P a t h o p h y s i o l o g y - I semester

1. Pathophysiology - definition, aim and constituent parts. (page 3)

2. Health and Disease - definition, classification and stages of disease. (page 3)
3. Death and Reanimation - Terminal state, agony, clinical death, biological death. Aim and methods
of reanimation (page 3)
4. Pathological reaction, pathological process and pathological state, "vicious circle". (page 4)
5. Etiology and Pathogenesis (page 4)
6. Cellular injury and adaptation – atrophy, hypertrophy, dystrophy, dysplasia, metaplasia(page 4)
7. Cell necrosis and apoptosis. Mechanisms of development (page 5)
8. Disorders of cell membrane – toxic free radicals, POL and Antioxidant system. Role of NO in
pathology(page 5)
9. General Adaptation Syndrome - Stress reaction (page 5)
10. Stress proteins, acute phase reactions. Activation of proteolytic system (page 6)
11. Shock, Collapse and Coma – definition and pathogenesis (page 7)
12. Damaging action of environmental factors on organism. Mechanical injuries of the brain.
Pathogenesis and clinical manifestations. (page 8)
13. Effects of acceleratory forces on the body. Pathogenesis and clinical manifestations (page 9)
14. Effects of thermal agents on the body. Pathogenesis and clinical manifestations. Hyperthermia,
Heat stroke. (page 9)
15. Fever – Definition, etiology, pathogenesis, pyrogens, stages of fever (page 11)
16. Difference between fever and hyperthermia. (page 10)
17. Thermal injuries. Burn disease (page 11)
18. Effects of low temperature on the body. Hypothermia, Pathogenesis and clinical manifestations.
19. Electrical injury. Pathogenesis and clinical manifestations.
20. Effects of low partial pressure on the organism - Mountain disease.
21. Effects of high partial pressure on the organism - Caisson disease.
22. Damaging effects of Ionizing radiation. Pathogenesis and clinical manifestations
23. Role of inheritance in pathology. Etiology of inherited diseases.
24. Immunopathology. Congenital and acquired immuno-deficiencies.
25. Role of constitutional types in pathology. Reactivity of the organism
26. Hypoxia. Types and compensatory mechanisms at hypoxia
27. Acid-base imbalance. Respiratory and metabolic acidosis and alkalosis
28. Types of blood vessels. Principles of hemocirculation (hemodynamics). Hemodynamic laws.
29. Arterial hyperemia, definition, reasons, types and manifestations

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30. Venous hyperemia, definition, reasons, types and manifestations
31. Ischemia - definition, reasons, types and manifestations
32. Clinical manifestations of disorders of microhemocirculation
33. Slag phenomenon, Stasis, and their pathogenesis
34. Thrombosis and Emboli - definition, pathogenesis, types and outcome
35. Disseminated intravascular coagulation - definition, reasons, pathogenesis and treatment
measures.
36. Inflammation - definition, etiology, pathogenesis and outcome
37. Exudation, mechanisms of development and types of exudate
38. leukocytes emigration, phagocytosis at inflammation
39. Inflammatory mediators.
40. Allergy - definition, classification, etiology and pathogenesis of hypersensitivity reactions.
41. Pathogenesis of Type I hypersensitivity reaction
42. Pathogenesis of Type II hypersensitivity reaction
43. Pathogenesis of Type III hypersensitivity reaction
44. Pathogenesis of Type IV hypersensitivity reaction
45. Hyperbiotic processes
46. Cancer growth. Etiology and pathogenesis. Malignant and benign tumors. Characteristics of
malignant growth. Process of metastasis.
47. Experimental modeling of cancer growth.
48. Disorders of metabolism. Starvation
49. Water-electrolyte imbalance. Types of edema
50. Hydrocarbonates metabolism disorders. Diabetes mellitus.

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QUESTION 1:Pathophysiology - definition, aim and constituent parts.
Pathophysiology is a science about origin, development and outcome mechanisms of disease or
pathologic process.
Pathophysiology is the study of the:
a. mechanisms by which disease occurs in living organisms
b. responses of the body to disease processes
c. effects of these pathophysiological mechanisms on normal function
d. Pathophysiology is the Science that coordinates the clinical signs and symptoms of disease with
laboratory research.

The object of pathophysiologic research is pathologic process. The general aim is to establish
developmental mechanisms of pathologic process and on the basis of these findings select
appropriate methods of treatment.
The course of Pathophysiology consists of three general parts:
1. General pathophysiology (and typical pathological processes,).
2. Pathophysiology of organs and systems
3. Clinical pathophysiology.

In the first part we study common nosology or study about disease, relationship between norm and
pathology, disease essence, its classification, stages and outcome, etiology and pathogenesis,
reactivity, allergy, immunity etc. We discuss also basic reactions of cells and tissues to abnormal
stimuli that underlie all diseases, and typical pathological processes such as inflammation, fever,
alterations of metabolism, arterial and venous hyperemia, ischemia, starvation etc.

The second part involves pathophysiology of blood, cardio-vascular, respiratory, digestive,

endocrine and other systems.

QUESTION 2:Health and Disease - definition, classification & stages of disease.

Answer: Disease is the set of reactions developed in organism in response to abnormal stimuli
characterized by activated compensatory reactions, altered homeostasis, functional and structural
changes leading to disability.
Any disease has its Etiology or cause and conditions. Etiologic factors can be inherited or acquired.
Disease conditions can be subdivided into External and Internal conditions or factors.
External and Internal factors either support or prevent disease development.
External factors involve: ecologic state (ambient temperature, humidity, radiation, partial pressure
etc.) and conditions of daily life. Internal factors are: sex, age, genetics, reactivity, and
constitutional type of individuals.
Disease periods:
1. Latent or Incubative or Hidden period involves the period from exposure to causative agent
till manifestation of first clinical symptoms.
2. Prodromal period or prodrome - is the period from manifestation of first nonspecific clinical
symptoms till full exhibition of the clinical picture of the disease.
3. The period of perfect manifestation of clinical symptoms of disease.
4. The outcome of disease (recovery or death). Recovery in turn may be complete or
incomplete.

QUESTION 3:Death and Reanimation - Terminal state, agony, clinical death,

biological death. Aim and methods of reanimation
Answer: The death is a dynamic process and goes through stages:
1. Terminal state - characterized by hypotensia, tachycardia, unconsciousness followed by
bradycardia and bradipnea. After the above–mentioned disorders respiration stops for about
3-4 minutes. This pre-terminal interval or pause is due to increased vagal tonus.

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 Hypercapnia, developed during apnea, stimulates respiratory center leading to deep
inhalation with widely opened mouth (as if "swallows" air).
2. Agony or extreme suffering when last burst of vital activities take place. Decreased arterial
blood pressure normalize, heart work and respiration become stronger. Duration of
mentioned delusive "revival" is time limited and is accomplished by full oppression of all
vital function activities.
3. Clinical death - begins when heart beating and respiration stop functioning. Metabolism is
maintained on a minimal level, therefore clinical death is reversible process and reanimation
is possible. Clinical death lasts for about 5-6 minute after cardio-respiratory arrest.
4. Biologic death is the end stage of the death. It is irreversible process during which
metabolism is definitively stopped. Biologic death is characterized by cell necrosis.

Reanimation means revival.

The general aim of reanimation is to restore heart beating and respiration.
Methods of reanimation
1. Artificial respiration
2. Cardiac massage(direct and indirect)
3. Defibrillation
4. Intra-arterial hemotransfusion in brachial artery (blood reaches aorta, stimulates receptors,
flows through the coronaries and improves cardiac trophic).

QUESTION 4: Pathological reaction, pathological process and pathological

state(condition), "vicious circle".
Answer: Pathological reaction is a short, specific , frequently inadequate response to irritation.
After the irritation is over, reaction stops.
When the organism maintains its basic functions and only local change of structure and function
is appeared, we call it pathological process, not disease.
Pathological processes and reactions often are met with permanent combinations that are called
as typical pathological processes (e.g. inflammation, tumor, fever etc)
Typical pathological processes may be caused by several reasons or their characteristic is
polietiology
Pathologic condition on itself can be occurred as a cause of pathologic process, e.g. endocarditis
is pathological process that caused often cardiac compensated defect, Cardiac Defect- (this
pathologic condition) can be derived into its decompensate phase, - (pathologic process).
“vicious cycle” I wasn’t able to find the answer on this…

QUESTION 5: Etiology and Pathogenesis

Answer: Etiology is a science that studies terms and causes of disease initiation, development
and outcome.
Theories of etiology: monocausalism and conditionalism.
Pathogenesis is a science that studies mechanisms of a disease initiation, development and
outcome.

QUESTION 6: Cellular injury and adaptation – atrophy, hypertrophy,

dystrophy, dysplasia, metaplasia.
Answer: cellular atrophy-decreases the cell substance and results in cell shrinkage. The size of
all structural components of the cell decreases as the cell atrophies. Causes: denervation, lack of
endocrine stimulation, decreased nutrition or ischemia.
Hypertrophy: increases the amount of functioning mass by increasing cell size.
Dystrophy: any of various bodily disorders, characterized by wasting of tissues. Faulty or
inadequate nutrition or development. Any of a number of disorders characterized by weakening or

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degeneration but the cell maintains vital capacity. Types of dystrophy: dysproteinosis,
dyslipidosis, dyscarbohydratosis, pigmental and mineral.
Dysplasia: basic functional and structural dysfunction, cell doesn’t maintain vital capacity e.g.
sickle cell anemia. It is deranged cell growth that results in cells that vary in size, shape and
appearance of mature cells and it is related to hyperplasia.
Metaplasia: is a reversible conversion of one adult cell type to another. It allows for replacement
with cells that are better able to tolerate environmental stresses.

QUESTION 7: Cell necrosis and apoptosis. Mechanisms of development

Answer: Necrosis: involves process of cellular self digestion known as autodigestion or
autolysis. As necrosis progresses, most organelles are disrupted and karyolysis, nuclear dissolution
from the action of hydrolytic enzymes becomes evident. In necrosis we have cell swelling and lysis.
Types of necrosis: coagulative, caseous, liquefactive and fat.
Apoptosis: programmed cell death. Here we have shrinkage of the cells.
Mechanism: trigger effect of cytokines and hormones or moderate injury in oxygen availability
leads to activation of long living RNA of cytoplasm, expression of apoptotic genes, suppression of
apoptotic blockators, which then results in activation of cytoplasmic proteases, intensification of
active oxygen species production, accumulation of calcium in cytoplasm andbingind of apoptosis
proteins with RNA, which lead to fragmentation of nucleus and cytoplasm, then production of
apoptotic bodies and finally autophagocytosis takes place.

QUESTION 8: Disorders of cell membrane – toxic free radicals, POL and

Antioxidant system. Role of NO in pathology.
Answer: Most frequent injury of cell membrane, which is Lipid peroxidation is caused by free
radicals. These are: Superoxide radical O2-( Initiates free radical oxidation, O2 -+ H2O2 = O2 +
OH- + OH-(Huber-Vice Reaction) ), Hydroxile radical HO –, Hydro peroxide H2O2 (It also
initiates hydroxyle radical formation , 2O2 + FE+2 = Fe+3 + OH- +OH- (Fenton Reaction) ), .
Their formation ways are: 1. Phagocytes:
a. tissue macrophages
b. monocytes
c. blood granulocytes
2. Electrons transportation disorder in respiration chain of mitochondria
3. Metabolic transformation of catecholamines
4. Process of prostaglandin synthesis
The role of NO in pathology: generally NO is a free radical air , NO is synthesed from L-
Arginin by help of NOS – No synthase, 2 types of NO synthases are revealed:
a. Constitutional
b. Inductive
The main role of NO is that it causes vasodilation. it has key roles in maintaining haemostasis
and in smooth muscle (especially vascular smooth muscle), neurons and the gastrointestinal tract. It
is intimately involved in regulating all aspects of our lives from waking, digestion, sexual function,
perception of pain and pleasure, memory recall and sleeping.

