GENERAL ILLNESS DEVELOPMENT CONFORMITIES TO NATURAL
LAWS.
ETIOLOGY AND PATHOGENESIS.
ACTION
OF CHANGED
ATMOSPHERIC PRESSURE UPON ORGANISM
ROLE
OF HEREDITY IN HUMAN PATHOLOGY
GENERAL
ILLNESS DEVELOPMENT CONFORMITIES TO NATURAL LAWS.
ETIOLOGY
AND PATHOGENESIS
Pathological physiology is the science, which studies the general natural lawfullness of disease genesis, development and the end. This is the science about the vital activity of sick organism. Pathological physiology is the study of the most common options of the disease genesis and development, while clinical sciences study specific items of disease prevention, diagnostics and treatment.
Pathological physiology, as a science, solves the following problems: illness essence establishment; disease causes and it’s beginning conditions study; illness development, display, course and the convalescence mechanisms separate explanation; diseaseses prophylaxy and cure general principles determination.
The pathological physiology is related to the other sciences. The following connections are:
a) to the sciences, which study illness causing environmental factors (physics, chemistry, biology, microbiology,
the social sciences), they are necessary
for etiology studying;
b) to the sciences, which study the organism
properties and its vital functions (cytology, embryology, histology, the normal
physiology, biochemistry, immunology, genetics), they create a base for pathogenesis study;
c) to general theoretic sciences, which study an
the disease (pathological anatomy, pharmacology), in common with pathological
physiology create a total picture of the illness;
d) to
the clinical sciences, helping to determine the basic etiological and
pathogenic principles of disease prophylaxy, diagnostics and cure.
The clinic arises the problems and gives the necessary material for
their solvation to pathophysiologists.
The pathophysiology, as a scientific medical base (medical philosophy),
establishes illness etiology and pathogenesis and determines the main directions
of their prophylaxy and cure on this base.
The medicine uses clinical, epidemiological, anatomic, experimental disease study methods.
The peculiarity of pathophysiological experiment
is the reproducing of the experimental disease models upon laboratory animals
with the purpose to establish the mechanisms of their genesis, development and
in human organism.
Pathophysiological
experiment
The experimental disease model is the artificial
reproducing of disease up the laboratory animals, which has the same lines of
the proper human disease.
Though an experiment up animals does not give us
the full picture of the proper human
disease, it enables to observe and to study the disease course the beginning to
its completion, that is impossible in clinics. During the experiment one can
control the environmental conditions, which influence upon the illness course
and have the objective material for the scientific theories construction.
The experiment can be divided into the acute and the chronic one. The acute
experiment is based on the surgical intervention in animal organism. It
examines the acute disorders in organism ( shock, collapse, sharp breathing
insufficiency, blood circulation
insufficiency, etc). The chronic experiment is a protracted one, shows the
illness development dynamics. It is used for a chronic diseases modeling
(diabetes, atherosclerosis, arterial
hypertension, ulcerous disease etc).
Pathological physiology consists of such parts:
·
the
general pathology
·
the
pathophysiology of the organs and systems.
The general
pathology unites such parts:
·
nosology,
·
pathogenic environmental factors
action, inner factors role in pathology,
·
typical pathological processes,
·
the typical metabolic disturbances.
The pathophysiology of organs and systems studies the general development of pathological processes in separate functional systems; the most widespread nosological forms etiology and pathogenesis as well.
The general nosology
The general nosology includes
such notions:
·
health
·
disease
·
pathological
process
·
pathological
state
·
pathological
reactions
Health is the condition of complete physical, psychic and social
well-doing, but not only diseases or the physical defects absence (WHCO – World
Health Care Organization). In doctor’s practical activity determination is
used, according to which health is the condition of a norm.
There is a question: what the
norm is? There are two approaches to this notion determination: the statistic
and the general physiologic one. According to the first one, the norm is the
condition,which is the most frequently observed among people. According to the second one, the norm
is the biological optimum of the organism functioning and development. The
second determination reflects the scientific approach to the notion which is “a
norm”. However this approach remains still unrealized because of our knowledge and possibilities limitation.
Therefore a doctor uses the statistic norm determination in daily activity.
The disease is a disturbance of human organism vital activity
under the influence of extraordinary factors of external or inner environment
which is characterized by lowering of capacity for work and adaptation with
simultaneous mobilization of protective forces.
The new quality is created in
the disease because of quantitative changes into qualitative transition. As a
rule, there are two contrary processes, two phenomenas of disease. One of them
is a damage, and the other is called as a protective response of organism
(which makes the first one perform the physiological measures against the
disease, and the second one – pathological proper or the damage). The two
beginnings of disease exist simultaneously. For example, in case of abscess we
see the limited necrotic tissue area, but we can also see here the leucocytes
emigration, phagocytosis which protect the organism. The treatment is always
directed to damage limitation or removal, that means – to protective reactions
stimulation.
