Hematopoiesis and Bone Marrow Flashcards
What are the two types of hemopoietic tissue?
myeloid tissue (bone marrow) lymphatic tissue
Where is myeloid tissue located?
in the medullary cavity of bones
Where is lymphatic tissue located?
thymus, lymph nodes, spleen, and non-encapsulated lymph nodes
Hemopoietic tissue is derived from mesenchyme except for where?
thymus
Where is the first site of hemopoiesis
the yolk sac
What are the two cell types formed in the yolk sac?
endothelial cells and undifferentiated pluripotential stem cells
From the 6th week of fetal life until the middle of fetal life, where does hemopoiesis occur?
in the liver
What type of blood cell is being formed the most during fetal development in th eliver?
red blood cells
At what point in development do red blood cells become non-nucleated?
11 weeks
WHen does hemopoiesis begin in the spleen?
during the 3rd month of fetal life
When does hemopoiesis begin in the bone?
5th month of fetal life
Which bone is the first to develop a medullary cavity for myeloid tissue?
the clavicle
When does lymphopoiesis begin in the thymus?
5th month of fetal life
What do you call it when hematopoietic tissue develops elsewhere than bone marrow, spleen and liver?
extramedullary myelopoiesis
What are the two types of marrow?
yellow marrow and red marrow
Where is yellow marrow located? what is it made of?
It’s in the diaphysis of long bones - made of fat cells with blood vessels coursing thorugh
Where is red marrow located?
diploe of skull, ribs, sternum, bodies of vertebrae, areas of cancellous bone, long and short bones of the body and the iliac crest
What are the components of myeloid tissue?
stroma, sinusoids, developing blood cells
What do the sinusoids do?
they’re wide, thin-walled vessels that allow newly formed blood cells to gain access to the blood stream
What cells types are found in the stroma of myeloid tissue?
- fibroblasts
- macrophages
- fat-storing cells
- osteogenic cells
- endothelial cells
What type of endothelium lines the walls of sinusoids?
simple squamous endothelium (supported by a poorly developed basal lamina and reticular fibers)
RBCs and WBCs can diapedese through the sinusoids via what two spaces?
intercellular gaps and endothelial cell pores
What glycoprotein made in the kidney stimulates the stem cells to multiple and differentiate into hemoglobin cells?
erythropoietin
What stimulates erythropoietin release?
hypoxia
As the RBC matures, what happens to the size? color? nucleus? chromatin structure?
size shrinks
color goes from basophilic to eosinophilic
nucleus goes from large to small to absent (from light to dark staining til it’s not there)
chromatin goes from a fine pattern to a clumped pattern
What percentage of the bone marrow is actively producing RBCs at any given time?
20-30%
How long does it take to produce a mature erythrocyte from a basophilic erythroblast?
1 week approximately
What are the 6 recognizable cells of the erythrocyte series in order of development?
- proerythroblast
- basophilic erythroblast
- polychromatophilic erythroblast
- orthochromatophilic erythroblast
- reticulocyte (or orthochromatophilic erythrocyte)
- RBC
What are the general features of granulocyte maturation?
- gradually goes from a basophilic staining to a lack of it
- granules increase in number
- nucleus goes from round to variably shaped
- nucleoli disappear gradually
How many days does it take for a granulocyte to mature?
14 days
How long do granulocytes function for in the connective tissue?
1-2 days
What are the 6 recognizable cells of the granulocyte series in order of development?
- myeloblast
- promyelocyte
- myelocyte
- Metamyelocyte
- Banded leukocyte
- mature leukocyte
Which cell in the granulocyte series is the first that’s non-mitotic?
the metamyelocyte (juvenile)
What are the three questions to ask yourself when identifying cells of the granylocytopoieisis series?
- nucleus round?
- are there nucleoli?
- are there granules?
