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Xerox University Microfilms
300 North Zeeb Road
Ann Arbor, Michigan 48106
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LD3907 . 15' 2.Zf1 8 0
flT IfAe Ate A . 1 Q91l«
19^0 C a p illa ry 0 f r a g i l i t y in the skin, of
,Ko the alb in o r a t and i t s r e la tio n t o
the h a ir cy cle, [New York] 19i>0,
[2 ],6 6 ty p e w ritte n le a v e s, c o l,
p la te s ,c h a r ts , d ia g r s , 29c®*
T hesis (Ph.D ,) - New York U n iv e r
s ity , G raduate School, 195&•
" L ite ra tu re c ite d " : p , 51-58,
C57640
M List
XorOX University Microfilms, Ann Arbor, Michigan 48106
THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED.
UBRARI Of
war
TORI WIV1R8TTT
0IT71RSITT HEIGHT?
CAPILLARY FRAGILITY IN THE SKIN OF THE ALBINO RAT
AND ITS RELATION TO THE HAIR CYCLE
A d is s e r ta tio n in the Department of Anatomy
subm itted to the fac u lty o f the
Graduate School of A rts and Science
in p a r t i a l fu lfillm e n t o f the
requirem ents fo r the degree of
Doctor of Philosophy
George Kozam
June 1950
CAPILLARY FRAGILITY IN THE SKIN OF THE ALBINO RAT
AND ITS RELATION TO TH1\ HAIR CYCLE
In tro d u ctio n
Page
T ests fo r th e study of C a p illa ry F r a g i li t y .................................1
The Negative P ressu re P r in c ip le ....................................1
The P o s itiv e P ressu re P r in c ip le ................................ 2
Chemical M ethods........................................................................ 4
The Ecchymosis T e s t . . . ........................................................ 7
Mechanisms o f C ap illary Hemorrhage................................................... 8
F acto rs R egulating C ap illary Hemorrh- g e ...................................... 9
H em ostatic F a c to rs......................................................................11
S trength o f C a p illary V a il.................................................11
In tra v a sc u la r P re s s u re ............................................................12
Tonus.........................................................................................................13
H air Cycles o f the Albino R a t.................................................................15
Methods
The A p p licatio n and S tan d ard izatio n of the N egative
P ressu re P rin c ip le to th e Albino R a t..............................................17
O bservations
The Normal Animal.................................................................................................21
Thyroxin A d m in istratio n .................................................................................25
The A dm inlstrarion o f Sex Hormones....................................................26
E strogen.................................................................................. 26
P ro g estero n e ......................................................................................28
Estrogen and P rogesterone Com bination....................28
T e sto ste ro n e ......................................................................................29
2 0 a 5 ^ 0
Page
The E ffe c t of Orchidectomy, Ovariectomy,
Adrenalectom y..................................................................................................... 29
I n a n itio n ............................................................................................................... 30
I r r a d ia tio n .......................................................................................................... 32
P h y sical Agents: H eat, Cold, and High Barom etric
P re s s u re .................................................................................................................. 34
Chemical A gents. . .......................................................................................... J6
Local: H istam ine, N ico tin e, A d ren alin e 36
G eneral: H eparin, D icoum arol...................................... 37
D iscussion
T issue Turgor and the Damping E f fe c t........................................ 38
C a p illary F ra g ility and H air E ru p tio n .........................................45
Summary
Graphs and Photographs
L ite ra tu re C ited
INTRODUCTION
T ests fo r C a p illary F ra g ility
The cutaneous m an ifesta tio n s of c a p illa ry f r a g ility
and hem orrhagic d ia th e s is have been observed since an cien t
tim es. During the l a s t f i f t y y e a rs, however, many o f th ese
