MINISTRY OF HEALTH OF UKRAINE

STATE INSTITUTION "DNIPROPETROVSK MEDICAL ACADEMY OF

THE MINISTRY OF HEALTH OF UKRAINE"

PATHOLOGICAL PHISIOLOGY
training manual for students of the second level
of training (master) in the field of knowledge 22 Health
222 Medicine and 221 Dentistry

Khmel O.S., Kozlova Yu.V., Khudyakov A. E.

Dnipro-2021
UDC 616-092

Recommended by the Academic Council of State Institution "Dnipropetrovsk Medical Academy of the
Ministry of Health of Ukraine" as a training manual for english-speaking foreign students of higher
education of the Ministry of Health of Ukraine

Minutes of the meeting of the Academic Council of State Institution "Dnipropetrovsk Medical
Academy of the Ministry of Health of Ukraine" № ____ of _________________

Team of authors:
Khudyakov Olexander Evgenovich - PhD, associate professor, head of the Department of
pathological physiology, State Institution "Dnipropetrovsk Medical Academy of the Ministry of
Health of Ukraine".
Khmel Olena Stanislavyvna - PhD, lecturer at the Department of pathological physiology State
institution "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine".
Kozlova Yuliia Vasilyevna - PhD, lecturer at the Department of Pathological Physiology State
Institution "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine".

Reviewers:

Gancheva O.V. - Professor, MD, Head of the Department of Pathological Physiology with a course
of normal physiology of Zaporizhzhia State Medical University
Turytska T.G. - Associate Professor, PhD (Biological Sciences), Associate Professor of General
Medicine with a course of physical therapy at the Faculty of Medical Technologies of Diagnosis and
Rehabilitation of Oles Honchar Dnipro National University.

Khmel O.S., Kozlova Yu.V., Khudyakov A. E. - Training manual of Pathological phisiology. A

training manual for practical lessons and independent work. – Dnipro: 2021. – 210p.

ISBN
The physiopathology training manual: designed for English-speaking foreign students in higher
education institutions, contains a set of educational material for the study of pathological physiology.

ISBN

The training manual of pathophysiology will promote high-quality theoretical training of students, the
acquisition of the necessary skills in practical lessons and independent preparation.
UDC 616-092
©State Institution
"Dnipropetrovsk Medical
Academy of the Ministry
of Health of Ukraine", 2021

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 CONTENT:

Part І General nosology…………………………………………... 5

Chapter 1. Subject and methods of pathophysiology. The doctrine of a 5
disease……………………………………………………...
Chapter 2. Pathogenic effect of physical factors on the body………… 11
Chapter 3. The role of heredity and constitution in human pathology… 25
Chapter 4. The role of reactivity and resistance in pathology………… 31
Chapter 5. Allergy…………………………………………………….. 37
Part II Typical pathological processes…………………………….. 43
Chapter 1. Peripheral blood circulation and microcirculation disorders. 43
Chapter 2. Inflammation………………………………………………. 49
Chapter 3. Fever……………………………………………………….. 55
Chapter 4. Tumors……………………………………………………... 60
Chapter 5. Hypoxia……………………………………………………. 68
Part ІII Disorders of metabolism…………………………………… 72
Chapter 1. Pathophysiology of carbohydrate metabolism…………….. 72
Chapter 2. Starvation. Violations of vitamin metabolism…………….. 79
Chapter 3. Disorders of water-electrolyte exchange…………………... 84
Chapter 4. Violations of acid-basic state………………………………. 90
Part IV Pathological physiology of organs and systems…………… 96
Chapter 1. Pathophysiology of the blood system. Anemia caused by
blood loss............................................................................... 96
Chapter 2. Hemolytic and dyserythropoietic anemias…………............ 104
Chapter 3. Disorders of the wbc system……………………....……….. 112
Chapter 4. Disorders of the hemostasis system………………………... 121
Chapter 5. Pathophysiology of the heart………………………………. 130
Chapter 6. Pathophysiology of blood vessels…………………………. 140
Chapter 7. Pathophysiology of external breathing…………………….. 146

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Chapter 8. Pathophysiology of the digestive system………………….. 151
Chapter 9. Pathophysiology of liver…………………………………… 161
Chapter 10. Pathophysiology of the kidneys……………………………. 169
Chapter 11. Pathophysiology of extreme conditions…………………… 176
Chapter 12. Pathophysiology of the endocrine system…………………. 191
Chapter 13. Pathophysiology of the nervous system…………………… 202

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 PART I
GENERAL NOSOLOGY

Chapter 1. Subject and methods of pathophysiology. The doctrine of the

disease.

"Pathophysiology" is the science of the vital activity of a sick organism.

Pathological physiology studies the basic patterns of origin, development and outcome
of the disease. The ultimate goal of pathophysiology is to reveal the laws by which the
disease develops.
The first section - general pathophysiology consists of general nosology and the
doctrine of typical pathological processes. General nosology considers the nature of
diseases, causes (etiology) and mechanisms of development (pathogenesis), as well as
mechanisms of recovery (sanogenesis).
Nosology forms the basic concepts and categories of pathology, creates
classifications and nomenclature of diseases, and studies the social aspects of the
disease.
Basic concepts of general nosology:
Health is a state of complete physical, mental and social well-being and not merely
the absence of disease or infirmity (WHO definition, 1946). This is, first, the state of
the organism, which indicates the conformity of structure and function, as well as the
ability of regulatory systems to maintain the stability of the internal environment
(homeostasis).
The norm is a state of optimal vital activity and development of the organism.
Disease - a violation of the normal functioning of the body when exposed to
damaging agents, resulting in reduced adaptive capacity.

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 A pathological reaction is an inadequate and biologically inappropriate response
of the body to the action of normal or excessive stimuli. Examples: various types of
pathological reflexes, allergies, short-term increase in blood pressure after nervous
tension or lower blood sugar due to the introduction of large doses of insulin, etc.
The pathological process is a sequence of reactions that naturally occur in the
body to the harmful effects of pathogenetic factors. Examples of pathological processes
are inflammation of the lung tissue in pneumonia, hypoxia in obliterative endarteritis,
inflammation of the heart muscle in myocardial infarction, fever in typhoid fever, etc.
A pathological condition is a set of pathological changes in the body that occur
due to the development of a pathological process. In the narrow sense of the word - a
persistent deviation from the norm, which has a negative biological significance.
Examples of pathological conditions are stump after limb amputation, scar tissue
changes after thermal burns, atrophy of the alveolar processes of the jaw due to removal
or loss of teeth, acquired valve defect hearts.
Typical pathological processes are those processes that have the same laws of
their development, regardless of the cause, location, and species of animals and
individual characteristics of the organism. Examples: inflammation, tumor growth,
local circulatory disorders, hypoxia, starvation, fever.
In the development of the disease, there are 4 periods (stages):
- Latent (for infectious diseases - incubation) lasts from the moment of exposure to the
cause until the first clinical manifestations of the disease;
- Prodromal - is the period from the first nonspecific signs of the disease to the full
manifestation of its symptoms;
- The period of exacerbation of the disease is characterized by the full development of
the clinical picture: convulsions in parathyroid insufficiency, leukopenia in radiation
sickness, hyperglycemia and glycosuria in diabetes mellitus;
- The period of the end of the disease: complete and incomplete recovery, relapse,
transition to a chronic form, remission, complications, death.
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 Complete recovery is a condition in which all manifestations of the disease
disappear and the body fully restores its functions.

At incomplete recovery, consequences of an illness are expressed. They stay for a

long time or forever.
Remission is a temporary improvement in the patient's condition, which is
manifested in the slowing or cessation of the disease process, partially reversible or
disappearance of clinical manifestations or pathological process.
Exacerbation - a stage of chronic disease, characterized by an increase in existing
symptoms or the appearance of new ones.
Complications are a secondary pathological process in relation to existing
diseases, which occurs in connection with the peculiarity of the pathogenesis of the
primary (main) disease or as an unforeseen consequence of treatment.
Recurrence - the restoration or intensification of the disease after their temporary
disappearance, weakening or cessation of the pathological process.
Death is the most unfavorable outcome of the disease. It can be natural
(physiological from aging) and premature, which can be violent (murder) and disease.
In addition, there are brain death (sudden death of the brain against the background of
all healthy organs supported by artificial ventilation) and somatic, resulting from
irreversible, incompatible with life damage to any organ, organ or system. It is more
common in chronic diseases, when simultaneously but slowly die the cerebral cortex
and internal organs.
The terminal state is a reversible attenuation of the body's functions, which
precedes biological death, when the complex of protective and compensatory
mechanisms is insufficient to eliminate the effects of pathogenic factors on the body.
The cessation of vital functions occurs gradually and the dynamics of this process
allows us to identify several phases that are observed in the death of the organism:
preagony, agony, clinical and biological death.

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 Preagony is a terminal condition that precedes agony, which is characterized by
the development of inhibition in the higher parts of the central nervous system and is
manifested by a darkening of consciousness, sometimes with a violation of the bulbar
centers. Blood pressure is low; the pulse in the peripheral arteries is very weak or not
detected at all. Respiration due to increasing circulatory hypoxia and the accumulation
of carbon dioxide, which stimulates the respiratory center, increases sharply. Then
tachycardia and tachypnea are replaced by bradycardia and bradypnea. Progression of
consciousness, electrical activity of the brain and reflex activity progresses. The depth
of hypoxia in all organs and tissues increases, with which cyanosis and pallor of the
skin are associated. The body continues to maintain energy metabolism due to the
reactions that go with oxygen consumption - aerobic metabolism predominates.
Agony is a terminal condition that precedes clinical death and is characterized by
profound dysfunction of the higher parts of the brain, especially the cerebral cortex,
with a simultaneous violation of the medulla oblongata. Consciousness is absent
(sometimes briefly clarified), eye reflexes and reaction to external stimuli disappear.
There is a relaxation of the sphincters; there is an involuntary excretion of feces and
urine. Auxiliary muscles take part in respiration - muscles of a neck and the person,
there is a "gasping" - breath (it is the pathological breath, which is characterized by
rare, short and deep convulsive respiratory movements). During agony, metabolism
changes dramatically, catabolic processes prevail over synthesis, the amount of
glycogen in organs and tissues decreases, glycolysis sharply increases and lactic acid
content in organs and tissues increases, macroergic phosphate breakdown sharply
increases and inorganic phosphate levels increase. Decreased body temperature -
hypothermia. Agony as a reaction of a dying organism is compensatory in nature and
aims to support life, but it cannot last indefinitely. In the last stages of agony, vascular
paresis develops, blood pressure drops to almost zero, heart sounds are deaf or unheard.
Only the carotid pulse is determined. Typical type of patient: "face of Hippocrates" -

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"inflamed eyes and cheeks", pointed nose, gray-earthy complexion, corneal opacity,
dilation of the pupil. Then the agony turns into clinical death.
Clinical death is a terminal condition that occurs after the cessation of cardiac
activity and respiration and lasts until the onset of irreversible changes in the higher
parts of the central nervous system. During clinical death, external signs of life
(consciousness, reflexes, respiration, heart contractions) are absent, but the body as a
whole is not dead, energy substrates are stored in its tissues and metabolic processes
continue, so timely resuscitation can restore all body functions.
Biological death is an irreversible state when the recovery of the organism as a whole
is no longer possible, and the restoration of its individual functions (for example,
cardiovascular activity) through resuscitation loses its meaning.
General etiology - the doctrine of the causes and conditions of the disease and the
principles of etiotropic prevention and therapy.
The cause of the disease should be considered a pathogenic factor without which
it cannot occur under any circumstances. Conditions of the disease are factors that
significantly increase the likelihood of the disease. Example: the cause of SARS - a
virus, conditions - hypothermia, fatigue, decreased immunity.
Risk factor - the general name of factors that are not the direct cause of a disease,
but increase the likelihood of its occurrence.
Classification of etiological factors.
- Physical - mechanical action, ionizing radiation, high and low temperature, electric
current, etc;
- Chemical - inorganic and organic compounds of natural and artificial origin;
- Biological - viruses, rickettsiae, bacteria, protozoa, etc.
- Psychogenic - negative emotions, etc.
General pathogenesis - the study of the general mechanisms of development, course
and consequences of the disease and the principles of pathogenetic prevention and
therapy.
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 The relationship between the cause of the disease and its pathogenesis.
1. The etiological factor plays the role of a trigger and includes the process of disease
development. For the further course of the pathogenesis, the continued existence of the
cause is not mandatory (eg, radiation sickness, mechanical trauma, thermal damage).
2. The parallel existence of cause and pathogenesis. The mechanism of disease
development functions as long as the causal factor acts. Most infectious diseases can
serve as an example of this kind of interaction between the cause and mechanism of the
disease.
3. Persistence of the etiological factor. The agents that cause the disease linger in the
body longer than the actual pathogenesis itself. At the same time, properties of an
etiological factor under the influence of an organism can change. An example is
bacteriocarriers after infectious diseases.
Causal links in the pathogenesis:
- "Straight chain" is characterized by the development of pathogenesis in a straight line,
when one phenomenon is a consequence of the previous and the cause of the next.
- "Branched chains": divergence and convergence. In divergence, one cause has many
consequences. In convergence, several causes lead to the same consequence.
- "Vicious circle" is a type of causal relationship, when each link of pathogenesis
through a sequence of events leads to self-strengthening.
The main link in the pathogenesis is the leading process that is necessary for the
deployment of all others. Timely removal of this leading link leads to the rupture of the
pathogenetic chain of causal relationships and stops the further development of the
disease.
Adaptation is the adaptation of the organism and its structures to changing
environmental conditions. Adaptation ensures the preservation of homeostasis and
prevents damage under conditions of normal environmental factors.

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Compensation is a condition that develops as a result of the implementation of
compensatory reactions and processes aimed at restoring disturbed homeostasis due to
the influence of pathogenic factors.
The second section of general pathological physiology - the doctrine of typical
pathological processes. The section contains data on the processes underlying many
diseases, namely: inflammation, tumor growth, fever, hypoxia, typical metabolic
disorders, and starvation.
Research methods, the importance of experiment in pathophysiology.

Pathophysiology is an experimental science. Therefore, its main method is an

experiment on living objects. Pathophysiological experiment, different from
physiological, modeling of human disease in laboratory animals. At present, it is
possible to reproduce in animals such pathological processes as traumatic shock,
diabetes, atherosclerosis, myocardial infarction, nephritis, and hypertension.
Meanwhile, we must not forget that the human body is much more complex and is
under the constant influence of social factors, and therefore get the full extent of human
disease in animals is almost impossible. You can reproduce only certain
pathogenetically important links, symptoms and syndromes of human disease.
Pathophysiological experiment, in contrast to clinical observation, has a number of
advantageous advantages. These benefits include the ability to:
1. Finding out the causal factors of the disease;
2. Observations from the period of pre-disease and the earliest stage of the disease to
the result;
3. Research of incurable forms of the disease;
4. Conducting experimental therapy.

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Chapter 2. Pathogenic effect of physical factors on the body

The effect of ultraviolet radiation

Pathogenic effect of excessive ultraviolet radiation:
- skin lesions cause its photochemical burns, with the development of erythema
and blisters on the skin, fever, headache, general pain; pathogenic effect is associated
with the activation of lipid peroxidation, which leads to damage to membranes, the
breakdown of protein molecules, cell death in general;
- lesions of the conjunctiva of the eyes (photoophthalmia), manifested by redness
and swelling, a burning sensation and "sand" in the eyes, tearing;
- can provoke exacerbation of some chronic diseases (rheumatism, gastric ulcer,
tuberculosis, etc.);
- due to the increased formation of melanin and the destruction of proteins, the
body's need for essential amino acids, vitamins, calcium salts, etc;
- excessive UV radiation in the wavelength range of region C can lead to
inactivation of cholecalciferol - to its conversion into indifferent (suprasterols) and even
harmful (toxisterins) substances;
- prolonged excessive UV radiation can promote the formation of peroxides and
epoxy substances that have a mutagenic effect, and induce the occurrence of basal cell
and squamous cell carcinoma of the skin, especially in people with fair skin;
- the effect on the nervous system is mediated through irradiated in the capillaries
of the skin blood proteins and cholesterol. There is excitation of the autonomic centers
of the hypothalamus and subcortical nodes, fever, increase and then decrease in blood
pressure, drowsiness, collapse and death from paralysis of the respiratory center.
Photosensitization - increased sensitivity to UV radiation. Photosensitizers can
enhance the effects of UV radiation. These include paints (methylene blue), cholesterol
and porphyrins, as well as contact photosensitizers (perfumes, lipsticks, creams, etc.).

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People with a high content of porphyrins in the blood due to impaired hemoglobin
conversion (for example, in hematoporphyria), even after a short stay in the sun, may
experience burns and a state of severe intoxication with toxic products of irradiated
porphyrins - photoallergy.
Harmful effects of thermal energy.
Exposure to high temperatures can cause burns, burns and overheating.
Burns (thermal) - local tissue damage as a result of flames, hot liquids, steam,
heated solids. According to the depth of tissue damage, there are 4 degrees of burns:
I degree - redness of the skin (erythema);
II degree - blistering;
IIIA degree - partial or complete necrosis of the germ layer of the skin;
IIIB degree - complete necrosis of the skin to its full thickness;
IV degree - necrosis of the skin, tendons, muscles.
The mechanism of burns is associated with the development of an inflammatory
reaction at the site of action of the thermal agent and coagulation of proteins, which
leads to cell death and tissue necrosis.
Burn disease - functional disorders of internal organs and systems due to large
(more than 10-15% of the body surface) and deep burns.
There are 4 periods of burn disease:
1. Burn shock - in the first 12-36 hours in the burn area sharply increases the
permeability of capillaries, this leads to a significant release of fluid from the vessels
into the tissues. A large amount of swollen fluid evaporates at the site of injury, the
volume of circulating blood decreases. Leading pathogenetic factors: hypovolemia,
pain and increased vascular permeability.
2. Burn toxemia - develops as a result of autointoxication by tissue breakdown
products at the burn site (denatured protein, biologically active amines, polypeptides,

13
etc.) and the production of specific burn autoantibodies (skin autoantigens specific for
this type are found in the skin);
3. Burn infection;
4. Burning exhaustion;
5. Recovery.

Overheating (hyperthermia) - an increase in body temperature due to the

accumulation of excess heat when exposed to high ambient temperatures.
The increase in body temperature is accompanied by:
- a sharp increase in respiratory movements (irritation of the respiratory center
with hot blood), develops shortness of breath;
- increase in heart rate and blood pressure;
- due to water loss due to increased sweating, blood thickens, electrolyte
metabolism is disturbed, hemolysis of erythrocytes increases;
- damage to various tissues leads to the accumulation of toxic products of their
decomposition;
- in connection with the destruction of VII, VIII, X and other plasma factors, blood
clotting is disturbed.
Overexertion of thermoregulatory mechanisms leads to their depletion, with
subsequent inhibition of central nervous system functions, respiratory depression, heart
function, lowering blood pressure and, as a consequence - to profound hypoxia.
Heat stroke - acute overheating of the body with a rapid rise in body temperature
or prolonged exposure to high ambient temperatures. Death from heat stroke occurs
from paralysis of the respiratory center.
Exposure to low temperatures can cause hypothermia and frostbite.
Hypothermia (hypothermia). In the pathogenesis of the following phases:
1. Compensation. Reactions are aimed at limiting heat transfer: reflex vasospasm,
decreased sweating, slow breathing. Increased heat production: muscle tremors (chills),

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increased glycogenolysis in the liver and muscles, increased blood glucose, increased
basal metabolism.
2. Decompensation (with prolonged exposure to low temperatures). Body
temperature decreases, muscle tremors stop, oxygen consumption and intensity of
metabolic processes decrease, peripheral blood vessels dilate. As a result of inhibition
of the functions of the cerebral cortex and suppression of the subcortical and bulbar
centers, blood pressure decreases, the heart rate slows down, progressively weakens
and the frequency of respiratory movements decreases. All vital functions gradually
fade away. Death occurs from paralysis of the respiratory center.
Hibernation - an artificial decrease in body temperature in medical practice, which
is achieved under anesthesia through physical exposure, is used to reduce the body's
need for oxygen and prevent temporary cerebral ischemia.
Freezing. The immediate cause of frostbite is the effect of low temperature on
the human body.
The depth of tissue frostbite can be:
• Frostbite of the I degree. The first signs are a burning sensation, tingling with
subsequent numbness of the affected area. Then there is itching of the skin and pain of
varying severity. The affected area of skin is pale, red after warming, sometimes with
a crimson-red tinge; edema develops. After a few days, there may be a slight peeling of
the skin. Complete recovery occurs within 5 - 7 days after frostbite.
• Frostbite of the II degree. After warming up the pain becomes more intense and
longer than with frostbite of the I degree, disturbed by itchy skin, burning. In the initial
period there is pallor, cooling, loss of sensitivity, the formation of blisters filled with
transparent contents. Complete restoration of the integrity of the skin occurs within 1-
2 weeks, granulation and scarring are not formed.
• Frostbite of the III degree. Prolonged intense pain. Blisters are formed in the
initial period, which are filled with blood, their bottom is blue-red, insensitive to
irritation. All skin elements die with the development of granulations and scars.
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Rejection of dead tissue ends in 2-3 weeks, followed by scarring, which lasts up to 1
month.
• Frostbite of the IV degree. All layers of soft tissues are damaged, bones and joints
are often affected. The damaged area of the limb is sharply bluish, sometimes with a
marble color. Absence of blisters at the developed considerable hypostasis, loss of
sensitivity testify to frostbite of the IV degree. The skin temperature is much lower than
in the surrounding areas of tissue.
Effects on the body of altered barometric pressure.

Influence of reduced barometric pressure (hypobaria). Hypobaria occurs in

humans when climbing mountains, when climbing to heights in leaky aircraft, in
spacecraft accidents, in pressure chambers.
At an altitude of 3-4 thousand meters (corresponding to the barometric pressure of
530-460 mm Hg) is the expansion of gases and increase their pressure in closed and
semi-closed body cavities, which leads to irritation of the wall receptors, causing pain
(especially eardrums) and mucous membranes of the middle and inner ear, maxillary
and frontal sinuses).
At an altitude of 9 thousand meters and more (corresponding to 225 mm Hg and
below) there are symptoms of decompression. This is due to the transition to a gaseous
state of oxygen dissolved in body fluids and, especially, nitrogen. The formed free gas
bubbles (gas emboli) spread through the vessels to different parts of the body, causing
embolism. This in turn leads to the development of tissue ischemia. Particularly
dangerous are emboli of coronary vessels and cerebral vessels.
Mountain sickness. At high altitudes, humans are affected by 4 main pathogenic
factors:
- reduced partial pressure of oxygen in the inhaled air (the main pathological
factor);
- increased sun exposure;

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 - cold;
- dryness of inhaled air.
Pathogenesis: oxygen deficiency causes a number of adaptive responses aimed at
maintaining a normal oxygen supply to organs and tissues, and, at the same time, to
more economical energy expenditure and life in conditions of oxygen starvation.
Compensatory reactions at the level of the organism:
- increased pulmonary ventilation;
- increase in oxygen capacity of blood (emission of erythrocytes from blood depots
- spleen, liver; at long stay in the conditions of hypoxia strengthening of erythropoiesis);
- increase in minute volume of circulating blood, acceleration of a blood-groove.
Compensatory reactions at the tissue level:
- capillarity increases;
- increases myoglobin;
- systems of regulation of redox processes are improved, etc.
Excess carbon dioxide in the blood excites the respiratory center. As a result of
hyperventilation in the blood the CO2 content decreases, as a result respiratory alkalosis
develops, the regulation of respiration is disturbed. In humans, the most sensitive and
vulnerable to hypoxia are brain tissues.
Explosive decompression usually occurs during rapid depressurization of the
aircraft at high altitudes (more than 16 km above sea level).
Pathogenesis: the partial pressure of oxygen in the inhaled air decreases sharply,
multiple gas embolism of tissues and organs joins (rapid formation of gas bubbles,
mainly nitrogen, due to a sharp decrease in its solubility in tissue and interstitial fluids).
There is an effect of "boiling" of blood, intercellular and even intracellular fluids, which
leads to rupture of blood vessels, lungs and other organs.
Influence of increased barometric pressure (hyperbaria).
There are two main types of hyperbaria: natural and artificial.

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 Artificial hyperbaria, performed for various purposes, occurs when a human or
experimental animal is in a pressure chamber (eg, hyperbaric oxygenation).
Natural hyperbaria - compression of the body when immersed in water (when
diving to great depths, diving and caisson work, in the fleet, especially underwater).
Periods (stages) of development of hyperbaria:
1. Immersion period (transition period from normal to high pressure). At
immersion under water already on depth of 20-40 m superficial vessels, a thorax, lungs
are compressed, blood supply of internals (including lungs, heart, brain) increases that
is followed by overstretching of walls of their vessels, up to a rupture, an indentation
(up to rupture) of the eardrum. Displacement and compression of internal organs, as
well as ruptures of lung tissue and even death are possible.

2. The period of saturation (the period of constant increased saturation of liquids

and tissues with gases as a result of increasing their solubility). Dissolved in plasma,
tissues (especially nerve and fat) nitrogen causes first euphoria, then - anesthesia and
finally - toxic effects. Toxic effects of nitrogen and oxygen are manifested by the
development of headache, dizziness, disorders of the cardiovascular system, damage to
the epithelium of the respiratory tract and alveoli, their surfactant layer, the
development of metabolic acidosis, seizures, and even death.
3. The period of desaturation (period of rise, or decompression, characterized by
the formation and increase of gas, especially nitrogen, bubbles in extracellular and
intracellular fluids). It develops during the transition of the organism from the area of
high pressure to normal atmospheric pressure. When the rules of lifting, caisson disease
develops. The faster the diver rises from the depths, the faster, in large quantities and
larger gas bubbles are formed (especially nitrogen and helium), because it goes from
dissolved to gaseous. Gas accumulates in the form of bubbles in the blood, extracellular
fluids, adipose and nervous tissues. Urgent care: placing the patient in a pressure
chamber (under strict medical supervision), creating a hyperbaria (with the required

18
amount and composition of the gas mixture), and then strictly controlled slow,
prolonged, gradual reduction of barometric pressure and the amount of inert gases in
the respiratory mixture.
Effect of electric current on the body
Features of harmful effects of current:
- damages tissues all the way;
- irritates a huge number of receptors;
- causes biological effect, chemical, mechanical, thermal damage.
-important is the direction of the current (through the heart or brain), the physical
properties of the current and the state of the organism;
Mechanism of current action:
1. Mechanical action is due to significant thermal and mechanical energy of high
concentration currents. The combined action of thermal and mechanical energy has an
explosive effect. Events:
• stratification of tissues;
• separation of body parts;
• formation of cut wounds;
• bone fractures, skull injuries.
2. Electrochemical action of current includes: electrolysis; polarization of cell
membranes; accumulation in some areas of positively charged ions, the occurrence of
an acid reaction and protein coagulation coagulation necrosis; on others negatively
charged ions accumulate, there is an alkaline reaction, there is a swelling of colloids,
there is a colic necrosis; movement of protein molecules; accumulation of toxic
electrolysis products; gases pass from the dissolved state to the gaseous state.
3. Thermal action is due to the conversion of electrical energy into heat with the
release of large amounts of heat in the tissues. Manifestations of thermal action of
current:

19
 • "pearl necklace" occurs when the bone substance melts with the release of
calcium phosphate;
• "signs of current" - areas of coagulated epidermis, having a round or oval shape,
gray-white color, solid consistency, bordered by roller-like elevations and depressions
in the center;
• branched red pattern due to paralysis of blood vessels.
Mechanisms of lethal outcome:
- cardiac arrest due to ventricular fibrillation; coronary vasospasm; lesions of the
vascular center; increase in tone n. vagus;
- respiratory arrest due to damage to the respiratory center; spasm a. vertebralis,
supplying blood to the respiratory center; spasm of the respiratory muscles,
laryngospasm, and hence impaired airway patency.

Harmful effect of ionizing radiation.

By their nature, all ionizing radiation is divided into electromagnetic (X-rays and
γ-rays that accompany radioactive decay) and corpuscular.
The pathogenesis of radiation damage includes the primary action of ionizing
radiation at the level of atoms and molecules, the action at the level of the cell and the
whole organism.
Primary action of IR at the level of atoms and molecules:
- Direct action of IR - energy absorption, excitation and ionization of atoms and
molecules, the formation of radicals. Free radicals cause chain chemical reactions,
interact with the most reactive protein structures of enzyme systems.
- Indirect action - the interaction of radicals with nucleic acids, proteins, lipids,
carbohydrates, active centers of enzymes. As a result, primary radio toxins are formed,
which inhibit the synthesis of nucleic acids. This, in turn, inhibits the activity of various
enzymes that increase the permeability of biological membranes and changes the

20
diffusion processes in the cell. As a result, there are violations of metabolic processes,
functional and structural damage to cells, organs and systems of the body.
Radiosensitivity of cells. Radiosensitive include cells that are actively dividing
and poorly differentiated cells: hematopoietic cells of the bone marrow, germ cells of
the testes, intestinal and cutaneous epithelium. Despite the differentiation, lymphocytes
have high radiosensitivity.
Radioresistant tissues include the brain, muscles, liver, kidneys, cartilage, and
ligaments.
The action of IR at the cell level: increased membrane permeability, activation and
release of lysosomal enzymes (DNAse, RNAse, cathepsin, phosphatase), inhibition of
tissue respiration, degenerative changes in the nucleus. Mitotic (reproductive) cell death
- the occurrence of chromosomal aberrations leads to disruption of DNA synthesis and
cell death at the time of mitotic division.
The effect of IR at the body level:
- Acute radiation sickness
- Chronic radiation sickness
- Local action of IR (radiation burns, cataracts, necrosis)
Long-term effects of IR: can develop in 10-20 years or more, after general or local
irradiation of the body.
There are somatic consequences (manifested in the irradiated organism):
- non-neoplastic forms - reduction of life expectancy, hypoplastic conditions in
hematopoietic tissue, mucous membranes of the digestive system, respiratory tract,
skin; sclerotic processes (liver cirrhosis, nephrosclerosis, atherosclerosis, radiation
cataracts), as well as dyshormonal conditions (obesity, pituitary cachexia, diabetes
mellitus).
- development of tumors, radiation leukemias.
Genetic consequences (as a result of germ cell damage) can be manifested by the
death of the zygote or embryo, the birth of individuals with hereditary abnormalities or
21
those who carry mutant genes. The "genetic burden" can be passed down from
generation to generation.
Acute radiation sickness occurs with total, single, uniform, external
irradiation of the body at a dose of more than 0.5 Gy.
There are 4 forms:
1. Bone marrow form occurs when irradiated in doses of 0.5-10 Gy. Depending
on the dose, there are 4 degrees of severity of the bone marrow form: I - mild (1-2 Gy);
II- medium degree (2-4 Gy); III- severe (4-6 Gy); IV- extremely severe (more than 6
Gy).
In its course, the bone marrow form goes through 4 periods:
- period of primary reactions - occurs in the first minutes or hours after irradiation.
The duration of the phase is 1-3 days. Manifestations: agitation, headache, general
weakness; dyspeptic disorders (nausea, vomiting, loss of appetite); lability of
autonomic functions - fluctuations in blood pressure, heart rate; activation of the
pituitary-adrenal system, increased secretion of hormones of the adrenal cortex; at
doses of 8-10 Gy there is the development of a shock-like state with a decrease in blood
pressure, short-term loss of consciousness, fever, diarrhea. Peripheral blood:
neutrophilic leukocytosis with a shift to the left, absolute lymphopenia.
- period of imaginary well-being - inclusion in the pathological process of the
body's defense mechanisms. The duration depends on the radiation dose and ranges
from 10-15 days to 4-5 weeks. In very severe forms of the lesion, this phase is absent.
Manifestations: the well-being of patients becomes satisfactory, visible clinical signs
fade. Peripheral blood: lymphopenia progresses on the background of leukopenia, the
number of reticulocytes and platelets decreases. Devastation (aplasia) develops in the
bone marrow.
- the period of exacerbation of the disease - a sharp deterioration in health. The
duration of the phase is from several days to 2-3 weeks. When irradiated more than 2.5

22
Gy, death is possible. Manifestations: weakness, fever; there are bleeding and
hemorrhages in the skin, mucous membranes, gastrointestinal tract, brain, heart and
lungs; decreased body weight, hypoproteinemia. Peripheral blood: leukopenia,
thrombocytopenia, anemia, increased ESR. In the bone marrow - a picture of
devastation with the initial signs of regeneration. Infections as a result of decrease in
immunity join.
- recovery phase - gradual normalization of impaired functions. Duration 3-6
months, in severe cases 1-3 years, can become chronic. Manifestations: the general
condition significantly improves, the temperature normalizes, hemorrhagic and
dyspeptic manifestations disappear, after 2-5 months the function of sweat and
sebaceous glands is normalized, hair growth is restored. Peripheral blood: blood and
metabolism are restored.
2. Intestinal form occurs when irradiated with 10-20 Gy. Manifestations: nausea,
vomiting, bloody diarrhea, increased t0 of the body, there may be complete paralytic
intestinal obstruction and bloating. Hemorrhages and deep leukopenia with complete
absence of lymphocytes, a picture of sepsis develop. Death as a result of dehydration,
which is accompanied by loss of electrolytes and protein, shock.
3. Cerebral form of GPC occurs when irradiated in doses of 20-50 Gy, death in 1-
3 days. Manifestations: convulsive-paralytic syndrome, circulatory disorders,
lymphatic circulation in the CNS, vascular tone and thermoregulation, digestive and
urinary systems; progressive decrease in blood pressure. The cause of death - the death
of cells of the cerebral cortex, neurons, nuclei of the hypothalamus.
Chronic radiation sickness occurs with prolonged exposure of the body in small,
but exceeding acceptable doses. The disease is characterized by gradual development
and a long wave-like course, the timing and nature of the changes are determined by
the intensity and total dose. The development of unstable leukopenia, signs of asthenia,
autonomic vascular instability, and others characterize the initial period of the disease.
Extensive period of the disease is characterized by a lack of physiological regeneration
23
of the most radiosensitive tissues in combination with functional changes in the nervous
and cardiovascular systems. The smoothing of destructive and a clear predominance of
reparative processes in the most radio-damaged tissues characterize the recovery
period.

24
 Chapter 3. The role of heredity and constitution in human pathology
Hereditary diseases are diseases that are caused by a violation of hereditary
information as a result of a mutation process and are acquired by the human body with
the germ cells of the parents.
Congenital diseases manifest themselves from birth. They can be caused by both
hereditary and external, teratogenic influences.
Classification of hereditary diseases. Depending on the extent of violations of the
amount of genetic information, hereditary diseases are divided into 3 major groups:
monogenic, polygenic and chromosomal.
A mutation is a permanent DNA damage. Classification: spontaneous (occur
spontaneously, without the influence of external factors) and induced (caused
artificially by the action of external factors called mutogens); somatic (occur in somatic
cells) and sexual (occur in germ cells); useful, harmful, neutral; genomic, chromosomal
and genetic.
Causes of mutations - mutagens. Classification:
- physical mutagens: all types of ionizing radiation, ultraviolet rays and fever.
- chemical mutagens: a) deaminating agents (nitrous and nitric acid, as well as
other nitro compounds); b) substances that are capable of transferring alkyl (methyl,
ethyl, etc.) to DNA molecules; c) compounds of nitrogenous bases (5-bromurocyl, 2-
aminopurine, etc.); d) compounds that are embedded in the DNA molecule and cause
violations of its configuration (Acredin and its derivatives).
- biological mutagens - viruses.
Chromosomal diseases are hereditary diseases that are caused by genomic
(changes in the number of chromosomes) and chromosomal (changes in the structure
of chromosomes) mutations.
Chromosomal mutations:
1. deletion - the loss of individual sections of chromosomes;
2. duplication - doubling of individual sections of chromosomes;
25
 3. translocation - the transfer of a site from one chromosome to another;
4. inversion - rotation of a part of a chromosome on 1800.
There are chromosomal diseases caused by:
1) changing the number and structure of autosomes;
2) by changing the number of sex chromosomes.
Chromosomal diseases caused by changes in the number and structure of
autosomes. Is a consequence of chromosome mismatch in gametogenesis.
Down syndrome - trisomy on chromosome 21, karyotype 47 XX (XU) + 21.
Clinical diagnostic signs: short stature, varying degrees of mental retardation,
craniofacial anomalies: "Mongoloid" incision of the eyes, short neck, face, epicanthus,
plaque small short nose, large tongue, small deformed ears. Also characteristic are
muscular hypotension, loose joints, transverse folds on the palms, clinodactyly of the
little finger. Congenital malformations of the internal organs (heart), reduced immunity
are often the cause of death of these children.
Patau syndrome - trisomy on chromosome 13, karyotype 47 XX (XU) + 13.
Clinical diagnostic signs: cleft upper lip and palate ("hare's lip" and "wolf's mouth"),
reduced skull volume, low forehead, microphthalmia, anophthalmia (absence of one or
both eyeballs), deformed auricles, polydactyly; congenital defects of the heart and other
internal organs. Most babies die in the first weeks or months.
Edwards syndrome - trisomy on chromosome 18, karyotype 47 XX (XU) + 18.
Clinical diagnostic signs: abnormalities of the brain and facial skull, the skull has a
dolichocephalic shape; heart and large vessel defects; hypoplasia of the cerebellum and
corpus callosum, changes in the structures of oils, severe mental retardation, decreased
muscle tone.
Chromosomal diseases caused by changes in the number of sex chromosomes.
Shereshevsky-Turner syndrome (karyotype 45XO). Clinical diagnostic signs:
female phenotype; short stature, short neck with lateral folds of skin (sphinx neck),
primary amenorrhea, infertility. There is no mental retardation.
26
 Klinefelter's syndrome (karyotype 47XXU). Microscopic examination reveals 1
Barr's body, male sex. Clinical signs: tall stature, long limbs, eunuchoidism,
gynecomastia (enlargement of the mammary glands), lack of spermatogenesis,
underdevelopment of the gonads, mental retardation.

