STUDIES ON ABSORPTION FROM MAMMALIAN INTESTINE
Helen Ogilvie Wood
A Thesis Submitted for the Degree of PhD at the
University of St Andrews
1945
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Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/11245
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—2—
"S tu d o n ta o f a b o o rp tlo o —- — — have I n th o p a s t
r e l i e d to o nxucii on th o o l n s s i o a l n eth o d a o f b lo ch em latry *
I n o u f f ic i o n t a t t e n t i o n l a p a id t o th e c o l l a s an a c t iv e
op^^an**#
D a n lo ili and hovson (1943)
P c m e a b i l i t y o f N a tu ra l î/îonbranoe» C anbridee
«»3»
G enoral I n tr o d u c tio n • • . « • . • • . • • . . • • . . • • • • « • • • • « • • • • • • • • • • • • • p v S *
S e c tio n A .. . # e P * 2 1 #
S u rfa c e Area o f th o Skmll X a te a tin o i n th o Rat and i n th e
Cat#
I . In tro d u c tio n # I I # Methods#
H I # R e su lts#
a)
H i s to lo c ic n l Apyieorances# b) Area o f t h e Mucous Membrane. IV# D iscu ssio n #a ) A bsolute Values# b) R o la tlv o V alu es,
V# 3 w m ary .
SOCMOn^^# # • • • • • • • • • • • • e# # • • • • # # e • • • • • • # e• • # é# • • e. # # • # # . • • • • • #P•37«
R e la tiv e K ates o f A bso rp tio n o f M onosaoeharldos from Je ju n im * and Ileum o f R ate undor U rethane A naosthosia#
I # In tro d u c tio n # I I # P a s t Works#
I I I # P re s o n t Work. a) Elethod#
b) R e su lts#
c) D iscu ssio n #
4
-S e c tio n G.### , # # . # , # # ... 67# H ate o f "A b so rp tio n " o f Gluooso and X ylose from th e I n t e s t i n e
o f Dead Hats#
I # In tro d u c tio n # H . Metlio i s .
XIX# H osu its# IV# Sxannory#
S e c tio n D###»##»*####.♦##♦♦#.##♦•##»###•••»*#«»«###.######D# 73# P o s t-i ortam C h a n ts i n th o ü p lth o llu c i o f th e Sm all I n t e s t i n e
o f th e Hat#
I # X n tro d u cti on# I I # l^ th o d #
H I # H esulta#
IV# D iscu ssio n #
a) "A b so rp tio n " o f ŒLucose and Xylose from th e Sm ell
I n t e s t i n e o f th e Dead Ret#
b) Hi s to lo n ! c o l iia a a ln e tlo n o f th e E p ith e liu m .
V, Siromery#
S e c tio n 5# . . . . • . «. • . »#. #>#. . #>#. . . ####p« 79# *016 C o n d itio n o f th o Mucous Membrfino i n th e S u rv iv in g
I s o l a t e d I n to s tin o #
I # I n t r o d u c t i on#
I I . Methods# R abbit#
I I I . R e su lts # Dieeuselcm #
5
-V* Simmery.
S e c tio n F* , , ... . . p . 8 6#
The E f f e c t o f L ocal P o is o n ln c w ith tSonolodoccetic Acid upon
th e I n t o o t i n a l IHiCOUS y en h ran e o f Rnto#
I# I n tro d u c tio n # I I . rîethod#
XXI# R e su lts# IV# D isc u ssio n
V. Swanary#
s e c tio n G#. .####.## ### ### .## # . . # ... ... . . ###p# 92# The E f fe c t o f S y c te n ic P ol c an in e v /ith M onoiodoaoetic A cid upon th e I n t e o t l n a l Mucous Maabrono o f R ats#
I# I n tro d u c tio n # I I # Method#
a) E f f e c t o f Subcutaneous I n j e c t i o n o f
M bnolodoacetic Acid in to R ats#
b) Subeutanoous I n j e c t i o n o f U onoio d o ao etio A cid i n to R ats un d er D rethane A n a esth e sia #
c) R o u tin e A b so rp tio n Experim ent u s in g
M anoiodoacotio Acid#
I I I # R e su lts #
a) G eneral C o n d itio n o f tho i\niraals#
-•6—
I .V . DlBousslon» V# Suraoary*
S e o tlo n n . ...*... • . V ... .. • . • • . • «P.1C2.
Tho iSffeot o f C thor Toxic A gents upon th e E p ith eliu m o f th e S b o ll I n te s tin e *
I # In tro d u c tio n *
I I * riothods*
a ) Sodium F lu o rid e *
b) Sodium Cyanide* I I I * R e su lts*
a ) Sodiw i F lu o rid e *
b) Sodium Cyanide* ^
IV# Disouoaion*
V* suDFiary*
S e c tio n I * ***.# ... ...* $ . p . 108. The E f f e c t o f A drenalectom y upon th o E p ith eliu m o f th e
Sbinll I n te s tin e *
I* In tro d u c tio n * I I * Method*
I I I * R e su lts*
IV* D iscussion*
7* Summary*
G eneral Di s c us s i on* * # # , * p * 11 4 .
G eneral S u n a a ry i *p* 124*
-y.
J L S - S JlA A Il I ^ ^ x i t O D U C T l O H
8
G ia m w INntODÜCTIOH.
I n th e h i s t o r i c a l aevolo]%aont o f th e c o n o o p tlo n s o f th o mechanism o f a b s o r p tio n from th e i n t e s t i n e i t i s o v id o n t t h a t , from th e v e ry
b e g in n in g , th e view s f a l l i n t o two m ain c a t e g o r i e s , namely %»
(1) t h a t a b s o rp tio n from th e i n t o s t i n o i s p u r e ly a p h y sie o • mechan
i c a l p ro o o se .
