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 1: ANEMIA. QUANTITATIVE CHANGES OF ERYTHROCYTES
AND HEMOGLOBIN
Chernivtsi – 2008
1.Actuality of the theme. Anemia appear on the base of various diseases,
intoxycations, bloodloss. Therefore clinicists of various specialities often find them
in the practical activity. The quantitative changes erythrocytes and hemoglobin
are one of the most important parameters, on the basis of which diagnostics of
anemia is carried out. On changes of these parameters also judge about the
efficiency of treatment. Using the quantitative characteristics of erythrocytes and
hemoglobin, it is possible to define one more clinicaly important parameter colour index. Basing on a colour index one can judge about the saturation of
erythrocytes by hemoglobin. The value of a colour index (norm, decrease,
increase) has diagnostic mean.
2.Length of the employment – 2 hours.
3.Aim:
To khow: anemia is a hematologic syndrome or independent disease
characterized by reduction of erythrocytes and changes of the qualitative
composition of red blood cells.
To be able: to analyse of the pathogenesis of the posthemorrhagic anemia.
To perform practical work: to analyse of the Classification of the anemias:
By etiology: anemia due to the blood loss (post hemorrhagic);
anemia due to increased blood destruction (hemolytic);
anemia due to disturbance of erythropoiesis.
By type of hemopoiesis: anemia with erythroblast type of hematogenesis;
anemia with megaloblast type of hematogenesis.
By abilities of the bone marrow to regenerate:
regenerative;
hyperregenerative;
hyporegenerative;
aregenerative.
By color index: - normochromic (CI=0.85-1.15);
hyperchromic (CI < 1.15);
hyperchromic (CI > 1.15)
By size of erythrocytes: normocytic (average size 7.2 mcm), microcytic
(< 6.5mcm), macrocytic (> 8mcm)
By clinical course: acute, chronic.
4. Basic level.
The name of the previous disciplines The receiving of the skills
1.
histology
Scheme of erythropoiesis.
2.
biochemistry
Quantitative parameters of red blood.
3.
physiology
Technique of erythrocytes account.
Technique of determination of the
hemoglobin content.
Technique of determination of a colour
index.
5. The advices for students.
1. Anemia, definition of concept, hematological indexes.
The anemia is decrease of erythrocytes amount and hemoglobin
maintenances in unit of blood volume which is accompanied by qualitative
changes of erythrocytes.
Hematological attributes of anemias are subdivided on quantitative and
qualitative.
The quantitative displays include:
1) reduction of the maintenance of erythrocytes in unit of blood volume – in
men is lower than 4×1012, in women is lower than 3,5×1012 in 1L of blood;
2) reduction of hemoglobin concentration – in men is lower than 130 g/l, in
women is lower than 120 g/l;
3) reduction of hematocrit – in men is lower than 0,43 l/l, in women is lower
than 0,40 l/l;
4) change of a color index – is not lower than0,85 and not higher than 1,15.
Qualitative attributes of anemias are presence in blood of:
1) regenerative, but not mature forms of erythrocytes;
2) degenerative changes of erythrocytes;
3) cells of pathological regeneration.
2. Regenerative forms of erythrocytes. (cells of physiological regeneration)
are young immature cells of red blood sprout appearance of which in peripheral
blood testifies to amplification of regeneration of cells erythroid lines in red bone
marrow or increase of medullar barrier permeability.
Regenerative forms include:
а) reticulocytes. They are found in smear of blood after supravital staining.
Represent denuclearized cells dirty – staining colouring with black inclusions as
granules (substantia granulofilamentosa). In norm their contents in blood is 0,2-2
%. At the strengthened regeneration of cells red sproud blood their quantity may
increase to 50 %.
b) polychromatophils. They are found in blood smear colored as in the
method bu Romanovsky-Gimza. They are denuclearized cells cytoplasm of which
shows property to perceive both acid, and the basic dye-stuffs. Therefore
polychromatophils different from mature erythrocytes by cyanotic shade of the
colouring. In essence reticulocytes and polychromatophils are cells of an identical
degree of maturity – direct predecessors of erythrocytes. Different names are
connected with their different properties which come to light at different ways of
staining.
c) normocytes (basophilic, acidophilic, polychromatophilic). They are nuclear
predecessors of erythrocytes. In norm its absent in peripheral blood, and contain
only in a red bone marrow. At the intensification of regeneration of cells erythroid
lines they may occur in blood as acidophilic and polychromatophilic rarely as
basophilic normocytes. Sometimes,
erythroblasts can be found in blood
(predecessors of normocytes) during hyperregenerative anemias.