Trisomy on the X chromosome (karyotype - 47XXX, superwoman). Microscopic

examination reveals 2 Barr bodies. In such patients there is a slight mental retardation
and underdevelopment of the ovaries and, consequently, a disorder of sexual
development.
Genetic diseases are caused by gene mutations. Types of inheritance of genetic
diseases: autosomal dominant, autosomal recessive, X-linked (dominant and recessive),
Y-linked.
Autosomal dominant type of inheritance. The action of the mutant gene is
manifested in both homo- and heterozygous states. Sick girls and boys are born with
the same frequency. For example: brachydactyly, syndactyly, Huntington's disease,
Marfan's syndrome, neurofibromatosis.
Autosomal recessive type of inheritance. The action of the mutant gene is
manifested in a homozygous state. Diseases caused by defects in enzyme proteins such
as enzymopathy (phenylketonuria, alkaptonuria, albinism, etc.) are transmitted by this
type of inheritance.
Recessive type of inheritance linked to the X chromosome. The effect of the
mutant gene is manifested only in the XU set, ie only in boys, women are carriers of
the pathological gene. For example: hemophilia, color blindness and some types of
muscular dystrophy.
Dominant type of inheritance linked to the X chromosome. The pathological gene
is manifested in any variant of the set of sex chromosomes: XX, XU, XO.
Manifestations do not depend on sex, but are more severe in boys. A sick father has all
sons - healthy, all daughters - sick. From the mother, the pathological gene is passed on

27
to half of the daughters and sons. For example: phosphate-diabetes, vitamin-D-resistant
rickets.
Multifactorial diseases - diseases with a hereditary predisposition caused by a
combination of genetic and non-genetic factors (external environment). Such diseases
include: atherosclerosis, gout, rheumatism, coronary heart disease, hypertension,
epilepsy, gastric and duodenal ulcers, liver cirrhosis, diabetes, asthma, tuberculosis,
psoriasis, schizophrenia.
Methods of studying hereditary diseases:
1. Genealogical - the study of pedigrees of families in a number of generations;
2. Gemini;
3. Population-statistical;
4. The cytological method allows to carry out research of a karyotype in nuclei of
dividing cells, to study sexual chromatin in cells of a mucous membrane of an oral
cavity, to investigate a phenomenon of "drumsticks" in nuclei of neutrophils;
5. Biochemical method is used as a method of rapid diagnosis of hereditary
metabolic diseases;
6. Molecular genetic - DNA diagnostics.
Types of disorders of fetal development depending on the time of their occurrence:
1. Gametopathies occur before fertilization, during the process of gametogenesis.
2. Blastopathy - pathologies that are formed in the first 15 days of embryonic
development.
3. Embryopathies - disorders that cover a complex of pathologies that occur after
the differentiation of the embryoblast to the end of the bookmark organs (16 days to 12
weeks).
4. Fetopathy - a violation of fetal development. Neonatologists distinguish
between pathology of early fetogenesis, when the formation of thin structures of tissues
and organs and fetal viability (12 weeks - 7 months), as well as disorders of late

28
fetogenesis, when the process of fetal function and placental aging (7 months - before
birth).
The Constitution is a complex of morphological, functional and mental features
of an organism which have developed on a hereditary basis under the influence of
environmental factors and defines its reactivity and resistance.
Classification of constitutional types:
- according to Hippocrates: sanguine, choleric, phlegmatic, melancholic;
- by type of Nervous Activity (Pavlov IP): strong balanced mobile, strong
unbalanced excitable, strong balanced calm, weak;
- according to Chernorutsky: hypostenic, hypersthenic, normosthenic;
- according to Kretschmer: athletic, picnic, asthenic;
- according to Sigo: respiratory, digestive, muscular, cerebral;
- according to Bogomolets: asthenic, fibrous, lipomatous.
Aging is a biologically destructive process that develops with age and leads to
limited adaptation of the body, the emergence of age-related pathology and increase the
likelihood of death.
Theories of aging. Currently, there are the following groups of theories that
explain the causes of aging.
1. Theories of genetically programmed aging.
2. Theories of damage accumulation.
3. Synthetic theories of aging (generally combining the first and second type).
Basic laws of the aging process.
1. Heterochronism - different times of appearance of age-related changes
in different tissues, organs and systems.
Thus, the involution of the thymus gland begins at the age of 13-15 years, and the
involution of the gonads - at the age of 48-52 years.
2. Heterotopicity - unequal severity of the aging process in different organs and
structures of the same organ.
29
 For example, aging of the fascicular zone of the adrenal cortex is less pronounced
than glomerular and reticular.
3. Heterokineticity - the development of age-related changes with a personal
speed. In some organs, age-related changes develop early, slowly and smoothly, in
others - later, but rapidly.
Progeria is a pathological aging that occurs as a result of the action of pathogenic
factors on the body. An example is Hutchinson-Guildford syndrome. It is an autosomal
recessive inherited disorder. Its first signs appear very early, already in the first year of
life. Characterized by growth retardation, graying of hair, baldness, the skin becomes
senile, cataracts, atherosclerosis develop. Death usually occurs within 1-2 decades of
life.

30
Topic 4. The role of reactivity and resistance in pathology

Reactivity is a property of an organism to react to the action of environmental

factors.

Classification of types of reactivity:

A) Species, group, individual.

Species reactivity - a set of reactivity features characteristic of this species of

living beings. For example, animals are indifferent to the pathogens that cause
whooping cough, scarlet fever, and humans are indifferent to the pathogens that cause
swine fever in pigs.
Group reactivity is formed on the basis of species and is divided into age, sex and
constitutional. Age reactivity determines the specificity of reactions to stimuli,
characteristic of this age. In particular, newborns compared to adults have a greater
ability to maintain bioenergy through anaerobic glycolysis; adults do not get whooping
cough. Sexual reactivity is determined by the reactive features inherent in this article:
for example, women are more resistant to blood loss and pain, and men - to exercise.
Constitutional reactivity is determined by heredity and long-term influence of
environmental factors that form stable morpho-functional features of the organism. In
particular, normosthenics and hypersthenics are more resistant to prolonged and
increased physical and emotional stress compared to asthenics.
A typical example of the manifestation of individual reactivity are allergic
reactions in individuals.
B) Nonspecific and specific reactivity.
Specific reactivity (immunological reactivity) is manifested by the development
of immunity to antigenic stimulation. Specific reactions form in the patient a

31
characteristic clinical picture of each nosological form (for example, lesions of
hematopoietic organs in radiation sickness; spasm of arterioles in hypertension).

Nonspecific reactivity is manifested by general programmed standard reactions

characteristic of many diseases (development of fever, hypoxia, activation of
phagocytosis and the complement system, etc.).
Complement system. This is a system of serum proteins, the sequential activation
of which as a result of limited proteolysis reactions causes damage to bacterial cell
membranes and leads to lysis. The complement system consists of 11 proteins that form
9 fractions.
C) Physiological and pathological reactivity.
Physiological reactivity is the reactivity to physiological stimuli in adequate
conditions of existence of the organism. It has a protective and adaptive nature and is
aimed at maintaining the dynamic stability of the internal environment of the organism
and the full interaction of the organism with the environment.
Pathological (painfully altered) reactivity - reactivity that occurs as a result of
exposure to a pathogenic stimulus and is characterized by reduced adaptation of the
body to the environment (eg, allergic reactions).
D) According to the severity of the process, where there are hyperergic
reactivity, hypoergic and dysergic (increased, decreased, perverted).
Normergic reactivity is characterized by a reaction adequate to the nature and
strength of the influence of this factor.
Hyperergic reactivity - increased reactivity, which is manifested by an excessive
reaction to a pathogenic factor (for example, the occurrence of anaphylactic shock in
response to repeated, often parenteral administration of a specific antigen). In
hyperergy, the processes of excitation dominate, and in hypoergy - inhibition, as well
as parabiosis.

32
 Hypoergic reactivity - reduced reactivity of the organism, characterized by a weak
response to the influence of any agent (weak immune response to the antigen in the
presence of secondary immunodeficiency).

Anergy - the lack of reactions of the body to any stimuli, indicating a deep violation of
the body's systems, designed to form a response to the effects of any agent.
Resistance is the body's resistance to pathogenic factors of the external and
internal environment.
Types of resistance: passive and active.
Passive resistance is resistance to the action of a pathogenic factor, immunity to
it. It occurs when it is impossible or difficult for the body to interact with a pathogenic
agent. Passive resistance is independent and is provided by the following mechanisms:
cell reactivity, physical and physicochemical factors, biological barriers.
Active resistance is resistance, which is due to a set of protective and adaptive
reactions aimed at destroying the pathogen and the consequences of its action. Active
resistance is energy dependent and is based on phagocytosis and the compliment
system.
Biological barriers of an organism are one of mechanisms of resistance which
serve for protection of an organism or its separate parts, prevent disturbance of stability
of internal environment at action on an organism of the factors capable to destroy this
constancy - physical, chemical and biological properties of blood, lymph, fabric liquid.
Conditionally distinguish between external and internal barriers.
The external barriers include:
1. Skin, which protects the body from physical and chemical changes in the
environment and is involved in thermoregulation.
2. Outer mucous membranes, which have strong antibacterial protection, secreting
lysozyme. Antimicrobial protein - immunoglobulin A, secreted by mucous membranes
and immune organs (in the absence of immunoglobulin A - inflammatory diseases).

33
3. Gastrointestinal barrier - bactericidal action of gastric juice + lysozyme and
immunoglobulin A, then the alkaline reaction of the duodenum - is the first line of
defense.
Internal barriers regulate the flow of necessary energy resources from the blood to
the organs and tissues and the timely outflow of cellular metabolic products, which
ensures the stability of the composition, physicochemical and biological properties of
tissue (extracellular) fluid and maintaining them at a certain optimal level.
Internal barriers include barrier organs (liver) and histohematological (separating
tissue and blood). Histohematic barriers are divided into non-specialized (capillary
wall) and specialized.
Specialized barriers differ from the first in that they include additional structures
that have a noticeable effect on their permeability. Specialized barriers include
hematoencephalic, hematoophthalmic, hematocochlear, hematothyroid,
hematotesticular and hematoovarian.
The blood-brain barrier is a physiological mechanism that selectively regulates
metabolism between the blood and the central nervous system, preventing the
penetration of foreign substances and intermediate products into the brain. It provides
the relative stability of the composition, physical, chemical and biological properties of
the cerebrospinal fluid and the adequacy of the microenvironment of individual nerve
elements.
Immunological reactivity - the ability of an organism to respond to the introduction
of antigens by the formation of antibodies and a complex of cellular reactions specific
to this antigen.
There are two mechanisms of immunological reactivity: cellular and humoral.
The cellular type of immune is represented by T-killer lymphocytes.
The humoral type of immune response is represented by antibodies
(immunoglobulins) - products of synthesis of B-lymphocytes.

34
 Antigens are substances, mainly of a proteinaceous nature, that, when ingested,
are able to elicit an immune response and interact with the products of that response by
antibodies or activated T lymphocytes.
Antibodies are proteins (immunoglobulins) that are synthesized under the
influence of antigens and specifically interact with them.
Cells involved in the immune response: macrophages, B-lymphocytes, T-
lymphocytes.
Immunological insufficiency - a congenital or acquired defect of the immune system,
which is manifested by the inability of the body to fully carry out the reactions of
humoral and cellular immunity.
Primary immunological insufficiency and its causes. Primary immunological
insufficiency occurs due to congenital defects of the immune system. Depending on the
level of disorders and the location of the defect in the process of hematopoiesis, the
following types of primary immunodeficiency are distinguished:
1) combined immunodeficiency,

2) cellular or T-cell immunodeficiency,

3) humoral or B-cell immunodeficiency.

Combined primary immunodeficiency:
a) Louis-Barr syndrome. There is a combination of immunological insufficiency with
ataxia (impaired coordination of movements) and telangiectasia (lesion of small
vessels). The average life expectancy of patients is up to 20-25 years.
b) Viscott-Aldrich syndrome. Immunological insufficiency is accompanied by the
development of skin lesions and thrombocytopenia. Humor and cellular mechanisms of
the immune response suffer. Life expectancy does not exceed 10 years.
Primary T-cell immunodeficiency.
Arise because of disturbance of processes of formation and differentiation of T
lymphocytes. The most common are: Di-Georgie syndrome - congenital aplasia of the
35
thymus. The differentiation of T-lymphocyte progenitor cells into T-lymphocytes is
disturbed. There is no cellular immune response, but the humoral response to thymus-
independent antigens is preserved.
Primary B-cell immunodeficiency.
Arise because of disturbance of formation and differentiation of B-lymphocytes.
This group of diseases includes Bruton's hypogammaglobulinemia. The hereditary
defect is transmitted linked to the X chromosome, so it manifests itself in boys. The
differentiation of B-lymphocyte progenitor cells is disturbed. The T-system of
lymphocytes is not disturbed, cellular immunity is preserved.
Secondary immunological insufficiency is called acquired immunological
insufficiency (immunosuppressive states). The reasons for its occurrence can be
ionizing radiation, drugs - corticosteroids, cytostatics, protein starvation, tumor growth,
B12 vitamin deficiency, HIV, aging, nephrotic syndrome.
HIV affects cells that have the CD4 receptor protein on the membrane. This protein is
able to interact with the protein - glycoprotein of the viral envelope GR-120. The
immunodeficiency virus mainly affects T-helpers (each cell has about 10,000 CD4
receptors).
Immunological tolerance - this state of specific immunological reactivity to this
antigen, due to previous contact with this antigen. The ability of the body to give a full
immune response to all other antigens is preserved.

36
Topic 5. Allergy

Allergy - an immune reaction (qualitatively altered immune response),

accompanied by damage to the body's own tissues.
Causes of allergies - allergens.
Classification of allergens: exoallergens and endoallergens.
Exoallergens:
1) infectious: a) bacterial, b) viruses, c) fungi,
2) pollen of flowering plants, poplar down, dandelion, ragweed, cotton,
3) household - detergents, house and library dust, as a product of the life of a house
mite, specific to a particular apartment,
4) food - especially in children - cow's milk, chicken eggs, chocolate, citrus fruits,
strawberries, fish, crabs, lobsters, cereals,
5) drugs - especially medical serums, antibiotics, vitamins,
6) products of chemical synthesis.
Endoallergens:
1) natural (primary): lens and retina, nervous system tissue, thyroid gland, male gonads,
2) acquired (secondary), induced from their own tissues under the influence of external
influences: infectious, non-infectious (cold, burns, irradiation).
Classification of allergic reactions:
1. At the time of the reaction after re-entry of the allergen (according to Cook):
- Allergic reactions of immediate type (hypersensitivity of immediate type) - I, II, III -
develop in 15-20 minutes after repeated receipt of an allergen.
- Allergic reactions of the delayed type (hypersensitivity of the delayed type) - IV -
develop in 24-48 hours after repeated receipt of an allergen.
2. On the pathogenesis (according to Coombs and Jell):
- I. Anaphylactic;
- ІІ. Cytotoxic;
37
- ІІІ. Immunocomplex;

- IV Delayed type hypersensitivity.

General pathogenesis of allergic reactions:
I. Immunological stage
1. Formation of antibodies or sensitized T-lymphocytes at primary contact with the
allergen (sensitization);
2. The formation of complexes allergen + antibody (type I, II, III) or allergen +
sensitized-T-lymphocyte (type IV) upon repeated contact with the allergen.
II. Pathochemical stage. It is characterized by the release, activation, synthesis of
biologically active substances - allergy mediators.
III. Pathophysiological stage (stage of clinical manifestations). Characterized by
structural and functional changes in organs and tissues:
• vasomotor reactions (local and systemic), leading to changes in blood pressure,
peripheral circulation and microcirculation;
• increased permeability of vessel walls, which leads to the development of edema;
• spastic contractions of the smooth muscles of the bronchioles, intestines, which may
be manifested by asphyxia, dyspeptic disorders;
• imbalance between coagulation factors, anticoagulant and fibrinolytic blood systems,
which can lead to both hemorrhagic syndrome and thrombosis;
• irritation of nerve receptors, which leads to the development of pain, itching, burning;
• inflammatory reactions accompanied by significant cellular tissue infiltration.
Sensitization - the formation of hypersensitivity to this allergen. It is characterized
by the formation of specific antibodies or sensitized T lymphocytes to a specific
allergen. Clinically sensitization is not manifested. The state of sensitization can be
detected by allergic tests.
There are active (develops 10-14 days after the allergen enters the body; the body's
immune system is actively involved in the formation of specific antibodies or sensitized

38
T-lymphocytes) and passive sensitization (develops after the introduction of serum
containing finished antibodies, or cell suspension with sensitization T-lymphocytes,
while the body's own immune system is not involved in the formation of antibodies and
sensitized T-lymphocytes).
ALLERGIC REACTION OF TYPE I (anaphylactic)
Immunological stage: allergen AG → recognition of allergens by dendritic cell
(DC) → reading information, its processing, isolation of hypertension determinants and
its incorporation into the membrane of DC → activation of T-helpers (Th0) →
formation of Th2 → B-lymphocytes → transformations of B-lymphocytes cells →
synthesis of antibodies - immunoglobulins Ig E, G4 → fixation of antibodies on the
surface of mast cells (antibodies with their end Fc (constant fragment) are fixed on the
corresponding receptors of mast cells and basophils, vascular nerve receptors, intestinal
smooth muscle and blood cells → re-contact with allergen → formation of allergen-
antibody complexes on the surface of mast cells (Fab (antigen-binging fragment)
antibody fragment binds to hypertension, and 1 molecule of IgE can bind 2 molecules
of AG).
There is an activation of the cell and the transition of the process to a
pathochemical stage, which includes degranulation of mast cells and the release of
granules from them: histamine, heparin, chemotaxis factors of eosinophils and
neutrophils; formation of leukotrienes and prostaglandins from membrane
phospholipids; migration to the zone of allergic reaction of eosinophils, neutrophils and
their release of secondary mediators: histaminase, arylsulfatase, protease,
phospholipase.
Pathophysiological stage: spasm of bronchial smooth muscle → bronchospasm;
vasodilation → arterial hyperemia; increase in permeability of a vascular wall →
hypostasis; hypersecretion of mucus, irritation of nerve endings → itching, pain.
Clinical forms: urticaria, hay fever, Quincke's edema, bronchial asthma, anaphylactic
shock.
39
 TYPE II ALLERGIC REACTION (cytotoxic)
Immunological stage: allergen (altered components of cell and basement
membranes (autoallergens) → recognition of allergens by dendritic cell (DC) →
reading information, its processing, isolation of hypertension determinants and its
incorporation into the membrane of DC → activation of T-Th2 helpers) B-lymphocytes
→ transformation of B-lymphocytes into plasma cells → synthesis of Ig G1,2,3, IgM
→ fixation of antibodies on the surface of target cells → upon repeated contact with
the allergen formation of allergen + antibody complex on their surface.
Pathochemical stage: activation of complement components; release of lysosomal
enzymes and superoxide radicals (O, OH, H2O2) during phagocytosis; granzyme,
perforin from NK cells.
Pathophysiological stage. Lysis of target cells, destruction of basement
membranes:
1. Complement-dependent cytolysis (activation of individual fragments of complement
components): C3a, C5a - neutrophil chemotaxis and phagocytosis; C5b-C9 - the
formation of channels in the cell membrane and osmotic lysis of cells.
2. Complement Independent cytolysis (the role of opsonins is performed by antibodies
(IgG).
3. Antibody-dependent cellular cytotoxicity (activated NK cells that have receptors on
their surface to the Fc fragment of antibodies).
Clinical forms: blood transfusion shock, hemolytic disease of newborns,
autoimmune thrombocytopenic purpura, autoimmune agranulocytosis, Dressler's
syndrome (postinfarction myocarditis), acute rheumatic fever, hyperthyroidism,
allergy.
ALLERGIC REACTION OF TYPE III (immunocomplex)
Immunological stage: allergen (soluble proteins, drugs, therapeutic sera) →
recognition of allergens by dendritic cell (DC) → reading information, its processing,
isolation of hypertension determinants and its incorporation into the membrane of DC
40
→ activation of T-helpers (Th2 →) B-lymphocytes → transformation of B-
lymphocytes into plasma cells → synthesis of precipitating antibodies - Ig G; Ig M →
upon repeated contact with the allergen formation of soluble complexes → fixation of
allergen + antibody complexes on the walls of microvessels.
Pathochemical stage: activation of complement components; chemotaxis of
granulocytes and macrophages (C3a, C5a); activation of phagocytosis (C3b) and
release by phagocytes of lysosomal enzymes and superoxide radicals; activation of
mast cells (C3a, C5a), their degranulation and release of histamine, heparin,
chemotactic factors; isolation of Hagemann factor in vascular endothelial damage by
immune complexes; and activation with it kallikrein-kinin system, coagulation systems,
anticoagulation and fibrinolysis.
Pathophysiological stage. Circulating immune complexes are deposited in the
vessels of the glomeruli of the kidneys and cause various types of glomerulonephritis,
in the lungs - alveolitis, in the skin - dermatitis. In severe cases, inflammation may take
an alternative nature with tissue necrosis, partial or complete thrombosis, hemorrhage.
Initially, the focus is dominated by neutrophils, which actively phagocytose immune
complexes, releasing lysosomal enzymes and factors that increase permeability and
chemotaxis for macrophages. Macrophages accumulate in the site of inflammation and
phagocytose the destroyed cells, clearing the affected area. Inflammation ends with the
proliferation of cellular elements.
Clinical forms: serum sickness, nodular periarteritis, Arthus phenomenon,
poststreptococcal glomerulonephritis, vasculitis, systemic lupus erythematosus,
rheumatoid arthritis, etc.
TYPE IV ALLERGIC REACTION (delayed type hypersensitivity)
Immunological stage: allergen → recognition of allergens by dendritic cell (DC)
→ reading information, its processing, isolation of hypertension determinants and its
incorporation into the membrane of DC → activation of T-helpers (Th0) →
accumulation of Th1 clones (sensitized T-lymphocytes), lymphocytes which are built-
41
in structures that act as blood pressure, able to bind to the corresponding allergen →
when re-application of the allergen T-lymphocytes diffuse from the bloodstream to the
site of application and bind to the allergen, which is located on target cells.
Pathochemical stage: lymphocytes release lymphokines, NK cells secrete
granzyme and perforin.

Pathophysiological stage: development of foci of allergic exudative inflammation

of dense consistency.
Clinical forms: contact dermatitis, infectious-allergic diseases (tuberculosis,
brucellosis, syphilis, fungal diseases); tuberculin reaction; graft rejection reaction.
Hyposensitization - a decrease in the body's sensitivity to the allergen. There are
specific and nonspecific hyposensitization.
Specific hyposensitization - is achieved by the introduction of the allergen that
caused the allergy (the introduction of serum by the method of AM Bezredko). Specific
hyposensitization is effective for type I allergic reactions.
Nonspecific hyposensitization - is achieved by changes in the reactivity of the
organism (normalization of the neuroendocrine system: working conditions, rest,
nutrition, reflexology, physiotherapy; administration of drugs (antihistamines,
corticosteroids, leukotriene receptor blockers).
Pseudoallergic reactions - a group of reactions similar in manifestation to
allergies, but characterized by the absence of an immunological stage. They develop
under the influence of factors that cause degranulation of mast cells and the release of
biologically active substances.
Development mechanisms:
• Histamine: degranulation of mast cells, impaired histamine inactivation, increased
intake of histamine with food, dysbacteriosis.
• Violation of complement system activation: excessive activation of the complement
system, deficiency of complement inhibitors.

42
• Metabolic disorders of the arachidonic system: imbalance between prostaglandins and
leukotrienes (aspirin use).

43
 PART II
TYPICAL PATHOLOGICAL PROCESSES

Chapter 1. Peripheral blood circulation and microcirculation disorders

Arterial hyperemia - an increase in blood supply to an organ or area of tissue due

to increased inflow of arterial blood.
Reasons:
- physical (temperature, UV radiation);
- chemical (turpentine, mustard powder);
- biological (toxins and mediators);
- psychogenic (emotions).
Types:
- physiological (develops in connection with the increased need of tissue for
oxygen and nutrients): working (functional) - due to the metabolic needs of the body or
tissue in connection with the increase in their functioning. For example, hyperemia in
the muscle during physical activity, hyperemia of the pancreas and intestinal wall at the
time of digestion, hyperemia of the endocrine gland during secretion, hyperemia of the
salivary glands. The increase in the contractile activity of the myocardium leads to an
increase in coronary blood flow, activation of the brain is accompanied by an increase
in its blood supply. Reactive (post-ischemic) arterial hyperemia is observed after
temporary cessation of blood flow (temporary ischemia) and has a protective and
adaptive nature (removal of the tourniquet).
- pathological - develops in pathological processes such as allergies, fever,
inflammation.
Leading link of pathogenesis: expansion of arterioles and increase in inflow of
arterial blood.
The mechanism of dilation of arteries:
44
- neurogenic: decreased tone of vasoconstrictors (neuroparalytic), increased tone of
vasodilators due to acetylcholine (neurotonic);

- humoral (myoparalytic) - vasodilation with BAS: histamine, bradykinin, lactic

acid, excess carbon dioxide, nitric oxide, adenosine, hypoxia, some prostaglandins, etc.
Manifestations of arterial hyperemia:
- redness of the tissue due to an increase in the number of functioning capillaries
and arterialization of venous blood;
- local increase in temperature (increase in arterial blood flow and intensification
of redox processes in the tissue;
- increase in tissue turgor (vasodilation, increased blood supply);
- dilation of arterioles, increase in blood flow velocity, increase in intracapillary
pressure, increase in the number of functioning capillaries.
Consequences: - positive: improved delivery of oxygen and nutrients to the body,
increased metabolic processes and organ function; - negative: rupture of a vessel with
hemorrhage in the presence of pathology, generalization of infection, progression of
tumor growth and metastasis.
Venous hyperemia - an increase in blood supply to an organ or area of tissue due
to difficulty in the outflow of venous blood.
Reasons:
- venous thrombosis;
- compression of the veins from the outside by a tumor, enlarged uterus during
pregnancy, scar, exudate, tourniquet;
- violation of general hemodynamics in right ventricular heart failure;
- constitutional insufficiency of the valvular apparatus of the veins.
Leading link in the pathogenesis: difficulty in the outflow of venous blood.

45
 Mechanism of development: circulatory hypoxia → cell damage → cell death →
sclerosis; local intoxication due to accumulation of lactic acid, carbon dioxide →
metabolic acidosis
Manifestations of venous hyperemia:
- cyanosis of the tissue due to an increase in blood restored hemoglobin;
- local decrease in temperature (decrease in regenerative processes in fabric,
increase in heat transfer);
- increase in the volume of the body (increased blood supply, edema);
- varicose veins and capillaries, slowing blood flow;
- increase in fluid filtration, decrease in its reabsorption, difficulty of lymph
outflow.
Consequences: - positive: slowing down the development of the local infectious
process, facilitating the migration of leukocytes into the site of inflammation; negative
- atrophy of parenchymal elements, connective tissue growth and the development of
multiple sclerosis.
Ischemia is a decrease in the blood supply to an organ or area of tissue due to a
decrease in arterial blood flow.
Reasons:
- compression of the arteries from the outside,
- thrombosis and embolism of arteries,
- angiospasm of the arteries,
- atherosclerotic damage to the inner lining of the arteries.
TYPES:
1. Compressive.
2. Obstuctive.
3.Angiospastic.
Leading link of pathogenesis: reduction of arterial blood flow.

46
 Mechanism of development: disturbance of energy metabolism: ↓ O2 →
disturbance of oxidative phosphorylation in mitochondria → ↓ ATP → disturbance of
contractile and secretory functions of cells, disturbance of active transport of substances
→ necrosis, strengthening of biosynthesis of connective tissue components → sclerosis.
Manifestations of ischemia:
- pallor of the tissue due to the reduction of blood supply and the number of
functioning capillaries;

- local decrease in temperature (decrease in inflow of warm arterial blood,

decrease in redox processes in fabric);
- pain or paresthesia (irritation of nerve endings by metabolic products) (H +, K
+);
- reduction of the body in size (reduction of blood supply);
- reduction of intravascular pressure, slowing of blood flow rate, reduction of the
number of functioning capillaries, reduction of fluid filtration, reduction of lymph
outflow.
Consequences of ischemia: restoration of blood circulation in collateral vessels,
malnutrition and tissue necrosis (necrosis).
Stasis - cessation of blood flow in the vessels of the microcirculatory tract.
TYPES:
- ischemic in connection with the cessation of arterial blood flow;
- venous in connection with the cessation of venous blood outflow;
- capillary (true) - intracapillary aggregation of erythrocytes.
Pathogenesis of erythrocyte aggregation in capillary stasis: etiological factors →
damage to capillary walls → increase in their permeability → filtration of fluid and
albumin into surrounding tissues → increase in blood levels of macromolecular
proteins (globulins and fibrinogen) → adsorption of proteins on membrane membranes
→ changes in membranes erythrocyte aggregation. Etiological factors → damage to

47
erythrocyte membranes → changes in physicochemical properties of membranes
(reduction of the ability to deform) → changes in the surface potential of erythrocyte
membranes → aggregation.
Consequences of stasis: restoration of blood circulation (reversible stasis),
necrosis (irreversible stasis).
Thrombosis - lifelong deposition of a clot of stabilized fibrin and blood cells on
the inner surface of blood vessels with partial or complete obstruction of their lumen.
The mechanisms of formation and structure of blood clots depend on the
characteristics of blood flow in the vessel. At the heart of arterial thrombosis -
thrombosis in the arterial system with high blood flow velocity - is the activation of
vascular-platelet (primary) hemostasis, and at the heart of venous thrombosis - the
formation of thrombi in the venous system, characterized by low blood flow velocity -
activation.
Virkhov's triad:
1. Endothelial damage: endothelial cell death; violation of their function -
endothelial dysfunction; endothelial cell death → basement membrane exposure →
collagen unmasking → ↑ platelet adhesion; endotheliocytes release Willebrand factor,
which forms a "bridge" between collagen and platelets.
2. Violation of blood flow - when changing blood flow from laminar to turbulent
shaped elements of the blood gain the ability to contact the endothelium.
3. Increased blood viscosity.
Embolism - the movement of blood (lymph) and blockage of blood vessels by
foreign bodies (emboli).
Embolism of endogenous origin:
a) thromboembolism;
b) tissue - pieces of tissue with injuries or tumors during their disintegration;
c) fat - droplets of fat in fractures of the tubular bones or damage to fat during
liposuction;
48
 d) embolism of amniotic fluid - amniotic fluid during childbirth in the damaged
vessels of the uterus.
Embolism of exogenous origin:
a) air - air bubbles that fall from the environment into the large veins (superior
vena cava, jugular, subclavian), in which blood pressure may be below atmospheric;
b) gas - gas bubbles that form in the blood with a rapid decrease in barometric
pressure, such as the rapid rise of divers from the area of high pressure to normal; when
depressurizing the cockpit at high altitudes (transition from normal to low atmospheric
pressure);
c) foreign bodies - with gunshot wounds.

Microcirculation is the movement of blood and lymph along the microcirculatory

bloodstream and lymphatic channels.
The microcirculatory bloodstream consists of vessels, the diameter of which does
not exceed 100 microns, i.e. arterioles, metarterioles, capillary vessels, venules and
arterio-venular anastomoses.
Microcirculation disorders are divided into three types: intravascular; disorders
associated with changes in the vessels themselves, and extravascular.
Sludge-syndrome refers to intravascular microcirculation disorders associated
with a change in the rheological properties of blood. The main factors of such changes
are violations of the suspension stability of the blood, as well as an increase in its
viscosity.
The main features of blood with sludge are the adhesion of erythrocytes,
leukocytes and platelets to each other, an increase in blood viscosity, which makes it
difficult for its movement through microvessels. In this case, the blood flow slows down
sharply and resembles the movement of silt along the bottom of a river.

49
 Insufficiency of lymph circulation is a condition in which the lymphatic vessels
do not fulfill their main function - the implementation of constant and effective drainage
of the interstitium.
There are the following forms of insufficiency of lymph circulation.
1. Mechanical failure. It is manifested by the difficulty of lymph outflow due to
the presence of organic or functional reasons.
2. Dynamic failure. It occurs when the volume of extravasation of interstitial fluid
exceeds the capacity of the lymphatic system to provide effective drainage.
3. Resorption insufficiency. It is caused by structural changes in the interstitial
tissue, accumulation of proteins and their deposition in the interstitium.
The main manifestations of insufficient lymph circulation in the acute stage are
edema, the accumulation of proteins and their decay products in the interstitial tissue,
and in the chronic stage - the development of fibrosis and sclerosis.

50
Chapter 2. Inflammation

Inflammation is a typical pathological process that occurs under the influence of

phlogogenic factors, characterized by the phenomena of alteration, microcirculation
disorders (with exudation and emigration) and proliferation, aimed at localization,
destruction and removal of the damaging agent, as well as recovery (or replacement) of
damaged tissues.
Causes of inflammation - phlogogens. Classification of phlogogenic factors:
Exogenous:
- Physical (mechanical trauma, exposure to high and low temperatures, ionizing
radiation);
- Chemicals (acids, alkalis, salts of heavy metals);
- Biological (bacteria, viruses, fungi).
Endogenous:
- Products of tissue breakdown during tumor growth;
- Toxic metabolites formed in renal and hepatic dysfunction;
- Products of tissue breakdown in heart attack, burns;
- Immune complexes.
Components of inflammation:
1. Alteration
2. Exudation and emigration of leukocytes
3. Proliferation
Alteration - a violation of the structure and function of cells, intercellular
substance, nerve endings, blood vessels. Alteration can be primary or secondary.
Primary alteration develops immediately after exposure to the harmful factor and is
formed at the level of the functional element of the organ. Secondary alteration is a
consequence of the primary and is associated with changes in metabolism,
physicochemical changes, the action of inflammatory mediators.
51
 Inflammatory mediators are biologically active substances, the appearance of
which in the inflammatory focus determines its further course.

Cellular mediators:
Lysosomal enzymes. Cause secondary tissue alteration, chemotaxis, increase the
permeability of the vascular wall, activate complement systems, blood clotting and
fibrinolysis, facilitate the migration of leukocytes.
Cationic non-enzymatic proteins. Increase the permeability of the vessel wall,
stimulate the emigration of leukocytes, cause bactericidal action on microbes.
Serotonin Increases the permeability of the vascular wall, intact vessel - dilates,
damaged - narrows.
Leukotrienes. Stimulate neutrophil chemotaxis, narrowing of arterioles, increased
vascular wall permeability, bronchospasm
Prostaglandins. Cause dilation of arterioles, increased vascular permeability,
chemotaxis of leukocytes, decreased sensitivity of nerve endings to stimuli.
Thromboxanes. Activate platelet adhesion and aggregation, vasoconstriction,
increased blood clotting.
Prostacyclins. Cause platelet disaggregation, vasodilation.
Cytokines:
- Interleukins
- Interferons
- Colony-stimulating factors
- Chemokines
- Factors of apoptosis. Stimulate increased adhesion and emigration of
leukocytes, increase vascular permeability, stimulation of neutrophils and monocytes.
Stimulate phagocytosis, antibody formation, cell proliferation and differentiation
Active metabolites of O2: O2-, NO-, H2O2

52
 Nitric oxide (NO). Increase vascular permeability, bactericidal action of
phagocytosis, vasodilation, bactericidal action.
Humoral mediators:
Complement system proteins C3a, C5a, C3b, complex C5b-C9 cause chemotaxis,
increased permeability of postcapillary venules, release of cellular mediators, cytolysis.
Kinins (bradykinin, kalidin) dilate arterioles, increase the permeability of venules,
stimulation of T-lymphocytes, fibroblast proliferation, release of cellular mediators,
pain, itching.
Factors of coagulation and fibrinolysis systems - regulate blood clotting,
chemotaxis.
Vascular reactions in inflammation:
1) short-term vascular spasm (reflex spasm, action of endothelin, catecholamines,
thromboxane A2);
2) arterial hyperemia (paralysis of vasoconstrictors, exposure to mediators with
vasodilating activity - histamine, bradykinin, nitric oxide);
3) venous hyperemia: intravascular factors: blood clotting, the formation of
microthrombi, margination of leukocytes, swelling of the formed elements
blood and vessel walls in an acidic environment; extravascular factors:
compression of the walls of venous and lymphatic vessels by exudate and cellular
infiltrate; destruction of connective tissue fibers surrounding the walls of capillaries and
venules).
4) stasis.
Exudation is the release of a liquid part of the blood that contains proteins and
formed elements into the site of inflammation.
Pathogenesis of exudation:
1. Increased vascular permeability: reduction of endothelial cells under the action
of histamine, bradykinin, leukotrienes; direct damage to arterioles, capillaries, venules;
2. Increase in hydrostatic pressure in capillaries and venules;
53
 3. Increased osmotic and oncotic pressure in the inflammatory focus - due to
electrolytes and protein in the tissues.
Types of exudates:
- serous - contains 2-3% protein (albumin), transparent, observed in viral, allergic
inflammation, burns;
- hemorrhagic - contains a significant number of erythrocytes, is formed in severe
vascular damage with destruction of the basement membrane, develops in influenza
pneumonia, anthrax;
- purulent - yellow-green color, contains destroyed cells, leukocytes, bacteria,
caused by bacterial microflora;
- putrid - gray with an unpleasant odor, develops when exposed to anaerobic
infection;
- catarrhal - transparent, contains mucus, lysozyme, immunoglobulin A, develops
in viral infections;
- fibrinous - is formed with significant damage to the endothelium, contains
fibrinogen, which in contact with tissues is converted into fibrin (diphtheria, dysentery).
The value of exudation:
- positive: dilution of the concentration of bacterial and other toxins and their
destruction by proteolytic enzymes that come from blood plasma; entry into the
inflammatory focus of serum antibodies; emigration of blood leukocytes, which
contributes to phagocytosis; localization of the pathological process;
- negative: microcirculation disorders and ischemic tissue damage; excessive
growth of connective tissue; organ dysfunction.
Leukocyte emigration - the release of leukocytes into the site of inflammation.
Stages of emigration:
1. Marginal position of leukocytes near the inner wall of blood vessels and rolling:
- slowing of blood flow;
- activation and expression of E and P -selectins on the surface of the endothelium;
54
- receptor interaction of L-selectins of leukocytes with E- and P selectins of
endothelium → rolling → reversible adhesion;
- expression of integrins on the surface of leukocytes and their interaction with adhesive
molecules on the endothelium (ICAM, VCAM) → irreversible adhesion to the
endothelium.
2. The output of leukocytes through the vessel wall:
- formation of pseudopodia and passage between endothelial cells
- lysis of the basement membrane by proteases;
- thixotropy effect.
3. The movement of leukocytes in the inflammatory focus:
- chemotaxis - chemoattractants → interaction with receptors on the surface of
leukocytes → increase of Ca2 + in the cytoplasm → activation of the microtubular
system of leukocytes, formation of pseudopodia, activation of intracellular enzymes →
active movement of leukocytes (energy due to anaerobic glycolysis).
Proliferation - reproduction of cellular elements of connective tissue. Proliferation
stimulators: epidermal and endothelial growth factor, platelet-derived growth factor,
cytokines (IL-1). Proliferation inhibitors: keylons, tumor necrosis factors.
Local signs of inflammation (Celsus-Galen pentad):
- redness (development of arterial hyperemia);
- local fever (influx of warm arterial blood and increased metabolic rate);
- swelling (exudation and inflammatory infiltrate);
- pain (irritation of nerve endings BAR, K +, H +; mechanical compression by exudate);
- dysfunction.
General signs of inflammation:
- fever - due to IL-1;
- synthesis in the liver of acute phase proteins: C - reactive protein, fibrinogen,
ceruloplasmin, haptoglobin;
- neutrophilic leukocytosis with a shift to the left - leukopoietins stimulate leukopoiesis;
55
- accelerated ESR by increasing the amount of globulins and fibrinogen.

