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Front 1

Hematopoietic functions of the liver and bone marrow

Back 1

- The first blood cells form in the yolk sac mesoderm, but these are transitory meaning they don't last.
- The first definitive blood cells that form come from aorta-gonad-mesonephros region (AGM). This area is around the developing aorta. These cells colonize the liver which is major hematopoietic organ of the embryo and fetus from 2-7 months of development.
- Liver stem cells colonize into the bone marrow, and they become the primary blood forming tissue from 7 months onward.

Front 2

Pluripotent hematopoietic stem cells

Back 2

Precursors of all blood cells. They are found in the bone marrow and have capacity for self-renewal, asymmetric replication (1 mitotic daughter cell retains a self-renewing capability, and the other differentiates into a non-dividing population of stem cells), and differentiation. They are small, mono-nucleated (hard to see under a microscope)

Front 3

Progenitor cells (CFU units)

Back 3

- Have the ability to differentiate into different cell types, but not with as much freedom as stem cells do. They also cannot replicate indefinitely like stem cells can.
- Progenitor cells are colony forming units and there are four different kinds of colonies they form depending on the parent cell type:
1) CFU-E, erythrocyte takes 7-8 days
2) CFU-GM, granulocyte-monocyte, takes 14-18 days
3) CFU-Me, megakaryocyte
4) CFU-L, Lymphocyte
- Later stages involve transformation of these progenitor cells to precursor (blast) cells.

Front 4

Hematocrit

Back 4

Total volume of red blood cells when packed under centrifugation. Should be about 45% of total volume of blood.

Front 5

Buffy coat

Back 5

After centrifugation, this thin layer on top of the RBCs, it's made of WBCs and platelets--should be 1% of volume.

Front 6

Blood serum

Back 6

Top layer after centrifugation

Front 7

Red blood cells

Back 7

- Carry O2 and CO2
- Anucleate
- Biconcave
- 120 day life
- Staining: pink from cytoplasm due to acidophilia of hemoglobin.

Front 8

Eosinophils

Back 8

- Nucleus is bilobed w/ clumped chromatin
- Cytoplasm is large w/ coarse, red granules

- They phagocytize antigen-antibody complexes and parasites

Front 9

Neutrophils

Back 9

- Nucleus has 3-5 lobes
- Dark purple staining
- Pale granules in cytoplasm
- They phagocytize bacteria and multiply during infections

Front 10

Basophils

Back 10

- Nucleus is bilobed or segmented
- Cytoplasm is dark with large blue granules, obscuring nucleus.
- Involved with anticoagulation and increase vascular permeability

Front 11

Lymphocytes (agranular)

Back 11

- Entire cell is very small compared to others, including nucleus
- Nucleus takes up most of cell
- Cytoplasm is pale blue/gray
- They act in humoral (B cell) and cellular (T cell) immunity.

Front 12

Monocytes (agranular):

Back 12

- Nucleus is indented, looks like a kidney
- Cytoplasm is agranular, with pale blue cytoplasm and has lysosomes.
- Motile and give rise to macrophages.

Front 13

Distinguish between the thymic cortex and medulla

Back 13

The Thymic cortex typically stains dark, it is lymphocyte dense. The inner medulla stains lightly.

Front 14

Epithelial reticular cells and the blood-thymus barrier

Back 14

- By electron microscopy, ERCs contain lysosomes, electron-dense granules and abundant intermediate filaments (tonofilaments)
- Thymic nurse cells are invested by a basal lamina and form part of the blood-thymus barrier in the cortex. This basal lamina is often fused with the thick basal lamina of the capillary endothelium. This creates a physical barrier:
1) Protects immature lymphocytes from foreign blood-borne antigens.

2) Prevents premature exposure of lymphocytes to foreign and self-antigens so that an immune reaction does not occur.
- Their cytoplasms are linked by desmosomes, they support clusters of maturing lymphocytes in the subjacent intervening spaces of the cortex.

Front 15

Information about T cells and B cells

Back 15

- All lymphocytes derive from bone marrow stem cells; those that differentiate and mature in the thymus are T cells, and those that develop in bone marrow where they acquire specific cell surface antigens are B cells.
- B and T cells are indistinguishable in conventional blood smears.
- In normal peripheral blood, 60%-80% of lymphocytes are T cells, while 10-15% are B cells, the rest are null cells which lack markers for B or T cells.
- T cell subpopulations:
1) CD4+ (Helper) - Depleted in HIV and AIDs
2) CD8+ (Suppressor)
3) Killer (cytotoxic)
4) Memory cells

- T cells are involved in cell-mediated immunity.
- B cells are involved in humoral (antibody) immunity.
- By electron microscopy, many free ribosomes and scattered profiles of rough endoplasmic reticulum (RER) dominate the cytoplasm. A small Golgi complex, small numbers of mitochondria and occasional lysosomes are also present.

