NURS201 PHYSIOPATHOLOGY

2023-2024 ACADEMIC YEAR, FALL TERM

ASST. PROF. DR. UFUK KAYA

BLOOD AND RELATED PROBLEMS
 STRUCTURE OF BLOOD

• Blood consists of plasma and shaped elements.

• Plasma is a yellowish liquid and contains foods, hormones and

minerals.

• Shaped elements are erythrocytes, leukocytes and platelets.

 PROPERTIES OF BLOOD
• Blood constitutes 7-9% of the total body weight in a healthy person.

• The average is 4-5 L in women and 5-6 L in men.

• The color of blood depends on the pigment in the hemoglobin in the

erythrocytes and changes with the amount of oxygen combined with
the hemoglobin.

• When the oxygen concentration increases, the color of the blood

becomes bright red.

• Blood has a slightly alkaline reaction and its pH is between 7.35-7.45.

 FUNCTIONS OF BLOOD
• It is possible to group the functions of blood into three categories.

Transport: Transport of various substances (oxygen, carbon dioxide, nutrients, metabolic

products, vitamins, electrolytes, etc.), transport of heat (heating, cooling),
transport of waste products produced by cells to the kidneys, liver and lungs.
Regulation: It regulates the clotting mechanism to stop bleeding, the acid-base balance to
keep body temperature and blood pH within normal limits by decreasing and
increasing blood flow to the skin.
Protection: Blood protects the body against pathogenic bacteria and viruses in various
ways. Leukocyte subgroup cells such as neutrophils and lymphocytes attack
microorganisms in various ways. Antibodies produced by lymphocytes play an
important role in the immune system and inflammation.
 PLASMA-01
• Plasma is the liquid part of blood and
constitutes 55% of total blood.

• 91% of plasma is water, 8% is proteins

(albumin, globulin, prothrombin and
fibrinogen), 0.1% is nutrients (amino acid,
glucose, lipid), 0.9% consists of salts (sodium
chlorite, sodium bicarbonate, etc.),
respiratory gases (oxygen, carbon dioxide),
substances produced by cells (hormones,
enzymes, uric acid, creatinine), clotting
factors, anticoagulants and antibodies.
 PLASMA-02

• Plasma Proteins-01:

• The large compartment found in plasma consists of plasma proteins.

• The normal density of plasma proteins is approximately 60-80 g/L.

• Plasma contains three basic protein fractions. These are albumin,

globulin and fibrinogen.
 PLASMA-03
• Plasma Proteins-02:

Albumin: Serum albumin constitutes about 60% of the total plasma protein and
is produced in the liver. Plasma colloid is the most important protein
that maintains osmotic pressure and serves as a carrier of free fatty
acids, bilirubin, thyroxine, cortisol and in some cases.

Globulin: It is produced by the reticuloendothelial system (phagocytic in the

spleen, lymph nodes, diseases and bone marrow). Globulin
constitutes about 36% of total plasma proteins.
Fibrinogen: Produced prolifically and constitutes 3% of plasma proteins. It plays a
role in clotting rates.
SHAPED ELEMENTS OF BLOOD
 FORMATION OF BLOOD CELLS (HEMATOPOIESIS)

• Hemopoietic tissue (red bone marrow in the adult, spleen and liver in
the fetus) contains pluripotent stem cells, and these cells differentiate
into myeloid, erythroid and lymphoid precursor cells under the
influence of hematopoietic development factors.

• Erythrocytes and myeloid precursor cells proliferate and mature in the

bone marrow and are then released into the peripheral blood.
 ERYTHROCYTE-01
• Normal erythrocytes are elastic, nucleus-free, biconcave disk-shaped.

• They have the ability to change shape under pressure.

• The most important function of erythrocytes is to transport

hemoglobin. They also contain large amounts of the enzyme carbonic
anhydrase.

• This enzyme accelerates the combination of carbon dioxide and water.

This rapid reaction allows water to combine with large amounts of
carbon dioxide in the blood and be transported from the docks to the
lungs in the form of bicarbonate ions.
 ERYTHROCYTE-02

• Hemoglobin in erythrocytes is an excellent acid-base buffer.

