Download Methodological Instruction to Practical Lesson № 3

MINISTRY OF PUBLIC HEALTH OF UKRAINE
BUKOVINIAN STATE MEDICAL UNIVERSITY
Approval on methodological meeting
of the department of pathophisiology
Protocol №
Chief of department of the pathophysiology,
professor
Yu.Ye.Rohovyy
“___” ___________ 2008 year.
Methodological Instruction
to Practical Lesson
Мodule 2 : PATHOPHYSIOLOGY OF THE ORGANS AND SYSTEMS.
Contenting module 4. Pathophysiology of blood system.
Theme 3: Leucocytosis and leucopenia
Chernivtsi – 2008
1.Actuality of the theme. Leucocytosis are considered as a reaction
hematopoietic system due to action of physiological and pathological irritations.
Leucocytosis is a pathological symptom of many diseases. In a basis of
leucocytosis lay pathophysiological mechanisms connected with proliferation,
maturation going out of leucocytes and their flow into vessels and redestribution.
Different kinds of leucocytosis may be the additional criteri for establish the
diagnosis. Eosinophilia, for example, is characterized for allergy reactions,
neutrophile leucocytosis - for acute inflamation processes.
Leucopenia may depend upon oppressive influence of some toxines on the
maturation and outflow of leucocytes from the bone-marrow. Often these
phenomenas are observed during the infectious diseases. They have significanse
for the differential diagnostic. If for the disease is characterised leucocytosis, the
availability of leucopenia testifies on depression of hemopoietic system. It is
regarded as a criteri weakenes of reactivity of the body on action of pathological
factors.Directness and character of changes of white blood cells due to various
diseases - significant for the diagnosis and control of the treatment.
2.Length of the employment – 2 hours.
3.Aim:
To khow: types of the left nuclear deviation.
To be able: to analyse of the quantitative and qualitative changes of
leucocytes in blood.
To perform practical work: to analyse of the pathogenesis of the
quantitative and qualitative changes of leucocytes in blood. The increase of
leucocyte quantity is called leucocytosis, and the decrease-leucopenia. The norm
is 4-9G/l or 4-9*109/l. The quantitative changes are increased quantity of immature
forms in blood and degeneration of leucocytes.
4. Basic level.
The name of the previous disciplines
1.
histology
2.
biochemistry
3.
physiology
The receiving of the skills
Scheme of leucopoesis.
Leucocytes formula of blood.
Function of leucocytes.
Methods of counting of leucocytes
maintenance in blood.
5. The advices for students.
1. Leucocytosis. Leucocytosis –is the increase of total leucocyte quantity in
blood – over 9G/l (9/109/l).
2.Classification of leucocytosis. Absolute leucocytosis is the increase of
leucocyte number in blood, caused by the increased production of leucocytes of
reactive of reactive or tumor character in the organs or their increased coming from
the bone marrow depot into the blood vessels. Relative leucocytosis –is the
increase of leucocyte number in blood caused by their redistribution from the
parietal pool into circulating one or their accumulation in the focus of
inflammation. Leucocytosis is divided into neutrophilosis, eosinophilosis,
basophilosis, lymphocytosis and monocytosis, depending on the type of
leucocytes being increased.
3. Etiology of the leukocytosis. The causes of neutrophilosis are various.
They are infectious factors (strepto- and staphylococci, fungi), the products of
tissue malignant tumours in myocardial infarction, hemolysis, disintegration toxic
metabolites in uremia, hepatic coma, physical factors (cold, heat), chronic
myeloleucosis and psychical factors (fear, fury). Eosinophilia is observed in
allergic and parasitical diseases, chronic myeloleucosis. Basophilia is caused by
ulcerative colitis, chronic myeloleucosis after splenectomy and myxedema. Some
viruses (infectious mononucleosis, hepatitis, measles) microorganisms (causative
agents of whooping cough, tuberculosis and syphilis), chronic lympholeucosis
provoke lymphocytosis. Monocytosis develops under the influence of viruses,
microorganisms, protozoa, specific endocarditis.
4.The mechanisms of leucocytosis. There are the following mechanisms of
leucocytosis:
1. The increase of leucocyte production in the bone marrow.
2. The acceleration of leucocyte entrance from the bone marrow into blood,
as a result of increased permeability of the bone marrow.
