerous cells, resulting in
uninhibited and unregulated growth,

- promotion of secondary bacterial
infection in tissues or organs damaged
by viruses.
66
ANTI-VIRAL IMMUNE MECHANISMS
Innate:

interferons and NK cells
Adaptive (specific):


antibody – neutralize virus infectivity but act only
when viral particles are outside cell (prodromal
stage of infectious disease),
cytotoxic T cells – recognize and destroy virus
infected cells early (by apoptosis), before new viral
progeny appear
67
INTERFERONS (IFNs)
Type I

IFN-,leucocytes-13g./chr. 9

IFN-,fibroblasts-1g./chr.9

IFN-,leucocytes-1g.

IFN-,keratinocytes,1g

IFN-,leucocytes,-1g
Receptors: IFNAR- 1 and 2
of MHC class I expression
Antiproliferative activity
Produced: after virus infection of
cells
Type II
IFN--1 gene / chrom.12
 immunomodulating, activation
of macrophages, NK, T cells
 of MHC class I and class II
expression
Receptors: IFNGR-1 and 2
Antiproliferative activity
Synergism with IFN’s type I
Produced: only after antigenic or
mitogenic stimulation of T and
NK cells

68
1- ANTI-VIRAL HUMORAL IMMUNITY
a- Virus neutralization
* In viraemic infections,
Antibodies neutralize virus, preventing its
attachment
to receptor sites on susceptible cells
e.g. Poliovirus, mumps, measles, rubella
* In superficial non-viraemic infections (infleunza)
Secretory IgA neutralizes virus infectivity at the
mucous surfaces
69
b- Antibodies destroy free virus particles directly by:
i- Aggregation of virus and opsonization
ii- Complement mediated lysis
* Both mechanisms also act on virus infected cells
70
2- ANTI-VIRAL CELL-MEDIATED IMMUNITY
Cell mediated cytotoxicity, mediated by :
- Cytotoxic T-cells (CTLs)
- NK cells
- Activated macrophages
71
2- ANTI-VIRAL CELL-MEDIATED IMMUNITY
CMI acts on virus infected cells through:
- CTLs kill virus infected cells directly after recognition of viral
antigens on cell surface in association with MHC I
- TH-cells stimulated by viral antigens release cytokines
Cytokines attract and activate macrophages to kill
virus infected cells
- Nk-cells destroy virus infected cells early in infection before
appearance of antibodies
- Antibody-dependent cell mediated cytotoxicity (ADCC):
Antibody binds to virus infected cells such cells are lysed by
NK cells, macrophages and polymorphs
72
3- ANTI-VIRAL ACTIVITY OF INTERFERONS
1- Virus infected cells produce INF-α;
- IFN-α inhibit intracellular replication of viruses
- IFN-α activate NK-cells to kill virus infected cells
- IFNs have no direct effect on extracellular virus
- IFNs act early in viral diseases before antibody
- IFNs activity is not specific
73
IMMUNOPATHOLOGY OF VIRAL
INFECTIONS
1.
Immune cytotoxic response to viral antigens
(hepatitis)
2.
Immune complexes (glomerulonephritis)
3.
Infection of cells of the immune system
(EB virus, HIV, measles virus, CMV)
4.
Virus induced autoimmunity (MS?)
74

Examples of human diseases caused by specific viruses are
listed in table 9-6
75
Fungal infection anf injury

Fungi are relatively
large microorganisims
with thick walls that
grow as either singlecelled yeasts (spheres)
or multi-celled molds
(filaments or hyphae).
76
Some fungi can exist in either form and are
called dimorphic.
 The cell walls of fungi are rigid and
multilayered.
 The wall is composed of polysaccharides
different from the peptidoglycans of
bacteria.
 The lack of peptidoglycans allows fungi to
resist the action of bacterial cell wall
inhibitors such as penicilin and
cephalosporin.

77

Pathologic fungi cause disease by adapting
to the host envorinment. Fungi that colonize
the skin can digest keratin.

Other fungi can grow with wide temperature
variations in lower oxygen environments.

Phagocytes and T lymphocytes are
important in controlling fungi, and low white
blood cell promote fungal infection.
78




Disases caused by fungi are called mycoses.
Mycoses can be superficial, deep or
opportunistic.
Fungi that invade the skin, hair, or nails are
known as dermatophytes. (Tinea capitisskalp; tinea pedis-feet, tinea cruris-groin)
Fungi causing deep infection enter the body
through inhalation or through open wounds.
79
Common pathologic fungi are
summarized in table
80
Anti-Fungal Immunity
Immune response to fungi consist mainly of :
1) Innate immunity is mediated by:
- Neutrophils and macrophages
- Fungi are readily eliminated by phagocytes
2) Acquired immunity (cell mediated immunity)
- CMI acts in a manner similar to its action against
intracellular bacteria
* Disseminated fungal infection are seen in:
immunodeficient persons
81
IMMUNE RESPONSES TO FUNGI