• Erythrocytes are responsible for 50% of the buffering power of the

whole blood.

• The number of erythrocytes varies depending on gender, age and the

altitude where the individual lives.
 ERYTHROCYTE-03
• The production of erythrocytes is called erythropoiesis.

• The main factor that stimulates erythrocyte production is the

erythropoietin hormone.

• In case of lack of oxygen (hypoxia), erythropoietin produced in the

kidneys is released into the circulation.

• 80-90% of erythropoietin is secreted from the kidneys, a small amount

from the liver and excreted through the kidneys.

• A very small amount of erythropoietin is sufficient to increase the

erythrocyte count 10-fold.
 ERYTHROCYTE-04

• Erythropoietin enables hemopoietic stem cells to transform into

proerythroblasts and accelerate the subsequent cycles, and new
erythrocytes enter the circulation within 5 days.

• When the number of erythrocytes reaches a level that can carry the
necessary oxygen to the tissues, hormone secretion decreases and the
number of cells is maintained at that level.
 ERYTHROCYTE-05

• Erythrocyte production is under feedback control.

• While this production is inhibited if the number of erythrocytes in

circulation increases above normal, it is stimulated if the number of
erythrocytes in circulation falls below normal (anemia) and in hypoxia.

• Oxygen saturation of the blood is an important factor in regulating

the production of erythrocytes.
 ERYTHROCYTE-06

Normal erythrocyte production depends on three factors:

1. Genetically normal precursor cells

2. Functional bone marrow

3. Regular intake of iron, vitamin B12, folic acid, protein, pyridoxine and
small amounts of copper
 ERYTHROCYTE-07
Hemoglobin-01:

• It is the major element of the erythrocyte cell (35%).

• The function of hemoglobin is to take oxygen from the lungs and

deliver it to the tissues.

• Iron is required for the formation of hemoglobin.

• The total amount of iron in the body is about 4 g. Approximately 65%

of this is in the hemoglobin composition, and 15-30% is found as
storage iron in the liver in the form of ferritin and hemosiderin.
 ERYTHROCYTE-08
Hemoglobin-02:

• Excess iron in the blood is stored in the form of ferritin in all cells of
the body, especially in the liver.

• Most of the iron used in making hemoglobin is obtained from the

destruction of aged erythrocytes.

• The absorption of iron from the intestines is very slow.

• A small part of the ingested iron (5-10%) is absorbed from the

intestines, and the rest is excreted with the feces.
 ERYTHROCYTE-09
Hemoglobin-02:

• If erythropoiesis increases, the amount of iron absorbed from the

intestines also increases.

• Iron stores are higher in men than in women, and while men lose 1
mg of iron per day, women lose up to 2 mg of iron per day due to
blood loss during menstruation.

• The average lifespan of erythrocytes is 120 days. Cell fragments are

engulfed by macrophages in the liver and spleen.
 LEUKOCYTE-01
• They are mobile units of the body's defense systems that resist
foreign substances.

• Leukocytes are cells that are larger, fewer in number, and have nuclei
than erythrocytes. These cells constantly scan the body, looking for
foreign substances such as tumors, viruses, bacteria and fungi.
 LEUKOCYTE-02

• The leukocyte count is between 5,000-10,000 mm³ and tends to be

low after a period of rest, but increases after activity or a meal.

• There is a rapid increase in body defense (25,000 mm³) above normal

in many infections.

• If the leukocytes are higher than normal, it is called leukocytosis, and

if they are lower than normal, it is called leukopenia.
 LEUKOCYTE-03
• Leukocytes are divided into two major groups: Granulocyte and
Agranulocyte.

Granulocyte Agranulocyte
Neutrophil Monocyte
Eosinophil Lymphocyte
Basophil
 LEUKOCYTE-04

Granulocytes-01:

• Neutrophil: They constitute 60-70% of total leukocytes.

• They are the body's first line of defense against bacterial infections.

• In acute infections, the number of neutrophils increases rapidly.

