Summary of a textbook on pathological anatomy.
Faculty of Medicine, 3rd year. Author: Assistant of the Department of General Pathology A.A.
Sivolobov.
Topic: The infectious process. Flu. HIV.
Section No. 1: The infectious process.
Infectious diseases are among the most common diseases on Earth.
Types of interaction between microorganisms and macroorganisms.
1. Symbiosis is the close coexistence of living organisms belonging to different biological
species. There is a symbiosis between humans and many microorganisms, a relationship of
immunity, acquired and innate immunity.
The symbiosis includes:
2. Mutualism is the mutual benefit of a microorganism and a host.
3. Commensalism is the benefit of one of the partners.
4. Parasitism is an antagonistic symbiosis in which harm is inflicted on the host.
Infectious pathology is caused by microorganisms with which there is no symbiotic relationship
or these relationships are disrupted for some reason. A number of special terms are used to
understand the features of the interaction of macro-and microorganisms.
1. Pathogenicity is the ability of microorganisms to cause an infectious disease. Pathogens are
microorganisms that cause an infectious disease.
2. Infectivity is the ability of microorganisms to overcome the protective mechanisms (cellular,
tissue, humoral, etc.) of humans or animals.
3. Invasiveness is the ability of pathogenic microorganisms to multiply and spread throughout
the body.
[Link] – the ability of microorganisms to produce and release various toxins, which also
determines their pathogenicity.
5. Virulence is the degree of pathogenicity of a microorganism, depending on many conditions:
the characteristics of the strain, the way it enters the body, immunogenicity, toxicity, etc.
6. Infection (infection) – the ingestion of the causative agent of an infectious disease into the
cells or tissues of the body.
These properties of micro- and macroorganisms make it possible to formulate the concept of an
infectious disease and an infectious process.
An infectious disease or infection is the introduction and reproduction of microorganisms in a
macroorganism with the development of various forms of their interaction: from the cell of
pathogens to a pronounced disease.
The infectious process is a complex of reactions of a macroorganism to the introduction and
reproduction of pathogenic microorganisms in it, aimed at restoring homeostasis and balance
with the environment.
Susceptibility to infection is the ability of a person or animal to respond to the introduction of a
pathogen by developing a disease or carrier.
The following groups of infectious diseases are distinguished:
1. Anthroponoses are a group of diseases that are unique to humans.
2. Zoonoses – animal diseases
3. Anthropozoonoses are diseases characteristic of humans and animals.
4. Biocenoses are human infectious diseases that occur in the presence of an intermediate host.
Biocenoses are classified as infectious diseases with natural foci, for example, malaria.
An infectious disease is impossible without a pathogen, it is the cause of the disease. Depending
on the etiology, infectious diseases are divided into prion, viral, mycoplasma, rickettsia,
bacterial, fungal, protozoal, parasitic, and arthropod-induced.
Mechanisms of action of pathogens.
Pathogens of infectious diseases have certain pathogenic mechanisms of action: 1) cause direct
cell death, 2) release toxins and enzymes, damaging cells and blood vessels far from the site of
penetration into the body, 3) lead to inflammatory, often specific reactions that damage organs
and tissues.
The mechanisms of interaction between different pathogens and the macroorganism are
diverse.
Viruses enter cells due to the presence on their surface of specific proteins capable of binding to
receptors on the outer membrane of a number of cells. Next, the virus enters the cytoplasm, its
genome is integrated into the genome of the host cell.
Microorganisms have a damaging effect on tissues depending on their ability to attach to cells
with the help of adhesion proteins, penetrate into cells, and release exo- or endotoxins.
Endotoxin is a lipopolysaccharide of the outer part of the wall of gram–negative organisms.
Their action is mediated by cytokines (IL-1, TNF, etc.).
Exotoxins are various enzymes of microorganisms (leukocidins, hemolysins, hyaluronidases,
fibrinolysins, etc.).
Inside the cells of a macroorganism, some bacteria disrupt protein synthesis, others suppress
oxidation in the phagocytic vacuole, and others multiply in phagolysosomes, and then lyse the
cells.