QUESTION 9: General Adaptation Syndrome - Stress reaction

Answer: Stress – organism’s non specific reactions entirety, which is characterized by
neuroendocrinological metabolic changes as a response to stressors
Physiologists define stress as how the body reacts to a stressor, real or imagined a stimulus that
causes stress. Acute stressors affect an organism in the short term; chronic stressors over the
longer term.
Alarm is the first stage. When the threat or stressor is identified or realized, the body's stress
response is a state of alarm. During this stage, adrenaline will be produced in order to bring about
the fight-or-flight response. There is also some activation of the HPA axis, producing cortisol.

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Resistance is the second stage. If the stressor persists, it becomes necessary to attempt some means
of coping with the stress. Although the body begins to try to adapt to the strains or demands of the
environment, the body cannot keep this up indefinitely, so its resources are gradually depleted.
Exhaustion is the third and final stage in the GAS model. At this point, all of the body's resources
are eventually depleted and the body is unable to maintain normal function. The initial autonomic
nervous system symptoms may reappear (sweating, raised heart rate, etc.). If stage three is
extended, long-term damage may result, as the body's immune system becomes exhausted, and
bodily functions become impaired, resulting in decompensation.

QUESTION 10: Stress proteins, acute phase reactions. Activation of proteolytic

system
Answer: stress proteins- Heat shock proteins (HSP) are a class of functionally related proteins
involved in the folding and unfolding of other proteins. Their expression is increased when cells are
exposed to elevated temperatures or other stress. This increase in expression is transcriptionally
regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock
response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all
living organisms, from bacteria to humans.
Heat-shock proteins are named according to their molecular weight. For example, Hsp60, Hsp70
and Hsp90 (the most widely-studied HSPs) refer to families of heat shock proteins on the order of
60, 70 and 90 kilodaltons in size, respectively. The small 8 kilodalton protein ubiquitin, which
marks proteins for degradation, also has features of a heat shock protein.
Production of high levels of heat shock proteins can also be triggered by exposure to different kinds
of environmental stress conditions, such as infection, inflammation, exercise, exposure of the cell to
toxins (ethanol, arsenic, trace metals and ultraviolet light, among many others), starvation, hypoxia
(oxygen deprivation), nitrogen deficiency (in plants), or water deprivation.
Heat shock proteins function as intra-cellular chaperones for other proteins. They play an
important role in protein-protein interactions such as folding and assisting in the
establishment of proper protein conformation (shape) and prevention of unwanted protein
aggregation. By helping to stabilize partially unfolded proteins, HSPs aid in transporting proteins
across membranes within the cell.
Acute phase reaction: They are organism’s general, non specific, adaptive reactions. During this
reactions interleukin 1 synthesis is stimulated(macrophagues, neutrofiles). Interleukin 1 causes
acute phase globulin synthesis in liver and its transfer in blood. Such proteins are: C reactive
protein, haptoglobin, complement, ceruloplasmin, fibrinogen, etc.

Proteolytic system activation: Proteolysis systems have important role in physiologic processes and
frequently in non specific adaptive reactions. When their activation is non adequate , they self
become pathogenetic factors and cause pathological process. One of them is Kallikrein kinin system
activation .
The kinin-kallikrein system or simply kinin system is a poorly understood system of blood
proteins that plays a role in inflammation, blood pressure control, coagulation and pain. Its
important mediators bradykinin and kallidin are vasodilators and act on many cell types.
Activation of kinin-kallikrein system causes synthesis of neurovasoactive polypeptides – Kinins.
Immensely important of them are mediators polypeptide bradykinin and kallidin. They are
vasodilators and act on many cell types.
The system consists of a number of large proteins (High-molecular weight kininogen (HMWK) and
low-molecular weight kininogen (LMWK), some small polypeptides and a group of enzymes
(Kallikreins and Prekallikrein) that activate and deactivate the compounds .

Antioxidative system provides destruction of oxygen active forms, free radicals and hydroxides.

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 Fermental antioxidation Non Fermental antioxidation

Superoxidedismutase, catalase, micro molecular compounds:

peroxidases, ferritin, ceruloplasmin: (Fe2+ a. Tocoferol (Vitamin E)
+O2 = Fe3+ + O2-) b. Glutatione
c. Cisteine
d. Cistamine
e. Ascorbic acid
f. Ubiquinone
g. Steroid hormones

11. Shock, Collapse and Coma – definition and pathogenesis

Circulatory shock, relate to a problem with the
body's circulatory system, and may lead to
hypoxemia or cardiac arrest. It progresses by a
positive feedback mechanism. At a cellular level
shock is oxygen demand greater than oxygen
supply

There are four stages of shock; Initial,

Compensatory, Progressive & Refractory

Initial: hypoperfusion  hypoxia cell membrane

damage & anaerobic respiration  systemic
metabolic acidosis.

Compensatory: the body employs physiological

mechanisms, including neural, hormonal and bio-chemical mechanisms in an attempt to reverse the
condition. A) Acidosis  hyperventilate. B) The baroreceptors detect hypotension  release
adrenaline (predominately causes an increase in heart rate) and noradrenaline (causes predominately
vasoconstriction)  increase in blood pressure. C) Renin-angiotensin axis is activated and arginine
vasopressin ADH is released to conserve fluid via the kidneys & cause the vasoconstriction of the
kidneys, gastrointestinal tract, and other organs to divert blood to the heart, lungs and brain. The
lack of blood to the renal system causes the characteristic low urine production.

Progressive: the compensatory mechanisms begin to fail. Decreased perfusion of the cells 
sodium ions build up within while potassium ions leak out. Anaerobic metabolism  the arteriolar
smooth muscle and precapillary sphincters relax such that blood remains in the capillaries 
increase hydrostatic pressure and, combined with histamine release  leakage of fluid and protein
into the surrounding tissues the blood concentration and viscosity increase, causing sludging of
the micro-circulation. Prolonged vasoconstriction  vital organs are compromised.

Refractory: vital organs fail and the shock can no longer be reversed. Brain damage and cell death
are occurring, and death will occur imminently.

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Collapse: is a sudden and often unannounced loss of postural tone (going weak), often but not
necessarily accompanied by loss of consciousness. Clinical signs are similar to shock but collapse is
first of all vasoconstrictive deficiency & is characterized by hypotonia. There are no stages. They
differ: Hemorrhagic, toxic, infectious, pancreatic, orthostatic collapse

Coma: a state of unconsciousness, lasting more than 6 hours in which a person cannot be
awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake
cycle and does not initiate voluntary actions. Coma may result from a variety of conditions,
including intoxication, metabolic abnormalities, central nervous system diseases, acute neurologic
injuries such as strokes or herniations, hypoxia, hypothermia, hypoglycemia or traumatic injuries
such as head trauma caused by falls or vehicle collisions. It may also be deliberately induced by
pharmaceutical agents in order to preserve higher brain functions following brain trauma, or to save
the patient from extreme pain during healing of injuries or diseases.

12. Damaging action of environmental factors on organism. Mechanical injuries

of the brain. Pathogenesis and clinical manifestations.

Damaging environmental factors can be:

1. Physical (e.g. mechanical, thermal, electrical and ray energy, acceleratory forces etc.)
2. Chemical (acids and basics etc)
3. Biological (viruses)
4. Psychogenic
There are some factors to which organism does not have compensating and adaptation reactions.
They are called EXTREME factors: Cosmic Factors (Overload), Ionizing radiation (exposure of an
atomic bomb) and etc.

Mechanical injury of cranium

1.concussion
2.contusion
3.compression

1. Cerebral concussion causes disorder of microcirculation only in brain but not in structure.
Permeability of micro vessels is increased. Plasma moves from micro vessels into tissues and
intracranial pressure is increased. (edema, inflammation, etc) As a result begins: headache, irritation
of nervus vagus, that causes dizziness, head ache, irritation of brain centers with following effects:
irritation of vagus nerve causes bradicardia and nausea, irritation of vomiting center causes –
vomiting, irritation of thermo regulation centre – fever, irritation of centers of optic nerve -
Involuntary eye movements – nystagmus.

2.Brain contusion. During brain contusion brain tissue is damaged. Clinical signs are depended on
damage location. Correspondingly to brain contused part functions, in head, body and limbs several
parts sensitivity disorder is marked, paralysis develops. Speech disorders, Inhibition of reflexes or
creation of pathologic reflexes may occur.

3.Brain Compression. Brain compression can be caused by fragments of broken skull bones or by
hematoma – trauma damage of blood vessels permeability. In this case, as well as during
contusion, brain regional parts injury can be revealed.

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13. Effects of acceleratory forces on the body. Pathogenesis & clinical
manifestations (Also see pages 26-29 Zukov)
Kinetosis – any disorder due to unaccustomed motion is complex of symptoms that develops during
influence of acceleration on organism or during flashing objects fast in front of eyes. Most common
types of kinetosis are: Sea sickness and Travel sickness.

In pathogenesis of kinetosis most important are:

1. Irritation of retina receptors because of flashing objects fast in front of eyes.
2.Irritation of vestibular nerve receptors during fast changes of body location in space - fast
movement, shaking, spin, fluctuation.
3. Irritation of receptors located in serous and mucous membranes of abdominal organs during
shaking, spin, fluctuation.
4. Irritation of proprioceptors, skin and visceral organs’ mechanoreceptors.

Symptom complex, characteristic to kinetosis is: dizziness, movement coordination disorder,

asymmetry of neck and back mussels (Related with irritation of retina and vestibular apparatus
receptors), nausea, vomiting, excessive sweating, bradicardia, and hypotension. All of these
symptoms are related with irritation of sensitive and motor centers of vagus nerve, as well as to
excitation of vestibular organs’ receptors and visceral organs interoceptors.

Influence of strong acceleration (during cosmic ship or aero plane flight) causes overload.

14. Effects of thermal agents on the body. Pathogenesis and clinical

manifestations. Hyperthermia, Heat stroke.
Normal range of body temp. 300C and 420C. Abnormaly high and low temperature produce
different patterns of tissue damage. High temperature causes local (burn) and general
(hyperthermia) changes.

Cutaneous Burns; Burns can be caused by heat, hot liquids, strong chemicals, electricity and
radiation. They are measured by the amount of body surface that has been burned, the burn
degree, and their depth or thickness. Burns are classified in stages as first, second, third or forth
degree, depending on how deeply the layers of skin (dermis and epidermis) are damaged. The size
of the area of the body affected by a burn plays a large part in determining whether it is classified as
a major or minor injury. Burn is characterized by different stages of local destructive and reactive
changes.

I stage: skin hyperemia. A burn that causes reddening of the skin but no blistering is a first-degree
burn. This type of burn is painful but does not leave a scar.
II stage: Acute exudative inflammation of skin and exudate containing blisters formation.
causes blisters, divided into superficial and deep second degree burns. A superficial second-
degree burn involves only the most superficial dermis. A deep second degree burn involves more
of the epidermis. It may present as blisters, or a wound with white or a deep red base.
III stage: Partial necrosis of skin and development of ulcers penetrates the entire thickness of
skin layers and permanently destroys tissues.
IV stage: Tissues are reduced to coal. injure and expose muscle, bone, and tendons, and may
require amputation of extremities.

The place where thermal agent action is occurred protein coagulation and cell necrosis are marked.
Inflammation reactions and tumor are revealed. Small area burn is followed by short-term reactions
such are: fever, head ache, leukocytosis. (also see question 17)

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Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs
when the body produces or absorbs more heat than it can dissipate. Our bodies, which create a
tremendous amount of internal heat, are normally cooled through sweating and radiating heat
through our skin. Under certain circumstances, such as unusually high temperatures, high humidity,
this natural cooling system may begin to fail. The result may be heat illness, or heatstroke.
Overheating can be occurred while increased heat production (during muscular work), when heat
radiation via skin is restricted (during high temperature) or during increased humidity in the
environment when perspiration and evaporation of sweat from the skin surface is failed.
During overheating temperature is raised, vessels are enlarged, skin is getting red as a result, heat
radiation from skin and perspiration are increased. Logically they are called as compensative
thermoregulation reactions. During excessive sweating a lot of amount of water is lost, blood
viscosity is raised, causes hypertension, microcirculation disorder is marked.