• When bacteria attack the body, the bone marrow is stimulated to

produce and release large amounts of neutrophils.
 LEUKOCYTE-05
Granulocytes-02:

• Neutrophil: The attraction of neutrophils passively circulating in the

blood towards the infection site is called chemotaxis.

• Neutrophils, who pass into the tissue through diadepes (neutrophils

and monocytes passing into the tissues), engulf the bacteria by
phagocytosis.

• The number of neutrophils increases in pregnancy, infection,

metabolic diseases such as leukemia, acute gout, inflammation and
myocardial infarction.
 LEUKOCYTE-06
Granulocytes-03:

• Eosinophil: They are 2-4% of all leukocytes and are weak in terms of
phagocytosis.

• They attack and kill parasites that are too large to be phagocytosed.

• Eosinophil levels are high in individuals with allergic diseases.

• Eosinophils penetrate tissues and are especially abundant in the

mucosa of the respiratory, urinary tract and gastrointestinal tract.
 LEUKOCYTE-07

Granulocytes-04:

• Basophil: They carry histamine and heparin and constitute about 1%

of all blood leukocytes.

• They release histamine when activated by histamine-releasing factor.

• They have a role in early type hypersensitivity reactions. These

reactions vary from mild urticaria to severe anaphylactic shock.
 LEUKOCYTE-08

Agranulocytes-01:

• Monocyte: Monocytes produced in the bone marrow make up

approximately 5% of leukocytes.

• Monocytes remain in the circulation for approximately 72 hours and

pass into the tissues.

• Since they are immature while circulating in the blood, they have
little ability to fight infectious agents.
 LEUKOCYTE-08
Agranulocytes-02:

• Monocyte: The volume of monocytes that enter the tissues increases

and their diameters expand fivefold. These are called tissue
macrophages.

• Tissue macrophages include Kupffer cells of the liver, lung alveolar

macrophages, and microglia of the brain.

• Lymphokines secreted from T-lymphocytes activate macrophages.

• Activated macrophages engulf and kill bacteria.

 LEUKOCYTE-09

Agranulocytes-03:

• Lymphocyte: They have a large, round nucleus that fills most of the
cell.

• Although some lymphocytes are formed in the bone marrow, most of

them are produced from precursor cells that have previously come to
the lymphoid tissue from the bone marrow and constitute 25% of the
total leukocytes.
 LEUKOCYTE-10
Agranulocytes-04:

• Lymphocyte: They are key building blocks of the immune system and
have the remarkable ability to produce antibodies against foreign
agents.

• They produce a faster and greater response when a foreign substance

is encountered for the second time.

• They are divided into two main groups: T and B lymphocytes.

 PLATELET-01
• They are small particles produced from megakaryocytes in the bone
marrow.
• Platelets are found in circulating blood between 150,000-500,000
mm³ and their normal life span is 5-9 days.
• As long as the integrity of the vascular endothelium is not disrupted,
platelets circulate inactively in the blood and provide
thrombokinase, which has an important role in blood clotting.
• Activated platelets change shape, form pseudopods, discharge
granules and adhere to other platelets (platelet aggregation).
• This aggregation is also exacerbated by platelet-activating factor
secreted by platelets, neutrophils and monocytes.
• Thus, a chain of events begins to stop the bleeding.
HEMOSTASIS
 HEMOSTASIS-01
• The process of preventing clot formation and blood loss in the walls
of damaged blood vessels is called hemostasis.

• The systemic mechanism works to maintain the balance between

coagulation (coagulation) and anticoagulant (anticoagulation)
events.

When a blood vessel is cut or destroyed, it initiates a series of events

that lead to the formation of a clot. These.
1. Vasoconstriction
2. Platelet aggregation
3. Coagulation
 HEMOSTASIS-02

• The first event seen is the formation of a temporary hemostatic plug

made of platelets, triggered by vasoconstriction and binding of
platelets to collagen (platelet aggregation). This is also called primary
hemostasis.

• Loose clusters of platelets in the temporary plug are bonded to each

other with fibrin and turned into a permanent clot.
 HEMOSTASIS-03
• The basic reaction in blood clotting is the conversion of fibrinogen, a
soluble plasma protein, into insoluble fibrin.

