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0 | e5
HISTORICAL INTRODUCTION
required to operate on real patients, or on soldiers injured at Sebastopol
or some other battlefield. The book they planned together was a practi -
cal one, designed to encourage youngsters to study anatomy, help them pass exams, and assist them as budding surgeons. It was not simply an
anatomy textbook, but a guide to dissecting procedure, and to the major
operations.
Gray and Carter belonged to a generation of anatomists ready to
infuse the study of human anatomy with a new, and respectable, scien -
tificity. Disreputable aspects of the profession’s history, acquired during the days of body-snatching, were assiduously being forgotten. The
Anatomy Act of 1832 had legalized the requisition of unclaimed bodies
from workhouse and hospital mortuaries, and the study of anatomy
(now with its own Inspectorate) was rising in respectability in Britain.
The private anatomy schools that had flourished in the Regency period
were closing their doors, and the major teaching hospitals were erecting
new, purpose-built dissection rooms (Richardson 2000).
The best-known student works when Gray and Carter had qualified | 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
0 | were probably Erasmus Wilson’s Anatomist’s Vade Mecum , and Elements
of Anatomy by Jones Quain. Both works were small – pocket-sized – but Quain came in two thick volumes. Both Quain’s and Wilson’s works
were good books in their way, but their small pages of dense type, and
even smaller illustrations, were somewhat daunting, seeming to demand
much nose-to-the-grindstone effort from the reader.
The planned new textbook’s dimensions and character were serious
matters. Pocket manuals were commercially successful because they
appealed to students by offering much knowledge in a small compass.
But pocket-sized books had button-sized illustrations. Knox’s Manual
of Human Anatomy, for example, was a good book, but was only 6 inches
by 4 (15 × 10 cm) and few of its illustrations occupied more than one-
third of a page. Gray and Carter must have discussed this matter between themselves, and with Gray’s publisher, JW Parker & Son, before deci-
sions were taken about the size and girth of the new book, and espe - | 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
0 | cially the size of its illustrations. While Gray and Carter were working on the book, a new edition of Quain’s was published; this time it was
a ‘triple-decker’ – in three volumes – of 1740 pages in all.
The two men were earnestly engaged for the following 18 months
in work for the new book. Gray wrote the text, and Carter created the illustrations; all the dissections were undertaken jointly. Their working
days were long – all the hours of daylight, eight or nine hours at a
stretch – right through 1856, and well into 1857. We can infer from the
warmth of Gray’s appreciation of Carter in his published acknowledge-
ments that their collaboration was a happy one.
The Author gratefully acknowledges the great services he has derived in
the execution of this work, from the assistance of his friend, Dr. H. V.
Carter, late Demonstrator of Anatomy at St George’s Hospital. All the
drawings from which the engravings were made, were executed by him.
(Gray 1858) | 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
0 | With all the dissections done, and Carter’s inscribed wood-blocks at the engravers, Gray took six months’ leave from his teaching at St George’s
to work as a personal doctor for a wealthy family. It was probably as
good a way as any to get a well-earned break from the dissecting room
and the dead-house (Nicol 2002).
Carter sat the examination for medical officers in the East India
Company, and sailed for India in the spring of 1858, when the book
was still in its proof stages. Gray had left a trusted colleague, Timothy
Holmes, to see it through the press. Holmes’s association with the first
edition would later prove vital to its survival. Gray looked over the final galley proofs, just before the book finally went to press.
THE FIRST EDITION
The book Gray and Carter had created together, Anatomy, Descriptive
and Surgical, appeared at the very end of August 1858, to immediate Gray’s Anatomy is now on its way to being 160 years old. The book is a
rarity in textbook publishing in having been in continuous publication
on both sides of the Atlantic Ocean, since 1858. One and a half centu - | 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
0 | ries is an exceptionally long era for a textbook. Of course, the volume now is very different from the one Mr Henry Gray first created with his
colleague Dr Henry Vandyke Carter, in mid-Victorian London. In this introductory essay, I shall explain the long history of Gray’s, from those
Victorian days right up to today.
The shortcomings of existing anatomical textbooks probably
impressed themselves on Henry Gray when he was still a student at St George’s Hospital Medical School, near London’s Hyde Park Corner, in
the early 1840s. He began thinking about creating a new anatomy
textbook a decade later, while war was being fought in the Crimea. New
legislation was being planned that would establish the General Medical
Council (1858) to regulate professional education and standards.
Gray was twenty-eight years old, and a teacher himself at St George’s.
He was very able, hard-working and highly ambitious, already a Fellow
of the Royal Society, and of the Royal College of Surgeons. Although
little is known about his personal life, his was a glittering career so far,
achieved while he served and taught on the hospital wards and in the | 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
0 | dissecting room (Fig. 1) (Anon 1908).
Gray shared the idea for the new book with a talented colleague on
the teaching staff at St George’s, Henry Vandyke Carter, in November
1855. Carter was from a family of Scarborough artists, and was himself a clever artist and microscopist. He had produced fine illustrations for
Gray’s scientific publications before, but could see that this idea was a
much more complex project. Carter recorded in his diary:
Little to record. Gray made proposal to assist by drawings in bringing
out a Manual for students: a good idea but did not come to any plan …
too exacting, for would not be a simple artist (Carter 1855).
Neither of these young men was interested in producing a pretty book,
or an expensive one. Their purpose was to supply an affordable, accurate
teaching aid for people like their own students, who might soon be
Fig. 1 Henry Gray (1827–1861) is shown here in the foreground, seated
by the feet of the cadaver. The photograph was taken by a medical
student, Joseph Langhorn. The room is the dissecting room of St | 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
0 | George’s Hospital Medical School in Kinnerton Street, London. Gray is shown surrounded by staff and students. When the photo was taken, on 27 March 1860, Carter had left St George’s, to become Professor of Anatomy and Physiology at Grant Medical College, in Bombay (nowadays Mumbai). The second edition of Gray’s Anatomy was in its proof stages,
to appear in December 1860. Gray died just over a year later, in June 1861, at the height of his powers.
| 20 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | Historical introduction
e6Fig. 2 Henry Vandyke Carter (1831–1897). Carter was appointed
Honorary Surgeon to Queen Victoria in 1890.
acclaim. Reviews in The Lancet and the British Medical Journal were
highly complimentary, and students flocked to buy.
It is not difficult to understand why it was a runaway success. Gray’s
Anatomy knocked its competitors into a cocked hat. It was considerably
smaller and more slender than the doorstopper with which modern
readers are familiar. The book held well in the hand, it felt substantial,
and it contained everything required. To contemporaries, it was small
enough to be portable, but large enough for decent illustrations: ‘royal
octavo’ – 912 × 6 inches (24 × 15 cm) – about two-thirds of modern A4
size. Its medium-size, single-volume format was far removed from
Quain, yet double the size of Knox’s Manual.
Simply organized and well designed, the book explains itself confi -
dently and well; the clarity and authority of the prose are manifest. But
what made it unique for its day was the outstanding size and quality | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | of the illustrations. Gray thanked the wood engravers Butterworth and
Heath for the ‘great care and fidelity’ they had displayed in the engrav-
ings, but it was really to Carter that the book owed its extraordinary
success.
The beauty of Carter’s illustrations resides in their diagrammatic
clarity, quite atypical for their time. The images in contemporary
anatomy books were usually ‘proxy-labelled’: dotted with tiny numbers
or letters (often hard to find or read) or bristling with a sheaf of num -
bered arrows, referring to a key situated elsewhere, usually in a footnote, which was sometimes so lengthy it wrapped round on to the following
page. Proxy labels require the reader’s eye to move to and fro: from the
structure to the proxy label to the legend and back again. There was
plenty of scope for slippage, annoyance and distraction. Carter’s illustra -
tions, by contrast, unify name and structure, enabling the eye to assimi -
late both at a glance. We are so familiar with Carter’s images that it is
hard to appreciate how incredibly modern they must have seemed in
1858. The volume made human anatomy look new, exciting, accessible | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | and do-able.
The first edition was covered in a brown bookbinder’s cloth embossed
all over in a dotted pattern, and with a double picture-frame border. Its
spine was lettered in gold blocking:
sense of calamity. The grand old medical man Sir Benjamin Brodie, Sergeant-Surgeon to the Queen, and the great supporter of Gray to
whom Anatomy had been dedicated, cried forlornly: ‘Who is there to
take his place?’ (Anon 1908).
But old JW Parker ensured the survival of Gray’s by inviting Timothy
Holmes, the doctor who had helped proof-read the first edition, and who had filled Gray’s shoes at the medical school, to serve as Editor for
the next edition. Other long-running anatomy works, such as Quain,
remained in print in a similar way, co-edited by other hands (Quain
1856).
Holmes (1825–1907) was another gifted St George’s man, a scholar -
ship boy who had won an exhibition to Cambridge, where his brilliance
was recognized. Holmes was a Fellow of the Royal College of Surgeons
at 28. John Parker junior had commissioned him to edit A System of | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | Surgery (1860–64), an important essay series by distinguished surgeons on subjects of their own choosing. Many of Holmes’s authors remain
important figures, even today: John Simon, James Paget, Henry Gray,
Ernest Hart, Jonathan Hutchinson, Brown-Séquard and Joseph Lister.
Holmes had lost an eye in an operative accident, and he had a gruff
manner that terrified students, yet he published a lament for young
Parker that reveals him capable of deep feeling (Holmes 1860).
John Parker senior’s heart, however, was no longer in publishing.
His son’s death had closed down the future for him. The business, with
all its stocks and copyrights, was sold to Messrs Longman. Parker retired
to the village of Farnham, where he later died.
With Holmes as editor, and Longman as publisher, the immediate
future of Gray’s Anatomy was assured. The third edition appeared in
1864 with relatively few changes, Gray’s estate receiving the balance of his royalty after Holmes was paid £100 for his work.
THE MISSING OBITUARY
Why no obituary appeared for Henry Gray in Gray’s Anatomy is curious. | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | Gray had referred to Holmes as his ‘friend’ in the preface to the first
edition, yet it would also be true to say that they were rivals. Both had just applied for a vacant post at St George’s, as Assistant Surgeon. Had Gray lived, it is thought that Holmes may not have been appointed, despite his seniority in age (Anon 1908).
Later commentators have suggested, as though from inside knowl -
edge, that Holmes’s ‘proof-reading’ included improving Gray’s writing … with ‘DESCRIPTIVE AND SURGICAL’ in small capitals underneath.
Gray’s Anatomy is how it has been referred to ever since. Carter was given
credit with Gray on the book’s title page for undertaking all the dissec -
tions on which the book was based, and sole credit for all the illustra -
tions, though his name appeared in a significantly smaller type, and he
was described as the ‘Late Demonstrator in Anatomy at St George’s Hospital’ rather than being given his full current title, which was Profes -
sor of Anatomy and Physiology at Grant Medical College, Bombay. Gray was still only a Lecturer at St George’s and he may have been aware that | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | his words had been upstaged by the quality of Carter’s anatomical
images. He need not have worried: Gray is the famous name on the
spine of the book.
Gray was paid £150 for every thousand copies sold. Carter never
received a royalty payment, just a one-off fee at publication, which may
have allowed him to purchase the long-wished-for microscope he took
with him to India (Fig. 2).