Heat stroke - rapid and strong overheating causes heat stroke, disease progresses with several
stages: muscular weakness, deep excitation of nervous system, hallucination, loss of consciousness.
Blood viscosity is significantly raised, heart is overloaded, bradicardia begins. Heart failure and
hypotonus of peripheral vessels cause hypotension. At the same time periodical, rare breathing is
marked. Patient may die because of paralysis of the respiratory center.

16. Difference between fever and hyperthermia. (Unit 8 Zukov)

18. Effects of low temperature on the body. Hypothermia, Pathogenesis and

clinical manifestations.
Hypothermia - Hypothermia is the opposite of hyperthermia. The signs and symptoms vary
depending on the degree of hypothermia and may be divided by the three stages of severity: mild,
moderate, severe.
Hypothermia usually occurs by low temperatures, and is frequently complicated by alcohol. Any
condition that decreases heat production, increases heat loss, or impairs thermoregulation causes
hypothermia.

Because of irritation of skin thermoreceptors during low temperature produced impulses affects
hypothalamus, from which efferent signals reach the organs and systems that take part in
thermoregulation. During compensation stage because of above mentioned efferent impulse
activity muscular tonus is raised, heat production is increased, tremor, tachycardia begins. Vessels
are narrowed, heat giving is decreased.
In case of prolonged or severe low temperature influence, thermoregulation mechanisms are
exhausted, lost heat is not compensated (decompensation), rare breathing begins, brain and later
under brain bark centers' functioning is inhibited. The cause of death is cessation of breathing.

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15. Fever – Definition, etiology, pathogenesis, pyrogens, stages of fever (Unit 8

Zukov)

17. Thermal injuries. Burn disease

When significant amount of body surface has been burned, long-term and severe reaction develops,
that is known as burn illness. In its duration following stages are differed: burn shock, burn
toxemia, burn infection and exitus.

In the mechanism of burn shock development major role plays pain and provoked pathologic
afferent impulsation to central nervous system. Deep excitation of neural centers of central nervous
system causes their function exhaustion: blood vessels tonuses, respiratory and heart functioning
changes. The last is facilitated by hyperkaliemia, developed because of Potassium ions transferring
from damaged cells to blood plasma.
During burn illness sharp hemodynamic changes are developed. Because of increased permeability
of blood vessels and inflammation hyperemia in injured area exudation (An exudate is any fluid
that filters from the circulatory system into areas of inflammation) develops. This reduces
circulated blood volume (Policytemic hypovolemia) and increases blood viscosity, this for another
part, causes microcirculation disorders even in undamaged tissues. In certain cases hemolysis is

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marked. Nevertheless because of decreased volume of plasma there is "surplus" amount of
erythrocytes, false or relative policytemia develops.
During tissues destruction in burn area toxic substrates are formed, as a result toxemia develops. In
this regard immensely important are denaturized proteins and products of their fermental
hydrolyzing.

19 Electrical injury. Pathogenesis and clinical manifestations.

Electric power damaging action
During action of electric power, injury severity is depended on features of electric power, tissues
resistance towards electric power, duration and direction of electricity pass in the organism,
individual reactivity.
Different tissues reveal different resistance towards electric power. E.G. Highly resistant are: bones,
skin, and low resistance have: blood, lymph. Skin resistance towards electric power sharply
decreases during illness and excessive sweating. Skin humidity severs the condition, because
resistance of humid skin is low.
Action of electric power on organism causes local and general reactions.
General Reactions are: Loss of consciousness, cessation of breathing , hypotension, heart
fibrillation and heart arrest. In general reactions mostly important is electric power action on
respiratory centre and heart.
Local effect of electric power is related with its electrochemical, thermal and mechanical action.

20. Effects of low partial pressure on the organism - Mountain disease.

Low atmospheric (hypobaric ) pressure injuring influence, “mountain sickness”
Altitude sickness—also known as acute mountain sickness (AMS), altitude illness,
hypobaropathy—is a pathological effect of high altitude on humans, caused by acute exposure to
low partial pressure of oxygen at high altitude. It commonly occurs above 2,400 meters (8,000 feet).
The changes that take place during disease are caused by direct action of hypobaric pressure and
decreased partial pressure of oxygen in the environment. Acute mountain sickness can progress to
high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE), which are
potentially fatal.
The fallen atmospheric pressure causes decompression syndrome. Extended air in hollow organs
(e.g. antrum of Highmore) causes suppression on hollow organs’ membranes, irritation of their
neural receptors and pain that can be followed by decrease of working ability or even by loss of
consciousness. Air is extended in intestines also, because of what meteorism is observed.
Following primary symptoms can be met:
1. Lack of appetite, nausea, or vomiting
2. Fatigue or weakness
3. Dizziness
4. Insomnia
5. Shortness of breath upon exertion
6. Nosebleed
7. Persistent rapid pulse
8. Peripheral edema (swelling of hands, feet, and face).
9. Diarrhea

Severe symptoms

Symptoms that may indicate life-threatening altitude sickness include:

1. Pulmonary edema (fluid in the lungs)
2. Symptoms similar to bronchitis
3. Persistent dry cough

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 4. Fever
5. Shortness of breath even when resting
6. Cerebral edema (swelling of the brain)
7. Headache that does not respond to analgesics
8. Gradual loss of consciousness
9. Increased nausea
Prevention

Ascending slowly is the best way to avoid altitude sickness. Avoiding strenuous activity such as
skiing, hiking, etc. in the first 24 hours at high altitude reduces the symptoms of AMS. As alcohol
tends to cause dehydration, which exacerbates AMS, avoiding alcohol consumption in the first 24-
hours at a higher altitude is optimal.

21. Effects of high partial pressure on the organism - Caisson disease.

Atmospheric (barometric) pressure injuring influence, caisson disease
High atmospheric pressure acts pathologically on the organism during working in the underwater
and in caissons (special underwater camera where high pressure is created in order to balance
atmospheric pressure acting on the caisson).

Symptoms revealed during caisson disease are related to high atmospheric pressure action,
impregnation of tissues with Nitrogen and excess of Oxygen, Hyperoxia. Signs:
 Earache - caused by myringe injury;
 Hyperemia of visceral organs because of vasoconstriction of peripheral vessels;
 Breathing is deepened and rare.
 Tissues are saturated with airs, immensely with nitrogen, which is saturated in tissues like
brain, bone marrow, five times more than in blood. Saturated Nitrogen in neural tissues
causes euphoria, hallucinations, movement incoordination.
During decompression from high pressure to low pressure desaturation (transfer of airs from
tissues) is occurred. During rapid desaturation nitrogen is not sufficiently eliminated from an
organism, comparatively big nitrogen vesicles are formed in blood that can cause life threatening
air embolism.
Cumulated nitrogen vesicles in tissues suppress neural terminals and cause myalgia, arthralgia,
itching, skin emphysema.
For prevention workers in caisson are given Helium –Oxygen mix, because helium is less saturated
in tissues. They also apply to partial decompression, in result desaturated nitrogen is eliminated
from organism without vesicle forming.

The only method to cure caisson disease is recompression in barocameras, when vessels are freed
from vesicles.
Hyperoxia also causes damaging action on organism during which vessels chemoreceptors are not
sufficiently irritated as response breathing is getting rare, heart work is decreased.
Severe hyperoxia has an effect similar to ionized radiation, characterized by initiation of free radical
oxidation processes.

22. Damaging effects of Ionizing radiation. Pathogenesis and clinical

manifestations
Ionized radiation damaging action
Human organisms are used to natural ionized radiation such as cosmic rays, earth’s crust rays. But
nowadays a lot of artificial sources of ionized radiation exist (atomic energy, x-rays, isotopes, etc).
To ionized radiation belong: £ -,β – and γ –rays, neutrons, x-rays, their damaging action stress is
depended on their ability of tissue transparency and on density of created ions during radiation
influence on tissues.

13
 Energy of ionized radiation is stronger than molecular junctions are, and the first effect of its action
is caused by disruption of molecular junctions in organism.
Among radiochemical transformations immensely important is water ionization. Because of this
effect free radicals are formed (H+; OH -, which react with tissue oxygen and form hydroperoxide
(HO2), peroxide (H2O2) and atomic oxygen (O-).

Ray Sickness
According to dosage of ionizing radiation, symptoms can vary from weak general reactions to acute
ray sickness.
1-10 Grey dosage x-rays can acute ray sickness typical - bone marrow form, rays primarily
damage bone marrow, disease has 4 stages. 1. First Reaction from radiation to 48 hours. 2. Latent
period 3.Manifestation 4. Recovery

Intestinal form (10-20 Grey)–massive interphasive death of intestine cells, dehydration, loss of
proteins and electrolytes. Mucous membrane is damaged and infections are easily caused. Microbes
and tissues toxins are absorbed; as a result shock may be occurred.
During radiation by highest death causing dosage – 20- 80 grey -toxemic form is developed. Severe
intoxication, Oliguria is marked. Patient dies on 4-7th day of illness.
More than 80 grey radiation causes cerebral form of disease, during which patient may die
immediately or few minutes or few hours after radiation.

23. Role of inheritance in pathology. 24. Immunopathology. Congenital

Etiology of inherited diseases. and acquired immuno-deficiencies.

14
25. Role of constitutional types in pathology. Reactivity of the organism

26. Hypoxia. Types and compensatory mechanisms at hypoxia

15
 27.Acid-base imbalance. Respiratory and metabolic acidosis and alkalosis

28. Types of blood vessels. Principles of hemocirculation (hemodynamics).

Hemodynamic laws.Blood circulation physiology /pathophisiology are divided into two main parts:
1. systemic (central) blood circulation and 2. Peripheral (local, regional) blood circulation
Different sections of blood circulatory system differ from each other with morpho-functional
specificities, functions, regarding which, blood vessels are divided to following groups:
1. Paddy (Compensating, buffer) blood vessels – Aorta (the largest artery, carries blood out
of the heart), big arteries (or arteries of elastic type). These types of arteries do not directly
take part in circulation regulation; they provide blood supply to different parts of organism.
Their important function is to transfer intermittent blood flow to continuous blood flow
(because about half of their structure is composed of elastic fibers).
2. Resistance vessels of the circulation - these are small arteries, arterioles and veins (muscle
type vessels) and are responsible for determining blood pressure and peripheral resistance of
the blood flow. Their particular significance is that they have very thick walls in relation to
their diameters. Furthermore, the main constituent in their walls is smooth muscle, and the
degree of contraction of this muscle regulates the diameter of the vessels and consequently
the amount of blood flowing through them, for adequate supply.
3. “Exchange vessels”, these are capillaries and initial parts of veins allowing passage of
nutrients and gases between blood and tissues. They consist of a single layer of endothelial
cells, with microscopic spaces between adjacent cells which allow the solutes of the blood,
including salts, glucose, and dissolved oxygen, to pass into the tissues, and products of
tissue metabolism, including carbon dioxide, to pass into the blood. Their overall resistance
to blood flow is low and blood passes through them slowly. Disturbance of the balance of

16
 the fluid exchange at capillaries can lead to oedema, which is swelling caused by excess
tissue fluid
4. “Volume vessels” – Veins. Blood returns from the tissues to the heart along veins. Larger
veins possess valves which ensure that blood travels in the correct direction and prevents the
development of undue back pressure. Veins have
another important role in addition. Approximately 70% of the entire blood volume is
contained within the veins, and these are very distensible. This capacity change determines
the amount of blood flow backward to heart. When filled, the elastic tissue in their walls is
readily distensible, although expansion is eventually limited by the relatively indistensible
fibrous tissue (collagen).
5. Arteriovenous anastomosis – bypasses communication between an artery and a veinlet by
collateral channels, they ensure blood flow directly from arteriole to veinlet by omitting
capillaries. They were first discovered and described by Georgian Physiologist –
Tarkhnishvili; their function is taking part in thermoregulation and microcirculation.