(2) t h a t th e p ro c e ss o f i n t o s t i n a l a b s o rp tio n i s due t o th o p h y sio l o g i c a l a c t i v i t y o f th o l i v i n g i n t e s t i n a l c e l l s and t h a t th o
phoncmona observed cannot bo e x p la in e d on knwm p h y s ic a l laws*
Amongst th e e a r l i e s t re c o rd e d view s on th e p ro c e s s o f a b so rp
t i o n wore th o so o f Rudolph! (lEXW) and Mogendio (1828) who b o lie v e d t h a t a b s o r p tio n was caused by mere p h y s ic a l " im b ib itio n " w h ile , on th o o th e r h an d , TiodenonSr and (X tielin (1820) b e lie v e d t h a t th e v i l l i a c te d l i k e in v e r te d s e c r e t in g g la n d s . h i t h th e advance o f
knowlodgo co n ce rn in g osm otic phenomena, D u tro ch o t (1826) p u t
forw ard h ie th e o r y o f q domaoaia to e x p la in th e p ro c e ss o f i n t e s t i n a l a b s o r p tio n . For many y e a rs an osm otic e x p la n a tio n i n a
m o d ified f o m h o ld th e f i e l d .
Kowovor, i n 1851^BrQloke p u t forw ard a g a in th e th e o ry propounded
by lioborkO hn i n th e p re v io u s o o n tu ry t h a t th e p e r i s t a l t i c p r e s s u r e b rin g s about a b s o rp tio n by f o r c i b l e f i l t r a t i o n o f th e g u t c o n te n ts
i n to th e l i v i n g t i s s u e s . L a to r , V o it and B auer (1869) su p p o rte d
t h i s view a s a r e s u l t o f t h e i r in v e s ti g a t i o n s on th e a b s o r p tio n o f p r o te in s o l u t i o n s , se rw i and s a l t s . They conéwcted t h a t osm osis
9
-beoed p a r t l y upon th o oaronoouB id o a t h a t th e p aeaeco o f s o lu tio n » t h r o u ^ th o I n t e e t i n a l t r a i l sh o u ld im lta to th o d l f f u o lo n o f th e
aarao so lu tlc m s th ro u (ÿ a r t i f i c i a l mambrenos. Tho f a c t t h a t a n in a l nerabronea nay v a ry i n t h e i r p o n a o a b ility m a n o t known
a t th e tim e#
Iloppe - SeyXar (1881) was th o f i r s t t o c o s t g rav e doubt» oa th o adequacy o f a m o c h e n ls tlc th o o ry o f o s n o s is and f i l t r a t i o n to e x p la in a l l th o phenomena observed d u rin g i n t e s t i n a l ab so rp » tio n # He s t a t e d d e f i n i t e l y t h a t a b s o rp tio n from th e i n t e s t i n e i s a f u n c tio n o f l i v i n g e p i t h e l i a l o o lla # The ovidonoe was
b asod upon tho a c tio n o f th e g u t i n c h o le ra and when poisoned by c e r t a i n to x ic su b sta n c es# S in o o , i n th e se cases# norm al a b s o rp tio n d id n o t ta k e p la c e Iloppe * ü e y lo r concluded t h a t th e v i t a l a c t i v i t y o f tho o p i t h o l i a l c e l l s had boon d e s tr o y e d . I n
c h o le r a , where th o c p ith o liim o f th e i n t e s t i n e i s l a r g e l y sh e d ,
th o a b s o rp tio n i s a t a s t a n d s t i l l a lth o u f ^ th in n in g o f th e membrane m l ^ t fav o u r osm otic t r a n s f e r o f tlio g u t c o n te n ts #
Waysiouth Hold (1900) p o in te d o u t t h a t th o s e ex p erim en ts d id n o t
n e c e s s a r il y prove t h a t th e e p lth o lix m a c t iv e l y t r a n s f e r r e d th e s o lu tio n s i n to th o blood i n th o norm al s t a t e o f a f f a i r s # He co n sid o ro d t h a t th e e p i t h e l i u a m ight a c t a s ”a b a r r i e r , p h y s ic a lly
ixapermsablo t o c e r t a i n su b s ta n c e s i n s o lu tio n I n th e plasm a and o x e rtin i! oem otlc pro sau ro and t h a t w ith th o rcsnoval o f th e
b a r r i e r such subotancos can d i f f u s e o v e r in to th e g u t so t h a t th e v a lu e o f t h o i r osm otic p re o su ro a s a f a c t o r in a b s o rp tio n o f
-10-ISoidônbain (1894) and h ia p u p ils Leubuschea (1 8 8 5 ), OuBllowekl
(1886) and UOlicuann (1887) oone t o th o am e o o n clu eio n a s t h a t o f Hoppe - ü e y lo r b u t i i l t h one im p o rta n t m o d ific a tio n » H eidenhaln
b e lie v e d t h a t a c o r t a i n p o rtio n o f s o lu o n t and s o lu té nus a b so rb ed by a prooooa o f oanooia « b ile a n o th e r p o r tio n was absorbed by th o
p h y a lo lo g io a l a c t i v i t y o f th e l i v i n g c e l l and d id n o t obey th e known p h y s ic a l laws# By tho " a c t i v i t y o f th e l i v i n g c e l l "
H aidonbain m ain ta in e d t h a t th e c e l l could e x e r t an In flu e n c e upon
i t s p h y s ic a l o r ohom ioal prooosaoc#
Cohnhsim (XB98-1900) made th e d isc o v e ry t h a t th e a b s o r p tiv e
p ro c e ss was a one - way laoohanism from th e g u t lumen# He showed t h a t th e d i f f u s i b l e blood c o n s titu a n ts d id n o t , under norm al con d i t i o n s , p u ss i n t o th e in te s tin e # There wore two m ain f a c to r o i n
Cohnhoim^e th o o ry o f a b so rp tio n