The first edition print-run of 2000 copies sold out swiftly. A parallel
edition was published in the United States in 1859, and Gray must have
been deeply gratified to have to revise an enlarged new English edition
in 1859–60, though he was surely saddened and worried by the death
of his publisher, John Parker junior, at the young age of 40, while the
book was going through the press. The second edition came out in the
December of 1860 and it too sold like hot cakes, as indeed has every
subsequent edition.
The following summer, in June 1861, at the height of his powers and
full of promise, Henry Gray died unexpectedly at the age of only 34. | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
1 | Gray had contracted smallpox while nursing his nephew. A new strain
of the disease was more virulent than the one with which Gray had
been vaccinated as a child; the disease became confluent, and Gray died
in a matter of days.
Within months, the whole country would be pitched into mourning
for the death of Prince Albert. The creative era over which he had pre -
sided – especially the decade that had flowered since the Great Exhibi -
tion of 1851 – would be history.
THE BOOK SURVIVES
Anatomy Descriptive and Surgical could have died too. With Carter in
India, the death of Gray, so swiftly after that of the younger Parker, might have spelled catastrophe. Certainly, at St George’s there was a GRAY’S
ANATOMY | 21 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | Historical introduction
e7
were not as yet perfected, and in any case could not provide the bold
simplicity of line required for a book like Gray’s, which depended so
heavily on clear illustration and clear lettering. Recognizing the inferior -
ity of half-tone illustrations by comparison with Carter’s wood-engraved
originals, Pick and Howden courageously decided to jettison the
second-rate half-tones altogether. Most of the next edition’s illustrations
were either Carter’s, or old supplementary illustrations inspired by his
work, or newly commissioned wood engravings or line drawings,
intended ‘to harmonize with Carter’s original figures’ . They successfully
emulated Carter’s verve. Having fewer pages and lighter paper, the 1905
(sixteenth edition) weighed less than its predecessor, at 4 lb 1 1 oz/2.1 kg.
Typographically, the new edition was superb.
Howden took over as sole editor in 1909 (seventeenth edition) and
immediately stamped his personality on Gray’s. He excised ‘Surgical’
from the title, changing it to Anatomy Descriptive and Applied, and | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | removed Carter’s name altogether. He also instigated the beginnings of an editorial board of experts for Gray’s, by adding to the title page ‘Notes
on Applied Anatomy’ by AJ Jex-Blake and W Fedde Fedden, both St George’s men. For the first time, the number of illustrations exceeded
one thousand. Howden was responsible for the significant innovation
of a short historical note on Henry Gray himself, nearly 60 years after
his death, which included a portrait photograph (1918, twentieth
edition).
THE NOMENCLATURE CONTROVERSY
Howden’s era, and that of his successor TB Johnston (of Guy’s), was
overshadowed by a cloud of international controversy concerning ana -
tomical terminology. European anatomists were endeavouring to stand -
ardize anatomical terms, often using Latinate constructions, a move
resisted in Britain and the United States. Gray’s became mired in these
debates for over 20 years. The attempt to be fair to all sides by using multiple terms doubtless generated much confusion amongst students,
until a working compromise was at last arrived at in 1955 (thirty-second
edition, 1958). | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | Johnston oversaw the second retitling of the book (in 1938, twenty-
seventh edition): it was now, officially, Gray’s Anatomy, finally ending
the fiction that it had ever been known as anything else. Gray’s suffered
from paper shortages and printing difficulties in World War II, but suc -
cessive editions nevertheless continued to grow in size and weight, while illustrations were replaced and added as the text was revised.
Between Howden’s first sole effort (1909, seventeenth edition) and
Johnston’s last edition (1958, thirty-second edition), Gray’s expanded
by over 300 pages – from 1296 to 1604 pages, and almost 300 addi -
tional illustrations brought the total to over 1300. Johnston also intro -
duced X-ray plates (1938) and, in 1958 (thirty-second edition), electron micrographs by AS Fitton-Jackson, one of the first occasions on which
a woman was credited with a contribution to Gray’s. Johnston felt com -
pelled to mention that she was ‘a blood relative of Henry Gray himself’, perhaps by way of mitigation.
AFTER WORLD WAR II | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | The editions of Gray’s issued in the decades immediately following the
Second World War give the impression of intellectual stagnation. Steady expansion continued in an almost formulaic fashion, with the insertion
of additional detail. The central historical importance of innovation in
the success of Gray’s seems to have been lost sight of by its publishers
and editors – Johnston (1930–1958, twenty-fourth to thirty-second editions), J Whillis (co-editor with Johnston, 1938–1954), DV Davies
(1958–1967, thirty-second to thirty-fourth editions) and F Davies
(co-editor with DV Davies 1958–1962, thirty-second to thirty-third
editions). Gray’s had become so pre-eminent that perhaps complacency
crept in, or editors were too daunted or too busy to confront the ‘massive undertaking’ of a root and branch revision (Tansey 1995). The
unexpected deaths of three major figures associated with Gray’s in this
era, James Whillis, Francis Davies and David Vaughan Davies – each of whom had been ready to take the editorial reins – may have contributed
to retarding the process. The work became somewhat dull.
KEY EDITION: 1973 | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | DV Davies had recognized the need for modernization, but his unex -
pected death left the work to other hands. Two Professors of Anatomy
at Guy’s, Roger Warwick and Peter Williams, the latter of whom had been involved as an indexer for Gray’s for several years, regarded it as
an honour to fulfill Davies’s intentions.
Their thirty-fifth edition of 1973 was a significant departure from
tradition. Over 780 pages (of 1471) were newly written, almost a third style. This could be a reflection of Holmes’s own self-regard, but there
may be some truth in it. There can be no doubt that, as Editor of seven
subsequent editions of Gray’s Anatomy (third to ninth editions, 1864–
1880), Holmes added new material, and had to correct and compress passages, but it is also possible that, back in 1857, Gray’s original
manuscript had been left in a poor state for Holmes to sort out. In other
works, Gray’s writing style was lucid, but he always seems to have paid
a copyist to transcribe his work prior to submission. The original manu - | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | script of Gray’s Anatomy, sadly, has not survived, so it is impossible to
be sure how much of the finished version had actually been written by
Holmes.
It may be that Gray’s glittering career, or perhaps the patronage that
unquestionably advanced it, created jealousies among his colleagues,
or that there was something in Gray’s manner that precluded affection,
or that created resentments among clever social inferiors like Carter and
Holmes, especially if they felt their contributions to his brilliant career
were not given adequate credit. Whatever the explanation, no reference
to Gray’s life or death appeared in Gray’s Anatomy itself until the twen -
tieth century (Howden et al 1918).
A SUCCESSION OF EDITORS
Holmes expanded areas of the book that Gray himself had developed
in the second edition (1860), notably in ‘general’ anatomy (histology)
and ‘development’ (embryology). In Holmes’s time as Editor, the
volume grew from 788 pages in 1864 to 960 in 1880 (ninth edition),
with the histological section paginated separately in roman numerals | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | at the front of the book. Extra illustrations were added, mainly from
other published sources.
The connections with Gray and Carter, and with St George’s, were
maintained with the appointment of the next editor, T. Pickering Pick,
who had been a student at St George’s in Gray’s time. From 1883 (tenth
edition) onwards, Pick kept up with current research, rewrote and inte -
grated the histology and embryology into the volume, dropped Holmes from the title page, removed Gray’s preface to the first edition, and
added bold subheadings, which certainly improved the appearance and
accessibility of the text. Pick said he had ‘tried to keep before himself
the fact that the work is intended for students of anatomy rather than
for the Scientific Anatomist’ (thirteenth edition, 1893).
Pick also introduced colour printing (in 1887, eleventh edition) and
experimented with the addition of illustrations using the new printing
method of half-tone dots: for colour (which worked) and for new black-
and-white illustrations (which did not). Half-tone shades of grey com - | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | pared poorly with Carter’s wood engravings, still sharp and clear by comparison.
What Henry Vandyke Carter made of these changes is a rich topic
for speculation. He returned to England in 1888, having retired from
the Indian Medical Service, full of honours – Deputy Surgeon General,
and in 1890, he was made Honorary Surgeon to Queen Victoria. Carter
had continued researching throughout his clinical medical career in
India, and became one of India’s foremost bacteriologists/tropical
disease specialists before there was really a name for either discipline.
Carter made some important discoveries, including the fungal cause of
mycetoma, which he described and named. He was also a key figure in
confirming scientifically in India some major international discoveries,
such as Hansen’s discovery of the cause of leprosy, Koch’s discovery of
the organism causing tuberculosis, and Laveran’s discovery of the organ -
ism that causes malaria. Carter married late in life, and his wife was left with two young children when he died in Scarborough in 1897, aged
65. Like Gray, he received no obituary in the book.
When Pick was joined on the title page by Robert Howden (a profes - | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
2 | sional anatomist from the University of Durham) in 1901 (fifteenth
edition), the volume was still easily recognizable as the book Gray and
Carter had created. Although many of Carter’s illustrations had been
revised or replaced, many others still remained. Sadly, though, an entire
section (embryology) was again separately paginated, as its revision had
taken longer than anticipated. Gray’s had grown, seemingly inexorably,
and was now quite thick and heavy: 1244 pages, weighing 5 lb
8 oz/2.5 kg. Both co-editors, and perhaps also its publisher, were dis -
satisfied with it.
KEY EDITION: 1905
Serious decisions were taken well in advance of the next edition, which
turned out to be Pick’s last with Howden. Published 50 years after Gray had first suggested the idea to Carter, the 1905 (sixteenth) edition was a landmark one.
The period 1880–1930 was a difficult time for anatomical illustra-
tion, because the new techniques of photo-lithography and half-tone | 22 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
3 | Historical introduction
e8had developed a distinct character of its own in the interval), and sold
extremely well there (Williams and Warwick 1973).
The influence of the Warwick and Williams edition was forceful and
long-lasting, and set a new pattern for the following quarter-century.
As has transpired several times before, wittingly or unwittingly, a new
editor was being prepared for the future: Dr Susan Standring (of
Guy’s), who created the new bibliography for the 1973 edition of
Gray’s, went on to serve on the editorial board, and has served as
Editor-in-Chief for the last two editions before this one (2005–2008,
thirty-ninth and fortieth editions). Both editions are important for dif -
ferent reasons.
For the thirty-ninth edition, the entire content of Gray’s was reorgan-
ized, from systematic to regional anatomy. This great sea-change was not just organizational but historic, because, since its outset, Gray’s had
prioritized bodily systems, with subsidiary emphasis on how the systems interweave in the regions of the body. Professor Standring
explained that this regional change of emphasis had long been asked | 23 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
3 | for by readers and users of Gray’s, and that new imaging techniques in
our era have raised the clinical importance of local anatomy (Standring 2005). The change was facilitated by an enormous collective effort on
the part of the editorial team and the illustrators. The subsequent and
current editions consolidate that momentous change. (See Table 1.)