There is about thousand diseases
nowaday. However, their amount changes in course of time. Some diseases
disappear, the other appear. For example, the radiacion disease did not exist
before the X-rays started to be used. The cosmic medicine didn’t exist either
before the cosmic flights began.
The diseases classifications are based on the following criterias:
1. The etiological classification is founded on the cause community for the diseases
group. For example, there are the infectious
and uninfectious diseases. According
to the same principle one can group the diseases caused by an intoxication
(food, professional), genes violations and chromosomal mutations (hereditary
diseases) etc.
2. The topography-anatomic classification is based on the organ
principle: the cardiovasculars diseases, diseases kidneys, diseases
of nervous system etc. It is comfortable for practice. Besides, it corresponds
to the modern specialization of the medical help. It combines with the
classification of the functional systems: blood system, digestive system,
musculosceletal apparatus diseases etc.
3. The age and sex disease classification. There are the children’s diseases, the senile age diseases. The female genitals
diseases are studied by the gynecology.
4. The ecological diseasees classification proceedes from the human dwelling conditions: the air temperature, the atmospheric
pressure, the sun illumination.
5. The classification according to the
pathogeny commonness: allergic
and inflammatory diseasees, neoplasms, shock, hypoxia.
Every disease is the suffering of the
whole organism irrespectively the diffuse organs and tissues damage. At the
same time there are the definite localization and the scantiness of
pathological changes, they are peculiar to the diseases majority.
The
pathological process is
combination of local and general reactions, which arise in organism retaliating
to the morbific agent damaging action. The development of pathological process
depends both on etiological factor
and the organism reactive properties.
There are the destruction (damages) processes combination and the protective
compensational reactions, which arise at different organism levels because of
pathogenic factor influence. The pathological process can develop at the
molecular, cellular, tissue, organ, system levels. If pathological process
envelops the whole organism, that means disturbs its vital functions, then it
turns into disease.
Therefore the pathological process is
not the disease obligatorily, however there isn’t the disease without the
pathological process.
The pathological processes may
be typical, they course identically
with the diverse pathogenic influences, in
different organs and in different organisms.
The examples of typical processes are:
·
inflammation
·
neoplastic
process
·
local blood
circulation disorders
·
hypoxia
·
fever
The
pathological state is the
pathological process, which develops more slowly. Herewith the sickly
violations remain invariable during a long time (years, tenth anniversaries).
Frequently the pathological state is the result of the pathological process.
So, the inflammation of the cornea may turn
into the formation of the leukoma, which preserves for all life.
Total Leukoma
It’s possible to reverse
pathological state transition into
pathological process. For example, the cancer swelling can be formed under the
influence of carcinogenic factors in the place of the afterburning scar.
The
pathological reaction is
inadequate and biologically inexpedient answer of organism or its systems
to usual or excessive irritants
influence. The pathological reaction is destructive element of pathological
process.
There are four periods (stages) of the disease development:
1) the latent (incubation)
2) the prodromal
3) the expressed clinical signs
period
4) the disease ending.
Such division arose up to the
clinical analysis of the acute infectious diseases (a scarlet fever, an
abdominal typhus). The other diseases (cordiovascular and endocrine diseases,
tumours) course another lawfullness.
A.D. Ado distinguishes three
disease development stage:
·
the
beginning
·
the stage
of the disease proper
·
the end
The diseases endings are following:
·
convalescence
( complete and incomplete)
·
recurrence
·
into
chronic form transformation
·
the death
The convalescence is the process, which conduces to the violations liquidation, caused by an disease, and normal relations with the environment restoration, for human beings – foremost the ability to work restoration. The full convalescence is the state when all the disease signs disappear and organism restores its adaptation possibilities completely. When the convalescence is incomplete the disease consequences are expressed. They remain for a long time or forever. The convalescence is provided by the urgent (emergency) and lasting protectively-compensational reactions of the organism.
The
remission is the temporal state improvement of the human being, which is displayed
by the disease progressing slowing down or cessation, the partial reverse development
or the disappearance of the pathological process clinical signs.
The
recurrence is the new disease display
after its seeming or incomplete cessation.
The
complication is secondary as for reference
to the disease pathological process.
The transition in the chronic form signifies that disease courses slowly with the protracted remission
periods ( months and even years). So, many diseases acquire chronic nature in
old age ( chronic pneumonia, chronic
colitis).
The
terminal states are the
boundary ones between life and death.
This is also the dying, which
include a few stages:
·
pre-agony
·
agony
·
clinical
death
·
biological
death
The
pre-agony is characterized by the
diverse duration (during hours, days) of deep violations of the vitally
important organism functions. The dyspnea, the decreasing of the arterial
pressure, the darkening down of the consciousness, which are observed in this
period. Gradually the pre-agony gets across in the agony.
