Blood & Hematopoiesis

Haemato

- Blood

Poesis

- Formation, production

Blood

- Fluid connective tissue made of plasma, erythrocytes, leukocytes, and platelets that circulates through cardiovascular system

Plasma

- Liquid part of blood

Functions of blood

1. Delivery of nutrients & oxygen // transport of waste & CO2

2. Delivery of hormones, regulatory substances

3. Maintains homeostasis via: acting as a buffer, thermoregulation, and participating in coagulation

Formed Elements

- Cellular portion of blood : erythrocytes, leukocytes, platelets

Hematopoiesis

- Refers to the commitment/differentiation process of a stem cell to the different types of cells found in the blood

i.e Blood cell formation

Where does hematopoiesis predominantly occur in adults?

- Bone marrow (red)

What are the other sites of hematopoiesis?

- Liver

- Thymus

- Spleen

Medullary vs Extramedullary Hematopoiesis

- Medullary: Normal production of blood cells inside marrow

- Extramedullary: Blood cell formation outside of bone marrow (liver, spleen, lymph nodes)

When does extramedullary hematopoiesis occur?

- Rises as the body's response to severe stress, chronic anemia, or bone marrow failure

It is inherently a benign, lifesaving compensatory method

What stem cells are located in the bone marrow?

- Hematopoietic Stem Cells

Hematopoietic Stem Cells

- Cell in the bone marrow that gives rise to ALL types of blood cells

What can hematopoietic stem cells first differentiate into?

- Common lymphoid progenitors

- Common myeloid progenitors

Lymphoid Progenitor

- Stem cell in bone marrow cell that gives rise to all lymphocytes

Lymphoblast

- Immature lymphocyte → can become B/T/NK cells

What is a lymphocyte?

- It is the second most abundant white blood cell in the

human blood

Lymphocyte vs Leukocyte

- Leukocytes: General term for all white blood cells

- Lymphocytes: One specific TYPE of leukocyte

Common lymphoid progenitor cells can also become what? What is its fate?

- Immature dendritic cells → moves into tissues → becomes lymphoid dendritic cells

Dendritic Cells

- Specialized white blood cells that patrol the body searching for antigens that produce infections

- Are "peripheral" antigen presenting cells

Antigen Presenting Cells (APCs)

- Cells such as B cells, macrophages, and dendritic cells that can present exogenous antigens to naive or memory T cells, activating them → elicits immune response

What systems do dendritic cells connect?

- Provide an important connection between the innate and adaptive immune system

Common Myeloid Progenitor

Give rise to: (these are all precursors/immature)

- Myeloblasts

- Promonocytes

- Mast cell precursors

- Megakaryocytes

- Erythroblasts

What can Myeloblasts give rise to?

The Granulocytes:

- Band Neutrophils

- Band Basophils

- Band Eosinophils

Why do myeloblasts initially give rise to "band" cells

- Neutrophils/Basophils/Eosinophils start off as "band" cells because they are immature

What happens to band cells once they enter circulation?

- They mature into → neutrophils/basophils/eosinophils

Which immune cell is important in the acute immune response?

- Neutrophils: First responders to infection/inflammation

Neutrophil: Appearance

- Multi lobed nucleus, pale red and blue cytoplasmic granules

What are Basophils important for?

- Release histamine and other mediators of inflammation

- Helps defend your body against parasites, manage allergies/allergic reactions

Basophil appearance

- Bilobed nucleus, purplish-black cytoplasmic granules

Looks like nerd gummy cluster

Eosinophils

- Plays an important role in allergies and parasitic infections

- IgE mediated

Eosinophil appearance

- Bilobed nucleus, red cytoplasmic granules

Promonocytes

- Precursor cells that develop into monocytes.

Monocytes

- An agranular leukocyte that is able to migrate into tissues and transform into a macrophage.

What happens when circulating monocytes move into tissues?

- Differentiate into macrophages

Macrophages

- Phagocytize foreign substances and help activate T cells

- APCs

What can circulating monocytes also differentiate into?

- Dendritic cells → i.e myeloid dendritic cells

When do mast cell precursors mature?

- After entering circulation and move into tissues

Mast cells

- Cells that release chemicals (such as histamine) that promote inflammation

- Very important in allergies, inflammatory response, and hypersensitivity

Mast cell appearance

- An oval or irregularly shaped blob filled with dense, dark purple or blue granules that often hide the cell's center nucleus

What do common myeloid progenitors differentiate into when exposed to thrombopoietin?

- Megakaryocytes

Thrombopoietin

- Hormone from liver stimulates platelet formation

What can Myeloid progenitor cells differentiate into when exposed to erythropoietin?

- Erythroblasts

Erythropoietin

- A hormone produced and released by the kidney that stimulates the production of red blood cells by the bone marrow

Erythroblast

- An immature red blood cell; still nucleated at this stage

Where are megakaryocytes typically located?

- In bone marrow, NOT circulation

How are platelets released into circulation?

- Megakaryocytes INSIDE bone marrow rupture → releases platelets into circulation

Platelets

- Thrombocytes; cell fragments that aid in blood clotting

What do erythroblasts mature into?

- Erythrocytes (mature RBCs, NO nucleus)

Erythrocytes

- Red blood cells responsible for oxygen transport

Erythrocyte: Appearance

- Pink, anucleate, biconcave discs with central pallor

Granulocytes vs Agranulocytes

Granulocytes (neutrophils, eosinophils, basophils) and agranulocytes (monocytes, lymphocytes).

