MODULE 1 GENERAL PATHOLOGY

CM 2(3)

FEVER

PATHOPHYSIOLOGY OF TISSUE GROWTH.

EXPERIMENTAL STUDY OF  NEOPLASIA.

The temperature within the deep tissues of the body (core temperature) is normally maintained within a range of 36.0°C to 37.0°C. Within this range, there are individual differences and variations; internal core temperatures reach their highest point in late afternoon and evening and their lowest point in the early morning hours. Virtually all biochemical processes in the body are affected by changes in temperature. Metabolic processes speed up or slow down, depending on whether body temperature is rising or falling.

One of the most important examples of homeostasis is the regulation of body temperature. Not all animals can do this. Animals that maintain a fairly constant body temperature are called homeotherms, while those that have a variable body temperature are called poikilotherms. The homeotherms maintain their body temperatures at around 37°C, so are sometimes called warm-blooded animals, but in fact poikilothermic animals can also have very warm blood during the day by basking in the sun.

Human organs and the organs of warm-blooded animals also can be divided into two groups:

а) organs with permanent and high temperature;

b) organs with changeable and more lower temperature.

So, our organism consists of two parts: warm-blooded and cold-blooded. To the first part one belong the inner organs. The highest temperature has a liver. Then blood comes in aorta, after that the organs of pectoral and abdominal cavity, brain and spinal cord. These organs and tissues aresituated in deep areas of the body. They have permanent temperature and are called by coore, kernel. Other organs have a more low temperature. It depends on temperature of envirenment and easely changes. These organs are situated on periphery, they are called as envelope. To these organs one belong, first of all a skeletal muscles and skin. Conditional middle temperature of the skin in axillary domain is 37 °C. It is taken as a norm.

Regulation of body temperature realizes by the centre of thermoregulation. It is situated in arterior part of the hypothalamus in bottom of its third ventricle. A centre coordinates thermogenesis and delivery of the heat. It provides maintenance of temperature of inner organs (kernel) in necessary limits.

 

A centre of thermoregulation consists of a few anatomic and functional units. The main of them are

sensative area (thermostat),

thermoestablishing area (adjusting point)

and two effector areas (centres of thermogenesis and delivery of the heat).

 

Mechanisms of fever.

(1) Release of endogenous pyrogen from inflammatory cells, (2) resetting of hypothalamus thermostatic set point to a higher level (prodrome), (3) generation of hypothalamicmediated responses that raise body temperature (chill), (4) development of fever with elevation of body to new thermostatic set point, and (5) production of temperaturelowering responses (flush and defervescence) and return of body temperature to a lower level.

 

Body temperatures under different conditions.

 

Thermostat is a part of brain, which takes temperature of the body with very high exactness (0,01 °С). The neurons of this area register the temperature of arterial blood, which flows over brain straightly. Besides, they receive signals from receptors of skin and from thermoreceptors of inner organs. The neurons of thermostat analyse and integrate all this temperature signalling. They determine a middle temperature of inner organs (kernel) continously and pass this information on adjusting point.

 

 

Adjusting point is a group of neurons, which determine a necessary temperature of the body at this moment. It reconstructs the center of thermogenesis and delivery of the heat. If a temperature of the body is low, a centre of thermogenesis becomes excited. If temperature of the  body is high, centre of delivery of the heat become excited.

A centre of thermogenesis regulates a temperature by rising of general metabolic activity. The most quantity of heat is maked in skeletal muscles. At the lowering of body temperature in cold regions at first rises muscules tone, однако этот механизм not always can give sufficient amount of supplementary heat. In these cases starts muscular trembling. This is spontaneous rhythmic abbreviations is skeletal muscules. They can raise a metabolism speed in five times (retractive thermogenesis). Forming energy partially comes on mechanical work, but more part of it disengages in the form of the heat. Body temperature rises. Essential significance in maintenance of body temperature has a liver. In usual conditions in liver about 30 % of heat are maked.

A heat emission centre regulates a heat exchange by following ways:

separate of sweat and evaporation of water over skin and respiratory organs;

radiation is lossing of heat in form of electromagnetic waves without contact with surrounding objects;

conduction is loss of warm at straight contact with objects;

convection is heat transfer by air molecules or liquid.

Centre of thermoregulation receives input from two sets of thermoreceptors: receptors in the hypothalamus itself monitor the temperature of the blood as it passes through the brain (the core temperature), and receptors in the skin monitor the external temperature. Both pieces of information are needed so that the body can make appropriate adjustments. The thermoregulatory centre sends impulses to several different effectors to adjust body temperature:

The thermoregulatory centre is part of the autonomic nervous system, so the various responses are all involuntary. The exact responses to high and low temperatures are described in the table below. Note that some of the responses to low temperature actually generate heat (thermogenesis), while others just conserve heat. Similarly some of the responses to heat actively cool the body down, while others just reduce heat production or transfer heat to the surface. The body thus has a range of responses available, depending on the internal and external temperatures.

 

 

The thermoregulatory centre normally maintains a set point of 37.5 ± 0.5°C in most mammals. However the set point can be altered is special circumstances.

 

Body temperature reflects the difference between heat production and heat loss. Body heat is generated in the tissues of the body, transferred to the skin surface by the blood, and then released into the environment surrounding the body. The thermoregulatory center in the hypothalamus functions to modify heat production and heat losses as a means of regulating body temperature.

Mechanisms of Heat Production

Metabolism is the body’s main source of heat production. The sympathetic neurotransmitters, epinephrine and norepinephrine, which are released when an increase in body temperature is needed, act at the cellular level to shift metabolism so energy production is reduced and heat production is increased. This may be one of the reasons fever tends to produce feelings of weakness and fatigue. Thyroid hormone increases cellular metabolism, but this response usually requires several weeks to reach maximal effectiveness. Fine involuntary actions such as shivering and chattering of the teeth can produce a threefold to fivefold increase in body temperature. Shivering is initiated by impulses from the hypothalamus. The first muscle change that occurs with shivering is a general increase in muscle tone, followed by an oscillating rhythmic tremor involving the spinal-level reflex that controls muscle tone. Because no external work is performed, all of the energy liberated by the metabolic processes from shivering is in the form of heat. Physical exertion increases body temperature. With strenuous exercise, more than three quarters of the increased metabolism resulting from muscle activity appears as heat within the body, and the remainder appears as external work.