Front 16

Thymic (Hassall's) Corpuscles

Back 16

- Spherical bodies with lamellar centers, their presence helps differentiate the thymus from other lymphoid organs.
- They vary in diameter from 20 to 150 mm and have a central hyaline core that is eosinophilic and may show signs of keratinization.
- Appear to contain clusters of degenerating ERCs arranged concentrically and rich in cytokeratins.
- Their function is not well understood, but they express the cytokine, thymic stromal theymopoietin, which instructs dendritic cells in the thymus to induce CD4+ regulatory T cell development.
- They may also play a role in removing apoptotic thymocytes.
- Their size and number increase in the elderly. Often calcify with advancing age.

Front 17

Organs systems with abundant lymphatic capillaries

Back 17

- Organ systems that open to the external environment
- Integument, respiratory, urogenital and digestive systems

Front 18

Mucosa-associated lymphatic tissue (MALT)

Back 18

Diffuse subepithelial lymphocyte aggregates that occur throughout the body (gastrointestinal, respiratory, and other genitourinary tracts). MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium.

Front 19

Lymphoid nodules

Back 19

- More densely packed, spherical clusters of lymphocytes (also known as follicles) and can be found within MALT as well as other sites. The nodules may appear as single collections of lymphocytes or as more permanent, multiple aggregates such as tonsils and peyer patches (within the intestinal mucosa).

Front 20

Germinal Centers

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- Major sites of B cell proliferation
- Contain small and large lymphocytes, lymphoblasts and follicular dendritic cells
- The surrounding mantle zone contains small lymphocytes.
- Antigen-dependent T cell differentiation and proliferation occur in the paracortex, beneath and between nodules.

Front 21

Distinguishing between the cortex and medulla of the lymph nodes

Back 21

- Lymph nodes are composed of a central medulla and outer cortex.

- They are surrounded by a fibrous connective capsule which sends trabeculae deep into the node.
- The outer cortex is consists of mostly B lymphocytes. Deeper parts of the cortex (paracortex) consists of mostly T lymphocytes.
- Lymphoid nodules, which contain a germinal center, account for the dark-stained cortex.
- In the pale stained medulla, there are medullary cords, which consist mainly of lymphocytes, macrophages and plasma cells. They lie near fluid filled medullary sinuses.

Front 22

Location and function of high endothelial venules (HEV)

Back 22

- HEVs are specialized blood vessels in the paracortex of a lymph node. They are specialized to allow passage of B and T cells from blood to perivascular areas.
- The B and T cells squeeze between the endothelial cells and penetrate the basement membrane. The endothelial cells lining the HEV have cell adhesion molecules to facilitate the movement of B and T cells.

Front 23

Sinus system of Lymph nodes

Back 23

Lymph is delivered to lymph node by afferent lymphatics that pierce the capsule of a lymph node. Lymph first goes into the sub-capular sinus, then into the trabecular/cortical sinuses, which converge into the medullary sinuses, that become continuous with the efferent lymphatics to leave the lymph node.

Front 24

Afferent and Efferent lymphatic vessels of the lymph nodes

Back 24

Lymph is delivered by the afferent lymphatic vessels directly into the sub-capular sinus. Lymph then flows from the sub-capular sinus into the cortical sinuses. Cells of medullary chords coalesce to form an efferent lymphatic vessel that returns filtered lymph fortified with activated lymphocytes and plasma cells to the lymphatic circulation.

Front 25

Arteries and veins of the lymph nodes

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Lymphocytes enter the node via incoming arteries and can leave the bloodstream by crossing the walls of specialized blood vessels, HEVs. They are located in the paracortex, have thin walls and are 30-50 nm in diameter.

Front 26

White pulp

Back 26

Grayish white islands of lymphoid tissue, mostly surrounding a central arteriole to form periarteriolar lymphatic sheaths (PALS). T cells found mostly in PALS. B cells are found in lymphoid nodules, located between PALS and the marginal zone.

Front 27

Red pulp

Back 27

Makes up most of the spleen, its red color is due to abundant erythrocytes. Its primary function is to filter the blood of antigens, microorganisms, and defective red blood cells.

Front 28

Blood flow through spleen (white pulp)

Back 28

- The splenic artery enters at the hilum and divides into several smaller trabecular arteries.
- They become arterioles in the white pulp, they are known collectively as central arterioles.
- Some branches of the central arteriole end as marginal sinuses that supply the marginal zone of the white pulp.
- Other arterial branches enter the red pulp as short straight penicillar arterioles. These drain into sheathed capillaries.