Mechanisms that allow microorganisms to avoid the immune actions of the host body:
1. Unavailability for immune reactions.
2. Adaptability to lysis and phagocytosis.
3. Change or loss of antigens.
4. Suppression of immunity.
Pathogen transmission mechanisms: 1)fecal-oral, 2) airborne, 3)transmissible (through blood),
4)transplacental, 5) contact, 6) mixed.
Depending on the clinical and morphological features, the following groups of infectious
diseases are distinguished. Each of them is characterized by damage to certain organs and
systems.
1. Infections with predominant skin lesions (pyoderma, erysipelas, smallpox, fungal diseases).
2. Respiratory tract infections (pneumonia, bronchitis, influenza).
3. Infections of the digestive tract (typhoid fever, dysentery, salmonellosis).
4. Infectious diseases of the nervous system (polio, encephalitis, etc.)
5. Vector-borne infections associated with the blood system (malaria, recurrent typhus,
hemorrhagic fevers).
6. Infections with predominant damage to the cardiovascular system (syphilis, brucellosis).
7. Infections of the genitourinary system (glomerulonephritis, pyeloneritis, gonorrhea).
There is a group of opportunistic or opportunistic infections caused by normal human flora. With
a decrease in natural human immunity, these microorganisms can cause infectious diseases, and
without the nosological specificity characteristic of all other infectious diseases. Conditionally
pathogenic infection occurs in premature or weakened infants, in people with reduced immunity
with severe somatic diseases, after extensive surgical interventions, the use of
immunosuppressants (cytostatics) or broad-spectrum antibiotics. Opportunistic pathogens are the
most common cause of nosocomial infections.
The causative agent of the disease can enter the body either from the external or internal
environment of the body. According to this feature, all infections are divided into exogenous and
endogenous.
The entrance gate is the place where the causative agent of infection enters the body (skin,
mucous membranes, blood, etc.). Morphological changes are usually found in the entrance gate
that are specific to a particular pathogen and characteristic of the corresponding infectious
disease (the development of inflammation, often a focus of necrosis).
Primary affect is the primary localization of the pathogen and inflammatory changes around it.
The primary affect develops in the tissue to which the pathogen is adapted. The first protective
barrier, the lymphatic system, reacts to damage first of all. The pathogens themselves, their
waste products, and toxins enter the lymph nodes through the lymph vessels. They become
inflamed, develop lymphangitis and regional lymphadenitis.
The primary infectious complex is a triad of changes that has arisen: primary affect,
lymphangitis, and regional lymphadenitis. It is a characteristic and necessary component of all
infectious diseases. For example, with tuberculosis, primary affect (a small focus of caseous
necrosis and peripheral serous inflammation), tuberculous lymphangitis and regional
lymphadenitis (caseous necrosis of the peribronchial lymph node) is localized in one of the
segments of the lung.
Infectious diseases have local and general manifestations, depending on the reactivity of the
body.
An infectious disease is a violation of the relationship between micro– and macroorganisms,
which manifests itself in a special, increased reaction of the body to the pathogen and is called an
allergy. It manifests itself in the form of hyperergia, that is, an immediate type of
hypersensitivity reaction (HT) or delayed type (HRT). It is also possible to reduce the reactivity
of the body – hypo-ergia, as well as the absence of an organism's reaction to the pathogen-
anergy.
A common feature of all infectious diseases is the cyclical nature of their course, so infectious
diseases have certain periods or phases.
1. The incubation (latent) period is the time when an infect enters the body and goes through
its development cycle, including reproduction. The duration of the period depends on the
characteristics of the pathogen. At this time, there are still no subjective sensations of the
disease, but reactions between the infect and the macroorganism are already taking place,
mobilization of the body's defenses, changes in homeostasis, increased oxidative processes in
tissues, and allergy and hypersensitivity are increasing.