56
Chapter 3. Fever

Fever is a typical pathological process characterized by a change in

thermoregulation on the influence of pyrogenic stimuli, which is expressed by the
restructuring of thermoregulatory homeostasis of the body.
Stages of fever:
1) Stadium incrementi - stage of raising body temperature,
2) Stadium fastigii - the stage of standing the temperature at a high level,
3) Stadium decrementi - the stage of lowering the temperature and returning it to
normal.
Clinical characteristics of stages:
Stage 1 - fever - is characterized by chills, accompanied by a feeling of cold.
Pathogenesis of chills - there is a spasm of blood vessels in the skin and a decrease in
skin temperature. This causes irritation of cold receptors (feeling cold) and the
corresponding reaction to cold - muscle tremor. Subjectively, all this is perceived as a
chill. Heat production prevails over heat transfer.
In the second stage - is characterized by the appearance of a feeling of heat, due
to the expansion of blood vessels in the skin at high body temperature. Heat transfer is
equal to heat production. According to the features of the temperature curve (height of
rise), depending on the nature of its fluctuations during the day, there are the following
types of fever:
1) subfebrile - up to 380,
2) moderate - 38-390,
3) high - 39-400 and
4) excessive - hyperpyretic (410 and above). If this limit is exceeded, there are
deep CNS dysfunction and the patient's life may be endangered.
Types of (temperature) curves:

57
 1) constant temperature curve (febris continua) - temperature fluctuations within
no more than 10 (observed in typhoid and typhoid fever, lobar pneumonia);
2) laxative (febris remittens) - temperature fluctuations in the range of 1.5 - 20)
(for viral infections);
3) intermittent or intermittent - febris intermittens - is the correct alternation of
normal temperature with periods of rise (in malaria);
4) recurrent - febris recurrens - the intervals between the febrile period and the
periods of the norm, as a rule, are not the same (5-7 days of fever and 3-4 days of the
norm) - recurrent typhus;
5) exhausting or hectic - febris hectica - temperature fluctuations during the day
reach 3-50 (normal in the morning, 400 in the evening) - with sepsis. The fever may be
atypical when the temperature is higher in the morning than in the evening.
The pathogenesis of stage 3 (decrease in temperature) is manifested clinically by
sweating. Sweating is the main type of heat transfer during the period of lowering the
temperature and returning it to normal. Body temperature can drop quickly (critically)
and slowly (lytically). Lytic fever can be dangerous, especially in the elderly who have
suffered a myocardial infarction or have cardiosclerosis. A crisis can lead to collapse
from acute heart failure.
Heat production returns to normal due to the reduction of the action of pyrogens
on the installation point, heat transfer is increased.
Etiological factors of fever - pyrogens. They are divided into infectious and non-
infectious: these are bacterial lipopolysaccharides, their exo- and endotoxins, viruses,
rickettsiae, foreign graft cells, breakdown products of their own tissues, lymphokines,
chemotaxins, allergen-antibody complex, allergens.
By origin, pyrogens are divided into:
1. Exopyrogens (from microbial endotoxins - bacterial), by chemical structure -
are high-molecular lipopolysaccharides.
2. Endopyrogens (cellular).
58
 It is established that:
1) exopyrogens cause fever indirectly due to the formation of endopyrogens, so
the temperature rises after 45-60 minutes and a maximum of 3-4 hours,
2) non-toxic,

3) heat-resistant (for destruction it is necessary to autoclave within 1-2 hours at a

temperature of 2000),
4) non-allergenic,
5) are not antigenic, but carry antigenic chemical specificity - ie are haptens. To
acquire antigenic properties, they must combine with proteins of cells and tissues,
7) with daily administration of 5-6 times to exopyrogens there is tolerance and
fever does not develop,
8) exopyrogens cause a number of protective effects.
Endogenous pyrogens: their source is neutrophils, macrophages and blood
lymphocytes - these are leukocyte pyrogens.
Properties of leucopyrogens:
1) are produced only by living leukocytes, the structure is a protein such as
albumin,
2) unstable to heat - are destroyed at a temperature that causes protein coagulation
(60-700),
3) temperature reaction to endopyrogen develops in 10-15 minutes. Maximum
temperature rise after the introduction of endopyrogen in 1-2 hours (exopyrogen 3-4).
Characteristics of interleukin-1:
1) it is produced in micro- and macrophages, does not cause tolerance, non-toxic,
acts on all major regulatory systems of the body and, above all, those that determine
reactivity and resistance - nervous and endocrine,

59
 2) acts on the cells of the hypothalamus and enhances the production of CRF,
which trigger a stress response, mobilize energy resources, develop hyperglycemia,
lipemia.
Endopyrogens give the same biological effect as exopyrogens, increasing the
protective properties of the body:
1) enhance phagocytosis,
2) enhance the production of glucocorticoids,
3) enhance tissue regeneration,
4) enhance the detoxification function of the liver,
5) improve microcirculation processes - this is why pyrogens are used in sluggish
diseases, in chronic gastric ulcer to accelerate healing and scarring of ulcers, in renal
hypertension to improve microcirculation in the kidneys (nephron, glomeruli) and
reduce renin production.
Pathogenesis of fever. The rise in temperature in the initial stage is associated
with a decrease in heat transfer - this is the main link in the pathogenesis. Increased
heat production helps to raise the temperature faster.
Chains of pathogenesis of fever:
1) the entry of exogenous pyrogens into the body,
2) the interaction of exopyrogens with the body's phagocytes,
3) activation of phagocytes,
4) selection of activated phagocytes endopyrogens - IL-1, IL-6, IL-8, TNF (tumor
necrosis factor),
5) transfer of IL-1 by blood flow to the center of thermoregulation in the
hypothalamus,
6) the interaction of IL-1 with receptors located on the endotheliocytes of the
capillaries of the hypothalamus,

60
 7) the release of arachidonic acid from membrane phospholipids under the action
of Ca2 + ions and the formation under the action of COX PGE1,2 (prostaglandins) and
their effect on the neurons of the setting point,
8) distortion of information from peripheral thermoreceptors (normal temperature
is perceived as low),
9) limiting heat transfer (due to spasm of superficial vessels) and increasing heat
production,
10) shifting the set point of temperature homeostasis to a higher level.
The biological significance of fever is mainly the creation of a higher temperature
background for metabolic processes, which leads to an increase in the level of
protective reactions:
1) activation of enzymes,

2) increased phagocytosis,
3) activation of antibody formation,
4) synthesis of interferon,
5) violation of the reproduction of microbes and viruses,
6) increasing the sensitivity of microbes to antibiotics.
The difference between fever and hyperthermia:
1) various etiological factors: with fever - pyrogenic factors, with hyperthermia -
environmental factors,
2) various manifestations of the stage of temperature rise - with fever - chills and
moderate stimulation of functions (with a rise in temperature by 10 - an increase in
heart rate by 8-10 beats per minute and 2-3 respiratory movements), and with
hyperthermia, sharp sweating, fever, a sharp increase in heart rate and respiration - by
10-15 respiratory movements with an increase in body temperature by 10),
3) when the body cools with fever, the temperature does not change, with
hyperthermia - decreases,

61
 4) antipyretic drugs reduce the temperature with fever and do not affect
hyperthermia.
At fever processes of oxidative phosphorylation are activated, synthesis of ATP
increases, protective reactions are accelerated. At a hyperthermia there is a blockade of
synthesis of ATP and their disintegration, a lot of heat is formed.

62
 Chapter 4. Tumors

Tumors are a typical pathological process, the main feature of which is the endless
and uncontrolled reproduction of cells by the body with a violation of their ability to
differentiate and form organized structures.
Features of tumor growth:
1. Atypia of reproduction: unregulated, unlimited growth, loss of the "limit" of
the number of cell divisions (Hayflick's limit). Pathogenesis:
- Activation of tumor cell oncogenes, as a result of which cells switch to autocrine
regulation - they themselves synthesize proliferation stimulators.
- Change in the structure and function of tumor cell membranes:
• reducing the number of receptors that provide control of the nervous and
endocrine systems;
• appearance of "defective" receptors;
• reducing the number of adhesive molecules that provide intercellular contacts
and contact inhibition of fission. The loss of the upper "limit" of the number of cell
divisions is associated with changes in the function of genes that regulate apoptosis.
2. Morphological atypia (cellular and tissue).
- Atypia of differentiation - partial or complete cessation of cell differentiation -
Anaplasia.
3. Biochemical atypia (features of metabolism in tumor tissue).
1) Features of carbohydrate metabolism:
a) tumor - a "trap" of blood glucose;
b) the negative effect of Pasteur - glycolysis in tumor cells can continue in the
presence of oxygen;
c) activation of the pentose phosphate pathway of glucose oxidation.
2) Features of protein metabolism:

63
 a) tumor cells - "trap" of blood nitrogen - tumor cells intensively capture nitrogen-
containing substances from the blood (amino acids, nitrogenous bases) and use them
for the synthesis of their own proteins;
b) protein synthesis predominates over decay - sharply increased synthesis of
DNA, RNA. The activity of nucleic acid synthesis enzymes is increased, while the
activity of enzymes that break them down is reduced;
c) synthesis of oncoproteins;
d) synthesis of embryonic proteins (alpha - fetoprotein);
e) reducing the synthesis and content of histones - proteins - suppressors of DNA
synthesis;
e) decreases the content of c-AMP, which has, as a rule, an inhibitory effect on
cell division; increases the content of c-GMF, which stimulates cell proliferation.
3) Features of fat metabolism:
a) tumor cells capture from the blood LDL (low density lipoproteins) and
antioxidants (alpha-tocopherol);
b) weakened synthesis of fatty acids, enhanced synthesis of altered membrane
phospholipids.
4. Antigenic atypia:
a) antigenic simplification - a decrease in the number of organ-specific antigenic
proteins (antigens of the main histocompatibility complex disappear on the surface of
many cells);
b) antigenic complication:
- antigenic divergence - the synthesis of antigens inherent in other tissues;
- antigenic reversion - synthesis of embryonic antigens.
5. Functional atypia:
a) decreased tissue function (gastric cancer reduces the secretion of gastric juice;
in leukemia immature leukocytes are not able to participate in phagocytosis);

64
 b) increased tissue function (adenomas of the endocrine glands increase the
synthesis of hormones);
c) performing a function that is not characteristic of the tissue from which the
tumor grows (tumor cells of the lungs, bronchi can synthesize pituitary hormones).
6. Monoclonality - tumor growth from 1 transformed cell.
7. Autonomy of growth - tumor growth does not depend on the regulatory effects
of the body.
8. Neovascularization - a new tumor vessels formation.

Biological features that are characteristic of malignant tumors:

1. Infiltrative (invasive) growth - the main sign of malignant tumors - the
penetration of tumor cells into the surrounding tissues. Pathogenesis:
a) reducing the adhesion forces between tumor cells:
- reducing the number of adhesive molecules - cadherins (E-cadherin), integrins
on the surface of tumor cells, providing adhesion of cells to each other;
- change in the location of receptors for connective tissue proteins.
b) increased motility of tumor cells:
- cell movement is stimulated by growth factors, connective tissue destruction
products;
- tumor cells synthesize cytokines (chemokines) and cancer proteins that have the
properties of chemoattractants.
C) isolation of hydrolytic enzymes by tumor cells:
- tumor cells themselves secrete hydrolytic enzymes - matrix metalloproteinases
(proteases, collagenases, glycosidases);
- cytokines of tumor cells stimulate the secretion of enzymes and cells of the host
organism (fibroblasts);
- decreased activity of tissue hydrolase inhibitors.
d) violation of neuroendocrine regulation of tumor cells.
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 Benign tumors are characterized by expansive growth, limited inside the
capsule and without penetration into the surrounding tissues.
2. Metastasis - the process of transfer of individual tumor cells to other organs and the
development of secondary tumor nodes of the same histological structure.

Ways of metastasis of tumor cells:

• lymphogenic (transfer of lymph cells through lymphatic vessels) - characteristic
of carcinoma,
• hematogenous (through blood vessels) - characteristic of sarcoma,
• hematolymphogenic,
• "cavity" (transfer of tumor cells by fluids in body cavities, such as cerebrospinal
fluid),
• implantation - the direct transition of tumor cells from the surface of the tumor
to the surface of the organ or tissue with which it comes into contact.
Stages of lymphogenic and hematogenous routes of metastasis:
1. Stage of intravasation - the penetration of tumor cells through the wall of a blood
or lymphatic vessel into its lumen. Pathogenesis:
2. Stage of dissemination - transportation of tumor cells through blood vessels and
the formation of cell emboli.
3. Stage of extravasation - the release of tumor cells from blood vessels and their
penetration into normal tissue, reproduction and formation of new tumor nodes.
3. Recurrence - re-development of the tumor at the site of its removal.
Causes of recurrence:
a) incomplete removal of tumor cells.
b) implantation of tumor cells into normal tissue during rough massive surgery.
c) immunosuppression.
d) the action of carcinogens that is still ongoing or the preservation of the causative
factors of tumor growth.

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 4. Cachexia - a syndrome of exhaustion and general weakness. Pathogenesis:
a) the phenomenon of "substrate traps";
b) synthesis by tumor cells of toxohormone, which reduces the activity of catalase,
iron content in the blood, causes the breakdown of skeletal muscle protein, inhibits
erythropoiesis;
c) the formation of tumor cells and macrophages of interleukin-1 and tumor
necrosis factor, which have a systemic effect on the body (decreased appetite,
breakdown of muscle proteins, fever);
d) anorexia and impaired food intake. Anorexia - lack of appetite - a symptom that
is common in tumors. The pathogenesis of anorexia is a violation of the central
mechanisms of appetite regulation;
e) violation of neuro-endocrine regulation of metabolism of the tumor-bearing
organism;
e) intoxication with tumor decay products.
Causes of tumors - carcinogens.
Classification of carcinogenic factors:
- physical;
- chemical;
- biological.
Physical carcinogens:
1. Ionizing radiation: X-rays, γ-radiation. Ionizing radiation has a mutagenic
effect: it causes breaks in DNA strands, translocations, point mutations.
2. Ultraviolet rays damage DNA, causing the formation of pyrimidine dimers.
These damages are corrected by DNA repair enzymes. With a hereditary defect in DNA
repair enzymes, the incidence of skin cancer increases. People with fair skin are most
sensitive to the effects of ultraviolet rays.

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 3. Repeated burns ("kangaroo" cancer in people who use for heating warm coal-
filled clay pots, which are strengthened on the skin of the abdomen; esophageal cancer
when eating excessively hot food).
4. Repeated mechanical impact (incorrectly selected prostheses).
Chemical carcinogens:
- By origin:
• exogenous;
• endogenous;

- By mechanism of action:
• direct (alkylating compounds capable of attaching alkyls to DNA);
• indirect - procarcinogens - induce tumors after metabolic transformations in the
body.
Biological carcinogens - oncoviruses:
- RNA-containing viruses (DNA provirus must be synthesized) - Human T-
lymphotropic virus HTLV-1 (causes T-cell leukemia in humans). A similar action with
HIV.
- DNA-containing viruses:
• papal viruses: human papilloma virus,
• adenoviruses: not oncogenic to humans,
• herpesviruses: Epstein-Barr virus (causes Burkitt's lymphoma, nasopharyngeal
cancer),
• hepadnoviruses: hepatitis B virus (causes liver cancer, especially when co-
administered with aflatoxin).
Carcinogenesis is a long process of accumulation of genetic damage.
Stages of carcinogenesis:
1. Initiation
2. Promotion

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 3. Progression
Initiation(transformation) - irreversible violations of the genotype of a normal
cell and its transition to a state prone to transformation (latent cell). Initiation is the
occurrence of mutations in one of the genes that regulate cell proliferation, under the
influence of various carcinogens:
- Activation of oncogenes (conversion of protooncogenes into oncogenes),
- Inactivation of suppressor genes (antioncogenes),
- Damage to genes that regulate apoptosis,
- Damage to DNA repair genes.
Transformation mechanisms:
1. Transformation of proto-oncogenes into oncogenes - activation of
oncogenes.
Protooncogenes are normal genes that stimulate cell division. They encode the
synthesis of growth factors, receptors for growth factors, secondary mediators of
mitogenic signal transmission to the nucleus, transcription factors.
The mechanism of conversion of proto-oncogenes into oncogenes:
a) Point mutation of protooncogene,
b) Translocation of protooncogenes,
c) Amplification of the protooncogene - an increase in the number of
protooncogenes with normal low activity,
d) Inclusion (insertion) of a promoter - a section of DNA that activates adjacent
genes.
2. Inactivation of cell division suppressor genes.
In addition to oncogene activation, inactivation of proliferation suppressor genes,
including the p53 system, is required to convert a normal cell into a tumor cell in vivo.
3. Inhibition of the activity of genes that regulate apoptosis.
Apoptosis is the programmed death of a cell, which includes various external
stimuli in relation to the cell and intracellular "conflicts" that cannot be resolved
69
(impossibility of DNA repair, increase of intracellular calcium). External stimuli
include tumor necrosis factor (TNF), the action of ionizing radiation, free radicals.
4. Damage to DNA repair genes.
Damage to the repair genes weakens the cell's ability to eliminate errors that occur
when DNA structure is disrupted.
Phase II of carcinogenesis - promotion, in contrast to the stage of initiation,
reversible at an early stage of the process. During the promotion initiated, as a result of
gene changes, the cell acquires the phenotypic properties of the transformed cell.
However, the emergence of tumors requires long-term and continuous exposure to
promoters: they affect cell differentiation and block intercellular connections, promote
the formation of free radicals, induce the exchange of sister chromatids, stimulate the
expression (strength) of DNA proviruses and some retroviruses with reverse
transcriptase, which synthesizes DNA on the RNA template, ie there is a reverse flow
of information from RNA to DNA). During the promotion stage, cell division is
stimulated, which leads to the formation of a tumor node.
Phase III - Progression - the stage of carcinogenesis, when more malignant
clones of tumor cells appear - the most resistant to the body's defenses and the action
of drugs.

Mechanisms of antiblastoma resistance:

1. Anticancer - act against carcinogens:
2. Antitransformation - prevent the transformation of a normal cell into a tumor
(function of DNA repair enzymes, suppressor genes, apoptosis genes).
3. Anti-cellular - aimed at destroying or suppressing the growth of tumor cells
(natural killers) (NK cells), sensitized T-lymphocytes (T-killers), macrophages and
interferons that they secrete, tumor necrosis factor, immunoglobulins, keilons, heparin.

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 Chapter 5. Hypoxia

Hypoxia is a typical pathological process that develops as a result of insufficient

oxygen supply to tissues or violation of its use by tissues in redox processes.
Classification of the main types of hypoxia by pathogenesis:
1. Hypoxic;
2. Respiratory;
3. Circulatory;
4. Chemical;
5. Fabric;
6. Mixed - a combination of different types of hypoxia.
Classification by rate of development and duration of the course:
a) lightning - for several tens of seconds,
b) acute - a few minutes or tens of minutes (acute heart failure),
c) subacute - a few hours,
d) chronic - weeks, months, years.
Hypoxic hypoxia is an exogenous type of hypoxia that develops when the
barometric pressure of O2 decreases (altitude and mountain sickness) or when the
partial pressure of O2 in the inhaled air decreases. Hypoxemia develops (decreased pO2
in arterial blood, saturation of hemoglobin (Hb) with oxygen (O2) and its total content
in the blood. Hypocapnia leads to impaired blood supply to the brain and heart, gas
alkalosis, electrolyte imbalance in the internal environment of the body and increased
consumption of O2 tissues.
Respiratory (respiratory) type of hypoxia occurs as a result of insufficient gas
exchange in the lungs due to alveolar hypoventilation, disorders of ventilation-
perfusion relations, or with difficulty in diffusion of O2, impaired airway patency, or
disorders of central respiratory regulation. The minute volume of ventilation decreases,
the partial pressure of O2 in alveolar air and tension of O2 in blood decreases
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(hypoxemia) and hypercapnia joins hypoxia (pCO2 in arterial blood increases), gas
acidosis develops.
Circulatory hypoxia occurs in circulatory disorders that lead to insufficient blood
supply to organs and tissues with massive blood loss, dehydration, cardiovascular
disorders. Circulatory hypoxia of vascular origin develops with excessive increase in
vascular capacity due to reflex and centrogenic disorders of vasomotor regulation,
glucocorticoid deficiency, increased blood viscosity and the presence of other factors
that prevent the normal movement of blood through the capillary network. For the gas
composition of the blood is characterized by normal concentration and O2 content in
arterial blood, their decrease in venous and high arterio-venous difference in O2.
Hemic hypoxia occurs as a consequence of decreased blood oxygen capacity in
anemia, hydremia and impaired ability of Hb to bind, transport and give tissues O2, CO
poisoning, methemoglobin (MetHb) and some Hb abnormalities.
There are two forms of blood hypoxia:
a) anemic - occurs as a result of anemia;
b) hypoxia associated with hemoglobin inactivation.
1. Carboxyhemoglobin is a product of the interaction of hemoglobin with
carbon monoxide (carbon monoxide, CO).
2. Methemoglobin - hemoglobin, in which iron is in an oxidized, trivalent
state.
3. Sulfhemoglobin is a compound of hemoglobin with hydrogen sulfide.
Tissue hypoxia occurs due to impaired ability of tissues to absorb O2 from the
blood or due to reduced efficiency of biological oxidation due to a sharp decrease in
the combination of oxidation and phosphorylation, due to inhibition of biological
oxidation by various inhibitors, disruption of enzyme synthesis or damage to cell
membrane structures. heavy metals, barbiturates. The concentration, saturation and O2
content in the arterial blood may be normal up to a certain point, and in the venous

72
blood significantly exceed normal values. The decrease in arteriovenous difference in
O2 is characteristic of tissue respiration disorders.
Changes in metabolism primarily occur from carbohydrate and energy
metabolism. In all cases of hypoxia, the primary shift is a deficiency of macroergs.
Glycolysis increases, which leads to a decrease in glycogen content, an increase in
pyruvate and lactate. Excess lactic, pyruvic and other organic acids contribute to the
development of metabolic acidosis. There is a negative nitrogen balance. As a result of
disorders of lipid metabolism, hyperketonemia develops.
Electrolyte metabolism is disturbed and, first, the processes of active movement
and distribution of ions on biological membranes, the amount of extracellular potassium
increases.
Adaptive and compensatory reactions:
Responses of the respiratory system to hypoxia are an increase in alveolar
ventilation due to the deepening and frequency of respiratory excursions and
mobilization of reserve alveoli. Increased ventilation is accompanied by increased
pulmonary blood flow. Compensatory hyperventilation can cause hypocapnia, which
in turn is offset by ion exchange between plasma and erythrocytes, increased excretion
of bicarbonate and basic phosphates in the urine.
The reactions of the circulatory system are expressed by increased heart rate,
increased mass of circulating blood due to emptying blood depots, increased venous
inflow, shock and minute OS, blood flow rate and redistribution of blood in favor of
the brain and heart. When adapting to prolonged hypoxia, new capillaries may form.
Due to cardiac hyperfunction and changes in neuroendocrine regulation, myocardial
hypertrophy may occur, which has a compensatory-adaptive nature.
Reactions of the blood system are manifested by an increase in blood oxygen
capacity due to increased leaching of erythrocytes from the bone marrow and activation
of erythropoiesis due to increased formation of erythropoietins. Acidosis enhances the
dissociation of HbO2.
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 Tissue adaptive mechanisms - limiting the functional activity of organs and tissues
that are not directly involved in providing O2 transport, increasing the conjugation of
oxidation and phosphorylation, enhancing anaerobic ATP synthesis by activating
glycolysis. Increases the synthesis of glucocorticoids, which stabilize the membranes
of lysosomes, activate the enzyme systems of the respiratory chain. The number of
mitochondria per unit cell mass increases.

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 PART ІII
DISORDERS OF METABOLISM

Chapter 1. Pathophysiology of carbohydrate metabolism

Normally, fasting plasma glucose levels range from 3.3 to 5.5 mmol / L.
Hypoglycemia is a condition characterized by a decrease in plasma glucose levels
below 3.3 mmol / L.
Etiology:
• Carbohydrate starvation is observed as a result of prolonged general starvation.
Deficiency in food only carbohydrates does not lead to hypoglycemia due to activation
of gluconeogenesis.
• Pathology of the liver. In most hereditary and acquired liver diseases, the
deposition of glucose in the form of glycogen is disturbed and the intensity of
gluconeogenesis is reduced. As a result, the body is unable to maintain glucose levels
for a long time within normal limits without glucose from the outside.
• Indigestion. Violations of cavity and parietal breakdown and absorption of
carbohydrates lead to the development of hypoglycemia.
• Pathology of the kidneys. Hypoglycemia develops when glucose reabsorption is
impaired in the proximal tubules of the renal nephron, which leads to the development
of a syndrome characterized by hypoglycemia and glucosuria (renal glucosuria).
• Endocrinopathy. The main reasons for the development of hypoglycemia in
endocrinopathies: lack of contingent hormones (adrenal glands, hypothyroidism,
pituitary insufficiency) or excess insulin (insulinoma). To continsular hormones include
glucocorticoids, thyroid hormones, HGH, catecholamines and glucagon. Excess insulin
activates the utilization of glucose by cells, inhibits gluconeogenesis, inhibits
glycogenolysis. These effects are observed in insulinomas or insulin overdose.

75
 • Prolonged intense physical activity causes depletion of glycogen stores deposited
in the liver and skeletal muscle (marathon running).
• Capture of glucose by tumor cells.
Clinical manifestations of hypoglycemia:
Hypoglycemic syndrome is a persistent decrease in blood glucose below normal,
which is combined with impaired vital functions. Manifestations of hypoglycemic
syndrome can be adrenergic (due to excessive secretion of catecholamines) and
neurogenic (due to CNS disorders).
• Adrenergic manifestations: hunger, anxiety, fear of death, muscle tremors,
tachycardia, sweating.
• Neurogenic manifestations: headache, confusion, dizziness, impaired vision.
Hypoglycemic coma is a condition characterized by a decrease in blood glucose
levels below normal (usually less than 2.0-1.5 mmol / l), loss of consciousness, lack of
response to external and internal stimuli, cardiovascular and respiratory disorders.
Pathogenesis of hypoglycemic coma:
• The energy supply of cells, especially neurons, is disrupted due to glucose
deficiency; deficiency of metabolites of free fatty acids - acetoacetic and β-
hydroxybutyric, which can provide neurons with energy even in conditions of
hypoglycemia. Ketonemia develops only after a few hours and in acute hypoglycemia
can not eliminate the energy deficit in neurons.
• Imbalance of ions and water in cells due to disruption of energy-dependent ion
carriers: loss of K +, accumulation of H +, Na +, Ca2 +, water.
↓ glucose uptake into neurons → substrate hypoxia → impaired ATP formation
→ neuronal damage → coma
Principles of hypoglycemia therapy:
Etiotropic treatment is aimed at filling glucose deficiency and eliminating the
cause.

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 • Elimination of hypoglycemia is achieved by the introduction of glucose into the
body.
• Treatment of the underlying disease that caused hypoglycemia (diseases of the
liver, kidneys, gastrointestinal tract, endocrine glands).
Pathogenetic treatment is aimed at blocking the main pathogenetic links (energy
disorders, damage to membranes and enzymes, water-electrolyte imbalance).
Symptomatic treatment is aimed at eliminating the symptoms that aggravate the
patient's condition (severe headache, fear of death, sharp fluctuations in blood pressure,
tachycardia).
Hyperglycemia is a condition characterized by an increase in plasma glucose
levels above 5.5 mmol / L.
Etiology:
• Alimentary overeating. When eating easily digestible carbohydrates in large
quantities, glucose levels rise rapidly and exceed the ability of hepatocytes to form
glycogen.
• Endocrinopathy is the most common cause of hyperglycemia. In this case, they
are due to an excess of continuum hormones or a deficiency of the effects of insulin. 1.
Insulin deficiency:
a) violation of glucose utilization by cells,
b) activation of glycogen synthetase → glycogenesis,
c) inhibiting the transition of glucose into fats,
d) activation of gluconeogenesis.
2. Hyperproduction of counterinsular hormones (adrenaline - pheochromocytoma,
glucagon, corticosteroids - Itsenko-Cushing's disease and syndrome, thyroid -
thyrotoxicosis, STG - gigantism and acromegaly on the background of pituitary
adenoma) glycogen glycogen activation
• Neurological and psychogenic disorders. States of mental excitement, stress are
characterized by activation of the sympathoadrenal, hypothalamic-pituitary-adrenal and
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thyroid systems. Hormones of these systems (catecholamines, glucocorticoids, T4 and
T3) activate glycogenolysis and gluconeogenesis, inhibit glycogenesis.
• Pathology of the liver. With hepatic insufficiency (hepatitis, cirrhosis) may
develop hyperglycemia after a meal due to the inability of hepatocytes to transform
glucose into glycogen.
Clinical manifestations of hyperglycemia:
Hyperglycemic syndrome is a condition characterized by a prolonged increase in
blood glucose levels above normal, which is combined with impaired vital functions.
Hyperglycemic syndrome includes a number of interrelated symptoms.
• Glucosuria - the result of exceeding the possibility of tubular reabsorption of
glucose from primary urine at a blood glucose level greater than 10 mmol / l
(physiological renal threshold for glucose).
• Polyuria - the formation and excretion of urine in excess (more than 1800-2000
ml / day), which is associated with increased osmolality of urine due to the presence of
glucose (glucose increases the osmotic pressure of primary urine, which prevents water
reabsorption).
• Hypohydration (dehydration) - a decrease in fluid content in the body due to
polyuria.
• Polydipsia (thirst) - increased fluid intake due to thirst due to hypohydration and
increased plasma osmolality (hyperosmolar hypohydration).
• Hypotension is caused by hypovolemia due to hypohydration of the body.
Type 1 diabetes mellitus (DM) is a disease based on the absolute insufficiency
of insulin in the body, which occurs as a result of the death of b-cells of the pancreatic
islets, which causes metabolic disorders.
Etiology of type 1 diabetes:
Insulin deficiency can occur under the influence of factors of biological, chemical,
physical nature, as well as inflammation of the pancreas.
• Biological factors
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 ♦ Genetic defects of β-cells of the islets of Langerhans. Genetic defects of the
MHC system cause the inclusion of immune autoaggressive damage to the pancreas or
repression of genes encoding insulin synthesis.

♦ Immune factors. Autoaggressive immunoglobulins and cytotoxic T-

lymphocytes can damage β-cells.
♦ Viruses that are tropic to β-cells: Coxsackie, hepatitis, measles, chickenpox,
mumps, rubella. Viruses have a direct cytolytic effect and initiate autoimmune
processes.
♦ Endogenous toxic substances. As a result of violation of pyrimidine metabolism,
alloxan is formed, which blocks insulin synthesis.
• Chemical factors: high doses of ethanol, some anticancer drugs
(cytostatics).
• Physical factors: ionizing radiation, mechanical trauma, tumor
compression.
• Inflammatory processes in the pancreas caused by factors of chemical,
physical or biological nature. Chronic pancreatitis in about 30% of cases is the cause of
insulin deficiency.
Pathogenesis:
Insulin deficiency is based on the development of an immunoaggressive process,
which is accompanied by the gradual destruction of β-cells. There are two options for
development:
1. A) Intake into the body of genetically predisposed to diabetes persons carrying
foreign hypertension, usually viruses. B) Formation of an immune response with the
formation of blood pressure and cytotoxic lymphocytes to foreign hypertension. C)
Specific blood pressure and lymphocytes act on the antigenic structures of β-cells,
which have a similar structure to foreign hypertension. This phenomenon is referred to

79
as "cross-immunoaggressive reaction". During this reaction, β-cells are destroyed, and
individual plasmolemma proteins are also denatured and become autoantigenic.
2. A) The pancreas is initially damaged by chemical, physical or infectious factors.
B) Release of "foreign" to the immune system proteins (normally they are only
intracellularly and do not enter the bloodstream): cytoplasmic proteins of heat shock,
proinsulin. Some proteins denature and become autoantigenic. C) The formation of an
immune response with the formation of blood pressure and cytotoxic lymphocytes to
denatured and those that entered the blood of intracellular proteins. D) Autoaggressive
blood pressure and lymphocytes act on the antigenic structures of their own β-cells,
which is accompanied by their destruction.
Type 1 diabetes
Type 1 diabetes is manifested at a young age, the level of insulin in the blood is
reduced. Polyuria, polydipsia, polyphagia, weight loss, ketoacidosis progress rapidly.
Natural complications. Insulin treatment is required.
Type 2 diabetes mellitus (DM) is a disease based on relative insulin deficiency or
insulin resistance, which causes metabolic disorders.
Type 2 diabetes occurs in most cases after the age of 40, develops slowly, often in
obese people. Develops polyuria, polydipsia, weakness. Insulin levels are high or
normal. Complications and ketoacidosis are less common. Insulin is not used in its
treatment.
Hereditary predisposition to type 2 diabetes, in contrast to type 1 diabetes, is not
associated with HLA genes.
Risk factors:
• Excess body weight, combined with increased insulin resistance of target tissues
and stimulation of the production of contrainsular hormones. This excessively activates
the synthesis of insulin by β-cells of the pancreas, leading to their "depletion" and
damage.
• Hypertension, which leads to impaired microcirculation in the pancreas.
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 • Chronic stress, accompanied by a steady increase in blood levels of contrainsular
hormones.
Metabolic disorders in diabetes.
- Disorders of fat metabolism:
1. Hyperlipacidemia (activation of lipolysis).
2. Ketonemia, ketonuria = ketoacidosis:
3. Fatty infiltration of the liver (increased intake of fat acids in the liver, decreased
synthesis of lipoproteins and their secretion into the blood).

- Disorders of protein metabolism:

1. Decreased protein synthesis (hyperaminacidemia, aminoaciduria).
2. Activation of protein catabolism - negative nitrogen balance, hyperazotemia.
3. Decreased antibody synthesis and body resistance to infection.
- Disorders of carbohydrate metabolism:
1. Hyperglycemia occurs due to insufficient effects of insulin and impaired
glucose utilization by cells.
2. Glucosuria is mainly a consequence of hyperglycemia.
3. Hyperlactatacidemia - develops due to inhibition of lactate catabolism in the
Krebs cycle, impaired glycogen resynthesis from lactate.
Acute complications of diabetes - coma.
Types:
1. Ketoacidotic - High content of ketone bodies, significant hyperglycemia
2. Hyperosmolar - Very high blood glucose, significant increase in osmotic
pressure in the blood, a small level of ketone bodies (because insulin levels are
sufficient for fat oxidation).
3. Lactacidemic - Increased lactic acid level with low levels of glucose and
ketone bodies in the blood
Chronic complications of diabetes:

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 Microangiopathy - pathological changes in the vessels of the microcirculatory
tract.
Pathogenesis:
• Glycosylation of capillary basement membrane proteins under conditions of
hyperglycemia.
• Thickening and compaction of the vascular wall under the influence of excess
sorbitol.
• Swelling, thickening and dystrophy of vascular endothelium.
• Change in the structure of proteins of the vascular membrane of blood vessels
and their acquisition of antigenic properties, which leads to immune-mediated damage
to the walls of microvessels.

• Tissue ischemia due to a decrease in vascular lumen due to reduced NO

formation and thickening of the vascular wall.
Macroangiopathy - the development of sclerotic changes in the walls of arteries
of medium and large caliber. In diabetes, atherosclerosis of blood vessels appears early
and progresses rapidly.
Pathogenesis:
• Glycosylation of basement membrane proteins and interstitium of vascular walls.
Modification of protein molecules stimulates atherogenesis.
• Accumulation of sorbitol in the wall of arterial vessels.
• Increased levels of atherogenic LDL and decreased levels of antiatherogenic
HDL.
• Activation of thromboxane A2 synthesis by platelets, which potentiates
vasoconstriction and platelet adhesion on vascular walls.
• Stimulation of proliferation of smooth myocytes of arterial vessels.

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 • These changes lead to the formation, calcification of atherosclerotic plaques,
thrombosis and occlusion of arteries, impaired blood supply to tissues with the
development of heart attacks and gangrene.
Neuropathy
• Glycosylation of peripheral nerve proteins.
• The formation of blood pressure to modified proteins with the development of
immune autoaggression reactions.
• Activation in neurons and Schwann cells of glucose transformation into sorbitol.
• Decreased intraneural blood supply with the development of chronic ischemia
and hypoxia of nervous structures. The main factor of ischemic nervous tissue is
considered to be a deficiency of the vasodilator NO.
• Disorders of myelin synthesis and demyelination of nerve fibers; slowing down
the speed of nerve impulses.
• These changes lead to peripheral polyneuropathy, autonomic system neuropathy,
radiculopathy (changes in the roots of the spinal cord).

Retinopathy. Causes: microangiopathy in the tissues of the eye and hypoxia of

the tissues of the eye, especially the retina.
Nephropathy. Diabetic nephropathy is characterized by:
• thickening and compaction of the walls of the glomerular arterioles;
• thickening of the basement membranes of the glomeruli and tubules with
violations of the processes of filtration, reabsorption, secretion;
• increase in blood pressure as a result of activation of SAS and RAAS.