p urpuric co nd itio ns have been c la s s if ie d and a few of th e ir
1
underlying p rin c ip le s understood. Some are considered to
occur in conjunction w ith system ic d ise a se s, such as s c a rle t
fev e r, m easles, d ip h th e ria , sm allpox, and urem ia, in which
the c a p illa ry endothelium i s damaged d ire c tly by to x in s, and
in vitam in d e fic ie n c ie s such as scurvy. Others are seen in
system ic d ise a se s in which the c a p illa ry endothelium is i n
d ir e c tly a ffe c te d , e .g ., m enstrual d iso rd e rs, endocrine dys
fu n c tio n s, and d ise a se s of the spleen and the re tic u lo -e n d o -
t h e l i a l system . A type of c a p illa ry f r a g i l it y has a lso been
a scrib ed to in creased c a p illa ry p erm eab ility where th ere i s
a d istu rb ed vasomotor a c tio n . A s ta te o f c a p illa ry f r a g ility ,
m oreover, i s not uncommonly found in the more lo c a liz e d , derm-
a to lo g ic co n d itio n s such as M ajocchi*s d ise a se , angioma s e r -
pigenosum, te le a n g ie c ta s ia , Shamberg’s d ise a se , o rth o s ta tic
2
purpura, and d e rm a titis hem ostatica •
V arious te s ts have been d ev ised , since the pioneer
3
work of Hecht in 1907, to estim ate c a p illa ry stre n g th and
to understand th e d istu rb ed physiology which brings about
th ese m a n ife sta tio n s. This in v e s tig a to r employed the su ctio n
or neg ativ e p ressu re p rin c ip le to determ ine th e amount of
-1
p a r t i a l vacuum necessary fo r the production of c a p illa ry or
p e te c h ia l hemorrhage in th e skin of humans. He te s te d d i f
fe re n t age groups and v ario u s reg io ns of the body by th e use
4
o f graded suctio n p re ssu re s. F ro n ta li performed experim ents
5
which co rro b orated th is work. Da S ilva-M ello co n stru cted a
m o d ifica tio n of H echtTs apparatus which he c a lle d " c a p illa ry
6
re s is to m e te r" . A sim ila r device was developed by Von Borbely
. 7
and employed by Armentano and Szent-Gyorgy in stu d ie s on
8 ,9
Vitem in P. C u tter, M arquardt, and Johnson introduced th e
f i r s t method for th e m icroscopic o bservation of c a p illa r ie s
te s te d by negative p re ssu re . The end of the n a il bed was ob
served under the m icroscope a f te r i t had been su bjected to
su c tio n by means of a g la s s fin g er appliance and pump appara
tu s .
The second approach to the study of c a p illa ry f r a -
10,11
g i l i t y , th e Rumpel-Leede t e s t , was based on the p o sitiv e
p ressu re p rin c ip le . I t employed the in crease of i n tr a c a p il
la ry p ressu re by means of a cu ff placed on th e upper arm and
In fla te d u n til p e te c h ia l hemorrhages appeared in the sk in be
low th e c o n stric te d area. This method was introduced in to
t h i s country as the " c a p illa ry re s is ta n c e t e s t" by Hess and
12 1
F ish . otephan used th e term " e n d o th e lia l symptom" to
d e scrib e a p o sitiv e fin d in g re s u ltin g from th e use of th is
t e s t and which he considered as in d ic a tin g a p ath o lo g ic con
d itio n of the e n d o th e lia l c e lls of the e n tire c a p illa ry sy s-
13
tern. G oethlin fu rth e r stan d ard ized th is p o sitiv e p ressu re
p rin c ip le fo r ro u tin e c lin ic a l usage. The number of p etech iae
produced in a 1 sq. cm. a re a, dem arcated in th e a n te c u b ita l
fo ssa, by a cu ff p ressu re of 50 mm Hg in 15 m inutes i s
m u ltip lie d by a fa c to r o f two. This product i s then added
to th e p e te c h ia l count obtained in th e same a re a by in c re a s
ing th e cu ff p ressu re to 70 mm Hg fo r an oth er 15 m inutes.
This has come to be known as the Groethlin Ind ex. Many v a r i
atio n s of th is method have been employed, some using an in fra -
d ia s to lic , others using a su p ra d ia sto lic v a lu e .
Thus, the two p ressu re p rin c ip le s , negative and pos
i ti v e , are used fo r te s tin g the stren g th of blood v e sse ls w ith
the end point of each being th e production of p e te c h ia l hem
orrhage in the sk in . A ll other pressure t e s t s have been
fu rth e r m o d ificatio n s of these methods. Of th e se , the one em-
26,14
ploying negative or su c tio n pressure has been found to be
more adaptab le and s u ite d to the te s tin g o f a g re a te r number
of region s on the human body. The p o sitiv e p ressu re te c h
n iqu es, however, though lim ite d in th e ir u se, most n e arly ap
proxim ate the co n d itio n s of spontaneous hemorrhage in c a p il
lary f r a g i l i t y s ta te s .
