1. Hematology Introduction
Organization of blood and blood forming organs

2. What is hematology? Hematology is the study of blood.
Blood: is the fluid where the cells are free and suspended.
It can cross the tissues.
has red color.
Has volume of 5-6 liters, this is 7-8% of the total body weight.

3. Has PH of (alkaline).
Specific gravity is
It is composed of plasma (~53-58% of the blood volume), before clotting occurs, and serum after clotting occurs.
Plasma consists of 91-92% water, and 8-9%solids.

4. Solids are:
Albumin.
Glucose.
Fibrinogen.
Sodium.
Calcium.
Potassium.
Cholesterol.
Magnesium.
Carbon dioxide.
Phosphorus.
Neutral fats.
NPN group.
Oxygen.
Many other products.

5. Also there are such substances, like antibodies, hormones, complement and enzymes.
Cellular parts of the blood (45-47%):
Consists of:
The erythrocytes (RBCs) (~45%)
Contain hemoglobin
Function in the transport of O2 and CO2

6. The Leukocytes (WBCs) and platelets (thrombocytes) (~1%) Leukocytes are involved in the body’s defense against the invasion of foreign antigens. Platelets are involved in hemostasis which forms a barrier to limit blood loss at an injured site.

7. The cells are forming about 45-47% of the total blood volume in male and 42% in female. This percentage is determined by centrifugation and is known as heamatocrit (PCV), which is the percentage of the packed red blood cells.

8. Functions of the blood:

9. Nutritive: The blood transports nutrients from the gut to all parts of the body for use or storage.
Respiratory: the blood carries the oxygen to the tissue and remove carbon dioxide and other waste products from the tissues to be excreted by the lung, kidney, liver, and skin

10. 3- The blood regulates the temperature of the body, because it is constantly in motion.
4- Transportive: The blood transports the hormones from the endocrine glands to the tissues.
5- Excretory: To excrete the waste products of metabolism, for example urea, and uric acid.

11. Hematopoiesis
Hematopoiesis is a term describing the formation and development of blood cells.
Cells of the blood are constantly being lost or destroyed. Thus, to maintain homeostasis, the system must have the capacity for self renewal. This system involves:
Proliferation of progeny stem cells
Differentiation and maturation of the stem cells into the functional cellular elements.
In normal adults, the proliferation, differentiation, and maturation of the hematopoietic cells (RBCs, WBCs, and platlets) is limited to the bone marrow and the widespread lymphatic system and only mature cells are released into the peripheral blood.

12. Sites of production: Fetus: 0-2 months (yolk sac).
2-7 months ( liver and spleen).
5-9 months (bone marrow).
infants: bone marrow
Adults: bone marrow, ribs, sternum, skull, sacrum and pelvis.

13. Hematopoiesis in the bone marrow is called medullary hematopoiesis
Hematopoiesis in areas other then the bone marrow is called extramedullary hematopoiesis
Extramedullary hematopoiesis may occur in fetal hematopoietic tissue (liver and spleen) of an adult when the bone marrow cannot meet the physiologic needs of the tissues. This can lead to hepatomegaly and/or splenomegaly (increase in size of the liver or spleen because of increased functions in the organs).
Hematopoietic tissue includes tissues involved in the proliferation, maturation, and destruction of blood cells

14. Thrombocytopenia (decrease in platlets in the blood)
Splenectomy (removal of the spleen), Hypersplenism (splenomegaly) – in a number of conditions the spleen may become enlarged.
Leukopenia decreased WBCs.
Thrombocytopenia decreased plateletets.
Pancytopenia: when all three cell types are decreased.

15. Derivation of blood cells
The committed lymphoid stem cells will be involved in lymphopoiesis to produce lymphocytes
The committed myeloid stem cell can differentiate into any of the other hematopoietic cells including erythrocytes, neutrophils, eosinophils, basophils, monocytes, macrophages, and platlets.
Hematopoietic cells can be divided into three cellular compartments based on maturity:
Pluripotential stem cell capable of self-renewal and differentiation into all blood cell lines.
Committed proginator stem cells destined to develop into distinct cell lines
Mature cells with specialized functions

16. Second lecture

17. Erythrocyte:
Normal erythrocyte is a round biconcave disk like cell, it is non-nucleated, containing haemoglobin. It measures about microns.
Life span: the average is days.
Function: RBC carry oxygen from the lung to the body cells and carry carbon dioxide from the body cells to the lung.

18. Erythrocytosis: increased in the blood cells count, which may lead to polycythemia. The decrease in the blood cells count may lead to anaemia.
Reticulocyte: is a very young erythrocyte which contains remainant of RNA. The precipitated RNA is seen when stained with a supravital stain such as new methylene blue or brilliant crystal blue dyes.
Reticulocytosis: increased blood reticulocyte count.

19. Blood Cell Production (Hemopoiesis)
Hemopoietic tissues produce blood cells
Red bone marrow produces RBCs, WBCs and platelets
Stem cells called hemocytoblasts, multiply continually and are pluripotent (capable of differentiating into multiple cell lines)
committed cells are destined to continue down one specific cell line
Stimulated by erythropoietin, thrombopoietin and colony stimulating factors (CSFs).

20. B. Erythropoietin and Its Receptor:
Human erythropoietin is a 193-amino acid glycoprotein.
About 90% is produced in the kidney, and the rest is produced in a variety of extrarenal sites.
The signal that causes erythropoietin-secreting cells to synthesize and release the cytokine is hypoxia.
Whenever the oxygen level within the cytoplasm of erythropoietin-producing cells falls below a critical level, erythropoietin is synthesized and secreted into the bloodstream.