Front 29

Blood flow through spleen (red pulp)

Back 29

Closed system: About 90% of capillaries supplying red pulp drain directly into venous sinusoids, such as normally occurs elsewhere in the body.
Open system: Remaining open-ended capillaries discharge blood freely into the inter-sinusoidal meshwork so blood seeps out and percolates slowly between splenic cords before regaining access to sinusoids.
- Open and closed systems operate at different times according to physiologic conditions.
- A thin, discontinuous basal lamina forms circular bands around the endothelial cells, like hoops around staves of a leaky barrel.
- This leaky barrel disallows worn out or fragile erythrocytes to reenter circulation are are phagocytosed by macrophages. Sinusoids drain into large venules.
- Sinusoids drain into larger venules, which empty into trabecular veins. These merge to form the splenic vein, which leaves the organ at the hilum. The spleen lacks afferent lymphatics, but efferent lymphatics beginning in white pulp exit at the hilum.

Front 30

Why does the cytoplasm change from blue to gray to reddish pink during erythropoiesis?

Back 30

As maturation occurs, the primitive cells become smaller along with their nucleii. Their nuclei shrink at a faster rate than the rest of the cell, meaning cytoplasm is more visible. The blue cytoplasm in young cells is due to lots of rRNA, which make hemoglobin. Slowly the hemoglobin increases and rRNA concentration decreases, shifting the color from blue to reddish.

Front 31

Why is hypoxia the principal stimulus for erythropoietin secretion, and what is the normal duration of erythropoiesis?

Back 31

Erythropoiesis is regulated by a glycoprotein hormone called erythropoietin. This is secreted by interstitial peritubular cells in kidneys, mostly in response to hypoxia. Since the body must compensate for low O2, it must create more RBCs. This helps relieve hypoxia. Erythropoiesis is 7-8 days from pro-erythroblast to mature RBC

Front 32

Why do recurrent opportunist infections characterize DiGeorge syndrome (thymic aplasia)?

Back 32

In DiGeorge Syndrome, the thymus does not develop properly. Because the thymus is needed for T cell maturation, a T cell deficiency occurs. Thus a state of immunodeficiency is always present in these patients, and they cannot fight off infections as well as a normal immune system.

Front 33

What are lymphangitis and lymphadenitis and why are these conditions potentially dangerous?

Back 33

Lymphangitis = inflammation of lymphatic vessels
Lymphadenitis = inflammation of lymph nodes
- These conditions may occur when the lymphoid system is involved in chemical or bacterial transport after severe injury or infection. The lymphatic vessels, not normally evident, may become apparent as red streaks in the skin, and the nodes become painfully enlarged. This condition is potentially dangerous because the uncontained infection may lead to septicemia (blood poisoning).

Front 34

What is lymphedema?

Back 34

Localized type of edema, occurs when lymph does not drain from an area of the body. For instance, if cancerous lymph nodes are surgically removed from the axilla (compartment superior to the armpit), lymphedema of the limb may occur. Solid cell growths may permeate lymphatic vessels and form minute cellular emboli (plugs), which may break free and pass to regional lymph nodes. In this way, further lymphogenous spread to other tissues and organs may occur.

Front 35

What conditions can cause lymphadenopathy?

Back 35

- Abnormal enlargement of the lymph nodes
- Increased number of lymphocytes and macrophages in the node during antigenic stimulation in a bacterial or viral infection.
- Metastasis: neoplastic cells (cells undergoing abnormal growth, sometimes forms a mass called tumor) spread from local site of development to distal locations. Neoplastic cells carried by lymphatics to nearest lymph node.

Front 36

How are lymphocytes and plasma cells, which were activated in local lymph nodes by incoming lymph from the MALT, able to exit the lymph nodes and relocate to the MALT?

Back 36

Exiting the lymph nodes:
- Lymphocytes exit the lymph node by entering the efferent lymphatics to travel in the lymph and eventually re-enter the systemic circulation.
Relocating to the MALT
- HEVs are thin walled vessels that facilitate the highly specific transmigration of T and B cells.
- The lymphocytes squeeze between adjacent HEV and penetrate the basement membrane in order to re-enter the lymph nodes and other sites.
- Movement is determined by specific cell-adhesion molecules on lymphocyte surfaces. The adhesion molecules bind to complementary cytokines on the endothelial cells.

Front 37

How do the clinical consequences of splenectomy in children differ from those in adults?

Back 37

Splenectomy, or removal of the spleen is used as therapy for some chronic disorders or an emergency procedure for traumatic rupture of the spleen.
- Splenectomy in adults usually has no clinical consequence, but in children it leads to increased occurrence and severity of infections.