The agony is characterized
by the gradual turning down of all organism functions. The agony lasts 2-4
minutes, sometimes more.
The
clinical death is such
condition when all of the visible sparks of life have already disappeared (the
breathing and the heart work are ceased, however the metabolism still
continues). The life can be restored on this stage.
The
biological death is
characterized by the irreversible changes in the organism.
The reanimation of the organism includes number
of measures which are directed foremost to blood circulation and breathing
renewal:
·
heart massage
·
artificial lungs ventilation
·
heart defibrillation
The
reanimation of the organism
The indirect heart massage is widely used
for the renewal of blood circulation, it can be used at once after the clinical
death setting in any conditions and even not by specialist. The artificial ventilation of the lungs
also must be started as soon as possible. The heart fibrillation is observed in
the terminal period ordinary. In such cases the electric defibrillation is
used. A single digit to 6000 V removes
the fibrillation and promotes the renewal of the blood circulation.
Defibrillation
All of these measures are
directed to renewal of cerebral cortex function. Herewith the respiratory
centre is paramount significant. It is the main pacemaker of cerebral rhythms
and the impulses,which promote the appearance of the electric cortex and the subcortical centres activity, vasomotoral
one also. The renewal of the independent breathing promotes renewal of the blood circulation.
The etiology is the learning
of disease beginning causes and conditions. The notions of
causality and determinism are base of etiology.
A causality reflects an objectively existent phenomenas
connection, when one phenomenon (cause) inevitably causes beginning of the
other phenomenon (result) by the definite conditions. Any disease just like a
phenomenon has its own cause. The beginning and the development of the disease
are not by chance but subordinated to the definite lawfullness.
That factor without the
disease can not arise in any conditions must be a cause of it.
A factor can be a cause if it
exist objectively, irrespective of consciousness, co-operates with the
organism, imparts the specificity of the disease.
If there is the typical
pathological process or the nosological unit, then one can arrive to the
conclusion about existence of many diseases causes. This is so-called principle
of the polyetiology. For example, the lungs fever causes, as the nosological
unit can be viruses, staphylococcus, pneumococcus, funges, radiation, poisons.
However when concrete man’s disease
arises, then the principle of the polyaetiology is incorrect. The assertion “one
disease – one cause” is right solely in these conditions.
The
conditions of the disease beginning are
the different factors combination, where no one is absolutely necessary for its
development. All the conditions are divided into two groups, according to the
disease beginning influence.
1. The conditions which
increasecause action and promote disease development. For example, viruses are
the cause of acute respiratory diseases, and cooling, tiredness,
immunodeficiency are cooperant conditions. Sometimes these conditions can
matter decisive. Without the definite conditions, in spite of cause presence,
the disease does not arise (for example, the food products allergy).
2. The conditions which weaken
the cause action and prevent the disease development. They are the nutrition,
correcting day routine organization,
physical culture, correct care of sick. Sometimes the conditions may
neutralize completely the cause action (for example, the presence of natural or
ecquired immunity to the infectious diseases).
The combination of causes and
conditions, relating to the disease beginning, were named the etiological
factors. They are exogenous (external)
and endogenous (internal).
The exogenous factors are:
·
physical –
mechanical influence, radiation, high and low temperature, electric current,
overloading, zero-gravity and others;
·
chemical –
the inorganic and organic compound;
·
biological – viruses, rickettsias, bacterias, Protozoas, helmints, Arthropodes;
·
psychic – a
word;
·
social –
society development level, traditions and others.
The endogenous factors are:
·
heredity
·
constitution
·
age
·
sex
·
organism reactivity
There are risk factors as a
notion, besides the etiological factors.
The risk
factors are the factors combinations,
the presence of which in people population statistically increases morbidity by
definite diseases. The belonging of these or those conditions to the risk
factors is determined by epidemiological
methods, which envelop the large people contingent. So it was established, that
the violation of blood plasma lipid composition, arterial hypertension, the
age, belonging to male, obesity, hypodynamia, hereditary factors, stress are
the atherosclerosis risk factors.
The pathogeny is the study
about the mechanisms of the development, the course and the end of disease. The
pathogeny studies everything taking place after the cause action.
It is necessary to mention the
following questions in disease pathogeny consideration:
1) the role of etiological
factor in disease development;
2) the organism reactivity
significance for the disease beginning and the course;
3) the significance of the
general and local changes and their
correlation;
4) the basic link of pathogeny
and causally-investigation intercourses;
5) the significance of
functional and morphological changes and their correlation in disease;
6) the significance of nervous
system functional changes for disease development.
There are three variants of connections between a cause and a pathogeny:
1. The etiological factors
play pushing role and turn the pathogeny on. The further cause existence is not
obligatory for course of the pathogeny (burns, radial sickness).