 

Mechanisms of Heat Loss

Most of the body’s heat is produced by the deeper core tissues (i.e., muscles and viscera), which are insulated from the environment and protected against heat loss by the subcutaneous tissues. Adipose tissue is a particularly good insulator, conducting heat only one third as effectively as other tissues. Heat is lost from the body through radiation and conduction from the skin surface; through the evaporation of sweat and insensible perspiration; through the exhalation of air that has been warmed and humidified; and through heat lost in urine and feces. Contraction of the pilomotor muscles of the skin, which raises the skin hair and produces goose bumps, reduces the surface area available for heat loss. Of these mechanisms, only heat losses that occur at the skin surface are directly under hypothalamic control. Most of the body’s heat losses occur at the skin surface as heat from the blood moves to the skin and from there into the surrounding environment. There are numerous arteriovenous (AV) shunts under the skin surface that allow blood to move directly from the arterial to the venous system (Fig. 9-13). These AV shunts are much like the radiators in a heating system. When the shunts are open, body heat is freely dissipated to the skin and surrounding environment; when the shunts are closed, heat is retained in the body. The blood flow in the AV shunts is controlled almost exclusively by the sympathetic ner-vous system in response to changes in core temperature and environmental temperature. The transfer of heat from the skin to the environment occurs by means of radiation, conduction, convection, and evaporation.

Radiation. Radiation involves the transfer of heat through the air or a vacuum. Heat from the sun is carried by radiation. The human body radiates heat in all directions. The ability to dissipate body heat by radiation depends on the temperature of the environment. Environmental temperature must be less than that of the body for heat loss to occur.

Conduction. Conduction involves the direct transfer of heat from one molecule to another. Blood carries, or conducts, heat from the inner core of the body to the skin surface. Normally, only a small amount of body heat is lost through conduction to a cooler surface. However, loss of heat by conduction to air represents a sizable proportion of the body’s heat loss.

The conduction of heat to the body’s surface is influenced by blood volume. In hot weather, the body compensates by increasing blood volume as a means of dissipating heat.  Exposure to cold produces a cold diuresis and a reduction in blood volume as a means of controlling the transfer of heat to the body’s surface.

Convection. Convection refers to heat transfer through the circulation of air currents. Normally, a layer of warm air tends to remaiear the body’s surface; convection causes continual removal of the warm layer and replacement with air from the surrounding environment. The wind-chill factor that often is included in the weather report combines the effect of convection

caused by wind with the still-air temperature.

Evaporation. Evaporation involves the use of body heat to convert water on the skin to water vapor. Water that diffuses through the skin independent of sweating is called insensible perspiration. Insensible perspiration losses are greatest in a dry environment. Sweating occurs through the sweat glands and is controlled by the sympathetic nervous system. In contrast to other sympathetically mediated functions, sweating relies on acetylcholine, rather that the catecholamines, as a neurotransmitter. This means that anticholinergic drugs, such as atropine, can interfere with heat loss by interrupting sweating.

Evaporative heat losses involve insensible perspiration and sweating, with 0.58 calories being lost for each gram of water that is evaporated.12 As long as body temperature is greater than the atmospheric temperature, heat is lost through radiation. However, when the temperature of the surrounding environment becomes greater than skin temperature, evaporation is the only way the body can rid itself of heat. Any condition that prevents evaporative heat losses causes the body temperature to rise.

 

Etiology and pathogenesis of the fever

Rise of body temperature is very frequent symptom attached to much diseases. There are two type of rising temperature: a fever and hyperthermy.

Fever is typical pathological process. He describes by change of thermoregulation and rise of body temperature, irrespective of temperature of environment. Attached to fever thermoregulation centre oneself aspires to rise of temperature.

Hypothermy is a fortune, when body temperature rises under dominance of external and inlying factors. Thermoregulation centre tackles body temperature within the pale of normal sizes, however this to him does not turn out well.

On origin distinguish two fevers – appearance infectious and uninfectious. Evolutional fever arose as reaction on penetration in microorganisms organism and their toxins, therefore she most typical for infectious illnesses.

Infectious fever. microorganisms contain the pyrogenetic matters (exogenous pyrogens). They go into composition of toxins of mycroorganisms. Most are studied the endotoxins of Gramnegative bacterium. They consist of three parts: lipid, polysacharid and albuminous. Pyrogenetic properties has lipid fraction (lipoid A).

Under influence lipoid А in organism forms endogenous pyrogen – interleukin 1. It exudes by neutrophils, monocytes, macrophags and with by other cells, that is apportionment of interleukin 1 is function of phagocyting cells. Attached to contact exogenous pyrogens with these cells acceterate the genes, which encode synthesis of interleukin 1. It immediatly influences on thermoregulation centre.

Many microorganisms do not pick out the endotoxins, but are followed with fever (flu exciters, diphtheria, stupor). Here displays general conformity to natural laws: any phagocytosis stimulates apportionment inlying of pyrogen. Bacterium and viruses actively eliminate from blood by system of mononuclear phagocytes cells. These cells initiate production inlying of pyrogen in liver, spleen and other organs.

 

 

The uninfectious fevers divide by two hinds appearance on origin: fever attached to allergy and fever attached to aseptical inflammation. Their pathogeny identical: they call inlying by pyrogen. Attached to aseptical inflammations (myocardium heart attack, illness of connecting tissue) takes place phagocytosis of lost and damaged cells and ferments. Attached to allergies phagocytes eat the complexes of antigen-antibody.

Interleukin 1 acts on thermosensitive neurons of thermoregulation centre,  that is on thermostat. These neurons have on its membranes the sensible receptors. After their irritation activates adenilatecyclase thermostat neurons system.  In them grows cyclic adenosinemonophosphate. It changes sensitiveness of these neurons to cold and thermal signals. To cold signals sensitiveness grows, and to thermal – falls.

In these conditions adjusting of thermoregulation centre point values blood-heat of inlying organs as low. Referenting temperature of adjusting point displaces up starts to fever. Transmission of information from thermostat neurons oeurons of adjusting point performs with the help of prostaglandins.

Fever stages

Pick out three fever stages:

stage of temperature rising  (stadium incrementi), 

stage of high temperature standing (stadium fastigii),

stage of temperature lowering’s (stadium decrementi) .

 

In the first stage of heat production prevails over heat emission. Mechanisms of heat production and heat emissions reform like so, to retain body temperature on more high level. Foremost, heat emission limits. This mechanism matters decisive. The peripheral vessels narrows, diminishes an influx of warm blood to peripheral tissues, diminishes sweat separate and evaporation. In-parallel with that increases heat production. Grows muscles tone. Appears muscles thremor. Grows heat production in liver. Rising of body temperature is attended with shivering. By this term designate strong of cold feel in combination with intensive thremor.

