Structure + Function of Hematopoietic Organs

development of hematopoiesis

begins as early as the 18th day after fertilization in an extraembryonic location —> yolk sac (primitive erythropoiesis)

at 4 weeks of gestation, intraembryonic hematopoiesis begins in the aorta-gonad-mesonephros (AGM) region located in the ventral lumen in the developing aorta

AGM region can make a broader range of hemopoietic cells than those made in the yolk sac

definitive erythropoiesis begins with the formation of self-renewing HSC in the AGM

aorta-gonad-mesonephros (AGM) region

located in the ventral lumen in the developing aorta

where intraembryonic hematopoiesis occurs after 4 weeks of gestation

intraembryonic hematopoiesis

occurs after 4 weeks of gestation

begins in the aorta-gonad-mesonephros (AGM) region

AGM region

can make a broader range of hematopoietic cells than those made in the yolk sac

definitive erythropoiesis

begins with the formation of self-renewing hematopoietic stem cells (HSC) in the AGM

yolk sac

where hematopoiesis initially begins

occurs on 18th day after fertilization

is an extraembryonic location

primitive erythropoiesis

when hematopoiesis occurs as early as the 18th day after fertilization in the yolk sac

hematopoietic stem cell (HSC)

common precursor cell for all developing hematopoietic cells and is characterized by its ability to proliferate without differentiation

liver

region that becomes the chief site of blood cell production after the yolk sac and the AGM have discontinued their role

liver

continues to provide a high proportion of erythroid cells, but myeloid and lymphoid cells begin to appear in greater numbers

3-8 weeks

length of hematopoiesis in yolk sac

6 weeks to birth

length of hematopoiesis in the liver

8 - 28 weeks post birth

length of hematopoiesis in the spleen

18 weeks post birth to adult

length of hematopoiesis in bone marrow

spleen

kidneys

thymus

lymph nodes

as fetal development progresses, hematopoiesis begins to a lesser degree in these 4 places

bone marrow

hematopoiesis gradually shifts to the _______, which becomes the primary site during fetal and neonatal life (after liver)

BM

thymus

spleen

lymph nodes

structures of adult hematopoietic system

myeloid

erythroid

lymphoid

megakaryocyte cell development

development in the bone marrow

thymus

spleen

lymph nodes

structures responsible for later lymphoid cell development

primary lymphoid tissues

BM + thymus

T and B cells develop into cells capable of responding to foreign antigens

secondary lymphoid tissues

spleen + lymph nodes

T and B cells further divide and differentiate into effector cells and memory cells in response to antigens

bone marrow

blood-forming tissue that is located between the trabecular of spongy bone

bone marrow

made up of cellular, highly vascularized, loose connective tissue

vascular

endosteal

2 major compartments of bone marrow

BM arteries + veins

stromal cells

hematopoietic cells

components of vascular bone marrow compartment

bone remodeling

HSC

components of endosteal bone marrow compartment

nutrient artery

periosteal artery

two arterial sources that make up the vascular supply of the BM

by central vein

how blood is drained from the bone marrow

nutrient artery

artery in bone marrow that branches around the central sinus

arterioles

radiate outward from the nutrient artery to the endosteum

arterioles

give rise to capillaries that merge with capillaries that merge with capillaries from periosteal arteries to form sinuses within the bone marrow

stroma

provides a favorable microenvironment for the sustained proliferation of hematopoietic cells

stroma

provides cytokines that regulate hematopoiesis

macrophages

reticular cells (fibroblasts)

adipocytes (fat cells)

stroma is composed of these 3 major cell types

stroma macrophages

phagocytose extruded nuclei of maturing RBCs

B cells that do not mature properly

differentiating cells that die during development

stroma reticular cells

abundant source of CXCL12 (SDF-1) which activate leukocytes

CXCL12 (SDF-1)

what activates leukocytes

stroma adipocytes

cells with a single fat vacuole

mechanically control the volume of BM in which active hematopoiesis takes place

hematopoietic cells

arranged in distinct niches within vascular compartment of marrow cavity

erythroblasts

constitute of 25-30% of the marrow cells

develop into erythroblastic islands

erythroblastic islands

a central macrophage surrounded by erythroblasts in varying stages of maturation

macrophage cytoplasm

extends to surround the erythroblasts and regulate erythropoiesis by secreting cytokines

cytokines

macrophage cytoplasm surrounds the erythroblasts and regulates erythropoiesis by secreting ?