2. The existence of cause and
pathogeny. The pathogeny continues while the etiological factor is active (the
majority of infectious diseases).
3. The persistence of etiological factor. The agents caused the disease stay in organism longer than pathogeny continues. Herewith the properties of etiological factor can interchange under dominance of organism (bacteria carrying after the infectious disease).
The pathogeny of disease
always includes two types of processes and phenomenas. On the one hand it is
damage, destruction, that is properly pathological changes and processes. They
conduce to the violation of homeostasis. On the other hand this is protective,
adaptation reactions and processes. They direct to the remove of homeostasis
violations, creating under the dominance of pathogenic factors and destructive
processes in organism.
The adaptation is suitability
of the organism and its structures to environmental conditions changing, it
provides the preservation of homeostasis and prevents the damage of
environmental factors influence conditions.
The compensation is the state,
which develops as the realization result of the compensatory reactions and
processes, directed to renewal of changed homeostasis along with pathogenic
factors influence. The compensation liquidates the damage consequences.
The base of adaptation and compensation are the same
mechanisms which are named protectively-adaptation or
protectively-compensatory. The distinction between these notions: is adaptation
develops in augmentation of the action intensity of usual factors
environmental. The damage hasn’t happed yet, and the homeostasis indexes are
coming to the extreme norm borders. The compensation develops in the action of
the pathogenic factors when a damage takes place and the homeostasis indexes
are beyond the extreme borders norms.
There are two adaptation and compensation development stages.
1. The stage of immediate
adaptation and compensation. The mobilization of existing mechanisms and
reserves begins and as a result of loading on
functioning system unit increases, its hyperfunction develops.
On this stage the events
develop according to such scheme:
the action of pathogenic
factors ® the violation of homeostasis ® the perception of homeostasis violation ® regulatory centres ® immediate protective reactions (specific and
unspecific) ® the hyperfunction of proper structures, supporting homeostasis.
2. The stage of the long duration adaptation and compensation. The augmentation of systems power, responsible for adaptation and compensation is its base. It is reached by the augmentation of the structures amount, providing a hyperfunction, so hypertrophy develops. The following changes sequence develops on the cellular level. The hyperfunction ® violation of intracellular homeostasis ® activation of genomes ® the augmentation of the proper albumens synthesis ® cell hypertrophy.
The changes in organism which arise during disease development are in definite causally-investigation relations, it means that the same phenomenon of pathogeny is the result of violations and cause of other. Such type of causally-investigation relations when the definite links the pathogeny over violation sequence bring to their heightening over so called “the vicious round”. It supports itself the pathogeny of the disease and redoubles its course. So, in pathogeny of any shock lowering of arterial pressure has big significance that becomes cause of anoxaemia. The cerebral hypoxia brings to the oppression of vasomotor centre and greater lowering of arterial pressure (a circle locked).
The main link of pathogeny is the process which is necessary for a development of all the rest. The liquidation of the main link in time brings to removal of pathological process as a whole. The main principle of pathogenetic diseases cure is founded on it. So, in diabetes mellitus the insulin lack is the main link of pathogeny. Its liquidation (the introduction of hormone) brings to disappearance of other displays ( hyperglycemia, glucosuria, polydipsia, ketonemia, comas).
In pathogeny specific and unspecific processes and mechanisms are always combined. The specific ones depend on the cause properties and determine the basic disease descriptions. A search of the specific signs lays in base of diseases recognition (diagnostics).
The unspecific ones are determined by the genetic organism properties. They are the mechanisms of standard answer of any pathogenic factor. They are directed to reinforcement of the organism resistance to damage and get performed in participation of the nervous and endocrine regulation systems. So nervous and endocrine unspecific mechanisms of pathogeny are picked out.
There are two types of connections between local and general in pathogeny.
1. The local violations develop originally. They can bring to general changes of the organism proper conditions. So, inflammation, neoplasms, burns – are the local violations. However if their expression arrives to definite level they can cause the development of general violations: fever, cachexie, burn disease.
2. The general violations develop originally. They can be displayed by general changes. So, in diabetes mellitus (general disease) the local processes – furuncles, defeats of the joints, nerves, kidneys, eyes retina develop secondary. The general changes of the lipid metabolism in the organism conduce frequently to the development of atherosclerosis that can be displayed by such local defeats as myocardium heart attack, strokes, the gangrene of lower extremity.
The structural changes on different levels (molecular, subcell, cultural and etc.) are in base of any functional violations. It means that there are not clear functional diseases. On the other hand the functional violations may be the cause of structural development changes. So, cells and organs hyperfunction approviatery brings to their hypertrophy (the structural changes).
So, each disease includes the complex
of complicated specific and unspecific,
general and local, morphological and functional changes of the organism.