Changes of erythrocytes, which testify about inferiority of these cells, named
degenerative. Such changes are characterized by the following phenomena:
а) anisocytosis – change in the size of the erythrocytes. Occurrence of macrocytes
and microcytes;
b) poikilocytosis – change in the form of the erythrocytes. In conditions of a
pathology may occur pear-shaped, extended, sickle-cell, oval erythrocytes, and
also erythrocytes with the spherical form (spherocytes);
c) change in the staining of the erythrocytes, that depends on the contents of
hemoglobin in them. Erythrocytes, intensively colored, are named
hyperchromatic, with pale staining – hypochromatic.
d) presence of pathological inclusions. They include Jolly’s bodies – are the rests
of nuclear substance; Cabot’s rings – the rests of nuclear environment having
the form of ring or eight; basophilic granularity – the rests basophilic
substances of cytoplasm significative of toxic defeat of red bone marrow.
Cells of pathological regeneration occur when there is changed of
erythropoesis from erythroblastic to megaloblastic:
а) megaloblasts are big cells with basophilic, polychromatophilic or acidophilic
cytoplasm, containing large, located usually eccentrically nucleus with soft
chromatin grid;
b) megalocytes – denuclearized cells which are formed during maturing of
megaloblasts. They usually intensively stained, some the oval form, non an
brighten up in the central part.
Occurrence of the specified cells in red bone marrow and blood is typical for
megaloblastic anemias, in particular of the B12-deficiency anemia.
3. Classifications of anemias.
І. According to color index:
а) normochromic (the color index is within the limits of 0,85-1; for example,
acute posthemorrhagic anemia during first days after hemorrhage);
b) hypochromic (the color index is lower than 0,85; for example, irondeficiency
anemia);
c) hyperchromic (the color index is higher than 1,0; for example, B 12-deficiency
anemia).
ІІ. Pathogenetic classification:
А. Posthemorrhagic anemias: a)acute posthemorrhagic anemia; b) chronic
posthemorrhagic anemia.
B. Hemolytic anemias.
1. Acquired: а) toxic-hemolytic; b) immune; c) mechanical; d) acquired
membrane pathy.
2. Hereditary: а) hereditary membrane pathy; b) enzymopathy;
c) hemoglobinopathy.
C. Anemias as a result of erythropoiesis disorders.
1. Deficient: а) irondeficient; b) B12-deficient; c) proteindeficient.
2. Hypo-, aplastic.
3. Metaplastic.
4. Dysregulative.
Posthemorrhagic anemia is an anemia which develops as a result of
hemorrhage. There are two types of anemias of this group according to the character
of hemorrhage: 1) acute posthemorrhagic and 2) chronic posthemorrhagic anemia.
4. Acute posthemorrhagic anemia arises after fast massive hemorrhage as a
result wounding of vessels or their damage by pathological process.
Chronic posthemorrhagic anemia develops after repeated hemorrhages,
caused by injury of blood vessels during number diseases (dysmenorrhea, ulcer of
stomach, hemorrhoids etc.)
The picture of blood of acute posthemorrhagic anemias depends on time
which has passed after hemorrhage. Depending on it it is possible pick out three
periods, each of them is characterized by the certain picture of peripheral blood.
1. The first several hours after acute hemorrhage. At this period of time the
total amount of blood, and also total number of erythrocytes in an organism
decreases. However in unit of blood volume the contents of erythrocytes and
concentration of hemoglobin do not vary.
2. The period of time from several hours untill several days after acute
hemorrhage. Dillution of blood takes place as a result of transition of liquid from
interstitial spaces into blood vessels. As a result of it the quantity of erythrocytes
and hemoglobin in unit of volume of blood decreases, as well as hematocrit. A color
index stays without changes (normochromic anemia). Qualitative changes of
erythrocytes in blood smear are not found yet.
3. The period of time from several days untill 1-2 weeks after acute
hemorrhage. The most typical feature of picture of blood in this period is
occurrence of plenty regenerative forms of erythrocytes, due to amplification of
erythropoiesis in red bone marrow. Because young unripe erythrocytes contain less
hemoglobin in comparison with mature cells, the color index decreases also and
anemia becomes hypochromic.
5. During chronic posthemorrhagic anemia after the loss of iron
hematologic attributes of irondeficiency anemia develop: concentration of
hemoglobin and color index decrease, in blood smear there are degenerate forms of
erythrocytes (micro- and poikilocytosis, hypochromy). Quantity of erythrocytes and
hematocrit may remain without changes.
6. Irondeficiency anemia arises as a result of:
1) Insufficient receipt of iron with organism: а) an alimentary anemia in the
infants (feeding with cow or goat milk); b) disorder of iron absorbtion
(resection of stomach, intestines, gastritises, enteritis);
2) Hemorrhage. It is the most widespread reason of iron deficiency in
organism;
3) Strengthened use of iron – pregnancy, lactation.