Some Principles of Hemodynamics:

Hemodynamics, meaning literally "blood movement" is the study of blood flow or the
circulation. Concretely it is the study of the relationship among pressure, viscous resistance to
flow, and the volume flow rate in the cardiovascular system.
For understanding hemodynamics we need to discuss Continuance Equation which is a
concrete case of Law of Eternity: V= q x v = const, were V is volumetrical blood flow speed, q
– vessel diameter area,v -laminar blood flow speed. Generally in the body, blood flow is
laminar. However, under conditions of high flow, particularly in the ascending aorta, laminar
flow can be disrupted and become turbulent.
In blood circulatory system volume velocity in Aorta and big cycle all capillaries is the same

Bernoulli equation Z+ (P/X) + (V2 /2g) + const. Z is blood location energy, P/X hydrodynamic
pressure - the pressure due to the motion of the fluid; (V2 /2g) – kinetic energy

29. Arterial hyperemia, definition, reasons, types and manifestations.

According to causes, we can differ physiologic and pathologic arterial hyperemia. They can be
converted between each other: e.g. physiological vasodilatation during heat influence can be
turned to pathologic condition – burn. Arterial hyperemia during vasodilatation is also called
active hyperemia, paralyses of vasoconstrictive nerves can cause Neuroparalitic arterial
hyperemia, excitation of vasodilatative nerves –Neurotonic hyperemia, thermal influence –
thermal hyperemia .

Reactive hyperemia is the transient increase in organ blood flow that occurs following a brief
period of ischemia. Following ischemia there will be a shortage of oxygen and a build-up of
metabolic waste
Local ischemia of tissue causes metabolic disorders, created substrates irritate neural receptors
and reflexive postishemic hyperemia develops. When vessels myocytes are damaged
myoparalytic hyperemia can be developed.

Because of vasodilatation during hyperemia, resistance towards blood flow is decreased and
blood volume velocity is increased. Vessel diameter area is also increased. From one look, it is
opposite to law of continuance, V = qv = const but we must remember, that it is normal
situations when volume velocity is constant and during hyperemia, volume velocity is abnormal
due to several causing reasons.
Types of Arterial hyperemia

17
Symptom Arterial Hyperemia Ischemia Venous Hyperemia

Vessel diameter area Increased Decreased Increased

(q)
Blood flow Increased Decreased Decreased
volumetrical velocity
(v)

Blood stream Increased Decreased Decreased

laminar flow (V)
Blood pressure Increased Decreased Increased

Color of Organ or Light red Pale Cyanosis

tissue

Temperature (on the Increased Decreased Decreased

surface of body)

Creation of tissue Increased Decreased Increased (Tumor)

fluids
Tissue Trophicity Increased Decreased Decreased

30. Venous hyperemia, definition, reasons, types and manifestation

Causes, mechanisms and results of venous hyperemia

From the causes of venous hyperemia we must mention local processes: the pressure on the
veins (Tumor, hypertrophied organ, etc), oppression of the lumen of veins from inside (clot of
blood, inflammation process). General cause of venous hyperemia is heart failure, when heart
can no longer pump enough blood in the parts of body far from heart, e.g. in lower limbs. Those
who have constitutionally cased veins weak elastic apparatus (weak tonus of vein walls or
incomplete development of muscle cells in walls of veins) are predisposed to obtain venous
hyperemia. In those people who are for long time in vertical position venous hyperemia can also
be occurred.
Characteristic Signs of venous hyperemia are:
1. Blood flow speed is decreased (because of appeared obstacles in the lumen)
2. As low blood flow speed resistance towards blood flow is dropped, blood pressure in
veins is increased
3. Because of increased pressure veins are dilated passively that is also called passive
hyperemia, the diameter of lumen is increased
4. In spite of increased lumen diameter, blood volume velocity is lowered, because of
dropped blood flow laminar speed.
5. Corresponding organs or tissues are bloodshed
6. The color of organ is cyanosis – red – bluish color, because venous blood under
epidermal cover is recognized as blue.
7. Organ or tissue temperature is decreased because of lowered blood volume velocity.

18
 8. Exudation is enforced correspondingly to risen hydrodynamic pressure and filtration,
because of which, In contrast with arterial hyperemia, swelling develops. In this
mechanism dilatation of capillary fenestrae and increased permeability also plays
important role. Because of transudate pressure on lymph vessels, lymph circulation
disorder is also occurred.
9. Trophicity of organs is lowered, because blood volume velocity is decreased.

Results caused by venous hyperemia can be:

2. Tissue Hypoxia - main reason causing function disorder, local changes in tissues such are
atrophy, dystrophy, and parenchyma degeneration and in it surplus connective tissue
development (Cirrhosis).
3. Induration – hardening of organ because of venous stagnation – (Liver, kidney, lungs),
especially dangerous when associated with lymphostasis.

Symptom Arterial Hyperemia Ischemia Venous Hyperemia

Vessel diameter area Increased Decreased Increased

(q)
Blood flow Increased Decreased Decreased
volumetrical velocity
(v)

Blood stream laminar Increased Decreased Decreased

flow (V)
Blood pressure Increased Decreased Increased

Color of Organ or Light red Pale Cyanosis

tissue

Temperature (on the Increased Decreased Decreased

surface of body)

Creation of tissue Increased Decreased Increased (Tumor)

fluids
Tissue Trophicity Increased Decreased Decreased

31. Ischemia – definition, reasons, types and manifestation

Ischemia
In medicine, ischemia (from Greek ischaimía; ischo- meaning restriction, haema blood) is a
restriction in blood supply, generally due to factors in the blood vessels, with resultant
damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia. It also means
local anemia in a given part of a body

Causes and Consequences of Ischemia

19
 Rather than hypoxia ischemia is an absolute or relative shortage of the blood supply to an
organ, i.e. a shortage of oxygen, glucose and etc. Ischemia results in tissue damage because
of a lack of oxygen and nutrients.
Ischemia can also be described as an inadequate flow of blood to a part of the body, caused
by constriction or blockage of the blood vessels supplying it
There are various types of ischemia. The mechanism of ischemia may differ based on the
organ involved, but generally the following forms of ischemia are known:
1. Compressive Ischemia - any pressure on the trophic artery (tumor, foreign body, etc.)
2. Obstructive Ischemia – Arteries can be plugged by thrombus or embolus in their lumen.
The lumen also can be suppressed because of inflammation changes in the vessels walls,
atherosclerosis, endarteritis and etc.
3. Neurotonic Ischemia is frequently reflexive and developed during pain, emotions,
mechanical irritation, coldness, and rarely may it be related to angiospasm- sudden
contraction of blood vessels.
We must mention that the severe pain is revealed in the ischemic organ.

32. Clinical manifestation of disorders of microhemocirculation

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 DISORDERS OF VASCULAR FLOW: EDEMA, CONGESTION, HEMORRHAGE,
THROMBOSIS, EMBOLISM.
survival of cells is dependent on the oxygen provided in a normal blood supply
 -disorders of blood supply and exchange of fluid cause some most commonly encountered
disorders in medicine: edema, congestion, hemorrhage, shock, and three interrelated conditions:
infarction, thrombosis, embolism.
 -thrombosis, embolism and infarction underlie the most important diseases and immediate causes
of death in industrialized countries: myocardial infarction, pulmonary embolism, brain strokes
33. Slag phenomenon, Stasis, and their pathogenesis

Stasis (medicine), a state in which the normal flow of a body liquid stops, for example the flow of
blood through vessels or of intestinal contents through the digestive tract

Stasis – is the last phase of vascular changes - Increased permeability of the vessels results in the
movement of plasma into the tissues, with resultant stasis due to the increase in the concentration of
the cells within blood - a condition characterized by enlarged vessels packed with cells.
Stasis allows leukocytes to marginate (move) along the endothelium. Normal flowing blood
prevents this, as the shearing force along the periphery of the vessels moves cells in the blood into
the middle of the vessel.

34. Thrombosis and Emboli – definition, pathogenesis, types and outcome

 THROMBOSIS
thrombosis= formation of clotted mass of blood, the clotted mass itself= thrombus
thrombus may flow downstream in blood vessel system= embolism
the process of clotting and embolism- closely related= thromboembolism
 pathogenesis of thrombosis =inappropriate activation of normal hemostasis
Normal hemostasis: three major contributing aspects of normal hemostasis- platelets, endothelial
cells and coagulation system

-1- intact endothelial cells serve to protect blood platelets and coagulation protein from highly
thrombogenic subendothelial substance (collagen)
- injury to endothelial cells represent a loss of anticoagulative mechanism
- endothelial injury- the most important influence in thrombogenesis in arteries
-thrombi appear often on ulcerated atherosclerotic plaques in arteries, at sites of
inflammatory or traumatic injury to arteries, in arteries whose walls have been infiltrated by cancer
-thrombi appear regularly in heart chambers adjacent to myocardial infarct due to hypoxic
injury to endocardium
-2- stasis and turbulence of blood - constitutes major thrombogenic influence in veins
-in normal blood flow- all blood cells are separated from the endothelial surface by a plasma
zone devoid of cells
- stasis and turbulance and decrease of rate of blood flow result in:
1.- erythrocytes and platelets come to contact with endothelial cells
2.- permits the formation of platelets aggregates and fibrin often in pockets of stasis
3.- prevents dilution of clotting factors in plasma
4.- decreases inflow of clotting factor inhibitors
5.- promotes endothelial cell hypoxia and injury
Stasis play dominant role in thrombosis in veins because of low speed of blood flow in veins
- origin of venous thrombi in sinuses behind venous valves in deep vein in low extremities
similar phenomenon- in auricular appendices of heart chambers - in atrial fibrillation
- stasis and turbulence contribute to thrombosis in arterial aneurysmal dilatations

21
 -3- hypercoaguability of the blood -is defined as alteration of the blood and the clotting
mechanism that predispose to thrombosis- is called thrombotic diathesis
rare- good example is inherited lack of natural anticoagulant antithrombin III- patients suffer of
recurrent thromboembolic attacks
thrombotic diathesis in several chronic diseases - such as
- nephrotic syndrome
- late pregnancy
- disseminated cancer
- use of intraoral contraceptives- increase in plasma level of prothrombin, fibrinogen and other
coagulative factors can be demonstrated
-trauma, surgery, burns
-cardiac failure
-advanced age, immobilization and reduced physical activity increase the risk of venous thrombosis

 MORHOLOGY OF THROMBI
-thrombi may develop in any part of cardiovascular system (heart, veins, arteries,
capillaries)
-arterial and cardiac thrombi: arise at sites of endothelial injury, atherosclerosis- often at
the site of branching of the artery- white or mixed thrombi- composed of fibrin white blood cells
and erythrocytes
-mural thrombus- thrombus attached to one wall of the artery- mural thrombi also develop
in abnormally dilated arteries-aneurysms
-occlusive thrombi - thrombus completely obstructs the lumen- in smaller arteries
most commonly affected arteries: coronary, cerebral, femoral, iliac, mesenteric, popliteal
-venous thrombi: also known as „phlebothrombosis„- mural or occlusive
-in slower-moving blood in veins- red coagulative or stasis thrombi -composed mostly of
fibrin and erythrocytes
most commonly affected veins: veins of lower extremity (deep calf, femoral, popliteal, iliac),
periprostatic plexus, portal vein etc
venous thrombi can be confused with postmortem clots at autopsy
postmortem clots- are not attached to the endothelial surface, are rubbery and gelatinous,
have smooth surface, do not contain platelets
in contrast, thrombi are more firm, almost always have point of attachment, on the section
show barely visible strands of fibrin
areas of attachment are characteristic for thrombi -frequently the attachment is most firm at point of
origin of thrombus
the tail of thrombus may not be attached- in arterial circulation-the tail builds up retrograde to
direction of blood flow, on the contrary in veins, the tail extends in the direction of the blood flow
the tail is only loosely attached in veins- its fragments readily creates emboli
-heart valvular thrombi : thrombi may be deposited on heart valves- only in special
circumstances- blood-borne infections may attack heart valves- endocardial damage- associated
with development of thrombus - in bacterial or infective endocariditis
less commonly- verrucous endocarditis-appear in patients with systemic lupus erytemathodes-
autoimmune complex disease affecting skin, kidney and other organs
nonbacterial or thrombotic endocarditis - in older patients with terminal cancers or severe
malnutrition-marasmus
= marantic endocarditis- hypercoagulative state + minor endocaridial injury are leading
pathogenetic aspects
 ORGANIZATION OF THROMBUS:
1.- thrombus may continue to grow into adjacent vessels
2.- thrombus may embolize
3.- thrombus may be removed by fibrinolytic activities

