Bone marrow

Medulla ossium

Also known as: red marrow, yellow marrow, red bone marrow, haematopoietic marrow, hematopoietic marrow, myeloid tissue

The soft tissue filling the medullary cavities and spaces of spongy bone: red marrow makes all blood cells and B lymphocytes (a primary lymphoid organ), while yellow marrow is mostly fat that can revert to red marrow under demand.

Show on body map Long Bone — Structure

Overview

Mass≈ 4–5% of body mass

Daily output≈ 2 × 10¹¹ red cells, ≈ 10¹¹ neutrophils and ≈ 10¹¹ platelets

Adult distributionRed ≈ 50%: skull, vertebrae, ribs, sternum, pelvis, proximal femur & humerus

Bone marrow makes up about 4–5% of body mass. Red (haematopoietic) marrow consists of haematopoietic cords — clusters of developing blood cells of every lineage — lying in a stroma of reticular cells, adipocytes, macrophages and osteoblast-lineage cells, between wide, thin-walled sinusoids whose discontinuous endothelium lets mature cells squeeze into the blood. Yellow marrow is mainly adipocytes with a sparse vascular stroma; it is not inert, and can be reconverted to red marrow when demand for blood cells rises (e.g. chronic haemolysis, hypoxia).

At birth virtually all marrow is red. From about 5–7 years conversion to yellow marrow begins in the diaphyses of the distal limb bones and progresses proximally, so that in adults red marrow persists mainly in the axial skeleton — skull, vertebrae, ribs, sternum and pelvis — and in the proximal epiphyses of the femur and humerus; overall the adult marrow is roughly half red and half yellow.

As a primary lymphoid organ, the marrow is where B cells develop (pro-B → pre-B → immature IgM⁺ B cell, with V(D)J recombination and removal or receptor-editing of self-reactive cells) and from which T-cell precursors leave to mature in the thymus. It is also the long-term home of most long-lived plasma cells, which maintain serum antibody levels for years, and a reservoir of memory T cells.

Location: Medullary cavities of long bones and the intertrabecular spaces of spongy bone; in adults red marrow mainly in the skull, vertebrae, ribs, sternum, pelvis and proximal femur and humerus.

Parts & subdivisions

Red marrow
Haematopoietically active marrow in the axial skeleton and proximal femur/humerus of adults; cellularity falls with age (roughly 100 − age %).
Yellow marrow
Adipocyte-rich marrow occupying the limb diaphyses; can reconvert to red marrow.
Sinusoids
Wide discontinuous capillaries through which new cells enter the circulation; megakaryocytes extend proplatelets through their walls.
Stem-cell niches
Perivascular and endosteal microenvironments (CXCL12-abundant reticular cells, endothelium, osteoblasts) that maintain haematopoietic stem cells via CXCL12 and stem-cell factor.
Erythroblastic islands
A central macrophage surrounded by maturing erythroblasts, supplying iron and engulfing extruded nuclei.
Haematopoiesis
Production of all blood cell lineages from stem cells.

Anatomy

Arterial supply: Nutrient artery → central longitudinal artery → radial branches → sinusoids (also fed by cortical capillaries from periosteal and endosteal vessels) → central venous sinus → nutrient vein. The marrow has no lymphatic vessels.
Histology: Sinusoids separated by haematopoietic cords containing erythroid islands, granulocytic precursors (near the endosteum), giant polyploid megakaryocytes (beside sinusoids), plasma cells, macrophages and adipocytes. A normal myeloid:erythroid ratio is about 2–4:1.
Development: Colonised by haematopoietic stem cells from the fetal liver from late in the first trimester; becomes the principal site of haematopoiesis in the third trimester and the only normal site after birth.

Function

Haematopoiesis: production of red cells, platelets, granulocytes, monocytes and lymphocytes.
Primary lymphoid organ for B-cell development and central B-cell tolerance.
Home of long-lived plasma cells and memory lymphocytes.
Storage of iron (in macrophages) and fat; source of osteoclast precursors.

Physiology: Output is matched to demand by growth factors: erythropoietin (kidney), thrombopoietin (liver), G-CSF, GM-CSF, M-CSF, IL-3, IL-5 and IL-7. The marrow holds a reserve of mature neutrophils several times larger than the circulating pool, released within hours by infection or corticosteroids.

Clinical significance

Aspiration and trephine biopsy

Usually from the posterior superior iliac spine (aspirate for cytology, trephine core for architecture and cellularity). Sternal aspiration is possible in adults but trephine is not performed there because of the risk to the heart and great vessels. The same principle allows intraosseous access for emergency drugs and fluids (proximal tibia, humeral head) — the marrow is a non-collapsible venous space.

Marrow failure and infiltration

Aplastic anaemia (idiopathic/autoimmune, drugs such as chloramphenicol and carbamazepine, viruses, radiation, Fanconi anaemia) gives pancytopenia with a hypocellular, fatty marrow. Infiltration by leukaemia, lymphoma, myeloma, metastatic carcinoma (breast, prostate, lung) or fibrosis produces a leucoerythroblastic blood film; myelofibrosis gives a "dry tap" and teardrop cells.

Haematopoietic stem-cell transplantation

Stem cells harvested from marrow or mobilised into the blood with G-CSF (± plerixafor, a CXCR4 antagonist) are used to rescue marrow after high-dose therapy (autologous) or to replace a diseased marrow and immune system (allogeneic — with a risk of graft-versus-host disease).

Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.