ACTION
OF CHANGED ATMOSPHERIC PRESSURE UPON
ORGANISM
Reduced
atmospheric pressure. A person meets with it,
while rising the height (climbers, researchers), residing at high-mountainous
areas constantly, and in case of flying apparatus decompression (a plane, a
spacecraft).
Negative influence
of low atmospheric pressure is connected to two factors: low oxygen partial
pressure, inside and outside the organism pressure difference. The first one
causes hypoxic hypoxia, the second one acts like mechanical factor
(decompression). Decompression is connected to such phenomena, as pain in
sinuses (frontal and H³ghmore), murmur in ears, vessels breaks, nasal
bleedings, meteorism. In case of fast decompression alveolar partitions, lung vessels get
injured, then gas embolia and death may appear.
Atmospheric
pressure increase acts upon persons which do diving and
caisson works.
At diving on depth
mechanical influence of a high pressure arise first of all (alveoluses injury,
heavy breathing). Besides, solubility of gases
and their contents in blood and tissues (saturation) gets raisen. Owing
to accumulation of nitrogen, which is easily dissolved in lipids, there comes
infringement of central nervous system functions.
The intoxication
begins from excitation (euphoria), and
is finished by the deep oppression, similar to a narcosis. Toxic influence also
includes the increased oxygen
contents in blood and tissues
(hyperoxia). Oxyhemoglobin dissociation is slowed down, free radicals, which
depress activity of enzymes, are produced.
During getting
risen of the person from the depth and
atmospheric pressure decrease desaturation comes. Nitrogen, oxygen,
carbogen turn from the solution into
gas. Vascular embolism appear, which almost completely consist of nitrogen; as
carbonic gas is quickly deduced, and oxygen is consumed by an organism. Fast
desaturation causes the defeats of organs, where embols are located.
ROLE OF
HEREDITY IN HUMAN PATHOLOGY
Heredity is ability of living beings to recreate them
like, this is property of living individual
to pass for their descendants own
metabolism type.
Structural unit of heredity is gene. It is a molecule area of DNA with specific purine and pyrimidine foundations sequence .
In DNA molecule the genes are situated linearly. Their main and primary function consists of biosynthesis in cell, foremost
albumens – enzymes management .
Gene
In cultural nucleus genes
together with albumens, enzymes, RNA
are packed into special structures,
which are called by chromosomes.
Structure of chromosomes
In healthy man there are 46 chromosomes in somatic
cells, that is 23 pair. 22 pairs of them are called
autosomes and one pair are sexual chromosomes. Such admission is named double (diploid).
Normal kariotypes
In sexual cells a single amount of chromosomes is contained, 23 (gaploid
admission).
A
human X chromosome
Mutations and mutagenes
Major genes property
is their ability to be inherited from
generation to generation in unchanged
appearance. But this stability is not absolute. Sometimes genes are exposed to
accidental changes. These changes are called mutations.
The mutations arise
in sexual and in somatic
cells. Those mutations, which had happened in
sexual cells (if they not lethal), got
passed down to the following generations. They can be displayed in descendants cells, which became by their somatic bearers. Somatic mutation do not pass on legacy. They are displayed only in posterity of proper mutated
cell.
There are three mutation types:
·
genomic
·
chromosomal
·
genic
Genomic mutation consist of chromosomes amount
changes.
Two variants are possible:
à) aneuploidy is separate chromosomes deficit
or surplus (monosomy, trisomic);
b) polyploidy is aliquot augmentation of genome.
A few mechanisms of genome mutations are established. Major of
them is undivergence
of chromosomes. Normally amount of chromosomes in time of
cultural division increases twice in somatic
cells there will be 92 of them, in sexual – 46. In anaphase the sisters
chromosomes must be divided, and go for different poles:
Then a necessary amount of
chromosomes is found 46 and 23 in daughters cells. But there are the cases,
when both danghters chromosome remain
coupled and move away to one pole.
This phenomenon meets frequent during mejosis, that is fission of sexual cells.
The superfluous chromosome hits one gamete and the other one goes without
chromosome. After the fecundation the zygote will perform as trisomia (47),
or monosomia (45). If happened in
somatic cell on early stages of
embrion development, this would bring to mosaicism.
There would be three cell populations presence in such organism – normal (46), trisomia (47) and monosomia (45). Such faces
are named as mosaicisms.
Following mechanism of genome mutations – is anaphase
deficiency.
During the of anaphase moving from
equator down to the pole one of chromosomes gets retarded and lost. One from
daughter gametes gets the normal
amount of chromosomes, and the other one – less.
After the impregnation, zygote can be normal (46), or monosomic (45).