Body temperature gradually rises. It reaches referenting temperature of adjusting point, that is necessary temperature. On this level it holds on a few hours or days. This is the second stage (stage of high standing). In this stage heat production anew becomes equal as heat emission. However an equilibrium supports on more higher level. Sick feels a heat’s flow (heat). Rises not only the temperature of inlying organs, but the skin’s temperature also.

On temperature up degree in second stage distinguish such types of fever:

subfebrile – to 38 °C,

moderate – 38-39 °C,

high – 39-41 °C, 

hyperpiretic –   above 41 °C.

 

In third stage the action of interleukin 1 on thermoregulation centre ceases. Referenting temperature of adjusting point anew goes down. The centre of heart production oppresses. Heat emission centre,  inside out, activates. Diminishes heart production in muscles and hepar. Heat return grows on all possible ways. Lowering of body temperature is gradual (lytical) or rapid (critical).

 

Rapid (critical) (А) and gradual (lytical) (HB) lowering of body temperature on third stage of fever reaction

 

 

Types of the temperature curves

Nature of curve depends on two factors – illness exciter peculiarities and organism reactivity. Major types of temperature curves:

Febris continua – permanent fever. Oscillations between morning and evening temperature do not exceed 1 °C. Such temperature curve is observed on the first period of abdominal typhus, attached typhus, crupose pneumonia.

Febris remittens – indulgence fever. Oscillations between morning and evening temperature exceeds 1 °C. Such type of curve observes attached to viral infections, sepsis, in second half of abdominal typhus.

Febris intermittens. It is alternating fever. Describes ot the rising periods of temperature (paroxysmuses) right alternate with the periods of normal temperature (apirrhexions). Temperature of the body rises to the level of 40 °C and higher, holds on a few hours, goes down to the norm and rises again. This fever type is observed to the malaria. The paroxysmuses can arise every fourth day (febris quartana), every third day (febris tertiana) or daily (febris quotidiana). Periodicity of the temperature rise depends on duration of development cycle of malarial plasmodium. Paroxysmuses coincide in course of the time of destruction of erythrocytes (after completion of cycle).

Febris  recurrens. It is recurrent fever. Describes by more protracted periods of rising temperature (5-8 days) and lack of clear regularity in beginnings of paroxysmuses. Example is recurrent typhus.

Febris hectica. It is exhausting fever. Daily oscillations of it are equal 2-3 °C and more. Sometimes temperature goes down below the norm. Such fever is typical to sepsis, tuberculosis.

Febris undulans. It is undulating fever. It is typical for brucellosis.

 

Later clean types of temperature curves are rare. This related to wide antibiotics application and antipyretics.

 

Types of the temperature curves: a – Febris continua, b – Febris remittens, c – Febris intermittens, d – Febris  recurrens

 

Biological role of the fever

Fever, as regulations, renders positive influence on sick organism. It is instrumental in convalescence. In the same time fever is followed with undesirable changes in the organism. At first we will bring arguments to the fever benefit as protective, adaptated reaction.

Fever is negatively for the growing and reproduction of some microorganisms. For example, gonococcuses and treponems perish at the temperature of 40-40,1 °C. Fever creates inauspicious sfere for development of some types of the pneumococcuses, prevents to reproduction of some pathogenic viruses. Typical example is oppression of the reproduction of poliomyelitis virus

Fever decrease resistibility of microorganisms to medical preparations, stimulates immunological answer of the organism on encroachment of infectious agent. The fever activates phagocytosis, antibodies synthesis rises, T-lymfocytes increase the multiply synthesis and secretion of interferon, which makes antiviruses action.

Fever is a strong stressor. Attached to fever rises activity of hypothalamic kernels, аfter takes place an activation of front pituitary gland part and of suprarenal glands cortices.  These phenomena is typical for general adaptation syndrome. In-parallel rises activity of sympathetic-adrenal system.

Becomes stronger disintegration of glycogen, appears hyperglycemia. In conditions of raised metabolism and raised thermogeneration it provides to the tissues energy.

Fever is followed with much effects positive for organism. They served by foundation for elaboration and inculcation in practice of special cure appearance pyrotherapy.

Fever is absolutely adaptation reaction. But it is not always useful. In dependence on illness nature,  age, to individual reactivity she can begin undesirable, even harmful.

Fever makes worse sick state of hereth, followed with discomfort. It is attended with shivering, general indisposition, headache, heat sense,  sometimes – delirium.

 

 

Fever inauspiciously affects metabolic processes. It sharply raises the basic metabolism. Such rules is established conformity to natural laws: increases of body temperature on 1 °C conforms to rise of basic metabolism exemplarily on 10 %.

Diverse types of cargo exchangevariously react on fever. Not single conformity to natural laws in interchange changes of carbohydrates, fats, proteines. These changes depend on fever causes,  stage of feverish reaction, power reserves of organism,  reliability of regulation systems, nourishment character and other factors.

Attached to some infectious illnesses disorder of carbohydrates and fatty metabolism are very big. Carbohydrates backlogs are exhausted fully. By energy sources begin fat acids. Surplus receipt of fat acids in lever brings about surplus generation of ketone bodies. Develops metabolic acidosis.

The violations of albuminous exchange attached to fever are more various. Attached to infectious diseases smart few protein disintegration in organism reinforced. It does not compensate by protein receipt with food. Arises the negative nitrous balance. Heightened albuminous exchange attached to fever interconnect with action of microbic toxins and tissues disintegration products. Toxic protein disintegration in experiment is observed, for example, attached to introduction of dysenteric toxin, fresh pus, streptococci culture, blue pus bacillus. It typical, foremost,  for sharp infectious diseases.

Fever inauspiciously affects cardio-vascular system. As a regulations, frequency of cardiac abbreviations increases (tachycardia). It conditioned by much factors:

a) rise of activity of sympatical nervous system;

b) straight hormones dominance of thyroid on heart;

c) dominance of warm blood on sinus knot;

d) lowering of peripheral vessels resistance.

By Libermayster, rise of body temperature on 1 °C is attended with speed up of pulse on ten beat in one min. Except of tachycardia, rises a shock heart volume. Cardiac output increases on 25-30 %.

Change of arterial pressure depends on fever stage.  In first stage it rises, in second stage  will normalize or will bit lowers. Lowering of arterial pressure in third stage depends on temperature degradation speed.  Attached to slow temperature (lysis) degradation pressure lowers gradually and moderately. Attached to rapid temperature (crisis) degradation pressure lowers rapidly and sharply. In this case is possible collapse development.