Table 1 Gray’s Anatomy Editions
Edition Date Author/Editor(s) Publisher Title
1st 1858 Henry Gray JW Parker & Son Anatomy Descriptive and Surgical
The drawings by Henry Vandyke Carter. The dissections jointly by
the author and Dr Carter
2nd 1860 Henry Gray JW Parker & Son
3rd 1864 T Holmes Longman
4th 1866 T Holmes Longman
5th 1869 T Holmes Longman
6th 1872 T Holmes Longman
7th 1875 T Holmes Longman
8th 1877 T Holmes Longman
9th 1880 T Holmes Longman
10th 1883 TP Pick Longman
11th 1887 TP Pick Longman
12th 1890 TP Pick Longman
13th 1893 TP Pick Longman | 23 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
3 | Gray’s preface removed
14th 1897 TP Pick Longman
15th 1901 TP Pick & R Howden Longman
16th 1905 TP Pick & R Howden Longman
17th 1909 Robert Howden Longman Anatomy Descriptive and Applied
Notes on applied anatomy by AJ Jex-Blake & W Fedde Fedden
18th 1913 Robert Howden & Blake & Fedden Longman
19th 1916 Robert Howden & Blake & Fedden Longman
20th 1918 Robert Howden & Blake & Fedden Longman
First edition ever to feature a photograph and obituary of Henry Gray
21st 1920 Robert Howden Longman
Notes on applied anatomy by AJ Jex-Blake & John Clay
22nd 1923 Robert Howden Longman
Notes on applied anatomy by John Clay & John D Lickley
23rd 1926 Robert Howden Longman
24th 1930 TB Johnston Longman
25th 1932 TB Johnston Longman
26th 1935 TB Johnston Longman
27th 1938 TB Johnston & J Whillis Longman Gray’s Anatomy | 23 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
3 | 28th 1942 TB Johnston & J Whillis Longman
29th 1946 TB Johnston & J Whillis Longman
30th 1949 TB Johnston & J Whillis Longman
31st 1954 TB Johnston & J Whillis Longman
32nd 1958 TB Johnston & DV Davies & F Davies Longman
33rd 1962 DV Davies & F Davies Longman
34th 1967 DV Davies & RE Coupland Longman
35th 1973 Peter L Williams & Roger Warwick Longman
With a separate volume: Functional Neuroanatomy of Man – being the
neurology section of Gray’s Anatomy. 35th edition, 1975
36th 1980 Roger Warwick & Peter L Williams Churchill Livingstone
37th 1989 Peter L Williams Churchill Livingstone
38th 1995 Peter L Williams & Editorial Board Churchill Livingstone
39th 2005 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical Practice
40th 2008 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical Practice | 23 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
3 | 41st 2015 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical Practiceof the illustrations were newly commissioned, and the illustration cap -
tions were freshly written throughout. With a complete re-typesetting
of the text in larger double-column pages, a new index and the innova -
tion of a bibliography, this edition of Gray’s looked and felt quite unlike
its 1967 (thirty-fourth edition) predecessor, and much more like its
modern incarnation.
This 1973 edition departed from earlier volumes in other significant
ways. The editors made explicit their intention to try to counter the
impetus towards specialization and compartmentalization in twentieth-
century medicine, by embracing and attempting to reintegrate the com -
plexity of the available knowledge. Warwick and Williams openly renounced the pose of omniscience adopted by many textbooks, believ -
ing it important to accept and mention areas of ignorance or uncer -
tainty. They shared with the reader the difficulty of keeping abreast in
the sea of research, and accepted with a refreshing humility the impos-
sibility of fulfilling their own ambitious programme.
Warwick and Williams’s 1973 edition had much in common with | 23 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
3 | Gray and Carter’s first edition. It was bold and innovative – respectful
of its heritage, while also striking out into new territory. It was visually
attractive and visually informative. It embodied a sense of a treasury of
information laid out for the reader (Williams and Warwick 1973). It
was published simultaneously in the United States (the American Gray’s | 23 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
4 | Historical introduction
e9
Howden R, Jex-Blake AJ, Fedde Fedden W (eds) 1918 Gray’s Anatomy, 20th
ed. London: Longman.
Lewis H Sinclair 1925 Arrowsmith. New York: Harcourt Brace; p. 4.
Nicol KE 2002 Henry Gray of St George’s Hospital: a Chronology. London:
published by the author.
Quain J 1856 Elements of Anatomy. Ed. by Sharpey W, Ellis GV. London:
Walton & Maberly.
Richardson R 2000 Death, Dissection and the Destitute. Chicago: Chicago
University Press; pp. 193–249, 287, 357.
Richardson R 2008 The Making of Mr Gray’s Anatomy. Oxford: Oxford
University Press.
Standring S (ed.) 2005 Preface. In: Gray’s Anatomy, 39th ed. Elsevier:
London.
Tansey EM 1995 A brief history of Gray’s Anatomy. In: Gray’s Anatomy, 38th
ed. London: Churchill Livingstone. | 24 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
4 | Williams PL, Warwick R (eds.) 1973 Preface. In: Gray’s Anatomy, 35th ed.
London: Churchill Livingstone.THE DOCTORS’ BIBLE
Neither Gray nor Carter, the young men who – by their committed hard
work between 1856 and 1858 – created the original Gray’s Anatomy,
would have conceived that so many years after their deaths their book would not only be a household name, but also be regarded as a work
of such pre-eminent importance that a novelist half a world away would
rank it as cardinal – alongside the Bible and Shakespeare – to a doctor’s
education (Sinclair Lewis 1925, Richardson 2008). From this forty-first
edition of Gray’s Anatomy, we can look back to appraise the long-term
value of their efforts. We can discern how the book they created tri -
umphed over its competitors, and has survived pre-eminent. Gray’s is a
remarkable publishing phenomenon. Although the volume now looks
quite different to the original, and contains so much more, its kinship
with the Gray’s Anatomy of 1858 is easily demonstrable by direct descent, | 24 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
4 | every edition updated by Henry Gray’s successor. Works are rare indeed that have had such a long history of continuous publication on both
sides of the Atlantic, and such a useful one.
Ruth Richardson, MA, DPhil, FRHistS
Senior Visiting Research Fellow, Centre for Life-Writing Research,
King’s College London;
Affiliated Scholar in the History and Philosophy of Science,
University of Cambridge, UK
REFERENCES
Anon 1908 Henry Gray. St George’s Hospital Gazette 16:49–54.
Carter HV 1855 Diary. Wellcome Western Manuscript 5818; 25 Nov.Gray H 1858 Preface. In: Anatomy: Descriptive and Surgical. London: JW
Parker & Son.
Holmes T (ed.) 1860 I: Preface. In: A System of Surgery. London: JW Parker
& Son.ACKNOWLEDGEMENTS
For their assistance while I was undertaking the research for this essay,
I should like to thank the Librarians and Archivists and Staff at the
British Library, Society of Apothecaries, London School of Hygiene and
Tropical Medicine, Royal College of Surgeons, Royal Society of Medi - | 24 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
4 | cine, St Bride Printing Library, St George’s Hospital Tooting, Scarbor -
ough City Museum and Art Gallery, University of Reading, Wellcome
Institute Library, Westminster City Archives and Windsor Castle; and
the following individuals: Anne Bayliss, Gordon Bell, David Buchanan,
Dee Cook, Arthur Credland, Chris Hamlin, Victoria Killick, Louise King,
Keith Nicol, Sarah Potts, Mark Smalley, and Nallini Thevakarrunai.
Above all, my thanks to Brian Hurwitz, who has read and advised on
the evolving text. | 24 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
5 | xviANATOMICAL NOMENCLATURE
with the median plane; although often employed, ‘parasagittal’ is there -
fore redundant and should not be used. The coronal (frontal) plane is
orthogonal to the median plane and divides the body into anterior
(front) and posterior (back). The horizontal (transverse) plane is
orthogonal to both median and sagittal planes. Radiologists refer to
transverse planes as (trans)axial; convention dictates that axial anatomy
is viewed as though looking from the feet towards the head.
Structures nearer the head are superior, cranial or (sometimes)
cephalic (cephalad), whereas structures closer to the feet are inferior;
caudal is most often used in embryology to refer to the hind end of the
embryo. Medial and lateral indicate closeness to the median plane,
medial being closer than lateral; in the anatomical position, the little
finger is medial to the thumb, and the great toe is medial to the little
toe. Specialized terms may also be used to indicate medial and lateral.
Thus, in the upper limb, ulnar and radial are used to mean medial and | 25 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
5 | lateral, respectively; in the lower limb, tibial and fibular (peroneal) are
used to mean medial and lateral, respectively. Terms may be based on
embryological relationships; the border of the upper limb that includes
the thumb, and the border of the lower limb that includes the great toe
are the pre-axial borders, whilst the opposite borders are the post-axial
borders. Various degrees of obliquity are acknowledged using com-
pound terms, e.g. posterolateral.
When referring to structures in the trunk and upper limb, we have
freely used the synonyms anterior, ventral, flexor, palmar and volar, and
posterior, dorsal and extensor. We recognize that these synonyms are
not always satisfactory, e.g. the extensor aspect of the leg is anterior with
respect to the knee and ankle joints, and superior in the foot and digits;
the plantar (flexor) aspect of the foot is inferior. Dorsal (dorsum) and
ventral are terms used particularly by embryologists and neuroanato -
mists; they therefore feature most often in Sections 2 and 3. | 25 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
5 | Distal and proximal are used particularly to describe structures in
the limbs, taking the datum point as the attachment of the limb to the trunk (sometimes referred to as the root), such that a proximal structure
is closer to the attachment of the limb than a distal structure. However,
proximal and distal are also used in describing branching structures,
e.g. bronchi, vessels and nerves. External (outer) and internal (inner)
refer to the distance from the centre of an organ or cavity, e.g. the layers
of the body wall, or the cortex and medulla of the kidney. Superficial
and deep are used to describe the relationships between adjacent struc -
tures. Ipsilateral refers to the same side (of the body, organ or structure), bilateral to both sides, and contralateral to the opposite side.
Teeth are described using specific terms that indicate their relation -
ship to their neighbours and to their position within the dental arch;
these terms are described on page 517.Anatomy is the study of the structure of the body. Conventionally, it is
divided into topographical (macroscopic or gross) anatomy (which
may be further divided into regional anatomy, surface anatomy, neuro - | 25 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
5 | anatomy, endoscopic and imaging anatomy); developmental anatomy (embryogenesis and subsequent organogenesis); and the anatomy of
microscopic and submicroscopic structure (histology).
Anatomical language is one of the fundamental languages of medi -
cine. The unambiguous description of thousands of structures is impos -
sible without an extensive and often highly specialized vocabulary. Ideally, these terms, which are often derived from Latin or Greek,
should be used to the exclusion of any other, and eponyms should be
avoided. In reality, this does not always happen. Many terms are ver -
nacularized and, around the world, synonyms and eponyms still abound in the literature, in medical undergraduate classrooms and in
clinics. The Terminologia Anatomica,
1 drawn up by the Federative Com-
mittee on Anatomical Terminology (FCAT) in 1998, continues to serve
as our reference source for the terminology for macroscopic anatomy,
and the text of the forty-first edition of Gray’s Anatomy is almost entirely
TA-compliant. However, where terminology is at variance with, or, more likely, is not included in, the TA, the alternative term used either is cited | 25 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
5 | in the relevant consensus document or position paper, or enjoys wide -
spread clinical usage. Synonyms and eponyms are given in parentheses on first usage of a preferred term and not shown thereafter in the text;
an updated list of eponyms and short biographical details of the clini -
cians and anatomists whose names are used in this way is available in the e-book for reference purposes (see Preface , p. ix, for further discus -
sion of the use of eponyms).