2. The prodromal, or initial period of the disease. The first, unclear symptoms of getting sick
are characteristic: malaise, often chills, headache, slight muscle and joint pain. Inflammatory
changes and moderate hyperplasia of the lymph nodes and spleen often occur in the area of the
entrance gate. The duration of this period – 1-2 days. When the highest level of hyperergia is
reached, the next period begins.
3. The period of the main manifestations of the disease (the period of manifestation of
symptoms).
The symptoms of a specific infectious disease and characteristic morphological changes are
clearly expressed. This period has the following stages:
1) The stage of increasing manifestations of the disease.
2) The stage of peak, or maximum severity of symptoms.
3) The stage of extinction of the manifestations of the disease. This period means a manifestation
of hypo-ergia, indicating that the body has managed to limit the infection to some extent.
The period of extinction of the disease is the gradual disappearance of clinical symptoms,
normalization of temperature and the onset of reparative processes.
The period of convalescence (recovery), which may have a different duration depending on the
form of the disease, its course, and the patient's condition. Often, clinical recovery does not
coincide with the complete restoration of morphological damage, which is often longer.
Recovery may be complete or incomplete (for example, paralysis after polio). In addition, after
clinical recovery, the carrier of infectious agents may form, which is obviously associated with
insufficient immunity of the convalescent, improper treatment or other reasons. It is possible to
carry pathogens for years (malaria) or even for a lifetime (typhoid fever). The carriage of
pathogens is of great epidemiological importance, since carriers who are unaware of their release
of microorganisms can become an unwitting source of infection to others, as well as a source of
epidemic.
Morphology of infectious diseases. General and local morphological changes develop in the
pathogenesis of all infectious diseases.
The main patterns of infectious diseases that affect almost all infections, with minor
exceptions (sepsis, plague).
1. The presence of a specific pathogen.
2. Contagiousness.
3. Certain ways of transmission of infection.
4. The presence of an entrance gate.
5. Formation of the primary infectious complex.
6. Changes in the reactivity of the body and the increase of allergies in the dynamics of the
disease.
7. The cyclical nature of the disease.
8. In the pathogenesis and morphogenesis of all infectious diseases, general changes develop
associated with changes in reactivity and intoxication, and local changes due to the specific
action of the pathogen.
9. Formation of postinfectious immunity.
Along with these patterns, which are common to all infectious diseases, the characteristics of the
pathogen create specific morphological and clinical manifestations of a particular infection,
which allows for its diagnosis.
Section No. 2: Respiratory infections. Flu.
This is a group of the most common infectious diseases with a predominantly airborne
mechanism of transmission of the pathogen. Among them, viral infections occupy a special
position, which are usually acute and often have the character of epidemics and pandemics. The
source of infection is sick people. Infections affect the upper respiratory tract, causing their
inflammation, as well as the lower respiratory tract, which contributes to their obstruction. The
most common are influenza, parainfluenza, adenovirus and respiratory syncytial infections,
which make up the majority in the group of acute respiratory viral infections (ARVI).
Influenza is an acute highly contagious disease caused by an RNA virus with an affinity for the
epithelium of the respiratory tract. The disease usually occurs in the cold season.
Epidemiology. The disease can be caused by one of three influenza viruses: A, B, and C.
Serotype A is the most epidemically dangerous, infecting humans, pigs, horses, and birds.
With the help of lipoglycoprotein receptors, the virus is fixed on the surface of the epithelial cells
of the mucous membrane of the upper respiratory tract. Then the hemagglutinin antigen in the
lipid envelope of the pathogen allows it to penetrate into the cytoplasm of epitheliocytes, bind to
endosome proteins and membrane lipids. Next, the virus is introduced into the cytosol and its
reproduction begins with the help of RNA polymerase. Another virus envelope antigen,
neuraminidase– lyses cell membrane structures, ensuring that the virus exits the cell. It is to these
antigens - hemagglutinin and neuraminidase - that the body produces antibodies.
The body is freed from viruses by cytotoxic T-lymphocytes, which destroy infected cells, or
cytokines, which cause the formation of the anti-influenza protein Mx1 in macrophages.