22
4.- it may undergo organization- when thrombus persists in situ for several days- it may be
organized= ingrowth of granulation tissue and mesenchymal cells into the fibrinous thrombus
-thrombus is populated with spindle mesenchymal cells and capillary channels are formed
within thrombus
-the surface of thrombus becomes covered by endothelial cells
capillary channels anastomose- recanalization = reestablishing the continuity of original vessel
 CLINICAL SIGNIFICANCE of thrombosis:
1. they cause obstruction of arteries and veins and may lead to infarction
2. they may provide the source of embolism
most important arterial thrombi- myocardial infarction (coronary artery involved) or cerebral
infarction (brain artery involved)
most venous thrombi are occlusive-the great preponderance in veins of lower extremity,
-superficial veins-varicosities, such thrombi may cause local edema and congestion and
pain, rarely give rise to emboli, local edema predispose to infection-varicous ulcers difficult to heal
-deep veins of the leg (popliteal, femoral, iliac)- the most important source of emboli, they
also may cause edema, pain, tenderness but approximately half of the patients with deep vein
thrombosis are asymptomatic
 high risk patients for arterial thrombosis:
-arterial thrombi are most likely to develop in patients with myocardial infarction, with
atherosclerosis of the aorta and large arteries with ulcers of atherosclerotic plaques, rheumatic heart
disease, arterial aneurysms
In myocardial infarction- alteration in heart contraction, endocardial damage, stasis of blood
indilated heart chambers most often in auricular parts (dilated atrium and atrial appendices)
-fragments of arterial thrombi may cause emboli to such sites as brain, spleen, kidney, the
legs, etc.
 EMBOLISM
Embolism refers to occlusion of some part of the cardiovascular system by the impaction of
embolus transported to the site of occlusion by the blood stream.
- most emboli represent parts of thrombi, thus the term thromboembolism,
-much less commonly-other material such as fat droplets, gas bubbles, atherosclerotic debris, tumor
fragments, etc

 TYPES OF EMBOLISM:
1. pulmonary embolism
2. systemic embolism
3. paradoxical embolism
PULMONARY EMBOLISM: most common example of embolism- thrombus originates in
venous system of legs, especially of deep leg veins, occasionally from right side of heart and
embolus or emboli are transported into right heart ventricle and to pulmonary arteries
pulmonary emboli may have various forms:
-multiple small emboli in peripheric branches of pulmonary artery
-large snake-like emboli
-saddle embolus-massive embolism in main pulmonary artery
morphologic and functional consequences of pulmonary embolism depend on the state of
pulmonary circulation and the size of affected artery :
-large emboli impact in main pulmonary arteries-death usually follows suddenly from
hypoxia or right ventricle heart failure (acute cor pulmonale) - no time to develop morphologic
changes in lung tissue
-smaller emboli impacted in medium-sized arteries-
- pulmonary hemorrhage if pulmonary circulation is normal, the vitality of lung tissue is
maintained, but alveolar spaces are usually filled with erythrocytes

23
 - hemorrhagic infarction if pulmonary circulation is compromised, such as in congestive
heart failure. Pulmonary infarction is sharply circumscribed necrosis of triangular shape with apex
pointing towards the hilus of the lung, pleural surface is covered with fibrinous exudate
 CLINICAL COURSE OF PULMONARY THROMBOEMBOLISM:
-many pulmonary emboli are clinically silent- small embolic mass is rapidly removed by
fibrinolysis, or larger one may be subject of healing = organization of emboli - result in postembolic
recanalization - healing
-recurrent multiple emboli= successive thromboembolism- may cause chronic hypertrophy
of right ventricule and right-sided heart failure- chronic cor pulmonale (pulmonary hypertension
and chronic right ventricle failure)
-embolic obstruction of middle-sized arteries- not infarction, but foci of hemorrhages-
hemoptysis and dyspnoe
-obstruction of small peripheral arteries- usually cause infarctions
-massive pulmonary embolism-acute heart failure-sudden death
 SYSTEMIC EMBOLISM - is a embolism to systemic arteries, most commonly affected organs
are - brain, kidney, spleen
Sources of emboli for systemic embolism:
- intracardiac mural thrombi ( in myocardial infarction)
-atherothrombotic fragments from the aorta and the large arteries
-thrombi from the heart valves
-left heart atrium - in atrial fibrillation
- thrombi from left ventricle aneurysms
 PARADOXICAL EMBOLISM - is embolization from systemic veins to systemic arteries most
common source- clots in deep leg veins
abnormal opening between right and left atrium (foramen ovale) combined with higher blood
pressure on right side than on left allows
most common target organs- arteries of the brain, kidney, spleen

 FAT EMBOLISM = is lodgment of fatty droplets and minute globules of fat in blood capillaries
fat embolism appears as a complication of bone fractures -fragments of fatty bone marrow, soft
tissue traumas and burns
-about 90% patients with severe skeletal injuries have fat embolism, but very few have
clinical course known as fat embolism syndrome -acute respiratory insufficiency, neurological
symptoms, anemia and thrombocytopenia - syndrome appears about 2 - 3 days after injury
-the fat embolism syndrome has mortality of about 10%
 AIR EMBOLISM ( including CAISSON DISEASE )
= is defined as entry of air bubbles into venous or arterial blood vessels
-in venous air embolism- small quantities are innoculous, but 100 ml and more may be fatal
-in arterial air embolism- even small quantity may be fatal, most commonly occurs as
complication of abortion, chest surgery
caisson disease is a distinctive form of gas embolism =decompression sickness
-may appear in deep sea divers who ascend rapidly to high altitudes
-the gases within pressurized air are dissolved in the blood, tissues and fat, if the diver then
ascends up rapidly to the surface- the dissolved oxygen, nitrogen and carbon dioxide come out of
solution in the form of small bubbles
-the most dangerous seems to be nitrogen, because of its low solubility- nitrogen persists as
gas bubbles
The formation of bubbles of nitrogen- mainly in the brain - it may induce focal brain necroses
the same process may affect other highly vascularized tissues and organs, such as heart and kidney,
skeletal muscles, etc.
in the lungs- sudden respiratory distress syndrom

24
TREATMENT: rapid placing of the affected person into the compression chamber- and slow
decompression
 AMNIOTIC FLUID EMBOLISM -is characterized by sudden onset, rapid dyspnea, cyanosis,
collapse and coma with convulsions
-occurs rarely, is totally unpredictable, may be fatal - is one of major causes of maternal death after
delivery
typical findings:
-in pulmonary arteries and capillaries- epithelial squames from fetal skin, lanugo hairs,
-fibrin thrombi indicative of DIC - in small vessels of uterus, lungs, kidney, thyroid,
myocardium
-the main cause of DIC syndrome is infusion of amniotic fluid into the blood, via cervical
uterine veins, from the uteroplacental site , etc
- vasoactive substances from the amniotic fluid are responsible for pulmonary vasocontriction and
thrombogenic substances from amniotic fluid cause intravascular coagulation leading to DIC
Thrombosis and Embolism
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood
through the circulatory system. When a blood vessel is injured, the body uses platelets
(thrombocytes) and fibrin to form a blood clot to prevent blood loss. Alternatively, even when a
blood vessel is not injured, blood clots may form in the body if the proper conditions are present. If
the clotting is too severe and the clot breaks free, the traveling clot is now known as an embolus.
Thromboembolism is the combination of thrombosis and its main complication is embolism.
The formation of thrombi is complicated process were blood vessel wall and blood formed
elements are involved.

According to composition of the clot the following types of thrombi are differed:
1. White thrombi or agglutination thrombi (composed mainly by thrombocytes, leukocytes and
plasma proteins)
2. Red or coagulation thrombi (composed mainly of fibrin fibrers and erythrocytes fixed in
them)
3. Mixed thrombi composed of white and red layers
Most important reason of thrombi creation is blood vessel wall injury resulting in laminar blood
speed change to turbulent flow in the intact vessel, this by itself causes accumulation of formed
elements of blood to the vessel which is the basis of thrombi formation.
In normal condition blood vessel wall and blood formed elements have the same charge, due to
which they are repulsed. At the place of damage this charge of wall is lost, formed elements are
gathered together. Damaged wall of vessel releases in the blood tissue thromboplastin It initiates
coagulation.
On another side, during vessel wall injury local fibrinolysis is suppressed, prostacyclin synthesis
from endotheliocytes is decreased (they have desegregation function). Based on this,
Thrombocytes aggregation is signed, that is main principle in thrombi formation.

Another important role plays coagulation system activation, concentration increase of procoagulants
(thrombin, thromboplastin), as well as anticoagulation system activation decline.

Thrombogenesis is especially high in the vessels were blood linear speed is law, therefore we meet
frequent cases of thrombosis in veins.

Formation of Arterial Thrombi

1. Endothelium injury
2. Local angiospasm
3. Thrombocytes adhesion on the vessel bare area

25
 4. Thrombocytes aggregation
5. Blood coagulation activation at the same time with fibro lyses decline

Exitus of Thrombosis
1. Thrombi aseptic(fermented) autolysis
2. Organization of thrombi – partial or full replacement by connective tissue
3. Chanel formation in the thrombi because of blood flow, - blood circulation is partially
recovered.
4. Extraction of thrombi from the vessel and emboli formation – it may be plugged in the minor
vessel and cause local disorder of blood circulation in the corresponding organ
5. Purulent(Chirkovani) lyses of thrombi during infection of thrombi, - minor parts of the thrombi
are extracted and bacterias are disseminated in the organs and tissues causing multiple
abscesses and septicopyemia.

Embolism

It is the transmission of foreign bodies by lymph or blood and ssuppretion of their lumen with
these bodies.
Embolism may be exogenic and endogenic. Exogenic embolism may be:
1. Gas Embolism – blood transfers gas vesicles (during caisson disease, mountain disease)
2. Septic embolism (with microbes)
3. Parasitic embolism – frequently in warm countries, - parasitic embolism of limbs lymph
vessels
4. Embolism with foreign bodies
Endogenic Embolism is frequently the result of
1. Thromboembolism – extraction of the thrombis from the vessels’ wall.
2. Tissues embolism - emboli is formed by any tissue of the blood
3. Fat Embolism – is frequently developed during fracture of the bones, traumatic injury of
different organs saturated with fat.

35. Disseminated intravascular coagulation - definition, reasons, pathogenesis and treatment

measures.

 DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

= is characterized by activation of coagulation sequence that leads to formation of multiple minute
fibrin thrombi in capillaries and small venules
-the thrombi are mostly composed of fibrin and aggregations of platelets
this leads to widespread thromboses with consumption of platelets and of coagulation factors and
with subsequent fibrinolysis (secondary effect)
-thromboses cause focal ischemia - multiple foci of necrosis (lungs, kidneys, brain, heart)
-increased bleeding tendency causes multiple hemorrhages
main clinical disorders associated with DIC:
DIC is not primary disease, it is a complication of several underlying diseases, such as
-amniotic fluid embolism
- EPH gestosis
- septic abortion
-retained dead fetus or abruption of placenta
-severe infections (gram-negative sepsis for example)
-neoplasms, such as carcinoma of pancreas, prostate, lungs
-massive tissue injury, burns
-extensive surgery, etc

26
  morphology of DIC:
-widespread occurrence of fibrin thrombi in capillaries of kidney, adrenal glands, brain, and
other organs
-ischemia and multiple microinfarcts- necrosis in adrenals may cause Waterhouse-
Fridrichsen syndrom
necrosis in brain- severe neurologic complications
DIC leads to hemorrhagic diathesis, because of consumption of clotting factors in
multiple microthrombi
increased bleeding tendency - multiple hemorrhages

36. Inflammation - definition, etiology, pathogenesis and outcome

Inflammation
Inflammation is the complex biological response to harmful stimuli (microbes, toxins, irritants and etc).
It is a compensative-adaptive reaction with structural and vascular changes and increased function of
connective tissue that is directed towards localization and removal of the injurious stimuli and towards the
initiation of the healing process.
Its goal is to save the organism from both – the initial cause of cell injury and its consequences.^
Though inflammation is of defensive character for the organism (mainly local inflammation); it may be
potentially harmful (Generalized infection – e.g. – sepsis, peritonitis etc.). An overactive inflammatory
response (hypersensitivity) can lead to severe life threatening conditions and can cause death.
Inflammation is most widely spread reaction to pathogenic action among typical pathologic processes. It
is typical because its principles are not related to injurious agent or to the process localization.
Inflammation can be classified as acute or chronic.
Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the vascular
reaction - increased movement of plasma and leukocytes (especially neutrofiles) from the blood into the
injured tissues. Acute form is relatively short –from few hours to few days. A cascade of biochemical
events propagates and matures the inflammatory response, involving the local vascular system, the
immune system, and various cells within the injured tissue. Prolonged inflammation, known as chronic
inflammation, leads to a progressive shift in the type of cells present at the site of inflammation –
infiltration with macrophages, lymphocytes and vascular and connective tissue proliferation.

