06. Blood & Haemopoiesis

Secretory (glandular) epithelia are specialized for the production and secretion of substances such as:

• Hormones - secreted by endocrine glands into the bloodstream.
• Enzymes - secreted by exocrine glands into ducts leading to the target area.
• Mucus - produced by goblet cells and mucous glands to lubricate and protect surfaces.

Connective tissue is characterized by:

• Extracellular Matrix - composed of fibers (collagen, elastin) and ground substance.
• Variety of Cell Types - including fibroblasts, adipocytes, macrophages, and mast cells.
• Functions - providing support, binding other tissues, storing energy, and facilitating transport (e.g., blood).

The types of cartilage include:

Hemopoiesis is the process of blood cell formation, which occurs primarily in the bone marrow. It involves:

1. Myeloid Lineage - producing red blood cells, platelets, and some white blood cells.
2. Lymphoid Lineage - producing lymphocytes (a type of white blood cell).
3. Regulation - controlled by various growth factors and hormones, such as erythropoietin for red blood cell production.

Nervous tissue is responsible for:

• Transmission of Nerve Impulses - through neurons.
• Processing Information - by integrating sensory input and coordinating responses.
• Supporting Cells - glial cells provide support, nourishment, and protection to neurons.

The primary functions of blood include:

1. Transport of gases (O2, CO2)
2. Transport of nutrients
3. Transport of hormones
4. Transport of substances to be discarded
5. Coagulation mechanism
6. Immunity

• Serum: Contains no fibrinogen (resulting from blood clotting).
• Plasma: Contains fibrinogen (when anti-coagulant is added, e.g., EDTA).

Plasma is composed of:

• Water: 92% by weight
• Proteins: 7% by weight (including Albumins 58%, Globulins 37%, Fibrinogen 4%, Regulatory proteins 1%)
• Other solutes: 1% by weight (including Electrolytes, Nutrients, Respiratory gases, and Waste products)

The normal concentration range of erythrocytes (red blood cells) in whole blood is 3.5-5.5 million/mm³.

The hematocrit levels are:

• Males: 40-50%
• Females: 35-45%

The buffy coat contains leukocytes with a normal range of 4500-11,000/mm³. The types of leukocytes and their proportions are:

• Neutrophils: 54%-62%
• Lymphocytes: 25%-33%
• Monocytes: 3%-7%
• Eosinophils: 1%-3%
• Basophils: 0%-0.75%

Plasma cells are B lymphocyte-derived cells that primarily function as antibody-producing cells.

Plasma cells have an eccentric nucleus with 'clockwheel' heterochromatin, large basophilic rough endoplasmic reticulum (rER), and a pale Golgi apparatus.

The typical lifespan of a plasma cell is approximately 10-20 days.

Anemia is characterized by a decrease in RBCs or hemoglobin, leading to symptoms such as fatigue and pallor.

Leukemias involve the malignant proliferation of white blood cells (WBCs).

Thrombocytopenia is defined as a decrease in platelets, which increases the risk of bleeding.

RBCs, derived from CFU-E, primarily function in oxygen transport and have a lifespan of approximately 120 days.

Platelets, originating from CFU-Meg, play a crucial role in clotting and have a lifespan of about 7-10 days.

Neutrophils, produced from CFU-GM, are involved in phagocytosis and have a short lifespan of approximately 6-8 hours.

Lymphocytes, derived from CLP, are essential for adaptive immunity and can live for days to years.

The normal range of platelets in the buffy coat is 150,000-400,000/mm³.

The primary locations of hemopoiesis are:

1. Yolk sac (mesoblastic phase)
2. Liver and spleen (hepatic phase)
3. Bone marrow (medullary phase begins around the 5th month of gestation and becomes dominant after birth)

A multipotential hematopoietic stem cell differentiates into the common myeloid progenitor (CMP) and the common lymphoid progenitor (CLP).

The common myeloid progenitor (CMP) differentiates into several cell types including megakaryocyte, erythrocyte, mast cell, and myeloblast. The myeloblast further differentiates into basophil, neutrophil, eosinophil, and monocyte. Monocytes can further differentiate into macrophage and dendritic cell. These cells are labeled as INNATE.

The common lymphoid progenitor (CLP) differentiates into natural killer cells (large granular lymphocytes) and small lymphocytes. The small lymphocyte can further differentiate into T lymphocytes and B lymphocytes, with B lymphocytes further differentiating into plasma cells. These cells are labeled as ADAPTIVE.