The influenza A virus is characterized by mutations in the hemagglutinin and neuraminidase
genes, which each time changes their antigenic properties, avoiding the action of existing
antibodies. This phenomenon is called antigenic drift, or antigenic shift. As a result, each time
the body encounters a new influenza virus, which explains the epidemics and pandemics of this
disease, for example, the 1918-1920 pandemic, when more than 20 million people died from
influenza (“Spanish flu”).
A sick person is contagious 24 hours before the onset of clinical symptoms and within 2 days
after clinical recovery.
The pathogenesis of influenza includes several stages.
1. The introduction and primary reproduction of the virus into the epithelium of the respiratory
tract correspond to the incubation period of the disease. Duration – from several hours to 2-4
days.
2. Viremia is accompanied by prodromes and corresponds to the prodromal stage of the disease.
3. Secondary reproduction of the virus in epithelial cells, leading to the generalization of
infection, corresponding to the height of the disease.
Clinical characteristic: 1) fever, 2) headache, 3) catarrhal rhinitis, 4) cough, 5) conjunctivitis, 6)
often joint and condyle pain.
The pathogenesis and morphogenesis of influenza explain the following properties of the virus:
1. Cytopathic, leading to balloon dystrophy of the respiratory tract epithelium, its peeling and
lysis, and impaired bronchial drainage function.
2. Immunosuppressive, contributing to the development of immunodeficiency (decreased
chemotaxis, phagocytic activity of macrophages and neutrophils, the appearance of circulating
immune complexes).
3. Vasopathic (vasoparalytic), causing hyperemia, stasis, plasma impregnation of vascular
walls, perivascular edema and diapedetic hemorrhages.
In the dynamics of the disease, all these effects are interrelated.
There are mild, moderate, and severe forms of influenza.
1. The mild form of influenza is most common. Acute catarrhal rhinolaryngitis or
rhinolaryngotracheobronchitis is characteristic. The mucous membranes of the nose and larynx
are hyperemic, with abundant serous-catarrhal exudate, sometimes punctate hemorrhages. The
ciliated epithelium loses cilia, hydropic dystrophy is observed in it, cell peeling occurs, clusters
of viruses appear in the form of rounded basophilic bodies, accumulations of cell reaction
products to the virus in the form of eosinophilic bodies are determined. Moderate
lymphoplasmocytic infiltration of the mucous and submucosa, increased secretory activity of
goblet cells and glands are noted. The general changes are caused by viremia and intoxication.
The duration of the disease is 5-6 days, the outcome is recovery and repair of mucous
membranes. Sometimes the process may progress and complications may develop.
2. Flu of moderate severity. It is characterized by the spread of inflammation to all parts of the
bronchial tree, sometimes up to the alveoli. The inflammation is serous-hemorrhagic or
fibrinous-hemorrhagic, with infiltration by lymphocytes, macrophages, single neutrophils, and
areas of necrosis. The exfoliated epithelium and copious thick mucus form plugs that clog the
small bronchi, which leads to the development of atelectasis and perifocal emphysema. A
contributing factor is a decrease in the production of surfactant by pneumocytes. Against this
background, the development of focal or interstitial pneumonia is possible. At the same time, the
lung is enlarged in size, with dense airless areas of bluish-purple or purple color. In most cases,
recovery occurs after 3-4 weeks, but bronchopulmonary complications are possible.
3. The severe form of influenza occurs in 2 variants: toxic flu and flu with pulmonary
complications.
1) Toxic flu. Severe general changes and increased serous-hemorrhagic inflammation are
characteristic, with an increase in hemorrhagic and necrotic components of the inflammatory
response. It is possible to develop pulmonary edema, hemorrhagic syndrome (multiple
hemorrhages in the brain, mucous membranes and serous membranes, internal organs, skin), as
well as serous hemorrhagic meningitis, cerebral edema.
Possible hemorrhages in the adrenal glands with the development of Waterhouse-Friederiksen
syndrome, swelling of the mucous membrane of the larynx with stenosis of its lumen and
asphyxia (false croup).