PLANES, DIRECTIONS AND
RELATIONSHIPS
To avoid ambiguity, all anatomical descriptions assume that the body
is in the conventional ‘anatomical position’, i.e. standing erect and
facing forwards, upper limbs by the side with the palms facing forwards,
and lower limbs together with the toes facing forwards (Fig. 1). Descrip -
tions are based on four imaginary planes – median, sagittal, coronal and horizontal – applied to a body in the anatomical position. The
median plane passes longitudinally through the body and divides it
into right and left halves. The sagittal plane is any vertical plane parallel | 25 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
5 | 1Terminologia Anatomica (1998) is the joint creation of the Federative Committee on
Anatomical Terminology (FCAT) and the Member Associations of the Interna -
tional Federation of Associations of Anatomists (IFAA). | 25 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
6 | AnAtomic Al nomencl Ature
xvii
Fig. 1 The terminology widely used in descriptive anatomy. Abbreviations shown on arrows: AD, adduction; AB, abduction; FLEX, flexion (of the thigh at
the hip joint); EXT, extension (of the leg at the knee joint).
LEFT LATERAL ASPECTPOSTERIOR ASPECTSUPERIOR ASPECT
Lateral
InversionEversionMedial (internal) rotationLateral (external) rotationPronationSupinationDistallyProximally
DistallyProximallyMedial (internal) rotationLateral (external) rotationMedialPosterior or dorsalAnterior or ventralCoronal plane
Median or sagittal plane
Transverse or horizontal planeInferior or caudal
Superior or cranial
INFERIOR ASPECTANTERIOR ASPECTRIGHT LATERAL ASPECT | 26 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | xviiiBIBLIOGRAPHY OF SELECTED TITLES
Haaga JR, Dogra VS, Forsting M, Gilkeson RC, Ha KH, Sundaram M
2009 CT and MR Imaging of the Whole Body, 5th ed. St Louis:
Elsevier, Mosby.
Lasjaunias P, Berenstein A, ter Brugge K 2001 Surgical Neuroangio
graphy, vol 1. Clinical Vascular Anatomy and Variations, 2nd ed. Berlin, New York: Springer.
Meyers MA 2000 Dynamic Radiology of the Abdomen: Normal and
Pathologic Anatomy, 5th ed. New York: Springer.
Pomeranz SJ 1992 MRI Total Body Atlas. Cincinnati: MRI EFI.
Spratt JD, Salkowski LR, Weir J, Abrahams PH 2010 Imaging Atlas of Human Anatomy, 4th ed. London: Elsevier, Mosby.
Sutton D, Reznek R, Murfitt J 2002 Textbook of Radiology and Imaging,
7th ed. Edinburgh: Elsevier, Churchill Livingstone. | 27 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | Whaites E, Drage N 2013 Essentials of Dental Radiography and Radiol
ogy, 5th ed. Edinburgh: Elsevier, Churchill Livingstone.Wicke L 2004 Atlas of Radiologic Anatomy, 7th ed. Philadelphia:
Elsevier, WB Saunders.
CLINICAL
Birch R 2010 Surgical Disorders of the Peripheral Nerves, 2nd ed. Edin
burgh: Elsevier, Churchill Livingstone.Bogduk N 2012 Clinical and Radiological Anatomy of the Lumbar
Spine, 5th ed. Edinburgh: Elsevier, Churchill Livingstone.
Borges AF 1984 Relaxed skin tension lines (RSTL) versus other skin
lines. Plast Reconstr Surg 73:144–50.
Burnand KG, Young AE, Lucas JD, Rowlands B, Scholefield J 2005 The
New Aird’s Companion in Surgical Studies, 3rd ed. Edinburgh: Elsevier, Churchill Livingstone.
Canale ST, Beaty JH 2012 Campbell’s Operative Orthopaedics, 12th ed.
Philadelphia: Elsevier, Mosby. | 27 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | Cormack GC, Lamberty BGH 1994 The Arterial Anatomy of Skin Flaps,
2nd ed. Edinburgh: Elsevier, Churchill Livingstone.
Cramer GD, Darby SA 2013 Clinical Anatomy of the Spine, Spinal Cord,
and ANS, 3rd ed. MO: Elsevier, Mosby.
Dyck PJ, Thomas PK 2005 Peripheral Neuropathy: 2 Volume Set with
Expert Consult Basic, 4th ed. Philadelphia: Elsevier, WB Saunders.
Ellis H, Mahadevan V 2013 Clinical Anatomy: Applied Anatomy for
Students and Junior Doctors, 13th ed. Wiley Blackwell.
Ellis H Feldman S, Harrop Griffiths W 2004 Anatomy for Anaesthetists,
8th ed. Oxford: Blackwell Science.Morris SF, Taylor GI 2013 Vascular territories. In: Neligan PC (ed.)
Plastic Surgery, vol. I. Principles, 3rd ed. London: Elsevier, Saunders.
Rosai J 201 1 Rosai and Ackerman’s Surgical Pathology, 10th ed. London:
Elsevier, Mosby. | 27 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | Shah J 2012 Jatin Shah’s Head and Neck Surgery and Oncology: Expert
Consult Online and Print, 4th ed. London: Elsevier, Mosby.
Zancolli EA, Cozzi EP 1991 Atlas of Surgical Anatomy of the Hand.
Edinburgh: Elsevier, Churchill Livingstone.
CLINICAL EXAMINATION
O’Brien M 2010 Aids to the Examination of the Peripheral Nervous System, 5th ed. London: Elsevier, WB Saunders.
Lumley JSP 2008 Surface Anatomy: The Anatomical Basis of Clinical
Examination, 4th ed. Edinburgh: Elsevier, Churchill Livingstone.The following references contain information relevant to numerous
chapters in this edition. They are therefore cited here rather than at the
end of individual chapters. For an extended historical bibliography, all
references from the thirty eighth edition (which includes all references
cited in earlier editions, up to and including the thirty eighth edition)
are available in the e book that accompanies Gray’s Anatomy .
TERMINOLOGY
Federative Committee on Anatomical Terminology 1998 Terminologia Anatomica: International Anatomical Nomenclature. Stuttgart: Thieme. | 27 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | Dorland WAN 201 1 Dorland’s Illustrated Medical Dictionary, 32nd ed.
Philadelphia: Elsevier, WB Saunders.
BASIC SCIENCES
Abrahams P, Spratt JD, Loukas M, van Schoor A N 2013 McMinn and
Abrahams’ Clinical Atlas of Human Anatomy: with STUDENT CONSULT Online Access, 7th ed. London: Elsevier, Mosby.
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P 2007 Molecu
lar Biology of the Cell, 5th ed. New York: Garland Science.
Berkovitz BKB, Kirsch C, Moxham BJ, Alusi G, Cheeseman T 2002
Interactive Head and Neck. London: Primal Pictures.
Boron WF, Boulpaep E 2012 Medical Physiology: with STUDENT
CONSULT Online Access, 2nd ed. Philadelphia: Elsevier, WB Saunders.
Crossman AR 2014 Neuroanatomy: An Illustrated Colour Text, 5th ed.
Edinburgh: Elsevier, Churchill Livingstone. | 27 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | Fitzgerald MD 201 1 Clinical Neuroanatomy and Neuroscience: with
STUDENT CONSULT Online Access, 6th ed. Edinburgh: Elsevier, Saunders.
Hall JE 2010 Guyton and Hall Textbook of Medical Physiology: with
STUDENT CONSULT Online Access, 12th ed. Philadelphia: Elsevier, Saunders.
Kerr JB 2010 Functional Histology, 2nd ed. London: Elsevier, Mosby.
Kierszenbaum AL 2014 Histology and Cell Biology: An Introduction to
Pathology, 4th ed. St Louis: Elsevier, Mosby.
Lowe JS, Anderson PG 2014 Stevens & Lowe’s Human Histology,
4th ed. London: Elsevier, Mosby.
Male D, Brostoff J, Roth D, Roitt I 2012 Immunology: with STUDENT
CONSULT Online Access, 8th ed. London: Elsevier, Mosby.
Moore KL, Persaud TVN, Torchia MG 2015 Before We Are Born: Essen
tials of Embryology and Birth Defects, 9th ed. St Louis: Elsevier. | 27 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
7 | Pollard TD, Earnshaw WC 2007 Cell Biology: with STUDENT CONSULT
Access, 2nd ed. Philadelphia: Elsevier, WB Saunders.
Salmon M 1994 Anatomic Studies: Book 1 Arteries of the Muscles of
the Extremities and the Trunk, Book 2 Arterial Anastomotic Pathways of the Extremities. Ed. by Taylor GI, Razaboni RM. St Louis: Quality Medical.
Young B, O’Dowd G, Woodford P 2013 Wheater’s Functional Histology:
A Text and Colour Atlas, 6th ed. Edinburgh: Elsevier, Churchill Livingstone.
IMAGING AND RADIOLOGY/RADIOLOGICAL
ANATOMY
Butler P, Mitchell AWM, Healy JC 201 1 Applied Radiological Anatomy,
2nd ed. New York: Cambridge University Press.
Ellis H, Logan BM, Dixon AK 2007 Human Sectional Anatomy: Pocket
Atlas of Body Sections, CT and MRI Images, 3rd ed. CRC Press.
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8 | 4SECTION 1
CHAPTER 1 Basic structure and function of cells
Epithelial cells rarely operate independently of each other and com-
monly form aggregates by adhesion, often assisted by specialized inter -
cellular junctions. They may also communicate with each other either
by generating and detecting molecular signals that diffuse across inter -
cellular spaces, or more rapidly by generating interactions between membrane-bound signalling molecules. Cohesive groups of cells con -
stitute tissues, and more complex assemblies of tissues form functional systems or organs.
Most cells are between 5 and 50 µm in diameter: e.g. resting lym-
phocytes are 6 µm across, red blood cells 7.5 µm and columnar epithe -
lial cells 20 µm tall and 10 µm wide (all measurements are approximate).
Some cells are much larger than this: e.g. megakaryocytes of the bone
marrow and osteoclasts of the remodelling bone are more than 200 µm
in diameter. Neurones and skeletal muscle cells have relatively extended
shapes, some of the former being over 1 m in length.
CELLULAR ORGANIZATION | 31 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
8 | Each cell is contained within its limiting plasma membrane, which encloses the cytoplasm. All cells, except mature red blood cells, also
contain a nucleus that is surrounded by a nuclear membrane or enve -
lope (see Fig. 1.1; Fig. 1.2). The nucleus includes: the genome of the
cell contained within the chromosomes; the nucleolus; and other sub -
nuclear structures. The cytoplasm contains cytomembranes and several membrane-bound structures, called organelles, which form separate CELL STRUCTURE
GENERAL CHARACTERISTICS OF CELLS
The shapes of mammalian cells vary widely depending on their interac -
tions with each other, their extracellular environment and internal
structures. Their surfaces are often highly folded when absorptive or
transport functions take place across their boundaries. Cell size is
limited by rates of diffusion, either that of material entering or leaving
cells, or that of diffusion within them. Movement of macromolecules
can be much accelerated and also directed by processes of active trans -
port across the plasma membrane and by transport mechanisms within the cell. According to the location of absorptive or transport functions, | 31 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
8 | apical microvilli (Fig. 1.1) or basolateral infoldings create a large
surface area for transport or diffusion.