Predominant defense mechanisms differ
depending on the specific causative agent

Activated neutrophils are critical in the
defense against disseminated candidiasis
and aspergillosis
82
IMMUNE RESPONSES TO FUNGI


Cell-mediated immunity predominates in
protection against cryptococcosis,
histoplasmosis and mucosal C. albicans
infection
Virulence factors help pathogenic fungi to
evade host response and subvert basic
immune processes
83
Helminths:
They are large complex organisms with
complex life cycles.
 In general, the most severe tissue damage
arises by immunopathogenic hypersensitivity
reactions.
 ( For example ascaris lumbricoides )

84
HELMINTH-INDUCED IMMUNE
RESPONSES

Characterized by IgE antibody production,
tissue and blood eosinophilia, mast cell
involvement and type 2 cytokines

Implicated both in pathogenesis of helminth
infections and in mediating immunologic
protection

Regulated by T cells and other cells producing
IL-4, Il-5, IL-10 and/or IL-13
85
Helminth evasion of immune responses



Antigenic disguise – parasites synthetise host-like
antigens to mask their own foreigness.
Alternatively they absorb host molecules to their
surfaces (Schistosomes)
Concomitant immunity or premunition – worms live
in in host for years with no evidence of immune
response. The latter however is formed to prevent
reinfection of the same worm.
86
Protozoa:
Many species of protozoa, such as
Plasmodium, Trypanosoma cruzi and
Toxoplasma gondii are also obligate
intracellular parasites.
 Others such as Entamoeba histolytica are
free-living.
 They may cause direct tissue injury or elicit
hypersensitivity reactions.

87
IMMUNOPATHOGENESIS OF SEVERE MALARIA
(P. FALCIPARUM)

Release of malarial antigens stimulates TNF-
production.

TNF- induces expression of endothelial
adhesion molecules (VCAM, ICAM, E-selectin
etc) and NO.
88
IMMUNOPATHOGENESIS OF SEVERE MALARIA
(P. FALCIPARUM) -2

Trophozoite proteins interact with RBC to
form cell membrane abnormalities

Infected RBC with membrane defects adhere
to upregulated endothelial adhesion molecules

Trapped infected RBC cause microcapillary
plugging – tissue ischemia, inflammation
pathology.
89
Prions


The term “prion" was originally coined by
Prusiner to explain the unusual infectious
agent in transmissible spongiform
encephalopathies.
the term proin from Proteinaceous infective
particle and changed to prion to sound it
rhythmic.

90
Prions Diseases

Definition: Degenerative diseases of the central
nervous system caused by a pathogenic isoform of
a normal cell protein.
Human Prion Diseases
•Kuru
•Creutzfeldt-Jakob Disease
•Genetic
•Sporadic
•Iatrogenic
•Gerstmann-Straussler-Scheinker
Syndrome
•Fatal Familial Insomnia
• New Variant Creutzfeldt-Jakob
Disease
Animal Prion Diseases
•Scrapie
•Transmissible mink encephalopathy
•Chronic Wasting Disease (CWD)
•Bovine Spongiform Encephalopathy (BSE)
(Mad Cow Disease)
•Feline spongiform encephalopathy
91
Characteristics features of prion diseases:












Degenerative nervous system diseases with very long
incubation periods (months to years; decades)
No inflammatory response
Chronic progressive pathology (slow infection)
No remissions or recoveries: always fatal
“Degenerative” histopathology: amyloid plagues, gliosis
No visible virion-like structures by electron microscopy
No interferon production; No interferon sensitivity
No infectious nucleic acid demonstrable
No antigenicity
No alteration in pathogenesis (incubation period, duration,
course) by immunosuppression or immunopotentiation:
No cytopathic effect in infected cells in vitro
Varying individual susceptibility to high infecting dose in some
host species; Unpredictable ability to cross species lines
92
Prion-Related Diseases, Hosts, and Mechanism of Transmission
Disease
Kuru
Host
Mechanism
Human
Cannibalism
Human
Spontaneous PrP C to PrP Sc conversion or somatic
mutation
Iatrogenic CJD
Human
Infection from prion-containing material, eg, dura mater,
electrode
Familial CJD
Human
Mutations in the PrP gene
nvCJD
Human
Infection from BSE
GSS
Human
Mutations in the PrP gene
Sporadic CJD
FFI
Sporadic fatal
insomnia
Human
Human
D178N mutation in the PrP gene, with M129
polymorphism
Spontaneous PrP C to PrP Sc conversion or somatic
mutation
Scrapie
Sheep
Infection in susceptible sheep
BSE
Cattle
Infection from contaminated food
TME
Mink
Infection from sheep or cattle in food
CWD
Mule, deer, elk
Feline spongiform
encephalopathy
Exotic ungulate
encephalopathy
Unclear
Cats
Infection from contaminated food
Nyala, oryx, kudu
Infection from contaminated food
93
Prions: Isoform of Normal Host Protein

Normal Protein





Protease sensitive
Soluble
High alpha-helix content
Found in brain tissue
Physiological functions
of cellular prion protein
(PrPc) is not clear.
Disease Causing Prion





Protease resistant
Insoluble
Forms amyloid fibrils
High beta-pleated sheet
conformation
Prion peptide of 106-126
residues is found to be
neurotoxic.
94
How do Prions “Replicate”?