• The conversion of fibrinogen to fibrin is catalyzed by thrombin.

• Thrombin is produced from prothrombin under the influence of

factor X.

• Factor X can be activated by reactions in either of two systems, one

endogenous (intrinsic) and the other exogenous (extrinsic).

• Both are required to maintain hemostasis.

 HEMOSTASIS-04
• The resulting fibrin network catches the shaped elements of the
blood passing through it and after a few minutes, the fibrin filaments
begin to contract.

• In approximately 20-60 minutes, the remaining liquid in the mesh is

squeezed out.

• Then, erythrocytes and platelets adhere to the fibrin ball and control
tissue damage.

• After the vessel is repaired, it is covered with endothelial cells and

there is no longer a need for a fibrin clot.
 HEMOSTASIS-05
• The physiological mechanism that dissolves the clot is called fibrinolysis.

• These two opposite processes, such as clot formation and clot dissolution,
work together.

• Plasminogen circulating inactively in the blood turns into active plasmin.

• Plasmin breaks fibrin bonds and allows it to disperse. The resulting

fragments are then cleared by macrophages.

• In addition, prothrombin also breaks down plasma factors and thus the
clot is broken down.
BLOOD GROUPS
 BLOOD GROUPS-01
• There is a group of blood group antigens (agglutinogen) in the membrane
of human erythrocytes. The most important and best known of these are A
and B antigens, but there are many more antigens.

• When antigens combine with antibodies (agglutinin), they form lumps like
grape bunches (agglutination).

• Every person has one of the 4 main blood group types.

 BLOOD GROUPS-02
• Blood groups are named according to the antigens on erythrocytes.

According to this:

1. Group A erythrocytes contain A antigen.

2. Group B erythrocytes contain B antigen.
3. AB blood group erythrocytes contain both A and B antigens.
4. O blood group erythrocytes have no antigens.
 BLOOD GROUPS-03
• Blood plasma may or may not contain antibodies that react with the A or
B antigen on erythrocytes. However, there are 2 important rules.

1.Plasma does not contain antibodies against antigens on its own

erythrocytes.
2. Antibodies against A or B antigen are present in the plasma. That is, type A
blood contains anti-B antibodies, and type B blood contains anti-A antibodies.

• Thus, when a person of blood group A donates blood to another person of

blood group A, agglutination does not occur. However, when blood of
type A is given to someone of blood group B, agglutination occurs.
 BLOOD GROUPS-04
• On the other hand, group O does not have both antigens. On the other
hand, there are both anti-A and anti-B antibodies in its plasma. For this
reason, agglutination occurs when a donor from group O gives blood to a
recipient from groups A, B and AB.

• Similarly, there are no antibodies in the plasma of someone with blood

type AB. However, the antibodies in the A, B and O type blood to be given
externally combine with the antigens on the recipient's erythrocytes and
cause agglutination.

• For this reason, group 0 should not be considered as 'general donor' and
group AB as 'general recipient'.
 BLOOD GROUPS-05
Rh Factor-01:

• It is not an antigen, but the name given to a group of antigens.

• These antigens are designated C, D and E.
• These antigens are inherited.
• 'D', which has a strong antigenic feature, is the most common in society.
For this reason, D antigen is searched to determine the Rh factor in the
blood.
• In general, the term Rh positive indicates that the person has D antigen,
and Rh negative indicates that the person does not have D antigen.
• However, if an Rh-negative person has previously been given Rh-positive
blood, anti-Rh antibodies may be seen in that person's blood.
 BLOOD GROUPS-06
Rh Factor-02:

• Rh factor becomes most important during pregnancy.

• If the mother is Rh negative and the father is Rh positive and the baby
has received the Rh positive gene from the father, the mother produces
antibodies against the Rh factor, which she considers foreign.
• Since antibody production takes time, the first child is born healthy.
• However, these antibodies formed by the mother pass into the blood of
the second or third baby through the placenta and hemolyze the
erythrocytes.
• This condition is called hemolytic disease of the newborn
(erythroblastosis fetalis).
• This may cause the fetus to die in the womb.
BLOOD DISEASES
 ANEMIA-01
• It is clinically defined as 'blood hemoglobin or hematocrit value that is
below the valid reference range for the patient'.