Motility is a characteristic of most cells, in the form of movements
of cytoplasm or specific organelles from one part of the cell to another.
It also includes: the extension of parts of the cell surface such as pseu -
dopodia, lamellipodia, filopodia and microvilli; locomotion of entire cells, as in the amoeboid migration of tissue macrophages; the beating
of flagella or cilia to move the cell (e.g. in spermatozoa) or fluids overly -
ing it (e.g. in respiratory epithelium); cell division; and muscle contrac -
tion. Cell movements are also involved in the uptake of materials from
their environment (endocytosis, phagocytosis) and the passage of large
molecular complexes out of cells (exocytosis, secretion).
Fig . 1 .1 The main structural components and internal organization of a generalized cell . Plasma membraneActin filaments
Vesicle
Golgi apparatusIntermediate
filamentsMitochondrion
Smooth endoplasmic | 31 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
8 | reticulum
Rough endoplasmic
reticulumPeroxisomes
CytosolSurface invaginationSurface projections
(cilia, microvilli)
Cell junctions
Desmosome
Microtubules
Centriole pairNuclear envelope
Nucleus
RibosomeNucleolus
Lysosomes
Cell surface foldsNuclear pore | 31 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | Cell structure
5
CHaPTER 1
charides and polysaccharides are bound either to proteins (glycopro -
teins) or to lipids (glycolipids), and project mainly into the extracellular
domain (Fig. 1.3).
In the electron microscope, membranes fixed and contrasted by
heavy metals such as osmium tetroxide appear in section as two densely
stained layers separated by an electron-translucent zone – the classic
unit membrane. The total thickness of each layer is about 7.5 nm. The
overall thickness of the plasma membrane is typically 15 nm. Freeze-
fracture cleavage planes usually pass along the hydrophobic portion of the bilayer, where the hydrophobic tails of phospholipids meet, and
split the bilayer into two leaflets. Each cleaved leaflet has a surface and
a face. The surface of each leaflet faces either the extracellular surface
(ES) or the intracellular or protoplasmic (cytoplasmic) surface (PS). The
extracellular face (EF) and protoplasmic face (PF) of each leaflet are
artificially produced during membrane splitting. This technique has | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | also demonstrated intramembranous particles embedded in the lipid
bilayer; in most cases, these represent large transmembrane protein
molecules or complexes of proteins. Intramembranous particles are
distributed asymmetrically between the two half-layers, usually adher -
ing more to one half of the bilayer than to the other. In plasma mem -
branes, the intracellular leaflet carries most particles, seen on its face
(the PF). Where they have been identified, clusters of particles usually
represent channels for the transmembrane passage of ions or molecules
between adjacent cells (gap junctions).
Biophysical measurements show the lipid bilayer to be highly fluid,
allowing diffusion in the plane of the membrane. Thus proteins are able
to move freely in such planes unless anchored from within the cell.
Membranes in general, and the plasma membrane in particular, form
boundaries selectively limiting diffusion and creating physiologically
distinct compartments. Lipid bilayers are impermeable to hydrophilic
solutes and ions, and so membranes actively control the passage of ions
and small organic molecules such as nutrients, through the activity of | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | membrane transport proteins. However, lipid-soluble substances can pass directly through the membrane so that, for example, steroid hor -
mones enter the cytoplasm freely. Their receptor proteins are either cytosolic or nuclear, rather than being located on the cell surface.
Plasma membranes are able to generate electrochemical gradients
and potential differences by selective ion transport, and actively take up or export small molecules by energy-dependent processes. They also provide surfaces for the attachment of enzymes, sites for the receptors and distinct compartments within the cytoplasm. Cytomembranes
include the rough and smooth endoplasmic reticulum and Golgi appa-
ratus, as well as vesicles derived from them. Organelles include lyso -
somes, peroxisomes and mitochondria. The nucleus and mitochondria are enclosed by a double-membrane system; lysosomes and peroxi -
somes have a single bounding membrane. There are also non-membranous structures, called inclusions, which lie free in the cytosolic
compartment. They include lipid droplets, glycogen aggregates and pig - | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | ments (e.g. lipofuscin). In addition, ribosomes and several filamentous protein networks, known collectively as the cytoskeleton, are found in
the cytosol. The cytoskeleton determines general cell shape and sup -
ports specialized extensions of the cell surface (microvilli, cilia, flag -
ella). It is involved in the assembly of specific structures (e.g. centrioles)
and controls cargo transport in the cytoplasm. The cytosol contains
many soluble proteins, ions and metabolites.
Plasma membrane
Cells are enclosed by a distinct plasma membrane, which shares fea -
tures with the cytomembrane system that compartmentalizes the cyto -
plasm and surrounds the nucleus. All membranes are composed of lipids (mainly phospholipids, cholesterol and glycolipids) and pro -
teins, in approximately equal ratios. Plasma membrane lipids form a
lipid bilayer, a layer two molecules thick. The hydrophobic ends of each
lipid molecule face the interior of the membrane and the hydrophilic | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | ends face outwards. Most proteins are embedded within, or float in, the lipid bilayer as a fluid mosaic. Some proteins, because of extensive hydrophobic regions of their polypeptide chains, span the entire width of the membrane (transmembrane proteins), whereas others are only superficially attached to the bilayer by lipid groups. Both are integral (intrinsic) membrane proteins, as distinct from peripheral (extrinsic) membrane proteins, which are membrane-bound only through their association with other proteins. Carbohydrates in the form of oligosac-
Fig . 1 .2 The structural organization and some principal organelles of a
typical cell . This example is a ciliated columnar epithelial cell from human
nasal mucosa . The central cell, which occupies most of the field of
view, is closely apposed to its neighbours along their lateral plasma
membranes . Within the apical junctional complex, these membranes form
a tightly sealed zone (tight junction) that isolates underlying tissues from,
in this instance, the nasal cavity . Abbreviations: AJC, apical junctional
complex; APM, apical plasma membrane; C, cilia; Cy, cytoplasm; EN, | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | euchromatic nucleus; LPM, lateral plasma membrane; M, mitochondria;
MV, microvilli; N, nucleolus . (Courtesy of Dr Bart Wagner, Histopathology
Department, Sheffield Teaching Hospitals, UK .)
C MV
M
Cy
LPM
N
ENMAPMAJCV M C
M
Cy
LPM
N
ENMAPMAJC
Fig . 1 .3 The molecular organization of the plasma membrane, according
to the fluid mosaic model of membrane structure . Intrinsic or integral
membrane proteins include diffusion or transport channel complexes,
receptor proteins and adhesion molecules . These may span the thickness
of the membrane (transmembrane proteins) and can have both
extracellular and cytoplasmic domains . Transmembrane proteins have
hydrophobic zones, which cross the phospholipid bilayer and allow the
protein to ‘float’ in the plane of the membrane . Some proteins are
restricted in their freedom of movement where their cytoplasmic domains
are tethered to the cytoskeleton . Receptor
protein
Lipid bilayer
appearancein electronmicroscopeInternal
(intracellular) | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
9 | surfaceCarbohydrateresidues
TransmembraneproteinIntrinsic
membrane
protein
Transport
or diffusion
channelExtrinsic
proteinTransmembrane
pore complex
of proteins
External
(extracellular)
surface
Polar end ofphospholipidNon-polar tailof phospholipid
Cytoskeletalelement | 32 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
10 | Basic structure and function of cells
5.e1
CHaPTER 1
Combinations of biochemical, biophysical and biological tech -
niques have revealed that lipids are not homogenously distributed in
membranes, but that some are organized into microdomains in the bilayer, called ‘detergent-resistant membranes’ or lipid ‘rafts’, rich in sphingomyelin and cholesterol. The ability of select subsets of proteins
to partition into different lipid microdomains has profound effects on
their function, e.g. in T-cell receptor and cell–cell signalling. The highly organized environment of the domains provides a signalling, trafficking and membrane fusion environment. | 33 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | BaSIC STR uCTuRE aNd fu NCTION Of CEllS
6SECTION 1
abundant proteins; SER is abundant in steroid-producing cells and
muscle cells. A variant of the endoplasmic reticulum in muscle cells is
the sarcoplasmic reticulum, involved in calcium storage and release for
muscle contraction. For further reading on the endoplasmic reticulum,
see Bravo et al (2013).
Smooth endoplasmic reticulum
The smooth endoplasmic reticulum (see Fig. 1.4) is associated with
carbohydrate metabolism and many other metabolic processes, includ -
ing detoxification and synthesis of lipids, cholesterol and steroids. The membranes of the smooth endoplasmic reticulum serve as surfaces for
the attachment of many enzyme systems, e.g. the enzyme cytochrome
P450, which is involved in important detoxification mechanisms and
is thus accessible to its substrates, which are generally lipophilic. The
membranes also cooperate with the rough endoplasmic reticulum
and the Golgi apparatus to synthesize new membranes; the protein, carbohydrate and lipid components are added in different structural | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | compartments. The smooth endoplasmic reticulum in hepatocytes con -
tains the enzyme glucose-6-phosphatase, which converts glucose-6-
phosphate to glucose, a step in gluconeogenesis.
Rough endoplasmic reticulum
The rough endoplasmic reticulum is a site of protein synthesis; its
cytosolic surface is studded with ribosomes ( Fig. 1.5E). Ribosomes only
bind to the endoplasmic reticulum when proteins targeted for secretion begin to be synthesized. Most proteins pass through its membranes and
accumulate within its cisternae, although some integral membrane pro -
teins, e.g. plasma membrane receptors, are inserted into the rough endoplasmic reticulum membrane, where they remain. After passage
from the rough endoplasmic reticulum, proteins remain in membrane-
bound cytoplasmic organelles such as lysosomes, become incorporated
into new plasma membrane, or are secreted by the cell. Some carbohy -
drates are also synthesized by enzymes within the cavities of the rough endoplasmic reticulum and may be attached to newly formed protein
(glycosylation). Vesicles are budded off from the rough endoplasmic | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | reticulum for transport to the Golgi as part of the protein-targeting
mechanism of the cell.
Ribosomes, polyribosomes
and protein synthesis
Ribosomes are macromolecular machines that catalyse the synthesis of
proteins from amino acids; synthesis and assembly into subunits takes
place in the nucleolus and includes the association of ribosomal RNA
(rRNA) with ribosomal proteins translocated from their site of synthesis
in the cytoplasm. The individual subunits are then transported into the
cytoplasm, where they remain separate from each other when not
actively synthesizing proteins. Ribosomes are granules approximately
25 nm in diameter, composed of rRNA molecules and proteins assem -
bled into two unequal subunits. The subunits can be separated by their sedimentation coefficients (S) in an ultracentrifuge into larger 60S and
smaller 40S components. These are associated with 73 different pro -
teins (40 in the large subunit and 33 in the small), which have structural and enzymatic functions. Three small, highly convoluted rRNA strands | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | (28S, 5.8S and 5S) make up the large subunit, and one strand (18S) is
in the small subunit.
