Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
8.2.4 Navigational Osteography
The skeleton is the single largest organ system, representing ~14% of total mass and ~11% of the navigable volume of the human body. The bony skeleton supports and protects the vital organs -- the skull protects the brain; the spinal column shields the spinal cord and maintains erect posture; the ribs shelter the heart, lungs, and liver; pelvic bones protect the kidneys and internal sexual organs.
The total number of bones varies at different ages. At birth, the human body contains ~270 bones. This number declines slightly during infancy as a few separate segments join to form single bones. From young childhood through puberty, the bone count increases as wrist and ankle bones develop. Post-adolescence, the bone count steadily declines again with the gradual union of independent bones.
The adult skeleton (Fig. 8.22) consists of 206 bones: 28 skull bones (8 cranial, 14 facial, and 6 ear ossicles); the horseshoe-shaped hyoid bone of the neck (which breaks during hanging, choking the victim to death; see Figure 8.11); 26 vertebrae (7 cervical or neck, 12 thorax, 5 lumbar or loins, the sacrum which is five fused vertebrae, and the coccyx, our vestigial tail, which is four fused vertebrae); 24 ribs plus the sternum or breastbone; the shoulder girdle (2 clavicles, the most frequently fractured bone in the body, and 2 scapulae); the pelvic girdle (2 fused bones); and 30 bones in each of the four extremities (a total of 120). The paired bones include the 12 ribs on either side, 8 wrist bones, 5 hand bones, 14 finger bones, 7 ankle bones, 5 foot bones, 14 toe bones, 3 auditory ossicles, and the parietal, temporal, palatine, lacrimal, nasal, upper jaw, cheek, lower nasal concha, collarbone, shoulder blade, hip, arm, outer and inner forearm, thigh, kneecap, calf, and shin bones. There are also a variable number of sesamoid bones, ranging from 8-18 in number, which are small rounded masses embedded in certain tendons and usually related to joints.
The total mass of the skeleton is ~10,000 gm; skeletal density averages ~1.45 gm/cm3, so total volume is ~6875 cm3 (Table 8.9). The total exterior surface area of the bones is ~1 m2, which may be mapped to ~(20 micron)2 cellular resolution using 2.5 billion pixels, requiring ~0.02 terabits of onboard nanorobot memory assuming 8-bit pixels.
More interesting are the interior spaces of bones in which medical nanodevices may travel. Bone is composed mainly of ~50 nm long crystals of very dense calcium salts having the hardness of marble (mostly hydroxyapatite, ~45% of bone mass) held together by bone matrix containing large numbers of extremely strong ~200 nm-wide collagenous fibers arranged in a dense mat together with a mucopolysaccharide cement sometimes called "ground substance." In living bone, ~25% of bone weight is water and another ~30% is organic material.870
Embedded in this mineral structure are bone cells of three types.863 Osteoblasts, which secrete the substances that make up the bone matrix, line the outer surfaces of bone and also line many of the surfaces inside the internal cavities of the bone. Osteocytes, the most numerous bone cell type, originate from osteoblasts when those cells become trapped within small irregular matrix cavities called lacunae. After the trapped cells transform into osteocytes, they stop forming new bone but continue to support normal bone metabolism. Finally the osteoclasts (large multinucleated cells lining ~3% of internal bone cavity surfaces) remove old bone when it needs repair. Osteoclasts may be stimulated by parathyroid (endocrine) hormone to cause bone absorption when extra calcium ions are needed in the extracellular fluid. Bone is continually being resorbed and rebuilt to maintain its structural integrity.
Most of the compact bone is laid down in concentric layers, or lamellae, both on the outer surfaces of the bone and around the internal blood vessels that supply nutrition.863 Figure 8.23 illustrates this lamellar structure of bone, showing that the lacunae (irregular spaces) containing the osteocytes lie between the successive lamellae and are interconnected from one layer to another and between lacuna by small fluid-filled canaliculi averaging ~0.3 microns (range 0.1-1.0 micron) wide.935,936 The largest (Haversian) canal lies at the center of each system of concentric lamellae. Haversian canals are ~20 microns wide and carry blood vessels, lymph vessels, nerves, and also connect with the lacunae via the canaliculi. All osteocytes lie within ~200 microns of a blood capillary.936 The entire Haversian system allows nutrient and calcium flow through the bone interior volume and provides convenient navigable channels which medical nanorobots may utilize to gain direct access to bone cells and matrix materials.
Compact bone (providing the principal structural bearing strength of the body) is formed on the exterior of all bones. Deeper inside, the bone becomes a more open latticework with large spaces, called spongy or cancellous bone, whose solid parts nevertheless have an internal structure similar to compact bone. In the long bones of the extremities, the epiphyses (end knobs) are composed of spongy bone covered by a thin layer of compact bone. The diaphysis (central shaft) is made up almost entirely of compact bone surrounding a cavity containing marrow. Covering the entire bone is the periosteum, a nutrient-carrying fibrous membrane investing the surfaces of bones, except at the points of attachment of tendons and ligaments (where cartilage is substituted). The periosteum has an outer fibrous layer composed of dense fibrous tissue with blood vessels and an inner osteogenic layer containing many fibroblasts.750 Blood vessels traversing the periosteum enter the bone and pass through channels called Volkmann's canals to enter and leave the Haversian canals. In humans, there are few true voids in the bones.