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 Chapter 2. Starvation. Violations of vitamin metabolism

Starvation is a typical pathological process that develops due to the complete

absence of food or insufficient intake of nutrients, as well as in conditions of a sharp
violation of the composition of food and its assimilation.
Classification of starvation:
• Physiological, pathological and medical starvation are distinguished by origin.
Physiological starvation is characteristic of some species of animals during hibernation.
• Pathological type of starvation is divided into:
1. Complete fasting: a) with water consumption; b) without drinking water
(absolute).
2. Incomplete fasting (malnutrition).
3. Partial fasting (quality).
Complete fasting with water. Pathogenesis and periods:
I. Period of uneconomical energy consumption. Lasts 2-4 days. Characterized by
a strong feeling of hunger due to the excitation of the food center. With complete
starvation, it lasts up to 5 days, and then disappears. There is a rapid weight loss. The
main source of energy in this period are carbohydrates, as evidenced by the value of the
respiratory rate equal to 1.0. Hypoglycemia occurs, which increases the secretion of
glucocorticoids by the adrenal cortex. The consequence is increased protein catabolism
in peripheral tissues, in particular muscle, and activation of gluconeogenesis in the liver.
The basic exchange first increases slightly, and then gradually decreases and becomes
10-20% less than the original. A negative nitrogen balance develops.
ІІ. The period of maximum adaptation. Its average duration is 40-50 days. The rate
of weight loss slows down and is 0.5-1% per day. The feeling of hunger disappears.
The main source of energy is fat, as evidenced by the value of the respiratory rate equal
to 0.7. Hypoglycemia increases the flow of lipolytic hormones (adrenaline,

84
glucocorticoids, glucagon). As a result, fat is mobilized from the depot
hyperlipacidemia develops. It, in turn, is the cause of increased formation of ketone
bodies in the liver. Occurring ketonemia can lead to metabolic acidosis. The main
exchange in this period is 10-20% below baseline. Nitrogen balance is negative.
• III. Terminal period. Duration - 2-3 days. There is an intensive tissue breakdown,
intoxication develops. The main source of energy is protein, as evidenced by the value
of the respiratory rate equal to 0.8. Increased urinary excretion of nitrogen, potassium,
phosphates (signs of destruction of cells and tissue proteins). Death occurs when the
body weight decreases to 50% of baseline.
• Absolute fasting is complete fasting without drinking water. Its duration is 2-3
times less than the duration of complete starvation with water, due to the fact that there
is an increased breakdown of fats to form endogenous, resulting in the rapid
development of ketonemia and non-gaseous acidosis. The severity of absolute
starvation is also due to the accumulation of a large number of end products of
metabolism and other toxic products, the excretion of which requires water from the
body.
• Incomplete starvation (energy deficiency) develops when the energy value of
food does not meet the energy needs of the body.
• Protein-energy deficiency is a condition that occurs as a result of a combination
of incomplete and high-quality protein starvation. Types:
a) alimentary dystrophy - in its pathogenesis in addition to protein and energy
deficiency are important and additional factors: cold, physical fatigue, mental stress;
b) alimentary marasm. It develops in children under one year of age. Energy
insufficiency comes first;
c) kwashiorkor. It develops in children aged 3-6 years. the main pathogenesis is
protein deficiency, energy deficiency is compensated by excessive carbohydrate intake.
Clinical manifestations of protein-energy deficiency:

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 1. Insufficient intake of proteins leads to a violation of the protein-synthetic
function of the liver. This is the cause of hypoproteinemia, which, in turn, causes the
development of oncotic edema.

2. Energy deficiency is the cause of reduced basic metabolism. This is manifested by a

decrease in body temperature (hypothermia).
3. Atrophic syndromes. Their development is associated with violations of the plastic
and energy supply of cells. Manifestation of atrophic changes in the CNS is a slowdown
in mental development, in the digestive system - malabsorption and diarrhea, in the
cardiovascular system - hypotension, in the immune system - reduced antibody
synthesis and increased susceptibility to infections, in the red bone marrow - anemia,
in skeletal muscles - hypodynamia and muscle weakness, in the bones - delayed skeletal
growth.
• Partial (quality) starvation is insufficient intake of one or more nutrients with normal
energy value of food. Types: protein, fat, carbohydrate, vitamin, mineral, water
starvation.
Disorders of vitamin metabolism:
Causes of hypovitaminosis:
I. Nutritional deficiency of vitamins;
II. Inhibition of normal intestinal microflora, which produces a number of vitamins III.
Disorders of vitamin assimilation:
IV. Increased need for vitamins:
Vitamin A (retinol) contained in animal products: fish oil, liver, butter, dairy
products. Many products contain beta-carotene, which is converted in the human body
into vitamin A. In plant products: carrots, apricots, pumpkin, tomatoes, parsley. Vit. A
deficiency causes damage to the epithelium of the skin and mucous membranes,
hyperkeratosis, keratinization of the endometrium (prevents implantation of a fertilized
egg), keratinization of cells in the biliary and urinary tracts (contributes to formation of

86
stones in them), gemeralopia (chicken blindness), violation of normal bone growth in
length, decreased antibody synthesis and phagocytosis, decreased immunity.
Vitamin D2 enters the body with food: tuna liver fat, cod, salmon, milk, egg yolk,
butter, white mushrooms. Vitamin D3 is formed in human skin under the influence of
sunlight. Deficiency causes disorders of bone and cartilage mineralization, the
development of rickets in children and osteomalacia in adults.
Vitamin E (tocopherol) vegetable oils, peas, beans, apples, potatoes, eggs, beef.
Causes degenerative changes in skeletal muscle, myocardium, malnutrition, gait
disturbances, paresis of oculomotor muscles, increased permeability and fragility of
capillaries, impaired spermatogenesis and ovogenesis, placental dysfunction, increased
miscarriage.
Vitamin B1 (thiamine) synthesized by green plants and microorganisms, found in
yeast, whole meal bread, pork, milk, egg yolk. Deficiency causes increased fatigue,
weakness, paraesthesia, polyneuritis, intestinal atony, heart failure, cardiac
arrhythmias. In severe cases, there are paresis and paralysis of skeletal muscles.
Vitamin B12 (cyanocobalamin) contained in animal products, especially in the
liver and kidneys, cheese. Deficiency manifestations: weakness, lethargy, paraesthesia,
glossitis, numbness of the lower extremities, anorexia, diarrhea, hair loss, megaloblastic
anemia.
Vitamin C (ascorbic acid) contained in vegetables and fruits: rose hips, berries,
cabbage, citrus fruits, apples, sweet peppers. Signs of deficiency: increased fatigue,
irritability, weakness, increased permeability of the vascular wall, bleeding gums,
loosening and loss of teeth, skeletal disorders, pain in the extremities, weakened
immunity.

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 Chapter 3. Disorders of water-electrolyte exchange
Water is the main component that ensures the stability of the body's internal
environment. In an adult, about 2/3 of water is in the intracellular sector and 1/3 - in the
extracellular.
The exchange of water and salts between plasma and extracellular medium occurs
in capillaries. Osmotic pressure under conditions of normal water-salt metabolism is
not significant. Filtration is carried out due to the difference between hydrostatic (32-
35 mmHg) and oncotic (22-25 mmHg) pressure in the arterial end of the capillary. At
the venous end of the capillary hydrostatic pressure of 13-15 mmHg, so the fluid moves
into the venous part. Most of the filtered fluid leaves the interstitial space through the
lymphatic vessels.
Violation of water-electrolyte balance (dyshydria). Dyshydria will be divided into
2 groups: dehydration (dehydration) and hyperhydration (water retention). Depending
on the predominance of disorders in the cellular or extracellular space, intracellular and
extracellular dyshidria are distinguished. According to the concentration of electrolytes
in blood plasma, there are hyperosmolar, isoosmolar and hypoosmolar dyshidria.
Hyperosmolar dehydration is characterized by the predominance of water loss
over electrolytes during hypersalivation, overheating, hyperventilation, diabetes
insipidus. Cell dehydration develops, catabolic processes and cellular exsiccosis
increase. Neurological disorders appear, body temperature rises.
Isoosmolar dehydration occurs with simultaneous loss of water and electrolytes in
acute blood loss. Circulatory disorders develop with a decrease in blood pressure up to
hypovolemic shock, there are neurological disorders, dry skin and mucous membranes,
soft eyeballs.
Hypoosmolar dehydration develops due to plasma electrolyte deficiency - loss
during diarrhea and vomiting. High osmotic pressure inside the cell promotes the
movement of water into the cell, causing its hyperhydration. This redistribution of water

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leads to circulatory disorders - tachycardia, hypotension, dry mucous membranes,
decreased tissue turgor.
Hyperosmolar hyperhydration occurs with increased sodium reabsorption (forced
use of sea water, use of hypertonic solutions, hyperaldosteronism), followed by water
retention in the tissues. Excess sodium in the extracellular space is accompanied by the
development of edema and the appearance of fluid in the cavities.
Isoosmolar hyperhydration occurs when plasma and extracellular space are filled
with isotonic fluid (transfusion of large amounts of isotonic solutions (0.9% NaCl, 5%
glucose); heart failure; oligo- and anuria in renal failure), while the intracellular sector
remains normal. Edema in isoosmolar hyperhydration occurs when the protein
concentration in the blood plasma begins to decrease. Diluted plasma due to low oncotic
pressure is not retained in the vascular bed and passes into the interstitial space.
Hypoosmolar hyperhydration occurs when the extracellular space overflows with
fluid with low osmotic pressure (hyponatremia) - with a long diet without salt,
hyperproduction of antidiuretic hormone. Due to the decrease in plasma osmolarity,
water passes into the cells and develops cellular hyperhydration - "water poisoning" of
the body with severe neurological disorders, vomiting, convulsions, impaired
consciousness up to coma.
Edema - water retention in the body mainly in the intercellular space with excess
water and sodium retention. In the pathogenesis of edema is important to increase the
hydrostatic pressure in the vessels, reduce the oncotic pressure of blood plasma,
increase the permeability of the vascular wall and lymphatic outflow.
The main pathogenetic factors of edema:
1. Hydrodynamic. Increase in filtration pressure due to: a) increase in venous
pressure (general venous stasis associated with heart failure, venous obstruction,
venous valve insufficiency, etc.); b) narrowing of the venules.

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 2. Osmotic. Reduction of the gradient of osmotic pressure between blood and
interstitial environment due to the accumulation of osmotically active substances
(electrolytes, metabolic products) in the intercellular space.
3. Oncotic. Decrease in oncotic blood pressure, or increase it in fabrics,
intercellular liquid. Hypoonky blood is most often caused by a decrease in the level of
protein and, mainly, albumin due to: a) insufficient intake of protein in the body; b)
violation of albumin synthesis; c) excessive loss of blood plasma proteins in the urine
in some kidney diseases.
4. Membrane. Increased permeability of capillaries due to: a) the action of humoral
factors (histamine, serotonin, kinins, prostaglandins, etc.); b) violation of trophic wall
of capillaries (violation of neuro-trophic supply, starvation, hypoxia, etc.).
5. Lymphatic. Impaired outflow, stagnation of lymph in the body (damage or
obstruction of lymphatic vessels, elephantiasis, etc.).
6. Violation of nervous and humoral regulation of water-electrolyte metabolism
(sensitivity of volume and osmoreceptors, secondary aldosteronism, hypothyroidism,
etc.).
Depending on the causes and mechanisms of development there are:
Cardiac or congestive edema is associated with impaired blood flow. As a result
of increased venous pressure (hydrostatic factor), fluid from the vessels more actively
passes into the interstitial space, which is facilitated by increased permeability due to
the development of hypoxia. The same mechanism is associated with increased
permeability of the glomeruli of the glomeruli and limited reabsorption of protein in
them, increases the production of renin, angiotensin I and II, stimulates the production
of aldosterone, increases reabsorption of sodium, increased ADH secretion, increases
reabsorption of water in the distal. The consequence of these processes is an increase
in the mass of circulating blood, the filtration pressure in the vessels becomes higher -
and the water again passes into the interstitial sector.

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 Renal edema is often associated with decreased glomerular filtration rate (acute
glomerulonephritis), increased plasma osmotic pressure. At a nephrotic syndrome
permeability of glomeruli for protein increases, oncotic pressure of plasma decreases
and liquid moves to interstitial space.
Hungry (cachectic) edema develops with protein deficiency, especially in chronic
diseases of the stomach and intestines. Hypovolemia develops and, as a compensatory
reaction, increases the reabsorption of sodium and water, which worsens edema.
Inflammatory edema is associated with increased vascular permeability, high
osmotic and oncotic pressure in the tissues.
Electrolyte metabolism disorders:
I. Na + (extracellular electrolyte, 130-145 mmol / l).
1. Primary hypernatremia (absolute increase in sodium ions in the body) can occur
either as a result of increased sodium intake (intake of large amounts of sodium
chloride, the introduction of its hypertonic solution), or due to reduced excretion of
sodium from the body (primary and secondary hyperaldosteronism, renal failure).
Secondary (relative) hypernatremia is an increase in the content of sodium ions in
the blood and intercellular fluid due to loss of water by the body. The total sodium
content in the body may not change, and sometimes decreases. This condition occurs
with hyperventilation, diarrhea, sweating, diabetes mellitus.
Protective-compensatory reactions: as a result of hypernatremia the osmotic
pressure of extracellular fluid increases, the central and peripheral osmoreceptors are
broken, the receipt of antidiuretic hormone in blood increases. The latter enhances the
reabsorption of water in the kidneys, resulting in an increase in extracellular fluid
volume and a decrease in its osmotic pressure.
Consequences: development of intracellular dehydration.
2. Primary (absolute) hyponatremia develops as a result of reduced sodium intake
(salt-free diet, anorexia) or due to increased excretion of sodium from the body by the
kidneys (hypofunction of the adrenal cortex, renal failure).
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 Secondary (relative) hyponatremia is excessive intake of water or its delay -
hyponatremia due to dilution.
Protective-compensatory reactions: a decrease in the concentration of sodium ions
in the extracellular fluid causes, on the one hand, increased secretion of aldosterone
through the renin-angiotensin mechanism, on the other - a decrease in blood antidiuretic
hormone, as it reduces impulses from osmoreceptors. Enhanced reabsorption of sodium
ions and inhibition of water reabsorption in the kidneys - the osmotic pressure of
extracellular fluid is restored.
Consequences: generalized cell edema.
II. K + (intracellular electrolyte, 3.5-5.5 mmol / l).
1. Hyperkalemia. Causes: 1) excess potassium in the body; 2) transition of
potassium ions from intracellular to extracellular space at massive damage of cells, at
increase in intensity of catabolic processes and acidosis; 3) impaired excretion of
potassium from the body (oligo- and anuria, adrenal insufficiency).
Protective-compensatory reactions: increasing the concentration of potassium ions
in the blood directly activates the cells of the glomerular zone of the adrenal cortex and
causes increased secretion of aldosterone. The latter increases the secretion of
potassium ions in the renal nephrons and thus restores their concentration in the blood.
Consequences: 1) violation of the activity of excitable tissues (nervous and
muscular), resulting in the development of disorders of the CNS, cardiovascular system,
skeletal muscles, smooth muscles of the digestive tract; 2) the development of non-
gaseous acidosis.
2. Hypokalemia. Reasons: 1) insufficient intake of potassium in the body with
food (long-term use of a diet that does not contain plant products); 2) enhanced
transition of potassium ions from the extracellular space to the cells, which occurs with
the intensification of anabolic processes and alkalosis; 3) loss of potassium by the body
(polyuria, hyperaldosteronism, prolonged use of diuretics).

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 Protective-compensatory reactions: the development of hyperpolarization of the
membranes of secretory cells and in this regard decreases the secretion of aldosterone
by the adrenal cortex. This causes a decrease in the secretion of potassium ions by cells
of the renal epithelium.
Consequences: a) the threshold of excitability of cells increases and, as a
consequence, there is a general weakness, flatulence, hypotension of skeletal muscles,
skin sensitivity decreases; 2) develops hypokalemic alkalosis.

III. Ca2 + (2.25-2.75 mmol / l).

1. Hypocalcemia. Reasons: - reduction of calcium intake from the small intestine
into the blood: a) reduction of calcium content in food; b) violation of the ratio of
calcium / phosphorus in food; c) the formation in the intestines of insoluble calcium
compounds; d) impaired absorption of calcium in lesions of the small intestine
(enteritis); e) hypovitaminosis D; - loss of ionized calcium by the body: a) in the urine
in disorders of reabsorption processes; b) during pregnancy - losses associated with the
formation of the fetal skeleton; - violation of calcium mobilization from bone tissue: a)
hypoparathyroidism; b) tumors of C-cells of the thyroid gland that produce calcitonin;
- soft tissue mineralization: a) hyperphosphatemia; b) alkalosis; - the transition of
calcium from blood plasma from ionized form to non-ionized - in complexes with
proteins and organic acids: a) oxalic acid poisoning, transfusion of citrate blood; b)
increasing the concentration of whey proteins; c) alkalosis.
Protective-compensatory reactions: 1) increased secretion of parathyroid
hormone; 2) increased formation in the kidneys of 1.25 (OH) 2-vitamin D; 3) reduction
of calcitonin secretion. Due to these reactions, the absorption of calcium and
phosphorus in the intestines increases, their transition from bone to blood increases.
Consequences: 1) skeletal bone disorders - the development of rickets in children
and osteomalacia in adults; 2) syndrome of increased neuromuscular excitability -
tetany.

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 2. Hypercalcemia. Causes: - Increased intake of calcium from the small intestine
into the blood: a) excessive calcium in food; b) reinforcement absorption of calcium in
the intestines, which is most common in hypervitaminosis D; - reduction of calcium
excretion from the body: a) acquired disorders - chronic renal failure; b) hereditary
disorders - familial hypocalciuric hypercalcemia; - increased calcium intake into the
blood from bone tissue: a) hyperparathyroidism; b) malignant tumors with metastases
to bone tissue; c) multiple bone fractures; - violation of calcium deposition in bone
tissue, which is observed in hypophosphatemia.
Protective-compensatory reactions: 1) reduction of parathyroid hormone
secretion; 2) decrease in formation in kidneys of 1,25 (OH) 2-vitamin D and increase
in formation 24,25 * (OH) 2-vitamin D; 3) increased secretion of calcitonin.
Consequences: 1) damage to cells by calcium ions; 2) soft tissue calcification -
calcification; 3) reduction of excitability of excitable tissues; 4) the formation of
calcium stones in the kidneys; 5) increased gastric secretion with the formation of peptic
ulcers in the stomach; 6) the development of hypertension.

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 Chapter 4. Violations of acid-basic state

Acid-base balance is the relative constancy of the hydrogen index of the internal
environment of the organism, due to the combined action of buffer and some
physiological systems.
At change of reaction of the environment physicochemical characteristics of
colloids of cells and intercellular structures - degree of their dispersion, hydrophilicity,
ability to adsorption, etc. change. Normally, the pH is in the range of 7.37-7.44, and the
level of 6.8-7.8 is incompatible with life.
Maintenance of pH constancy is carried out by means of a complex of buffer
systems:
1. Carbonate buffer system.
2. Phosphate buffer system.
3. Buffer system of blood proteins, primarily Hb.
Disturbances of acid-base balance are divided into:
1) acidosis - ie a violation of COR in which either the amount of organic and
inorganic acids increases, or the number of bases decreases,
2) alkalosis - the number of bases increases or the amount of acids decreases.
According to the degree of compensation, all violations are divided into
compensated and decompensated.
Acidosis is divided into:
I) non-gaseous metabolic acidosis - occurs with the accumulation of intermediate
acidic metabolic products, such as ketone bodies, lactic acid, uric acid. It develops with
hypoxia of all kinds, diabetes, starvation, severe liver damage, prolonged fever.
Hypoxia and hyperH + ion cause increased vascular permeability with a tendency
to edema. At sharp increase in permeability in renal tubules there is a filtration
suppression, oliguria develops, insufficient removal of potassium, sodium, chlorine and
other electrolytes, increase in their concentration in blood and intercellular liquid. The
95
increase in osmotic pressure caused by potassium and other low molecular weight
substances causes dehydration of cells with a profound violation of redox processes,
the progression of acidosis and severe general intoxication.
II) non-gaseous excretory acidosis occurs when reducing the release of non-
volatile acids in renal failure; loss of alkalis in the case of renal tubules - impaired
reabsorption of bicarbonate, in case of loss of alkalis with intestinal juice - diarrhea,
intestinal fistula.
III) non-gaseous exogenous acidosis: taking drugs, especially ammonium
chloride, acetylsalicylic acid, poisoning by salicylates, acetic, boric acids.
Compensation for non-gaseous acidosis:
1. binding of H + bicarbonate buffer, proteins;
2. ion exchange with bone tissue;
3. elimination of HCO3- through pulmonary hyperventilation.
III) gas acidosis is characterized by the accumulation of carbonic acid in the blood
with insufficient respiratory function or a significant amount of CO2 in the inhaled air,
ie in all cases of hypercapnia. Increased pCO2 in the blood, regardless of the cause,
leads to hemodynamic disorders in the form of spasm of the arterioles. Increasing the
tone of the renal arterioles leads to a decrease in blood supply to the renal tubules,
stimulation of the renin-angiotensin-aldosterone system and increase systemic vascular
tone. This creates increased resistance to the heart. In contrast to peripheral vessels, the
vessels of the brain under the influence of increased CO2 dilate, which is accompanied
by an increase in the formation of cerebrospinal fluid and increased intracranial
pressure.
Acidosis enhances the parasympathetic effect, causing bronchospasm, increased
secretion of bronchial glands; vomiting, diarrhea appear. There is a violation of CNS
function - dizziness, drowsiness until complete loss of consciousness.
Compensation for gas acidosis is aimed at neutralizing H +:
1. ↑ alveolar ventilation
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 2. ↑ acidogenesis
3. ↑ ammoniogenesis ↑ HCO3-
4. ↑ Na + reabsorption
Alkalosis is divided into:
I) non-gaseous secretory alkalosis: hypochloremic is an alkalosis associated with
the loss of chlorine anions, resulting in the development of hypochloremia. The most
common cause of such alkalosis is vomiting; Hypokalemic is an alkalosis that develops
due to the loss of potassium ions by the body. The most common cause is primary and
secondary hyperaldosteronism, which increases the secretion of potassium ions in the
urine and develops hypokalemia.
II) non-gas exogenous (hypernatremic) is an alkalosis associated with the entry
into the body of exogenous bases. It most often occurs with the introduction of large
amounts of sodium bicarbonate NaHCO3, for example, with incorrect correction of
non-gaseous acidosis in diabetes.
Compensatory mechanisms that develop in alkalosis are mainly to reduce the
excitability of the respiratory center due to increased pH, as well as the mobilization of
renal mechanisms. The effectiveness of blood buffer systems in alkalosis is less
pronounced than in acidosis. A decrease in the minute volume of respiration leads to a
compensatory increase in pCO2 in the blood, which causes the formation of large
amounts of carbonic acid, which is a source of H + ions.
Non-gas alkalosis compensation:
1. ion exchange with bone tissue;
2. preservation of HCO3- through pulmonary hypoventilation.
III) gas alkalosis occurs due to hyperventilation, which occurs in altitude sickness,
hysteria, brain damage (trauma, tumor), hyperthermia.
Symptoms of alkalosis are manifested in the weakening of respiratory function,
increased neuromuscular excitability, which can lead to tetany. This is due to a decrease
in plasma Ca2 + (similar to parathyroid hormone deficiency). At the same time Cl- in
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plasma increases, the amount of ammonia in urine decreases (inhibition of
ammoniogenesis), shift of urine to the alkaline side (result of the strengthened removal
of bicarbonates). Alkalosis increases the excitability of ꞵ -adrenoblockers of the heart,
intestinal vessels, bronchi, while reducing parasympathetic effects. This leads to
tachycardia, constipation, high blood pressure and others. The pathological effects of
gas alkalosis include increased vascular tone of the brain and heart and decreased
peripheral vascular tone, which leads to hypotension until collapse.
Compensation for gas alkalosis:
↓ alveolar ventilation
↓ acidogenesis ↓ HCO3-
↓ ammoniogenesis
↑ excretion of K + during H + reabsorption
Thus, acid-base homeostasis can be compensated for a long time, but when the
protective mechanisms of pH violation are reduced, they often lead to irreversible
changes.

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 PART IV
PATHOLOGICAL PHYSIOLOGY OF ORGANS AND SYSTEMS

Chapter 1. Pathophysiology of the blood system. Anemia caused by blood

loss.
Two volumes present the Blood System:
1) depot (not taking part in circulation and located in liver, spleen and skin),
2) circulating blood - CBV
Circulating Blood volume disorders manifest themselves in the form of
hypovolemia or hypervolemia - a decrease or increase in blood volume compared to
normal (normovolemia). Hypo- and hypervolemia are divided into simple (normal
ratio of plasma and blood cells is preserved), polycythemic (blood cells predominate)
and oligocytemic (plasma predominates).
Disorders of blood volume also include changes in the volume ratio between
cellular elements and plasma with normal total blood volume - oligo- and
polycythemic normovolemia (hemodilution and hemoconcentration). An indicator of
the volume ratio is the hematocrit, which determines the content of cellular elements
(mainly erythrocytes) in the total blood volume (normally 0.36-0.48, or 36-48%).
Hypovolemia is simple - a decrease in CBV without a change in hematocrit.
Occurs immediately after acute blood loss and persists until the fluid passes from the
tissue into the blood.
Oligocytemic hypovolemia is a decrease in CBV with a predominant decrease in
erythrocyte cells. Observed in acute blood loss in cases where the flow of blood and
tissue fluid into the bloodstream does not compensate for the volume and especially the
composition of the blood.
Polycythemic hypovolemia is a decrease in CBV due to a decrease in plasma
volume with a relative increase in erythrocyte content. It develops with dehydration

99
(diarrhea, vomiting, increased sweating, hyperventilation), shock (fluid leakage into the
tissues as a result of increased vascular permeability).
Hypervolemia is simple - an increase in CBV while maintaining a normal ratio
between erythrocytes and plasma. Occurs immediately after transfusion of large
amounts of blood. However, soon the fluid leaves the bloodstream, and erythrocytes
remain, which leads to blood clotting. Simple hypervolemia at the strengthened
physical work is caused by receipt in the general blood stream of blood from depot.
Oligocytemic hypervolemia - an increase in CBV due to plasma. It develops with
water retention in the body due to kidney disease, with the introduction of blood
substitutes. It can be modeled experimentally by intravenous administration of isotonic
sodium chloride solution to animals.
Polycythemic hypervolemia - an increase in CBV due to an increase in the
number of erythrocytes. It is observed at decrease in atmospheric pressure, and also at
various diseases connected with a hypoxia (heart disease, emphysema), and is
considered as the compensatory phenomenon. However, in Vakez's disease it is a
consequence of tumor growth of cells of the erythrocyte line of the bone marrow.
Oligocytemic normovolemia occurs in anemia due to blood loss (blood volume
was normalized due to tissue fluid, and the number of erythrocytes has not yet
recovered), hemolysis of erythrocytes, hematopoiesis.
Polycythemic normovolemia is observed when transfusing small amounts of
erythrocyte mass.
Blood loss is a pathological process that occurs due to bleeding and is
characterized by a complex set of pathological disorders and compensatory reactions
directed against the reduction of CBV and hypoxia due to decreased respiratory
function of the blood.
The etiological factors that cause bleeding include:
1) violation of vascular integrity in case of injury or defeat by a pathological
process (atherosclerosis, tumor, tuberculosis);
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 2) increased permeability of the vascular wall (acute radiation sickness);
3) decreased blood clotting (hemorrhagic diathesis).
Stages of pathogenesis of acute blood loss:
1. The initial stage. It is characterized by a decrease in CBV - simple
hypovolemia, lower blood pressure, hypoxia, mainly circulatory type.
2. Compensatory stage. Due to the inclusion of a set of protective and
compensatory reactions aimed at eliminating the effects of blood loss.
3. Terminal stage. It is characterized by an increase in pathological changes in
the body up to death. It develops in the absence of compensatory reactions.
Protective and compensatory reactions in blood loss:
I. Decrease in volume of a vascular bed:
1) spasm of the arterioles of the skin, muscles, organs of the digestive system;
2) opening of arteriovenous anastomoses of the specified bodies and fabrics as a
result of a spasm of precapillary sphincters;
3) venoconstriction (reduction of smooth muscles of veins), which increases
blood flow to the heart and reduces the capacity of the venous circulation.
Pathogenesis of relevant changes:
a) lowering blood pressure → violation of baroreceptors → activation of the
sympathoadrenal system → action of catechamins on α-adrenoceptors of smooth
muscles of arteries, arterioles, precapillary sphincters and veins;
b) decrease in circulating blood volume and blood pressure: excitation of volume
and baroreceptors → activation of neurosecretory cells of the hypothalamus that
produce vasopressin → the action of this hormone on Vj-receptors of vascular smooth
muscle with subsequent vasoconstriction;
c) decrease in circulating blood volume and activation of the sympathoadrenal
system: secretion by cells of the juxtaglomerular apparatus of renin kidneys →
activation of renin-angiotensin system with formation of angiotensin II → spasm of
smooth muscles of blood vessels.
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 ІІ. Circulated Blood Volume (CBV) Increase:
1) the transition of tissue fluid and blood vessels. As a result of the decrease in
CBV, the hydrostatic pressure in the capillaries decreases, which leads to a decrease in
water filtration in the arterial part of the capillaries and an increase in fluid reabsorption
in the venous;
2) increased reabsorption of water and sodium ions in the kidneys:
a) the effect of vasopressin on the receptors of the epithelium of the distal
convoluted tubules and collecting tubules of the kidneys, resulting in increased
facultative reabsorption of water;
b) activation of the renin-angiotensin system with subsequent release of
aldosterone, which increases sodium reabsorption in the distal convoluted tubules;
c) activation of the sympathoadrenal system, which leads to redistribution of blood
flow between the vessels of the cortical and juxtamedullary nephrons, resulting in an
increase in the area and intensity of tubular reabsorption of water and sodium.
3) the outflow of blood from the depot into the bloodstream - activation of the
sympathoadrenal system and the action of catecholamines on the vessels of the liver,
spleen, subcutaneous fat.
III. Restoration of peripheral blood composition in case of blood loss: develops
due to renal hypoxia, which results in the formation and entry into the blood of a large
number of renal erythropoietins, which stimulate erythropoiesis, increase the entry of
young regenerative forms of erythrocytes into the peripheral blood.
Pathological changes in blood loss:
1. Disorders of systemic hemodynamics (decrease in CBV, decrease in blood
pressure) and local blood circulation (microcirculation) until the development of
shock.
2. Development of acute post hemorrhagic anemia.
3. Development of hypoxia, first circulatory and then hemic type.

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 4. Development of metabolic acidosis due to the entry of lactic acid into the
blood due to hypoxia.
5. Impaired excretory function of the kidneys: decreased filtration rate and the
development of acute renal failure: oligo- and anuria, intoxication (azotemia).
Hemorrhagic shock is a shock that occurs because of profuse acute blood loss.
The leading mechanism of its development is a decrease in CBV, which causes a
decrease in blood pressure, impaired microcirculation, disorders of blood supply to
vital organs (brain, heart, kidneys). The result is the development of hypoxia, acidosis
and intoxication, which complicates the course of shock, creates "vicious circles" in
its pathogenesis and ultimately leads to death.
Disorders of the erythrocyte system. Normally, the number of erythrocytes in
men is 4 -5 T / l, in women - 3.5 - 4.5 T / l. The concentration of hemoglobin (Hb) in
men is 130-160 g / l, in women - 120-140 g / l.
In terms of pathology, there are two types of changes in the number of
erythrocytes and Hb in the peripheral blood:
1) erythrocytosis - an increase in the content of erythrocytes and hemoglobin;
2) anemia - a decrease in their number.
Quantitative changes of erythrocytes can be caused by:
a) violation of the relationship between their formation and destruction;
b) loss of erythrocytes in violation of vascular integrity (blood loss);
c) redistribution of erythrocytes.
Qualitative changes of erythrocytes:
1) the appearance of their regenerative forms (violation of erythrocyte
maturation in the red bone marrow or increased permeability of the bone barrier,
resulting in increased blood flow of immature cells with low hemoglobin content):
a) reticulocytes (Rt) - normally their content in the blood is 0.2-2%. At the
strengthened regeneration of cells of a red sprout of blood their quantity can increase
to 50%;
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 b) polychromatophiles are non-nuclear cells, the cytoplasm of which shows the
ability to perceive both acidic and basic dyes, they differ from mature erythrocytes by
a bluish tinge of their color, together with reticulocytes are the direct precursors of
erythrocytes;
c) normoblasts - nuclear precursors of erythrocytes, normally absent in the
peripheral blood, contained only in the red bone marrow. At the strengthened
regeneration of cells of an erythroid row acidophilic and polychromatophilic, less often
basophilic normoblasts can appear in blood. Sometimes, with hyperregenerative
anemia, erythroblasts (precursors of normoblasts) can be found in the blood.
2) degenerative changes of erythrocytes (acquired and hereditary disorders of
metabolism, composition and structure of erythrocytes, including hemoglobin
synthesis). Such changes are characterized by the following phenomena:
a) anisocytosis - a change in the size of erythrocytes. The appearance of
macrocytes - erythrocytes with a diameter of more than 8 μm and microcytes - cells
with a diameter of less than 6.5 μm (the average diameter of a normal erythrocyte is
about 7.2 μm) is possible;
b) poikilocytosis - a change in the shape of erythrocytes. Normally, erythrocytes
have the shape of biconcave discs. In the conditions of pathology pear-shaped,
extended, crescent-shaped, oval erythrocytes, and also erythrocytes of spherical form
can appear;
c) change in the color of erythrocytes, which depends on the content of Hb in them.
Erythrocytes, intensely stained, are called hyperchromic, with a pale color -
hypochromic. Erythrocytes, in which only the peripheral part is stained in the form of
a ring, where hemoglobin is located, and in the center there is an unstained
enlightenment, are called anulocytes. In case of the expressed differences in coloring
of erythrocytes speak about anisochromia;
d) the presence of pathological inclusions: Jolly bodies - formations 1-2 μm in
size, which are residues of nuclear substance; Kebot rings - remnants of the nuclear
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envelope, having the shape of a ring or figure eight; basophilic granularity - residues of
basophilic substance of the cytoplasm, indicating toxic lesions of the red bone marrow.
3) the appearance of cells of pathological regeneration from a change in the type
of hematopoiesis from erythroblastic to megaloblastic, when megaloblasts and
megalocytes appear in the bone marrow and blood The appearance of these cells in the
red bone marrow and blood is characteristic of B12-folate deficiency anemia.
Erythrocytosis is an increase in the number of erythrocytes in the blood over 6
T / l and a hemoglobin concentration over 170 g / l.
Absolute erythrocytosis is an increase in the content of erythrocytes and
hemoglobin per unit volume of blood due to increased erythropoiesis.
1. Acquired absolute erythrocytosis occurs because of increased production of
erythropoietin mainly in the kidneys due to hypoxia and ischemia, erythropoietin
production by some tumors (hypernephroma, liver cancer, etc.).
In addition, absolute erythrocytosis develops in true polycythemia (Vakez's
disease), which is a type of chronic leukemia.
2. Hereditary absolute erythrocytosis - a genetically determined defect of globin
in the hemoglobin molecule or a deficiency in erythrocytes of diphosphoglycerate,
which is a regulator of oxygenation and deoxygenation of hemoglobin. This increases
the affinity of hemoglobin for oxygen and reduces its impact on tissues. Hypoxia
develops, the production of erythropoietins is stimulated, under the influence of which
erythropoiesis intensifies.
Relative erythrocytosis is an increase in the content of erythrocytes and
hemoglobin per unit volume of blood due to a decrease in plasma volume. Its
development is associated with the action of factors that cause dehydration or
redistribution of blood, which causes polycythemic hypovolemia (shock, burns).
Anemia is a hematological syndrome or an independent disease
characterized by a decrease in the number of erythrocytes and (or) the

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hemoglobin content per unit volume of blood, as well as qualitative changes in
erythrocytes.
Classification of anemias:
I. By etiology:
1) hereditary (eg, thalassemia);
2) acquired (for example, chronic posthemorrhagic anemia).
II. By pathogenesis:

1) post hemorrhagic anemia (anemia after acute blood loss);

2) hemolytic anemia (sickle cell anemia);
3) anemia caused by disorders of erythropoiesis (dyserythropoietic).
III. By the regenerative ability of the red bone marrow:
1) regenerative (Rt up to 3%, for example, acute posthemorrhagic anemia);
2) hyperregenerative (Rt> 3%, for example, acquired hemolytic anemia);
3) hyporegenerative (Rt <0.2%, for example, iron deficiency anemia);
4) aregenerative (Rt 0%, for example, aplastic anemia).
IV. By color index (CI):
1) normochromic (this variant of anemia indicates a proportional, uniform
decrease in Hb and erythrocytes per unit volume of blood, KP = 0.85-1.05; for
example, acute posthemorrhagic anemia in the first few days after blood loss);
2) hypochromic (the amount of Hb is reduced more than the number of
erythrocytes, KP <0.85; for example, iron deficiency anemia);
3) hyperchromic (the total number of erythrocytes is reduced to a greater extent
than the total number of Hb, KP> 1.05; for example, B12-folate deficiency anemia).
V. By type of hematopoiesis:
1) anemia with erythroblastic type of hematopoiesis (eg, iron deficiency anemia);
2) anemia with megaloblastic type of hematopoiesis (eg, B12-folate deficiency
anemia).

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 VI. By erythrocyte size:
1) normocytic (≈ 7.1 - 7.9 μm);
2) macrocytic (> 7.9 μm);
3) microcytic (<7.1 μm);
4) megalocytic (> 12 μm).
VII. According to the clinical course:
1) acute (eg, anemia after blood transfusion shock);
2) chronic (eg, hypoplastic anemia).

VIII. By severity:
1) mild (Hb 120-90 g / l, er. - not less than 3.0 * 1012 / l);
2) medium degree (Hb 90-70 g / l, er. - not less than 2.5 * 1012 / l);
3) severe (Hb <70 g / l, er. - below 2.5 * 1012 / l).
Posthemorrhagic anemias can be acute or chronic.
Acute posthemorrhagic anemia occurs after a single, rapid, massive blood loss.
This situation occurs when large vessels are injured, bleeding from internal organs.
Stages of acute posthemorrhagic anemia:
1) In the first time after acute blood loss in the blood there is approximately the
same decrease in the number of erythrocytes and hemoglobin, the color index (CP)
within normal limits (normochromic anemia).
2) 2-3 days after blood loss, the number of erythrocytes decreases slightly due to
the inflow of tissue fluid into the vessels (relative erythropenia) and the destruction of
erythrocytes in the cells of the mononuclear phagocyte system (absolute erythropenia).
3) On day 4-5, erythropoiesis increases due to increased production of
erythropoietin during hypoxia. In the blood increases the number of polychromatophilic
erythrocytes, reticulocytes, there are normoblasts (regenerative anemia), CP decreases
(hypochromic anemia), because accelerated regeneration precedes the maturation of
cells that do not have time to lose signs of immaturity (nucleus, granules) and

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saturation. In addition, acute blood loss will lead to iron deficiency and decreased heme
synthesis.
Chronic posthemorrhagic anemias occur with small but frequent and prolonged
bleeding (gastric ulcer, hemorrhoids, hyperpolymenorrhea, etc.), with impaired
hemostasis (hemorrhagic diathesis). Blood picture: severe hypochromia of
erythrocytes, which indicates a sharp decrease in Hb synthesis due to iron deficiency,
microcytosis, hyporegenerative.