A typical cell contains millions of ribosomes. They may form groups
(polyribosomes or polysomes) attached to messenger RNA (mRNA),
which they translate during protein synthesis for use outside the system
of membrane compartments, e.g. enzymes of the cytosol and cytoskel -
etal proteins. Some of the cytosolic products include proteins that can be inserted directly into (or through) membranes of selected organelles,
such as mitochondria and peroxisomes. Ribosomes may be attached to
the membranes of the rough endoplasmic reticulum (see Fig. 1.5E).
In a mature polyribosome, all the attachment sites of the mRNA are
occupied as ribosomes move along it, synthesizing protein according
to its nucleotide sequence. Consequently, the number and spacing of
ribosomes in a polyribosome indicate the length of the mRNA mole - | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | cule and hence the size of the protein being made. The two subunits have separate roles in protein synthesis. The 40S subunit is the site of
attachment and translation of mRNA. The 60S subunit is responsible
for the release of the new protein and, where appropriate, attachment
to the endoplasmic reticulum via an intermediate docking protein that
directs the newly synthesized protein through the membrane into the cisternal space.
Golgi apparatus (Golgi complex)
The Golgi apparatus is a distinct cytomembrane system located near the nucleus and the centrosome. It is particularly prominent in secretory cells and can be visualized when stained with silver or other metallic
of external signals, including hormones and other ligands, and sites for
the recognition and attachment of other cells. Internally, plasma mem -
branes can act as points of attachment for intracellular structures, in particular those concerned with cell motility and other cytoskeletal
functions. Cell membranes are synthesized by the rough endoplasmic
reticulum in conjunction with the Golgi apparatus.
Cell coat (glycocalyx)
The external surface of a plasma membrane differs structurally from
internal membranes in that it possesses an external, fuzzy, carbohydrate- | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | rich coat, the glycocalyx. The cell coat forms an integral part of the
plasma membrane, projecting as a diffusely filamentous layer 2–20 nm
or more from the lipoprotein surface. The cell coat is composed of the
carbohydrate portions of glycoproteins and glycolipids embedded in
the plasma membrane (see Fig. 1.3).
The precise composition of the glycocalyx varies with cell type; many
tissue- and cell type-specific antigens are located in the coat, including
the major histocompatibility complex of the immune system and, in
the case of erythrocytes, blood group antigens. Therefore, the glycocalyx
plays a significant role in organ transplant compatibility. The glycocalyx
found on apical microvilli of enterocytes, the cells forming the lining
epithelium of the intestine, consists of enzymes involved in the diges -
tive process. Intestinal microvilli are cylindrical projections (1–2 µm
long and about 0.1 µm in diameter) forming a closely packed layer
called the brush border that increases the absorptive function of
enterocytes.
Cytoplasm | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | Compartments and functional organization
The cytoplasm consists of the cytosol, a gel-like material enclosed by
the cell or plasma membrane. The cytosol is made up of colloidal pro -
teins such as enzymes, carbohydrates and small protein molecules, together with ribosomes and ribonucleic acids. The cytoplasm contains
two cytomembrane systems, the endoplasmic reticulum and Golgi
apparatus, as well as membrane-bound organelles (lysosomes, peroxi -
somes and mitochondria), membrane-free inclusions (lipid droplets, glycogen and pigments) and the cytoskeleton. The nuclear contents,
the nucleoplasm, are separated from the cytoplasm by the nuclear envelope.
Endoplasmic reticulum
The endoplasmic reticulum is a system of interconnecting membrane-lined channels within the cytoplasm ( Fig. 1.4). These channels take
various forms, including cisternae (flattened sacs), tubules and vesicles.
The membranes divide the cytoplasm into two major compartments.
The intramembranous compartment, or cisternal space, is where secre - | 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
11 | tory products are stored or transported to the Golgi complex and cell exterior. The cisternal space is continuous with the perinuclear space.
Structurally, the channel system can be divided into rough or granu -
lar endoplasmic reticulum (RER), which has ribosomes attached to its
outer, cytosolic surface, and smooth or agranular endoplasmic reticu-
lum (SER), which lacks ribosomes. The functions of the endoplasmic
reticulum vary greatly and include: the synthesis, folding and transport
of proteins; synthesis and transport of phospholipids and steroids; and
storage of calcium within the cisternal space and regulated release into
the cytoplasm. In general, RER is well developed in cells that produce
Fig . 1 .4 Smooth endoplasmic reticulum with associated vesicles . The
dense particles are glycogen granules . (Courtesy of Rose Watson, Cancer
Research UK .)
| 34 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
12 | Basic structure and function of cells
6.e1
CHaPTER 1
The glycocalyx plays a significant role in maintenance of the integrity
of tissues and in a wide range of dynamic cellular processes, e.g. serving
as a vascular permeability barrier and transducing fluid shear stress to
the endothelial cell cytoskeleton (Weinbaum et al 2007). Disruption of
the glycocalyx on the endothelial surface of large blood vessels precedes
inflammation, a conditioning factor of atheromatosis (e.g. deposits of
cholesterol in the vascular wall leading to partial or complete obstruc -
tion of the vascular lumen).
Protein synthesis on ribosomes may be suppressed by a class of RNA
molecules known as small interfering RNA (siRNA) or silencing RNA.
These molecules are typically 20–25 nucleotides in length and bind (as
a complex with proteins) to specific mRNA molecules via their comple -
mentary sequence. This triggers the enzymatic destruction of the mRNA or prevents the movement of ribosomes along it. Synthesis of the
encoded protein is thus prevented. Their normal function may have | 35 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
12 | antiviral or other protective effects; there is also potential for developing
artificial siRNAs as a therapeutic tool for silencing disease-related genes. | 35 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
13 | Cell structure
7
CHaPTER 1
Fig . 1 .5 The Golgi apparatus and functionally related organelles . A, Golgi apparatus (G) adjacent to the nucleus (N) (V, vesicle) . B, A large residual body
(tertiary lysosome) in a cardiac muscle cell (M, mitochondrion) . C, The functional relationships between the Golgi apparatus and associated cellular
structures . D, A three-dimensional reconstruction of the Golgi apparatus in a pancreatic β cell showing stacks of Golgi cisternae from the cis-face (pink)
and cis-medial cisternae (red, green) to the trans-Golgi network (blue, yellow, orange–red); immature proinsulin granules (condensing vesicles) are
shown in pale blue and mature (crystalline) insulin granules in dark blue . The flat colour areas represent cut faces of cisternae and vesicles . E, Rough
endoplasmic reticulum (R), associated with the Golgi apparatus (G) . (D, Courtesy of Dr Brad Marsh, Institute for Molecular Bioscience, University of | 36 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
13 | Queensland, Brisbane . A,B,E From human tissue, courtesy of Dr Bart Wagner, Histopathology Department, Sheffield Teaching Hospitals, UK .)
M
Phagocytic pathway Secretory pathway Receptor-mediated endocytosis Membrane recycling
Early endosome
Late endosome
Secondary lysosome
Residual body
cis-Golgi network
Rough endoplasmic
reticulumGolgi cisternaeVesicle shuttling
between cisternaeLysosomal
fusionClathrin-coated pit
trans-Golgi networkA B
C
D EG
VN
G
G
RG
G | 36 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | BaSIC STR uCTuRE aNd fu NCTION Of CEllS
8SECTION 1
Endocytic (internalization) pathway
The endocytic pathway begins at the plasma membrane and ends in
lysosomes involved in the degradation of the endocytic cargo through
the enzymatic activity of lysosomal hydrolases. Endocytic cargo is
internalized from the plasma membrane to early endosomes and
then to late endosomes. Late endosomes transport their cargo to lyso -
somes, where the cargo material is degraded following fusion and mixing of contents of endosomes and lysosomes. Early endosomes
derive from endocytic vesicles (clathrin-coated vesicles and caveolae).
Once internalized, endocytic vesicles shed their coat of adaptin and
clathrin, and fuse to form an early endosome, where the receptor
molecules release their bound ligands. Membrane and receptors from
the early endosomes can be recycled to the cell surface as exocytic
vesicles.
Clathrin-dependent endocytosis occurs at specialized patches of
plasma membrane called coated pits; this mechanism is also used to | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | internalize ligands bound to surface receptor molecules and is also
termed receptor-mediated endocytosis. Caveolae (little caves) are struc -
turally distinct pinocytotic vesicles most widely used by endothelial and smooth muscle cells, when they are involved in transcytosis, signal
transduction and possibly other functions. In addition to late endo -
somes, lysosomes can also fuse with phagosomes, autophagosomes
and plasma membrane patches for membrane repair. Lysosomal hydro -
lases process or degrade exogenous materials (phagocytosis or hetero -
phagy) as well as endogenous material (autophagy). Phagocytosis consists of the cellular uptake of invading pathogens, apoptotic cells
and other foreign material by specialized cells. Lysosomes are numerous
in actively phagocytic cells, e.g. macrophages and neutrophil granulo-
cytes, in which lysosomes are responsible for destroying phagocytosed
particles, e.g. bacteria. In these cells, the phagosome, a vesicle poten -
tially containing a pathogenic microorganism, may fuse with several lysosomes.
Autophagy involves the degradation and recycling within an | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | autophagosome of cytoplasmic components that are no longer needed,
including organelles. The assembly of the autophagosome involves
several proteins, including autophagy-related (Atg) proteins, as well as
Hsc70 chaperone, that translocate the substrate into the lysosome (Boya
et al 2013). Autophagosomes sequester cytoplasmic components and
then fuse with lysosomes without the participation of a late endosome.
The 26S proteasome (see below) is also involved in cellular degradation
but autophagy refers specifically to a lysosomal degradation–recycling
pathway. Autophagosomes are seen in response to starvation and cell
growth.
Late endosomes receive lysosomal enzymes from primary lysosomes
derived from the Golgi apparatus after late endosome–lysosome mem -
brane tethering and fusion followed by diffusion of lysosomal contents into the endosomal lumen. The pH inside the fused hybrid organelle,
now a secondary lysosome, is low (about 5.0) and this activates lyso - | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | somal acid hydrolases to degrade the endosomal contents. The products of hydrolysis either are passed through the membrane into the cytosol,
or may be retained in the secondary lysosome. Secondary lysosomes
may grow considerably in size by vesicle fusion to form multivesicular
bodies, and the enzyme concentration may increase greatly to form
large lysosomes ( Fig. 1.5B).
Lysosomes
Lysosomes are membrane-bound organelles 80–800 nm in diameter,
often with complex inclusions of material undergoing hydrolysis (sec -
ondary lysosomes). Two classes of proteins participate in lysosomal
function: soluble acid hydrolases and integral lysosomal membrane
proteins. Each of the 50 known acid hydrolases (including proteases,
lipases, carbohydrases, esterases and nucleases) degrades a specific sub -
strate. There are about 25 lysosomal membrane proteins participating in the acidification of the lysosomal lumen, protein import from the
cytosol, membrane fusion and transport of degradation products to the
cytoplasm. Material that has been hydrolysed within secondary lyso - | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | somes may be completely degraded to soluble products, e.g. amino acids, which are recycled through metabolic pathways. However, degra -
dation is usually incomplete and some debris remains. A debris-laden vesicle is called a residual body or tertiary lysosome (see Fig. 1.5B), and
may be passed to the cell surface, where it is ejected by exocytosis;
alternatively, it may persist inside the cell as an inert residual body. Considerable numbers of residual bodies can accumulate in long-lived cells, often fusing to form larger dense vacuoles with complex lamellar inclusions. As their contents are often darkly pigmented, this may change the colour of the tissue; e.g. in neurones, the end-product of lysosomal digestion, lipofuscin (neuromelanin or senility pigment), gives ageing brains a brownish-yellow colouration. Lysosomal enzymes
salts. Traffic between the endoplasmic reticulum and the Golgi appara -
tus is bidirectional and takes place via carrier vesicles derived from the
donor site that bud, tether and fuse with the target site.