3. The redistribution of leucocytes to the circulating blood or to the focus of
inflammation.
Usually, leucocytosis is accompanied by the disturbance of maturation in
the bone marrow and the production of pathologic forms. Reactive hyperplasia of
the leucocytic tissue leads to the increase of the organism resistance. Neutrophilic
leucocytosis and monocytosis have parallel increase of the phagocytic activity of
leucocytes. Eosinophiles play a compensatory role in allergic reactions due to
antihistamine function of eosinophilic granulocytes. But, leucocytosis during
leukemia may life be accompanied by immunological hyporesistance. The
organism gets auto- and secondary infection.
5.Blood picture under the leukocytosis. The increase of total number of
leucocytes is accompanied by the change of leucocyte formula (of separate forms
of leucocytes in per cent, by counting 200 cells in the stained blood smear).
Absolute or relative character of these changes is established with counting
absolute amount of different forms of granulo- and agranulocytes in one litre. The
count is made on the basis of total amount of leucocytes in one litre of blood and
leucocytic formula. So, absolute neutrophile leucocytosis in purulent inflammatory
diseases is accompanied by decrease of the amount of leucocytes in percent in the
leucocytic formula (relative lymphopenia). However the count of absolute quantity
of lymphocytes on the back-ground of general leucocytosis allows establishing
absence of inhibition of lymphocytic stem.
In leucocytosis, especially neutrophilic one, immature cells not infrequently appear
in blood. A great number of generatively altered leucocytes in leucocytosis is noted
in blood in sepsis, purulent processes, infectious diseases, disintegration of
malignant tumor.
6. Leucopenia. Leucopenia –is the decrease of total leucocyte number in
blood –below 4G/l (4*109).
7.Classification of the leukopenia. There are absolute and relative
leucopenias. Depending on the type of leucocytes, there are neutropenia,
eosinopenia, lymphopenia and monocytopenia.
8.Etiology of the leukopenia. Neutropenia is caused by infectious gripe
viruses, measles, enteric fever toxin, rickettsia of typhus, physical factors (ionizing
radiation), medicines (sulfanilamides, barbiturates, cytostaties), benzol, the
deficiency of vitamin B12, folic acid, anaphylactic shock, hypersplenism, genetic
defects of neutrophile production and differentiation. Eosinophilia is observed in
the increase production of stress, Itsenco-Cushing disease, corticosteroids,
infectious diseases, introduction of corticotrophin and cortisone. Lymphopenia
develops under the influence of hereditary and acquired immunodeficiency, stress,
radiation disease, military tuberculosis, myxedema. Monocytopenia is found in all
syndromes and diseases, connected with the depressed myeloid stem shot of the
bone marrow hemopoiesis (for example, in radiation disease, severe septic
conditions, and agranulocytosis).
9.Pathogenesis of the leukopenia. The following mechanisms are in the
basis of leucopenia:
1. The decrease of leucocyte production in the hemopoietic tissue.
2. The disturbance of leucocytes entrance into blood.
3. Their destruction in blood and hemopoietic tissue.
4. Redistribution of leucocytes in the vessels.
5. The increase discharge of leucocytes from the organism.
The defect of the tissue membrane, leads to the decrease of leucocyte bile
ability. It is called the syndrome of “lasy leucocytes”. As a result, the granulocytes
come into blood from the bone marrow very slowly. The increased destruction of
leucocytes may be caused by the change of their physico-chemical features and
permeability of leucocyte membranes due to ineffective leucopoiesis. It leads to
increased lysis of leucocytes, including spleen macrophages, and by the action of
the same pathogenic factors provoking cell destruction in the hemopoietic organs.
The redistribution of leucocytes is observed in hemotransfusional shock,
inflammatory diseases, in altered ratio between the circulating and parietal pools of
leucocytes. Sometimes, leucopenia may be conditioned by the increased discharge
of
leucocytes
from
the
organism
(in
purulent
endometritis,
cholecystoangiocholitis). The main consequence of leucopenia is the decrease of
the organism resistance caused by reduction of phagocytic activity of neutrophile
granulocytes and lymphocyte function of antibody formation not only due to
reduction of their total quantity but also due to possible combination of leucopenia
with production of functionally inferior leucocytes. Such patients often suffer from
different infectious and tumor diseases, especially in hereditary neutropenias
deficiency of T- and B-lymphocytes. The examples of severe areactivity are AIDS
of viral and radiation origin as well as agranulocytosis and alimentary-toxic
aleukia. It is caused by different medicines, radiation and some infections.