2) Influenza with pulmonary complications occurs when a secondary bacterial infection is
associated with the development of severe focal bronchopneumnia, usually a week after the
onset of the disease.
Complications of the flu can be pulmonary and extrapulmonary.
1. Pulmonary complications: 1)bronchopnemonia, 2)purulent pleurisy, 3)pleural empyema,
4)purulent bronchitis, 5)bronchiectasis, 6)pneumosclerosis, 7)chronic obstructive pulmonary
disease.
2. Extrapulmonary complications: 1)purulent mediastinitis, 2)pericarditis, 3)toxic myocarditis,
4)acute warty endocarditis, 5)serous meningitis, 6)purulent encephalitis, 7)catarrhal otitis media,
8)frontitis, ethmoiditis, sinusitis, 9)serous neuritis, 10)glomerulonephritis, 11)cerebral
hemorrhages, 12)the development of a lightning-fast form of influenza is possible.
Flu outcomes. The flu of mild and moderate severity proceeds favorably, the outcome (through
5-7 and 20-25 days, respectively) is a complete recovery. In severe and complicated forms of
influenza, death is possible on day 4-5 from cardiopulmonary insufficiency against the
background of the progression of pneumonia and its complications, hemorrhages, intoxication,
hemorrhagic pulmonary edema. The flu is most dangerous for young children, the elderly, and
patients suffering from cardiovascular diseases. Children may develop false croup and die from
asphyxia, while the elderly may experience an exacerbation of chronic diseases.
Section No. 3: HIV infection and AIDS.
HIV infection is associated with the human immunodeficiency virus (HIV), a type of retrovirus
that affects lymphocytes, macrophages, and nerve cells. The disease is manifested by a slowly
progressive immunodeficiency, from asymptomatic carriage to fatal diseases.
Acquired immunodeficiency syndrome (AIDS) is a secondary immunodeficiency syndrome
resulting from HIV infection. It is characterized by complete suppression of the immune system,
the development of opportunistic infections caused by opportunistic pathogens, and tumors.
Etiology. The pathogens are HIV viruses of the genus retrovirus. There are 2 known types of
virus:
1. HIV-1 is the main causative agent of HIV infection and AIDS in the world.
2. HIV-2 is a less virulent virus, the main causative agent of AIDS in West Africa.
Epidemiology. The source of infection is a person at any stage of the disease. The virus is
isolated from blood, semen, vaginal secretions, saliva and other biological fluids. Transmission
routes are sexual, parenteral, and transplacental.
Risk groups were identified: homosexual and bisexual men (43%), drug addicts who inject
narcotic substances intravenously (31%), heterosexuals (10%), recipients of blood and its
components, transplanted organs (2%), patients with hemophilia (1%), heterosexual partners of
HIV patients, children whose parents belong to one of the risk groups.
The clinical picture. HIV infection has the following clinical stages.
1. The stage of seroconversion is the beginning of an acute disease. The incubation period is
from several weeks to several months after infection. Its duration depends on the pathways and
nature of infection, the infecting dose, and the state of the immune system at the time of
infection. The virus and viral antigens can be detected in the blood in the absence of specific
antibodies. Viremia reaches a peak by 10-20 days after infection and continues until specific
antibodies appear. After that, there is a sharp decrease in the number of viruses (with HIV-1 - 3-6
months after infection). Then 50-90% of patients have symptoms resembling infectious
mononucleosis or a cold (headache, fever, skin rash, lymphadenopathy), which spontaneously
disappear within a few weeks.
2. Asymptomatic stage. Patients report an increase in all groups of lymph nodes and headache.
3. The early symptomatic stage of HIV infection lasts 3-5 years. Fever, excessive sweating at
night, general weakness, chronic diarrhea, generalized lymphadenopathy, headache in the
absence of specific or opportunistic infections are characteristic. Then candidiasis of the oral
cavity, leukoplakia of the oral mucosa, upper and lower respiratory tract infections, pyoderma
and periodontal diseases develop.