-(1) He p o s tu la te d an im p e m s a b ility t o body f l u i d s duo t o th e a c t i v i t y
o f th e c a p i l l a r y endothelium which b ro u g h t ab o u t th e osm otic
o q u ilib riu m betwoon i n t e s t i n a l s o lu tio n o and th e blood w ith o u t th e
p assag e o f blood c o n s t! tu o n ts i n to th e gut s o lu tio n s #
(2 ) He a ls o p o s tu la te d t h a t tho g u t w a ll was a b le t o ta k e up th e
c o n te n ts o f i t s lu n en through th e in te rm o d ia tio n o f th e v i t a l a c t i v i t y
o f th e e p i t h o l i a l c e l l s and t h a t t h i s p ro c e ss was f r e e o f p h y s ic a l
in flu o n c o a# Cohnheiia %*ojectod th o id e a p u t fo rw ard by H oldenhain t h a t th e o o U u lo r a c t i v i t y o f th e o p ith e lu in m ig ^t be a f f e c t e d by
th o oamotio p r e s s u r e o f tho i n t e s t i n a l c o n te n ts#
b'oymouth R eid (1892-1902) on th o sama g e n o ra l grounds a s H oidonhain
intervontlcM i o f th e e p i t h o l i a l o o llo # lîs s t a t e d , howovor, t h a t th e forriC o f onorgy u t i l i s e d wore n o t o th e r th a n th o so known t o th o
p h y s i c i s t s . Rold a t t r i b u t e d th e power o f a b s o rp tio n s o l e ly t o th e o o t i v i t y o f th e e p i t h o l i a l c o l l s and oan so q u o n tly h i s th e o ry o f I n t o s t i n a l a b s o rp tio n was i n c lo s e r agroeciont w ith Cohnhoim th a n
w ith îîoldoxdialn who p o s tu la te d t h a t osm otic p re s s u ro p a r t i a l l y in flu o n c e d th o p roooas o f a b so rp tio n * Rold based h i s argum ent upon a s é r i a s o f oxporlm ents i n w hich ho showed serum c o u ld be
ab so rb ed from th e i n t e s t i n e under c o n d itio n s in w hich f i l t r a t i o n ,
osm osis and adoori t l o n wero s a id t o bo oxoluded* I n j u r y to o r rem oval o f th o o p l th e l ie d c o l l s o f th o I n t e s t i n e r e s u l t e d in a d o p rs s s io n o f th o e b so rirtlo n nschonlam . Held argued t h a t such
p ro ce d u res sh o u ld a c c o lo ra to tho a b s o r p tiv e p ro c e ss s in c e th e y fav o u red
th e p u r e ly p h y s ic a l f o r c e s o f a d s o r p tio n , osm osis and f i l t r a t i o n # I n f a c t , any c o n d itio n d e p ro s sin g c e l l u l a r a c t i v i t y ten d e d t o red u ce th e
a b s o rp tiv e a c t i o n . By moons o f a sim p le d i f f u s i o n a p p a ra tu s c a l le d
en omroMotor, R e id , u sin g f l u i d s o f th o seme com position on e i t h e r s id e o f th o mombrune showed t h a t th o movement o f su b sto n o o s to o k p la c e a c ro s s an is o la te d s u r v iv in g pioco o f in to s tin o # The movement to o k
p la c e from tho f l u i d in c o n ta c t w ith th e mucosa t o t h a t b a th in g th e
o p p o site a o ro s a l s id e o f th o i n t o s t i n o . By u sin g f l u i d s o f th e samo oocq)08i t i a n on b o th s i d e s o f th e membrane ho excluded th o in f lu e n c e
o f oom otic pi’o su u ro . I n t h i s way, i t was art^ued, th e c c tiv o f o r c e must bo u "vital*» f u n c tio n in h e r e n t i n th o e p i t h e l i a l c o l l s .
Tho work o f th o so th r o e a u th o rs p ro v id ed th e b a s i s f o r th e th e o r y
f o r a b s o rp tio n f rc ri th o in t^ a tin o *
Hembur{50P (1096-1908) d id n o t a c c e p t th e th e o r y t h a t th e p ro c e ss
o f a b s o rp tio n was duo t o " v i t a l " c e l l a c t i v i t y b u t from th o r e s u l t s o f a s e r i e s o f oxporlm onts deslf^ied t o d o to m ln e th e e f f e c t o f I n t r a -
I n t e s t i n a l p re s s u re upon a b s o rp tio n cane t o th e c o n c lu sio n t h a t , althou,*^ p liy s lo lo g lo a l and p a th o lo g ic a l ohanf^s could a f f e c t th e p h y s ic a l fo rc e s In v o lv ed , th e y d id n o t cease to be p u r e ly m echanical*
lie claim ed t o have Im ita te d a l l th e phenomena e x h ib ite d In th e
I n t e s t i n a l a b so rp tio n o f sodium c h lo rid e and serum w ith a r t i f i c i a l l y c o n s tru c te d membranes *
IIR&or (1890-1914), conquering tho r a t e s o f d i f f u s i o n o f v a rio u s s o lu tio n s o f s a l t s w ith t h e i r speed o f a b s o rp tio n I n th e i n t o s t i n o ,
ooncludod t h a t o lth o u ^ ^ p h y s ic a l f o o te r s d id p la y a p a r t In th e
mcchenlam o f a b so rp tio n th e y d id n o t eacplaln th e whole p ro cess* W allace and Cushny (1898-1899) compared th e r a t e s o f a b so rp
t i o n o f a la rg o number o f eq u lm o leo u lar s a l t s o lu tio n s w ith a one p e r c e n t s o lu tio n o f sodium c h lo r id e end found t h a t th o r a t e s o f a b s o rp tio n d id n o t correspond w ith th o d if f u s io n r a t e s * S a l t s
which woro e a s i l y d is s o c ia te d I n to io n s o f h i ^ speed wore n o t