In the series, which cell is the first wihtout nucleoli?
myelocyte
In the series, which is the first to lose the roundness of the nucleus?
metamyelocyte (this is also when it stops being mitotic)
Which cell in the series lacks granules?
the blast
The blast cells for erythropoiesis and granulopoiesis are similar except for what?
the cytoplasm of the erythropoesis blasts is more basophilic
What molecule stimulates platelet formation from megakaryocytes?
thrombopoietin
What is the life span of a platelet
10 days
What is the difference between central (primary) and peripheral (secondary) lymphatic tissues?
central - where the lymphocytes originate
peripheral - where the lymphocytes respond to antigens
What are the cellular components of the stroma in lymphoid tissue?
- reticular cells (like fibroblasts)
- macrophages
- dendritic cells
- follicular dendritic cells
Which are the antigen presenting cells: macrophages, dendritic cells, follicular dendritic cells.
macrophages and dendritic cells are, follicular dendritic cells are not (just don’t endocytose or process antigen, just bind antibody-antigen complexes)
What do the reticular cells do in the stroma?
they form the reticular fibers for the supporting framework
How are the different lymphatic tissues classified? What are the two types?
based on their gross histological arrangement:
- diffuse lymphatic tissue
- nodular lymphatic tissue
What characterizes the nodular lymphatic tissue/
solitary lymphatic nodules scattered through digestive, respiratory and urinary system in loose connective tissue - represents local immune response to antigens
What’s the difference between a primary lymphatic nodule and a secondary lymphatic nodule?
primary is just darkly staining while secondary have a reaction center (germinal center)
the secondary is only present with exposure to an antigen
What organ is required for development of secondary lymphatic nodules?
thymus - they’re numerous during childhood, but decline in number with age
What cells are located in the germinal center of secondary nodules?
Lymphoblasts, small lymphocytes, developing plasma cells, macrophages and follicular dendritic cells
Where are lymphatic nodules located and where are they not?
they are located in the lymph nodes and spleen, but not in the thymus (that would suggest pathology)
What are some examples of nodular NON-ENCAPSULATED lymphatic tissue?
- tonsils (palatine, pharyngeal, tubal, lingual)
- Peyer’s patches (in GI tract)
- Appendix
What is the function of non-encapsulated lymphatic tissue?
- trap antigen
- produce lymphocytes in response to antigens (the antigen stimulates the lymphocyte proliferation and then differentiation of B cells occurs)
- destroys antigen
Which lymphatic organ is the only one that’s located in the course of lymphatic vessles, the only one containing lymphatic sinuses and the only one filtering lymph?
lymph node
What are the three connective tissue components of a lymph node?
capsule, trabeculae and stroma
What are the two general areas of a lymph node?
cortex and medulla
How do lymphocytes leave the lymph nodes?
they travel thorugh the lymph node sinuses into the efferent lymphatics
Describe the lymph flow thorugh the lymph node?
- afferent lymphatic vessle
- subcapsular sinus
- trabecular sinus
- paracortical sinus
- medularry sinus
- efferent lymphtic vessel
Describe the flow of blood through the lymph node.
- it enters thorugh the arterial vessels in the hilum
- It flows to the trabecular vessels in the periphery
- arterioles and then thorugh capillarys
- then through post-caprillary venules in the outer cortex
- then thorugh venules in the deep cortex, which are specialized such that lymphocytes can pass out of the blood and into the lymph
- lymphocytes then flow thorugh the efferent lymphatics back to the blood in the vascular system
How are the venuoles in the deep cortex specialized to allow lymphocyte passage?
The endothelium is simple cuboidal instead of simple squamous. THere are special gaps between the endothelial cells such that the lymphocytes can pass trhough - these are called HIGH ENDOTHELIAL VENULES (HEVs)
If you have a thymectomy at birth, what happens tot he HEVs?
You don’t get the appropriate hormones secreted, so the venule endothelium goes from cuboidal back to simple squamous. This means the lymphocytes can’t pass through and you get a depletion of lymphocytes form the deep and mid-cortex.
Of the lymphocytes in the lymph nodes, are most made there or are most those that migrated there from the blood?
95% are those that migrated through the HEVs
Once recirculating lymphocytes enter the lymph node, what is their path back out?