When the normal prion protein changes shape it
becomes pathogenic
Mutations can occur that make the pathogenic
shape more likely
Prions don’t replicate but they do increase in
number
When an abnormal prion combines with a normal
one, the normal one changes it shape and becomes
abnormal……hence the numbers of abnormal
prions increases, but it is at the expense of the
normal ones. No new protein is created……
95
Mechanism of action of prions
96
sc
Mechanism of PrP induced apoptosis
97
Pathophysiologic changes




Brain vacuolation
Astrogliosis
Neuronal apoptosis
Accumulation of misfolded prion plaques.
98
Clinical manifestations of infectious diseases





Clinical manifestations of infectious diseases vary,
depending on the pathogen, the organ system
affected and severity.
Effects of infection may be acute, chronic, related
to immune responses or a consequence of bacterial
toxins.
The majority of manifestations results from the
host’s inflammatory and immune responses.
Infectious diseases typically begin with nonspecific
or general symptoms of fatigue,malaise,
weaknessand loss of concentration.
However, the hallmark of most infectious diseases
is FEVER.
99
Pathophysiology of fever






Body temperature is regulated by nervous system
feedback to the hypothalamus (central thermostat).
The normal range of body temperature is
considered to be 36.2º to 37.7ºC
A large number of agents (pyrogens) can produce
fever.
In current classification, those pyrogens:
- exogenous pyrogens derived from outside the
host,
- endogenous pyrogens produced by the host.
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exogenous pyrogens: (i.e. Endotoxins) the most
frequently encountered exogenous pyrogens are the
lipopolysaccharide complex in the cell wall of gram
positive bacteria and viruses.
endogenous pyrogens; including
-IL-1,
-IL-6,
-TNF-α,
- IFN-γ,
are produced by phagocytic cells as they destroy
microorganisms within the host.
The endogenous pyrogens act on the preoptic nucleus
of the hypothalamus, which release PGE2 and other
cytokines
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endogenous cryogens
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During fever, AVP, α-MSH and CRF are
released and can act as endogenous cryogens
to help diminish the febrile response.
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This antipyretic effect constitutes a negativefeedback loop.
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Benefits of fever
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Fever production aids responses to infectious
processes through several mechanisms.
Simple raising of body temperature kills many
microorganisms.
Higher body temperatures decrease serum levels
of iron, zinc and copper, all of which are needed
for bacterial replication.
The body switches from burning glucose to a
metabolism based on lipolysis and proteolysis,
thereby depriving bacteria of a food source.
Anorexia and somnolence reduce the demand for
muscle glucose.
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Increased temperature also causes lysosomal
breakdown and autodestruction of cells, thus
preventing viral replication in infected cells.
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Acute-phase proteins produced by the liver
during inflammation bind cations necessary for
bacterial reproduction.
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Heat increases lymphocytic transformation and
motility of polymorphonuclear neutrophils,
thus facilitating the immune response.
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Bacteremia or Septicemia….
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It is the presence of bacteria in the blood.
It is caused by a failure of the body’s defense
mechanisms.
The usual cause is proliferation of gramnegative bacteria (endotoxins).
Once in the blood, endotoxins cause the
release of vasoactive peptidis and cytokines
that affect blood vessels, producing
vasodilation (septic shock).
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SHOCK

Shock is a condition in which the cardiovascular
system fails to perfuse tissues adequately, resulting
in widespread impairment of cellular metabolism.
An impaired cardiac pump  inadequate tissue
perfusion:
 generalized cellular hypoxia (starvation)
 widespread impairment of cellular metabolism
 tissue damage
 organ failure
 death
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Septic shock
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Septic shock, is the endpoint of a continues
of progressive dysfunction.
The syndrome begins with
bacteriemia,
then sepsis,
then severe sepsis,
then septic shock….
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THANK YOU!
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References :
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Harrison's Principles of Internal
Medicine. (Dennis L. Kasper , Eugene
Braunwald Stephen Hauser)
Pathophysiology of Disease: An Introduction to
Clinical Medicine . Gary D. Hammer , Stephen J.
McPhee
Pathophysiology: The Biologic Basis for Disease
in Adults and Children. Kathryn L. McCance , Sue
E. Huethe
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