alw aj's aboorbod a t a f a s t e r r a t e th en s a l t s l e s s e a s i l y d is s o c ia te d and Tdios© Iona p o ssessed a low er spoed*
I t wan th e c a r o f u l stu d y o f tho a b s o rp tio n o f th e m anosaochorides
which lod. e v e n tu a l ly to th e s o lu tio n o f th e problem which h as d iv id e d th e m ech an ists end v i t a l i s t s * Corl (1925) f i n a l l y e a ta b - 11 shod th e f a c t t h a t , a l t h o u ^ th e knovm p h y s ic a l law s a re f a c t o r s
•13*»
e x p la in a l l th e phanornona concerned w ith a b so rp tio n * C ori used u n a n a e s th e tis e d r a t a a s l iis e x p e r in e n ta l e n icm la. He detortnined
th o r a t e s o f a b s o rp tio n o f o o n o sao o h arldes from th e sm a ll i n t e s t i n e
by fe o d in e a known «mount o f a c i von su c a r in s o l u t io n t h r o u ^ a stomach tu b e , k i l l i n ç th e anim al and e s t i n a t i n g th e amount o f su g a r r o n a in in c i n th e i n t e s t i n e * Ho was a b le to d eterm in e w ith (gpeat a c c u ra c y th e amount o f eu g ar absorbed i n n given tim e by a r a t o f
known w e if^ t* W ithin f a i r l y wide l i m i t s , tho amount o f g lu co se ab so rb ed d id n o t v a ry w ith th o c o n c e n tra tio n o f th e s o lu te * I n o th e r w ords, th o p ro c e s s o f a b s o rp tio n d id n o t conform to th e law s
o f d i f f u s i o n and ofssosls* I f a b s o rp tio n was m ere ly a m a tte r o f d i f f u s i o n th e number o f io n s bombarding tho a b so rb in g s u rfa c e in u n i t tim e would o b v io u sly be a f a c t o r o f g ro a t im portanoo*
I n 1930, A u ch in ach io , McLeod and tiagee s tu d ie d th e d i f f u s i o n o f s o l u t e s t h r o u ^ th e s u r v iv in g i s o l a t e d i n t e s t i n e o f r a b b its *
Theso w orkers fo m d t h a t 0*2 p e r c e n t i>d£asslum io d id e s o lu tio n p a sse d more r a p i d l y th ro u g h dead g u t th a n liv in g * B lo o d -is o to n ic
g lu co se (5 .4 p e r c e n t) a ls o d if f u s e d more r a p id ly th r o u i^ dead gut*
I n b o th th o se c a se s th o g u t was k i l l e d w ith h o t i s o t o n ic s a l i n e a t
65% f o r f o u r m inutes* A ll methods o f k i l l i n g in c r e a s e d th e
p e rm e a b ility o f th o g u t t o g lu c o se and dihydronyacetone* ^ x y lo se
U
s o l u t io n d if f u s e d more r a p i d l y th a n % gluooso s o l u t io n t h r o u ^ dead r a b b i t g u t b u t som etim es i n " liv in g " g u t, glucose p a sse d o u t more r a p i d l y th a n xylose* L ^ / e r i n g o f th e tem p era tu re allow ed g lu co se and xj^loeo t o d i f f u s e o u t a t th e sorrie r a t e from th o i n t e s t i n e o f
-14—
a t t h i s work w i l l bo diaowssoci l a t o r .
C o r i*8 nothod o f d o to n a ln in r th e r a t e o f a b s o r p tio n o f m onosaecharides
s u ffe ro d f r o a cno d e fo c t: neraoly th o er.iptyin(> tim e o f th o stom ach was v a r i a b l e . To ovorcomo t h i s , VorjoAr in jo o to d th o eu^.w s o lu tio n s
d i r e c t l y i n to lo o p s o f o tm ll i n t e s t i n e o f e n a o s th e tls o d r a t ^ e . The amount o f su g a r rem ain in g i n th a lo o p s , a f t e r a g iv en p e rio d o f tim e had e la p s e d was e s tim a te d . There i s a rcanorkable afcraemont bo tween
Voi%&r*s end C ori*a r e s u l t s • Both woilccrs found t h a t h ex o ses such a s g lu co se and g a la c to s e wore absorood a t a much f a s t e r r a t e from th e sm a ll i n t e s t i n e o f th o r a t suoli aa x y lo se and a ra b in o s e .
I n 1030, Luundsgaard d e s c rib e d an e3q)erim ent i n w hich i t was shown t h a t f r o g* 8 n u sc lo p oisoned w ith m onoiodoaootic a c id i n h i b i t s th e
fo rm atio n o f l a c t i c a c id i n s t r i p e d m u sc le . He a l s o found t h a t y e a s t
f o m e n ta tio n wliioh s t a r t s w ith a c a rb o h y d ra te - p h o sp h ate com bination i s i n h ib i t e d by m onoiddoucetlo a c i d . Yamasaki (1930) found t h a t t h i s
f o m e n ta tio n w i l l c o n tin u e i f haxosephosphatc i s ta k e n in s te a d o f
s u g a r . I t was concludod, t h e r e f o r e , t h a t m ono!odoacetic a c id sto p p ed
th e p h o sp h o ry la tio n o f s u g a r. L a te r work showod t h a t m onoiodoecetie
a c id in f lu e n c e s p h o sp h o ry la tio n p ro cesco a i n d i r e c t l y . M oniodoacotic a c id i s b o lie v o d t o i n l i i b i t th e o x y d o red u ctio n s lo a d in g from
hexosophoophorio a c id v ia trio e o p h o a p h o rio a c id t o p h o sp h o g ly cerio a c id
and (^yoorophoaphorio a c i d . Since th o so a re p a r t o f th e p ro c e s s e s connected w ith hexosophosphoric a c id p ro d u c tio n t h i s w i l l a ls o be
i n h i b i t e d .