What is the amount of each Leukocyte in blood?

Never let monkeys eat bananas:

1. Neutrophils

2. Lymphocytes

3. Macrophages

4. Eosinophils

5. Basophils

Where does Medullary Hematopoiesis occur in healthy adults?

Bone marrow of:

- Pelvis

- Vertebrae

- Sternum

Where does Hematopoiesis occur prior to birth as an embryo and then a fetus?

- Embryo: STARTS in umbilical vesicle (Yolk sac)

- Fetus: Predominantly the liver and spleen

Why does Hematopoiesis in the liver/spleen drop off when you are born?

- The bone marrow slowly takes over

Red vs Yellow Marrow

yellow marrow consists of fat that is energy reserve for the body, while red marrow produces cells that develop into blood cells

Where can hematopoiesis occur during infections (adults)?

- In lymph nodes, spleen, liver

Extramedullary

When a child has an infection, why can the liver/spleen enlarge?

- Bc they are working harder to make more blood → hepatosplenomegaly

Stem cells → progenitors → blasts → mature cells: What are the overall developmental abilities of the cells and how does it change with maturation?

- The ability to give rise to different cell types (potentiality), decreases from stem → progenitor cells

- Self-renewing properties also decrease as stem cells → progenitor cells

- The ability of cells to divide (mitotic activity) increases from Stem → blasts and then abruptly stops in later blast stages

- Cells begin to take on mature morphologies as they move from blasts → mature cells

What happens to the size of the cell/nucleus from stem → mature/differentiated cell?

- Cell and nucleus both get smaller

What are the developmental changes of the nucleus from Stem Cell → Mature/Differentiated cell?

- Nucleoli disappears

- Heterochromatin ↑, Euchromatin ↓

- Nucleus can become multilobed (granulocytes) or lost altogether (RBCs)

Steps of Erythropoiesis

1. Proerythroblast

2. Basophilic erythroblast

3. Polychromatophilic erythroblast

4. Orthchromatophilic erythroblast

5. Reticulocyte

6. Erythrocyte

Erythropoiesis Mnemonic

Physicians Buy Plenty Of Probes & Retractors:

- Proerythroblast

- Basophilic erythroblast

- Polychromatophilic erythroblast

- Orthochromatophilic

- Polychromatophilic reticulocyte

- RBCs

How long does erythrocyte development (from proerythroblast → erythrocyte) take?

- ~ 1 week

Which cells from the stages of erythrocyte development can be found in the blood?

- Erythrocytes (mature)

- Reticulocytes (immature) → don't really see them on smears bc/ they mature very rapidly

What are the general changes in appearance during Erythropoiesis?

- Cells get smaller, nucleus gets smaller faster

- Nucleoli disappear → chromatin clumps → nucleus extruded

- Cytoplasm becomes more eosinophilic as amt of hemoglobin ↑↑

Key Identifiers of Proerythroblasts

- Prominent nucleoli, very large nucleus

- Very thin, basophilic (blue) cytoplasm

Key Identifiers of Basophilic Erythroblasts

- Nucleus condenes, no visible nucleoli

- Very very basophilic cytoplasm

Key Identifiers of Polychromatophilic Erythroblasts

- Cell volume reduced

- Regions of BOTH eosinophilia/basophilia

What stage is the nucleus ejected during Erythropoiesis?

- Late stage orthochromatophilic erythroblasts

Key Identifiers of Orthochromatophilic Erythroblasts

- Cell and nucleus continue to condense

- NO basophilia

- Pink/grey cytoplam

What does the presence of Orthochromatophilic Erythroblasts in the blood indicate?

- Indicates early release of progenitors from bone marrow → possible pathology

Key Identifiers of Reticulocytes

- nucleus ejected

- acidophilic, but I have not lost the poly ribosomes used to synthesize globin

- matures very quickly in circulation

Reticulocyte counts are useful for what?

- To check if RBCs are actually being produced

- High amts indicate possible pathology (reason to replace blood fast)

Granulopoiesis

- The production of neutrophils, eosinophils and/or basophils

Granulopoiesis steps

1, Myeloblast

2. Promyelocyte

3. Myelocyte

4. Metamyelocyte

5. Band form

6. Mature form

Appearance of Myeloblast vs Promyelocyte

- Myeloblast: Finely disperse chromatin

- Promyelocyte: Basophilic cytoplasm with red/magenta GRANULES

Appearance of Myelocytes

- ↑ Granules, smaller nucleus/cell

- Nucleus more off center

Appearance of Metamyelocytes

- Bean shaped nucleus

Band cell appearance

- horseshoe shaped nucleus

Granulopoiesis: Band cell vs Mature Cell Appearance

- Left: Mature, segmented nucleus

- Right: Horseshoe band cell

Thrombopoiesis

production of platelets

Thrombopoiesis is driven by what?

- Thrombopoietin (TPO)

Appearance of megakaryocytes

- An exceptionally large size, a multilobulated nucleus, and abundant granular cytoplasm that produces platelets

How are platelets formed from megakaryocytes?

- Megakaryocytes extend long processes which extend into blood vessels → proplatelet "blebs" pinch off from processes → circulating platelets in blood

Margination

- The sticking of phagocytes to blood vessels in response to cytokines at the site of inflammation

Demargination

- Depletion of neutrophil stores reduces their accumulation at inflammatory sites and in exudates

Diapedesis

- The passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation in response to chemokine signaling