10. Aleukia – is an aplastic damage of the bone marrow, accompanied by
the sharp inhibition of total stopping of leucocyte production. Alimentary-toxic
form develops in eating grains, infected by mould. Usually, we can observe
pancytopenia in such cases –a sharp decrease of leucocytes (aleukia) and
thrombocytes (thrombocytopenia). However, we can observe some compensatory
reactions, manifested as the reactions of some stems of leucocytes, when the other
ones are inhibited. For example, neutropenia may be accompanied by
compensatory increase if production of monocytes, macrophages, eosinophiles,
plasmatic cells. It decreased as a little the severity of clinical manifestations. The
disturbance of correlation between mature and immature of leucocytes in blood.
The appearance of immature forms of leucocytes in blood is conditioned by the
disturbance of their maturation in the hemopoietic tissue and the increase of the
bone marrow permeability. These changes are usually on the background of
increased leucopoiesis due to reactive and tumor hyperplasia of the leucopoietic
tissue. If there is predominance of mature, segmentocellular cells, cells of the
granulocyte kind (first of all neutrophile granulocytes) and there are no stab
neutrophiles and metamyelocytes, such hematological picture is connected with
inhibition of the bone marrow hemopoiesis. If there are a lot of mature leucocytes
and no young forms, the bone marrow hemopoiesis is depressed.
11. Blood picture under aleukia. We must find out if there is a right or left
nuclear deviation of the neutrophile granulocytes. Immature of Shillings forms of
leucocytes (myelocytes, metamyelocytes, stab neutrophile granulocytes) are placed
in the left part of the leucocyte formula, the mature ones (segmentonuclear
neutrophile granulocytes) in the right part. The increase of the young neutrophiles
in blood is evidence of the left nuclear deviation. The prevalence of the mature
forms (5-6 segments) on the background of absence of young cells is evidence of
the right nuclear deviation.
There are the following types of the left nuclear deviation:
1. Regenerative one indicative of reactive activation of leucopoiesis.
2. Hyperregenerative deviation-reflects an excessive hyperplasia of the
hemopoietic tissue. Them maturation is broken. There are may immature forms in
blood. The number of stab neutrophile granulocytes and metamyelocytes increases
sharply. Myelocytes and promyelocytes appears the total number of leucocytes
may be increased, unchanging and even decrease due to exhaustion of the myeloid
stem after preceding activation.
3. Degenerative of deep disturbances and inhibition of leucocyte production.
On the background of general leucopenia here are many stab neutrophile
granulocytes with degenerative range and no metamyelocytes and nucleus with
decreased number of the segmentonuclear forms in blood.
4. Regenerative-degenerative deviation. It is observed in hyperproduction of
the pathologically changed leucocytes in the bone marrow and their immaturation.
In this case there is leucocytes and the number of stub neutrophile granulocytes,
metamyelocytes and myelocytes with signs of degeneration increases in the blood
smear.
A sharp increase of the immature forms is typical for the leukaemoid
reaction. Blood picture is close to leukemia but is differs by (the cause is often
known-infection, malignant tumors, acute hemolysis etc.) etiology and
pathogenesis (reactive hyperplasia of the leucopoietic tissue). This reaction is
temporary, reversible and doesn’t change into leukemia. There are some types of
leukaemoid reaction, they are: myeloid neutrophiles, eosinophiles, monocytes and
lymphoid ones (in sepsis cancer metastases into the bone marrow myeloid
reactions in infectious lymphocytosis and mononucleosis-lymphoid type
leukaemoid reactions).
The right nuclear deviations is evident of the depression of leucocyte
production in leucopenia (radiation disease, B12 and folic acid deficiency anemia).
The right nuclear deviation is observed in 20% of healthy people.