granulocytes

produced in nests close to the trabeculae and arterioles (distant from the venous sinuses)

not as apparent morphologically as the erythroblastic islands

megakeryocytes

located adjacent to the vascular sinus

lymphocytes

produced in lymphoid aggregates

lymphocytes

located near arterioles

lymphocytes

some leave BM —> travel to thymus —> mature into T cells

some remain in the BM —> mature into B cells

T cells

when lymphocytes leave BM and travel to thymus, they mature into ?

B cells

when lymphocytes stay in the BM, they mature into ?

hematopoietic cell + venous sinus

special properties when it comes time for mature cells to leave the BM

hematopoietic cell + venous sinus

migrate between reticular cells but through endothelial cells to reach the peripheral circulation —> reticular cells retract to create compartments between reticular cell layer and endothelial cell layer where mature cells accumulate and interact with sites on the sinus endothelial surface

mature cells accumulate and interact with sites on the sinus endothelial surface

when reticular cells retract, they create compartments between the reticular cell layer and the endothelial cell layer where ?

cells deform and move through the sinusoidal lining

after mature cells accumulate and interact with sites on the sinus endothelial surface they ?

extra medullary hematopoiesis (hematopoiesis outside of the BM (liver and spleen))

occurs when hyperplasia of the BM cannot keep up with the physiological needs of the tissue

results in organomegaly

thymus

lymphopoietic organ located in the upper part of the anterior mediastinum

serves as a compartment where T cells mature (3% of cells generated here exit as mature T cells, the rest die by apoptosis)

well-developed organ at birth, continues to increase in size until puberty, then begins to atrophy until old age (still capable of producing some new T cells if the peripheral pool becomes depleted)

spleen

filters foreign substances and old erythrocytes from the circulation, stores platelets, involved in immunity defense

not essential for life

upper left quadrant of the abdomen

spleen

contains the largest collection of lymphocytes and macrophages in the body

white pulp

red pulp

marginal zone

three zones of spleen

white pulp zone of spleen

composed of lymphocytes

surrounds the central artery, immune response

red pulp zone of spleen

includes sinuses and cords

marginal zone of spleen

lies at the junction of the white and red pulp

reticular meshwork containing blood vessels, macrophages, and specialized B cells

spleen

richly supplied with blood

receives 5% of the total cardiac output

blood follows either the rapid transmit pathway or slow transit pathway

blood flow of spleen

rapid transit pathway in spleen

unobstructed route of blood

blood enters the sinuses in the red pulp from arteries and passes directly into the venous collecting system

slow transmit pathway

blood moves sluggishly through a circuitous route of macrophage-lined cords before it gains access to the venous sinuses in the spleen

hypoxic

acidic

hypoglycemic

environment in the spleen

slow transit pathway

blood that empties into the cords of the red pulp or the marginal zone of the spleen takes the ___________

slow transit pathway in spleen

functions in culling, pitting, and storing RBCs

culling

filtering and destruction of aged or damaged RBCs

pitting

spleen plucks out particles form intact RBCs without destroying them (blood cells coated with antibody)

hypersplenism

caused from exaggeration of its normal activities of filtering and phagocytosing —> enlargement of the spleen

anemia

leukopenia

thrombocytopenia

combinations of cytopenias

effects of hypersplenism

presence of anemia, leukopenia, or thrombopenia in the peripheral blood

cellular or hyperplastic BM

occurrence of splenomegaly

three conditions that must be met to classify hypersplenism

splenectomy

relieves the effects of hypersplenism

performing a constructive role → producing antibodies or filtering protozoa or bacteria

splenectomy have be contraindicated if the spleen is ?

patients hereditary or acquired conditions when RBCs or platelets are undergoing increased destruction

types of patients that would benefit from splenectomy

culling function

after splenectomy is performed, the liver will assume the ?

lymph nodes

drain into the left and right lymphatic ducts

lymph

a filtrate of blood plasma

lymph nodes

act as filters to remove foreign particles from the lymph by dendritic cells and macrophages

lymph nodes

provide immune defense against the pathogens in all tissues