V erzèr and liio co -w o rk ers p o s tu la te d s i m il a r p h o s p h o ry la tio n system s
1 5
-s e l e c t i v e a b o o rp tio n o f gluGOoe# The f i r s t ojgporinonts were c a r r i e d o u t by W ilbrandt end L a s z t (1933) • Luunds^^ard (1930-31) had found
t h a t */î5000 n o n o io d o ec o tic a c id i n h i b i t s y e a s t f e m is n ta tio n and i n th o f i r s t e o rio o o f o x p o riiaen ts th o i n t e s t i n e was poisonod l o c a l l y by
a d d in g th e re q u ire d dose o f io d o a c o tic a c id to th e b lo o d - is o t o n ic g lu co se o r x y lo se i n je c t e d i n to l i g a t e d lo o p s o f i n t e s t i n e i n th e r a t# I n normal an im als 7 2 .8 i>or oont glucose was a b so rb ed ; i n th e
p o iso n ed Einlmels o n ly 5 4 .8 p e r c o n t glucose was absorbed# Tho amount o f x y lo se absorbed i n norm al anim als was 2 1 .4 p o r c o n t and i n poisoned a n im als t h i s v a lu e was 2 5 .4 p e r oont - on in c re a s e o f 20 p o r c e n t o f
p e rc en ta g e g lu co se ab so rb ed th o amount a b so rb e d . The r a t i o p e rc e n ta g e x y lo se a b so rb ed i n
one h o u r was 3 .4 s 1 i n th o norm al r a t and 2 .8 : 1 i n th e p o isoned r a t #
I n l a t e r ex p erim en ts th e p o iso n was i n je c te d su b c u ta n e o u sly " th u s a v o id in g any d i r e c t damage t o tho e p ith e liu m o f th e mucosa#" Tho dose g iv e n was 0#12 - 0#16 m^yis p e r {^n# body w e i^ ^ t g iv in g a
o o n o o n tra tlo n i n th e body o f 1/6000 t o 1/8,000# T h is cau sed a
d o creo se o f gluooso a b s o r p tio n from 73#3 p e r co n t t o 24#3 p o r cont# 'flu) r o l a t io n s h i p between absorbed gluooso and abeorbod x y lo se was
a g a in 3 .4 : 1 i n norm al r a t s b u t 1 .1 : 1 i n poisoned an im als# The
a c t io n o f m onoiodoaodtio a c id on th o a b so rp tio n o f g a la c t o s e , fru c to s e # a ra b in o se and rhomnoso vms a ls o s tu d io d . r a t e o f a b s o r p tio n o f
g a la c to s o and f r u c to s e was lo t/o r i n io d o a c o te te -p o i coned r a t e th a n i n norm al r a t s . The r a t e o f a b s o rp tio n o f g a la c to s e i n th e poisoned r a t s woo reduced to o n ly h a l f th e r a t e o f a b s o rp tio n i n norm al r a t s #
r^ en ao ea 2 1 *1 p o r o ont wus nbnopbod by a norm al r a t i n ono hour^ 28*5 p o r c o n t wao aboorbod by lodon.oetr.ta « p o iso n ed r a t*
F ran th eao ©xporim ento, wtior© io d o n o o tic was i n j e c t e d s u b c u t-
QDOoualy# Verzftr and h i s oo-w orkora concludod t h a t m o n o io d o acstlc a c id i n h i b i t s th e tre n o fo rm a tio n o f gluooso in s id e th o rm oosa and th e r o f o r e i n h i b i t s t h a t p a r t o f i t s a b s o rp tio n w hich i s duo t o a s p o c io l s y n th e tic proooas* narioly phoephonylation* P e n to se s wore
s a id n o t t o be p h o sp h o ry la te d durine: a b s o rp tio n s in c e m onoiodoaootic a c id d id n o t deoreaao t h e i r r a t e o f a b so rp tio n i n r a t s * Vorzftr claim ed t h a t p h o sp h o ry la tio n o f g lu co se and g a la c to s e d u rin g
a b s o r p tio n oauood a sto o p o r d i f f u s i o n g ra d ie n t f o r th o s e su g a rs th a n f o r su g a rs which a r e n o t p h o o p h o ty lated e.g * p en to ses*
M onoiodoaoetio a d d i n h i b i t e d tho s y n th e tic p ro c e ss conoom ed w ith th o s e l e c t i v e a b s o r p tio n o f gluooso and g a la c to s e and so a b o lis h e d
th o h i f ^ s r d i f f u s i o n 0?ad ien t w ith th e r e s u l t t h a t g lu c o se and g a la c to s e ought to have boon absorbed a t th e same r a t e a s x y lo se
end end rhannose* T h is h o U s f o r glucoso but g a la c to s e i s
absorbed a t h i ^ e r r a t e th a n x y lo se i n io d o a c e ta to p o iso n ed r a t s *
Vonyâr and h i s co-w orkoro su p p o rte d t h e i r ovidonco f o r a
phoB phonylation laechenian i n th e acjoll i n t e s t i n e by th e fo llo w in g
work*
(1) U sing ph o sp h ate b u f f e r s o lu tio n s * LasjEt (1935) to o te d th e in f lu e n c e o f pH upon th o a b o o rp tio n r a t e s o f gluooso and xylose* H© found t h a t th e a b s o r p tio n r a t e o f glucoso was g r e a t e s t a t JJR 7*0*
Tho a b o o rp tio n r a t e o f x y lo se was u n a ffe c te d by pH* S im ila r r e s u l t s
1 7
-t h a -t -th o e o lo o -tlrre a b so rp -tio n o f gluooso was b ^ u ^ ^ -t a b o u -t by a
p ro c e s s In v o lv in g c h o n io o l ro a o tio n s tjhioh had an o p tin u im pH o f ? •
Tho a b s o rp tio n o f x y lo n o , b ein g u n in flu e n c e d by changes i n $K* was s a id t o bo a phyaioo • rw o h en lco l p ro c e ss in v o lv in g sim p le d i f f u s i o n
; a c r o s s a mcmbrano#
(2 ) U sing m ucosal e x t r a c t s i n v i t r o U iM brjm dt and LaafCt shewed t h a t