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 Chapter 2. Hemolytic and dyserythropoietic anemias
Hemolytic anemias are characterized by the predominance of erythrocyte
destruction processes over the process of their formation. Increased erythrocyte
breakdown may be due to acquired or inherited changes in membrane metabolism and
structure, erythrocyte stroma or Hb molecules; harmful effects of physical, chemical,
biological hemolytic factors on the erythrocyte membrane; slowing of erythrocytes in
the inter sinus spaces of the spleen, which contributes to their destruction by
macrophages; increased activity of macrophages.
Types of hemolysis:
1 - intravascular hemolysis occurs in blood vessels under the influence of factors
that damage erythrocytes: a) factors of a physical nature (mechanical trauma, ionizing
radiation, ultrasound, temperature); b) chemical agents (hemolytic poisons); c)
biological factors (pathogens of infectious diseases, toxins, enzymes); d) immune
factors (antibodies).
Mechanisms of intravascular hemolysis.
I. Mechanical hemolysis. Occurs due to mechanical destruction of erythrocyte
membranes.
II. Osmotic hemolysis. Occurs when the osmotic pressure inside the erythrocyte
is greater than the osmotic pressure of blood plasma.
III. Oxidative hemolysis. It develops as a result of free radical oxidation of lipids
and proteins of the plasma membrane of erythrocytes.
IV. Detergent hemolysis. Associated with the dissolution of lipid components of
the erythrocyte membrane by detergents. This type of hemolysis is caused by bile acids
(cholemic syndrome), fat-soluble chemical agents, some bacterial toxins.
V. Complex-dependent hemolysis due to destruction of the erythrocyte membrane
by active complement. This mechanism underlies immune hemolysis.
2 - intracellular hemolysis develops due to the absorption and digestion of
erythrocytes by macrophages. Reasons:
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a) the appearance of defective erythrocytes. Reduction of plasticity of erythrocytes,
their ability to deform;

b) the appearance on the surface of erythrocytes of chemical groups that can

specifically interact with macrophage receptors. Such groups are found at aging of
erythrocytes, and also at fixing on their surface of antibodies;

c) hypersplenism - increased phagocytic activity of splenic macrophages.

Hemolytic anemias:
A. Hereditary:
1. Membranopathy: violation of the structure of the membrane with a change in
shape (hereditary microspherocytosis or Minkowski-Schoffar anemia, hereditary
ovalocytosis). Type of inheritance - autosomal dominant. Hereditary defect of
erythrocyte membrane proteins - spectrin and ankerin. As a result, the permeability of
the erythrocyte membrane to sodium ions is significantly increased, as a result of which
erythrocytes acquire a spherical shape. Spherocytes. lose their ability to deform and
therefore can not pass through the narrow interendothelial slits of the venous sinuses of
the spleen and linger in it for a long time. Spleen macrophages fragment part of the
erythrocyte membrane and convert them into microspherocytes. At the subsequent
passes of microspherocytes through a spleen macrophages completely phagocytose the
changed erythrocytes - there is an intracellular hemolysis.
2. Enzymopathy: deficiency of pentose-phosphate cycle enzymes, glycolysis, ATP
utilization and glutathione cycle enzymes (glucose-6-phosphate-dehydrogenase
deficiency anemia).
3. Hemoglobinopathies:
a) hereditary defect in the synthesis of chains of globin molecules (α- and β-
thalassemia). Thalassemia is a hereditary hemolytic anemia with intracellular
hemolysis. If the synthesis of α-chains is disturbed, then α-thalassemia develops. HbA1,
HbA2 and HbF are not formed, and pathological forms of hemoglobin appear: in adults
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- HbH, and in newborns - HbBart, which are unstable, so they easily precipitate, as a
result of which erythrocytes take the form of targets. Altered erythrocytes are
phagocytosed by macrophages - intracellular hemolysis develops.
In β-thalassemia (Bullet's disease), the synthesis of β-chains of hemoglobin
molecules is disrupted. Therefore, HbA1 is absent, compensatory increases the
formation of HbA2. In newborns, HbF synthesis is not impaired.
b) hereditary defect of the primary structure of globin (sickle cell anemia). The
essence of the defect is that in the β-chain of the hemoglobin molecule in the 6th
position from the N-terminus glutamic acid is replaced by valine. This leads to the
appearance of a pathological form of hemoglobin - HbS. Unlike the usual forms of
hemoglobin, HbS in the reduced state reduces its solubility, which leads to its
precipitation with the formation of crystals that deform erythrocytes. As a result,
erythrocytes do not pass through the narrow capillaries and interdendothelial space of
the venous sinuses of the spleen and are intensively phagocytosed by macrophages
(intracellular hemolysis).
Blood picture in hereditary hemolytic anemias: there is increased regeneration of
erythrocyte sprouts, but erythropoiesis can often be ineffective (when the bone marrow
destroys the nuclear forms of erythrocytes). In the blood smear, along with regenerative
forms (high reticulocytosis, polychromatophilia, single nuclear forms of erythrocytes),
there are degeneratively altered cells (eg, microspherocytes in Minkowski-Schoffar
disease).
B. Acquired:
a) toxic (hemolytic poisons: arsenic compounds, lead; toxins of infectious agents:
hemolytic streptococcus, anaerobic malaria plasmodium, snake, bee venom);
b) immune (transfusion of incompatible blood, Rh-incompatibility of mother and
fetus; the formation of autoantibodies against their own erythrocytes when their
antigenic properties change under the influence of drugs, viruses):

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 - Hemolytic disease of the newborn is a disease that occurs as a result of hemolysis
of erythrocytes of the fetus and newborn caused by maternal antibodies. The most
common are two variants of hemolytic disease of the newborn: rhesus conflict and ABO
conflict.

- Rhesus conflict. It develops in the case of pregnancy Rh - mother Rh + -fetus

(most often in repeated pregnancies). Initially, the mother is immunized with Rh + -
erythrocytes of the fetus, which can enter the mother's body during childbirth or
placental defects. In response to the influx of Rh + erythrocytes in the mother's body,
antibodies against D-antigen are synthesized. These antibodies (IgG) are able to
penetrate the placenta into the fetus and cause hemolysis of its erythrocytes.
- ABO conflict. Most often it occurs in situations where the mother has a blood
group of 0 (I), and the fetus - A (II) or B (III). Normal isoagglutinins in the ABO system
belong to the IgM class. These antibodies do not penetrate the placenta and therefore
cannot be the cause of ABO conflict. However, 10% of healthy people who have blood
group 0 (I) have antibodies against agglutinogens A and B, represented by IgG. The
presence of these antibodies does not depend on previous immunization. IgG
agglutinins penetrate the placenta and can cause hemolysis of fetal red blood cells with
blood groups A (II), B (III). Among first-born children, hemolytic anemia as a result of
ABO conflict occurs with the same frequency as in children born after the second, third
and subsequent births, in contrast to rhesus conflict, where the frequency of hemolytic
anemia increases with increasing number of births.
c) mechanical (mechanical damage to erythrocytes during prosthetics of vessels,
valves);
d) acquired membranopathies are hemolytic anemias that occur as a result of
erythrocyte membrane defects acquired in the course of individual development, for
example, paroxysmal nocturnal hemoglobinuria.

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 Blood picture in acquired hemolytic anemias: by type of hematopoiesis -
normoblastic, by bone marrow regenerative capacity - hyperregenerative, by CP -
normochromic. The degree of reduction in the number of erythrocytes and hemoglobin
depends on the intensity of hemolysis. The blood smear reveals cells of physiological
regeneration and degeneratively altered erythrocytes (poikilocytosis, anisocytosis). The
appearance of a large number of erythroblasts and normoblasts is characteristic of
hemolytic disease of newborns.
Clinical signs and syndromes in hemolytic anemia:

1. Hypoxia. Caused by anemia and manifested by severe weakness, discomfort in

the heart, palpitations, shortness of breath.
2. Hemolytic jaundice.
3. Increased formation of gallstones, especially bilirubin. Due to a significant
increase in bilirubin in bile and an increase in its viscosity.
4. Hemoglobinuria. If it is not possible to bind all the hemoglobin released from
the destroyed erythrocytes, then unconjugated hemoglobin passes through the renal
filter and appears in the urine.
5. Splenomegaly - enlargement of the spleen. Characteristic of the intracellular
mechanism of hemolysis of erythrocytes. At the heart of this phenomenon is the
increase in the functional activity of macrophages, which causes their intensive
proliferation. Splenomegaly is often accompanied by enlarged liver (proliferation of
hepatic macrophages).
6. Hemosiderosis - deposition of hemosiderin in macrophages.
7. Disorders of microcirculation. Often occur during intensive hemolysis and due
to the development of DIC.
8. Fever. It develops as a result of abrupt activation of the phagocytic function of
macrophages, as a result of which they secrete interleukin-1.
Anemia due to erythropoiesis disorders.

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 B12-deficient and folate-deficient anemia are anemias associated with impaired
nucleic acid synthesis and the replacement of the normoblastic type of hematopoiesis
by megaloblastic due to a lack of vitamin B12 and folic acid in the body.
Etiology:
1. Lack of vitamin in food.
2. Non-absorption of vitamin B12 in the stomach, which may be associated with
dysfunction of the fundus of the stomach, which produces gastromucoprotein (vitamin
B12 is absorbed in combination with gastromucoprotein). Dysfunction of the squamous
cells is caused by exposure to autoantibodies (pernicious anemia or Addison-Birmer).
In addition, a similar condition may occur after gastrectomy.

3. Non-assimilation of vitamin B12 in the intestine (during resection of the small

intestine, tumor, diphyllobotriasis, alcoholism).
4. Increased consumption of vitamins during pregnancy.
5. Violation of the deposition of vitamins in the liver with its diffuse lesion.
Pathogenesis. Deficiency of vitamin B12 and folic acid, involved in the formation
of thymine, which is part of DNA, reduces the rate of its formation. The slowing down
of DNA replication is primarily noticeable in tissues, where normal cell division occurs
most often - in blood cells and the epithelium of the gastrointestinal tract. Violation of
cell division leads to the formation of large blood cells: megalocytes, megaloblasts,
giant megakaryocytes. Maturation of megaloblasts to megalocytes is accompanied by
a violation of enucleation (as evidenced by the appearance in megalocytes of Jolie cells
(remnants of the nucleus) and Kebot rings (remnants of the nuclear envelope)). The
presence of a large number of megaloblasts and megalocytes saturated with hemoglobin
causes hyperchromia (CI > 1.05).
Normal physiological exfoliation of the epithelium of the gastrointestinal tract due
to disruption of cell division is not restored. Therefore, atrophic-inflammatory

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processes develop in the epithelium of the entire gastrointestinal tract. At the same time
absorption of vitamins is even more broken.
Because of vitamin B12 deficiency, methylmalonic acid accumulates in the body,
which is toxic to nerve cells. In addition, vitamin B12 deficiency in nerve fibers
synthesizes fatty acids with altered structure, which affects the synthesis of myelin and
leads to axonal damage. Degeneration of the posterior and lateral columns of the spinal
cord (funicular myelosis) develops, the craniocerebral and peripheral nerves are
affected.
Blood picture: megaloblastic, hyperchromic, macrocytic anemias. In a blood
smear there are megalocytes and megaloblasts, poikilocytosis, anisocytosis is found,
the number of reticulocytes decreases, thrombocytopenia and leukocytopenia are
observed.
Iron deficiency anemia is anemia caused by a lack of iron in the body as a result of
an imbalance between its intake, consumption and loss.

Etiology:
1. Chronic blood loss, leading to iron loss along with red blood cells.
2. Increased need for iron (during growth, maturation, pregnancy, lactation).
3. Alimentary iron deficiency.
4. Non-absorption of iron:
a) in achlorhydria (hydrochloric acid ionizes iron, which is necessary for its
assimilation);
b) in vitamin C deficiency (vitamin C stabilizes iron in divalent form, because
trivalent iron is not absorbed by the body);
c) with enteritis and resection of the small intestine.
5. Disorders of iron transport (transferrin deficiency in liver damage).
6. Insufficient utilization of iron from its reserve (in case of infection,
intoxication).

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 7. Violation of iron deposition (ferritin deficiency in hepatitis, cirrhosis).
Pathogenesis: iron deficiency in the body disrupts its inclusion in erythrocytes,
while reducing the synthesis of heme and globin, reduces the activity of some enzymes
in erythrocytes, which causes an increase in their sensitivity to oxidants. The lifespan
of erythrocytes decreases.
Along with pathological changes in erythropoiesis, iron deficiency in the body
leads to a decrease in myoglobin and the activity of iron-containing factors of tissue
respiration. Hemic anemic hypoxia develops, and this leads to atrophic and dystrophic
processes in tissues and organs (especially in the gastrointestinal tract and
myocardium).
Blood picture: normoblastic anemia, hypochromic, there is anisocytosis
(microcytosis), anemia can be first regenerative, and then hyporegenerative.
Hypoplastic (aplastic) anemia is a disease of the blood system, which is
characterized by suppression of hematopoietic function of the red bone marrow and is
manifested by insufficient formation of erythrocytes, granulocytes and platelets
(pancytopenia) or erythrocytes alone (partial hypoplastic anemia).

Etiology:
1) physical factors (ionizing radiation);
2) chemical agents (benzene, lead, mercury vapor, drugs: cytostatics,
chloramphenicol, sulfonamides);
3) biological factors (hepatitis virus).
Pathogenesis:
1. Stem cell damage with the development of pancytopenia.
2. Damage to cells of the microenvironment - a violation of stromal cells, which
have a significant impact on the processes of reproduction and maturation of blood
cells.

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 Blood picture: normochromic anemia, regenerative, agranulocytosis,
thrombocytopenia, the number of lymphocytes may remain unchanged. In the red bone
marrow, the number of hematopoietic cells decreases with increasing fat content.

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 Chapter 3. Disorders of the leucocytic system (wbc)

The content of leukocytes per unit volume of blood is normally 4.0 * 109 / l-9.0 *
109 / l. (G/L).
Leukocytosis is an increase in the number of leukocytes per unit volume of blood
over 10 * 109 / l.
Classification of leukocytosis:
I. Depending on the reasons of development allocate physiological and
pathological leukocytosis. Physiological leukocytosis is a physiological reaction of the
body to strong emotions (emotional), during intense physical activity (myogenic), after
meals (alimentary), during the transition of a person from horizontal to vertical position,
in pregnant women and newborns.
Pathological leukocytosis is associated with the pathological process in the body
in infectious diseases, inflammatory and allergic processes, intoxication of exogenous
and endogenous origin.
ІІ. Leukocytosis can be absolute or relative. Absolute leukocytosis is characterized
by an increase in the absolute number of leukocytes per unit volume of blood. Relative
leukocytosis is the case when the relative content of certain forms of leukocytes in the
peripheral blood increases.
III. By pathogenesis:
a) reactive, which occurs as a reaction of the red bone marrow to pathogenic
effects in infectious diseases, inflammation, low doses of toxic substances.
Pathogenesis: increased proliferation and maturation of leukocytes in the red bone
marrow under the action of leukopoietins; increasing the transition of reserve
leukocytes from the red bone marrow with interleukin-1 and bacterial endotoxins that
increase the permeability of the blood vessels of the red bone marrow.
b) redistributive, which occurs as a result of the transition of leukocytes from the
parietal pool to the circulating. Most forms of physiological leukocytosis by the
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mechanism of their development are redistributive. Its features are: a) short-term nature
with a rapid return of the number of leukocytes to normal after the end of the cause; b)
maintaining the normal quantitative ratio of different types of leukocytes (leukocyte
formula does not change); c) the absence of degenerative changes in leukocytes.
c) tumor origin.
IV. Depending on the types of leukocytes, the content of which in the blood is
increased, there are:
a) neutrophilic leukocytosis - is observed in: a) purulent-inflammatory processes
caused by purulent bacteria (abscesses, phlegmons, sepsis); b) severe hypoxia (acute
blood loss, acute hemolysis); c) endogenous intoxication (uremia);
b) eosinophilic leukocytosis - occurs in: a) allergic reactions of type I according
to the classification of Coombs and Jell; b) helminthiasis; c) chronic myelogenous
leukemia;
c) basophilic leukocytosis - is detected in: a) chronic myelogenous leukemia; b)
hemophilia; c) Vakez's disease (polycythemia);
d) lymphocytic leukocytosis - is observed in: a) acute infectious diseases
(pertussis, viral hepatitis); b) some chronic infectious diseases (tuberculosis, syphilis,
brucellosis); c) chronic lymphocytic leukemia;
e) monocytic leukocytosis - characteristic of: a) chronic infections (tuberculosis,
brucellosis); b) infectious mononucleosis; c) infections caused by rickettsiae and
protozoa (typhus, malaria).
Leukocyte formula is the percentage of different forms of leukocytes in the
peripheral blood.
Leukocyte formula shift (nuclear shift) is a violation of the relationship between
immature and mature forms of neutrophils. An increase in the content of young forms
of neutrophils in the blood indicates a nuclear shift to the left, the predominance of
mature neutrophils with a large number of segments on the background of the
disappearance of younger cells - a nuclear shift to the right.
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 Types of nuclear shift to the left:
1. Regenerative shift is an indicator of reactive activation of granulocytopoiesis.
2. Hyperregenerative shift reflects excessive hyperplasia of leukopoietic tissue
with impaired cell maturation and pronounced rejuvenation of the blood.
3. Degenerative shift indicates depression and profound disorders of leukopoiesis.
4. Regenerative-degenerative shift is observed at hyperproduction in a bone
marrow of pathologically changed leukocytes and disturbance of their maturation.
Leukopenia is a decrease in the number of leukocytes in the peripheral blood
below 4 * 109 / liter.
Classification of leukopenia:
I. The origin of leukopenia are acquired and hereditary. Acquired leukopenia can
be caused by physical (ionizing radiation), chemical (benzene, cytostatics, drugs),
biological (hepatitis viruses, infectious mononucleosis) and immune factors.
Examples of hereditary leukopenia are Kostman's neutropenia, hereditary
neutropenia of autosomal dominant type, lazy leukocyte syndrome.
II. By type of leukocytes, the number of which is reduced, there are:
a) neutropenia;
b) lymphopenia;
c) eosinopenia.
III. On pathogenesis distinguish:
a) leukopenia caused by a violation of the flow of leukocytes from the red bone
marrow into the blood. Pathogenesis: damage to hematopoietic cells of cytolytic and
antimetabolic nature; violation of mitosis (ineffective leukopoiesis) due to deficiency
of vitamin B12, folic acid and leukopoietins; impaired leukocyte maturation; violation
of the release of leukocytes from the red bone marrow into the blood; reduction of the
bridgehead of leukopoiesis.

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 b) leukopenia associated with a reduction in the residence time of leukocytes in
the peripheral blood. Pathogenesis: destruction of leukocytes, which is caused by
autoimmune mechanisms and hypersplenism (increased phagocytic activity of splenic
macrophages); increased use of leukocytes; enhanced excretion of leukocytes from
the body.

c) redistributive leukopenia.
Agranulocytosis is a clinical and hematological syndrome characterized by a
sharp decrease in the content of neutrophils below 0.75 * 109 / l with a decrease in the
total number of leukocytes below 1-109 / l.
Pathogenesis:
a) Myelotoxic lesion of the red bone marrow;
b) Immune destruction of granulocyte cells by antileukocyte antibodies.
Agranulocytosis is accompanied by a weakening of the body's reactivity due to
the exclusion of the protective function of leukocytes.

Hemoblastosis is the collective name for neoplastic diseases of the blood

system, which are malignant neoplasms of hematopoietic and lymphatic tissues with
the involvement of a number of organs and systems of the body. Typical forms of
hemoblastosis are neoplasms that occur in the bone marrow (leukemia) and outside the
bone marrow (lymphoma).
Leukemia is a systemic neoplastic disease in which a mutant tumor clone
emerges from stem cells (stem cells) and hematopoietic progenitor cells. It occurs
primarily in the bone marrow; manifested by unrestrained proliferation and
rejuvenation of hematopoietic elements with delayed maturation and metaplasia of
hematopoietic tissue.
Classification of leukemias:
1 - According to the degree of differentiation (maturity) of leukemic cells, there
are acute and chronic leukemias.
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 Acute leukemias are a heterogeneous group of tumors of the blood system, the
substrate of which are young immature hematopoietic cells that displace normal
elements. All acute leukemias arise from a single mutated hematopoietic cell.
In acute leukemia, the tumor substrate is blast cells. At acute leukemias in a bone
marrow more than 30% of leukemic blasts come to light, they on number prevail and
in peripheral blood, complete delay of maturation is characteristic, absent or
considerably reduced maturing and differentiated forms of leukocytes (leukemic failure
- hiatus leukoemicus). Leukemic failure is an unfavorable prognostic sign.
In chronic leukemia, cell maturation is partially delayed, the substrate of the tumor
is maturing and mature cells, which are found in the peripheral blood.
Acute leukemia does not become chronic over time, because the previously lost
ability to differentiate the neoplasm does not regain. However, chronic leukemia can
transform into acute.

2 - By the number of leukocytes in the peripheral blood. Leukemias at one stage

or another of their course are classified as:
- leukemic (a sharp increase in the number of leukocytes - from 50.0-100.0 * 109
/ l);
- subleukemic (increase in the number of leukocytes from 20.0-50.0 * 109 / l);
- aleukemic (the number of leukocytes is not changed);
- leukopenic (the number of leukocytes is reduced - <4 * 109 / l).
3 – according to the types of hemopoiesis they distinguish myelo- and lympho-
leukemias.
The etiology of leukemia is similar to most malignant neoplasms. Their
development is due to the action of chemical, physical, biological carcinogens. Among
them, special importance belongs to ionizing radiation, other types of radiation,
chemicals (benzene and its derivatives), RNA and DNA oncoviruses. The carcinogenic

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effect is realized in the conditions of the broken resistance and reactivity of an
organism, especially at hereditary and acquired defects of immune system.
The pathogenesis of leukemia is characterized by staged molecular genetic
disorders that underlie carcinogenesis. Leukemias, like other malignant tumors, are
monopathogenetic. Stages of pathogenesis of leukemia reflect the typical phase of
development of malignant neoplasms.
Stage I - initiation (tumor transformation). Under the influence of carcinogens in
the hematopoietic stem cell of the bone marrow there are point mutations (deletions) of
suppressor genes (antioncogens) and oncogenes with the disabling of the antiblastoma
program, including apoptosis. These key genetic disorders give the mutated stem cell
the ability to divide indefinitely, which is a fundamental property of tumor growth. The
hematopoietic stem cell becomes a leukemic (cancer) stem cell.
Stage II - promotion. In the presence of promoter factors in the body that enhance
cell proliferation, leukemic stem cell divides indefinitely, which leads to the formation
of an immortal monoclone with a subsequent increase in its number. Thus, the
formation of a tumor population in the bone marrow is based on the initial appearance
of one malignant stem cell, and then - a clone of leukemic cells.
Stage III - progression. During this stage, subsequent multiple mutations
contribute to the increasing destabilization of the genome of transformed monoclonal
cells with overexpression of new oncogenes and suppression of antioncogenes. This
leads to more aggressive subclones, the cells of which acquire malignant properties
with replacement (metaplasia) of normal hematopoiesis, spread (dissemination)
hematogenously into the tissues of the carrier and the formation of infiltrates of
proliferating blasts, foci of perverted (aberrant) hematopoiesis.
The main feature of the pathogenesis of acute leukemia is that leukemic cells,
having acquired the ability to infinite uncontrolled growth, completely lost the ability
to mature, ie to differentiate into the following forms.

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 At the same time at chronic leukemias leukemic cells together with ability to
infinite growth keep property to mature and give the following forms.
Thus, in acute leukemia, tumor cells only divide and do not mature, in chronic - divide
and mature. Given this circumstance, acute leukemia should be considered a more
malignant disease.
The source of acute leukemia can be hematopoietic cells of the first four classes.
If leukemia develops from cells of I-III classes, which do not have specific
morphological and cytochemical features, then such leukemia is called
undifferentiated. If leukemia develops from class IV cells, then with the help of
morphological and cytochemical methods it is possible to establish the cell from which
the tumor arises.
If the source of leukemic cells are lymphoblasts, then such leukemia is called
acute lymphoblastic, if myeloblasts - acute myeloblastic, etc.
Acute myeloblastic leukemia develops mainly in young and middle-aged people.
Characteristic features:
- in the blood will be found tumor cells - myeloblasts, which are the source of the
tumor;
- because the red bone marrow stores cells of normal hematopoiesis, they will be
a source of normal leukocytes, ie those that should be in the blood in the norm -
metamyelocytes, rod-shaped and segmental neutrophils;
- in the blood there are no transitional forms of leukocytes from myeloblasts to
those cells that are found in the blood in the norm, ie there are no promyelocytes and
myelocytes. This phenomenon is called leukemic failure.
- the total number of leukocytes is reduced or normal.
Acute lymphoblastic leukemia. Is a typical childhood leukemia. Characteristic
features:
- in the blood will be found tumor cells - lymphoblasts, which are the source of
the tumor;
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 - along with lymphoblasts are also all those cells that should be normal (due to
foci of normal hematopoiesis);
- there are no transitional forms of leukocytes from lymphoblasts to those cells
that are found in the blood in the norm, ie there are no prolymphocytes (leukemic
failure);
- the total number of leukocytes is reduced or normal.
Chronic leukemias develop from class IV hematopoietic cells.
Chronic myelocytic leukemia. The most likely source of this leukemia is
myeloblasts. Because leukemia is chronic, it means that leukemic myeloblasts retain
the ability to differentiate into the following forms. Therefore, from the leukemic tissue
of the red bone marrow into the blood in large quantities come all the cells that originate
from myeloblasts, namely promyelocytes, myelocytes, metamyelocytes, rod-shaped
and segmental granulocytes (no leukemic failure). The red bone marrow is dominated
by cellular elements of the myeloid series.
Chronic lymphocytic leukemia. The source of its development are lymphoblasts,
which have retained the ability to differentiate into the following forms -
prolymphocytes and lymphocytes. Therefore, the bulk of leukemic blood cells are
represented by lymphocytes. Their number in the leukocyte formula is 80-90%. In
addition to leukemic lymphocytes in the blood can be found prolymphocytes and single
lymphoblasts. Characteristic is the appearance of the so-called Botkin-Gumprecht
shadows - half-destroyed lymphocyte nuclei, which appear as an artifact in the
preparation of blood smears.
Chronic leukemias are most often characterized by leukemic and subleukemic
variants.
Clinical syndromes in the development of leukemia:
I. Hematological syndromes:
1. Pancytopenia - a decrease in the content of all formed elements of the blood.
2. Anemia. The basis of its pathogenesis is a violation of erythropoiesis.
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 3. Hemorrhagic syndrome. Caused mainly by thrombocytopenia and leukemic
infiltrates into the walls of blood vessels.
4. Violation of nonspecific antimicrobial protection, in connection with which the
body's resistance to infections decreases.
5. Immunological insufficiency. It develops as a consequence of lymphopenia or
inferiority of leukemic lymphocytes.
II. Syndromes associated with the peculiarities of the functioning of leukemic
cells:
1. Fever. Most fevers are of non-infectious origin.
2. Intoxication. Many components of dead leukemia cells have a toxic effect on
the central nervous system. Hence fatigue, general weakness, nausea, and others.
3. Autoimmune processes.
III. Syndromes associated with metastasis of leukemic cells and the development
of leukemic proliferates in various organs and tissues:
1. Enlargement of lymph nodes, liver and spleen.
2. Skin syndrome. Due to the appearance in the skin of proliferates of leukemic
cells - leukemids.
3. Ulcerative-necrotic lesions of the mucous membranes (stomatitis, sore throat,
enteropathy).
4. Osteoarticular syndrome, manifested by pain in the bones and joints.
5. Neuroleukemia syndrome. It can be manifested by a syndrome of increased
intracranial pressure, various neurological disorders: paresis, paralysis, paresthesias.
6. Leukemic pneumonitis. Leukemic proliferates disrupt the respiratory function
of the lungs - develops respiratory failure.
7. Heart failure. May be due to the proliferation of leukemic cells in the heart
muscle.
Leukemoid reactions are reactive, to some extent functional states of the
hematopoietic system, lymphatic and immune systems of the body, arising from various
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severe diseases. Leukemoid reactions are not independent diseases, but changes in
peripheral blood (leukocytosis and changes in leukocyte formula looking like
hyperactive shift to the left) and hematopoietic organs, resembling leukemia and other
tumors, but not transformed into them.

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 Chapter 5. Disorders of the hemostasis system

Hemostasis is a complex system of homeostasis, which on the one hand maintains

blood in a liquid state, to ensure normal blood supply to organs and tissues, and on the
other hand - stops bleeding and prevents blood loss from the body by maintaining the
structural integrity of blood vessel walls and rapid thrombosis in damage.
Hemostasis is realized by three interacting structural components:
1. the walls of blood vessels,
2. blood cells,
3-plasma enzyme systems - coagulation, fibrinolytic (plasmin), kallikrein - kinin.
Vascular and platelet hemostasis. The main role in the implementation of
primary hemostasis belongs to platelets. As a result of damage to blood vessels,
platelets come into contact with the subendothelium - mainly the main stimulator of
adhesion - collagen - swell, form processes and stick. The duration of this phase is 1-3
seconds. This requires Ca ions and a protein synthesized in the endothelium -
Willebrand's factor (VIII), and in platelets - interacts with this factor membrane
glycoprotein Ib, which in its absence leads to Bernard-Soulier disease.
Adhesion is followed by rapid aggregation of platelets to the site of damage - phase
II (tens of seconds), which leads to rapid growth of blood clots. The primary stimulus
for aggregation is given by collagen and to an even greater extent by ADP,
catecholamines and serotonin released from the vascular wall, from hemolyzed
platelets in the damaged area and already adhered platelets.
From platelets that have undergone adhesion and aggregation, granules with
substances that enhance the aggregation process and form its second wave are actively
secreted: adrenaline, noradrenaline, serotonin, antiheparin factor.
As a result of the interaction of platelet and plasma factors in the hemostasis zone,
thrombin is formed, small doses of which sharply enhance and complete the process of

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aggregation and simultaneously trigger blood clotting, as a result of which the platelet
clot becomes dense and retracts - phase III - viscous.
After platelet aggregation and fibrin formation, a special contractile protein of
platelets, thrombostenin, is reduced under the influence of retractosyme, which leads to
the convergence of platelets and fibrin threads. Retraction requires thrombin, which
promotes viscous metamorphosis.
In the regulation of platelet hemostasis play an important role derivatives of
arachidonic acid, released from the membrane phospholipids of platelets and the
vascular wall due to the activation of phospholipases. Under the influence of
cyclooxygenase, prostaglandins are formed, from which an extremely powerful agent
is formed in platelets under the influence of thromboxane synthetase - thromboxane
A2. The lifespan of thromboxane, prostacyclin and other prostaglandins is a few
minutes, but their importance in the regulation and pathology of hemostasis is very
high. At the same time, paraproteins, cryoglobulins and fibrinolysis products inhibit
platelet aggregation.
Coagulation hemostasis. Blood coagulation is a complex multi-stage process
involving a number of protease proteins, non-enzymatic accelerator proteins that ensure
the interaction of coagulation factors on phospholipid matrices (platelet factor 3,
micromembranes of other cells), calcium ions.
It is conventionally divided into 3 phases:
1 - the formation of thromboplastin,
2 - thrombin formation
3 - the final stage, where under the influence of thrombin fibrinogen is first
converted into fibrin monomers, and then into its polymer, which is stabilized by
activated factor XIII.
According to the modern cascade-complex theory of blood coagulation, the
activation of prothrombin is the result of a multistage enzymatic process in which
various coagulation factors are sequentially activated and interact with each other. Of
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these, factors III, VII, IX, X, XI and XII, as well as prekallikrein are protease enzymes,
and factors VIII and V are non-enzymatic accelerators of the process, which accelerate
the interaction and activation of enzyme factors many thousands of times.
There are two main mechanisms for starting the coagulation process - external and
internal. At the external mechanism of blood coagulation it is stimulated by receipt in
plasma of fabric thromboplastin. At the internal mechanism of blood coagulation occurs
without participation of fabric thromboplastin. The starting factor here is factor XII
(Hagemann), the activation of which occurs either due to contact with a foreign surface
(glass, metal) or due to its enzymatic cleavage by kallikrein, plasmin or by contact with
subendothelium (collagen) and other components of connective tissue in trauma,
vasculitis , atherosclerosis.
Physiological anticoagulants are needed to keep the blood in a liquid state and to
limit the process of thrombosis. They are divided into two main groups:
1. primary, or independently synthesized and constantly contained in the blood,
2. secondary, formed during proteolysis during blood clotting and fibrinolysis.
Among the primary most important are the following protein inhibitors:
Heparin is a natural anticoagulant (along with fibrinolysin is part of the
physiological anticoagulant system of the blood). Produced in basophils and labrocytes.
Heparin directly affects blood clotting factors, blocking or reducing their activity.
When administered intravenously, the effect occurs almost instantly and lasts 4-6 hours.
Heparin is destroyed in the tissues with the participation of heparinase (urogeparin is
formed, which is excreted through the kidneys). Heparin has antithromboplastin,
antiprothrombin and antithrombin effects, delays the transition of fibrinogen to fibrin,
increases fibrinolysis, in large doses inhibits platelet aggregation and adhesion,
increases vascular permeability.
Antithrombin III is a universal inhibitor of almost all enzymatic coagulation
factors, primarily thrombin - IIa and Xa. It accounts for more than 75% of all plasma
anticoagulant activity. It is the main plasma cofactor of heparin and if antithrombin III
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is low in the blood, it makes no sense to inject heparin to treat thrombosis. With
hereditary or acquired decrease in antithrombin III there is a severe thrombophilic
condition with recurrent thrombosis of the main veins of the extremities and internal
organs, pulmonary embolism, heart attacks.
Secondary physiological anticoagulants are formed in the process of blood
coagulation and fibrinolysis as a result of subsequent enzymatic degradation of a
number of coagulation factors. After initial activation, they lose the ability to participate
in hemostasis and often acquire anticoagulant properties. Thus, fibrin adsorbs and
inactivates large amounts of thrombin (and is referred to as antithrombin I). The enzyme
cleavage products of fibrinogen / fibrin by plasmin (fibrinolysin) inhibit both platelet
aggregation and the self-formation of fibrin monomers - ie the formation of fibrin.
Adrenaline in combination with fibrinogen and heparin is converted from a stimulator
of platelet aggregation and blood clotting into a factor that prevents hemocoagulation
and an activator of non-enzymatic fibrinolysis.
Fibrinolysis - an enzyme system (which causes asymmetric cleavage of fibrin /
fibrinogen into smaller fragments) is called fibrinolytic or plasmin. The main
component of this system is the enzyme plasmin (fibrinolysin), which is contained in
the plasma in the form of a proenzyme - plasminogen. Active plasmin is rapidly blocked
by antiplasminogens and excreted from the bloodstream. With the introduction of
streptokinase or urokinase, the level of plasminogen in the blood decreases very quickly
and deeply due to the transition to active plasmin, and then within 18-28 hours is
restored. In the body, the activation of fibrinolysis (as well as the activation of
coagulation) can be both external and internal.
Mechanisms and factors of maintaining blood in a liquid state. Maintaining blood
in a liquid state is due to the presence of anticoagulants, the activity of which should be
higher than coagulants. Given the many coagulation factors, there is a powerful system
of anticoagulants. It contains antithromboplastins, antithrombin, enzymes that prevent
the transition of fibrinogen to fibrin. When thrombin enters the blood, it irritates the
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chemoreceptors of the vascular wall. Hence, the stimulus is reflexively transmitted to
the medulla oblongata and as a result there is a release from the vascular wall of heparin
and heparin-like anticoagulants, which delay the formation of fibrin and its conversion
into fibrinogen (spherical shape).
Thrombosis occurs more often in violation of the biological reliability of the
hemostasis system with damage to its regulatory mechanisms, leading to thrombophilia.
Thrombophilia occurs due to changes in one or more components of the hemostasis
system, ie activation of the external and internal systems.
Causes of intravascular thrombosis:
1. Pathology of the vascular wall (intima and media):
a) atherosclerosis (vascular lesions with increased platelet aggregation) and
hypertension (vascular spasm) (80% of diseases - thrombosis),
b) inflammatory vascular lesions, rheumatism (50% accompanied by thrombosis),
c) postoperative thrombosis (in severe operations under general anesthesia -
violation of the regulation of the hemostasis system),
d) myocardial infarction - and spasm and thrombosis,
e) in the disintegration of malignant tumors (increased tissue thromboplastin),
e) diabetes mellitus (vascular damage and physicochemical changes in the blood).
Disorders of vascular and platelet hemostasis.
Thrombocytopenia is a decrease in the content of platelets per unit volume of
peripheral blood below 150 * 109 / l.
Etiology:
1. impaired platelet production in the bone marrow (Werlhof's disease) or essential
thrombocytopenia;
2. death of platelets in the bloodstream when exposed to autoantibodies,
infections, intoxications, increased spleen function (hypersplenism);
3. increased platelet consumption in ICE - consumption thrombocytopathy.
Pathogenesis:
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1) violation of angiotrophic function of platelets, resulting in dystrophic changes in
the endothelium and increased fragility of microvessels;

2) violation of platelet adhesion and aggregation. This causes a violation of platelet

thrombus formation and leads to an increase in bleeding time (Duke's test);
3) violation of the secondary spasm of damaged arterioles. At thrombocytopenias
few biogenic amines (catecholamines, serotonin) are allocated, causing reduction of
smooth muscles of vessels;
4) impaired blood clotting. Due to insufficient release of factor 3 plates and
thrombostenin. As a result, phase I blood clotting and clot retraction are disrupted.
Pathogenetic therapy - replacement - the introduction of fresh blood or platelet
mass.
Thrombocytopathy is a violation of the functional properties of platelets, their
qualitative inferiority. At the same time the number of thrombocytes can remain
normal.
Etiology:
1. violation of the ability of platelets to adhesion, aggregation and excretion of
coagulation factors;
2) lack of 3 factors - thromboplastic - thrombocytodystrophy;
3) lack of 6 factors - retractosyme - thrombocytoasthenia.
Vasopathies are hereditary or acquired hemorrhagic diathesis that occurs as a
result of primary disorders of the vascular wall. Types:
1) inflammatory vasopathy - vasculitis:
- infectious vasculitis (with viral hemorrhagic fevers, typhus, sepsis);
- immune vasculitis (as a consequence of immunocomplex diseases (allergic
reactions of type III according to the classification of Coombs and Jelly), for example,
in systemic lupus erythematosus);
3) infectious-immune vasculitis.