Golgins are long coiled-coil proteins attached to the cytoplasmic | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | surface of cisternal membranes, forming a fibrillar matrix surrounding
the Golgi apparatus to stabilize it; they have a role in vesicle trafficking
(for further reading on golgins, see Munro 201 1). The Golgi apparatus
has several functions: it links anterograde and retrograde protein and lipid flow in the secretory pathway; it is the site where protein and lipid
glycosylation occurs; and it provides membrane platforms to which
signalling and sorting proteins bind.
Ultrastructurally, the Golgi apparatus (Fig. 1.5A) displays a contin-
uous ribbon-like structure consisting of a stack of several flattened
membranous cisternae, together with clusters of vesicles surrounding
its surfaces. Cisternae differ in enzymatic content and activity. Small
transport vesicles from the rough endoplasmic reticulum are received
at one face of the Golgi stack, the convex cis-face (entry or forming
surface). Here, they deliver their contents to the first cisterna in the series by membrane fusion. From the edges of this cisterna, the protein
is transported to the next cisterna by vesicular budding and then | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | fusion, and this process is repeated across medial cisternae until the
final cisterna at the concave trans-face (exit or condensing surface) is
reached. Here, larger vesicles are formed for delivery to other parts of the cell.
The cis-Golgi and trans-Golgi membranous networks form an inte -
gral part of the Golgi apparatus. The cis-Golgi network is a region of
complex membranous channels interposed between the rough endo -
plasmic reticulum and the Golgi cis-face, which receives and transmits
vesicles in both directions. Its function is to select appropriate proteins synthesized on the rough endoplasmic reticulum for delivery by vesicles
to the Golgi stack, while inappropriate proteins are shuttled back to the
rough endoplasmic reticulum.
The trans-Golgi network, at the other side of the Golgi stack, is also
a region of interconnected membrane channels engaged in protein
sorting. Here, modified proteins processed in the Golgi cisternae are
packaged selectively into vesicles and dispatched to different parts of
the cell. The packaging depends on the detection, by the trans-Golgi | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | network, of particular amino-acid signal sequences, leading to their enclosure in membranes of appropriate composition that will further
modify their contents, e.g. by extracting water to concentrate them
(vesicles entering the exocytosis pathway) or by pumping in protons to
acidify their contents (lysosomes destined for the intracellular sorting
pathway).
Within the Golgi stack proper, proteins undergo a series of sequen -
tial chemical modifications by Golgi resident enzymes synthesized
in the rough endoplasmic reticulum. These include: glycosylation (changes in glycosyl groups, e.g. removal of mannose, addition of
N-acetylglucosamine and sialic acid); sulphation (addition of sulphate
groups to glycosaminoglycans); and phosphorylation (addition of
phosphate groups). Some modifications serve as signals to direct pro -
teins and lipids to their final destination within cells, including lyso-somes and plasma membrane. Lipids formed in the endoplasmic
reticulum are also routed for incorporation into vesicles.
Exocytic (secretory) pathway
Secreted proteins, lipids, glycoproteins, small molecules such as amines | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | and other cellular products destined for export from the cell are trans -
ported to the plasma membrane in small vesicles released from the trans-face of the Golgi apparatus. This pathway either is constitutive, in
which transport and secretion occur more or less continuously, as with
immunoglobulins produced by plasma cells, or it is regulated by exter-
nal signals, as in the control of salivary secretion by autonomic neural
stimulation. In regulated secretion, the secretory product is stored tem -
porarily in membrane-bound secretory granules or vesicles. Exocytosis is achieved by fusion of the secretory vesicular membrane with the
plasma membrane and release of the vesicle contents into the extracel-
lular domain. In polarized cells, e.g. most epithelia, exocytosis occurs
at the apical plasma membrane. Glandular epithelial cells secrete into
a duct lumen, as in the pancreas, or on to a free surface, such as the
lining of the stomach. In hepatocytes, bile is secreted across a very small
area of plasma membrane forming the wall of the bile canaliculus. This
region is defined as the apical plasma membrane and is the site of | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
14 | exocrine secretion, whereas secretion of hepatocyte plasma proteins into the blood stream is targeted to the basolateral surfaces facing the sinusoids. Packaging of different secretory products into appropriate vesicles takes place in the trans-Golgi network. Delivery of secretory
vesicles to their correct plasma membrane domains is achieved by sorting sequences in the cytoplasmic tails of vesicular membrane proteins. | 37 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
15 | Basic structure and function of cells
8.e1
CHaPTER 1
Carrier vesicles in transit from the endoplasmic reticulum to the
Golgi apparatus (anterograde transport) are coated by coat protein
complex II (COPII), whereas COPI-containing vesicles function in the
retrograde transport route from the Golgi apparatus (reviewed in Spang
(2013)).
The membranes contain specific signal proteins that may allocate
them to microtubule-based transport pathways and allow them to dock with appropriate targets elsewhere in the cell, e.g. the plasma mem -
brane in the case of secretory vesicles. Vesicle formation and budding at the trans-Golgi network involves the addition of clathrin on their
external surface, to form coated pits.
Specialized cells of the immune system, called antigen-presenting
cells, degrade protein molecules, called antigens, transported by the endocytic pathway for lysosomal breakdown, and expose their frag -
ments to the cell exterior to elicit an immune response mediated ini -
tially by helper T cells. | 38 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | Cell structure
9
CHaPTER 1
Mitochondria
In the electron microscope, mitochondria usually appear as round or
elliptical bodies 0.5–2.0 µm long ( Fig. 1.6), consisting of an outer
mitochondrial membrane; an inner mitochrondrial membrane, sepa-
rated from the outer membrane by an intermembrane space; cristae,
infoldings of the inner membrane that harbour ATP synthase to gener -
ate ATP; and the mitochondrial matrix, a space enclosed by the inner membrane and numerous cristae. The permeability of the two mito -
chondrial membranes differs considerably: the outer membrane is freely permeable to many substances because of the presence of large
non-specific channels formed by proteins (porins), whereas the inner
membrane is permeable to only a narrow range of molecules. The pres -
ence of cardiolipin, a phospholipid, in the inner membrane may con -
tribute to this relative impermeability.
Mitochondria are the principal source of chemical energy in most | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | cells. Mitochondria are the site of the citric acid (Krebs’) cycle and the
electron transport (cytochrome) pathway by which complex organic
molecules are finally oxidized to carbon dioxide and water. This process
provides the energy to drive the production of ATP from adenosine
diphosphate (ADP) and inorganic phosphate (oxidative phosphoryla -
tion). The various enzymes of the citric acid cycle are located in the mitochondrial matrix, whereas those of the cytochrome system and
oxidative phosphorylation are localized chiefly in the inner mitochon -
drial membrane.
The intermembrane space houses cytochrome c, a molecule involved
in activation of apoptosis.
The number of mitochondria in a particular cell reflects its general
energy requirements; e.g. in hepatocytes there may be as many as 2000, whereas in resting lymphocytes there are usually very few. Mature
may also be secreted – often as part of a process to alter the extracellular
matrix, as in osteoclast-mediated erosion during bone resorption. For
further reading on lysosome biogenesis, see Saftig and Klumperman
(2009).
lysosomal dysfunction | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | Lysosomal storage diseases (LSDs) are a consequence of lysosomal dysfunction. Approximately 60 different types of LSD have been identi -
fied on the basis of the type of material accumulated in cells (such as
mucopolysaccharides, sphingolipids, glycoproteins, glycogen and lipo -
fuscins). LSDs are characterized by severe neurodegeneration, mental decline, and cognitive and behavioural abnormalities. Autophagy
impairment caused by defective lysosome–autophagosome coupling
triggers a pathogenic cascade by the accumulation of substrates that
contribute to neurodegenerative disorders including Parkinson’s dis -
ease, Alzheimer’s disease, Huntington’s disease and several tau-opathies.
Many lysosomal storage diseases are known, e.g. Tay–Sachs disease
(GM2 gangliosidosis), in which a faulty β-hexosaminidase A leads to
the accumulation of the glycosphingolipid GM2 ganglioside in neu -
rones, causing death during childhood. In Danon disease, a vacuolar skeletal myopathy and cardiomyopathy with neurodegeneration in
hemizygous males, lysosomes fail to fuse with autophagosomes because | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | of a mutation of the lysosomal membrane protein LAMP-2 (lysosomal
associated membrane protein-2).
26S proteasome
A protein can be degraded by different mechanisms, depending on
the cell type and different pathological conditions. Furthermore, the
same substrate can engage different proteolytic pathways (Park and
Cuervo 2013). Three major protein degradation mechanisms operate
in eukaryotic cells to dispose of non-functional cellular proteins:
the autophagosome–lysosomal pathway (see above); the apoptotic
procaspase–caspase pathway (see below); and the ubiquitinated
protein–26S proteasome pathway. The 26S proteasome is a multicata -
lytic protease found in the cytosol and the nucleus that degrades intra -
cellular proteins conjugated to a polyubiquitin chain by an enzymatic
cascade. The 26S proteasome consists of several subunits arranged into
two 19S polar caps, where protein recognition and adenosine 5 ′-
triphosphate (ATP)-dependent target processing occur, flanking a 20S central barrel-shaped structure with an inner proteolytic chamber | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | (Tomko and Hochstrasser 2013). The 26S proteasome participates in
the removal of misfolded or abnormally assembled proteins, the deg -
radation of cyclins involved in the control of the cell cycle, the process -
ing and degradation of transcription regulators, cellular-mediated
immune responses, and cell cycle arrest and apoptosis.
Peroxisomes
Peroxisomes are small (0.2–1 µm in diameter) membrane-bound
organelles present in most mammalian cells. They contain more than 50 enzymes responsible for multiple catabolic and synthetic biochemi -
cal pathways, in particular the β-oxidation of very-long-chain fatty
acids (>C22) and the metabolism of hydrogen peroxide (hence the
name peroxisome). Peroxisomes derive from the endoplasmic reticu -
lum through the transfer of proteins from the endoplasmic reticulum to peroxisomes by vesicles that bud from specialized sites of the endo -
plasmic reticulum and by a lipid non-vesicular pathway. All matrix proteins and some peroxisomal membrane proteins are synthesized by
cytosolic ribosomes and contain a peroxisome targeting signal that | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | enables them to be imported by proteins called peroxins (Braverman
et al 2013, Theodoulou et al 2013). Mature peroxisomes divide by
small daughter peroxisomes pinching off from a large parental peroxisome.
