Toxicologic Pathology
, 34:548–565, 2006
Copyright
C
by the Society of Toxicologic Pathology
ISSN: 0192-6233 print / 1533-1601 online
DOI: 10.1080/01926230600939856
Normal Structure, Function, and Histology of the Bone Marrow
G
REGORY
S. T
RAVLOS
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health,
Research Triangle Park, North Carolina 27709, USA
A
BSTRACT
While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological
evaluation of bone marrow cytology and paraffin sections provides information about bone marrow tissue architecture that otherwise would be missed
by examination of peripheral blood alone. In decalcified, paraffin-embedded, hematoxylin and eosin (H&E)-stained sections of bone marrow, the
more mature stages of the erythroid and myeloid cells, adipocytes, mast cells, and megakaryocytes can be identified, but lymphoid cells as well as
immature progenitor cells can not be reliably identified. The quality of the marrow sections is governed by numerous variables related to specimen
collection and processing and must be considered. In addition to discussing normal structure, function, and histology of bone marrow, methods for
preparation and evaluation of bone marrow are presented.
Keywords.
Lymphopoiesis; hematopoiesis; fixation; decalcification; M:E ratio.
I
NTRODUCTION
Blood and bone marrow is one of the largest organs in the
body and is an important potential target organ of chemical
exposure (Lund, 2000). For example, it was suggested that
drug-related blood dyscrasias represented 10% of all blood
dyscrasias reported in Sweden, and, 40% of those resulted
in fatality (Bottinger and Westerholm, 1973). Since effects
of a compound may be elicited in the circulating blood cell
mass or the production of blood cells, evaluations of single
or serial whole blood samples and smears, bone marrow as-
pirates, and marrow tissue sections are needed to understand
the alterations in the leukon, erythron or thrombon that may
occur in toxicity studies. Examples of blood and bone marrow
toxicity can be found in Table 1.
Assessments of the blood and bone marrow have become
routine procedures in the investigation of hematologic disor-
ders in toxicology and safety assessment studies. Evaluation
of blood has been extensively described (Jain, 1986a; Perkins,
1999; Ryan, 2001). The focus of this article will be evalua-
tion of the bone marrow with the objectives of reviewing of
some concepts regarding the bone marrow structure and func-
tion and review of qualitative and quantitative bone marrow
evaluation methods. A review of various lesions of the bone
marrow in laboratory rats, mice and dogs will be presented
in a subsequent discussion (Travlos, 2006).
B
ONE
M
ARROW
S
TRUCTURE AND
F
UNCTION
The bone marrow is found within the central cavities of ax-
ial and long bones (Figure 1). It consists of hematopoietic tis-
sue islands and adipose cells surrounded by vascular sinuses
interspersed within a meshwork of trabecular bone. It ac-
counts for approximately 3% of the body weight in adult rats
Address correspondence to: Gregory S. Travlos, Laboratory of Experi-
mental Pathology, NIEHS/NIH, 111 Alexander Dr., MD B3-06, Research
Triangle Park, NC 27709, USA; e-mail: travlos@niehs.nih.gov
This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences.
(Schermer, 1967),
∼
2% in dogs (Jain, 1986b) and
∼
5% in hu-
mans (Picker and Siegelman, 1999). The bone marrow is the
major hematopoietic organ, and a primary lymphoid tissue,
responsible for the production of erythrocytes, granulocytes,
monocytes, lymphocytes and platelets. A brief discussion of
bone marrow structure and function will be presented here;
detailed descriptions can be found elsewhere (Jain, 1986b,
Weiss and Geduldig, 1991; Wickramasinghe, 1992; Picker
and Siegelman, 1999; Hoffman et al., 2000; Abboud and
Lichtman, 2001).
The inner surface of the bone cavities and the outer sur-
face of the cancellous bone spicules within the cavities are
covered by an endosteal lining consisting of a single layer of
flat “bone-lining cells” supported by a thin layer of reticular
connective tissue; osteoblasts and osteoclasts are also found
within the endosteal lining (Figure 2).
In long bones, one or more nutrient canals (containing a
nutrient artery and 1or 2 nutrient veins) pass through the cor-
tical bone entering the marrow cavity obliquely. In flat bones,
the marrow is served by numerous blood vessels of various
sizes entering the marrow via large and small nutrient canals.
After entry, the artery splits into ascending and descending
branches that run parallel to the long axis in the central part
of the marrow cavity, coiling around the primary venous mar-
row channel, the central longitudinal vein (Figure 3). These
artery branches give rise to a multitude of small thin-walled
arterioles (Figure 4) and capillaries that extend outwardly to-
ward the cortical bone. Near the bone, the arterioles open
up and anastomose with a plexus of venous sinuses. These
venous sinuses drain via collecting venules that lead back
centrally to the central longitudinal vein that then drains via
the nutrient veins. The marrow has an extensive blood supply
(Figure 5). Also, it appears that nutrient artery-derived capil-
laries extend into the Haversian canals, return to the marrow
cavity then open into the venous sinuses. Thus, there is a cir-
cular pattern to blood flow within the marrow cavity, from
the center of the marrow cavity toward the periphery of the
marrow cavity then back toward the center. In long and flat
bones, the blood supplies of the bone and bone marrow are
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