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2) dysplastic vasopathy - vascular lesions associated with a violation of their
connective tissue (inferiority of the vascular wall). Causes: hypovitaminosis C,
telangiectasia (hereditary local defects of connective tissue of blood vessels, causing
thinning of their walls and expansion of their lumen), hemangiomas, genetically
determined defects of collagen.

Violation of coagulation hemostasis

The working classification can be based on the scheme of normal blood clotting.
Then the disease can be grouped according to the phases of blood clotting:
● coagulopathies caused by violation of phase I coagulation (deficiency of
factors VIII, IX, XI and XII), the presence in the blood of inhibitors to factors VIII
(hemophilia A) and IX (hemophilia B), deficiency of platelet component of
thromboplastin formation, angiohemophilia.
Hemophilia - characterized by bleeding of large vessels - bruises (90% in
children). Hemophilia is transmitted by women and is manifested in men. In children,
hemophilia is manifested to a greater extent by vascular damage, because they have
trauma to the surfaces, joints swell - ankylosis, severe pain, limited movement →
disability. Pathogenesis - poorly activated blood clotting factors, or developing their
immune system.
Laboratory diagnosis - clinical - bruising, slowing of blood clotting, decreased
thromboplastic activity of blood.
Treatment - replacement of the missing factor (fresh plasma or cryoprecipitate or
specific factors - VIII, IX).
● caused by violation of phase II blood coagulation: deficiency of plasma
components of thrombin formation - factors II, V, VII and X in liver pathology, the
presence of thrombin antagonists (antithrombin I - fibrin, antithrombin II - heparin,
antithrombin III, IV, V, VI), the presence antagonists to prothrombin complex factors
(II, V, VII, X).

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 Coagulopathy with lesions of the prothrombin complex resembles hemophilia -
large bruises (vitamin K deficiency, cirrhosis, jaundice), heparin overdose.
Laboratory diagnosis - decrease in prothrombin index.
Therapy - replacement of the missing factor or blockade of heparin by protamine
sulfate.
● violation of phase III. Reasons:
a) violation of the formation of fibrinogen in liver pathology,
b) increased consumption of fibrin in thrombosis, DIC syndrome,

c) pathological enhancement of fibrinolysis. Factor XIII deficiency may be

congenital. The course is difficult.
Laboratory diagnosis - determination of fibrinogen and its fractions, the level of
fibrinolysis.
Therapy - the introduction of fibrinogen and, if necessary - blockade of
fibrinolysis.
Disseminated intravascular coagulation (DIC) is one of the most severe
and dangerous disorders of the hemostasis system. Is a nonspecific reaction
characterized by the widespread formation in the vascular bed of microclots and cell
aggregates that cause peripheral circulatory disorders with the development of
generalized hemorrhages and severe multiorgan failure.
Etiology:
• all types of shock (anaphylactic, traumatic, burn, cardiogenic),
• acute blood loss,
• infection,
• acute intravascular hemolysis,
• immune conflict,
• massive blood transfusion,
• tumors,

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 • obstetric pathology (premature detachment of the placenta, fetal death, vesical
drift, eclampsia),
• severe poisoning by hemolytic poisons,
• acute and chronic leukemias
The pathogenesis of DIC syndrome is the activation of blood clotting, thrombin
formation, widespread fibrin deposition and systemic thrombosis in the
microcirculatory tract. Widespread intravascular coagulation leads to intensive
consumption of coagulation factors and platelets (coagulopathy and consumption
thrombocytopenia) with the development of hemorrhagic syndrome, which is also
facilitated by the activation of fibrinolysis and proteolysis in general. Mandatory
component of the ICE is hemorrhagic diathesis in the form of petechial hemorrhages in
the skin, mucous membranes, endocardium, pericardium, pleura, peritoneum,
meninges, internal organs, possible large hemorrhages in the pleural and abdominal
cavities, gastrointestinal tract. The severity of DIC is determined by the severity of
coagulopathy and thrombocytopenia consumption.
Stages of DIC syndrome:
Stage 1 - hypercoagulation and platelet aggregation. It is characterized by
activation of platelet and coagulation hemostasis and the beginning of
microthrombosis.
Stage 2 - increasing hypocoagulation. This phase develops as a consequence of
depletion of the mechanisms of vascular-platelet and coagulation hemostasis as a result
of reduced activity of the coagulation system (consumption of factors I, V, VIII);
activation of the fibrinolytic system (entry into the blood of a large number of activators
of fibrinolysis); increasing the anticoagulant activity of the blood due to the formation
of fibrinolysis products; development of thrombocytopenia consumption; increasing
the permeability of the vessel wall (it is important to form large amounts of kinins).
Stage 3 - restorative. Occurs after the elimination of acute hemostasis and multiple
organ failure. It is characterized by gradual normalization of indicators of all links of
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hemostasis, improvement of function of the affected bodies, stabilization of the general
condition of patients.

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 Chapter 5. Pathophysiology of the heart

Heart failure is a condition in which the heart, like a pump, does not meet the
metabolic needs of organs and tissues with the required amount of blood.
Etiology:
• Overload of cardiac activity (overload);
• Primary myocardial infarction (myocardial);
• Primary pericardial damage (extramyocardial);
• Severe cardiac arrhythmias;
• Combined heart disease.
Classification:
- The predominant lesions of the heart are:
1. Left ventricular heart failure → blood stasis in the veins of the small circulation
→ pulmonary edema. Cardiac asthma (shortness of breath, paroxysmal nocturnal
dyspnea) occurs as a result of blood stasis in the small circle of blood circulation and
the development of pulmonary hypertension and interstitial pulmonary edema.
Manifested by the development of shortness of breath and cough without sputum.
Pulmonary edema is a consequence of the progression of cardiac asthma. Pulmonary
hypertension → transudation of plasma into the lumen of the alveoli. Manifested by
cough with foamy sputum.
2. Right ventricular heart failure → blood stasis in the great circle of blood
circulation → edema of the legs, ascites, enlarged liver.
3. Total heart failure.
- By course: acute and chronic.
- In the predominant failure of the phase of the cardiac cycle:
1. Systolic (impaired pumping function of the heart → decreased cardiac output);
2. Diastolic (violation of the relaxation of the walls and filling of the left ventricle
due to its hypertrophy or fibrosis → increase in end-diastolic pressure).
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 Types of overload:
1. Blood volume overload:
• Hypervolemia;
• Insufficiency of heart valves → ↑ filling of heart cavities with blood during
diastole.
2. Overload resistance:
• Stenosis of the heart valves;
• Hypertension of small and large circles of blood circulation → ↑ resistance of
emission of blood from heart to systole.
Mechanisms of compensation with increasing load on the heart:
Short-term:
• Heterometric mechanism - Frank-Starling's law (↑ length of myofibrils during
diastole enhances systole → tonogenic dilatation);
• Homeometric mechanism (↑ myocardial voltage capacity without increasing the
length of myofibrils);
• Chronoinotropic mechanism (Boudich's phenomenon) - with increasing heart
rate increases the strength of its contractions. At the same time, the relaxation time of
the myocardium decreases, which contributes to the rapid filling of the ventricles of the
heart with blood;
• The inotropic action of catecholamines (not Frank-Starling's law) is the leading
mechanism of adaptation of the heart to exercise, as a result of their action increases
the number of Ca-channels of sarcolemma, resulting in increased contractions of
cardiomyocytes as calcium-troponin complexes increase.
Long-term:
Myocardial hypertrophy
Stages of hypertrophy according to F.Z. Meerson:
1. Emergency (compensatory hyperfunction of the heart) increase in the intensity
of functioning of cell structures:
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 • Decomposition of macroergic phosphorus compounds, accumulation of ATP
degradation products (ADP, AMP, Fn);
• Increasing energy production;

• Activation of the genetic apparatus of cardiomyocytes;

• Increased synthesis of nucleic acids and protein.
Increased heart function → prostaglandins, angiotensin II → activation of
adenylate cyclase → ↑ intracellular cAMP → activation of the genetic apparatus →
increased synthesis of nucleic acids and protein.
2. Stage of complete hypertrophy and relatively stable hyperfunction:
• Normalization of the functioning of cell structures per unit of muscle mass;
• Normalization of energy production and protein synthesis per unit of
myocardium.
• Increasing myocardial mass by increasing the volume of each cardiomyocyte.
3. Stages of progressive cardiosclerosis and depletion of myocardial function:
Loss of vital activity of cardiomyocytes → proliferation of fibroblasts → growth
of connective tissue → gradual decrease in strength and speed of contraction and
relaxation of the heart → myogenic dilatation → chronic congestive heart failure.
Features of hypertrophied heart:
1. The growth of the cell surface lags behind the growth of muscle mass →
violation of membrane-bound processes.
2. The growth of mitochondrial mass lags behind the growth of muscle mass →
energy deficit.
3. The increase in the mass of the nucleus lags behind the growth of the sarcoplasm
→ deficiency of plastic supply.
4. The growth of blood vessels lags behind the growth of muscle mass →
deficiency of blood supply.

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 5. The growth of nerve fibers lags behind the growth of muscle mass →
deterioration of innervation.
6. Predominant diastolic dysfunction of the heart.
Myocardial form of heart failure (primary myocardial damage) (dystrophic and
necrotic changes as a result of metabolic disorders in the myocardium):
• coronary origin (coronary insufficiency);

• non-coronary origin (myocardial damage by chemical, physical, biological

factors).
Cardiac arrhythmias are disorders of frequency, rhythm, consistency and
sequence of its contractions.
The development of arrhythmias may be associated with violations of the basic
functions of the cardiac conduction system: automatism, excitability and conduction.
The classification of arrhythmias is based on this, according to which they distinguish:
I. Arrhythmias caused by violations of automatism.
II. Arrhythmias associated with disturbances of excitability.
III. Arrhythmias due to conduction disorders.
IV. Arrhythmias associated with combined disturbances of excitability and
conduction.
There are two groups of arrhythmias associated with impaired heart
automatism.
I. Nomotopic arrhythmias. The generation of impulses for contraction, as in the
norm, occurs in the sinus-atrial node. This group includes:
a) sinus tachycardia - an increase in heart rate;
b) sinus bradycardia - a decrease in heart rate;
c) sinus (respiratory) arrhythmia - a change in heart rate in different phases of the
respiratory cycle (increased frequency with inhalation and decreased exhalation).

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 II. Heterotopic arrhythmias - sick sinus syndrome. The generation of impulses
for contraction occurs not in the sinus-atrial node, but in other structures of the
conducting system, which are pacemakers of the II and III order. In this case, the
following types of pathological heart rhythms can develop:
a) atrial slow rhythm - the pacemaker is in the structures of the left atrium, the
heart rate is less than 70 per minute;

b) atrioventricular rhythm - the source of impulses is second-order pacemakers

(upper, middle or lower part of the atrioventricular node), the heart rate, depending on
the place of generation of impulses, decreases from 70 to 40 per minute;
c) idioventricular ventricular rhythm - the generation of impulses occurs in the
pacemakers of the III order (the bundle of Giss or its legs), the heart rate is less than 40
per minute.
Sinus tachycardia is an increase in heart rate of more than 90 minutes in adults.
There are physiological (increased heart rate under the influence of various influences
in the absence of pathological changes in the cardiovascular system: exercise,
emotional stress, changes in the environment) and pathological tachycardia
(intoxication, heart disease, myocardial infarction, rheumatism).
Sinus bradycardia (vagotonia - less than 60): in healthy individuals or as a result
of a congenital decrease in the automaticity of the sinus-atrial node, or in athletes as a
result of changes in energy and hemodynamics. Pathological sinus bradycardia is often
the result of irritation of the vagus nerve (nervus vagus) in CNS injuries, pathological
processes in the mediastinum, vagus nerve irritation in peptic ulcer and gallstone
disease, in pathological processes in the myocardium.
Sinus arrhythmia: variability in heart rate associated with fluctuations in the
activity of the sinus node. Under physiological conditions may be in young people and
is associated with the act of breathing - an increase in tone n. vagus. At pathology there

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can be an alternation of tachy- and bradycardia - an unfavorable indicator at a heavy
condition of heart - an indicator of heart exhaustion.
Arrhythmias associated with impaired myocardial excitability:
At the basis of arrhythmias associated with impaired excitability is the appearance
of the so-called ectopic foci of excitation located outside the sinus-atrial node,
generating extraordinary impulses for contraction.
There are two most typical disorders of excitability:
a) extrasystoles;
b) paroxysmal tachycardia;
Extrasystole - this is a type of arrhythmias caused by impaired excitability, which
is manifested by the occurrence extraordinary contractions of the heart or only the
ventricles. Divided into atrial, atrioventricular and ventricular. Each type of
extrasystole has its own electrocardiographic picture, which allows you to determine
the place of the ectopic focus of excitation.
Paroxysmal tachycardia is an arrhythmia caused by impaired excitability,
manifested by the emergence of a group of rapidly repeating extrasystoles that
completely suppress the physiological rhythm.
With paroxysmal tachycardia, the normal heart rhythm is suddenly interrupted by
an attack of contractions with a frequency of 140 to 250 beats per minute. The duration
of the attack can be different - from a few seconds to several minutes, after which it just
as suddenly stops and a normal rhythm is established.
Heart contractions in paroxysmal tachycardia are strictly rhythmic. There are 3
forms: atrial, atrioventricular and ventricular. The first two forms are also called
supraventricular paroxysmal tachycardia.
There are two groups of arrhythmias associated with conduction disorders.
1. Heart block. These are arrhythmias caused by a slowdown or
complete cessation of impulses through the conductive system.

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 2. Accelerated conduction of impulses - Wolff-Parkinson-White
syndrome.
Conduction abnormalities can occur between the sinus node and the atria,
within the atria, between the atria and ventricles, and in one of the bundle branch
legs. Therefore, the following types of blockade are distinguished:
a) sinoatrial,
b) intraatrial,
c) atrioventricular
d) intraventricular block.
Atrioventricular, or transverse, heart block can be complete or incomplete. In
incomplete heart block, three degrees are distinguished:

1. Atrioventricular block of the I degree is characterized by an increase in the time

of impulse conduction from the atria to the ventricles, which is accompanied by
an extension of the P-Q interval (0.2-0.5 s).
2. Grade II block (Wenckebach periods) is characterized by a progressive increase
in the P-Q interval until one of the excitations, usually the eighth to tenth, is not
carried out.
3. With blockade of the III degree, loss of every second or third contraction is
observed, or, conversely, only every second, third or fourth atrial excitation is
performed.
4. With complete atrioventricular block, the atria and ventricles contract
independently of each other, each in its own rhythm: the atria with a frequency
of about 70, the ventricles - about 35 beats per minute (idioventricular rhythm).

The Wolff-Parkinson-White syndrome is characterized by an accelerated

conduction of impulses from the atria to the ventricles, as a result of which the latter

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are prematurely excited, tachycardia develops, and the P-Q interval on the
electrocardiogram decreases.
The reason for the development of this syndrome is the existence of additional
pathways for conducting impulses. These paths include:
a) bundle of Paladino-Kent;
b) Mahaima bundle. Connects the upper part of the bundle of His to the ventricles;
c) James bundle. Connects the atria to the lower part of the atrioventricular node
or to the bundle of His.
Simultaneous disturbances in the functions of excitability and conduction:
1. Atrial flutter (atrial contraction rate - 250-400 in 1 min).
2. Atrial fibrillation (the frequency of impulses arising in the atria is 400-600 per
minute).
Atrial flutter and atrial fibrillation have the same developmental causes and can
pass into each other. Therefore, these two types of heart rhythm disturbances are united
by one concept - atrial fibrillation.
3. Ventricular flutter (ventricular rate - 150-300 in 1 min).
4. Flickering (fibrillation) of the ventricles (the frequency of impulses in the
ventricles is 300-500 per minute, the heart does not contract).
The most common causes of atrial fibrillation are: a) stenosis of the left
atrioventricular opening; b) thyrotoxicosis; c) atherosclerotic cardiosclerosis.
The most recognized at present is the theory of re-entry of impulses (re-entry),
which explains the mechanism of development of atrial fibrillation.
With ventricular fibrillation due to the chaotic contraction of individual muscle
fibers, the propulsive force of contractions is practically absent, blood circulation
ceases, loss of consciousness and death quickly occur. A decrease in the concentration
of intracellular potassium, as well as a change in the content of nerve mediators,
especially catecholamines, predispose to fibrillation.

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 In the treatment of ventricular fibrillation, it is most effective to send a short,
strong, single electrical shock through the heart. In this case, there is a simultaneous
depolarization of all myocardial fibers and the asynchronous excitation of muscle fibers
stops.

Extramyocardial insufficiency develops when little blood flows to the heart

through the veins or when it is unable to accept all the blood flowing. The first is
observed in hypovolemia (blood loss) or a sharp dilation of blood vessels (collapse),
the second - in the accumulation of fluid in the pericardial cavity, which makes it
difficult to dilate the cavities during diastole.
Coronary insufficiency is a pathological condition characterized by the inability
of the coronary vessels to supply blood to the heart in accordance with its energy needs.
Relative coronary insufficiency occurs in the case of a primary increase in the
energy needs of the heart (increased load on the heart during exercise, hypertension).
The intensity of coronary blood flow may increase, but this is insufficient to meet the
growing needs of the heart.
Absolute coronary insufficiency occurs in the case of primary coronary
circulation, resulting in reduced delivery of oxygen and myocardial nutrients both at
rest and with increasing energy needs of the heart. Pathogenesis: 1. Decrease in
perfusion pressure (arterial hypotension, disturbance of venous outflow); 2. Increase in
resistance of coronary vessels (increase in viscosity of blood at disturbance of its
rheological properties, decrease in radius of vessels).
Ischemic heart disease is a disease that develops as a result of absolute
insufficiency of the coronary circulation and is manifested by myocardial damage of
varying degrees.
Myocardial infarction - necrosis of the heart muscle due to circulatory disorders.
Occurs with reversible ischemia, which lasts more than 40-60 minutes, or with
irreversible disorders of coronary blood flow. Etiology:
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 1. Atherosclerosis of the coronary arteries.
2. Increased stress on the heart (physical exertion, hypertension).
3. Stress.
Clinical syndromes in myocardial infarction:
1. Pain syndrome.
2. Acute heart failure. Manifested by cardiac asthma and pulmonary edema or
cardiogenic shock.
3. Arrhythmic syndrome.
4. Resorption-necrotic syndrome.
Cardiogenic shock is a shock that occurs as a result of a sharp drop in the
pumping function of the heart. Pathogenesis:
Stage I - the primary drop in blood pressure. Reducing cardiac output leads to a
decrease in cardiac output and a drop in blood pressure.

Stage II - compensatory spasm of arterioles. The release of powerful

vasoconstrictors causes generalized spasm of the arterioles, resulting in increased total
peripheral resistance.
Stage III - a secondary drop in blood pressure. Prolonged spasm of arterioles in
peripheral tissues causes microcirculation disorders and hypoxia, which impairs the
contractile function of the heart and causes a further drop in blood pressure.
Stage IV - terminal changes. As a result of a significant drop in blood pressure,
coronary and cerebral circulation is disrupted, and acute renal failure develops. The
combination of these changes leads to death.

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 Chapter 6. Pathophysiology of blood vessels
According to the functional classification, blood vessels are divided into the
following groups:
1. Compensating vessels - aorta and elastic arteries. Their function is primarily to
convert the jerky discharge of blood from the heart into the bloodstream.
2. Resistive vessels, or vessels of resistance, - arterioles and venules located in the
pre- and postcapillary areas of the vascular bed. Resistance to blood flow in these
vessels is carried out due to the ability of the muscular structures of the wall to be in a
state of constant tone and actively change the size of the lumen.
3. Vessels of exchange - capillaries and venules. In the area of these vessels, a
bilateral exchange between blood and tissues takes place.
4. Capacitive vessels - mainly small veins. They deposit blood in order to
distribute it and return it to the heart. The bulk of blood (75-80%) is concentrated in
these vessels.
5. Vessels of redistribution - vessels-sphincters and arterio-venous shunts.
Regulate blood circulation in organs and tissues.
In accordance with the WHO recommendations (1955), all sclerotic lesions of the
arteries are divided into two groups.
I. Arteriosclerosis proper. Includes forms such as atherosclerosis, Menckeberg's
arteriosclerosis, arteriolosclerosis, age-related sclerotic changes in the arteries.
2. Diseases of the arteries of an inflammatory and inflammatory-allergic nature.
These include syphilitic aortitis, obliterating endarteritis, allergic vasculitis, rheumatoid
arteritis, etc.
Arteriosclerosis is a combination of four processes: infiltration, proliferation,
degeneration and sclerosis.
1. Infiltration - penetration from blood plasma into the vascular
wall and the deposition of lipids, complex carbohydrates and proteins in it.

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 2. Proliferation - multiplication of smooth muscle cells of the arterial wall, as a
result of which the so-called fibrous "plaques" are formed, protruding into the lumen of
the arteries and disturbing the blood flow in them.
3. Degeneration is a term that is used to denote damage and death of cells of the
vascular wall, as well as the development of degenerative changes.
4. Sclerosis - increased formation of connective tissue.
Atherosclerosis is a chronic focal lesion of arteries of elastic and muscular-elastic
type (ie large and medium caliber), in which their intima thickens due to lipid deposits
and the development of fibrous tissue.
Pathogenesis of atherosclerosis:
Regarding the pathogenesis of atherosclerosis, a large number of theories,
hypotheses, assumptions have been put forward:
• Theory of lipoprotein infiltration of the intima and its cellular response to altered
(modified) lipoproteins;
• Theory of endothelial dysfunction;
• Monoclonal theory;
• Autoimmune theory.
However, there are commonalities between them. Atherogenesis proceeds
sequentially in several stages: initiation, progression, atheroma formation,
fibroatheroma formation, development of atherosclerosis complications.
The following facts testify to the great physiological significance of cholesterol:
a) 300-500 mg of cholesterol enters the human body every day with food;
b) another 700 is synthesized in the body (mainly in the liver)
1000 mg cholesterol daily;
c) each cell of the body, with a few exceptions, has its own systems for the
synthesis of cholesterol, capable of meeting the needs of cells in this substance. It has
now been shown that for the onset of atherosclerosis, quantitative and qualitative
changes in blood plasma lipoproteins, which have received the general name
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"atherogenic dyslipoproteinemia", are of great importance. This condition is
characterized by the following symptoms:

a) an increase in the content of cholesterol and triglyceride-rich lipoproteins of

low (LDL) and very low (VLDL) density in blood plasma;
b) the appearance in the blood of lipoproteins not characteristic of the norm, which
are called "modified". These include glycosylated, acetoacetylated lipoproteins, etc.
c) a decrease in the content of high density lipoproteins (HDL) in blood plasma.
LDL, VLDL and "modified" lipoproteins are called atherogenic, and HDL -
antiatherogenic.
Arterial hypertension (AH) - a steady increase in blood pressure over 140/90 mm
Hg. There are primary (essential, hypertensive) and secondary (symptomatic)
hypertension.
Essential hypertension is a disease in which the increase in blood pressure is not
associated with primary organic damage to organs and systems. At the heart of the
disease is a violation of neurohumoral regulation of vascular tone.
Risk factors:
• Genetic factors (hereditary predisposition):
• Prolonged action of stressors:
- AH more often develops in people after emotional shocks;
- Hypertension occurs often in people whose professional activities are
associated with psycho-emotional stress.
• Excessive consumption (more than 5 g per day) of table salt.
• Smoking, alcohol, hypokinesia, noise, vibration, night work.
• Obesity, vascular atherosclerosis, endocrine diseases.
Pathogenesis:
1. Neurogenic mechanism

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Risk factors → Disorders of blood pressure control centers → Deficiency of inhibition
in the cerebral cortex → Persistent activation of the sympathetic autonomic nervous
system → Increased heart rate and strength, spasm of resistive vessels → ↑ minute
blood volume and total peripheral vascular resistance.
2. Hormonal mechanism

Activation of the hypothalamic-pituitary-adrenal system → Increased secretion of

glucocorticoids and other stress hormones.
3. Renal mechanism.
• Hereditary defects of the angiotensin-aldosterone system (RAAS) and tubular
epithelium;
• Activation of RAAS due to renal ischemia.
Secondary arterial hypertension occurs as a consequence of pathological
processes in various organs and systems. Types:
1. Renal hypertension:
a) hypertension may be in nephropathy of pregnant women; in autoimmune-
allergic diseases of the kidneys, both inflammatory (diffuse glomerulonephritis,
collagenosis) and dystrophic (amyloidosis, diabetic glomerulosclerosis).
b) in infectious interstitial diseases of the kidneys - in chronic pyelonephritis there
is hypertrophy and hyperplasia of the juxtaglomerular apparatus and a steady increase
in renin secretion.
c) renovascular or vasorenal - with impaired renal blood supply. In this case, the
leading role in stimulating renin secretion belongs to the reduction of blood flow in the
renal arteries. The formed angiotensin-II has a direct pressor effect and stimulates the
synthesis of aldosterone, which in turn increases the accumulation of Na + in the
vascular walls and enhances pressor reactions.
d) in urological diseases of the kidneys and urinary tract
e) renoprivny arterial hypertension develops after removal of both kidneys.

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 2. Neurogenic symptomatic hypertension:
a) centrogenic - associated with brain damage.
b) peripheral - associated with the defeat of the peripheral emergency - in polio,
polyneuritis.
3. Endocrine hypertension:
a) in hormonal tumors of the pituitary gland - acromegaly + increase in blood
pressure, Itsenko-Cushing's disease + increase in cortisol levels;
b) in tumors of the adrenal cortex - increased levels of glucocorticoids,
mineralocorticoids → hyperaldosteronism, pheochromocytoma → increased levels of
norepinephrine;
c) with diffuse toxic goiter - increased thyroxine levels → hyperkinesia;
d) with discrimination during menopause.
4. Hemodynamic arterial hypertension:
a) at decrease in elasticity of walls of an aorta and large vessels there is no adequate
stretching of a vascular wall by the pulse wave passing on vessels;
b) hypertension in aortic valve insufficiency due to an increase in the final diastolic
volume of blood in the left ventricle due to regurgitation of blood from the aorta during
diastole;
c) hypertension in coarctation of the aorta is associated on the one hand with a
sharp increase in blood flow resistance in the area of narrowing of the aorta, and on the
other hand - with impaired blood supply to the kidneys, as the renal arteries depart
below the coarctation site;
d) narrowing of the carotid, vertebral or basilar artery leads to cerebral ischemia -
cerebrospinal hypertension.
Hemodynamic variants of arterial hypertension:
1. Hyperkinetic type, which is due to a significant increase in heart rate, resulting
in an increase in its minute volume.

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 2. The eukinetic type occurs with a moderate increase in cardiac output and total
peripheral vascular resistance.
3. Hypokinetic type associated with a significant increase in total peripheral
vascular resistance.
Arterial hypotension (persistent decrease in blood pressure) is more common in
people with asthenic constitution and is manifested by general lethargy, fatigue,
tachycardia, shortness of breath, dizziness, hunger, fainting and depression with
periodic increase in nervous excitability.
Classification:

I. Physiological (not accompanied by painful symptoms in athletes,

asthenics).
II. Pathological (with a characteristic symptom complex):
1. Primary - hypotonic disease. It is believed that its main etiological and
pathogenetic factor, as well as hypertension, is the overstrain of the main processes of
the cerebral cortex (excitation and inhibition). However, in contrast to primary
hypertension, there is a prevalence of inhibition and its spread to subcortical vegetative
formations, in particular to the vascular center.
2. Secondary:
a) acute (shock, collapse, fainting);
b) chronic, which is a consequence of a number of general somatic acute and
chronic diseases of the heart (defects, myocarditis, myocardial infarction), brain, lungs
(lobar pneumonia, tuberculosis), liver (hepatitis, mechanical jaundice), blood (anemia),
endocrine glands, as well as exogenous intoxications.

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 Chapter 7. Pathophysiology of external breathing

Respiration is a set of processes that ensure the entry of oxygen into the body, its
use in the biological oxidation of organic substances and the removal of carbon dioxide.
External respiration: a) gas exchange in the alveoli between the lungs and the
external environment; b) exchange between alveolar gases and blood gases; c) transport
of gases by blood to tissues and cells - specifically to the functional elements of organs.
Respiratory failure is a condition of the body, which either does not maintain the
normal gas composition of the blood, or the latter is achieved through the intensive
work of compensatory mechanisms: increasing the minute volume of respiration due to
its depth and frequency - ie shortness of breath; increase in cardiac contractions,
increase in cardiac output, change in blood flow rate, increase in the number of
erythrocytes and hemoglobin, which leads to a decrease in the functional capabilities
of the organism.
Classification of respiratory failure:
I. Clinical course: acute (asphyxia) and chronic respiratory failure (bronchial
asthma, COPD).
II. According to the severity of clinical signs: compensated (gas composition of
the blood has not yet changed) and decompensated (gas homeostasis is disturbed).
III. By pathogenesis: A) ventilation and B) parenchymal insufficiency of
external respiration.
Pathogenetic variants of A) respiratory ventilation:
1. Dysregulatory insufficiency (violation of the central regulation of respiration).
2. Restrictive insufficiency.
3. Obstructive insufficiency.
Dysregulatory insufficiency can manifest itself in the following types:

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 1) tachypnea - frequent but shallow breathing with fever, functional disorders of
the central nervous system (hysteria), lung damage (atelectasis, pneumonia,
congestion), pain localized in areas of the body involved in the respiratory act (chest,
abdominal wall, pleura).
2. hyperpnoe - deep frequent breathing - when the partial pressure of oxygen in
the inhaled air or when it increases the concentration of CO2, anemia, acidosis, etc. The
extreme degree of excitation of the respiratory center is manifested in the form of
Kusmaul breathing, which is most often observed in patients with diabetic coma. It is a
loud frequent breathing, in which a deep breath is followed by increased exhalation
with the active participation of the expiratory muscles.
3) bradypnea - rare shallow breathing with increasing blood pressure (reflex of the
baroreceptors of the aortic arch and carotid sinus), with hyperoxia (due to periodic
excitation of chemoreceptors sensitive to lower oxygen tension in the blood).
Deep rare breathing can occur with increasing resistance to air movement in the
upper respiratory tract - stenotic breathing. The alveoli fill slowly, their irritation is
weak and there is a slow change in inspiration on exhalation (slowing of the Goering-
Breyer reflex).
4) apnea - a temporary cessation of breathing, which may be associated with a
decrease in reflex or direct chemical stimulation of the respiratory center (hypoxia,
intoxication, organic lesions of the brain).
Restrictive insufficiency - with a decrease in lung distensibility in pneumonia,
atelectasis, fibrosis, edema and congestion in the lungs, complete obstruction of the
large bronchi, after removal of part of the lung.
Obstructive insufficiency is observed as a result of decrease in passability of
bronchial tubes of small caliber because of reduction of their gleam: spasm of bronchial
muscles, hypostasis of mucous membrane and accumulation of sputum in a gleam of
bronchial tubes. First of all exhalations are broken owing to narrowing of bronchial
tubes.
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 B) Parenchymal insufficiency is called respiratory failure, which occurs as a
result of disorders of gas exchange between the alveoli of the lungs and blood. Its causes
are focal lesions of the lung parenchyma (exudative and proliferative inflammatory
diseases), which lead to pulmonary circulatory disorders.
There are three main mechanisms of gas exchange disorders between the alveoli
and blood:
1) violation of gas diffusion;
2) violation of pulmonary perfusion (blood circulation);
3) violation of general and regional ventilation-perfusion relations.
Disorders of gas diffusion in the lungs. Etiology:
1) reduction of the diffusion coefficient;
2) reducing the area of diffusion (respiratory surface of the lungs);
3) increase in the thickness of the alveolar-capillary membrane;
4) reducing the difference between the partial pressure of gases in the alveolar air
and their voltage in the blood of the pulmonary capillaries;
5) reducing the time of contact of blood with alveolar air.
Disorders of pulmonary perfusion. Etiology:
a) reduction of pressure in the right ventricle (right heart failure, reduction of
venous return in case of blood loss, shock, collapse);
b) increased pressure in the left atrium (stenosis of the mitral valve, left ventricular
failure);
c) increase in the resistance of the vessels of the small circle of blood circulation
(increase in blood viscosity, the presence of obstacles to blood flow - thrombosis,
embolism).
Periodic breathing is the following violation of the rhythm of respiration, in
which periods of respiration alternate with periods of apnea:

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 Cheyne-Stokes respiration is characterized by a gradual increase in the frequency
and depth of respiration, which, reaching a maximum, gradually decreases and
disappears completely. There is a complete, sometimes lasting up to (0.5 min) pause -
apnea, and then a new wave of respiratory movements.

Etiology: 1) chronic nephritis, 2) nephrosclerosis, 3) uremia, 4) heart

decompensation, 5) severe pulmonary insufficiency, 6) liver failure, 7) diabetic coma,
8) brain damage - tumors, hemorrhages, injuries, cerebral edema.
Pathogenesis: as a result of reduced excitability and lability of the respiratory
center to excite its normal concentration of CO2 in the blood becomes insufficient. The
respiratory center is not disturbed, respiration stops and CO2 accumulates. Its
concentration reaches such a significant level that it begins to act on the respiratory
center, despite the decrease in its excitability and leads to the appearance of respiration.
But because lability is reduced - respiration increases slowly. As respiration increases,
CO2 is excreted from the blood and its effect on the respiratory center weakens.
Breathing becomes less and less and finally stops completely - pause again.
Biota respiration - occurs with a deeper lesion of the respiratory center -
morphological lesions, especially inflammatory and degenerative in nerve cells.
Characterized by the fact that the pause occurs after 2-5 respiratory movements. The
pause is long, ie the slightest decrease in pCO2 leads to a pause. Etiology: 1) meningitis,
2) encephalitis, 3) severe poisoning, 4) heat stroke, and others.
Terminal respiration.
Gasping breaths are solitary, rare, diminishing "sighs" that are observed during
agony, such as in the final stage of asphyxia.
Apneastic breathing is characterized by a convulsive effort to inhale, which is
occasionally interrupted by exhalation.

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 Asphyxia is a pathological process, a syndrome with an acute course that occurs
due to lack of oxygen in the blood and tissues, followed by the accumulation of carbon
dioxide in the body.
The I period of asphyxia is characterized by a rapid increase in depth and
frequency of respiration with a predominance of the inspiratory phase over the
expiratory phase. General arousal develops, the tone of the sympathetic part of the
autonomic nervous system increases - the pupils dilate, tachycardia appears, blood
pressure increases, convulsions are possible.

In the second period, the respiratory rate gradually decreases while maintaining
the maximum amplitude of respiratory movements, the exhalation phase increases. The
tone of the parasympathetic part of the autonomic nervous system prevails - the pupils
narrow, blood pressure decreases, bradycardia is noted.
In the third period of asphyxia there is a decrease in the amplitude of respiration,
its frequency and, finally, respiratory arrest. Blood pressure drops significantly. After
a short cessation of breathing, there are usually several rare convulsive respiratory
movements (gasping breath), followed by respiratory paralysis.

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 Chapter 8. Pathophysiology of the digestive system

Indigestion is a pathological condition in which the digestive system does not

absorb nutrients that enter the body.
Classification of indigestion:
I. According to the clinical course there are acute and chronic indigestion.
II. According to the anatomical principle, indigestion can be disturbed: in the oral
cavity; in the stomach; in the intestine.
III. Insufficient digestion can be general (total) - impaired absorption of all
nutrients, and selective (partial) - only some of their classes (eg, lipids, lactose, etc.).
IV. The etiology distinguishes between hereditary (some types of malabsorption)
and acquired digestive failure (infectious origin; due to the effects of physical factors;
associated with the effects of chemical agents; alimentary).
V. By pathogenesis: a) impaired motor function of the digestive system; b)
violation of its secretory function; c) violation of suction processes.
Causes of indigestion:
I. Nutritional factors: a) intake of poor quality and coarse food; b) irregular meals;
c) unbalanced diet (for example, reducing the content of vitamins in the diet); e) alcohol
abuse.
II. Physical factors (ionizing radiation).
III. Chemical agents (poisoning by inorganic and organic compounds in the
workplace and in the home).
IV. Biological factors: a) bacteria (Vibrio cholerae, pathogens of dysentery,
typhoid fever, paratyphoid fever, etc.); b) bacterial toxins (with salmonellosis,
staphylococcal infection); c) viruses (adenoviruses); d) helminths.
V. Organic lesions: a) congenital anomalies of the digestive system; b)
postoperative conditions; c) tumors of the digestive system.