♦-th e m ucosal e x tr a c t phosphomylated b lo o i- lB o to iile ^ s o lu tio n s o f glu co se# The evldonoe f o r t h i s was tho f e c i t h a t th e r e was th o f a c t t h a t th o ro was a r e d u c tio n i n th e amount o f in o rg a n ic phosphate A d d itio n o f l/SOOO iodOGCctatic a c id p rev en ted th o d isa p p e a ra n c e o f
in o rg a n ic phosphates# The m ucosal o x tr a c t was s a id n o t t o
SL ^
p hoophoryloto ncnnoso o r xylose# 100 Soduiri FluoA lde was r e p o r te d
t o have no i n h i b i t i n g in flu e n c e on th e e x tra c t#
(3 ) The ort^anic phosphate c o n te n t o f th e i n t e s t i n a l mucosa In c ro c se d d u rin g th e a b s o rp tio n o f g lu co se b u t rem ained u n a lte r e d d u rin g th e
a b s o rp tio n o f xylose# R ats woro fe d w ith d i f f e r e n t s u g a r s , th e raucosa sc ra p e d o f f and e x tr a c te d w ith t r i c h l o r a c e t i c a c id # T h is
f in d in g was oonfirraod by LujKasgoard (1939) in r a t s b u t was n o t
found t o o c cu r i n o a t s .
(4) Vonyftr t r i e d th e e f f e c t o f o th e r p o iso n s on th e s e l e c t i v e
a b s o rp tio n o f glucose# Sodi«n cyonido In jo c to d su b c u ta n e o u sly i n
d o ses o f 0#8 rn^Tns p o r 100 ^ns body w eight r a t# Tho an im als
Burvivod ono day# Ilifdior d o ses were n o t given b e ca u se th e I n t e s t i n a l
A ltlia u sa a , Anderson and S to o k h o lc, 1939; C l e ^ and Maokay» 1 9 4 2 ).
(1940) h as ro p o rto d t h a t t e s t e d nonsol r a t a , sham o p e ra te d and u n i l a t o r a l l y a d re n a l 3C tomi ood r a t e sho¥.'od a do crooned r a t a o f
a b s o rp tio n o f th o oeno o rd e r a s t h a t found in a d re n n la c to a is e d r a t e ,
■4
-C r j.tlc ia n o f Vobqi^’ s p h o sp h o ty ln tlo a th o o ry cone n a in l y from W eatonbrlnk and from X lin c Jw ffe r. iVostoabriiik (1956) I n j e c te d 0*12
mcj'tB m onoiodoaootic a d d subcut ono ouoly in to r a ts * U sing C o r l 'a method o f d o to m ln in g tho r a t a o f ab eo ri)tio n o f c c rb o h y d ra to s , ha
found t h a t th o r a t e f o r itLucoao was lavorod* when e b c o riJtlo n
a to r to d h a l f an hour a f t e r th e i n j e c t i o n o f n o n o lo d o ac etato th e x y lo se ab so in itlo n r a t e n o t a f f e c t e d b u t i t was loworod whon an h o u rs
I n t e r v a l vma a llo w e d . By V eicjfr’s m ethod, u sin g u ro th an o and
io d o a c o ta te t o o t h e r , x y lo se a b s o rp tio n was ( ? e a t l y slo w ed , W estonbrink concludod t h a t tho a c tio n o f m onoiodoccotio a cid was i n p o r t a t l e a s t duo t o i t s a c tio n upon th o c i r c u l a t i o n , h o s tc n b ria k a lo o ohowod t h a t
th e pit-eon was more a o n o itiv e t o io d o a c o tic a cid th a n th o r a t . Doses which d id n o t k i l l th e p ig eo n i n two houpo d id n o t a f f e c t g lu c o se
a b s o r p tio n ,
K lin ^ iio ffo r (1938) a ls o found t h a t th e r a t e s o f a b s o r p tio n o f
x y lo se and o f aoduim c h lo r i d e , oo w e ll a s t h a t o f g lu c o s o , wore
lot?orod when m onoiodoaootic a c id was in je c te d su b c u ta n e o u sly . The m t e o f g lu c o s e a b s o rp tio n d id n o t f a l l to qui to th e norm al x y lo se
l a v o l , Thn doeo o f m onoiodoaootic a c id in jo c to d su b c u ta n e o u sly
v a rie d from 0*6 - 0 ,2 p e r r a t . Tho p a th o lè g ic a l f in d in g s wore n o t c o n s i s t e n t , gax5ti*o»int83tinel le s io n s b e in g th o m ost co n -
-ecK
th e a b s o rp tio n o f xylooo and sodium e h lo rid e vma in any way connooted
w ith p h o sp h o ry la tio n p ro c o sse o , and as tho i n t o s t i n a l p a th o lo g ic a l
ch an ces wore so ao v o ro , i n h i b i t i o n o f glucooo a b s o rp tio n by io d o a c o to te oould n o t bo a t t r i b u t e d t o a s p o c if io o ffo o t on p h o sp h o ry la tio n
prooooQOSf K l l n ^ o f f o r a ls o s t a t e d t h a t th e d e fe c t i n g lu co se a b s o rp tio n i n r a t s fo llo w in g a d m in is tra tio n o f so d iu n io d o a o o ta te
oould n o t be a t t r i b u t e d t o a d re n a l damage a s le s io n s o f th e a d re n a l
g la n d s could n o t alw ays be found i n io d o ao o tate p o iso n ed anim als# Hero r o o o n tly D e n ie lli (1943) o u g t^sted t h a t p o iso n s i n h l l n t i n g pliospho4tylation may p re v e n t a b so rp tio n not because th e su b sta n c e to
be ab so rb ed i s phosphoA ylatsd b u t due t o th e d e p r iv a tio n o f en erg y d e riv e d frcsa tho m etabolism o f oorbohydrfito f o r same o th e r p ro c e s s
a c t u a l l y concerned i n th o a b so rp tio n # He f i n a l l y co n clu d es t h a t " th e i n t e s t i n e i s such a conplex t i s s u e and so co m p licated by a c t iv e
p ro c e ss e s t h a t i t do es n o t seam p r o f i ta b le to make f u r t h e r ccement upon i t a t th e p r e s e n t tim e " .
