L1: Functions of cellular elements of blood and regulation of haematopoiesis

Question 1

What is the composition of blood and what is the composition of substances that forms blood?

Answer 1

❖ Blood is a complex reddish fluid that circulates within the cardiovascular system

❖ Blood consists of a yellowish fluid (plasma) (55% of blood volume) in which cellular
elements (45% of blood volume) are suspended.

Plasma:- consists of:

• 90% Water
• 0.9% Inorganic substance (Na+, K+, Cl-, HCO3, PO4, SO4)
• 9.1% Organic substances (plasma proteins, lipids, others)

Cellular elements:- Include:

• Red blood cells (RBCs)
• White blood cells (WBCs)
• Platelets

Question 2

What is the volume of blood in humans?

Answer 2

Its volume is about 8% of the bodyweight i.e. 5600 ml in a 70 kg man. “ One litter must be lost to show effect”

Question 3

What are the general functions of blood?

Answer 3

1) Major transport medium:
- Blood transports many substances like glucose, O2, CO2, end products of metabolism as urea, and hormones

2) Hemostatic function:
- Stoppage of bleeding from injured blood vessel by platelets and clotting

3) Homeostatic function:
- Keeping the composition (pH, electrolytes, and water) of the internal environment (ECF) constant.

• This is done by continuous exchange of substances between the interstitial fluid (ECF) and blood then between the blood and the external environment through the gastrointestinal tract, lungs, kidneys, and skin.

4) Defensive function:
- WBCs provide the main defense mechanisms against a wide variety of micro-organisms through phagocytosis and the formation of antibodies

Question 4

What is the size of RBCs?

Answer 4

• Its diameter → 7.5 um.
• Its thickness → at the thickest point is about 2.5 um.
• Its average volume → 90 to 95 u3.

Question 5

What is the structure of RBCs?

Answer 5

RBCs are not true cells, because they have no nuclei, so called corpuscles.

1) The cell membrane:
- They are surrounded by a plastic semipermeable membrane and has a large surface area, so RBCs are biconcave

2) Its contents:
- Hb is the main constituent of RBCs “carry o2” (34% of their weight). “Third!”
- K ion is the chief intracellular cation.
- Carbonic anhydrase enzyme, which is important for CO2 transport.
- NO Mitochondria in the RBCs, so they obtain their energy from anaerobic glycolysis. “For ion balance for example”

Question 6

What is hemoglobin and what are its levels?

Answer 6

• It is an iron-containing red pigment that is present inside RBCs.

- contents:
 in adult males→ 14-18 gm/dl "more RBCs"
 in adult females→ 12-16 gm/dl 
 in newborn → 18 gm/dl 
 in children → 12 gm/dl

Question 7

What are the functions of RBCs?

Answer 7

1) Functions of cell membrane:
❖ It has a large surface area than the actual cell volume:
- It gives RBCs its biconcave shape.
- It allows easy diffusion of gases through the cell membrane.

❖ It is plastic, so it enhances cell flexibility to allow RBCs to be squeezed in small capillaries without rupture of it.

❖ It keeps Hb inside RBCs, so prevent its loss in urine:
- Filtration of Hb into glomeruli causes its precipitation in
renal tubules and acute renal failure.

2) Functions of Hb:
❖ It transports CO2 “with carbonic anhydrase enzyme” and O2 between lungs and tissues.
❖ It is an excellent acid-base buffer. “Maintains pH”

3) Functions of carbonic anhydrase enzyme:
❖ It helps in the transport of CO2. “In the form of HCO3”

4) Blood viscosity:
❖ RBCs share in the production of blood viscosity, which maintains arterial blood pressure (ABP).

Question 8

What is the lifespan of platelets (thrombocytes)?

Answer 8

8- 12 days “Short”

Question 9

What is the function of platelets?