4. The late symptomatic stage of HIV infection (preSPID) lasts for several years. With a
progressive decrease in the number of CD4+T lymphocytes against the background of moderate
immunodeficiency, the risk of developing opportunistic infections increases.
5. The stage of disease progression (AIDS stage) lasts about two years. It is characterized by a
complete violation of the functions of the immune system and the development of opportunistic
infections. The level of specific antibodies is reduced, and the number of viral antigens is
increasing. Exhaustion in adults and developmental delay in adolescents are progressing.
Neurological and mental disorders, Kaposi's sarcoma, and lymphocytic interstitial pneumonitis
develop in adolescents and children. The combination of various infections and tumors gives the
AIDS picture a pronounced polymorphism.
Pathogenesis. When infected, the virus enters the blood directly, for example, by injection,
hemotransfusion, or through a damaged mucous membrane of the genital tract. The virus
selectively binds to activated CD4+ cells (T-lymphocytes, monocytes, macrophages), it uses the
CD4+ molecule as a receptor. These cells recognize the viral antigen and act as T-helper cells.
When infected, monocytes and macrophages do not die, but become the habitat and reproduction
of the pathogen. The main reservoir of HIV is lymphoid tissues, in which the pathogen is
constantly multiplying.
In the pathogenesis and morphogenesis of the disease, there are several stages that do not
contradict the clinical stages, but combine some of them to explain the clinical picture of HIV.
1. Early viremic stage (asymptomatic). The body's defense systems inhibit the reproduction of
the pathogen. The appearance of viral glycoproteins in the membrane of infected T cells triggers
immune mechanisms directed against these cells (activation of T-killer reactions of antibody-
dependent cytotoxicity). Virus replication is negligible. There is a temporary decrease in the total
number of CD4+ lymphocytes, but the number of circulating HIV-infected CD4+T lymphocytes
is increasing.
2. The stage of immunosuppression. The accumulation of non-integrated viral DNA in the
cytoplasm of infected cells causes rapid HIV replication and cell death. HIV infects progenitor
cells in the thymus and bone marrow, which reduces the number of CD4+T
[Link] HIV replication and the release of viruses from infected cells cause a
second wave of viremia, and CD4+T lymphocytes die. This happens 14-16 months before the
onset of AIDS symptoms. A drop in antibody levels coincides with the second wave of viremia.
3. Terminal stage. HIV-infected monocytes have impaired chemotaxis, interleukin synthesis,
and other functions. There is a decrease in viremia and antibody titers, a general reduction in the
CD4+ cell population, and a rapid transition to AIDS.
Pathological anatomy. Typical changes are in the lymph nodes, central nervous system,
respiratory and digestive organs, skin, as well as the appearance of tumors – Kaposi's sarcoma
and lymphoma. These changes occur from the second period of the disease.
The lymph nodes are enlarged, and they are characterized by hyperplasia of lymphoid follicles
and their germinal centers, which reflects the nonspecific activation of B cells. In the third
period, with complete depletion of lymphoid tissue, the lymph nodes are sharply reduced, they
are difficult to find. Patients develop encephalomyelitis. Foci of softening form in the brain and
spinal cord.
40% of HIV-infected patients develop tumors, mainly Kaposi's sarcoma. In AIDS patients, it has
a malignant character with generalization of the process, damage to the lymph nodes,
gastrointestinal tract, lungs and other internal organs. Macroscopically, Kaposi's sarcoma looks
like purplish-red spots, ulcerated plaques and nodules on the skin of the distal parts of the lower
extremities. Microscopically, the tumor consists of randomly arranged thin-walled vessels and
bundles of spindle-shaped cells. Hemorrhages and accumulations of hemosiderin are visible in
the stroma.
Lymphomas in AIDS patients occur less frequently, these are mainly B-cell lymphomas and
Burkitt's lymphoma.
The prognosis is unfavorable. Death occurs from opportunistic infections and generalization of
tumors. The mortality rate is 100%.