• In general, anemia is defined as a hemoglobin level in the blood below 13

g/100 mL in adult men and 12 g/100 mL in women.
 ANEMIA-02

The main causes of anemia:

1. Bleeding (hemorrhage)
2. Erythrocyte destruction (hemolysis)
3. Decrease in erythrocyte production due to bone marrow failure
4. Infections (such as malaria)
5. Insufficient intake of iron, folic acid and vitamin B12
6. Pregnancy
 ANEMIA-03

There are three basic types of anemia:

1. Microcytic anemias (erythrocytes are smaller than normal)

2. Macrocytic anemias (erythrocytes are larger than normal)

3. Normocytic anemias (erythrocytes are normal size)

 ANEMIA-04
Iron Deficiency Anemia-01:
• It is the most common type
of microcytic anemia.

• Causes: Insufficient iron

intake in the diet, iron loss
due to bleeding, inability to
absorb iron from the
gastrointestinal tract after
gastroctomemia, increased
iron need in situations such
as pregnancy and
adolescence.
 ANEMIA-05
Iron Deficiency Anemia-02:

Physiopathology:

• It develops slowly and in three stages.

1. In iron deficiency, bone marrow iron stores are completely depleted, but
erythropoiesis continues normally.
2. Iron transport to the bone marrow decreases, followed by a decrease in
hemoglobin and mean erythrocyte volume, respectively.
3. While the number of microcytic erythrocytes increases in the peripheral
circulation, the number of normal erythrocytes decreases.
 ANEMIA-06

Macrocytic Anemias-01

• It is also called megaloblastic anemia.

• Megaloblastic anemias are often seen together with leukopenia and

thrombocytopenia.

• Megaloblastic anemias are usually caused by disorders in DNA synthesis due to

cobalamin (vitamin B12) and folic acid deficiency.
 ANEMIA-07
Macrocytic Anemias-02

Folic Acid Deficiency:

• Folic acid is a vitamin necessary for erythrocyte production and maturation.
• Adults need 50 mg of folic acid per day.

The most important causes of folic acid deficiency:

1. Malnutrition (alcoholism, diet lacking in fresh vegetables and fruits)
2. malabsorption
3. Drugs that inhibit absorption from the jejunum (oral contraceptives,
anticonvulsants)
4. Anorexia
 ANEMIA-08
Macrocytic Anemias-03

Vitamin B12 deficiencies:

• The most common type of megaloblastic anemia is pernicious anemia caused

by vitamin B12 deficiency.
• Pernicious anemia is a megaloblastic anemia that develops due to autoimmune
chronic gastritis.
• The daily requirement for adults is 0.1 microgram.
• There are some neurological disorders that develop due to vitamin B12
deficiency. The earliest and most common symptoms are paresthesias in the
extremities.
 ANEMIA-09
Normocytic Anemias-01

Aplastic Anemia:
• It is an anemia that occurs as a result of the deficiency of hematopoietic stem
cells and progresses with pancytopenia (decrease in all erythrocytes, leukocytes,
and platelets).

Etiology:
1. Ionizing radiation
2. Chemotherapy drugs used in cancer treatment
3. Chemical substances (benzene)
4. Viral infections (hepatitis, HIV)
 ANEMIA-10
Normocytic Anemias-02

Aplastic Anemia:
Physiopathology:

• It develops due to damage in the bone marrow and results in low production of
all blood cells.
• Erythrocytes are immature and have low oxygen carrying capacity.
• Since the lifespan of leukocytes and platelets is shortened, patients are prone to
bleeding and infection.
• The mortality rate in these patients is high, and the most common causes of
death are severe bleeding, infection and septic shock.
 ANEMIA-11
Normocytic Anemias-03

Hemolytic Anemia:
• It is characterized by premature lysis of erythrocytes.
• Common types: Inside the erythrocyte (intrinsic) and outside the erythrocyte
(extrinsic).