Undivergence of chromosomes Anaphase deficiency
The chromosomal
mutations arise in
those cases, when amount of
chromosomes does not change, but their structure ruines. Each structural chromosome alteration begins with its break. Herewith,
DNA breaks. Sometimes
chromosome fragments endings successfully connect to each other with reparative enzymes.
Chromosome becomes
intact again. But happens so, that the
chromosomes fragments do not connect
at all or unite in break points of other chromosomes. So arise the diverse chromosome violations
types (aberrations, anomalies). It is known more then 30 of them.
More frequent the one can
meet following chromosome variety:
·
deletion – chromosome area loss
Deletion
·
inversion
– two breaks appear in chromosome,
free fragment turns over in 180o and gets combined with
chromosome again;
Inversion
·
translocation – is
fragment
transfer from one chromosome onto the
other, or mutual exchange by fragments.
Translocation
·
duplication
The duplication of a few bases or large regions of a
chromosome
Genic
mutations display in phenotype changes
appearance. Genes chemical structure violation in
DNA takes place (purines and pyraminidins foundations
sequence violation). Genic mutation in somatic
cell can cause tumour development. DNA defect in sexual cell (imperfect gene) gets passed to the
following generations. This brings to
hereditary illnesses appearance.
The mutagens are divided into three groups:
physical
chemical
biological
The major physical mutagens are: ionizing radiation and ultraviolet rays. Ionizing rays may cause all known mutations
types – genomic, chromosomal and genic.
They can be located in sexual, and somatic cells. Among the somatic cells,
the most sensible to radiations are those, which intensively get divided
(bone marrow cells, mucous epithelium, incretion glands cells). The ultraviolet rays calls out genic mutations.
The chemical mutagens are followed with such various mutations, as ionizing rays are. They damage
DNA. This mechanism depends on
chemical mutagens properties.
For example, nitric acid disaminates nitrous bases; nitrous
foundations analogues (5-bromuracil) get included
into the DNA molecule exchanging the normal foundations and cause irregular
coupling during DNA synthesis.
To biological mutagens belong measles viruses,
german measles, hepatitis, retroviruses.
The term “hereditary” illnesses carries a big group of nosologic units, which arise on
a base of genomic and chromosomal
mutations.
Chromosomical
diseases
Down’s illness is described
by English doctor S.Down in 1866 as
variety of mental retardation. Clinical signs: low growth, wide flat face, wide noseband, slanting eyes, parted
lips, fast ears lobes growing, short
extremities
and fingers, specific dermatoglyphic,
sexual undevelopment, mental
retardation.
Child with Downs Syndrome Specific dermatoglyphic
Three illness variants
exist:
·
classic
·
translocative
·
mosaicism based
Classic variant arises as a result of thrisomia
in 21 chromosomes pair, its karyotype is 47,XY(XX)+21. Trisomic is undivergence of 21 chromosomes pair outcome in anaphase.
Illness frequency increases with
mother’s age.
Karyotype
of patient with Down’s illness
Only one sick can be
registered in a family, repeated cases are very rare. The patients with Down’s syndrome are obligatorily sterile. Lifetime of patients is usually
short. Bid amount of children dies till first
year of life ending, the half – up to
third year ending. Remaining alive get
old much earlier, than healthy people do. The patients with Down’s
syndrome 20 times more frequent get ill
with acute leucosis, than people without
syndrome.
Translocational variant – general chromosomes amount
does not change. Illness arises because the fragment of sister’s 21 chromosome gets
carried onto the one of other
chromosomes (13-15 in females and 22 in males). Translocational Down’s syndrome is able to be passed
hereditary.
Another illness variant due to mosaicism is a
result of 21 chromosomes pair undivergence on
elementary stages of embryonic
development. Usually illness clinic
shows the physical defects. The mosaics take 2 % among Down’s syndrome patients.
Klinefelter’s illness was first described in 1942 as
a hypogonadismic syndrome in male. It
frequently takes 1/700 of males. Illness
cause – Õ-chromosome undivergence in mejosis Clinical signs are: high growth, hynecomasty, testicles atrophy, womanish heary type, barrenness, osteoporosis, high pitched voice, debility.
Nucleotype is 47,ÕÕY. Later were found the patients with big amount of Õ-chromosomes. Illness
display in them are more heavy.
Karyotype
of patient with Klinefelter’s illness
However, nonclassic illness variant meets more frequent among
patients, and mosaicism based variant
also. The presence of effaced and rudimentary forms explains this. Kleinfelter’s
illness is not passed hereditary.
So, 11 % of masculine barrenness is related
to this pathology.
Turner’s syndrome
was described in 1938 as hypogonadism
in women. Its frequency is 1/1250.