Peroxisomes often contain crystalline inclusions composed mainly
of high concentrations of the enzyme urate oxidase. Oxidases use
molecular oxygen to oxidize specific organic substrates (such as
L-amino
acids, D-amino acids, urate, xanthine and very-long-chain fatty acids)
and produce hydrogen peroxide that is detoxified (degraded) by per -
oxisomal catalase. Peroxisomes are particularly numerous in hepato -
cytes. Peroxisomes are important in the oxidative detoxification of various substances taken into or produced within cells, including
ethanol. Peroxin mutation is a characteristic feature of Zellweger syn -
drome (craniofacial dysmorphism and malformations of brain, liver,
eye and kidney; cerebrohepatorenal syndrome). Neonatal leukodystro - | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
16 | phy is an X-linked peroxisomal disease affecting mostly males, caused by deficiency in β-oxidation of very-long-chain fatty acids. The build-up
of very-long-chain fatty acids in the nervous system and suprarenal glands determines progressive deterioration of brain function and suprarenal insufficiency (Addison’s disease). For further reading, see
Braverman et al (2013).
Fig . 1 .6 A, Mitochondria in human cardiac muscle . The folded cristae
(arrows) project into the matrix from the inner mitochondrial membrane .
B, The location of the elementary particles that couple oxidation and
phosphorylation reactions . (A, Courtesy of Dr Bart Wagner,
Histopathology Department, Sheffield Teaching Hospitals, UK .)
A
B
Elementary
particlesCristae (folds)Inner membraneOuter membrane | 39 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
17 | Basic structure and function of cells
9.e1
CHaPTER 1
The transcription factor EB (TFEB) is responsible for regulating lyso -
somal biogenesis and function, lysosome-to-nucleus signalling and
lipid catabolism (for further reading, see Settembre et al (2013)). If any
of the actions of lysosomal hydrolases, of the lysosome acidification
mechanism or of lysosomal membrane proteins fails, the degradation
and recycling of extracellular substrates delivered to lysosomes by the
late endosome and the degradation and recycling of intracellular sub -
strates by autophagy lead to progressive lysosomal dysfunction in several tissues and organs.
Experimentally, TFEB activation can reduce the accumulation of
the pathogenic protein in a cellular model of Huntington’s disease (a
neurodegenerative genetic disorder that affects muscle coordination)
and improves the Parkinson’s disease phenotype in a murine model.
Cristae are abundant in mitochondria seen in cardiac muscle
cells and in steroid-producing cells (in the suprarenal cortex, corpus
luteum and Leydig cells). The protein steroidogenic acute regulatory
protein (StAR) regulates the synthesis of steroids by transporting | 40 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
17 | cholesterol across the outer mitochondrial membrane. A mutation
in the gene encoding StAR causes defective suprarenal and gonadal
steroidogenesis. | 40 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | BaSIC STR uCTuRE aNd fu NCTION Of CEllS
10 SECTION 1
ent and its electronic charge, and the potential difference across the
membrane. These factors combine to produce an electrochemical gradi -
ent, which governs ion flux. Channel proteins are utilized most effec -
tively by the excitable plasma membranes of nerve cells, where the
resting membrane potential can change transiently from about −80 mV
(negative inside the cell) to +40 mV (positive inside the cell) when
stimulated by a neurotransmitter (as a result of the opening and sub -
sequent closure of channels selectively permeable to sodium and potassium).
Carrier proteins bind their specific solutes, such as amino acids, and
transport them across the membrane through a series of conforma -
tional changes. This latter process is slower than ion transport through membrane channels. Transport by carrier proteins can occur either pas -
sively by simple diffusion, or actively against the electrochemical gradi -
ent of the solute. Active transport must therefore be coupled to a source
of energy, such as ATP generation, or energy released by the coordinate
movement of an ion down its electrochemical gradient. Linked trans - | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | port can be in the same direction as the solute, in which case the carrier protein is described as a symporter, or in the opposite direction, when
the carrier acts as an antiporter.
Translocation of proteins across
intracellular membranes
Proteins are generally synthesized on ribosomes in the cytosol or on the rough endoplasmic reticulum. A few are made on mitochondrial
ribosomes. Once synthesized, many proteins remain in the cytosol,
where they carry out their functions. Others, such as integral membrane
proteins or proteins for secretion, are translocated across intracellular
membranes for post-translational modification and targeting to their
destinations. This is achieved by the signal sequence, an addressing
system contained within the protein sequence of amino acids, which is
recognized by receptors or translocators in the appropriate membrane.
Proteins are thus sorted by their signal sequence (or set of sequences
that become spatially grouped as a signal patch when the protein folds
into its tertiary configuration), so that they are recognized by and enter
the correct intracellular membrane compartment.
Cell signalling
Cellular systems in the body communicate with each other to coordi - | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | nate and integrate their functions. This occurs through a variety of processes known collectively as cell signalling, in which a signalling
molecule produced by one cell is detected by another, almost always by
means of a specific receptor protein molecule. The recipient cell trans -
duces the signal, which it most often detects at the plasma membrane, into intracellular chemical messages that change cell behaviour.
The signal may act over a long distance, e.g. endocrine signalling
through the release of hormones into the blood stream, or neuronal
synaptic signalling via electrical impulse transmission along axons
and subsequent release of chemical transmitters of the signal at syn -
apses or neuromuscular junctions. A specialized variation of endocrine
signalling (neurocrine or neuroendocrine signalling) occurs when neu -
rones or paraneurones (e.g. chromaffin cells of the suprarenal medulla) secrete a hormone into interstitial fluid and the blood stream.
Alternatively, signalling may occur at short range through a paracrine
mechanism, in which cells of one type release molecules into the inter -
stitial fluid of the local environment, to be detected by nearby cells of a different type that express the specific receptor protein. Neurocrine | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | cell signalling uses chemical messengers found also in the central
nervous system, which may act in a paracrine manner via interstitial
fluid or reach more distant target tissues via the blood stream. Cells
may generate and respond to the same signal. This is autocrine signal -
ling, a phenomenon that reinforces the coordinated activities of a group of like cells, which respond together to a high concentration of a local
signalling molecule. The most extreme form of short-distance signalling
is contact-dependent (juxtacrine) signalling, where one cell responds to
transmembrane proteins of an adjacent cell that bind to surface recep -
tors in the responding cell membrane. Contact-dependent signalling also includes cellular responses to integrins on the cell surface binding
to elements of the extracellular matrix. Juxtacrine signalling is impor -
tant during development and in immune responses. These different
types of intercellular signalling mechanism are illustrated in Figure 1.7.
For further reading on cell signalling pathways, see Kierszenbaum and
Tres (2012).
Signalling molecules and their receptors | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | The majority of signalling molecules (ligands) are hydrophilic and so cannot cross the plasma membrane of a recipient cell to effect changes erythrocytes lack mitochondria altogether. Cells with few mitochondria
generally rely largely on glycolysis for their energy supplies. These
include some very active cells, e.g. fast twitch skeletal muscle fibres,
which are able to work rapidly but for only a limited duration. Mito -
chondria appear in the light microscope as long, thin structures in the cytoplasm of most cells, particularly those with a high metabolic rate,
e.g. secretory cells in exocrine glands. In living cells, mitochondria
constantly change shape and intracellular position; they multiply by
growth and fission, and may undergo fusion.
The mitochondrial matrix is an aqueous environment. It contains a
variety of enzymes, and strands of mitochondrial DNA with the capacity
for transcription and translation of a unique set of mitochondrial genes
(mitochondrial mRNAs and transfer RNAs, mitochondrial ribosomes
with rRNAs). The DNA forms a closed loop, about 5 µm across; several | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | identical copies are present in each mitochondrion. The ratio between its bases differs from that of nuclear DNA, and the RNA sequences also
differ in the precise genetic code used in protein synthesis. At least 13
respiratory chain enzymes of the matrix and inner membrane are
encoded by the small number of genes along the mitochondrial DNA.
The great majority of mitochondrial proteins are encoded by nuclear
genes and made in the cytosol, then inserted through special channels
in the mitochondrial membranes to reach their destinations. Their
membrane lipids are synthesized in the endoplasmic reticulum.
It has been shown that mitochondria are of maternal origin because
the mitochondria of spermatozoa are not generally incorporated
into the ovum at fertilization. Thus mitochondria (and mitochondrial genetic variations and mutations) are passed only through the
female line.
Mitochondria are distributed within a cell according to regional
energy requirements, e.g. near the bases of cilia in ciliated epithelia, in the basal domain of the cells of proximal convoluted tubules in the
renal cortex (where considerable active transport occurs) and around
the proximal segment, called middle piece, of the flagellum in sperma - | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | tozoa. They may be involved with tissue-specific metabolic reactions, e.g. various urea-forming enzymes are found in liver cell mitochondria.
Moreover, a number of genetic diseases of mitochondria affect particu -
lar tissues exclusively, e.g. mitochondrial myopathies (skeletal muscle) and mitochondrial neuropathies (nervous tissue). For further informa -
tion on mitochondrial genetics and disorders, see Chinnery and Hudson (2013).
Cytosolic inclusions
The aqueous cytosol surrounds the membranous organelles described
above. It also contains various non-membranous inclusions, including
free ribosomes, components of the cytoskeleton, and other inclusions,
such as storage granules (e.g. glycogen), pigments (such as lipofuscin
granules, remnants of the lipid oxidative mechanism seen in the supra -
renal cortex) and lipid droplets.
lipid droplets
Lipid droplets are spherical bodies of various sizes found within many
cells, but are especially prominent in the adipocytes (fat cells) of
adipose connective tissue. They do not belong to the Golgi-related vacu - | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | olar system of the cell. They are not membrane-bound, but are droplets of lipid suspended in the cytosol and surrounded by perilipin proteins,
which regulate lipid storage and lipolysis. See Smith and Ordovás
(2012) for further reading on obesity and perilipins. In cells specialized
for lipid storage, the vacuoles reach 80 µm or more in diameter. They
function as stores of chemical energy, thermal insulators and mechani -
cal shock absorbers in adipocytes. In many cells, they may represent end-products of other metabolic pathways, e.g. in steroid-synthesizing
cells, where they are a prominent feature of the cytoplasm. They may
also be secreted, as in the alveolar epithelium of the lactating breast.
Transport across cell membranes
Lipid bilayers are increasingly impermeable to molecules as they increase in size or hydrophobicity. Transport mechanisms are therefore
required to carry essential polar molecules, including ions, nutrients,
nucleotides and metabolites of various kinds, across the plasma mem -
brane and into or out of membrane-bound intracellular compartments. Transport is facilitated by a variety of membrane transport proteins, | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |
18 | each with specificity for a particular class of molecule, e.g. sugars. Trans -
port proteins fall mainly into two major classes: channel proteins and
carrier proteins.
Channel proteins form aqueous pores in the membrane, which open
and close under the regulation of intracellular signals, e.g. G-proteins, to allow the flux of solutes (usually inorganic ions) of specific size and charge. Transport through ion channels is always passive, and ion flow through an open channel depends only on the ion concentration gradi - | 41 | Gray's Anatomy: 41st Edition | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Gray%27s%20Anatomy%2041E%202015.pdf | PyPDF2TextLoader | https://archive.org/details/GraysAnatomy41E2015PDF |