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 VI. Violations of nervous and humoral regulation in: a) psycho-emotional
disorders (neurotic and neurosis-like states); b) mental illness (schizophrenia, manic-
depressive syndrome); c) organic diseases of the central nervous system (encephalitis);
d) lesions of peripheral structures of the autonomic nervous system; e) reflex disorders
(various viscero-visceral reflexes).
Disorders of humoral regulation of digestion may be associated with disorders of
the synthesis and secretion of gastrointestinal hormones (gastrin, secretin,
cholecystokinin-pancreozymin, etc.).
Clinical syndromes in indigestion:
1. Dyspeptic syndrome includes various combinations of the following
symptoms: a) anorexia; b) heartburn; c) belching; d) nausea; e) vomiting; g) flatulence;
g) constipation; h) diarrhea.
2. The main causes of dehydration in digestive disorders are:
- hypersalivation - increased saliva formation and secretion - hyperosmolar
dehydration;
- unrestrained vomiting and diarrhea - hypoosmolar dehydration.
3. Violation of the acid-base state:
1) non-gaseous alkalosis - due to unrestrained vomiting;
2) non-gaseous acidosis - due to the loss of large amounts of bicarbonate of
pancreatic juice and bile with diarrhea.
4. Intestinal autointoxication - associated with dysbacteriosis and the formation
of large amounts of toxic products of fermentation and putrefaction.
5. Pain syndrome in lesions of the digestive system. Mechanisms:
a) spastic mechanism - pain caused by spasm of smooth muscles of various parts
of the digestive tract;
b) hypotonic mechanism - with a decrease in smooth muscle tone (hypotension)
pain occurs as a result of stretching the walls of the hollow organs (stomach, intestines,

160
gallbladder) their contents; c) the effect of biologically active substances (histamine,
serotonin, kinins, prostaglandins, etc.) on nerve endings.
Dyspeptic syndrome includes various combinations of the following symptoms:
a) anorexia; b) heartburn; c) belching; d) nausea; e) vomiting; g) flatulence; g)
constipation; h) diarrhea.
Anorexia is a complete lack of appetite with an objective need for food. There are
the following types of anorexia:
a) intoxication - develops in acute and chronic poisoning (eg, mercury salts, drugs,
bacterial toxins);
b) dyspeptic - occurs in diseases of the digestive system, often has a conditionally
reflex nature;
c) neurodynamic - develops as a result of reciprocal inhibition of the center of
appetite at excitation of separate structures of limbic system (for example, a pain
syndrome at a myocardial infarction, colic, peritonitis);
d) neurotic - associated with excessive excitation of the cerebral cortex and strong
emotions (especially negative);
e) psychogenic - is the result of conscious restriction of food (for example, in order
to lose weight or as a result of an obsession with mental disorders).
Heartburn is a feeling of heat or burning along the esophagus. Its development is
associated with irritation of the receptors of the esophagus when throwing the contents
of the stomach into the esophagus (reflux). This may be due to: a large amount of gastric
juice and functional insufficiency of the cardiac sphincter.
Belching is the sudden involuntary release of gas from the stomach or esophagus
into the mouth, sometimes with small portions of stomach contents. Increased gas in
the stomach can be caused by: the intake of large amounts of gas with food and
beverages (eg, carbonated beverages), ingestion of air (aerophagia); the formation of
gas in the stomach, especially with a long delay of food there (sometimes with peptic
ulcer disease, stomach cancer).
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 Nausea is a kind of severe sensation in the epigastric region, chest and mouth,
often preceded by vomiting and often accompanied by general weakness, sweating,
increased salivation, cold extremities, pale skin, decreased blood pressure, ie signs of
activation of the parasympathetic nervous system. The basis of nausea is the excitation
of the vomiting center, but still insufficient for vomiting.
Vomiting is a complex reflex act that causes the stomach contents to erupt through
the mouth. Occurs as a result of violation of the vomiting center located in the medulla
oblongata. There are 3 main types:
1. Central. 2. Toxic. 3. Visceral.
Constipation is a slow, difficult or systematically insufficient bowel movement.
There are two mechanisms of constipation - spastic and atonic. The first is due to
prolonged continuous contraction of intestinal smooth muscle (spasm), the second -
their atony.
Flatulence is an excessive accumulation of gases in the digestive tract due to their
increased formation (when eating foods high in fiber, starch (beans, cabbage, potatoes),
digestive disorders (enzymopathy, malabsorption, intestinal dysbacteriosis) or
insufficient excretion from the intestine). as a result of intestinal obstruction (spasms,
adhesions, tumors), with disorders of motor function of the intestine).
Diarrhea is an accelerated bowel movement with the release of sparse, and in
some cases, copious bowel movements. Diarrhea occurs when the normal relationship
between secretion and absorption of fluid in the intestines, with disorders of intestinal
motility.
Impaired motor function of the digestive tract:
1) chewing disorders. Etiology: dental lesions; damage to the masticatory muscles;
violation of the innervation of the masticatory muscles; damage to the
temporomandibular joints; lesions of the mucous membrane of the mouth and gums
(stomatitis, gingivitis); hyposalivation. Consequences: reduction of reflex secretion of

162
gastric and pancreatic juices; slow digestion in the stomach; trauma to the mucous
membrane of the mouth, esophagus, stomach;
2) swallowing disorders. Dysphagia is a violation of a complex reflex act of
swallowing. Etiology: lesions of the receptors of the oral mucosa (stomatitis) and
pharynx (sore throat); lesions of sensitive afferent and motor efferent nerve conductors
involved in the implementation of swallowing reflexes (fibers V, VII, IX, X, XII cranial
nerves); lesions of the nerve centers - in the cerebral cortex and the center of
swallowing, located in the area of the bottom of the IV ventricle; lesions of the muscles
of the tongue, pharynx and esophagus; congenital and acquired defects of the soft and
hard palate; mechanical obstacles (tumors, scars, compression of the esophagus from
the outside). Consequences: extremely difficult eating leads to starvation and
exhaustion.
3) gastric dyskinesia - a violation of the motor function of the stomach. The
hypertensive variant of gastric dyskinesias is characterized by an increase in gastric
muscle tone (hypertension) and increased peristalsis (hyperkinesia). Etiology: some
dietary factors (roughage, alcohol); increase in gastric secretion; increase in the tone of
the vagus nerve; hypersecretion of motilin. Consequences: prolonged retention of
stomach contents, which increases gastric secretion and the development of ulcers on
the mucous membrane; development of gastric antiperistalsis, which causes belching,
nausea, vomiting. The hypotonic variant, on the contrary, is characterized by
hypotension and hypokinesia. Etiology: nutritional factors (fatty foods); reduction of
gastric secretion; reduction of vagus nerve tone; general weakening of the body.
Consequences: a decrease in the residence time of food in the stomach, which leads to
a violation of its digestion, which causes increased intestinal motility and diarrhea.
4) intestinal dyskinesias - disorders of motor (motor) function of the intestine. The
hyperkinetic variant of intestinal dyskinesias is characterized by increased intestinal
motility, manifested by the development of diarrhea. Etiology: increased excitability of
intestinal receptors; increase in excitability of the centers of a vagus nerve; increase in
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the formation of motilin. Consequences: digestive disorders (digestion, absorption);
dehydration; secretory non-gaseous acidosis (loss of hydrocarbons). The hypokinetic
variant is characterized by a weakening of the motor activity of the intestines, resulting
in constipation (spastic and atonic). Etiology of spastic constipation: persistent long-
term tonic contraction of intestinal smooth muscle (spasm), exposure to toxic factors
(eg, lead poisoning). Etiology of atonic constipation: low fiber content in foods
consumed; excessive digestion of food in the stomach (for example, gastric
hypersecretion); reduction of vagus nerve tone. Consequences: development of
intestinal autointoxication; occurrence of flatulence; formation of fecal stones;
intestinal obstruction.
5) dyskinesia of the gallbladder and bile ducts;
6) violation of defecation. Etiology: loss of influence of the cerebral cortex on
the spinal center of defecation (fear, fear); damage to the center of defecation in the
lumbosacral spinal cord; peripheral nerve damage; disorders of muscle function
involved in defecation.
Disorders of the secretory function of the digestive system:
a) hypersecretory states:
1) hypersalivation - increased formation and secretion of saliva. Etiology:
disorders of the receptors of the mouth, esophagus and stomach (reflex mechanism);
excitation of the salivary center located in the medulla oblongata; irritation of the
autonomic nerves innervating the salivary glands. Consequences: development of
hyperosmolar hypohydration; neutralization of gastric juice, which is associated with a
slightly alkaline environment of saliva.
2) gastric hypersecretion - increased formation and secretion of gastric juice.
Etiology: increased vagus nerve tone, hyperproduction of gastrin, histamine.
Consequences: long delay of contents in a stomach causes decrease in peristalsis of
intestines and development of constipations; strengthening of fermentation and gas

164
formation processes; increase in motor activity of the stomach - hypertension and
hyperkinesia of its smooth muscles; formation of ulcers in the stomach and duodenum.
3) pancreatic hypersecretion - increased formation and secretion of pancreatic
juice. Etiology: increased tone of the parasympathetic nervous system (vagus nerve);
increased production of gastrointestinal substances - secretin and cholecystokinin-
pancreozymin. Consequences: improvement of the processes of cavity digestion.
4) hypercholia.
b) hyposecretory states:
1) hyposalivation - reduction of saliva formation and secretion. Etiology: central
inhibition of salivary gland secretion (fear, fright, pain); damage to the secretory cells
of the salivary glands (inflammation, tumors); violation of secretion (obstruction of the
ducts of the salivary glands by stones); dehydration. Consequences: disturbance of
chewing, formation of a food lump, swallowing; trauma to the oral mucosa with the
development of inflammation (stomatitis); active development of microorganisms;
violation of the trophic effects of saliva on the teeth, which contributes to the
development of caries.
2) gastric hyposecretion - reducing the formation and secretion of gastric juice.
Etiology: decrease in vagus nerve tone, hypoproduction of gastrin, histamine.
Consequences: insufficient formation of gastric juice leads to inhibition of secretion
production, as a result of which the secretion of pancreatic juice decreases and the
processes of cavity digestion in the intestines are disturbed; increased intestinal motility
and the development of diarrhea; activation of pathogenic microflora.
3) pancreatic hyposecretion - a decrease in the formation and secretion of
pancreatic juice. Etiology: neurogenic inhibition of exocrine function of the pancreas
(reduction of vagus nerve tone, atropine poisoning, etc.); reducing the formation of
secretin and cholecystokinin-pancreozymin; violation of the excretion of pancreatic
juice. Consequences: disorders of intestinal digestion in the intestines - the development

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of maldigestion syndrome. Maldigestion syndrome is manifested by: indigestion of fats,
proteins, carbohydrates, disorders of absorption of fat-soluble vitamins - A, D, E, K;
violation of nucleic acid cleavage.
4) acholia.
Absorption dysfunction - malabsorption syndrome.
Etiology:
1) preenterocytic disorders: disorders of motor function of the digestive tract,
cavity digestion (maldigestion syndrome), parietal digestion (disorders of formation
and incorporation of enzymes into the plasma membrane of enterocyte microvilli);
2) enterocytic: decrease in the area of absorption (condition after intestinal
resection, atrophy of villi and microvilli); hereditary disorders and acquired disorders
of the formation of proteins - carriers of monosaccharides (intolerance to glucose,
galactose, fructose), amino acids, calcium ions (hypovitaminosis D); dysfunction of ion
pumps of enterocytes; energy deficit; 3) postenterocytic: circulatory disorders in the
intestinal wall (ischemia, venous hyperemia, thrombosis, embolism, vascular reactions
in inflammation); lymphatic outflow disorders.
Peptic ulcer is a chronic recurrent disease characterized by the formation of ulcers
in the stomach or duodenum.
According to modern ideas, gastroduodenal ulcers occur both when the aggressive
properties of gastric contents are enhanced and when the protective capabilities of the
mucous membrane of the stomach and duodenum are weakened.
Factors of aggression:
1. Negative stress effects on the body. Pathogenesis: cause increased secretion and
acidity of gastric juice; prolonged spasm of blood vessels and muscles of the stomach
and intestines;
2. High concentration of hydrochloric acid and pepsin, which causes destruction
of the mucous membrane.

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 3. Helicobacter pylori.
4. Nonsteroidal anti-inflammatory drugs.
5. Smoking.
6. Corticosteroids during long-term pharmacotherapy.
7. Hypergastrinemia, as well as an increase in other gastrointestinal hormones (eg,
cholecystokinin).
Protection factors:
1. Mucus and bicarbonate anions.
2. Normal microcirculation.
3. Prostaglandins of the stomach.
4. Regeneration - complete renewal of the epithelium of the gastroduodenal zone
occurs within 2 - 6 days. Small damage to the mucosa can be restored within 15 -30
minutes, but not due to cell division, but as a result of their movement from the crypts
of the glands along the basement membrane and thus closing the defect in the area of
damaged epithelium.
Acute pancreatitis is an inflammation of the pancreas characterized by an acute
course. Etiology: eating fatty foods; alcohol abuse; gallstones and polyps of the duct of
the pancreas; mechanical damage to the pancreas in trauma and surgery; infectious
agents (mumps virus, Coxsackie, bacterial infection); intoxication, including the action
of certain drugs (immunosuppressants, thiazides, etc.).
Pathogenesis: premature activation of pancreatic juice enzymes in the ducts of the
pancreas causes self-digestion of glandular tissue. Active enzymes of pancreatic juice,
prostaglandins, kinins cause secondary alteration of pancreatic tissue, increased
vascular permeability with the development of edema, hemorrhage; occurrence of pain.
Pathogenetic variants of acute pancreatitis:
I. Primary-alterative.
II. Hypertensive (pancreas hypersecretion or obstruction of a duct).
III. Reflux.
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 Pancreatic shock is a severe general manifestation of acute pancreatitis, which is
characterized by disturbances in general hemodynamics (lowering of blood pressure)
and generalized disorders of microcirculation.
Pathogenesis:
I. Pain mechanism. Acute shingles pain that occurs in pancreatitis, on the one
hand, due to edema of the pancreas (pressure on the solar plexus), on the other - the
action of active digestive enzymes (trypsin, phospholipase, etc.) and biologically active
substances (kinins, prostaglandins) nerve endings of the gland.
II. Humoral mechanism. Caused by fermentemia - the entry into the blood of
active pancreatic enzymes. As a result of activation of the kallikrein-kinin system,
blood coagulation system and fibrinolysis, there is a generalized vasodilation, which
leads to a decrease in total peripheral resistance, increased vascular permeability,
resulting in reduced circulating blood volume and reduced blood pressure; development
of DIC syndrome and microcirculation disorders.
Intestinal obstruction is a disease characterized by impaired passage of intestinal
contents due to obstruction, compression or dysfunction.

Types:
-mechanical: -1. obturation (due to obstruction of the intestinal lumen by a tumor,
fecal stones, a tangle of helminths);
2 - strangulation (as a result of compression of the intestine from the outside) (torsion,
pinching in the hernia gate),
- dynamic: -1. spastic (spastic contraction of smooth muscle of the intestine),
2 - paralytic (due to deep suppression of motor function of the intestine)
Pathogenesis: pain due to smooth muscle spasm, necrosis of the intestinal wall, its
stretching by fluid lead to dehydration, impaired digestion, acid-base disorders (as a
result of unrestrained vomiting develops non-gaseous alkalosis), intestinal
autointoxication, acute peritonitis, general circulation and microcirculation disorders.

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169
 Chapter 9. Pathophysiology of the liver

Causes of primary and secondary liver damage:

1. Biological factors:
- viruses (hepatitis A, B, C, D; infectious mononucleosis),
- bacteria (pathogens of tuberculosis, syphilis),
- the simplest (Giardia, amoebae),
- fungi (actinomycetes),
- helminths (echinococcus, roundworms).
2. Chemical factors (hepatotropic poisons):
- alcohol, industrial poisons (carbon tetrachloride, heavy metals, chloroform,
arsenic, organophosphorus insecticides),
- plant poisons (aflatoxin, muscarine),
- products of tissue decay in burns, necrosis; products of impaired metabolism,
- drugs (sulfonamides, tetracycline, cytostatics, etc.).
3. Physical factors:
- ionizing radiation, mechanical trauma.
4. Nutritional factors:
- protein, vitamin starvation, fatty foods.
5. Dysfunction of other organs and systems:
- circulatory failure (ischemia, venous hyperemia, thrombosis, embolism),
- endocrine and metabolic diseases (diabetes, thyrotoxicosis, obesity),
- tumors, tumor metastases,
- allergy to the introduction of vaccines, serums, foods and drugs.
Liver failure is a pathological condition in which the activity of this organ is not
able to ensure the stability of the internal environment of the body in accordance with
its requirements.
Depending on the causes of hepatocyte damage, liver failure can be:
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 a) hepatocellular; b) cholestatic; c) hepatovascular.
Hepatocellular insufficiency develops due to direct damage to hepatocytes by
pathogenic agents.
Cholestatic insufficiency develops due to primary disorders of bile production and
bile secretion.
Hepatovascular insufficiency develops because of primary circulatory disorders in
the liver. The main mechanism of hepatocyte damage is hypoxia.
The following functions may be impaired:
I. Metabolic - the participation of the liver in carbohydrate, fat, protein
metabolism, the metabolism of vitamins, hormones and biologically active substances.
II. Protective - phagocytic and antitoxic functions of the liver.
III. Excretory - the formation and secretion of bile. Secretion of bile determines
the excretory and digestive functions of the liver.
IV. Hemodynamic - the participation of the liver in maintaining the systemic
circulation.
A. Metabolic disorders in hepatic insufficiency:
1. Disorders of carbohydrate metabolism → hypoglycemia, hypoglycemic coma.
2. Disorders of fat metabolism:
- reducing the formation of cholesterol esters (free cholesterol);
- reducing the formation of phospholipids;
- increasing the synthesis of ketone bodies;
- fatty infiltration of the liver.
3. Disorders of protein metabolism:
- decreased albumin synthesis → hypoalbuminemia → edema;
- decreased synthesis of blood coagulation factors (prothrombin, fibrinogen,
thromboplastin, V, VII, IX, X, XII, XIII factors) → hemorrhagic syndrome;
- violation of deamination of amino acids, decreased synthesis of urea from
ammonia.
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 4. Disorders of vitamin metabolism:
- reduction of intestinal absorption of fat-soluble vitamins A, D, E, K;
- decreased ability of hepatocytes to convert provitamins into active vitamins;
- reduction of vitamin deposition in the liver (A, D, K, PP, E, B1, B2) - hypovitaminosis.
5. Disorders of hormone metabolism:
- violation of inactivation of T3, T4, insulin, glucagon, STG, ADH, aldosterone,
estrogen, androgens;
- violation of BAS inactivation (catecholamines, histamine, serotonin).
B. Violation of the protective and antitoxic function of the liver:
1) disrupted neutralization in hepatocytes:
- intestinal poisons (phenol, indole, skatole, ammonia);
- exogenous poisons, including drugs.
2) decreases the phagocytic activity of Kupffer cells (absorption from the
bloodstream of microorganisms, toxins, immune complexes, fat droplets, damaged
erythrocytes).
C. Violation of the excretory function of the liver:
- disorders of bile formation and function.
D. Violation of the Hemodynamic function of the liver:
- disorders of systemic and portal blood circulation.
Hepatocerebral insufficiency is a pathological process that occurs as a result of
disorders of antitoxic function of the liver and is manifested by a complex of mental
and neurotic disorders up to loss of consciousness and the development of coma:
a) emotional and mental disorders: emotional instability, insomnia at night and
drowsiness during the day, headache, dizziness;
b) severe disorders of consciousness - the development of stupor (drowsiness,
confusion);
c) hepatic coma.

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 The development of the syndrome of hepatocerebral insufficiency is based on the
accumulation in the blood of so-called cerebrotoxic substances (ammonia, oxidation
products of amino acids in the intestines, derivatives of lactic and pyruvic acids, low
molecular weight fatty acids).
Hepatic coma is a pathological condition that occurs because of severe disorders
of antitoxic function of the liver and is manifested by loss of consciousness, loss of
reflexes to internal and external stimuli, disorders of vital functions (circulation,
respiration).
Types of pathogenesis:
1. Hepatocellular
2. Shunt (portocaval)
Hepatocellular coma: massive necrosis of the liver parenchyma with violation of
all its functions.
1) increase in cerebrotoxic substances in the blood
2) hypoglycemia;
3) hypokalemia (secondary aldosteronism);
4) metabolic acidosis.
Shunt hepatic coma
Portal hypertension, the development of porto-caval anastomoses (through
hemorrhoids, esophagus, umbilical veins) discharge of blood, bypassing the liver, into
the general bloodstream → intoxication with metabolic products that cause
cerebrotoxic effects.
In connection with the general intoxication of the body, systemic hemodynamics
are disturbed: cardiac output decreases, arterial hypotension develops, the volume of
circulating blood decreases. Disturbances in the blood coagulation system (deficiency
of prothrombin, fibrinogen and other factors) create conditions for the development of
bleeding, blood coagulation in the microvessels of organs and tissues. There is a
progressive general hypoxia of the mixed character.
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 Jaundice - jaundice of the skin, mucous membranes, sclera as a result of
deposition of bilirubin in them.

Types of jaundice by pathogenesis:

1. Suprahepatic (hemolytic)
Etiology: increased hemolysis of erythrocytes.
Pathogenesis: hemolysis of erythrocytes → receipt of indirect bilirubin in the liver
→ formation of direct bilirubin → entry of direct bilirubin into the small intestine in
bile → formation of urobilinogen and stercobilinogen → appearance of urobilinogen in
urine due to insufficient ability of the liver to excrete bile.
In the blood: hyperbilirubinemia due to indirect bilirubin;
Urine: dark;
Feces: hypercholic (dark) due to the high content of stercobilinogen.
2. Hepatic (parenchymal)
By pathogenesis:
- hepatocellular;
- enzymopathic.
Hepatocellular jaundice occurs when hepatocytes are damaged.
In the blood: hyperbilirubinemia due to indirect (damaged hepatocytes do not
capture it) and direct bilirubin (as a result of bile entering the blood through
anastomoses between the bile and blood capillaries);
Urine: dark due to direct bilirubin, which is filtered in the kidneys - bilirubinuria);
Feces: hypocholic (due to low stercobilinogen content)
Enzymopathic:
- violation of the capture of indirect bilirubin by hepatocytes (Gilbert's syndrome);
- bilirubin conjugation disorders - glucoronyltransferase defect - Kriegler-Nayar
syndrome;
- impaired excretion of direct bilirubin (Dabin-Johnson syndrome, Rotor).

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 3. Subhepatic (mechanical)
Etiology:
difficulty in the outflow of bile from the gallbladder into the duodenum as a result
of gallstone disease; obturation by helminths, thick bile; tumors of the head of the
pancreas
Pathogenesis:
impaired bile flow → increased intrahepatic bile pressure → rupture of bile
capillaries → bile flow into the blood → cholemia; violation of bile flow into the
intestine → acholia
In the blood: hyperbilirubinemia due to direct bilirubin; appearance of bile acids -
cholemia;
Urine: dark ("beer color") due to direct bilirubin; appearance of bile acids -
cholauria;
Feces: acholic (no stercobilinogen is formed).
Cholemia - the presence of bile acids in the blood. Effects:
1. Toxic effect on the CNS (suppression of tissue respiration) - general asthenia,
irritability, drowsiness during the day and insomnia at night, fatigue;
2. Bradycardia and lowering of blood pressure (activation of the vagus nerve,
action on the sinoatrial node);
3. Itchy skin (irritation of nerve endings).
4. Cell death due to the detergent action of bile acids.
Acholia - a lack of bile in the intestine. Effects:
1. Disorders of fat absorption → steatorrhea (fatty feces);
2. Disorders of absorption of fat-soluble vitamins - hypovitaminosis of vitamins
A, D, E, K;
3. Violation of peristalsis and decreased intestinal tone (constipation). Bile - a
stimulant of contractions of smooth muscles of the gastrointestinal tract;

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 4. Intensification of putrefaction and fermentation processes as a result of
reduction of bactericidal action of bile. Development of dysbacteriosis.
Dyscholia is a violation of the physicochemical properties of bile, as a result of
which it acquires lithogenic properties, ie the ability to form stones (stones) in the
gallbladder and bile ducts. The result is the development of gallstone disease.
Pathogenesis: decrease in cholato-cholesterol and lecithin-cholesterol indices
(ratio of bile acids and lecithin to bile cholesterol). As a result of reducing the
concentration of bile acids and lecithin, which provide a suspended state of cholesterol,
cholesterol precipitates and gives rise to the formation of cholesterol stones. Stones
cause disorders of bile secretion and the development of mechanical jaundice.
The syndrome of portal hypertension develops as a result of impaired blood
flow from the abdominal organs through the vessels of the portal vein.
The main manifestations of portal hypertension syndrome.
1. The inclusion of collateral circulation due to the disclosure of portocaval
anastomoses. This causes the development of:
a) varicose veins of the esophagus and the cardiac part of the stomach;
b) gastrointestinal bleeding due to damage to varicose veins;
c) dilation of the subcutaneous veins of the anterior thoracic and abdominal walls
("jellyfish head");
d) discharge of blood from the portal vein into the vena cava bypassing the liver,
which causes the effects of intoxication, and in severe cases, the development of
exogenous (shunt) hepatic coma.
2. Hepato-lienal syndrome.
3. Ascites.
4. Hepato-renal syndrome. Manifested by violations of the filtration capacity of
the glomeruli while maintaining the functions of the tubular epithelium.
Ascites is a significant accumulation of free fluid in the abdomen.
Etiology:
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 a) portal hypertension of various origins; b) edema in chronic heart failure, kidney
disease, alimentary dystrophy; c) violation of the outflow of lymph from the thoracic
duct (its injury, compression).
Pathogenesis:
1) Hydrostatic. Associated with increased blood pressure in the capillaries of the
vessels of the portal system;
2) Oncotic. Caused by a decrease in the protein-synthetic function of the liver,
resulting in the development of hypoproteinemia and decreased oncotic blood pressure;
3) Sodium retention in the body. Associated with an increase in aldosterone in the
blood.
4) Lymphogenic mechanism. In connection with the violation of lymph outflow is
the transition of protein-rich lymph into the abdominal cavity. This causes an increase
in the oncotic pressure of the abdominal fluid with the subsequent release of water from
the blood vessels and interstitial space.
Cirrhosis of the liver is a chronic progressive disease characterized by the growth
of connective tissue, pathological regeneration of liver tissue and restructuring of the
structure of the organ, which is manifested by signs of liver failure. Cirrhosis is the
result of irreversible damage to a large number of liver cells.
Pathogenetic variants of liver cirrhosis:
a) postnecrotic. Manifested by signs of hepatocellular insufficiency of the liver;
b) biliary. Accompanied by cholestatic liver failure;
c) portal. Is the structural basis of hepatovascular insufficiency.

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 Chapter 10. Pathophysiology of the kidney
There are two groups of processes in the kidneys, which maintain homeostasis:
1- urine formation (excretory function).
2- release of hormones, enzymes, biologically active compounds into the
blood (endocrine functions).
Disorders of their excretory function may be caused by disorders:
1) glomerular (glomerular) filtration;
2) tubular reabsorption;
3) tubular secretion.
Disorders of renal excretory function are associated with:
1) violation of water homeostasis - changes in the volume of extracellular fluid
(hyper- and hypohydria);
2) violations of osmotic homeostasis - hyper- and hypoosmia;
3) imbalance of electrolytes in the extracellular fluid (dysionium);
4) violations of the acid-base state (most often non-gaseous acidosis);
5) disturbances in the chemical composition of blood plasma, manifested, on the
one hand, by the accumulation of end products of metabolism (azotemia), on the other,
by the loss of chemical compounds necessary for the body (hypoproteinemia,
hypoaminocidemia, hypoglycemia).
Disorders of endocrine functions of the kidneys may manifest by:
1) secretion of renin by the juxtaglomerular apparatus of the kidneys, as well as
renal depressor factors;
2) the release of erythropoietins and erythropoiesis inhibitors;
3) the formation of a hormonally active form of vitamin D.
Disorders of endocrine functions of the kidneys can cause the development of:
1) arterial hypertension;
2) anemia;
3) disorders of phosphorus-calcium metabolism - renal osteodystrophy.
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 Renal failure is a pathological condition characterized by a violation of the
stability of the internal environment of the body due to the inability of the kidneys to
perform their homeostatic functions.
Classification:
I. According to the clinical course, there are acute and chronic renal failure.
II. By etiology: prerenal, renal, postrenal and arenal.
III. Depending on the extent of impaired function, renal failure can be total (all
functions are impaired) and partial (only certain functions are impaired).
IV. According to the mechanism of development, kidney failure is distinguished:
1) associated with the primary lesion of the glomeruli - glomerular;
2) associated with the primary lesion of the tubules - tubular.
Acute renal failure (ARF) is a sudden onset of renal dysfunction.
Etiology:
Prerenal: blood loss, dehydration → hypovolemia, shock, collapse →
hypotension; acute heart failure, massive hemolysis of erythrocytes;
Renal: local circulatory disorders in the kidneys (thrombosis, renal artery
embolism, renal vein thrombosis), acute kidney disease (acute glomerulonephritis,
acute pyelonephritis), damage by nephrotoxic poisons (heavy metal salts, antibiotics,
organic drugs, sulfins) poisons, bacterial toxins, toxic metabolites).
Postrenal: obstruction of the ureters (stones, blood clots, inflammatory edema),
compression of the ureter from the outside (tumors of the abdominal cavity, adhesions),
delayed urination at the level of the bladder (prostate adenoma).
Pathogenesis:
- temporary renal ischemia, mainly of the cortical substance;
- direct damage to the glomeruli and tubules;
- increase in pressure in the Bowman-Shumlyansky capsule.
Drop in effective filtration pressure → a sharp decrease in the filtration process →
a sharp decrease or complete cessation of urine production.
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 In the clinical course of ARF there are 4 stages: 1) initial; 2) oligo-, anuria; 3)
polyuria; 4) recovery.
Chronic renal failure (CRF) is a progressive decrease in kidney function.
Etiology: chronic kidney disease: glomerulonephritis, pyelonephritis, polycystic
kidney disease, renal amyloidosis, urolithiasis, kidney damage in diabetes,
hypertension, atherosclerosis.
Pathogenesis:
Progressive death of nephrons and their replacement by connective tissue
(nephrosclerosis) → progressive decrease in the function of tubules and glomeruli →
decrease in urine production → uremia → uremic coma.
In the pathogenesis of CRF there are the following stages: 1) initial, 2) early
polyuric; 3) late oliguric and 4) terminal.
Quantitative changes in urine: 1) oligo- and anuria; 2) polyuria; 3) nocturia;
4) hypo- and isostenuria.
Oliguria is a decrease in daily urine output below the obligatory volume, ie less
than 700 ml / day. Causes: glomerular filtration disorders. Consequences: 1) increase
in the volume of extracellular fluid - hyperhydria; 2) accumulation in the body of
osmotically active substances (hypernatremia, hyperkalemia); 3) accumulation in the
blood of end products of metabolism - azotemia.
Anuria is a complete absence of diuresis.
Polyuria is an increase in daily urine output of more than 1.8 liters. Causes:
extrarenal (psychogenic polydipsia, disorders of water-salt metabolism and its
regulation, such as diabetes mellitus) and renal (polyuric stage of acute and chronic
renal failure) factors.
Nocturia is the predominance of nocturnal diuresis over daytime. Causes: 1)
cardiac nocturia - develops in heart failure. During the day, patients have an increased
load on the heart and water intake, which leads to blood stasis and water retention in
the tissues (edema). At night, in a horizontal position, venous outflow improves and the
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load on the heart decreases. This causes the secretion of atrial natriuretic hormone,
increased diuresis and decreased edema;
2) renal nocturia - characteristic of kidney damage. It is explained by the
improvement of impaired renal blood flow at night. As a result, the movement of blood
through the vessels of the kidneys accelerates, hypertensive diuresis develops.
Hypostenuria - a decrease in the relative density of urine (less than 1,008 in all
portions of the sample according to Zymnytsky).
Isostenuria - constantly the same relative density of urine, equal to the density of
primary urine (1,010 - 1,012), indicates a lack of concentration capacity of the kidneys.
Hyperstenuria - an increase in the relative density of urine.
Qualitative changes in urine: 1) proteinuria; 2) hematuria; 3) cylindruria;
4) leukocyturia (pyuria).
Proteinuria - excretion of protein in the urine. Pathogenesis: 1) increased
permeability of the glomerular filter due to damage to the basement membrane
(glomerular proteinuria); 2) reduction of tubular reabsorption of filtered protein (tubular
proteinuria); 3) pathological entry of protein into the lumen of the tubules from
damaged cells of the tubular epithelium or from the peritubular lymph fluid (secretory
proteinuria). Selective proteinuria - only low molecular weight proteins are detected in
urine. Nonselective proteinuria is the appearance of both low- and high-molecular-
weight proteins in the urine.
Hematuria - the appearance of erythrocytes in the urine. Causes: 1) damage to
the glomerular filter and the entry of erythrocytes into the primary urine. At the same
time in the final urine "leached" erythrocytes are defined; 2) damage to the urinary tract.
Leukocyturia - the appearance in the urine of more than 5 leukocytes in the field
of view. Causes: inflammatory processes in the kidney tissue and urinary tract.
Cylindruria - the appearance of cylinders in the urine. Causes: damage to the
epithelium of the tubules. Depending on the structure, there are hyaline, granular and
epithelial cylinders.
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 Uremia is a syndrome that occurs when kidney function is decompensated.
Pathogenesis:
1. Autointoxication of the body by metabolic products (ammonia, creatinine, uric
acid, urea, phenol, skatol, indol, etc.);
2. Violation of water-electrolyte metabolism:
- hypoosmolar hyperhydration;
- hyperkalemia, hypermagnesemia, hypocalcemia, hyponatremia,
hyperphosphatemia, hypersulfatemia;
3. Disturbances of acid-base balance - metabolic acidosis (violation of bicarbonate
reabsorption, decreased secretion of hydrogen ions);
4. Disorders of metabolism of hormones, vitamins (vitamin D);
5. Disorders of erythropoietin, prostaglandins, kinins, etc.
Changes in the body with uremia:
I. Neuropsychiatric symptoms: fatigue, headache, suppression of reflexes, taste
and hearing impairment, tremor, insomnia, depression, cerebral edema, coma.
II. Cardiovascular dysfunction: myocardial dystrophy, cardiac arrhythmias
(electrolyte disturbance, hypoxia, intoxication), pericarditis (excretion of toxic
substances through the serous membranes), hypertension (activation of the renin-
angiotensin-aldosterone system, decreased formation of depressants).
III. Respiratory disorders: pulmonary edema, pneumonia, pleurisy.
IV. Hematological changes: anemia (erythropoietin deficiency, hemolysis of
erythrocytes), blood coagulation disorders (hemorrhagic syndrome, DIC syndrome).
V. Dysfunction of the gastrointestinal tract: nausea, vomiting, anorexia.
VI. Dermatological changes: itching (irritation of nerve endings by nitrogenous
residues), "uremic hoarfrost" - excretion of uric acid salts, urea by sweat glands,
hyperpigmentation.

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 VII. Disorders of the musculoskeletal system: impaired formation of the active
form of vitamin D, hypocalcemia, secondary hyperparathyroidism, osteomalacia,
calcification (renal rickets).
Nephrotic syndrome - a condition that occurs in various kidney lesions and is
manifested by massive proteinuria, hypoproteinemia, edema, hyperlipidemia.
Glomerulonephritis is a bilateral diffuse kidney disease of allergic nature. There
are acute and chronic glomerulonephritis.
Acute glomerulonephritis is characterized by a rapid onset, oliguria, proteinuria,
azotemia, hypertension, edema, hematuria, disorders of the central nervous system.
Occurs during (or after) any infection, often streptococcal in nature.
There are two main pathogenetic variants of acute glomerulonephritis:
1. Damage to the basement membrane of the glomeruli of the nephrons by
antibodies against its antigens - nephrotoxic glomerulonephritis (passes rapidly with a
progressive course).
2. The development of the inflammatory process in the glomeruli due to fixation
on the basement membrane and intramembrane immune complexes - immunocomplex
glomerulonephritis. As an antigen in this mechanism is exogenous (infectious or non-
infectious origin) or endogenous (tissue protein, DNA) antigen. The formed antibodies
(IgG, IgM) directly in blood serum interact with the specified antigens, then in the form
of immune complexes (antigen-antibody-complement) arrive in glomeruli, being
deposited on their basement membrane. The implementation of the harmful effects of
immune complexes, as well as nephrotoxic antibodies, is carried out by induction of
immune inflammation.
Chronic glomerulonephritis is a long-term progressive diffuse bilateral kidney
disease of inflammatory nature, heterogeneous in origin, clinical manifestations and
pathogenesis. Depending on the causes of its development, the following forms are
distinguished: 1) of infectious origin (poststreptococcal, with prolonged septic
endocarditis, malaria, syphilis, tuberculosis and other infections); 2) non-infectious
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(serum, vaccine, drug, poisoning by various poisons, traumatic, cooling, renal vein
thrombosis); 3) in diffuse connective tissue diseases (rheumatoid arthritis, lupus
erythematosus, hemorrhagic vasculitis, etc.).
The immunological concept of development of chronic glomerulonephritis is
generally accepted. Along with nephrotoxic and immunocomplex mechanisms,
delayed-type hypersensitivity is of some importance in its pathogenesis.
Pyelonephritis is an infectious-inflammatory disease of the mucous membrane of
the urinary tract and renal parenchyma with a predominant lesion of interstitial tissue.
The clinical course of pyelonephritis is characterized by signs of severe infectious
process, which is manifested by severe intoxication (especially in the acute stage);
development of arterial hypertension, moderate edema and anemia; urinary syndrome
(polyuria, in the late stage - oliguria, pollakiuria - frequent urination, hypostenuria; in
the final stage - isostenuria, leukocyturia, hematuria, moderate proteinuria, cylindruria).
The disease occurs in connection with the introduction of the pathogen into the
kidneys by hematogenous or its spread in an ascending direction through the urinary
tract. The most common pathogens are Escherichia coli, cocci. The emergence of the
disease, the transition from acute to chronic pyelonephritis contribute to various
conditions that cause stagnation of urine (narrowing, obstruction of the ureters, prostate
adenoma), trophic disorders of the urinary tract, common diseases that reduce the
reactivity of the body, diabetes, atherosclerosis, obesity and chronic intoxication).
Urolithiasis is a disease caused by the formation of stones in the parenchyma of
the kidneys and in the pelvic-ureteral segment of the urinary tract. In its severe form,
urolithiasis is characterized by attacks of renal colic, the cause of which is acute urinary
retention caused by mechanical obstruction and spasm of the pelvis and ureter;
hematuria caused by damage to the urinary tract; fever, leukocytosis. A complication
of the disease is the accession of infection and the development of calculous
pyelonephritis, kidney abscess, infected hydronephrosis, etc. In these cases, the
obligatory symptom is pyuria (the presence of pus in the urine). The composition of the
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stones includes salts of oxalic and phosphoric acids, uric acid, sodium and ammonium
urate, sometimes cystine, xanthine. Most often, the composition of the stones is mixed.