Insufficiency of iron in organism results in disorder of ferriferous proteins
synthesis and consequently to the following disorders: 1) disorder
of heme
synthesis, 2) disorder of cytochromes formation and tissue hypoxia, 3) decrease of
catalase activity hemolysis of erythrocytes and development of dystrophic changes
in cells, 4) reduction of synthesis myoglobin and decrease(reduction) of resistance
to hypoxia.
Decrease of hemoglobin concentration in peripheral blood and reduction of
color index are typical for iron deficiency anemia. The quantity of erythrocytes
decreases a little.
In blood smear the quantity regenerative forms of erythrocytes (reticulocytes,
polychromatophils) decreases and their degenerative forms (anulocytes,
microcytosis, poikilocytosis).
7. B12-(folate)deficiency anemia. The reasons of vitamin B12 insufficiency in
an organism:
1. Exogenous (alimentary) insufficiency – insufficient receipt in an organism
with food stuffs. May develop in small children as a result feeding goat milk or dry
dairy mixes.
2. Disorders of vitamin B12 absorbtion:
а) Disorder of formation and secretion of gastromucoprotein (internal
Castle’s factor). It happens at hereditary caused disorders, an atrophy of a
mucous membrane of stomach, autoimmune damages of parietal cells of
stomach mucous, due to gastrectomy or removal of more than two thirds
of stomach;
b) Disorder of small intestine function: chronic diarrheas (celiac disease,
sprue), resection of the big parts of intestine;
c) Competitive use of vitamin B12 by helmints and microflora of intestines
(diphyllobothriasis).
3. Disorder of transcobalamines formation in liver.
4. Disorder of vitamin B12 deposition in liver.
5. Increased use of vitamin B12 (at pregnancy).
Deficiency of vitamin B12 results in development of the frustration connected
with formation disorder
of its two coenzyme forms: methylcobalamine and
5-desoxyadenosilcobalamine. In a red bone marrow erythroblastic type of
hemopoiesis is replaced on megaloblastic, inefficient erythropoesis increases, life
expectancy of erythrocytes is shortened. The anemia with the expressed degenerate
shifts not only in a bone marrow, but also in blood develops. Changes in cells of
myeloid and megacariocytic lines are shown by reduction of leukocytes quantity
and thrombocytes, expressed by atypia of cells (huge neutrophils, megacaryocytes
with degenerative changes in a nucleus). Occurrence of atypic mitosis and huge
cells of epithelium digestive tract results in development of inflammatory-atrophic
processes in mucous membrane of its parts (glossitis, stomatitis, esophagitis,
achylic gastritis, enteritis). As a result of the second coenzyme forms insufficiency
of vitamin B12 – 5-desoxyadenosilcobalamine in organism propionic and
methylmalonic acids, which are toxic for nervous cells. Besides fatty acids with the
changed structure are synthesised in nervous fibres results in disorder formation of
myeline and to damage of axones. The degeneration of back and lateral columns of
a spinal cord develops (funicular myelosis), cranial and peripheral nerves are
damaged.
Occurrence in blood and red bone marrow of pathological regeneration cells
– megaloblasts, megalocytes is the most typical feature of this anemia. The color
index is increased, that is explained by the big saturation of cells by hemoglobin.
The phenomenon of degeneration erythrocytes is typical: anisocytosis
(macrocytosis), poikilocytosis (occurrence of the oval form cells), pathological
inclusions (Jolly’s bodies, Cabot’s rings). The maintenance granulocytes
(especially neutrophils) and thrombocytes in blood is reduced. Huge neutrophils
with the hypersegmented nucleus are found out.
Such syndromes are observed for B12-(folate)deficiency anemia:
1. Hematologic syndrome: а) anemia; b) leukopenia; c) thrombocytopenia.
2. Damages of the digestive tract which are shown by development inflammatory –
atrophic changes in mucous membrane.
3. Damages of the central and peripheral nervous system: funicular myelosis,
degeneration of peripheral nerves.
8. Hypoplastic anemias
Hypoplastic (аplastic) anemia is characterized by oppression hemopoietic
functions of red bone marrow and shown by insufficient formation of erythrocytes,
granulocytes and throrombocytes or only erythrocytes.
There are acquired and is hereditary caused forms of hypoplastic anemia. The
type of hereditary is autosomal-recessive type of inheritance concerns.
The acquired forms may be caused by the following reasons:
1) physical factors (ionizing radiation);
2) chemical agents (benzene, lead, steams of mercury, medical products:
cytostatic agents, chloramphenicol, sulfanilamids);
3) biological factors (virus of hepatites).
Essential forms of anemia, which reason is not established belongs to
acquired anemias.
Reduction of erythrocytes maintenance and concentration of hemoglobin
when color index is within the limits of norm is characterised for the peacture of
peripheral blood. Regenerative of erythrocytes (reticulocytes, polychromatophils )
as a role are not found in a blood smear. The maintenance of granulocytes
(especially neutrophils) and thrombocytes decreases. The quantity of lymphocytes
may remain without changes.