Answer 9

Have a role in hemostasis:

• Release of V.C. substances such as serotonin and thromboxane A2.
• Formation of a primary hemostatic plug.
• Release of platelet phospholipids (PF3) which is essential for blood clotting.
• Stabilization of the blood clot and induction of clot retraction.
• Help repair the damaged vessel wall.

Question 10

Where are granular leukocytes formed?

Answer 10

Formed in the bone marrow

Question 11

What percent does each type of granular leukocyte represent?

Answer 11

 60-70% (neutrophils) “ as they are continuously lost”
 1-5% (eosinophils)
 0.0-1.0% (basophils)

Question 12

What is the lifespan of granular leukocytes?

Answer 12

4 -5 days

Question 13

What is the function of neutrophils?

Answer 13

The first line of defense against bacterial infection by phagocytosis

Question 14

What is the function of eosinophils?

Answer 14

• Defense against parasitic infection e.g. schistosomiasis

- Prevent the spread of the local inflammatory during an allergic reaction

Question 15

What is the function of basophils?

Answer 15

• Synthesize and liberates heparin (anticoagulant) into the blood.
• Releases histamine, serotonin, and bradykinin during allergic reactions.

Question 16

Where are lymphocytes formed what percent do they represent?

Answer 16

Formed in the lymphoid tissues.

20-30%

Question 17

Where are monocytes formed and what are their percent?

Answer 17

Formed in bone marrow

3-8%

Question 18

What is the lifespan of agranular leukocytes?

Answer 18

months or even years “Very long”

Question 19

What is the function of lymphocytes?

Answer 19

 T lymphocytes for cell-mediated immunity

 B lymphocytes secrete antibodies

Question 20

What is the function of monocytes?

Answer 20

Phagocytosis “100 and doesn’t dye” of bacteria and old cells such as RBCs by forming tissue (fixed) macrophage system or reticuloendothelial system (RES)

Question 21

What is the definition of hematopoiesis?

Answer 21

It is the process of formation of blood cells

Question 22

What are the sites of hematopoiesis?

Answer 22

In the early few weeks of embryonic life
 blood cells are produced in the yolk sac.

In the middle trimester of gestation
 blood cells are produced in the liver, spleen, and lymph nodes. (RES)

In the last trimester and after birth
 hematopoiesis is restricted to the red bone marrow (bone marrow of all bones).

After the age of 20 years
 the bone marrow of all long bones becomes fatty and the RBCs are produced only by the membranous (flat) bones, such as the vertebrae, sternum, ribs, and ilia.

Question 23

What are the steps of hematopoiesis?

Answer 23

All blood cells originate from pluripotential hematopoietic stem cells (PHSCs), which divide and differentiate into 2 cells lines by hemopoietic growth factors:

1) Lymphoid stem cells: gives rise to lymphocytes, which include the T cells, B cells, and natural killer (NK) cells. These cells quickly migrate from the bone marrow to lymphatic tissues e.g. lymph nodes, spleen, and thymus.
2) Myeloid stem cells: gives rise to all the other formed elements, including the RBCs; megakaryocytes that produce platelets; and a myeloblast lineage that gives rise to monocytes and granular leukocytes: neutrophils, eosinophils, and basophils

Question 24

What are the factors affecting hematopoiesis?

Answer 24

Hemopoietic growth factors
Healthy bone marrow. 
Healthy liver
Hormones
Nutritional factors

Question 25

What is erythropoietin and where it is secreted?

Answer 25

- It is a glycoprotein hormone secreted in the adults by the kidney (90%) and liver (10%) and during fetal life, is formed mainly by the liver.

Question 26

What stimulates the secretion of erythropoietin?

Answer 26

Its secretion is stimulated mainly by hypoxia "Low o2 due to low RBCs", cobalt and androgens.

Question 27

What does erythropoietin act on?

Answer 27

It acts on stem cells to differentiate them into proerythroblasts and on proerythroblasts to differentiate them into mature RBCs.

Question 28

What is Thrombopoietin and where is it secreted?

Answer 28

Is a glycoprotein hormone, is produced by the liver and kidneys.