12. Leucocyte degeneration in blood. They are: unisocytosis vacuoles in
cytoplasm, toxigenic granules, the appearance of inclusions in cytoplasm such as
Cnyazcov-Dele’s bodies basophilically stained small bundle of cytoplasm and
others, the presence of large asurophilic granulation and absence of the normal
one, the swelling of the nucleus, its hypo- and hypersegmentation, different degree
of mutation of the nucleus and cytoplasm, cytolysis. Degenerative changes are
most frequently observed in neutrophile granulocytes and monocytes. The causes
are the disturbance in leucocyte metabolism, which to structural anomalies (in
leucosis and hereditary enzymopathy), and the damage of leucocytes in the
hemopoietic organs and blood under the influence of different pathologic factors
(bacteria, viruses and antibodies).
5.1. Content of the theme. What is leukocytosis? Classification of the
leukocytosis. Etiology of the leukocytosis. The mechanisms of leucocytosis. Blood
picture under the leukocytosis. What is leukopenia? Classification of the
leukopenia. Etiology of the leukopenia. The mechanisms of leucopenia. What is
aleukia ? Blood picture under the leukopenia. Leucocyte degeneration in blood.
5.2. Control questions of the theme:
1.What is leukocytosis?
2.Classification of the leukocytosis.
3.Etiology of the leukocytosis.
4.The mechanisms of leucocytosis.
5.Blood picture under the leukocytosis.
6.What is leukopenia?
7.Classification of the leukopenia.
8.Etiology of the leukopenia.
9.The mechanisms of leucopenia.
10.What is aleukia ?
11.Blood picture under the leukopenia.
12.Leucocyte degeneration in blood.
5.3. Practice Examination.
Task 1. During the medical examination of a boy 5 years old were founded the
significant increase of eosinophiles in the blood. What from mentioned
below can be the cause of eosinophilia?
A. Helminthiasis B. Obesity C. Hypodynamia D. Hypotermia
E. Physical strain
Task 2. In the liquidator of consequences of failure in Chornobil atomic power
station, which has received dose of ionising radiation 5 Gr, after one week
during the blood examination leucopenia is revealed. Which pathogenetic
mechanism is main in occurrence it?
A . Emigration of leucocytes from vessels in tissues B. Excessive
destruction of leucocytes in blood C. Depression of leucopoiesis in bonemarrow D. Delay of go out the leucocytes from bone-marrow
E. Appearance autoantibodies against leucocytes
Task 3. In different diseases due to activation of leucopoiesis occurs not only
increase of number of leucocytes, but also appearance in blood of the
young forms. Hyperregenerative nuclear shift to the left is expressed for.
A. Pneumonic fever B. Acute appendicitis C. Leukemoid reaction
D. Disintegration of tumor
C. Abscess of lung
Task 4. The patient suffering for a long time of bronchial asthma. What changes of
cellular structure of blood are characterized for this illness?
A. Neutrophilousis B. Lymphocytosis C. Monocytosis D. Basophilia
E. Eosinophilia
Task 5. The patient with systemic red lupus was treated for a long time with
glucocorticoids. From his blood is expect:
A. Lymphocytosis B. Neutrophilousis C. Eosinophilia D. Monocytopenia
E. Eosinopenia
Real-life situations to be solved:
Amount of Baso- Eosinoleucocytes philes philes
Task1
12,0∙109/l
Task 2
18,3∙109/l
Task 3
1,35∙109/l
Task 4
11,4∙109/l
Myelocytes
Neutrophiles
LymMetaStab- Segmen- phocytes
myelo- nucleo- tonuccytes
nic
leonic
Monocytes
1%
2%
-
1%
15 %
57 %
20 %
4%
1%
3%
Single
3%
38 %
48 %
4%
3%
0,5 %
1,5 %
-
-
4%
17 %
65 %
12 %
2%
16 %
-
-
1%
55 %
24 %
2%
Control questions
1. Analyze above mentioned leucocytes formulas and indicate, what changes of
total leukocytes and separate forms are present in each of them.
2. What pathological processes and diseases ites are characteristed for? Give
examples.
Literature:
1. Gozhenko A.I., Makulkin R.F., Gurcalova I.P. at al. General and clinical
pathophysiology/ Workbook for medical students and practitioners.-Odessa, 2001.
2. Gozhenko A.I., Gurcalova I.P. General and clinical pathophysiology/ Study
guide for medical students and practitioners.-Odessa, 2003.
3. Robbins Pathologic basis of disease.-6th ed./Ramzi S.Cotnar, Vinay Kumar,
Tucker Collins.-Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.-1999.