Clinical symptomcomplex: low growth,
short neck, jugular folder, short thick legs,
short fingers, wide hands, and physical defects: pulmonary artery and aorta
stenosis, interventricular septum
anovergrowning, arterial hypertensia,
undeveloped sexual glands, amenorrhea, mammary glands unpresence,
infantilism. Intellect suffers very little. Therefore diagnosis is established not attached to birth and child age, but much later,
when growth retardation and sexual infantilism is noticed.
Turner’s syndrome
Illness genome is 45, ÕÎ. This is
Õ-chromosomes undivergence result in mejosis
process. In one case arises
Õ-trisomic,
in other – Õ-monosomic (Turner’s syndrome).
Is possible also illness development at anaphasic lagging and chromosome losses
background. Part of Turner’s syndrome patients are mosaicists. Illness
does not pass hereditary. The
patients are sterile.
Õ-threesomic syndrome arises with frequency of 1/1000
in women. Standard genome is 47, ÕÕÕ, but genoms
of 48, ÕÕÕÕ and more are known. Clinical displays are:
infantilism, amenorea, skin depigmentation, hair depigmentation, mental undeveloped, frequent schisophrenia combination. The more Õ-chromosomes are in presence, the stronger infantilism and debility are expressed.
Causes of illness are Õ-chromosome
undivergence in mejosis or in
early zygote division stages. The
reasons of this can be old mother’s age,
alcoholism, syphilis. In
separate families illness is inherited. Such mother can have normal
posterity, and Õ-trisomy posterity also.
Syndrome of catlike cry – is an example of well studied delecic syndrome. Kariotipe is 46, del 5ð-.
Such children cry reminds of
cat miaow. Syndrome signs are: microcephalia,
larynx undevelopement, slanting eyes cut, ear conchas deformation, muscular hypotonia, hypogonadism,
mental backwardness.
Hereditary
molecular diseases
During last 50 years the genetic blocks are exposed , which
disturb an enzymes synthesis and
metabolism. Due to these violations genic illness arise. Enzymes defects, which relate to amino acids transformation
are studied the best.
Phenylketonuria
was described by Felling in 1934. The children are born externally
healthy and normally reseive up the weight. In second year half they begin to
fall behind in the psychic development. Then
other symptoms appear: physical
undevelopment, teeth growing delay,
speech delay, cramp, paralyses, dermatitis, tow-heads, blue eyes.
Phenylketonuria is
comparative rare disease (1/20000 of
new-borns). Its pathogenesis is well reputed. In
human organism phenylalanine transforms into tyrosine with the help
of phenylalaninhydroxylaze, and into melanyn,
thyroxine, adrenalin after that. Attached
to enzyme lack phenylalanine can not
get transform into tyrosine.
Pathogenesis of phenylketonuria
It
accumulates in tissues and transforms into phenylpyruvic and phenylacetic
acids. The phenylalanine and both ketoacids are very toxic for cerebrum in its
forming stage. They prevent to amino acids penetration in neurons. Cultural albumens and mediators synthesis is lower.
As a result, mental backwardness develops. Melanine,
adrenalin and thyroxine production diminishes
also. Therefore patients have
light hairs, blue eyes and arterial hypotension.
Phenylketonuria
Illness inherits due to autosomic-recessive
type. Gene locates in 12 chromosome.
Albinism develops in case of melanine pigment lack. There are generalized
and local forms (eyes).
Albinism caused by the lack of tyrosinasa,
which converts tyrosine into melanine.
Illness inherits in autosomic-recessive way. Frequency is
1/20000, in Panama american indians it
is 1/132.
Clinical symptoms of albinism
Alkaptonuria described by Bedecker in 1859, dechiphered by Garrod in 1902. In this case
a tyrosine exchange get blocked in homogenteuzive
acid into maleinacetative acid transformation
stage. The reason is in hereditary homogenteuzive
acid oxydaza enzyme deficit. This acid
exudes with urine. Urine becomes
dark. Homogenteuzive
acid in tissues deposit painting them in gray colour (ochronosis).
Diagnostics methods of
hereditary diseases
The essence of the cytogenetical method consists of chromosome admission, separate chromosomes structure, sexual chromatine, drumsticks peculiarities
research. Lymphocytes and cheek
epithelium cells serve as research
objects. By this method chromosomal diseases are diagnosed.
Genealogical method consists of hereditary man properties with the own genealogy study. Method allows to define an illness
inheritance type. There are three basic inheritance types:
·
autosomic-dominative
·
autosomic-recessive
·
Õ-chromosome connected
Autosomic-dominative is such an inheritance type,
when illness is inherited straight from parents to children. Dominative gene displays itself phenotypically and
in homozygote,
and in heterozygote. In patients, homozygote
is on dominative gene, illness courses much more heavy, than in heterozygotes.