Question 29

What is the function of Thrombopoietin?

Answer 29

Stimulates the production of megakaryoblasts and the development of megakaryocytes into platelets

Question 30

What is the percentage of platelets that are released in blood?

Answer 30

60-75% of platelets are released in the blood and 25% are trapped in the spleen, so splenectomy rises the platelets levels in the blood (thrombocytosis)

Question 31

What are cytokines and from where are they secreted?

Answer 31

Are glycoproteins secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells. It includes 2 groups:

Question 32

What are the types of cytokines?

Answer 32

a) Colony-stimulating factors (CSFs): 1) Granulocyte CSFs: trigger the differentiation of myeloblasts into granular leukocytes (neutrophils, eosinophils, and basophils). 2) Monocyte CSF: induces the production of monocytes 3) GM-CSF: induce the production of both granulocytes and monocytes 4) granulocytes, monocytes, platelets, and erythrocytes are stimulated by multi-CSF. b) Interleukins: interleukin 3, promotes the growth and reproduction of virtually all the different types of committed stem cells. "First step"

Question 33

What is the role of healthy bone marrow in affecting hematopoiesis?

Answer 33

 Healthy bone marrow is essential to produce RBCs and other blood cells  Destruction of bone marrow by irradiation or chemicals, drugs leads to deficiency of all blood cells (aplastic anemia).

Question 34

What is the role of a healthy liver in hematopoiesis?

Answer 34

A healthy liver is essential for normal RBC formation and Platelets because it is the site for secretion of erythropoietin and thrombopoietin and stores iron and Vit B12

Question 35

What is the role of hormones in hematopoiesis?

Answer 35

Most hormones including thyroid hormones, androgens "testosterone, that's why males have more RBCs" and glucocorticoids are essential for hematopoiesis, as they promote tissue metabolism in general.

Question 36

What is the role of nutritional factors in hematopoiesis?

Answer 36

1) Proteins: ❖ Animal proteins (high biological value proteins) that present in the liver, kidney, and muscles are superior in the production of RBCs to other proteins 2) Minerals: ❖ Copper and cobalt act as cofactors in hemoglobin synthesis. ❖ Iron is essential for heme synthesis 3) Vitamins: ❖ All vitamins are needed for hematopoiesis especially vitamin B12 and folic acid ❖ Vitamin B12 and folic acid are important for the final maturation of the blood cells because they are essential for the synthesis of DNA ❖ Deficiency of either vitamin B12 or folic acid causes megaloblastic anemia, Leukopenia, and thrombocytopenia.

Question 37

What is the definition of anemia?

Answer 37

is a ↓ in O2 carrying capacity of blood due to deficiency of Hb which can be caused by either ↓ed number of RBCs or too little Hb in the cells.

Question 38

What are the causes of anemia?

Answer 38

1) Blood loss anemia: due to blood loss as in hemorrhage, 2) aplastic “ALL BLOOD CELLS” anemia: due to failure of functions of bone marrow 3) megaloblastic anemia: due to lack of Vit B12 and folic acid and "causes rupture" 4) hemolytic anemia: due to excessive RBCs destructions as in thalassemia "disturbance in HB synthesis"

Question 39

What is the definition of Purpura?

Answer 39

is a bleeding disorder (manifested by red spots in the skin) due to deficiency in platelets count (thrombocytopenia) or functions (non-thrombocytopenic purpura)

Question 40

What are white blood cells disorders?

Answer 40

include: 1) Leucopenia means WBCs count is less than 4000/mm3 2) Leukocytosis means WBCs count is more than 11000/ mm3 3) Leukemia means an abnormal increase in the number of WBCs (cells are immature and undifferentiated cells)

Question 41

What is administrated to various forms of cancer who are receiving chemotherapy?

Answer 41

Synthetic forms of CSF and interleukin hormones are often administered to patients, with various forms of cancer who are receiving chemotherapy, to revive their WBC counts.