21. Intracellular hypoxia can result from a number of causes, including: [1] Low partial pressure of oxygen (pO2) dissolved in the plasma (hypoxemia), such as may occur in lung disease, or climb to high altitude [2] Anemia of any cause.
All of these conditions limit oxygen delivery to all cells in the body, including the cells which produce erythropoietin.

22. Considerable evidence supports the concept that the biochemical "oxygen sensor" within erythropoietin-producing cells is a type of specialized heme protein, which detects the intracellular oxygen level and translates it into a "message" that results in stimulation or suppression of erythropoietin synthesis.
Once synthesized and released from the cell, erythropoietin travels in the bloodstream to the bone marrow, where it binds to receptors on erythroid cells, thereby initiating their proliferation and differentiation.
Activated proteins regulate the activation of specific genes involved in cell division or differentiation.

23. Multiplicity of Lineages
1- Erythrocyte Homeostasis
Classic negative feedback control
Hypoxemia in kidneys causes increased EPO production.
Stimulation of bone marrow
RBC count will be increased in 3-4 days

25. Stimuli for erythropoiesis
Low levels of O2
Increase in exercise
Hemorrhaging
Erythrocyte Production
Erythropoiesis produces 2.5 million RBCs/second from stem cells (hemocytoblasts) in bone marrow

26. First committed cell is pro-erythroblast
Has receptors for erythropoietin (EPO) from kidneys; EPO stimulates development of erythroblast
Erythroblasts multiply & synthesize hemoglobin

27. Normoblasts discard their nucleus to form a reticulocyte named for fine network of endoplasmic reticulum
Enters bloodstream as 0.5 to 1.5% of circulating RBCs (retics).
Development takes 3-5 days & involves
Reduction in cell size, increase in cell number, synthesis of hemoglobin & loss of nucleus
Blood loss speeds up the process increasing reticulocyte count

28. Nutritional Needs for Erythropoiesis
1- Iron :
Is key nutritional requirement for erythropoiesis
Lost daily through urine, feces, and bleeding
Low absorption rate requires consumption of mg/day
Dietary iron in 2 forms: ferric (Fe+3) & ferrous (Fe+2)
Stomach acid converts Fe+3 to absorbable Fe+2
Gastroferritin from stomach binds Fe+2 & transports it to intestine

29. Absorbed into blood & binds to transferrin to travel bone marrow uses to make hemoglobin, muscle used to make myoglobin and all cells use to make cytochromes in mitochondria
Liver binds surplus to apoferritin to create ferritin for storage
B12 & folic acid (for rapid cell division)
vitamin C & copper (for cofactors for enzymes synthesizing RBCs)

30. 2- Leukocyte Production (Leukopoiesis)
Committed cell types -- B and T progenitor lymphocytes and granulocyte-macrophage colony-forming units
Possess receptors for colony-stimulating factors released by mature WBCs in response to infections
Red bone marrow stores and releases granulocytes and monocytes
Some lymphocytes leave bone marrow unfinished go to thymus to complete their development (T cells)

31. Circulating WBCs do not stay in bloodstream
Granulocytes leave in 8 hours & live 5 days longer
Monocytes leave in 20 hours, transform into macrophages and live for several years
WBCs providing long-term immunity
(lymphocytes) last decades

33. Leukocyte Descriptions (WBCs)
Granulocytes
eosinophils - 2-4%
basophils - <1%
neutrophils %
Agranulocytes
Lymphocytes (B and T cells) %
Monocytes - 3-8%

34. Granulocyte Functions
Neutrophils
(↑ in bacterial infections)
Phagocytosis of bacteria
Releases antimicrobial chemicals
Eosinophils
↑ in parasitic infections or allergies
Phagocytosis of antigen-antibody complexes, allergens & inflammatory chemicals
Release enzymes destroy parasites such as worms
Basophils
(↑ in chicken pox, sinusitis, diabetes)
Secrete histamine (vasodilator)
Secrete heparin (anticoagulant

35. Agranulocyte Functions
Lymphocytes (↑ in diverse infections & immune responses)
Destroy cancer & foreign cells & virally infected cells
“Present” antigens to activate other immune cells
Coordinate actions of other immune cells
Secrete antibodies & provide immune memory
Monocytes (↑ in viral infections & inflammation)
Differentiate into macrophages
Phagocytize pathogens and debris
“Present” antigens to activate other immune cells (APC)

36. Platelet Production (Thrombopoiesis)
Hemocytoblasts that develop receptors for thrombopoietin from liver or kidney become megakaryoblasts
Megakaryoblasts repeatedly replicates its DNA without dividing forms gigantic cell that remains in bone marrow called megakaryocyte (100 μm in diameter)
Infoldings of megakaryocyte cytoplasm splits off cell fragments that enter the bloodstream as platelets (live for 10 days)
Some stored in spleen and released as needed

37. Platelets Small fragments of megakaryocyte cytoplasm
2-4 μm diameter & containing “granules”
Pseudopods provide amoeboid movement & phagocytosis

38. Functions:
Secrete clotting factors, growth factors for endothelial repair, and vasoconstrictors in broken vessels
Form temporary platelet plugs
Dissolve old blood clots
Phagocytize bacteria
Attract WBCs to sites of inflammation