Tho whole problem o f a b so rp tio n from th o i n t e s t i n e i s o b v io u sly v e ry complex# Thoro i s o b v io u sly no a p r i o r i re a s o n s why th e
moehanism o f a b s o rp tio n should bo tho some f o r d i f f e r e n t su b sta n c o s o r even th e sane i n d i f f e r e n t spooios# I t i s c l e a r t h a t o u r
knowledge i s s t i l l v e ry d e fe c tiv e # work f o r many y o a rs by many
i n v e s t i (sators w i l l c e r t a i n l y be re q u ire d b e fo re wo can hope t o bo p in
t o so lv e th e problem s o f ab so rp tio n # In t h i s th o s is # an atterript i s mode t o do no more th a n in v e s ti g a t e as c r i t i c a l l y a s p o s s ib le c e r t a i n
i ' - . '
b a 0 y J 0 M A.
Lei
m
Ir'' "' I ,' " ^
S 'p '.'& V - ': ,^1
. . . . . -f.
,:'r ':
i . , , i
W P j M r '
: m
■ / ' U ■t-:‘y'?. '■aA
w
,:■ I' ' '. - ■ I m ■'
•■ ' ' ■ ■ '• '■' 4 ' '. .
üurfgioe Aroa o f tho a a a ll In te stin e in the Rat and 0#t#
Introduotlon*
Method# H o su lts#
a) IEatoXo{^oaI Appoaranoos#
b) Area of the Muooua f)@mbran@.
D io cw alo n #
a) AbeoXuto Valuoa#
b) RoXatlvo Vnluoa#
i^urfaeo Aroa o f tho In te stin a l Muoosa in the Rat and in tho Cat.
I* I n tr o d u c tio n .
W ithin r e c e n t t lr w s th e r e h a s boon a ren ew al o f I n t e r e s t i n th e
problem s o f a b s o r p tio n from th e I n t e s t i n a l t r a c t # I t i s %nore th a n p ro b a b le t h a t odo f a c t o r o f primo im portance i s th o a r e a o f th e
miooua laKibrano a c ro s s w hich a b s o rp tio n ta k e s p lac e# U n fo rtu n a te ly
t h i s fundam ental a s p e c t sooma t o havo ro c e iv o d b u t s c a n t a tte n tio n # A dm ittedly# a tt o n p t s have been xnedo t o e s tim a te - m easure im p lie s p ro b a b ly to o g r o a t a degroo o f a cc u ra c y - th o i n t e s t i n a l m ucosal
a re a i n v a rio u s anim als# b u t th e o ld e r d a ta and m ethods o f p r e s e n t a t i o n lo av e much t o bo d o siro d #
I t seemed w orth w hile# th o ro fo ro t o t r y t o o b ta in f i g u r e s f o r
tho i n t e s t i n a l a b so rb in g s u r f a c e s b o th i n th e r a t and i n th e c a t# th e a n im als m ost f r e q u e n tly u sed i n a b s o rp tio n s tu d io s # & o re over# s in c e i n ro c o n t tim o s work h a s been done on th e r e l a t i v e r a t e s o f
a b s o rp tio n i n th e cronif:JL and c a u d a l r e g io n s o f th e sm a ll gut# on a tte m p t was mode t o compare th e a ro a o f th e mucous membrano i n th e
c r a n i a l re g io n o f th e jejunum w ith t h a t i n th e c a u d a l r e g io n o f th e
iloum#
Warren (1939)# w ith iij^rovod tech n iq u e# made a d e t a i l e d s tu d y o f
th o muooBal a re a a t d i f f e r e n t l e v e l s i n th e i n t e s t i n e o f one dog and h i s s u m a r y o f th e in fo n ?iatio n a v a ila b lo a t th o p r e s e n t tim e i s
g iv en bolow# Thoro seoci t o b e , however# no d a ta f o r th e r a t o r f o r th o c at# two anim als# a s r.ontionod above# m ost f r e q u e n tly used f o r
A u th o r.
Ëteidouhaln (1088) froRi Spoe (1085)
K a il (1887)
Krauao (1879)
fie ld , K*W. (1900)
Krosh (1922) ( f r o c t i a l K i æ ? )
Ylmtnanp (q u o ted by Kgog^ , 1922) Vè*at r (1956)
S a rro n (1039)
A n ln a l
Dog
Dog
Man
Dog
Dog
R ab b it PlGOOB
Dog
TABLK I.
C cm dition o f T is s u e F lzo d spoclnunc
(oam le a o id )
F ix e d a p o e ir^ n a
F ix ed speeliaena
G e la tin e c a s t
F ix ed apoelmons and c a l c u l a t i o n s froci !Aall*B J a t a
F ix ed specim ens D iro e t neesurecTonts
i n th e l i v i n g . F ix e d Spocimens
I n t o s t l c n l
L evel K cacurem ents.