Changes blood circulation. On periphery of the body it limits. But in inlying organs (buds, liver, spleen) resistance of vessels lowers, and circulation of the blood becomes stronger.

Breathing attached to rise of temperature becomes more frequent (tachypnoe). High frequency of breathing are accounted for by straight dominance of high temperature on respiratory centre.

Permanent fever satellite – violation of function of digestive organs. Function of alimentary canal strongly disturbs attached to abdominal typhus, diphtheria, measles, less – attached to flu, recurrent typhus, tuberculosis. Nature of these similar violations attached to fever of any origin. The very frequent displays: appetite loss,  lowering of saliva secretion, bowels atony (constipation, flatulency),  lowering of pancreas excretory function, lowering of motored and secretory function of stomach.

Disorders of digestion unconnected immediately with fever. They related to water loss and chlorids. Therefore antipyretics do not give medical effect. For removal of digestion disorders it is need a special diet.

Heavy fever oppresses the central nervous system. In sick appear such symptoms, as leading pain, weariness, insomnia. Attached to expressed intoxication are the hallucinations, delirium, consciousness loss,  in children – the cramp. In pathogenesis of these symptoms an essential significance has brain anoxaemia.

If disease flows with high temperature, always stands up a question of medical tactics: as will make away fever or not? Absolute testimonies for symptomatic cure fevers following: body temperature sick above 39 °C, cramps presence in anamnesis, concomitant heart diseases and vessels, sharp neurulogic diseases, sepsis, shock.

For wrestling with fever adapt antipyretics. Mechanism of their action is very various: braking of synthesis leukocytes pyrogen interleukin 1, oppression of synthesis of fever mediator – prostaglandins,  oppression of thermoregulation centre excitability, lowering of intensity of oxydizing processes and diminution of heat making,  augmentation of blood flow in peripheral vessels, reinforcement of sweat separate processes.

 

NEOPLASTIC GROWTH

Pathophysiological description

Neoplastic growth – is the typical pathophysiological process in appearance of tissue excrescence. It is described by potential unlimited growth, growth unregulation and atypic cells anaplasia.

 

Central bronchus cancer

Universal and obligatory property of all high quality and malignant neoplasms – is their capacity for unrestricted growth. In their excrescence base uncontrolled cultural elements surplus proliferation lies. Neoplastic cells mitoses speed does not exceed the one of normal cells – embryonic bone marrow cells, bowels epithelium and other. Tumor cells differ from normal not by the cell division speed, but  by the character of proliferation. Neoplastic cells acquire ability to divide boundlessly. Growth unlimitation carries the fact, that the swelling cells are not able to exhaust division resources. In each cell a genetic program is pawned, which limits its division amount. Tumor cells do not have any limiting program. They lost it somatic mutation.

Unrestricted growth. Brain tumor

 

Within the organism –tumor cells divide up to its death. They can be carried into the other biological kind of living organism of (that is from mouse to mouse, from rat to rat etc.). They start living and get divided up to organism-recipient’s death.  Transplantation of neoplastic cells from one organism to the other is called transplantation.

Tumor  cells can also be carried into nourishing sphere, where they can also divide endlessly for a long time. Their cultivation there is called explantation. Neoplasms, which support artificially, are called neoplastic cultures. First transplantation culture – Erlich carcinoma in mise (mammal gland cancer) –is known since 1905 and the first cell explantation HeLa (cervix cancer) – since 1950.

Tumor cells have one more typical caracteristic – growth autonomy. Cultural growth is controlled at two levels – organism and tissue ones.  At organism level such control is realized with  nervous and endocrine systems,  at tissues level – with biologically active matters which are mitogenes and keylones. Neoplastic cells display independence, growth autonomy. They stop reacting upoervous, endocrine and local regulation stimuls.

Autonomy of tumor cells develops gradually. At first swelling cell gets partially hormonal regulated (hormone dependent tumor). Later it is perfectly irresponsible for hormones (hormone independent tumor).

Some researchers mention considerable role of cultural division local regulation violations. In particular, ieoplastic tissue keylones maintenance sharply falls down.

The third characteristic feature of tumor cells – is anaplasia, which is cells structural and biochemical organization simplification, coming back to embryonic state. Neoplastic cells lose a capacity for differentiation and caot form the specific tissue complexes.

Tumor arises from one mutational maternal cell. However such cells differ from their general ancestor by much parameters. These distinctions consearn the cell structure,  its organelles, metabolism, specific properties and functions.

 

Therefore the following kinds of anaplasia:

·        morphological

·        biochemical

·        physical

·        chemical

·        functional

·        immunological

 

The essence of morphological anaplasia is in atypic cultural and tissue  appearance. Description of cultural atypic – lays in cells polymorphism:

 

Melanoma. Cells polymorphism

 

Another signs of morphological anaplasia are: nuclear dimensional increase, polynuclear state, nuclear hyperchromatosis, nucleoluses amount augmentation, mitochondrias changes – quantative and dimensional diminution,  membranes thickness decrease,  crests disappearance.

Epidermal cancer. Polynuclear state, nuclear hyperchromatosis of cells

 

Tissue atypism – is dimensions and shapes of tissue structures change, sometimes is the total loss of morphological tissue signs.

Anaplastic cancer cells

Biochemical anaplasia – is the tumor cells metabolism peculiarities. They called by their genetic system changes,  enzymic spectrum of such cells gets changed. All cells get alike by the enzymic admission (unification of isoenzymic spectrum).

The most typical biochemical peculiarities of neoplastic cells bear upon albumens and carbohydrates metabolism. Albuminous metabolism peculiarities are: synthesis activation of nucleic acids, DNA-polymerase inactivation,  augmentation of albumens synthesis and diminution of albumens disintegration. 

Carbohydrates and energetics  tumor cells metabolism is also out of norm. The main energy sources iormal cells are anaerobic and aerobic carbohydrates disintegration,  that is glycolysis and Krebs cycle. Neoplastic cell also accords the energy in account of glycolysis and Krebs cycle. However glycolysis role  in tumor cell is more, than iormal one.

The  tumor cells energetic supply include: anaerobic glycolysis activation,  aerobic glycolysis presence, oppression of Krebs cycle by powerful glycolytical enzymes system.

Physical and chemical peculiarities of neoplastic cells: acidosis along of milky acid accumulation, intracellular hydration, raised conductivity, colloids visciditydiminution, membranes surface-tension diminution, negative membranes charge augmentation.