Bone marrow fills the spaces of spongy bone and the medullary (marrow) cavity of long bones. It is composed of a supporting framework of reticular tissue in which there are blood vessels and blood cells in various stages of development. A thin membrane called the endosteum, more delicate than the periosteum but resembling it in structure, lines the medullary cavity. In the adult, there is red and yellow marrow.750 Red cells and some white cells are formed in the red marrow; in the newborn all marrow is red, but in the adult the red marrow is found in the spongy bone such as the proximal epiphyses of long bones and in the sternum, ribs, vertebrae and diploe of the cranial bones. Yellow marrow contains many fat cells and is found in the medullary cavity of long bones, producing macrophages and granulated white cells. There is ~3 kg of marrow in the adult body,817 occupying a volume of ~2400 cm3.
Even the relatively low capillary density of <100/mm2 in bone832 implies a total investiture of ~3 x 108 skeletal capillaries and a total luminal surface area of ~8 m2 for the entire vasculature, which would require a ~0.16 terabit vascular map at cellular resolution. A full cellular map identifying each individual osteocyte in the entire skeletal system requires ~1 terabit.
An interesting navigable volume within the skeletal system is the human spine, which averages 71 cm in length in men and 60 cm in women with remarkably little variation.870 The body of each vertebra has a ring-shaped neural arch, through which passes the spinal cord. The spinal cord, measuring ~46 cm long and ~1 cm in diameter, descends from the brain and medulla oblongata through the foramen magnum and passes through the hollows of the spinal column, giving off 31 pairs of spinal nerves until it reaches the level of the disc between the first and second lumbar vertebrae, where the lower end tapers off to a point called the conus medullaris. The cord itself (Fig. 8.24) is composed of H-shaped gray matter in the center, extending forward as the anterior nerve roots (motor control) and backward as the posterior nerve roots (sensory), with solid white tracts of nerve fibers descending from the brain or ascending to it.
Cerebrospinal fluid (CSF) fills the ventricles of the brain and the subarachnoid cavity surrounding the spinal cord. The fluid is formed mainly by the choroid plexuses (large, reddish tufted organs) in the four ventricles of the brain. The plexuses are rich in blood vessels and separated from the cavity of the ventricles by only a single layer of secretory cells, thus affording ready access to the fluid by medical nanorobots (Chapter 16). The fluid, once formed in the brain, is later mostly reabsorbed by the arachnoid villi in the brain, but a small amount drifts slowly downstream along the spinal cord and is absorbed by the arachnoid villi through the spinal regions. Among other things, CSF is regarded as "the drainage system of the brain," crudely analogous to urine, and the entire fluid volume is replaced once every ~30,000 sec.
The human body contains 90-150 cm3 of cerebrospinal fluid, normally maintained at an average pressure of 11 mmHg (range 5-13 mmHg1712). The fluid is clear and watery, normally containing 1-10 white cells/mm3 (all mononucleocytes) and similar chemical constituents as blood plasma, but with only 0.4% as much protein as the plasma; to first approximation, it may be regarded as an almost protein-free filtrate of the blood. The specific gravity of cerebrospinal fluid is 1.007 (1.0062-1.0082); viscosity at 310 K typically ranges from 0.7-1 x 10-3 kg/m-sec;3325 and pH averages 7.4 (7.35-7.70), with ~1% (0.85-1.7%) total solids, 6 x 10-4 gm/cm3 glucose, 2.4-5.0 x 10-6 gm/cm3 cholesterol, and no acetylcholine or fibrinogen.585 Protein content increases from 1.0 x 10-4 gm/cm3 in the ventricles of the brain, to 1.5 x 10-4 gm/cm3 in the cisterna of the upper spinal column, to a high of 2.5 (2.0-4.0) x 10-4 gm/cm3 in the lumbar vertebrae585 -- a potentially useful chemonavigational gradient.
Most of the ~150 bone joints in the human body are freely movable diarthroses (Fig. 8.25). There are ball and socket joints, saddle joints, ~40 hinge joints,870 and pivot joints. In the diarthrodial joint, two or more bones are united by an encircling band of fibrous tissue called the articular or fibrous capsule. The articular capsule is lined with synovial membrane, and the apposed ends of bone are covered by a layer of hyaline cartilage, called articular cartilage. The fibrous capsule is reinforced and strengthened by ligament cords woven into it. Joint cavities sometimes extend into pouches or recesses or communicating bursae, and the shape of the sac changes with motion, as in the knee joint.
Synovial fluid, which lubricates and nourishes the joint, is exuded by the synovial membrane and fills the capsule cavity. There may be a total of ~30 cm3 of synovial fluid in all of the human body joints. Synovial fluid is a colorless, viscid mucin-containing material resembling egg white. The human knee contains ~1.1 cm3 (range 0.13-3.5 cm3) of synovial fluid at an average osmotic pressure of 11 mmHg (9-13 mmHg). The specific gravity of the fluid is 1.008-1.015; absolute viscosity is highly variable but averages ~160 (4-800) x 10-3 kg/m-sec; pH is 7.39 (7.29-7.45); with 3.4% (1.2%-4.8%) total solids, 0.7-1.0 x 10-3 gm/cm3 glucose, 8.5 x 10-3 gm/cm3 mucin, and no fibrinogen.585
There are also ~140 bursae (synovial sacs) in the body, located in fibrous tissue wherever friction occurs, probably containing at least ~20 cm3 of additional synovial fluid. The best-known include the subdeltoid bursa, which lies beneath the shoulder muscle; the prepatellar bursa, located in front of the kneecap; and the Achilles bursa, which lies between the heel bone and the Achilles tendon at the back of the heel.
Last updated on 19 February 2003