There has been much v a rie ty in th e siz e of th e te s t
cup and the len g th o f the te s t period used in th e production
3 15
of cutaneous p e te c h ia l hemorrhages. Hecht , Mengler ,
5 16
Da S ilva-M ello , and Tey used cups of very la rg e diam eters
(3 to 5 cm.) fo r a p erio d of one m inute. The one-m inute te s t
period w ith 2 cm. cups was believed to be more su ita b le by
, 6 17 18 14
von Borbely , J e r s ild and Elmby , and Franke • Copley
found, by varying the t e s t period from 15 seconds to 4 m inutes,
th a t the longer te s tin g time appeared to produce more p e te c h ia l
-3
hem orrhages. A two-minute su c tio n tim e, w ith a 4*5 cup,
however, gave the most c o n siste n t r e s u lts .
19
Hess developed th e f i r s t chem ical t e s t by applying
20
th e puncture technique of Koch in which the skin is lig h tly
pricked w ith a fin e needle and observed the follow ing day
fo r the presence of bleeding p o in ts . These were considered to
in d ic a te a bleeding tendency. Hess observed w hether c a p illa ry
hemorrhages re su lte d from subcutaneous in je c tio n s of diph
th e r ia a n tito x in . He found no p etech iae a t the s i t e of in -
21
je c tio n . Leschke and Y/ittkower found th a t so lu tio n s of
0.25/& sodium chloride in je c te d subcutaneously produced an
i r r i t a t i o n leading to the developm ent of subcutaneous hemato-
mata in p a tie n ts having bleeding ten d e n cies. A more recen t
and b e tte r co n tro lled chem ical method was introduced by Peck,
22 23
R osenthal, and E rf who in je c te d in tra d erm ally a standardized
co n cen tratio n of mocassin snake venom of known hemorrhagin
c o n te n t. Readings were made a t 30 and 60 m inutes and a p o sitiv e
re a c tio n was considered to be the appearance, w ith in one
hour, of p e te c h ia l hemorrhages or ecchymosis a t the in je c tio n
s i t e . This venom te s t can be used to determ ine c a p illa ry
f r a g i l it y in a lo calized area not a c c e ssib le to to u rn iq u et
t e s t s , such as the cheek, gums, p e ria n a l, and p e rin e a l reg io n s.
Other techniques u tiliz in g the chem ical p rin c ip le
24
have been designed by Chambers and Copley for the study
o f c a p illa ry stren g th in the mucous membranes of anim als.
V arious hemorrhagims were in je c te d in tra d e rm a lly in to the
4
- -
n i c t i ta ti n g membrane of the r a b b it’s eye and the flow of
blood and ru p tu re of v e sse ls were observed by means of a
25
binocular d is s e c tin g m icroscope. Copley has also app lied
th is technique to the o ra l pouch of the golden ham ster. The
in d iv id u a l blood v e sse ls of the tra n s-illu m in a te d pouch were
te s te d by su c tio n procedure a fte r the in trad erm al a d m in istra
tio n o f drugs to the te s t a re a.
26
As pointed out by Frischknecht , and Peck and
31
Copley , however, both p o sitiv e and neg ativ e p ressu re p rin
c ip le s are o b jectio n ab le because they induce a com pletely
non-physiologic stim ulus to act on the c a p illa ry bed. The
form er produces p e te c h ia l hemorrhage by an increased in tr a -
v ascu lar p ressu re w hile the l a t t e r low ers the p e riv a sc u la r
p ressu re w ith passive d ila ta tio n o f the c a p illa ry bed. Chem
ic a l m ethods, m oreover, introduce a fo reig n medium in to the
te s t area whose method of a c tio n is not e x ac tly known.
The g e n erally accepted r e s u lts of a l l these t e s ts ,
however, in d ic a te th a t th ere are g re a t re g io n a l v a ria tio n s
of s e n s itiv ity in the same human su b je c t. This has been con-
,
6
firm ed rep eated ly by many in v e s tig a to rs . Von Borbely ,
15 27 18
Mengler , Wiemer , and Franke found the upper reg io n s
14
o f the body more se n sitiv e than the lower ones. Copley
has n o t been able to v e rify statem ents th a t symmetric skin
areas in th e same in d iv id u a l always m aintained the same cap
i ll a r y re s is ta n c e . This au th o r, a ls o , could not concur in
the view th a t c a p illa ry re s is ta n c e remained co n stan t as meas
ured on the same region of the body on d if f e r e n t days.
-5-