Functional anaplasia displays in loss or perversion of tumor cells function. For example, ieoplastic thyroid cells  a surplus amount of hormones thyroxine and triiodothyronine can be synthesized,  thyrotoxicosis arises.

In other cases separate functions of timor cells fall out, for example, bilirubin does not get conjugated in liver. In very malignant neoplastic cells functions are totally lost. sometimes such cells start doing the functions, which are not specific for them (bronchus cancer  synthesizes the alimentary canal hormones).

 

Thyroid cancer

 

Immunological anaplasia – is the change of tumor cell antigen properties. In such cells  antigen admission is changed.  Several deviation kinds of antigen out of norm admission are distinguished –  antigen simplification, antigen divergence and antigen reversion. Antigen simplification – is the general number of neoplastic cells antigens  diminution. For example, the cells of normal tissue synthesize up to 7 typical antigens, while same tissue tumor cells synthesize only 2-3 antigens.

The idea of antigen divergence is in the fact of neoplastic cells starting to synthesize heterologous antigens. For example, hepatoma (liver tumor) begins synthesizing organospecific  spleenic antigens, or other organs antigens.

Antigen reversion means neoplastic embryonic antigens synthesis. For example, human liver cancer synthesizes a special embryonic albumen, which is a-fetoprotein. 

 

Tumor etiology

Swellings are caused by carcinogens, which include such groups: chemical, physical and biological.

Chemical carcinogenesis. The first clinical supervisions in this direction had been done by Pott. He described scrotum, internal thighs surfaces and stomach cancer in young chimney-sweepers.

Yamagiva and Ichikawa proved a carcinogenous of chemical matters in experiment at first. They drifted carbonic resin onto the rabbit ear for fifteenth months. This process was followed with skin cancer in rabbit. In 1930-1932 pure carcinogenes were extracted out of carbonic resin, including benzoapyrene, dibenzanthracene, methylcholanthrene. 

Chemical carcinogenes are presented by several groups. The main are:

polycyclic aromatic hydrocarbons

aromatic amines and amides

nitrosamines and nitrosamides

Substances, that contain three or more benzoic cycles belong to the first group. More than 200 of them are known. But the only one of them, which is 3,4-benzopyrene is carcinogenic for a human.

Carcinogenes of this group, are usually of antropogenous origin. They are in tobaccosmoke, car-petroleum gases, blast-furnaces smoke, chemical productions wastes, overfried food. They cause cancer or sarcoma by their injection way. Polycyclic aromatic hydrocarbons exude from organism by kidneys, skin, mammal glands, therefore are followed with the neoplasms of these organs.

 

3,4-benzopyrene

 

        Aromatic amines and amides are mainly dyestuffs. They include monoazobenzene, benzidine, chlornaphthisine and others. These substances are usually used for natural or synthetic fabrics colouring, polygraphy, cosmetics production, colour-photography processes, medications or eather insecticides synthesis that is followed with neoplastic growth attached to skin or gastrointestinal contacts. Tumors are usually located in liver, urinary cyst, bowels, kidneys.

The third carcinogenes group (nitrosamines and nitrosamides) cause neoplastic processes in 40 animals species. Their carcinogenous effects upon the humans are  not proved, however the experimental data are of the great attention. A man contacts to nitrosamines at productions. Besides, they form in digestive canal of nitrites, nitrates and other junctions of nitrogen.

Almost all of carcinogenic matters are not active. But they acquire carcinogenic properties due to their entering the organism. The final cancerogenes get formed with them. Nominally these matters are followed with neoplastic growth. It is proved, that carcinogenes  react with purine bases of DNA obligatorily.

The most frequent target – is guanine, which gets methylated or eather alkylated by cancerogenes (that means its combining to the methyl or eather alkyl group). Changed guanine is unable to bind with cytosine, but gets associated with thymine. The sequence of bases in DNA molecule gets disturbed.  Genes mutation arises.

Physical carcinogenesis. To physical cancerogenes belong ionizing and ultraviolet rays.

The ionizing rays cause diverse genetical and chromosomal mutations. They are followed with neoplastic growth in all of organs almost.

Skin, bones, lungs, thyroid, mammal gland neoplasms arise in case of external irradiation. In case of ionizing radionuclides entering inside, the tumor arises at their accumulation locations. For example barium, calcium, strontium radionuclides  cause the bone neoplasms. Caesium, thorium radionuclides, able to cause liver, bone marrow, stomach, thick bowel tumors.

The ultraviolet rays render weak carcinogenic action, but they damage the mechanisms of DNA reparation. In particular, dimerization of thymine takes place under their dominance. As a result  an usual bases sequence in DNA molecule gets disturbed.

 

 

Viral carcinogenesis. It is proved, that tumors can be caused by viruses. Here are some neoplasms examples of viral origin: Rauss sarcoma in chicken, Shope papilloma in rabbits, mammal gland cancer in rats, which arises in case of Bittner milk factor. Viruses, which cause neoplastic growth, are called oncogenous. They belong to the group of retroviruses.

Not many human tumors, which get caused by viruses are known. They are Burkitt’s lymphoma (Central Africa), nasopharyngeal cancer (China), cervix cancer.

 

Conception of oncogen

A special theory was formulated by the end of last century,due to the  foundation of contemporary knowledge, which united all of known carcinogenesis forms (chemical, physical, biological) into a single universal mechanism. It had been called as conception of oncogen.

 

Conception of oncogen

 

Appearance of neoplastic growth is related to genetic system somatic cells changes. Tumor is a hereditary phenomenon at the cell level. There are many causes of cancer and all of them get DNA damaged. This damage must be located in that area DNA, where  cellular oncogenes are situated. These gens are the usual components of the cell genome. They control growth and cells differentiation. 

These growth stimulators normal function  can be preserved in case of insignificant damages, but they stop to submit the supervisory dominances of the surrounding genes and the cell. The normal dirigible cells reproduction and maturation  process get lost. It is substituted by an unterminable stream of cellular division.

 Cellular oncogenes are also called as cencer genes. Carcinogenic agents damage either oncogenes or genes-repressors, which are serial located. In effect of chemical, physical and viral factors, their activity gets raised sharply and they turn the normal cell into the neoplastic one. A few cellular oncogenes activative mechanisms are known. They are: viral transduction, chromosomal mutation, genetic material insertion, genetic amplification, dot mutations.

viral  transduction. Retroviruses are the cause of cellular DNA damage due to  the transforming genes invasion, they are called viral oncogenes and have cellular origin. These are the cellular DNA areas, which were seized by virus into the own genome occasionally. Now more than 20 viral oncogenes are known. All of them have cell twins. These cell twins (cell oncogenes) are  situated in different chromosomes.

