Pathophysiology of blood

Red blood cell disorders

 Lecture content

• Physiological basics: creation and breakdown of erythrocytes

• Polycythemia and Erythrocytosis

• Definition and division of anemia

• Anemias caused by disorders in the formation of erythrocytes

• Аnemias caused by increased breakdown of erythrocytes

 Blood

• Is a liquid connective tissue

• Red in color and has a salty taste
• The volume of blood is 5 l
• Blood plasma
- Water and soluble substances(salts,
беланчевинеproteins,nutriens,hormo
nes,metabolic products Blood
- Disease-causing agents and drugs plasma
can be found in the blood
• Blood cells Blood cells
 Krv
Blood
 Blood cells

erythrocytes platelets

leukocytes
Hematopoiesis

Platelets
B
lymphocyte
precursor
erythrocyte
Granulocyte

Lymphocite B
Home station
 ЕRYTHROPOIESIS
• The bone marrow produces about 200 billion erythrocytes per day

• Erythrocytes lives 90-120 days,after wich they are removed from the
circulation

3 million erythrocytes dissapear from the circulation every second

• Normal bone marrow has the ability to increase the production of

erythrocytes 6 to 8 times as needed

• Reticulocytosis reflects erythroid hyperplasia of the bone marrow

Еrythropoiesis
- simultaneous reproduction and differentiation

- 3 – 5 division (8 – 32 Er)
- volume reduction by50% 12 hour

- gradual reduction of mitochondrial content

- Increase in the amount of hemoglobin and
gradual degeneration of the core 20 hour

- The acidophillic erythroblast can no longer

divide but hemoglobin synthesis continues in it
30 hour

48 hour

30-48 hour
Erythropoiesis

Proerythroblast:
- is the first morphologically
recognized cell of erythropoiesis
- has loose chromatin
- has severial sails
- does not contain visible
hemoglobin
- has a large number of
ribosomes
Еrythropoiesis

Basophillic erythroblast:
- condensation of chromatin begins
in this cell
- has neither a nucleus nor nucleoli
- has visible hemoglobin
- has a large number of ribosomes
 Erythropoiesis

Polychromatophillic erythroblast:
- has a higher chromatin
condensation
- has a reducter number of
mitochondria
- has a higher amount of hemoglobin
wich gives acidophillity to the
cytoplasm
 Еrythripoiesis

Acidophillic erythroblast:
- has a pyknous degeneration of the
nucleus
- Has a 80% of total Hb
- has a reduced nucleus
- becomes a reticulocyte after the
nucleus has been expelled
 Еrythropoiesis
Reticulocyt:
- has not nucleus
- the cytoplasm of reticulocytes contains
mitochondria,ribosomes and Goldzi”s
apparatus
- as the reticuloczt matures it loses these
organells
- synthesis of 10-20% Hb
- transferrin receptors are lost
 Еrythrocyte
• has not nucleus
• biconcave shape
• live 120 days
• transports oxygen to the tissuesd and
carbon dioxide from them
• as erythrocyte ages the intensity of
metabolic processes decreases and the
rigidity of the membrane increases
• erythrocytes are broken down the most
in the spleen then in liver
 Red blood cell disorders

• Polycythemia
• Anemia
 Polycythemia
• Is an excess of all blood cells

• Is a condition in wich the total volume of blood and erythrocytes and blood
viscosity are increased

• Polycythemia is divided into:

– Relative (decreased plasma volume and unchanged erythrocyte volume)

– Absolute (increased volume of erythrocyte):

• Primary (polycythemia rubra vera)

• Secondary (occurs with increased production of erythropoietin)

 Polycythemia rubra vera

• Is a disorder at the pluripotent stem cell level

• Еrythrocytosis, thrombocytosis, leukocytosis

• Symptoms are caused by increased blood viscosity, and icreased total

volum of blood, blood plasma volume is normal
 Secondary polycythemia

• Is increased production of erythrocytes caused by increased secretion

of erythropoietin in :

– Tissue hypoxia in cardiopulmonary diseases.

– When breathing air with a low partial pressure of oxygen

– The development of kidney tumors that secrete erythropoietin

 Аnemia

• Anemia is a term used in clinical practice for reduced hemoglobin

concentration ,reduced number of erythrocytes and reduced hematocrit

• Definition:

– Decreased concentration of hemoglobin in peripherial blood

– Decreased in the mass of erythrocytes in peripherial blood

 Аnemia

• Anemia is a condition characterized by a reduced abillity of the blood to

carry oxygen due to a reduced amount of Hb.Anemia is not a diagnosis but
an objective sign of the present disease.

• In the diagnosis of anemia the first step is to determine the existence and
severity of anemia, and the second step is to determine the pathogenesis of
anemia.
 Аnemia

Reference values:
Important parameters:
Hb male 150±20 g/l
female 140±20 g/l MCV = Hct / br Er (83 -99fl)
Hct male 0.42 – 0.49%
female 0.39 – 0.46% MCH = Hb / br Er (28 – 32
pg)
Er male 4.2 – 5.8 x 1012/l
female 3.9 – 5.2 x 1012/l
MCHC = Hb / Hct (32 – 36
g/dl)
 Pathophysiological classification of anemia

Аnemias occur as a consequence:

• Disturbances in the formation of Er

• Increased breakdown of Er

• Acute or chronic blood loss

 Pathophysiological classification of anemia

Disorder of the creation Er:

• Disrupt the reproduction and differentiation of hematopoietic stem cell (aplastic

anemia)

• Disorder of reproduction and differentiation of unipotent stem cell destined for

erythropoiesis

• Disorder or reproduction and differentiation of morphologically recognized

precursors of erythropoiesis(megaloblastic anemia)

• Disorder of hemoglobin synthesis(iron, chем and globin)

• Unknown or multifactorial cause (chronic diseases,eating disorder)

 Pathophysiological classification of anemia

Increased breakdown of Er:

• Corpuscular anemia:

– Disorders of the Er membfrane

– Disorders of enzyme structure
– Disorders of hemoglobin structure

• Еxtracorpuscular anemia:

– Mechanical,
– Caused by physical and chemical factors,
– Caused by infections,
– Caused by аntibodies,
– Hypersplenism
 Morphological clasification of anemia

Macrocyt anemia
MCV increased

Normocyt anemia
MCV MCV normal

Microcyt anemia
MCV lowered
 Classification of anemia

Classification of anemia according to erythrocyte morphology and

HGB content:

– Normocytic normochromic anemia

– Macrocytic normochromic anemia

– Mycrocytic normochromic anemia

 Compensatory mechanisms of the body in
anemia
• Shift of the oxyhemoglobin dissociation curve to the right about to the
synthesis 2,3 diphosphoglycerol, wich reduces the affinity of
hemoglobin for oxygen.

• Adaptation of the cardiovascular system:

– peripheral (redistribution of blood to vital organs,heart and brain) and

– central (increase in cardiac output)

• Increased production or erythropoietin

• Decrease in physical activity

• Hyperventilation
 Symptoms and signs of anemia

Immune system
CNS Disturbance of T
• Pathological fatigue lymphocyte and
• Dizziness,weakness macrophage function
• depresion
Cardiopulmonary system
• Disorder or cognitive functions • Dyspnea on exertion
Gastrointestinas system • Tachycardia and palpitations
• anorexia • Cardiac muscle hypertrophy
• nausea • Increased pulse pressure
• Risk of worsening heart
Vascular system failure
• Cold skin
• Pale skin
Genital system
• Problems with menstruation
• Loss of libido

Adaptirano iz: Ludwig H, Fritz E. Semin Oncol 1998;25(Suppl. 7):2–6