Comparison between acute and chronic inflammation:

Acute Chronic
Persistent acute inflammation
due to non-degradable
Causative agent Pathogens, injured tissues pathogens, persistent foreign
bodies, or autoimmune
reactions
neutrophils (primarily), Mononuclear cells
eosinophils and basophils, (monocytes, macrophages,
Major cells involved
mononuclear cells lymphocytes, plasma cells),
(monocytes, macrophages) fibroblasts
Vasoactive amines, other cytokines, growth
Primary mediators
eicosanoids factors, reactive oxygen

27
 species, hydrolytic enzymes
Onset Immediate Delayed
Duration Few days Up to many months, or years
Resolution, abscess
Tissue destruction, fibrosis,
Outcomes formation, chronic
necrosis
inflammation

Classical signs of inflammation:

1. Redness (RUBOR)
2. Heat (CALOR)
3. Swelling (TUMOR)
4. Pain (DOLOR)
5. loss of function (FUNCTIO LAESA)
The first four (classical signs) were described by Celsus (I-st century BC), while loss of function was
added later by Galen in II-nd century. The descriptions are widely spread in Latin.
 Redness is due to increased blood flow to the inflamed site
 Heat is due to
a. increased blood flow to the inflamed site
b. increased metabolic processes at the inflamed site
c. Interleukin 1 (IL 1), Tumor necrosis factor (TNF ) and prostaglandins creation
 Swelling is caused by accumulation of fluid;
 Pain is due to release of chemicals that stimulate nerve endings;
 Loss of function (functio laesa) is probably the result of a neurological reflex in response to pain.
Among general clinical manifestations are the following clinical signs:
1. Fever
2. Neutrophilia
3. Decreased appetite
Inflammation Etiology
Inflammation is polietiological process. Causes of inflammation are exogenous and endogenous.
Exogenous factors:
1. Biological factors (Microbes and their toxins, parasites, viruses, insects)
2. Physical factors
a. Thermal injury (thermal burns)
b. Ionizing radiation, x- rays, ultraviolet rays of sunlight
c. Electrical injury
d. Mechanical trauma, foreign bodies
e. High and low temperature
3. Chemical factors: (acids, basics alcohol and other drug abuse, medicines and etc)
Endogenous factors:
1. Tissue destructive enzymes
2. Immune reactions due to hypersensitivity
3. Chemical - nitrogen substances (at uremia) can cause inflammation of the mucous layers of the
urinal tract
At inflammation we have active circulated cells
a. Neutrophiles
b. Eosinophiles
c. Basophiles
d. Lymphocytes
e. Monocytes
f. Thrombocytes
And we have fixed cells:
a. Mastocytes placed around the vessels (labrocytes)

28
 b. Fibroblasts of the connective tissue

Inflammation has three major components:

1. Alteration(Änderung) – tissue injury
2. Changes in microcirculation with emigration of leukocytes at inflammation area and Exudation
– (transition of blood components into the extracellular spaces)
3. Proliferation- multiplication of connective tissue elements
These processes are developed according to the sequence mentioned above, though some scientists
consider only vascular reaction to be the initiator of the process and not alteration.
1. Alteration
There is primary and secondary alteration. When phlogogen - injuring factor (Phlogosis – inflammation
in Greek) acts on the tissue, the first massive tissue destruction develops. Cell organelles progressively
degrade and there is a leakage of cellular enzymes. Consequences of these disorders increase metabolic
processes (“the fire of the metabolism”), focal hypoxia and its acidosis normal ph equals 7.34-7.36, under
acute inflammation -5.6 -6; under chronic inflammation – 6.0 -7.5).
Due to primary alteration there is primary damage of cell membrane, including lyzosomes. Their
membranes contain lyzosome enzymes – hydrolytic enzymes (approximately 30); they are able to destroy
practically all biological molecules within the tissues (proteins, nucleic acids, carbohydrates, lipids).
Liberation of these lyzosome enzymes together with acidosis induces lasting tissue damage (secondary
alteration). These enzymes destruct the connective tissue surrounding the micro vessels (pathogenesis of
inflammatory hyperemia). Then the next phase of inflammation develops.

2. a. Changes in Microcirculation (vascular changes) and b. Exudation

Acute inflammation is characterized by marked vascular changes, including vasodilatation, increased
permeability and the slowing of blood flow, which are induced by the actions of various inflammatory
mediators
The changes in microcirculation involve arterioles, precapillaries, capillaries, venules. It is a very
important phase because increased blood flow to the injured area and opening of capillary beds form
exudates and its stimuli to phagocytosis and repair. Changes in vascular flow and caliber begin very
soon after injury at varying rates depending on the severity of the injury. The changes occur in the
following order:
1. Vasoconstriction of arterioles lasting a few seconds (it may not always occur). The mechanism is
connected with binding of released epinephrine (norepinephrine) to receptors of sympathetic
nervous system.
2. Hyperemia (Dilation). It is the longest phase sustained not only by nervous but humoral
stimuli. Vessels dilation at inflammation is of diffusive, total manner. Firstly arterioles are
involved and than results in the opening of new microvascular beds in the area. All types of
capillaries are dilated: active (functioning), passive – (only plasma flows in them) as well as –
closed (nothing flows in them). Thus it turns out that increased blood flow is the cause of the first
clinical sign – redness (RUBOR) and second clinical sign - heat (CALOR). The latest is also
related with increased metabolism and Interleukin 1 (IL 1), Tumor necrosis factor (TNF ) and
prostaglandins creation. So far it is the most common mechanism of vascular leakage and is
elicited by histamine, bradikinin, H+ ions and all other chemical mediators.
Inflammatory hyperemia can be distinguished by other types of hyperemia with following
characteristics:
a. At inflammation primarily capillaries are dilated (together with narrow arterioles and venules).
Dilation of these capillaries is mainly primary, because their dilation is not as related to increased
blood flow as to local changes in them.
b. Dilation at inflammation is of diffusive manner. Both active (functioning), passive capillaries
(normally plasma flows only in them) and close capillaries are dilated.
c. The mechanism of increased capillary permeability is complicated process at inflammation. The
vessels’ walls do not contain constricting elements and changes in caliber are related to
surrounding connective tissue destruction due to inflammatory agent influence (lyzosomes’s
hydrolyzes destruct them). Inflammatory dilation of the capillaries is possible only when they are
29
 surrounded with elastic connective tissue. At inflammation connective tissue stretching is
increased and elasticity is decreased, that facilitates inflammatory hyperemia.
d. Another factor taking part in capillary dilation is hydrodynamic pressure increase. Capillary
caliber features are depended on in it existing blood pressure and on their wall resistance towards
blood flow. But as the resistance is decreased at inflammatory process capillary dilation may
occur even at normal blood pressure.
e. Axon reflex may contribute to hyperemia – At inflammation area axons are exited and transmit
the impulses towards arterioles and capillaries, blood pressure is increased and they dilate as there
is lower resistance from the vessels’ walls side.
f. Inflammation mediators play important role in inflammatory dilation.
A lot of inflammation mediators are created or liberated at inflammation, there are more than 20:
(histamine, serotonin, prostaglandins, kinins, leukotriens and etc.). They play main role in the
important events of inflammation: vascular hyperemia, increase of vascular permeability,
changes in blood micro rheological features.
3. Venous Hyperemia – venular dilation.
The sequence of microrheological changes at inflammation
1. Slowing of blood circulation
2. High hydrostatic pressure
3. Increased permeability by inflammation mediators
4. The outflow of protein rich fluid into extra vascular tissue (edema, local sign of swelling)
5. Increased viscosity of blood
6. Concentration of red cells in small vessels – blood flow laminar speed decrease causes
aggregation of erythrocytes, that on the other hand slows blood laminar speed (viscous circle)
7. Platelet adhesion as a result of endothelia cells detachment.
8. Thrombosis (dilated small vessels packed with red cells) - At inflammation Hageman factor
(factor XII) is activated, heparin is decreased, that causes increase of coagulation and
thrombi formation
9. Prestasis. Erythrocytes aggregates and thrombi partially or totally obstruct the lumen;
therefore slowing of the blood flow is deepened and is derived into prestasis and later in the
stasis.

37. Exudation, mechanisms of development and types of exudate

b. Exudation
The exudative component involves the movement of plasma fluid, containing important proteins such as
fibrin and immunoglobulins (antibodies), into inflamed tissue. This movement is achieved via the
chemically induced dilation and increased permeability of blood vessels, which results in loss of blood
plasma. The increased collection of fluid into the tissue causes it to swell (edema). (III rd clinical sign of
inflammation.
It is depended on 2 events: 1. Micro vessels; permeability increase and in them 2.blood
hydrodynamic pressure increase. Osmotic and colloid –osmotic pressure increase at inflammation
site plays an important role.
Main Types of exudates:
1. Serous exudate
2. Purulent exudate
3. Fibrin exudate
4. Catarrhal exudate
5. Hemorrhagic exudate
6. Mixed exudate

38. leukocytes emigration, phagocytosis at inflammation

Emigration of Leukocytes. Phagocytosis

30
The component involves leukocytes, which normally reside in blood and must move into the inflamed
tissue via extravasation to aid in inflammation. Some act as phagocytes, ingesting bacteria, viruses, and
cellular debris. Others release enzymatic granules which damage pathogenic invaders. Leukocytes also
release inflammatory mediators which develop and maintain the inflammatory response. Generally
speaking, acute inflammation is mediated by granulocytes, while chronic inflammation is mediated by
mononuclear cells such as monocytes and lymphocytes.
The sequence of events in the leukocyte journey consists in following:
1. Margination, rolling and adhesion
2. Emigration towards a chemotaxic stimulus
3. Phagocytosis and intracellular degradation
4. Leukocyte activation
Kinds of inflammation:
1. Serous inflammation
2. Fibrinous inflammation
3. Purulent inflammation

Repair - proliferation
After leukocyte emigration and phagocytosis repair begins – endothelial cells proliferate and form new
blood vessels (granulation tissue).
Outcomes of the inflammation depend on the nature and intensity of the injury, the site of the tissue
affected and to the ability of the organism to defense. Acute inflammation has generally 4 outcomes:
1. Complete resolution – neutralization and removal of the chemical mediators
2. Scarring and fibrosis – happens when inflammation occurs in the tissues that don’t regenerate
3. Abscess formation- setting of certain bacterial or fungal infections
4. Progression to chronic course

39. Inflammatory mediators.

Produced
Name Description
by
A vasoactive protein which is able to induce vasodilation,
Kinin
Bradykinin increase vascular permeability, cause smooth muscle
system
contraction, and induce pain.
Complemen Stimulates histamine release by mast cells, thereby producing
C5a
t system vasodilation.
Factor XII
A protein which circulates inactively, until activated by collagen
(Hageman Liver
and platelets.
Factor)
A complex of the complement proteins C5b, C6, C7, C8, and
Membrane multiple units of C9. The combination and activation of this
Complemen
attack range of complement proteins forms the membrane attack
t system
complex complex, which is able to insert into bacterial cell walls and
causes cell lysis with ensuing death.
Fibrinolysis Able to break down fibrin clots, cleave complement protein C3,
Plasmin
system and activate Factor XII.
Coagulation Cleaves the soluble plasma protein fibrinogen to produce
Thrombin
system insoluble fibrin, which aggregates to form a blood clot.