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 Chapter 11. Pathophysiology of extreme conditions

Extreme states are states of the body that are characterized by excessive stress or
depletion of adaptive mechanisms.
Shock is a severe pathological process that is accompanied by depletion of vital
functions of the body and brings it to the brink of life and death due to a critical
reduction in capillary circulation in the affected organs.
Depending on the causes, the following types of shock are distinguished:
traumatic, hemorrhagic, burn, tourniquet (develops after removal of the tourniquet four
hours or more after application), anhydremic, cardiogenic, pancreatic, anaphylactic,
septic, infectious-toxic, and others.
Depending on the primary mechanisms underlying the pathogenesis of shock,
there are: 1) hypovolemic shock (hemorrhagic, anhydremic); 2) shock associated with
impaired pumping function of the heart (cardiogenic); 3) vascular forms of shock
(anaphylactic, pancreatic); 4) painful shock, in which the central regulation of blood
circulation is violated (traumatic, burn).
The following mechanisms may underlie the development of circulatory disorders
in shock.
I. Decrease in the volume of circulating blood:
1) blood loss (hemorrhagic shock);
2) loss of blood plasma in severe exudative inflammation (burn shock);
3) the output of fluid from blood vessels into the tissues with a generalized increase
in vascular permeability (anaphylactic shock);
4) dehydration (anhydremic shock);
5) redistribution of blood in the vascular bed (thrombosis and embolism of the
main veins).
ІІ. Reduction of cardiac output:
1) violation of the contractile function of the heart (myocardial infarction);
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 2) cardiac tamponade (rupture of the heart-exudative pericarditis);
3) arrhythmias (ventricular fibrillation).
III. Reduction of total peripheral resistance - generalized vasodilation:
1) decrease in neurogenic tone of arterioles (painful forms of shock);
2) reduction of basal vascular tone under the action of biologically active
substances (anaphylactic, pancreatic shock) or toxic products (traumatic, turnstile,
infectious-toxic shock).
IV. Violation of the rheological properties of blood:
1) DIC syndrome (pancreatic shock);
2) aggregation of formed blood elements (septic, infectious-toxic shock);
3) blood clotting - hemoconcentration (anhydremic shock).
Traumatic shock develops due to extensive tissue damage. In his clinic there are
two stages: arousal (erectile) and inhibition (torpid).
The stage of excitation is short-lived, it is characterized by a state of excitation of
the CNS, which occurs as a result of a large number of pain impulses from damaged
tissues. Painful stress develops, which is manifested by increased functions of the
circulatory system, respiration, some endocrine glands (adenohypophysis, cerebral and
cortical substances of the adrenal glands, neurosecretory nuclei of the hypothalamus)
with the release into the blood of excess corticotropin, adrenaline, noradine.
The stage of inhibition is longer (from several hours to days) and is characterized
by the development of inhibitory processes in the CNS. Generalized inhibition also
captures the centers of vital functions (blood circulation, respiration), they are
disrupted, resulting in the development of oxygen starvation. Hypoxia, in turn,
exacerbates disorders in the cardiovascular and respiratory centers. Disorders of
hemodynamics and external respiration progress - the "vicious circle" closes.
Burn shock, which occurs with large thermal injuries, is also close to traumatic,
because the leading role in its pathogenesis belongs to the irritation of large receptor
zones and damage to tissue elements - the appearance of foci of excitation and then
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inhibition of the CNS. Together with changes in endocrine regulation, this leads to the
development of hemodynamic and metabolic disorders due to tissue dehydration and
disorders of water metabolism, blood clotting, increased viscosity, intoxication by the
breakdown products of damaged tissues, renal dysfunction.
Cardiogenic shock in extensive myocardial infarction is characterized by an
initial significant decrease in cardiac output due to a weakening of the contractile
function of the heart caused by disorders of myocardial trophism. Intense afferent
pulsation from the necrosis zone plays an important role. The venous return changes
disproportionately, which can lead to circulatory disorders in a small circle and under
the influence of other factors - to the development of pulmonary edema.
Anaphylactic shock is characterized by the fact that the trigger mechanism in its
pathogenesis is the antigen-antibody reaction, which activates blood proteases, releases
histamine, serotonin and other vasoactive substances that cause primary dilatation of
resistive vessels, decreased peripheral resistance and arterial hypotension.
Blood transfusion shock, where the main mechanism is the interaction of
antigens of foreign erythrocytes (incompatible with the AB0 system with serum
antibodies) - resulting in agglutination of erythrocytes, their hemolysis + release of
vasoactive substances → dilatation of blood vessels + blockade of microcirculatory
ruminants.
Collapse is a rapidly progressing vascular insufficiency, characterized primarily
by a decrease in vascular tone, as well as a sharp decrease in circulating blood volume.
At the same time there is a decrease in inflow of venous blood to heart, decrease in
cardiac output, drop in arterial and venous pressure, perfusion of fabrics and a
metabolism is broken, there is a hypoxia of a brain, vital functions of an organism are
suppressed.
Crash syndrome (long-term crushing syndrome) is a pathological process that
develops in victims as a result of long-term (4-8 hours or more) crushing of soft tissues
of the extremities by fragments of destroyed buildings, structures, boulders during
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landslides in mines and others. Three pathogenetic factors are of great importance in
the development of crash syndrome: a) painful irritation; b) traumatic toxemia due to
the absorption of toxic products of tissue autolysis from the lesion; c) plasma and blood
loss associated with edema and hemorrhage in the area of crushed or prolonged
ischemic tissue.
Coma is a pathological condition characterized by deep depression of CNS
functions and is manifested by loss of consciousness, lack of reflexes to external stimuli
and disorders of regulation of vital functions of the body.
Depending on the etiology, there are exogenous and endogenous coma:
1. Exogenous coma occurs due to the action of pathogenic environmental factors
or as a result of a deficiency of factors necessary for the existence of the organism.
Examples of exogenous coma are traumatic (occurs with brain damage), hypoxic,
hyper- and hypothermic, alimentary-dystrophic (occurs with severe starvation).
2. Endogenous coma develops due to disorders of the functional systems of the
body. Thus, in disorders of the circulatory system there may be apoplexy, coma -
hemolytic, excretory system - uremic, liver - hepatic, endocrine system - diabetic,
hypoglycemic, hypocorticoid, thyrotoxic, and others.

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 Chapter 12. Pathophysiology of the endocrine system

Endocrine system - a system consisting of specialized structures located in the

CNS, various organs and tissues, as well as endocrine glands that produce specific
biologically active substances (hormones). Along with the nervous system, it is
involved in regulating the functions of various systems, organs and metabolic
processes. This allows us to talk about a single neuroendocrine system. There are
several links:
1. The central link is the hypothalamic-pituitary system ("endocrine brain") in
general and the hypothalamic-pituitary neurosecretory apparatus in particular, is a
functional complex consisting of the hypothalamic region, diencephalon and pituitary
gland. Its main functional significance is the regulation of autonomic functions. From
the hypothalamus, this is done in two main ways:
1) transadenohypophyseal, when autonomic functions are regulated through a
complex of peripheral endocrine target glands dependent on the pituitary gland;
2) parahypophyseal - through a system of efferent central neurons of the brainstem
and spinal cord, peripheral sympathetic and parasympathetic neurons. This pathway
carries out secretory, vascular and trophic effects of the CNS and is most important for
the cerebral layer of the adrenal glands, islets of Langerhans, parathyroid glands.
In the formation of hypothalamic-pituitary relationships involved:
1) releasing factors, or liberins (thyroliberin, gonadoliberin, somatoliberin, etc.) -
stimulants and statins (thyrostatin, somatostatin, etc.) - inhibitors of the release of
pituitary hormones. These are substances of oligo- and polypeptide nature, which are
secreted in the hypothalamus and enter the capillaries of the portal system of the
adenohypophysis;
2) oxytocin and vasopressin - active substances that are synthesized in the
hypothalamus and accumulate in the pituitary gland (posterior pituitary gland);

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 3) opioid peptides, endorphins (enkephalins, β-endorphins) - morphine-like
compounds that play the role of neurotransmitters and neuromodulators.
Disruption of the formation of any liberin in the hypothalamus or increased
production of statins leads to a violation of the production of the corresponding tropic
hormone in the adenohypophysis.
2. Peripheral link - dependent glands (thyroid, adrenal cortex, gonads) and
independent (brain adrenal glands, parafollicular cells of the thyroid gland, α-, β-, γ-
cells of the pancreas, as well as hormone-producing cells of the stomach tract, thymus,
etc.) from the adenohypophysis.
3. Dispersed (diffuse) endocrine system - APUD-system. The discovery of this
system undermined the classical principle of "one cell - one hormone", as apudocytes,
as it turned out, are able to produce different peptides and even amines and peptides
within a single cell. The peptides act both as hormones and as mediators. Based on this,
the concept of diffuse endocrine epithelial organs was formulated. Similar cells have
been found in the gastrointestinal tract, bronchial mucosa, thyroid gland, kidneys, and
islets of Langerhans. In addition, endocrine functions of the heart (atrial natriuretic
polypeptide), kidneys (renin, erythropoietin), adipose tissue (leptin, resistin,
adiponectin) were established.
The main manifestations of endocrine dysfunction
Normal incretory function means a level of increment that meets the needs of the
organism at any given moment of its existence in specific environmental conditions.
Incretory dysfunction is called endocrinopathy.
There are three main mechanisms of endocrine pathology:
1. Violation of the central mechanisms of regulation of endocrine functions.
2. Primary glandular mechanisms of disorders.
3. Peripheral (extraglandular) mechanisms of hormone dysfunction.
Violation of the central mechanisms of regulation of endocrine functions may be
due to damage:
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 a) at the level of the cerebral cortex of CNS neurons that secrete hypothalamic
hormones (thrombosis, embolism, hemorrhage, infections (encephalitis), tumors);
b) adenohypophysis (disorders of its blood supply, genetic defects, injuries,
infections (tuberculomas, syphilis), tumors, autoimmune processes).
Primary glandular mechanisms of disorders:
Local pathological processes in the endocrine organs, changing their functional
activity, lead to disruption of biosynthesis and hormone secretion. Causes: infection,
intoxication: adrenal tuberculosis develops necrosis of tuberculous tubercles and
Addison's disease, syphilis - necrosis of syphilitic gum. Both lead to the gradual
destruction of glandular tissue and its hypofunction. With mumps, orchitis develops,
leading to testicular atrophy.
Characteristics of the etiology, pathogenesis and clinical manifestations of
dysfunction of individual endocrine organs:
Total hypopituitarism
Pituitary cachexia (Simmonds disease):
Pathogenesis: Circulatory disorders in the hypothalamus and adenohypophysis,
infections, starvation /→ Dystrophic changes in tissues and metabolic disorders caused
by decreased secretion of tropic hormones of the pituitary gland /→ Acute depletion,
premature aging, severe metabolic and trophic disorders, osteoporosis, hair loss,
insufficiency of all pituitary-depended glands.
Sheehan's disease (syndrome):
Pregnancy is accompanied by hyperplasia of the adenohypophysis, which
increases its susceptibility to hypoxia.
Partial hypopituitarism
Pituitary dwarfism (Nanism)
Various pathological processes in the hypothalamus and pituitary gland, including
in utero → Insufficient formation of HGH and gonadotropins leads to growth
retardation → Abrupt growth retardation, early cessation of physical development,
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body proportions are characteristic of children (predominance of torso length over limb
length), early appearance of wrinkles, underdevelopment of the reproductive system
(gonads), absence of secondary sexual characteristics, often infertility. There may be
infantilism in behavior, memory loss, and low mental performance.
Pituitary hypogonadism
Vascular, infectious, tumor, autoimmune lesions of the hypothalamus and
pituitary gland → Due to insufficient production of gonadotropins, the development
of gonads and secondary sexual characteristics is disrupted.
In men, the formation of androgens is suppressed, which manifests itself in the
form of eunuchoidism. Characterized by tall stature, long slender limbs, poor skeletal
muscle development, relatively wide pelvis, pale skin, decreased facial hair growth,
high tone of voice, sexual dysfunction and infertility. Girls have pituitary infantilism.
Characterized by subtle physique, underdevelopment of the mammary glands,
menstrual irregularities, sometimes inability to conceive. There may be mental
instability, mild vulnerability, mood swings
Hyperfunctional states (hyperpituitarism).
Pituitary gigantism
Eosinophilic pituitary adenoma, hypothalamic tumors → Hypersecretion of STG
or hyperproduction of somatoliberin by the hypothalamus in childhood leads to
increased skeletal growth rates → Increased growth of skeletal bones and internal
organs. In this case, the proportions of the body are usually preserved, although there
may be elongation of the legs and forearms. The growth of patients can reach more than
250 cm. There is muscle weakness, fatigue, depression, sleep disorders, infertility,
trophic disorders, hyperglycemia, hypofunction of the thyroid gland, adrenal glands,
weakened immune defenses.
Acromegaly

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Eosinophilic adenoma of the pituitary gland, tumors of the hypothalamus in the
development of the disease in adults HG overproduction leads to the restoration of
periosteal bone growth, increase in the size of internal organs and metabolic disorders
Growth of bones is accompanied by their thickening and deformation, leading to
superciliary, zygomatic arches, lower jaw. The soft tissues of the patient are
hypertrophied - the nose, ears, lips, tongue are enlarged. Characteristic:
splanchnomegaly, kyphoscoliosis, changes in hair, skin, general weakness, decreased
ability to work, headache, drowsiness, sexual dysfunction, urolithiasis, diabetes
mellitus.
Itsenko-Cushing's disease
Increased ACTH causes hyperproduction of corticosteroids by glands
Manifestations are the same as in Itsenko-Cushing's syndrome.
Hypofunction of the neurohypophysis
Diabetes mellitus
Tumors, infections, injuries, circulatory disorders in the hypothalamus, hereditary
defect of renal receptors for ADH (AntiDiuretic Hormon) → Deficiency of ADH leads
to a decrease in reabsorption of water in the renal tubules → Polyuria, sometimes up
to 10 liters per day (urine has a low relative density), severe thirst (polydipsia), frequent
urination are typical. The function of the digestive system is disturbed: hypoacid
gastritis, constipation and colitis. Headaches, insomnia are noted. When there is no
fluid, dehydration develops.
Hyperfunction of the neurohypophysis
Parkhon's syndrome
Hormone-producing tumors, injuries, inflammation, circulatory disorders of the
hypothalamus, ectopic synthesis of ADH by tumors → Increased reabsorption of water
in the kidneys due to excess ADH → Oliguria, hyponatremia, plasma hypoosmolarity
and hyperhydration are observed. Decreased sodium content below 110 mmol / l and

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plasma osmolarity below 250 mmol / kg is accompanied by drowsiness, apathy,
disorientation, convulsions, nausea, fever, associated with cerebral edema.
Etiology, pathogenesis and clinical manifestations of the adrenal glands
pathology.
Hypofunctional conditions of the adrenal cortex.
Acute insufficiency (Waterhouse-Friedrichsen syndrome).
Injuries, hemorrhage, adrenal vascular thrombosis, DIC syndrome, sepsis →
Deficiency of glucocorticoids, mineralocorticoids, catecholamines → Rapidly
developing progressive muscle weakness, severe hypotension, dyspepsia, death may
occur from acute circulatory failure.
Chronic insufficiency (Addison's disease, bronze disease)
Bilateral adrenal damage (tuberculosis, autoimmune processes), sometimes
ACTH deficiency → Decreased secretion of glucocorticoids, mineralocorticoids,
androgens causes metabolic disorders, disorders of electrolyte metabolism and
regulation of autonomic functions Aldosterone deficiency leads to water-electrolyte
imbalance - hyponatremia, polyuria, hypohydration with the development of
hemoconcentration. GCS (glucocorticosteroids) deficiency is accompanied by
hypoglycemia and hypotension. Androgen deficiency leads to a decrease in muscle
mass → muscle weakness, apathy, hypotension, polyuria, anorexia, indigestion.
Primary hypocorticism is accompanied by hyperpigmentation of the skin associated
with the melanophoric effects of ACTH
Hypoaldosteronism.
Impaired aldosterone synthesis or decreased sensitivity of the renal tubular
epithelium to aldosterone → Decreased sodium reabsorption due to aldosterone
deficiency → Hyponatremia, hyperkalemia, hypohydration. Rapid fatigue, muscle
weakness, hypotension, bradycardia, fainting, indigestion.
Hyperfunctional condition of the adrenal cortex.
Hyperaldosteronism (Conn's syndrome).
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 Hormonally active glomerular tumor → Excess aldosterone causes sodium
retention and water-electrolyte imbalance → Sodium retention and potassium loss lead
to the development of alkalosis → There are hypertension, headache, arrhythmia,
weakness, convulsions and paresthesias. At the beginning of the disease - a decrease in
diuresis, then persistent polyuria due to degeneration of the epithelium of the tubules
and a decrease in their sensitivity to ADH.
Itsenko-Cushing's syndrome.
Hormonal-active tumors of the adrenal cortex → Excess glucocorticoids cause
disorders of protein, fat, carbohydrate, water-salt metabolism → Local (torso) obesity
with fat deposition in the face (moon-shaped face), shoulder girdle, abdomen,
mammary glands and back. On the skin - pink-purple stripes - stretch marks, sometimes
- acne, ecchymoses, hirsutism. Osteoporosis, hypertension, hyperglycemia, muscle
weakness, decreased immunity are typical.
Congenital adrenogenital syndrome.
Genetic defect of enzyme systems of gluco- and mineralocorticoid biosynthesis→
Impaired synthesis of cortisol, corticosterone, aldosterone is accompanied by the
accumulation of androgenic precursors and increased formation of ACTH (on the
principle of feedback due to cortisol deficiency). → In the first years of life, children
grow rapidly. People of both sexes are characterized by short stature, disproportionate
physique: wide shoulder girdle, narrow pelvis, well-developed muscles (so-called
"baby Hercules"), rough voice, acne, hirsutism (growth of hair on the face, chest,
abdomen, limbs). Girls at puberty have no secondary female sexual characteristics and
menstruation. In boys, there is a premature development of secondary sexual
characteristics. At the hypertensive form besides virilization the raised arterial pressure
is noted. In the salt-losing form from the first weeks of life there is vomiting, stool
disorders, dehydration, low blood pressure, weight loss, darkening of the skin.
Hyperfunction of the adrenal glands medulla.

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Tumor of the adrenal medulla - pheochromocytoma → Hyperproduction of
catecholamines → tachycardia, vascular spasm and severe hypertension,
hyperglycemia. In the paroxysmal form - muscle tremors, anxiety, headache, profuse
sweating, sometimes abdominal pain, nausea, vomiting.
Etiology, pathogenesis and clinical manifestations of thyroid gland pathology.
Hypothyroidism
Myxedema
Lack of tyroliberin, TSH, thyroid dysfunction (iodine deficiency, autoimmune
damage). Due to the deficiency of thyroid hormones slows down the basic metabolism,
reduces the speed of nervous processes, impaired metabolism and physiological
regeneration. At the same time lipolysis is suppressed, the metabolism of proteins and
carbohydrates is disturbed. Patients complain of chills, weight gain, drowsiness, dry
skin, decreased attention and memory, depression, hair loss and brittleness, nails, often
develop bradycardia, myocardial infarction, hypoacid gastritis, decreased secretion and
motility of the intestine. In men, sexual function is impaired, in women - the menstrual
cycle.
Cretinism.
Hypoplasia of the thyroid gland, congenital defects in hormone biosynthesis,
iodine deficiency. In early childhood, a lack of thyroid hormones leads to disorders of
protein synthesis, CNS formation, secretion and effects of STH (SomatoTropic
Hormon) and mental disorders up to idiocy.
Endemic goiter (enlargement of the thyroid gland)
Iodine deficiency in the environment (water and food) → a decrease in the
concentration of thyroid hormones in the blood increases the production of thyrotropin,
which against the background of iodine deficiency leads to hyperplasia of glandular
tissue. In hypothyroidism - manifestations characteristic of myxedema or cretinism.
Hyperthyroid state.
Diffuse toxic goiter (Graves-Bazedov disease).
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 Disease of autoimmune nature Accumulation in the blood of Ig (mainly class G),
able to interact with TTH receptors on thyrocytes and stimulate the secretion of thyroid
hormones There are increased nervous and mental excitability, irritability, sleep
disorders, tremor. Characterized by increased appetite and weight loss due to increased
catabolism. Tachycardia and hypertension lead to the development of myocardial
hypertrophy. There is shortness of breath, increased sweating, heat transfer, muscle
weakness.
Etiology, pathogenesis and clinical manifestations of the main forms of
pathology of the parathyroid glands.
Hypoparathyroidism.
Removal of parathyroid glands in thyroidectomy, inflammation, autoimmune
damage leads to Parathyroid hormone deficiency. It reduces the resorption of calcium
from the bones, its absorption in the intestine, as well as enhances the reabsorption of
phosphorus and reduces the reabsorption of calcium in the kidneys. Hypocalcemia,
hyperphosphatemia, alkalosis. Characteristic paroxysmal convulsive muscle
contractions (tetany). Cramps more often occur in the muscles of the face, upper
extremities. Asphyxia due to laryngospasm is possible.
Hyperparathyroidism (Recklinghausen's disease).
Adenoma or hyperplasia of the parathyroid glands. Hyperproduction of
parathyroid hormone stimulates the release of calcium from bone tissue, reduces the
reabsorption of phosphorus in the renal tubules Hypercalcemia, hypophosphatemia.
Osteoporosis, deformity of the extremities, spontaneous, long-term healing, and bone
fractures. Increased excretion of calcium and phosphorus in the urine leads to the
development of urolithiasis. Characteristic: polyuria, polydipsia, muscle weakness,
drowsiness, loss of appetite.
Principles of treatment and prevention of endocrine disorders:
Replacement therapy - the introduction of natural hormonal substances, their
close derivatives and analogues derived from glands or synthesized, transplantation of
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endocrine organs, as well as normalization of cortico-hypothalamic-pituitary regulation
by filling the deficiency of hormone components, direct stimulation, direct stimulation
stimulation of the action of certain peripheral hormones. Used in disorders of
hypofunctional nature.
Suppressive therapy - partial or total extirpation of the gland with subsequent
transfer to replacement therapy, X-ray and radiotherapy, chemical suppression of
hormone-producing function, as well as inhibition of endocrine glands by blocking
certain stages of hormone biosynthesis, dosed by certain pericarmological damage. It
is used in hyperfunctional disorders.
Stimulating therapy - the use of stimulant hormones (corticotropin and other
trophic hormones), transplantation of endocrine organs.
Stress is a non-specific reaction of the body that occurs under the influence of
unusual and adverse stimuli and is accompanied by the activation of non-specific
mechanisms of adaptation. The term was introduced by G. Selye.
Causes of stress - stressors: physical, chemical, biological, social factors.
Stress manifests itself in the form of a general adaptation syndrome.
Selye Triad:
1. Involution of the thymus and lymphoid tissue;
2. Hypertrophy of the adrenal cortex;
3. Gastric and duodenal ulcers.
Stages of the general adaptation syndrome:
I. Stage of anxiety: a) shock phase - muscle hypotension, blood pressure,
hypothermia, hypoglycemia, negative nitrogen balance, eosinopenia, lymphopenia,
neutrophilia, increased capillary permeability, involution of lymphoid tissue, gastric
and duodenal ulcers; b) anti-shock phase - increase in blood pressure and muscle tone,
hyperglycemia, increased secretion of corticotropin and glucocorticoids.

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 II. Stage of resistance - hypertrophy of the adrenal cortex, increased concentration
of glucocorticoids in the blood, activation of anabolic processes, increased
gluconeogenesis. The adaptive capacity of the organism reaches the highest level.
III. Stage of depletion - atrophy of the adrenal cortex, decreased production of
glucocorticoids, blood pressure, hypothermia, hypoglycemia, increased breakdown of
tissue proteins, and depletion of the body's functionality.

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 Chapter 13. Pathophysiology of the nervous system

Classification of disorders of the nervous system:

I. According to the anatomical principle are:
1) disorders of the peripheral nervous system;
2) disorders of the central nervous system, including disorders of the spinal cord,
medulla oblongata, midbrain, and others.
II. By origin, there are hereditary and acquired disorders of the nervous system.
Acquired can be primary (with direct action on the nervous system of pathogenic
factors: physical (trauma, radiation, thermal exposure), chemical (toxins, poisons),
biological (viruses, bacteria), social (word) and secondary (primarily due to disorders
of homeostasis (hypoxia, hypoglycemia, acidosis, etc.), immune factors (autoallergic
reactions), cerebrovascular disorders).
III. Depending on the type of impaired functions, the following disorders of the
nervous system are distinguished:
1) violation of sensory functions (sensitivity);
2) violation of effector functions: motor, autonomic, trophic;
3) violation of integration functions.
The concept of somatovisceral sensitivity includes skin sensitivity (tactile,
temperature, pain), deep sensitivity (proprioception) and pain sensitivity of the whole
body (nociception).
There are the following types of disorders of somatovisceral sensitivity:
1) hyperesthesia - increased sensitivity;
2) hypoaesthesia - decreased sensitivity;
3) anesthesia - lack of sensitivity.
Mechanisms underlying disorders of somatovisceral sensitivity:
1. Violation of reception. With increasing threshold of excitation of receptors there is
a hypoesthesia, at decrease - a hyperesthesia.
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 2. Damage to peripheral nerves. At the same time all types of sensitivity in a zone
of an innervation of the given nerve drop out.
3. Damage to the posterior roots of the spinal cord. It is characterized by the loss
of all types of sensitivity in the area of the respective segments.
4. Spinal cord injury. When cutting half of the spinal cord (left or right) develops
Brown-Sekara syndrome. Thus, below the level of the cut on his side fall proprioceptive
and complex types of tactile sensitivity (damaged Lemnic pathway to its intersection),
and on the opposite side - temperature, simple tactile and partially painful sensitivity
(damaged anterolateral pathway after crossing).
5. Dysfunction of subcortical structures involved in the implementation of sensory
functions. The most important is the defeat of the nuclei of the thalamus.
6. Lesions of sensory areas of the cerebral cortex. Disorders of postcentral gyrus
neurons lead to disorders of complex tactile and proprioceptive sensitivity on the
opposite side of the body.
Pain is an unpleasant sensory and emotional sensation associated with the threat
or damage to tissues.
Classification:
I. According to the clinical characteristics (subjective sensations), the pain can be
sharp and dull, localized and diffuse, have the character of tingling, tingling, heat, and
others.
II. Depending on the duration of pain, the pain can be acute or chronic. Acute pain
passes quickly after the cessation of pain stimuli, chronic is prolonged, causing
suffering to the patient.
III. The importance of pain for the body can be physiological and pathological.
Physiological pain has a protective value. It signals damage or its possibilities,
promotes the inclusion of certain behavioral reactions aimed at repairing the damage,
limits the functions of the affected body. Pathological pain has no signal function, it

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becomes a mechanism of vital functions, including the brain, leads to dysfunction of
various organs and systems.
Somatic superficial pain is pain that occurs in the skin. There are two types: early
and late pain. If you inflict severe mechanical injury, then immediately there is an acute,
sharp, well-localized pain, which passes quickly after the end of the pathogenic factor
- this is the so-called early pain. After some time (0.5-1 s) there is a late pain. It is a
dull, aching, diffuse pain. It continues for some time after the cessation of the
pathogenic factor.
Somatic deep pain is pain that occurs in deep tissues. These include headache,
toothache, muscle and joint pain. It is often dull, has no clear localization, is
accompanied by affective (general malaise, morbidity) and autonomic (nausea,
sweating, decreased blood pressure) reactions.
Visceral pain is pain that occurs in the internal organs.
Types of pain depending on its location:
- Local pain - localized in the place of action of the stimulus, in the area of
development of the pathological process.
- Projection pain - the place where the pain stimulus acts, does not coincide with
where the pain is felt. For example, when the intervertebral discs are damaged, the
spinal nerves are compressed. At the same time it hurts in that site which is innervated
by the affected nerve, that is there is a projection of pain on sites which receive
innervation from the damaged nerve.
- Irradiating pain - a painful sensation caused by exposure to internal organs, often
localized not in this organ (or not only in it), but in distant superficial areas of the skin.
Chronic is a strong, prolonged, debilitating pain that causes suffering to the
patient. There are the following forms of chronic pain:
1. Neuralgia - a pain syndrome associated with disorders of the peripheral nerve
in viral infections, beriberi, circulatory disorders, metabolic disorders (diabetes).

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 2. Causalgia - severe burning pain that occurs when large somatic nerves are
damaged (incomplete nerve cutting).
3. Phantom pain. Occurs after amputation of limbs - "hurts" limb, which is no
more. The pain is very strong and often unbearable.
4. Thalamic pain - severe spontaneous pain throughout the body with a subjective
impression of hypersensitivity. It develops in lesions of the nuclei of the thalamus.
Antinociceptive natural mechanisms limit pain, suppressing the conduction of
pain signals at all levels of the nervous system involved in the formation of pain. There
are 4 antinociceptive systems in the body:
I. Neural opiate antinociceptive system. It is formed by enkephalinergic neurons
of three levels: Spinal cord, medulla oblongata and midbrain.
II. Hormonal opiate analgesic system. It consists of five levels: spinal cord,
medulla oblongata, midbrain, hypothalamus, and adenohypophysis.
III. Neuronal non-opiate analgesic system. It is represented by monoaminoergic
structures of the brainstem (the nuclei of the suture, locus coeruleus, and central gray
matter).
IV. Hormonal non-opiate analgesic system. Activated by stress response.
The main syndromes that characterize the motor function of the nervous
system.
Hypokinesia - limitation of the volume, number and speed of movements. They
are usually combined with a decrease in motor activity and muscle contraction
(hypodynamics).
Types of hypokinesia:
1. The severity of movement disorders:
- paresis (reduction of amplitude, speed, force and number of arbitrary
movements);
- paralysis (complete absence of voluntary movements).
2. The prevalence of movement disorders:
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 - monoplegia (paralysis or paresis of one limb);
- paraplegia (paralysis or paresis of both arms or both legs);
- hemiplegia (paralysis or paresis of the left or right half of the body);
- triplegia (paralysis or paresis of three extremities);
- tetraplegia (paralysis or paresis of the arms and legs).
3. By changing muscle tone:
- spastic (increased muscle tone, usually of one group in the defeat of central
motoneurons in any part of the pyramidal pathway);
- rigid (increased tone of one or more groups of antagonistic muscles, limb or torso
long retain their posture - "waxy rigidity", which is a consequence of damage to the
extrapyramidal system);
- sluggish (reduced muscle tone in the area of innervation of the damaged nerve
trunk or center in the defeat of motoneurons or anterior roots of the spinal cord).
4. Depending on the predominant lesion of nerve structures are:
- central,
- peripheral,
- extrapyramidal,
- myasthenic forms of hypokinesis.
Central paralysis and paresis. Etiology: damage to pyramidal neurons, damage
to the cortico-spinal pathways of the pyramidal system. Events:
- muscular hypertension (increased muscle tone by spastic type);
- hyperreflexia (increased segmental tendon and periosteal reflexes - increasing
the amplitude of the response and expanding the area of the reflex);
- pathological reflexes (for example, Babynsky, Rosolimo, Bekhterev, which are
due to increased segmental reflexes of the spinal cord due to the weakening of the
inhibitory descending effects of the brain);
- clonus (high degree of increase in tendon-muscle reflexes; manifested by a series
of rapid rhythmic contractions of individual muscles);
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 - synkinesis (involuntary joint muscle contractions and movements that occur in a
paralyzed limb when performing arbitrary movements with another limb or other part
of the body)
Peripheral paralysis and paresis. Etiology: inherited, congenital or acquired
lesions of peripheral motoneurons. Acquired paralysis and paresis develop as a result
of degenerative changes, inflammation, mechanical trauma and neuromuscular
disorders (eg, botulism, myasthenia gravis, toxins, toxins). Events:
- muscular hypotension (decreased muscle tone, muscles weak to the touch,
sluggish);
- hyporeflexia (reduction or absence of segmental reflexes);
- muscle atrophy (formed due to prolonged muscle inactivity, as well as as a result
of neurotrophic effects on them), degeneration of muscle fibers with their replacement
by adipose and connective tissue, decreased muscle excitability;
- Excessive passive movements in the paralyzed limb.
Myasthenic hypokinesia. These include myasthenia gravis, Lambert-Eaton
syndrome. Etiology: violation of synaptic transmission in cholinergic neuromuscular
synapses - from the terminal motor fibers to skeletal muscle fibers. Pathogenesis:
blockade of postsynaptic cholinoreceptors by antibodies - Ig are fixed on the
postsynaptic membrane of the muscle fiber and thus prevent the interaction of
acetylcholine with cholinoreceptors. Manifestations: muscle weakness (myasthenia) of
varying severity, rapid muscle fatigue during exercise.
Hyperkinesia.
An increase in the volume and number of involuntary movements - develops due
to damage to neurons of various brain structures (extrapyramidal system, thalamus,
subthalamic nucleus, cerebellar nucleus, red nucleus, cortex and their communication
systems).
Types of hyperkinesis:

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 1. By localization of the affected brain structures: cortical, subcortical, stem.
2. The prevalence of the process:
- general (involving several or most muscle groups);
- local (involuntary contraction of individual muscles or their fibers).
3. With the predominance of phase (rapidly changing) or tonic (slow) components
of reduction: rapid and slow.
Rapid hyperkinesias:
Seizures - involuntary muscle contractions of varying intensity, duration and
prevalence:
- clonic (short-term and irregular contractions of certain muscle groups, most often
occur as a result of excessive excitation of the cortex of the large hemispheres or
damage to the structures of the pyramidal system; common pronounced clonic seizures
are referred to as convulsions);
- tonic (prolonged muscle contractions, resulting in "hardening" of the torso or
limbs in various forced positions; develop with excessive excitation of subcortical
structures and some types of intoxication; editing may develop opisthotonus);
- mixed (clonic-tonic, tonic-clonic; observed in diabetic, hepatic or uremic coma;
burn or anaphylactic shock).
Chorea - chaotic, rapid, violent contractions of various muscle groups. May be of
hereditary origin (eg, Huntington's chorea).
Tremor - hyperkinesis type of tremor, characterized by involuntary, stereotyped
rhythmic oscillating movements of the body or its parts due to repetitive contractions
and muscle relaxations. Occurs mainly in brainstem damage. It is observed at organic
defeats of a brain, exogenous intoxication of an organism.
Tick - rapid involuntary stereotyped muscle contractions that cause violent
movements (eg, blinking, gesturing). Observed mainly in the defeat of the
extrapyramidal system as a result of encephalitis, intoxication, the use of
psychopharmacological drugs, as well as some mental disorders.
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 Slow hyperkinesias:
Athetosis - involuntary stereotyped, slow worm-like bizarre movements that occur
as a result of simultaneous prolonged activation of agonist and antagonist muscles. The
distal parts of the extremities of the fingers and toes are most often affected. They
develop in lesions of the caudate nucleus, shell in encephalitis, cerebrovascular
disorders, traumatic brain injury, tumors of the subcortical parts of the brain.
Spastic crooked neck - neck deformity and incorrect position of the head (tilt to
one side) as a result of prolonged neurogenic contraction - spasm of the neck muscles.
Cerebral circulatory disorders:
I. Acute disorders of cerebral circulation. Strokes are acute disorders of cerebral
circulation that lead to persistent brain dysfunction. There are:
a) hemorrhagic strokes - hemorrhages in the brain. Most often it is the result of
persistent arterial hypertension (rupture of the altered wall of the arterial vessel);
b) ischemic strokes (cerebral infarction). The reason for their development is
atherosclerotic vascular lesions (thrombosis, stenosis).
II. Chronic cerebrovascular disorders - vascular encephalopathy. They develop
as a result of atherosclerotic process and lead to focal dystrophic changes in brain
tissues.
Brain edema is the accumulation of fluid in the interstitial tissue of the brain, and
swelling is its intracellular edema.
According to the etiology, cerebral edema can be traumatic, tumorous,
postoperative, toxic, inflammatory, and others.
In the pathogenesis of cerebral edema are important:
I. Vascular factors:
a) increase in hydrostatic pressure in capillaries (arterial hyperemia, venous
hyperemia, hypervolemia);
b) reduction of oncotic blood pressure;
c) increasing the permeability of the blood-brain barrier.
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 II. Tissue factors:
a) increase in oncotic pressure in brain tissue (protein release from damaged cells,
protein breakdown);
b) reduction of hydrostatic pressure in brain tissue;
c) damage to glial elements of the blood-brain barrier.
"Enchanted circles" are of great importance in the pathogenesis of cerebral edema.
One of them: cerebral edema → increase in intracranial pressure → compression of
venous vessels (venous hyperemia) → increase in hydrostatic pressure in capillaries →
cerebral edema.
Intracranial hypertension is an increase in intracranial pressure. Reasons:
1) increase in blood supply to the brain (arterial hyperemia, venous hyperemia);
2) increase in the amount of cerebrospinal fluid (CSF) - hydrocephalus. It can be
caused either by an increase in the formation of cerebrospinal fluid, or a decrease in its
outflow from the ventricles of the brain;
3) increase in the volume of brain tissue - edema and swelling of the brain;
4) the appearance of additional three-dimensional structures in the cranial cavity.
These may be inflammatory exudate (meningitis), hematomas, tumors, abscesses.
Increased intracranial pressure leads to compression of the cerebral veins. This in turn
causes cerebral circulatory disorders and hypoxia, and on the other hand, contributes to
the development of cerebral edema.
Disorders of the integration functions of the central nervous system:
1. Violation of sensations and perception - higher sensory functions. An example
is agnosia - recognition disorders. There are visual, auditory and others types of
agnosia.
2. Disorders of consciousness. These include, in particular, varying degrees of stun
(form of darkening of consciousness): obnubulation (eclipse), somnolence
(drowsiness), sopor (insensitivity, unawakened sleep), coma.

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 3. Disorders of thinking. One of the extreme forms of thinking disorders is
dementia (dementia).
4. Speech disorders - aphasia. There are motor aphasia (complicated or
impossible reproduction of speech, language comprehension can be preserved) and
sensory aphasia (disorders of speech perception).
5. Violation of behavioral reactions. An example is apraxia - a violation of
purposeful actions (a person cannot wave his hand, cut bread, although his hands are
not paralyzed).
6. Violation of emotions. Among them are hypothymia (depressive syndrome),
hyperthymia (manic syndrome), neuroses (neurasthenia, obsessive-compulsive
disorder, hysterical neurosis).
7. Violation of motivation. There are abnormally increased motivations (bulimia,
polydipsia, sexual perversions), abnormally weakened motivations (anorexia, adipsia,
impotence, frigidity).
8. Impaired ability to learn. Inability to learn is one of the leading signs of
oligophrenia (congenital dementia). Depending on the degree of intellectual defect,
there are dementia, imbecility, idiocy.
9. Memory disorders - amnesia.
10. Disorders of sleep-wake cycles. They can be manifested by insomnia and
drowsiness.
Neurosis is a chronic disorder of higher nervous activity caused by psycho-
emotional overstrain and is manifested by disorders of the integral activity of the brain
- behavior, sleep, emotional sphere and somato-vegetative activity. This is a
psychogenic disease that occurs against the background of personality traits and lack
of mental protection with the formation of neurotic conflict.

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