Examples are: Raus sarcoma  virus in hens is located in 20-th chromosome, Molone sarcoma virus in mice – in 8-th chromosome, Rorru-Donal virus in cats – in 5-th chromosome, sarcoma virus in hairy moukeys – in 22-th chromosome.

Viral oncogenes differ from their cell predecessors. Usually, retroviruses holder cell oncogenes not totally, without the regulatory (repressive) genes. Viral oncogene preserves an ability to stimulate cells growth and differentiation, but at the same time loses genes-repressors and becomes uncontrolled. Therefore a recurrent entrance into the infected cell DNA is followed with unrestricted cell division. Cell oncogen itself gets changed also in its seizure  by retrovirus process. It consists of exones (encoding areas) and intrones (unencoding areas) in the cell. It combines exones only (encoding areas) in virus genome. Therefore it is very active.

chromosomal aberration. Translocatons are observed in human neoplastic growth cells  more often. It is thought, that translocation is one of the cell oncogenes activation ways majority. Chromosomes breaking  takes place close to the cellular oncogenes frequently. They get activated right after the breaking. Such tumor example is Berkit lymphoma. Mutual translocation between eigth and fourteenth chromosomes is typical for such lymphoma kind.

Insertion of genetic material. Neoplastic growth arises not only, in case of viral oncogene injury into the cell DNA. Cell oncogene activation is also possible, when any heterologous (viral) genetic material encroaches into the cell DNA close to it. It is not suppose to keep oncogene. Any viral DNA is able to activate cell oncogene, due to its incorporation into the cell DNA beside the oncogene.

Amplification of cell oncogene. Usually, cell oncogenes are represented by one copy. Amount of copies can increase as a result of spontaneous DNA  replication anomalies. Such phenomenon is named amplification. DNA copies amount  augmentation causes their summary expression augmentation.  Supplementary RNA and oncoalbumen amount gets synthesized on supplementary DNA matrices. Amplification is typical for some human tumors. Neuroblastoma and thick bowels carcinoma  arises due to such mechanism.

Point mutations. All cell oncogenes activation mechanisms, which were characterized earlier, obligatorily related to cell DNA changes. Eventually, all of them are of mutational origin. Now it is admitted, that dot mutations are a major carcinogenesis mechanism.  

 

Stages of carcinogenesis

Neoplastic growth beginning and development in multistage process. The main three stages are:

transformation

promotion

progression

transformation. The first stage (transformational stage) is followed with the cell oncogene activation. The cell acquires unusual property, which is called immortalisation. This is a potential unlimited division, immortality ability. However, the presence of active oncogene is a readiness to division only. A cell with active oncogene can resist in latent (condition) for years. It does not display itself with anything.

Promotion. Supplementary influences upon immortalisated cell, are necessary to exit it out of the latent state, for giving a push to irrepressible division. These are provoking factors, which are supplementary doses of chemical cancerogenes or x-rays, retroviral superinfection. They are named promotors.

Progression is the very last and the most protracted stage of neoplastic growth development. The clearest determination of this notion Fulds has given: “Progression is a neoplasm development in a way of constant, irreversible, qualitative changes of its one or a few signs”.

Stages of carcinogenesis

 

Progression is not just quantitative tumor growth, but native change of its biological properties. One of the major Fuld’s principles is an independent progression of separate neoplastic signs. Its essence is the following: each tumor sign (morphological anaplasia degree, hormones dependence degree,   invasive growth capacity, metastasing ability) evolutionizes irrespectively to the other signs, however  to the malignisation side always.

 Neoplastic growth progression reflects tumor admiring to autonomy. It holds a neoplastic cell much more further from maternal. The main progression index is organs and tissues structure loss by the tumor with simultaneous cell differentiation lowering.

 

Neoplastic growth progression reflects in its clinical symptoms and therapy possibilities. For example, some tumors (mammal gland cancer, uterius corpus, prostata) on the definite development stages react to hormones.

In other words, these neoplasms are hormone dependent. Tumor cells lose the specific receptors  and stop reacting to the hormones influence during the progression. Neoplastic growth becomes hormone independent. It is not sensitive to hormonal therapy.

Illustration showing hematogeneous metastasis

 

Metastasing

Metastasis, or metastatic disease, is the spread of a cancer from one organ or part to another non-adjacent organ or part. The new occurrences of disease thus generated are referred to as metastases (sometimes abbreviated mets). It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research. In origin metastasis is a Greek word meaning “displacement”, from μετά, meta, “next”, and στάσις, stasis, “placement”. The plural is metastases.

Cancer occurs after a single cell in a tissue is progressively genetically damaged to produce cells with uncontrolled proliferation. This uncontrolled proliferation, mitosis, produces a primary tumor. The cells which constitute the tumour eventually undergo metaplasia, followed by dysplasia then anaplasia, resulting in a malignant phenotype. This malignant phenotype allows for intravasation into the circulation, followed by extravasation to a second site for tumorigenesis.

Some cancer cells acquire the ability to penetrate the walls of lymphatic and/or blood vessels, after which they are able to circulate through the bloodstream (circulating tumor cells) to other sites and tissues in the body. This process is known (respectively) as lymphatic or hematogeneous spread.

After the tumor cells come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor. This new tumor is known as a metastatic (or secondary) tumor. Metastasis is one of three hallmarks of malignancy (contrast benign tumors). Most neoplasms can metastasize, although in varying degrees (e.g., basal cell carcinoma rarely metastasize).

When tumor cells metastasize, the new tumor is called a secondary or metastatic tumor, and its cells are similar to those in the original tumor. This means, for example, that, if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called metastatic breast cancer, not lung cancer.

The final progression stage of any tumor is its transformation into the malignant neoplasm. The major criteria of malignant tumor is its ability to generalisation, that is – to metastasing. Metastasing includes three stage: neoplastic invasion into the surrounding tissues, tumor cells transport with the blood and lymphatic vessles, their implantation in different organs and tissues.

Separate cells evacuation out of the neoplastic node takes place in case of intercellular contacts  relaxation. Tumor loses calcium, which must turn intercellular spaces cementated in malignisation process. Diminished amount of desmosomes, which create the intercellular contacts arises in pernicious neoplasms. The amount of gangliosides is disranked on the cellular surface of malignant tumor.

Metastatic tumors are very common in the late stages of cancer. The spread of metastasis may occur via the blood or the lymphatics or through both routes. The most common places for the metastases to occur are the lungs, liver, brain, and the bones.

Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases isn’t always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone. Breast cancer, for example, tends to metastasize to the bones and lungs. This specificity seems to be mediated by soluble signal molecules such as chemokines and transforming growth factor beta. The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as metastasis suppressors, of which about a dozen are known.

Human cells exhibit 3 kinds of motion: collective motility, mesenchymal-type movement, and amoeboid movement. Cancer cells often opportunistically switch between different kinds of motion. Some cancer researchers hope to find treatments that can stop or at least slow down the spread of cancer by somehow blocking some necessary step in one or the other or both kinds of motion.

Cancer researchers studying the conditions necessary for cancer metastasis have discovered that one of the critical events required is the growth of a new network of blood vessels, called tumor angiogenesis. It has been found that angiogenesis inhibitors would therefore prevent the growth of metastases.

There are several different cell types critical to tumor growth. In particular endothelial progenitor cells are a very important cell population in tumor blood vessel growth. This finding was published in the journals Science (2008) and Genes and Development (2007) together with the fact that endothelial progenitor cells are critical for metastasis and angiogenesis. The importance of endothelial progenitor cells in tumor growth, angiogenesis and metastasis has been confirmed by a recent publication in Cancer Research (August 2010). This seminal paper has demonstrated that endothelial progenitor cells can be marked using the Inhibitor of DNA Binding 1 (ID1). This novel finding meant that investigators were able to track endothelial progenitor cells from the bone marrow to the blood to the tumor-stroma and even incorporated in tumor vasculature. This finding of endothelial progenitor cells incorporated in tumor vasculature proves the importance of this cell type in blood vessel development in a tumor setting and metastasis. Furthermore, ablation of the endothelial progenitor cells in the bone marrow lead to a significant decrease in tumor growth and vasculature development. Therefore endothelial progenitor cells are very important in tumor biology and present novel therapeutic targets.

NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed NFAT1 (NFATC2) and NFAT5 are pro-invasive and pro-migratory in breast carcinoma and NFAT3 (NFATc4) is an inhibitor of cell motility. NFAT1 regulates the expression of the TWEAKR and its ligand TWEAK with the Lipocalin 2 to increase breast cancer cell invasion and NFAT3 inhibits Lipocalin 2 expression to blunt the cell invasion.

Routes of metastasis

Metastasis occurs by following four routes:

Transcoelomic

The spread of a malignancy into body cavities can occur via seeding the surface of the peritoneal, pleural, pericardial, or subarachnoid spaces. For example, ovarian tumors can spread transperitoneally to the surface of the liver. Mesothelioma and primary lung cancers can spread through the pleural cavity, often causing malignant pleural effusion.

Lymphatic spread

Invasion into the lymphatic system allows the transport of tumor cells to regional and distant lymph nodes and, ultimately, to other parts of the body. This is the most common route of metastasis for carcinomas. In contrast, it is uncommon for a sarcoma to metastasize via this route. It is worth noting that the lymphatic system does eventually drain into the systemic venous system via the azygous vein, and therefore these metastatic cells can eventually spread through the haematogenous route.

Haematogenous spread

This is typical route of metastasis for sarcomas, but it is also the favored route for certain types of carcinoma, such as those originating in the kidney (renal cell carcinoma). Because of their thinner walls, veins are more frequently invaded than are arteries, and metastasis tends to follow the pattern of venous flow.

Transplantation or implantation

Mechanical carriage of fragments of tumor cells by surgical instruments during operation or the use of needles during diagnostic procedures. Cancer cells may spread to lymph nodes (regional lymph nodes) near the primary tumor. This is called nodal involvement, positive nodes, or regional disease. (“Positive nodes” is a term that would be used by medical specialists to describe a patient’s condition, meaning that the patient’s lymph nodes near the primary tumor tested positive for malignancy. It is common medical practice to test by biopsy at least two lymph nodes near a tumor site when doing surgery to examine or remove a tumor.) Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of worse prognosis. Transport through lymphatics is the most common pathway for the initial dissemination of carcinomas

The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.

For instance, breast cancer cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as immunohistochemistry, FISH (fluorescent in situ hybridization), and others. Despite the use of techniques, in some cases the primary tumor remains unidentified.

Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor.

It was previously thought that most cancer cells have a low metastatic potential and that there are rare cells that develop the ability to metastasize through the development of somatic mutations. According to this theory, diagnosis of metastatic cancers is only possible after the event of metastasis. Traditional means of diagnosing cancer (e.g. a biopsy) would only investigate a subpopulation of the cancer cells and would very likely not sample from the subpopulation with metastatic potential.

The somatic mutation theory of metastasis development has not been substantiated in human cancers. Rather, it seems that the genetic state of the primary tumor reflects the ability of that cancer to metastasize. Research comparing gene expression between primary and metastatic adenocarcinomas identified a subset of genes whose expression could distinguish primary tumors from metastatic tumors, dubbed a “metastatic signature.” Up-regulated genes in the signature include: SNRPF, HNRPAB, DHPS and securin. Actin, myosin and MHC class II down-regulation was also associated with the signature. Additionally, the metastatic-associated expression of these genes was also observed in some primary tumors, indicating that cells with the potential to metastasize could be identified concurrently with diagnosis of the primary tumor.

Expression of this metastatic signature has been correlated with a poor prognosis and has been shown to be consistent in several types of cancer. Prognosis was shown to be worse for individuals whose primary tumors expressed the metastatic signature. Additionally, the expression of these metastatic-associated genes was shown to apply to other cancer types in addition to adenocarcinoma. Metastases of breast cancer, medulloblastoma and prostate cancer all had similar expression patterns of these metastasis-associated genes.

The identification of this metastasis-associated signature provides promise for identifying cells with metastatic potential within the primary tumor and hope for improving the prognosis of these metastatic-associated cancers. Additionally, by identifying the genes whose expression is changed in metastasis offers potential targets to inhibit metastasis.

Metastasing

 

The definite role ieoplastic cells abruption from the tumor node belongs to mechanical factors. The part of abrupted cells is carried with blood and lymph channel. 95-99,9 % get necrotiesed. An important role in their elimination the anti-neoplasm immunity mechanisms has. They are performed by Т-lymphocytes and natural killers (NК-cells). Natural killers recognize and kill the mutante cells without preliminary sensibilization.  The tumor cells lysis gets realized with proteolytical and lipolytical blood enzymes also.