31
40. Allergy - definition, classification, etiology and pathogenesis of hypersensitivity reactions.
Immune system disorders, ALERGY

The immune system consists of central parts:

 Bone marrow
 the thymus

And peripheral parts:

 the spleen,
 lymphatic nodes,
 tonsils,
 lymphatic tissue of digestive system and etc.

 Immune system also has movable lymphocytes transported through blood and lymph and
provides antigenous homeostasis in the organism.
 The aim of the immune system is to fix and destruct infectious and non- infectious
antigens by humoral and cellular responses.
 This ability is performed by two kinds of immunocytes - T (thymus dependable) and B
– lymphocytes
 T lymphocytes attack the antigens directly and accomplish the cellular immune reaction
 Under the antigen influence B lymphocytes turn into the plasmatic cells and produce
immunoglobulins responsible for humoral responses

Immune Responses

Thymus non - dependent Thymus dependent

I I
Ag Ag
I I
B lymphpcyte receptor Macrophage
I I
Plasmic cells Presentation of Ag
I I
Ig M T-helper
I
B- lymphocyte
I
Plasmic cells
I
Ig E, Ig G 32
Allergy is a changed reaction of the organism to the antigens and non –antigens.
It is a complex of disorders that is presented in the organism by humoral and cellular immunological
reactions.
Some hemi antigens – Haptens may also cause allergy. After entering the organism they interact with
human proteins and gain antigenic features (some chemicals, perfume and etc.)
Cold, burn and radiation are not allergens their self but may induce the changes in cell and tissue proteins
that are derived lately into autoallergens.

Allergy as well as inflammation is a response against exo- and endogenous factors. Though in contrast
with inflammation it is not of defensive manner, it is harmful for the organism; - it can lead to
inflammation, bronchial spasm, shock and etc.

According to ADO classification antigens are divided

Allergen
s

Exogenous Endogenou
s

Bacteria, viruses, dust, pollens, vegetable, food, Autoallergens, acquired

drugs

Autoallegens

Natural (CNS myelin, glomerular basement membrane, lens, thyroid gland)

33
 Acquired

Cold Burn Radiation

Cold, burn and radiation may cause the changes in cell and tissue proteins that are derived lately into
autoallergens.
Some hemi antigens – Haptens may also cause allergy. After entering the organism they interact with
human proteins and gain antigenic features (some chemicals, perfume and etc.)

Allergens may hit the organism through:

 lungs - inhalation (pollens, dust, bacteria, viruses)
 gastrointestinal tract -ingestion (food, medicine drugs)
 skin and mucosal membranes (chemical compounds: detergents, perfume and etc)
 infection
 injection

The severity of TH2 responses to allergens depends on the route of entry, dose, and chronicity of
antigen exposure; the absence of inflammation and innate immunity at the time of allergen
recognition.

Pathogenesis of Allergy
There are three stages of allergic reaction
1. The immunological stage. The antigen enters the organism, antibodies are forming, and
organism’s sensitivity is increased - Sensibiling. If the antigen enters second time in the organism
the allergic reaction develops.
2. The pathochemical stage – It a stage of the forming and activation of biologically active
substances
3. The pathophysiological stage (clinical manifestations)The pathophysiological stage is
accompanied by numerous clinical manifestations as cutaneus swelling (skin allergy), nasal and
conjunctival discharge(allergic rhinitis and conjunctivitis), high fever, bronchial asthma, food allergy

41-50
41. Type I hypersensitivity: Type I hypersensitivity (or immediate hypersensitivity) is an allergic reaction provoked by reexposure to a
specific type of antigen referred to as an allergen.
In type 1 hypersensitivity, an antigen is presented to CD4+ Th2 cells specific to the antigen that stimulate B-cell production of IgE antibodies
also specific to the antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1
hypersensitivity the antibody is IgE instead of IgA, IgG, orIgM. During sensitisation, the IgE antibodies bind to Fcε receptors on the surface of

34
tissue mast cells and blood basophils. Mast cells and basophils coated by IgE antibodies are "sensitised." Later exposure to the same allergen
cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such
as histamine, leukotriene(LTC4 and LTD4), and prostaglandin that act on the surrounding tissues. The principal effects of these products
are vasodilation andsmooth-muscle contraction.
Type 1 hypersensitivity can be further classified into an immediate and late-phase reaction. The immediate hypersensitivity reaction occurs minutes after
exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the
release of cytokines.
Mechanisms of immunologically mediated diseases:
Type: Immediate type 1 hypersensitivity
Clinical types: anaphylaxis, allergies, bronchial asthma (atopic forms)
Immune mechanisms: production if IgE antibody immediate release of vasoactive amines and other mediators from mast cells; recruitment of
inflammatory cells (late phase reaction)
Pathologic disorders: vascular dilation, edema, smooth muscle contraction, mucus production, inflammation

42. type II hypersensitivity: In type II hypersensitivity (or cytotoxic hypersensitivity)[1] the antibodies produced by the immune
response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the
patient's cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are
recognized by macrophagesor dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are
produced against the foreign antigen.
An example of type II hypersensitivity is the reaction to penicillin wherein the drug can bind to red blood cells, causing them to be recognized as different; B
IgG and IgM antibodies bind to these antigens to form complexes that activate
cell proliferation will take place and antibodies to the drug are produced.
the classical pathway of complement activation to eliminate cells presenting foreign antigens (which are usually, but not in this case,
pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The
reaction takes hours to a day.
Another example of type II hypersensitivity reaction is Goodpasture's syndrome where the basement membrane(containing collagen type IV) in the lung and
[2]
kidney is attacked by our own antibodies.
Another form of type II hypersensitivity is calledantibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the
foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer cells (NK) and macrophages
(recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.
Mechanisms of immunologically mediated diseases:
Type: Immediate type 2 hypersensitivity
Clinical types: autoimmune hemolytic anemia; goodpasture syndrome
Immune mechanisms: production of IgG, IgM binds to antigen on target cell or tissue phagocytosis or lysis of target cell by activated complement or
Fc receptors; recruitment of leukocytes
Pathologic disorders: phagocytosis and lysis of cells; inflammation; in some diseases functional derangements without cell or tissue injury
43. Type III hypersensitivity: Type III hypersensitivity occurs when antigen-antibody complexes that are not adequately
cleared by innate immune cells accumulate, giving rise to an inflammatory response and attraction of leukocytes.
Type III hypersensitivity occurs when there is an excess of antigen, leading to small immune complexes being formed that do not
fix complement and are not cleared from the circulation. It is characterized by solvent antigens that are not bound to cell surfaces (which is the case
in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form. Large complexes can be cleared
bymacrophages but macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into
small blood vessels, joints, andglomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like
blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as
being highly pathogenic.
Such depositions in tissues often induce an inflammatory response,and can cause damage wherever they precipitate. The cause of damage is as a result of the
action of cleaved complement anaphylotoxins C3a and C5a, which, respectively, mediate the induction of granule release from mast cells (from
which histamine can cause urticaria), and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action, leading to tissue
damage through frustrated phagocytosis by PMNs and macrophages). The reaction can take hours, days, or even weeks to develop, depending on
whether or not there is immunlogic memory of the precipitating antigen.
Disease Target antigen Main effects

 Nephritis
Systemic lupus erythematosus Nuclear antigens  Skin lesions
 Arthritis

Post-streptococcal glomerulonephritis Streptococcal cell wall antigens  Nephritis

Polyarteritis nodosa Hepatitis B virus surface antigen  Systemic vasculitis

Reactive arthritis Several bacterial antigens  Acute arthritis

 Arthritis
Serum sickness Various  Vasculitis
 Nephritis
Arthus reaction Various  Cutaneous vasculitis

35
 Farmer's Lung Inhaled antigens (often mould or hay dust)  Alveolar inflammation

Henoch–Schönlein purpura Unknown, likely respiratory pathogen

 Purpura
 Glomerulonephritis
Mechanisms of immunologically mediated diseases:
Type: Immediate type 3 hypersensitivity
Clinical types: systemic lupus erythematosus; different form of glomerulonephritis; serum sickness; Arthus reaction
Immune mechanisms: deposition of antigen-antibody complexes complement activation recruitment of leukocytes by complement products and Fc
receptors release of enzymes and other toxic molecules
Pathologic disorders: inflammation necrotizing vasculitis (fibrinoid necrosis)
44. Type 4 hypersensitivity: Type 4 hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three
days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response. CD4+ helper T cells recognize
antigen in a complex with Class 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that
secrete IL-12, which stimulates the proliferation of further CD4+ T h1 cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the
release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages
produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.
Examples
Disease Target antigen Effects

Pancreatic beta cell proteins

Diabetes mellitus  Insulitis
(possibly insulin, Glutamate
type 1  Beta cell destruction
decarboxylase)
Oligodendrocyte proteins  Demyelinating disease
 Perivascular inflammation
Multiple sclerosis (myelin basic
 Paralysis
protein, proteolipid protein)  Ocular lesions

Rheumatoid Antigen in synovial membrane  Chronic arthritis

 Destruction of articular cartilage and bone, a Type III
arthritis (possibly type II collagen) hypersensitivity (Antibodies made against IgG)

Some peripheral  Neuritis

Schwann cell antigen
neuropathies  Paralysis

 Hypothyroidism
Hashimoto's
Thyroglobulin antigen  Hard goiter
Thyroiditis
 Follicular thymitis

Crohn's disease Unknown  Chronic inflammation of ileum and colon

Allergic contact Environmental chemicals, e.g.poison

 Dermatitis with usually short-lived itching
dermatitis ivy, nickel
Mantoux test* Tuberculin  Skin induration indicates TB exposure
(diagnostic)
Mechanisms of immunologically mediated diseases:
Type: Immediate type 4 hypersensitivity
Clinical types: contact dermatitis multiple sclerosis; type 1 diabetes; transplant rejection; tuberculosis
Immune mechanisms: activated T lymphocytes 1)release of cytokines and macrophage activation 2)T-cell mediated cytotoxicity
Pathologic disorders: perivascular cellular infiltrates, edema, cell destruction, granuloma formation
45. NOT found any information about hyperbiotic processes
46.cancer growth: known medically as a malignant neoplasm, is a broad group of diseases involving unregulated cell growth. In
cancer, cells divide and grow uncontrollably, forming malignant tumors, and invading nearby parts of the body. The cancer may also spread to more
distant parts of the body through the lymphatic system or bloodstream. Not all tumors are cancerous; benign tumors do not invade
neighboring tissues and do not spread throughout the body. There are over 200 different known cancers that affect humans.
etiology: The factors causing tumor are called carcinogenic. there are chemical, physical and biological carcinogenic substances are related to exogenous
carcinogens
Chem ical agent s like caffein, polycyclic hydr ocarbons, heavy metallic ions etc. ar e also car cinogenic. Hor mones like testosterone
and estr ogens ar e known to cause pr ostate and br east cancer r espectively. Chewing of beetles is known to cause mouth cancer .
Cigar ette and cigar tobacco smoking cause s lip, mouth and lung cancer s due to presence of a car cinogenic agent, benzpyrene an d N-
nitroso-dimethylene. An ani mal pr otein-r ich diet is known to cause cancer of lar ge intestine. Dye wor ker s have a high r ate of
bladder cancer.
P hysical agent s like X-r ays, gamma -r ays and par ticulate r adiations fr om r adioactive sub stances ar e known to r upture DNA str ands
and induce mutations to cause cancer s e.g., excessive expo sur e to sunlight ma y stimulate the development of skin cancer in far mer s.
E vidence for the carcinogenic effect of X -rays is docume nted that the incidence of leukemia is about ten times in r adiologists than

36
 in other physicians. J apanese people exposed to r adiations r eleased fr om Wor ld War II nuclear explosions shoved five time s the
incidence of leukemia than the rest of the population.
4. Biological agent s. Cer vix cancer is caused by vir use s. Tumo ur causing vir use s e.g. Epstein-Barr vir us, Her pes si mplex type -2
vir us etc. ar e called oncovir uses.

pathogenesis:
3 stages: transformation, promotion and progression
Transformation: is characterized by the ability to transfer healthy cells into cells with endless growth. such ability can be the result of mutation or genome
changes as a consequence of disregulatory processes. If in cell a gene appears, which depressed the initiator of cell divisio n, can destroy or damage the
mechanism of this gene switching on or off, which leads to uncontrolled growth
Promotion: is the second stage in the mechanism of carcinogenesis. the transformed cell may remain in the tissue in inactive form for long time. addition
influence of cocarcinogenesis factor stimulates cell reproduction and formation of tumor node
Progression: is realized as stable qualitative changes of tumor properties towards malignization. these changes arise under the influence of several factors:
1. not one but several cells become involved into primary carcinogenic that promotes formation of law sublines of cells in the growing tumor. A constant
selection of the most viable cells goes on in the growing tumor under the influence of the changing conditions of its growth ( nutriation, blood suppay, and
innervations)
2. change of genotype and phenotype of the cells resulting in progression may be connected with continuation of the effect of carcinogenic factors on the
genome of tumor cells
3. acquisition of new properties by tumor cells, which is connected with superinfection by tumor and non tumor viruses.

benign and malignant tumors:

A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissue or metastasize. These characteristics are
required for a tumor to be defined as cancerous and therefore benign tumors are non-cancerous. Also, benign tumors generally have a
slowergrowth rate than malignant tumors and the tumor cells are usually moredifferentiated (cells have normal features).[1][2][3] Benign
tumors are typically surrounded by an outer surface (fibrous sheath of connective tissue) or remain with the epithelium.[4] Common examples
of benign tumors include moles (nevi) and uterine fibroids (leiomyomas).