The two major lineages of CFUs are:

1. Lymphoid (CFU-L or CLP) - stimulated by Interleukin-7 (IL-7).
2. Myeloid (CFU-GM) - stimulated by Granulocyte- (G-CSF) and Monocyte-Colony Stimulating Factor (M-CSF).

The following cytokines stimulate the respective CFUs:

The stroma in bone marrow is formed by reticular connective tissue, where specialized fibroblastic cells called stromal cells, reticular cells, or adventitial cells create a delicate web of reticular fibers.

The hemopoietic environment in bone marrow consists of hemopoietic cords (C) or islands of cells, sinusoidal capillaries (S), and discontinuous endothelium (E).

Erythrocytes are biconcave and disc-shaped. They are anucleate and lack organelles, with their cytoplasm primarily composed of hemoglobin.

The lifespan of erythrocytes is approximately 120 days.

Blood groups and Rh factors in erythrocytes are determined by surface antigens present on the cell membrane.

The typical concentration of erythrocytes in blood is between 4 to 6 million cells per microliter (µl).

During the early stages of erythropoiesis, there is a decrease in both ribosomes and basophilia.

In the later stages of erythropoiesis, there is an increase in both hemoglobin and eosinophilia levels.

The reticulocyte is the final stage in erythropoiesis where the cell nucleus is ejected, leading to the formation of a mature erythrocyte (red blood cell). It constitutes about 1% of RBCs in blood.

During erythropoiesis, there is a decrease in the concentration of RNA and an increase in the concentration of hemoglobin over time.

Maturation lasts approximately 7 days and is stimulated by erythropoietin (EPO) from the kidneys.

During maturation, cellular organelles such as mitochondria, Golgi apparatus, and endoplasmic reticulum are eliminated. This is significant because:

• They do not consume oxygen, allowing for maximum efficiency in O2 transport.
• More space becomes available for hemoglobin-Fe2+.

Rouleaux formations refer to the arrangement of red blood cells resembling a 'stack of coins'. This occurs when red blood cells are closely aligned and tightly packed together.

The two main categories of leukocytes are Granulocytes and Agranulocytes.

Leukocytes participate in both the innate and humoral (adaptive) immune responses.

Azurophilic granules contain lysosomal enzymes (e.g., hydrolases) and myeloperoxidase (MPO), and they are stained with azure (aniline blue) dye.

During the maturation of neutrophils, the nuclear shape changes, with the band neutrophil being the pre-mature form.

In granulopoiesis, Golgi activity changes to package proteins for the specific granules, which differ in each of the three types of granulocytes.

Neutrophils typically account for 60% of white blood cells (WBCs).

Neutrophils have a diameter range of 12-15 µm.

Neutrophil nuclei are multi-lobed, typically consisting of 3 to 5 segments joined by thin strands, which is why they are referred to as polymorphonuclear.

Neutrophils have a lifespan ranging from hours to a couple of days.

The primary functions of neutrophils are to kill and phagocytose bacteria.

Eosinophils typically make up about 3% of the total white blood cell count.

Eosinophils range from 12 to 17 µm in diameter.

Eosinophils have a bi-lobed nucleus.

The granules of eosinophils appear red or dark pink under a microscope.

Eosinophils have a lifespan of about 1 to 2 weeks in circulation.

Eosinophils primarily function to kill helminthic and other parasites and modulate local inflammation through substances like Major Basic Protein (MBP).

Basophils constitute the lowest percentage of white blood cells at 1%.

Basophils typically have a diameter of 12-15 µm.

Basophils have bi-lobed or S-shaped nuclei.

Basophils appear dark blue to purple, with large granules obscuring or overlying the nucleus.

Basophils can survive for several months in the bloodstream.

Basophils release histamine during allergies and help modulate inflammation.

Lymphocytes constitute 30% of white blood cells (WBCs).

Lymphocytes vary in size from 8 to 18μm, have a rather spherical nucleus, and possess scant cytoplasm. They do not have significant granules (s.g).

Lymphocytes can live from hours to many years or decades depending on their type and function.

Lymphocytes serve as effector and regulatory cells for adaptive immunity, specifically as T- and B cells.

Cluster of Differentiation (CD) surface molecules are specific markers found on the surface of lymphocytes that help in identifying and classifying different types of lymphocytes.

Monocytes typically range from 12 to 20 µm in diameter.

Monocytes constitute about 6% of the total white blood cell count.