Etiology:
• Spherocytosis (erythrocyte membrane ruptures easily)
• Hemoglobin defects (thalassemia and sickle cell anemia)
• Faulty blood transfusions
• Drugs destroy cells
• intravascular coagulation
• Hemoglobinopathies (abnormalities in hemoglobin structure)
 ANEMIA-12
Normocytic Anemias-04

Hemolytic Anemia:
Physiopathology:
• The normal lifespan of erythrocytes, which is 120 days, has been shortened
considerably.
• The cell membrane has a structure that can be torn easily. This causes the number of
cells to decrease rapidly and not enough oxygen to be carried to the tissues.
• As a precaution against developing tissue hypoxia, the bone marrow begins to produce
excessive erythrocytes.
• In hemolytic anemia, the destruction of erythrocytes occurs either intravascularly or
within the reticuloendothelial system.
• Excessive increase in erythrocyte destruction causes an increase in bilirubin and
urobilinogen levels in the blood.
 ANEMIA-13
Normocytic Anemias-05

Sickle Cell Anemia (Hemoglobin S):

• It is a genetic and chronic hemolytic
anemia characterized by abnormal
hemoglobin molecule (HbS).

• Hemoglobin S is the most common

hemoglobinopathy in the world.
 ANEMIA-14
Normocytic Anemias-06

Physiopathology:

• When HbS is deprived of oxygen, the erythrocyte takes a sickle shape.

• Any cause such as hypoxia, acidosis and high temperature predisposes to
sickling.
• Sickled erythrocytes can return to their previous state under oxygen.
• However, repeated sickling changes the structure of the erythrocyte and turns
into permanent sickle cells.
• Sickle cells that have lost their flexibility and become rigid can block small blood
vessels, causing tissue infarcts.
 LEUKEMIA-01

• It is a malignant disease characterized by the abnormal proliferation of one of

the leukocyte cell types (such as granulocyte, monocyte and lymphocyte)
without maturation.

• The most common feature of leukemia is the uncontrolled production of

leukocytes from the bone marrow.

• It is among the diseases that cause death in adults and is more common in men.
 LEUKEMIA-02
Etiology:
• Chemical agents (such as benzene)
• Chemotherapeutic agents
• Virus
• Radiation
• Cigarette
• Genetic disorders (such as Down syndrome)
• Immune deficiencies (such as HIV)
 LEUKEMIA-03
Classification:
Acute Leukemias
• Acute lymphoblastic leukemia (ALL)
• Acute myeloid leukemia (AML)

Chronic Leukemias
• Chronic lymphoblastic leukemia (CLL)
• Chronic myeloid leukemia (CML)
 LEUKEMIA-04
Physiopathology:
• Acute leukemias are characterized by the uncontrolled proliferation of
hematopoietic precursor cells that have lost their ability to mature and
differentiate. Malignant (blast) cells suppress normal blood production
(hematopoiesis) by filling the bone marrow. Since treatment and prognosis differ
from each other, it is important to diagnose ALL and AML correctly.

• CLL is characterized by the presence of increased numbers of small, mature-

looking lymphocytes in the peripheral blood. It is usually seen between the ages
of 50-70 and is more common in men. CML is common in men aged 30-50.
Although the cause of CLL is not known for certain, it is more common in people
working in the asbestos industry and in agriculture.
 THROMBOCYTOPENIA-01
• It is when the platelet count is below normal.

• The most important problem is the risk of bleeding.

• Trauma or spontaneous bleeding occurs when the platelet count is 20,000 mm3.
 THROMBOCYTOPENIA-02
Etiology:
• Anemia due to folic acid and vitamin B12 deficiency
• Systemic lupus erythematosus
• Sepsis, bacterial and viral systemic infections
• Chemotherapy
• Radiotherapy
• heparin
• HIV
 THROMBOCYTOPENIA-03
Physiopathology:
• Three basic mechanisms are effective in its development:

1. Increased platelet destruction

2. Decreased platelet production
3. abnormal platelet distribution

There are three different types:

4. Idiopathic thrombocytopenic purpura
5. Thrombotic thrombocytopenic purpura
6. Hemolytic-uremic syndrome
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