The secondary tumor nodes form at the third stage. Neoplastic cells delay by the vessel intima and thrombus forming around them arises firstly. Tumor cells accumulation in capillaries is sometimes provoked by mechanical causes: capillary lumen happens to be more narrow, thaeoplastic cells diameter.

Tumor cells exit into the out of vessels space after their adhesion to the endothelium. This exit is related to capillaries penetrability rising.

 

Metastasing cell

 

Cells fate out of blood channal is different. Many cells get perished. Other cells are staying  in a latent condition for a very long time, pending of years. And only small part of cells receive the further development. They reproduct and establish a new neoplastic node (metastasis).

 

Melanoma metastases

Signs and symptoms of metastases

Initially, nearby lymph nodes are struck early. The lungs, liver, brain, and bones are the most common metastasis locations from solid tumors.

Main sites of metastases for some common cancer types. Primary cancers are denoted by “…cancer” and their main metastasis sites are denoted by “…metastases”.

 

In lymph nodes, a common symptom is lymphadenopathy

 

Lungs: cough, hemoptysis and dyspnea (shortness of breath)

Liver: hepatomegaly (enlarged liver), nausea and jaundice

 

Cut surface of a liver showing multiple paler metastatic nodules originating from pancreatic cancer

 

Bones: bone pain, fracture of affected bones

Brain: neurological symptoms such as headaches, seizures, and vertigo.

Although advanced cancer may cause pain, it is ofteot the first symptom.

Some patients, however, don’t show any symptoms. When the organ gets a metastatic disease it begins to shrink until its lymph nodes burst, or undergo lysis.

 

Neoplastic growth and human organism correlation

Tumor appearance and growth depends on the organism state strongly. Two system perform  the primary role here, they are: endocrine and immune.

Endocrine system and oncogenesis. Neoplasms divide into two groups: dyshormonal tumors and unendocrine ones.

Dyshormonal neroplasms totally depend on the organism hormonal  status. Endocrine glands and organs-targets tumors, which underlie hormonal influence belong here. Human dyshormonal mammal gland, uterus, prostate neoplasms are the most expanded.

 

 

Mammal gland cancer

 

In case of mammal gland and uterus tumors development an important role belongs to the surplus production of estrogens, which stimulate cells proliferation in these organs.

Follicle stimulating hormone role in mammal gland cancer formation is proved. it activates estrogens synthesis and renders the straight influence upon the gland tissue.

 

Follicle stimulating hormone role in mammal gland cancer

 

The high estrogens synthesis regulation tension is observed in case of menopause. Menopause in women is followed with high hypothalamo-hypophyseal system activity. A big amount of gonadotrophic hormones get producted. the Sexual steroids synthesis get increased accordingly in ovaries. But they are out of hormonal properties already in this age, and still preserved their ability to stimulate proliferation. Therefore the tumor appearance risk is very high in this period.

Due to its way, the neoplasm, while growing, renders the influence upon the hormonal profile of an organism.  If the tumor does not appear from endocrine gland, it affects upon the hormonal background anyway. So-called paraneoendocrine syndrome arises.

Many neoplasms synthesize matters, which are similar to hormones. For example, bronchogenous cancer, synthesizes the matters with  adrenocorticotrophin or antidiuretic hormone activity.

Chorionepithelioma synthesizes a thyrotropic hormone. Some incretion glands tumors begin synthesing heterologous for the mentioned gland hormones – heterohormones. So, thyroid neoplasms synthesizes adrenocorticotrophin  hormone sometimes. Langerhans islands tumors are able to product up to seven hormones. Neoplastic growth synthesizes normal hormones in some circumstances, but caot transfer them into the active state.

Immune system and neoplastic growth. Tumor cells are heterologous for the organism. They synthesizethe proteins, which are not characteric for normal cells. Neoplasms product specific swelling antigen. Their specificity is conventional, but it is still sufficient for immune reaction development. a final result depends on immune attack intensity greatly: that means, if the transformed cell is going to reproduct,or not; is the tumor going to arise, or not. Neoplasms are observed in people with congenital immunodeficiency 10000 times more often, than in persons with normal immune system. 

The malignant neoplasms arise in patients, with transplanted organ (for example, kidney) very often. Immunodepressive drugs are beeng prescribed with the purpose of transplanted organ rejection prophylaxy in such patients. Tumors in are observed in such cases 100 times more frequent, than in the rest of population.

These facts testify, that the transformed cells underlie the organism immune system supervision.  In most people they eliminate in time. a transformed cell exists, reproducts, and produces the neoplasm in a fact of immune supervision insolvency.

Tumor renders an oppressive action upon the organism immune system in its own way. Immunodepression gets developed.

The matters, which render immunodepressive action are produced ieoplastic cells. Low-molecular metabolites (oligopeptides, unsaturated fatty acids), embryonic antigens (a–fetoprotein), glucocorticoids belong to them. Т–suppressors activity in patients with tumors is increased. They slow down antineoplastic immunity. One more reason of immunodepression in oncologic patients is the disparity betweeeoplastic growth speed and immune answer development speed. Lymphoid cells reproduct slower, than tumor cells do. Adequate immune answer is late.

 

Systemic neoplastic action upon the organism

Tumor is not locally isolated process. It renders an influence upon the diverse organism functions. This is concearning the malignant neoplasms espessially. Their systemic action displays the cancer cachexia.

 

Cancer cachexia

 

There are a few components of its development.

Tumor absorbs the glucose reinforcely. Chronic hypoglycaemia tendency arises. Glycogen disintegrates in liver and muscles reinforcely. Glyconeogenesis gets increased. However, this compensatory mechanism has the negative characteristics.

Firstly, glucocorticoids cause the albumens disintegration of immunocompetence organs (thymus, spleen, lymphoid tissue of other organs). Secondly, of big amount of aminoacids in glyconeogenesis usage gets the organic albumens synthesis limited. Diverse organs dystrophy develops, muscles – first of all.

Neoplastic growth can be described with the intensive synthetic processes. Plastic material (amino acids, nucleic acids) is very important for this. Neoplasm absorbs these matters not only nutritional, but from other organs also. It is named as nitrogen snare. all of other tissues are having aminoacid deficiency. They caot synthesize their own proteins in a necessary volume. This is one more link of cancer cachexia pathogeny.

Depending on whether or not they can spread by invasion and metastasis, tumors are classified as being either benign or malignant.

Difference between benign and malignant tumors

 

Benign tumors are tumors that cannot spread by invasion or metastasis; hence, they only grow locally. Malignant tumors are tumors that are capable of spreading by invasion and metastasis. By definition, the term “cancer” applies only to malignant tumors.