Malignant Tumors
The nomenclature of malignant tumors essentially follows that of benign tumors, with certain additions
and exceptions.
Malignant neoplasms arising in mesenchymal tissue or its derivatives are called sarcomas.
 A cancer of fibrous tissue origin is a fibrosarcoma, and
 a malignant neoplasm composed of chondrocytes is a chondrosarcoma.
 Sarcomas are designated by their histogenesis (i.e., the cell type of which they are composed).
 Malignant neoplasms of epithelial cell origin are called carcinomas.. Carcinomas that grow in a
glandular pattern are called adenocarcinomas.
 Sometimes the tumor shows little or no differentiation and must be called poorly differentiated
or undifferentiated carcinoma.
Nomenclature of
benign and
malignant tumors
Benign Malignant
Composed of One Parenchymal Cell Type
Connective tissue and derivatives Fibroma Fibrosarcoma
Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and related tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Certain features of tumor may indicate innocence, and others may indicate malignancy. There are four
fundamental features by which benign and malignant tumors can be distinguished. These are:
1. differentiation and anaplasia,
2. rate of growth,
37
 3. local invasion,
4. And metastasis.

Comparative characteristic of tumors

KIND BENIGN MALIGNANT

Growth rate Slow Rapid
Mitosis Few Many
Nucleus Chromatin Normal Increased
Differentiation Good Poor
Local Growth Expansive Invasive
Encapsulation Present Absent
Vessel Invasion None Frequent
Metastasis None Frequent
Effect of Host Often insignificant Significant cachexia, death

Metastasis
The term metastasis connotes the development of secondary implants (metastases) discontinuous with the
primary tumor, in remote tissues.
 The properties of invasiveness and, even more so, metastasis identify a neoplasm as malignant
than any of the other attributes of a tumor.
 Not all cancers have equivalent ability to metastasize, however.
Approximately 30% of newly diagnosed patients with solid tumors present with clinically evident
metastases. An additional 20% have occult (hidden) metastases at the time of diagnosis.
In general, the more anaplastic and the larger the primary neoplasm, the more likely is metastatic spread;
however, exceptions may be found. Extremely small cancers have been known to metastasize, and,
conversely, some large and ominous-looking lesions may not spread.
 Malignant neoplasms disseminate by one of three pathways:
 (1) seeding within body cavities,
 (2) lymphatic spread, or
 (3) hematogenous spread.
Spread by seeding occurs when neoplasms invade a natural body cavity.
Lymphatic spread is more typical of carcinomas, whereas hematogenous spread is favored by sarcomas.
There are numerous interconnections, however, between the lymphatic and vascular systems, and so all
forms of cancer may disseminate through either or both systems. The pattern of lymph node involvement
depends principally on the site of the primary neoplasm and the natural pathways of lymphatic drainage
of the site.
 Lung carcinomas arising in the respiratory passages metastasize first to the regional bronchial
lymph nodes, then to the tracheobronchial and hilar nodes.
 Carcinoma of the breast usually arises in the upper outer quadrant and first spreads to the axillary
nodes.
It should be noted that although enlargement of nodes near a primary neoplasm should arouse strong
suspicions of metastatic spread, it does not always imply cancerous involvement. The necrotic products of
the neoplasm and tumor antigens often evoke reactive changes in the nodes, such as enlargement and
hyperplasia of the follicles (lymphadenitis) and proliferation of macrophages in the subcapsular sinuses
(sinus histiocytosis).
Hematogenous spread is the most feared consequence of a cancer. It is the favored pathway for
sarcomas, but carcinomas use it as well. As might be expected, arteries are penetrated less readily than are
veins. With venous invasion, the blood-borne cells follow the venous flow draining the site of the
neoplasm, with tumor cells often stopping in the first capillary bed they encounter. Since all portal area
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drainage flows to the liver, and all caval blood flows to the lungs, the liver and lungs are the most
frequently involved secondary sites in hematogenous dissemination.

47. Exponential Growth Model

One model that has been used to describe tumor growth is the exponential growth model1.

Equation 1

The exponential does not describe the growth rate in vivo which slows are the tumor size increases.
Gompertz Model
Another model use to describe tumor dynamics is a Gompertz curve or Gompertz function. It is a type of mathematical model for a time
series, where growth is slowest at the end of a time period1.

Equation 2

where N∞ is the plateau cell number which is reached at large values of r and the parameter b is related to the initial tumor growth rate.
Models for Tumor Growth
Exponential Growth Law
All tumors follow a standard growth pattern, growing fastest in the beginning and eventually reaching a maximum size. There
are some weaknesses in the exponential growth model as it fails to model this behavior in vivo.
Gompertz Law
The Gompertz Model, while it does model the behavior as a tumor increases in size, it is not an empirical model. The model
has too many variables to consider, such as types of cancers as well as environmental conditions. These may even vary
considerably for patients with the same types of cancers 1.
Universal Law
The Universal Law model proposed by West, adequately describes the growth rates of organisms by taking energy
considerations into account. This model was tested against empirical data 5. As powerful as West’s model for growth is, it only
applies to organisms growing in unrestricted dietary conditions. Thus only fully replenished tumors will follow this universal
growth curve. Differences in growth rates and saturation sizes of up to a factor of 500 were found in tumor spheroids cultured
in media with different oxygen levels and glucose concentrations6. Thus deviations from West’s Law depend on particular
environmental conditions.
As a tumor reaches a certain size or volume, metastatic dissemination will occur 7. As the rate of cell growth is dependent on its
development phase, this may serve as a possible explanation why recurrent cancers grow at much slower rates than the primary
tumors2. In this case, the residual clonogenic cells of the primary tumor generate cells from an older development phase and
thus multiply at a slower rate.
In general, the West model for ontogenetic growth of living organisms applies to the case of solid malignant tumors. The
results fit a variety of in vitro and in vivo data5.

48) Metabolism Disorders - is the process your body uses to get or make energy from the food you eat. Food is made up of
proteins, carbohydrates, and fats. Chemicals in your digestive system break the food parts down into sugars and acids, your
body's fuel. Your body can use this fuel right away, or it can store the energy in your body tissues, such as your liver, muscles,
and body fat.
A metabolic disorder occurs when abnormal chemical reactions in your body disrupt this process. When this happens, you
might have too much of some substances or too little of other ones that you need to stay healthy.
Starvation is a severe deficiency in caloric energy, nutrient, and vitamin intake. It is the most extreme form of malnutrition. In
humans, prolonged starvation can cause permanent organ damage and eventually, death.

49) Water-electrolyte imbalance

Electrolytes play a vital role in maintaining homeostasis within the body. They help to regulate myocardial and neurological
function, fluid balance, oxygen delivery, acid-base balance and much more. Electrolyte imbalances can develop by the
following mechanisms: excessive ingestion; diminished elimination of an electrolyte; diminished ingestion or excessive
elimination of an electrolyte.
The most common cause of electrolyte disturbances is renal failure.
Electrolytes are important because they are what cells (especially nerve, heart, muscle) use to maintain voltages across their
cell membranes and to carry electrical impulses (nerve impulses, muscle contractions) across themselves and to other cells.

Edema is the medical term for buildup of excess fluids in the body’s tissues. This occurs when the body fails to excrete excess
fluid through kidneys or skin.

*Generalized Edema
Generalized edema is a condition when you notice swelling, puffiness, and water retention in various body parts, including
your abdomen, arms, legs, face, and feet.

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Skin Edema
Skin edema mainly occurs in the tissues and cells of the skin. It is usually harmless, but it can be very painful. In this type of
edema, some parts of your skin may seem tight, puffy, and have fluid retention.
Peripheral Edema
Peripheral edema mainly occurs in the legs, feet, and ankles. This is the most common type of edema and it causes swelling in
the lower extremities.
Corneal Edema
When there is water retention in the cornea, it causes corneal swelling, which is an eye problem known as corneal edema.
Cerebral Edema
In cerebral edema, fluids accumulate in the intracellular and extracellular spaces of the brain. It can be caused by metabolic
abnormalities due to an underlying disease or as a response to oxygen deprivation at high altitudes.
Pulmonary Edema
Pulmonary edema is the accumulation of fluids in the lungs due to the blockage of the pulmonary veins. As blood pressure
rises in the blood vessels of the lungs, fluids rush in to fill the lungs.
Myxedema
Myxedema is a rare form of edema. It occurs when the connective tissues are filled with water-loving carbohydrate-like
compounds such as hyaluronan. These compounds attract water into the tissue matrix, and swell up quickly.
Lymphedema
Lymphedema is caused by the failure of the lymphatic system to remove fluids from the interstitial spaces.

50 ) Disorders of hydrocarbon metabolism

Abnormalities of glucose, insulin, and lipoprotein metabolism are common in patients with hypertension. This constellation of
risk factors may be recognized at a young ages and is, at least in part, inheritable. Insulin resistance and compensatory
hyperinsulinemia may be primary events, and enhanced sympathetic activity and diminished adrenal medullary activity could
be important links between the defect in insulin action and the development of hypertension and the associated metabolic
abnormalities. But not all hypertensive patients have insulin resistance. It is possible that insulin resistance, and compensatory
hyperinsulinemia have major roles in the regulation of blood pressure in susceptible subjects predisposed to hypertension by
hereditary or environmental factors. Considerable evidence, both in experimental animal models and in humans, points to
hypertension as being of critical importance in the pathogenesis of severe diabetic heart disease. In diabetic hypertensive
cardiomyopathy, coronary artery disease as well as structural and functional abnormalities are more pronounced than would be
expected from either process alone. The hypertension increases the risk of diabetic nephropathy in non-insulin-dependent
diabetic patients. Microalbuminuria is a powerful predictor of mortality in these patients. It seems that angiotensin-converting-
inhibitors have efficacy in postponing nephropathy in hypertensive non-insulin-dependent diabetic patients. In patients with
hypertension and diabetes, additional clinical trials are required to identify the interventions that will most effectively reduce
not only overall risk but also improve cardiovascular disease prognosis.
Diabetes mellitus - a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not
produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the
classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger).
There are three main types of diabetes mellitus (DM).
 Type 1 DM results from the body's failure to produce insulin, and currently requires the person to inject insulin or
wear an insulin pump. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or
"juvenile diabetes".
 Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes
combined with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes
mellitus (NIDDM) or "adult-onset diabetes".
 The third main form, gestational diabetes, occurs when pregnant women without a previous diagnosis of diabetes
develop a high blood glucose level. It may precede development of type 2 DM.

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