In a red bone marrow the quantity of hemopoietic cells decreases with
increase of maintenance of fatty tissue (picture of devastation red bone marrow).
Because of iron is not used for the purposes hemopoiesis, its maintenance in
erythroblasts and extracelulary is increased.
Appearence of hypoplastic anemias are connected with reduction of three
kinds formation of form blood elements: erythrocytes, granulocytes and
thrombocytes. It results in development of the following clinical syndromes:
1. The anemia and connected to it hypoxic syndrome.
2. Hemorrhagic syndrome.
3. The inflammatory processes caused by infectious agents (pneumonia, otitis,
pyelitis etc.).
9. Metaplastic anemias
The metaplastic anemia is the result of hemopoietic tissue replacement on
tissues: leucosis cells, connective tissue (fibrosis ), metastasises of tumor.
10. Dysregulative anemias
Dysregulative anemias arise as a result of erythropoiesis regulation disorders
(infringement of ratio between erythropoietins and inhibitors of erythropoiesis due
to insufficiency of kidneys, damage of strome elements – microenvironments of
erythropoietins cells, hypofunction of hypophysis, thyroid gland).
5.1. Content of the theme.
Anemia, definition of concept,
hematological indexes. Regenerative forms of erythrocytes. Classifications of
anemias. Acute posthemorrhagic anemia. Chronic posthemorrhagic anemia.
Irondeficiency anemia. B12-(folate)deficiency anemia. Hypoplastic anemias.
Metaplastic anemias. Dysregulative anemias.
5.2. Control questions of the theme:
1. Anemia, definition of concept, hematological indexes.
2. Regenerative forms of erythrocytes.
3. Classifications of anemias.
4. Acute posthemorrhagic anemia.
5. Chronic posthemorrhagic anemia.
6. Irondeficiency anemia.
7. B12-(folate)deficiency anemia.
8. Hypoplastic anemias
9. Metaplastic anemias.
10. Dysregulative anemias.
5.3. Practice Examination.
Task 1. At 40 year old man, which is in branch of reanimation, the decrease of
hematocrite up to 0,30 l/l is revealed. What process, most probable, has
resulted in such state?
A. Intensive sweating B. Frequent vomiting C. Long diarrhea
D. A gastric bleeding E. Strengthened urineproduction
Task 2. Sportsman - climber before the training assembly in mountains the amount
of erythrocytes in blood was equal to 4,5∙1012/l. How the amount of
erythrocytes at height of 2500 meters above a sea level will be changed?
A. It will appear absolute erythropenia B. It will appear absolute
erythrocytosis C. It will appear relative erythropenia D. It will appear
relative erythrocytosis E. Contents of erythrocytes will not change
Task 3. In a patient with renal insufficiency the synthesis of hemopoetin is
disordered. What blood elements development suffers during this?
A. Erythrocytes B. Monocytes C. Lymphocytes D. Trombocytes
E. Neutrophils
Task 4. The person long time stayed in high mountain conditions. It is significant
for him the increase in blood of the amount of:
A. Neutrophiles B. Limphocytes C. Hemoglobin D. Glucose E.
Protein
Task 5. After acute posttraumatical blood-loss in the victims blood have appeared
single oxyphile normocytes. During the supravital staining 30 % of
reticulocytes is revealed. What kind of anemia basing on the regeneratory
ability of the bone-marrow does the victim have?
A. Hyperregeneratory B. Regeneratory C. Hyporegeneratory
D. Aregeneratory E. Hypo- and aregeneratory
Task 6. A patient has arrived in clinic with the complaints on headache, dizziness,
pain in members. Skin covers are cyanoticaly-red. During the research of
blood the following results were obtained: total erythrocyte ammount 9,0∙1012/l, contents of hemoglobin - 200 g/l, colour inderx - 0,66. The total
contents of leucocytes - 9,3∙109/l, trombocytes – 500∙109/l. Speed of
erythrocytes sedimentation (SES) - 1 mm / hour. Hematocrite parameter 0,7 l/l. About what kind of disease do these characteristics speak about?
A. Fallo’s triad B. Erythremia C. Emphisema of lungs
D. Renal artery stenosis E. Adenocarcynoma of kidney
Task 1
Amount of erythrocytes of the patient 3,5∙1012/l, contain of hemoglobin - 86 g/l.
1. How this state is named? 2. Define colour index.
3. What it testifies about?
Task 2
Amount of erythrocytes of the patient 3,0∙1012/l, contain of hemoglobin in the
blood - 125 g/l.
1. Analyse these data.
2. Define colour index.
3. What diseases is it characteristic for?
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.