Monocytes have an indented or kidney-shaped nucleus that is often described as C-shaped and is located eccentrically within the cell.

Monocytes can have a lifespan ranging from hours to years depending on their function and environment.

Monocytes serve as precursor cells for the mononuclear phagocytic system (MPS), which is crucial for immune response and phagocytosis.

Natural killer (NK) cells originate from the common lymphoid progenitor (CLP), similar to B and T cells, and are part of the innate immune system.

Natural killer (NK) cells express CD16 and CD56, but do not express CD3.

The lifespan of natural killer (NK) cells is approximately 2 weeks.

Natural killer (NK) cells comprise about 1.5% of circulating lymphocytes.

The primary function of natural killer (NK) cells is to provide direct cytotoxicity by eliminating tumor cells and virally-infected cells.

Natural killer (NK) cells act rapidly and without prior sensitization, bridging the gap between innate and adaptive immunity.

Thrombopoietin (TPO) is a hormone produced by the kidneys and liver that stimulates the production of platelets from megakaryocytes in the bone marrow.

Megakaryocytes are very large cells, measuring up to 150 µm in diameter, and contain a single, polyploid nucleus with multiple copies of DNA. They have cytoplasmic extensions known as proplatelets, which are involved in platelet formation.

Proplatelets are cytoplasmic extensions of megakaryocytes that play a crucial role in the formation of platelets (thrombocytes) as they bud off from the megakaryocyte's surface during thrombopoiesis.

Platelets, also known as thrombocytes, are small cell fragments derived from megakaryocytes found in the bone marrow. They have a diameter of 2-4μm and are produced in a quantity of 200,000-400,000 per μL of blood. The average lifespan of platelets is about 10 days.

The primary function of platelets is to promote coagulation and hemostasis. They undergo rapid degranulation upon contact with collagen, which triggers the blood clotting process.

The periphery of platelets contains actin and microtubules in the lightly stained hyalomere region. The center, known as the granulomere region, includes:

1. Alpha granules - components for blood clotting.
2. Delta (dense) granules - contain electron-dense calcium, too small to be seen in light microscopy.
3. Open canalicular system (OCS) - a network of invaginating membranes that facilitates degranulation.

Platelet-rich plasma (PRP) therapy is a form of regenerative medicine that utilizes a concentrated source of cellular signaling factors and growth factors derived from the patient's own blood. It is used to promote healing and tissue regeneration, particularly in conditions like osteoarthritis.

The main steps involved in the PRP therapy process are:

1. Withdraw blood from the patient's arm using a syringe.
2. Whole blood is collected in a test tube.
3. Separate the platelets by placing the blood in a centrifuge.
4. After centrifugation, the blood separates into three layers: platelet-poor plasma, platelet-rich plasma, and red blood cells.
5. Extract platelet-rich plasma from the middle layer.
6. Inject the platelet-rich plasma into the injured area using a syringe.

The main migratory cells of connective tissue involved in inflammation include:

• Neutrophils (N)
• Eosinophils (Eo)
• Basophils (B)
• Lymphocytes (L)
• Macrophages (M)
• Mast cells (Ma)
• Plasma cells (P)

Cytokines, such as IL-1 and TNF-α, are released by activated macrophages and induce the expression of selectins on endothelial cells, facilitating the interaction with neutrophils.

Neutrophils adhere to endothelial cells through the binding of integrins on the neutrophils to integrin receptors (ICAM-1) on the endothelial cells, leading to firm adhesion.

Diapedesis is the process by which neutrophils squeeze through the junctions of endothelial cells to enter the interstitial space in connective tissue after firm adhesion.

The sequence of events during extravasation includes:

1. Activation of macrophages releasing cytokines.
2. Expression of selectins on endothelial cells.
3. Rolling of neutrophils along the vessel wall.
4. Firm adhesion of neutrophils via integrins.
5. Diapedesis into the interstitial space.

Macrophages, also known as histiocytes, are large phagocytic cells measuring 10-30 µm. They have an eccentrically located, oval-shaped nucleus and are derived from monocytes. Their names can vary depending on the organ they are found in.

Mast cells contain basophilic secretory granules that include:

• Heparin: Acts locally as an anticoagulant.
• Histamine: Promotes increased vascular permeability and smooth muscle contraction.
• Eicosanoid lipids: Such as prostaglandins and leukotrienes, which are mediators of the inflammatory response.

Mast cells are primarily involved in immediate hypersensitivity reactions to allergens, which occur within minutes.