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37 Cards in this Set

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Hematopoietic functions of the liver and bone marrow

- 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.

Pluripotent hematopoietic stem cells

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)

Progenitor cells (CFU units)

- 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.


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

Buffy coat

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

Blood serum

Top layer after centrifugation

Red blood cells

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


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

- They phagocytize antigen-antibody complexes and parasites


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


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

Lymphocytes (agranular)

- 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.

Monocytes (agranular):

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

Distinguish between the thymic cortex and medulla

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

Epithelial reticular cells and the blood-thymus barrier

- 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.

Information about T cells and B cells

- 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.

Thymic (Hassall's) Corpuscles

- 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.

Organs systems with abundant lymphatic capillaries

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

Mucosa-associated lymphatic tissue (MALT)

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.

Lymphoid nodules

- 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).

Germinal Centers

- 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.

Distinguishing between the cortex and medulla of the lymph nodes

- 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.

Location and function of high endothelial venules (HEV)

- 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.

Sinus system of Lymph nodes

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.

Afferent and Efferent lymphatic vessels of the lymph nodes

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.

Arteries and veins of the lymph nodes

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.

White pulp

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.

Red pulp

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.

Blood flow through spleen (white pulp)

- 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.

Blood flow through spleen (red pulp)

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.

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

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.

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

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

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

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.

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

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).

What is lymphedema?

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.

What conditions can cause lymphadenopathy?

- 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.

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?

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.

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

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.