- lymphatic tissue
- lymphatic sinuses
- efferent lymphatic vessels
What is the function of the lymph nodes?
- filter the lymph
- produce lymphocytes and add them to the vascular system
- produce antibodies (via plasma cells)
Where in the lymph nodes are the plasma cells located?
in the periphery only - they rarely enter the sinuses
What cell is mostly responsible for the filtration in the lymph noes?
macrophages (they remove about 99% of the bacteria entering through the afferent lymph vessels)
Does the thymus have only afferent lymphatics, only efferent lymphatics, or both?
Only efferents - it does not have afferents
What is the thymus derived form embryologically?
endoderm of the third branchial pouch
Describe the appearance and location of the thymus.
It consists of two lobes located beneath the upper anterior thoracic wall (sternum)
Each lobe is enclosed by a connective tissue capsule
What partially divides the lobes into lobules?
the connective tissue trabeculae
What cellular network supports the developing T lymphocytes in the thymus?
a network of the reticular cells (very few reticular fibers)
WHere in the thymus do the T lymphocytes proliferate? How do they enter circulation?
they proliferate in the periphery and then enter circulation through post-capillary venules at the corticomedullary junction
What are the functions of the hormones secreted by the thymus (thymosin, thymopoietins, serum thymic factor, thymic humoral factor, etc)?
- promote differentiation of stem cells into T lymphocytes
2. Induce formation of T-lymphocyte surface markers
What does the blood-thymus barrier (made of reitcular cells) do?
It prevents any antigens form entering the thymic cortex
Describe the three regions of lymphocytes distinguished in the cortex fo the thymus.
- outer region: stem cells giving rise to LARGE lymphoblasts
- middle region: differentiating and maturing cells from the outer region move through towards the medulla
- inner region: contains the smallest lymphocytes - cell division no longer evident, mature T-lymphocytes in this region enter blood vessels at the corticomedullary junction
What is the characteristic feature of the medulla?
thymic (Hassall’s) corpuscles
Where does blood supply come from for the thymus?
internal thoracic and inferior thyroid arteries
What happens to patients who have a congenital absence of thymus?
they don’t have any T-lymphocytes so they don’t have cellular immunity
What is the largest lymphatic organ?
spleen
Does the spleen have only afferent lymphatics, only efferent lymphatics, or both?
Only efferents
What structures are located in the hilum for the spleen?
arteries, veins, efferent lymphatics, sympathetic nerve fibers
In the spleen, what occupies the space between trabeculae
splenic pulp
What are the two types of splenic pulp?
red pulp and white pulp
What does white splenic pulp consist of?
pariarterial lymphatic sheaths (surround the white pump artery or central artery and contains primarily T cells)
Splenic lymphatic nodules (scattered thorughout, containing primarily B cells)
What does red splenic pulp consist of?
splenic sinuse (sinusoids) - vascular passageways lined by specialized endothelial cells
splenic cords (Billroth cords) - located between the sinuses and contain RBCs, granulocytes, lymphocyts, macrophages, platelets, plasma cells, reticular cells and reticular fibers
What is the transition zone between red and white pulp?
the marginal zone
In the marginal zone, recirculating lymphocytes return to enter what two spaces?
either the lymphoid sheath or the splenic nodule
Describe splenic circulation.
- splenic arteri
- trabecular artery
- white pulp artery (central artery)
- red pulp artery
- sheathed artery (capillaries)
- terminal arterial capillaries (NOTE 4-6 IS THE PENCILLUS)
- venous sinusoids
- pulp veins
- trabecular veins
- splenic veins`
What’s the difference between closed circulation and open circulation in the splenic circulation? Which is most prevalent?
closed - terminal capillaries open into sinusoids
open - terminal capillaries open into red pulp
open is more prevalent
What are the main functions of the spleen?
- form antibodies in response to blood-borne antigens - main source of ciruclating antibody
- removal and dstruction of defective blood cells
- concentrates and stores blood cells and platelets
- in prenatal life, forms RBCs, granulocytes, lymphocytes and platelets