With autosomic-dominative type the
physical defects are inherited (syndactyly,
myopia, astigmatism, lack of lateral chisels, achondroplastic
dwarf), and Hentington’s chorea, Reklinhausen’s neurofibromatosis, thick intestine poliposis, inherited cataract, otosclerosis, hemeralopia. There are illnesses, when a dominative gene displays
only in part of persons, which it belongs
to. Percent of persons, in which a dominative gene appears as illness,
is called penetrantion. Very low penetrantion, for example, arises in polidactylia.
Autosomic-dominative
types
Autosomic-recessive inheritance differs, illness
is inherited not straightly from
parents to children, but over a few generations (with omissions). Illness appears
only in homozygotes and more frequent
is related to marriages. With this
type albinism, phenilketonuria, alkaptonuria, innate deaf-mute, fructosuria,
pigmental retinit, syndrome of Fankoni, cretinism, hypophysis nanizm get inherited.
Autosomic-recessive
type
Õ-coupled inheritance has a place in
case, when a pathological gene is situated
in Õ-chromosome.
Transmissional illness, as
regulations, is recessive. On such
type hemophilia A and B, color-blindness, youthful glaucoma, agammaglobulinemia of Bruton, Vyskote-Oldrych’s syndrom, atrophy of the
visual nerves of Leber gets inherited.
Sometimes illneses, which coupled with
Õ-chromosome, is inherited as a dominantes.
Examples are hypophosphatemical
rachitis, follicular hyperkeratosis.
X-linked recessive type X-linked dominant type
Twins method – one of main genetic
methods.
It
allows to differentiate the role of heredity and external environment in
some diseases beginning. For this
double morbidity (concordance) of monovular and diovular
twins are learned. If it is high in monovular twins,
that means – illness has a hereditary base. If illness due to exogenous causes (microbes, chemical matters, physical factors), concordantion identical in both twins
types.
Population-statistical method is the determination and illness appearance frequency comparison in separate families and in population
at all. Hereditary illnesses bear families nature. In separate families thir frequency is more, than in population.
Biochemical method studies the metabolic
disturbances of hereditary origin.
Biochemical method of phenylketonuria diagnostics
Dermatogliphycal method consists of analysis of
hereditary conditioned hands skin drawings,
fingers tips.
Dermatogliphyc picture of patients with Down’s illness
Hereditary illnesses prophylaxy and treatment principles
Prophylaxy of hereditary illnesses consist of such points:
à)
warning of physical and chemical mutagens
action upon the human genes
pool;
b)
warning of undesirable procreation, amniocyntesis
is established serious genetic defect in children;
c) explaining work about closerelative marriages undesirability;
d)
recommendations relating to children birth
in mother’s young age.
In the past they thought, that hereditary signs can not get corrected, impossible to treat hereditary illnesses. These conceptions are erroneous.
Genic engineering (genic therapy) is very perspective method. It is fully based on
achievements of contemporary molecular biology and includes a few original takings.
1.
Induction of specific mutations, in other words directed mutagenesis.
Some chemical substances electorally attack the definite foundations in DNA
and are followed with pointly
mutations. Mutagenesis activity of these matters can be
medically used, in DNA damages repair way.
2. Genes transfer. The very reputed example is – genes transfer
from intestinal wand (Å. ñoli) into human
fibroblasts. It was displayed in man and intestinal wand – that galactouse metabolism performed by the medium of identical enzymes. In human there is a
reputed hereditary illness – galactosemia. The cause is galactosa enzymes metabolism deficit. An idea appeared – to carry gene, which encodes synthesis of this
enzymes, from intestinal wand into the
man’s cells. Incubation was successful. Man fibroblasts burst out synthesize necessary enzyme.
3. Creation of artificial
genes, which with the help of restrictase can be inculcated into any gene.
Deputive therapy.
Classic example – cure of hemophilia À.
Such sick bring factor V²²²
concentrate into their blood.
Metabolit
removal before the blocked stage. Method
essence is in purging out of food the matters, which can not be assimilated with the organism. Successful
correction of such type was realizable attached to phenylketonuria cure for the first time (Bikkel et al., 1953). Nutrition with big phenylalanine
maintenance is exchanged with this irreplaceable amino acid hydrolisates minimal maintenance. Diet therapy begins in first life weeks under phenylalanine
in blood level control. Cure duration
is up to 5-10 years. Analogous therapy (up to 3 years) is attached to galactosemia.
The milk is purged out of food (galactose)
and replaced with galactoseless mixtures.
Metabolit
compensation
after the blocked stage. Therapy of such type widely attached to hormones synthesis
violations. For example, attached to
cretinism the thyroid hormones – thyroxine, triiodthyronine
are injected.
Physical deffects
removing. The majority of hereditary illnesses get treated with this method. This
approach does not need an exact knowledge of genetic and pathophysiologicals development mechanisms.
For example, we know nothing about biochemical bases of polydactylia, harelip or lupine pasture. However these illnesses get successfully surgically
treated.