;%amll S u rfa c e a r e a o f s i n g l e v i l l u s m* I n t e s t i n e th ic o sa l sui*faco a ro a • 23 eir^/ocf^
s e r o s a l s u r f a c e a r e a .
â o B ll T o ta l m ucosal s u rfa c e a r e a e x c lu d in g I n t e s t i n o th e v i l l i and c r y p t s # 667 c n f
Sfcsall S u rfa c e a re a o f s i n g l e v i l l u s « 0 .3 -I n t e S ti n e K noosal a r e a o f whole sm a ll 0»7ob^
I n t o s t ln o # 1 .6 s q . m e tr e s . R a tio m ucosal a r e a ^ ^
s e r o s a l a r e a 1
Ileun Mucosal s u r f a c e a r e a o f th e ileum
and Colon m 6 s q . cm /u n it s e r o s a l Im ag th . ^ Colcai; m ucosal s u r f a c e a r e a • Scm^/cm*^ s e r o s a l s u r f a c e a r e a .
t o t 7 mcf f o r each a e r o s o l s u r f a c e S p o o lfio d a r o a .
Duodenv® 1 7 .6 %zr^ f o r oach X mm^ o o ro o a l s u r f a c e am nil hlAicoael s u r f a c e a ro a a 4 .5 s q . m e tr e s . I n t e s t i n e
2 5
-I -I METHODS,
I t io v o ry p ro b ab le t h n t th e p o e t-m o rte o le n g th o f th e sm a ll i n t e s t i n e d i f f e r s f r c n th o le n g th d u rin g l i f e (Espd and Cannon, 1932: 1 9 4 0 ).
r'io reo ro r, i t i s n o to r io u s t h a t t i s s u e s f ix e d f o r h i s t o l o g i c a l woric
undergo d i s t o r t i o n * l ^ v i o u s w o rk e rs, to o , seam t o have made l i t t l e
Qttcnpt t o onoure t h a t th e g u t was f ix e d u n d er s ta n d a rd c o n d itio n s o f d lo to n o io n . Warren (1939) was p ro b a b ly more aware o f th o s e v a rio u s
d i f f i c u l t i e s th a n h ie p ro d eeo o so rs i n t h i s f i e l d * I lis m ethod, t h e r e f o r e ,
h as beon used w ith s o v o m l m o d ific a tio n s i n t h i s p r e s e n t work*
Tho a rra n g em e n t, shewn i n Fig* I , was employed* Tho a n im a l, r a t o r o a t , h a v in g boon s ta r v e d f o r th o p re v io u s 24 h o u r s , was a n a e s th e tis e d
w ith o th o r and th o abdomen w id e ly opened* A c a n n u la , d ir o o te d oattdad, was t i o d i n t o th e proxim al jejuniva and on OT>ening made i n th e iloum
j u s t C raniad to th o la r g e in to s tln o * The whole s m a ll i n t e s t i n e was
th o n washed f r e e o f f a e c a l m a tte r by moans o f a stre a m o f R inger s o lu tio n a t 38<%* T h e r e a f te r , a second c a n n u la , d i r e c te d e ra n in d , was t i o d i n t o th o i n t e s t i n e th ro u g h th o opening i n th e ileum * Midway
between th o se two oannulao a p ie c e o f i n t e s t i n e was c u t c o m p lete ly o u t
and th e rem aining: p o r tio n s o f th o iloum and jejunum connooted by t y in g
i n a T - p ie c e o f g la s s tu b in g * A ttach ed t o th e u p r lf A t lim b o f th e T - p io eo was a le n g th o f ru b b e r tu b in g . The le n g th o f t h i s tu b in g
d e te m ln e d th o head o f p ro ss u ro t o which a l l p o r tio n s o f th e g u t wore m if o im ly exposed* Tho g u t v m th o n fre e d from th e m esen tery and a l l p o r tio n s o f th e g u t a tta c h e d to th e c an n u las tr a n s f o r r o d t o a la r g e
W fisJL.
F lR # l. shows d la^ p ro n n atico lly th o arrangem ent onployed t o f i x th e g u t u n â o r u n if o m p r e s s u r e so t h a t measurcxaont o f s u rfa c e a re a may bo cornpurablo*
%
f t .
*
by b o th caim ulûo and lo a v in c by th o v o r t i c a l liüâ» o f th e T -p ia o e .
F l : » t i v » i n ipraûnally In c ro a a in g mtrenjTbh was th o n p o rfu o ed t h r o n g tlia * ^ t «Bd a le o pourod o v e r th e so ro o o l au rfa ee * The was th u s
r a p i d l y fix e d i n a û ieto n d ed s t a t e imdor a knoian head o f p r o s a u r e ,
7 cns« I n th e case o f th e r a t and 15 c i ^ . i n th o o at#
khon f i x a t i o n was o o rip letc s t r a i ^ ^ t p o r tio n s o f jejunum end llo im rou^^ily C a is # in le n g th wore o u t o ff# i^eoh o f th e s e p ie o e s
was f u r t h e r d iv id e d in to th r o e etiuiUor p o r t i o n s , a c e n tr e p ie c e àp v ro x liâo tu ly 4 em # lo n g and two and piooos#
Tho la r g o i n t e s t i n e woe t r e a t e d i n a somewhat s i n i l n r f a s h io n , th e o n ly r e a l d if f e r e n c e b ein g t h a t th e T-»piece f o r r e g u l a ti n g th e houd o f jKr^.:aisuro was unnecessary# P o r tio n s o f I n t e m e d l a te co lo n wore chosen f o r study#
I n s p i t e o f a l l c o re and o f ro p id f i x a t i o n , th o e p ith e liu m o f th e (SoaXl i n t e s t i n e was v e ry a p t to desquam ate u n d er th e hoad o f p rceo u re# S e v e ra l f i x â t iv o s wero t r i e d w ith v a ry in g d e ^ ^ e s o f
auoQoae# F o r th e sm all i n t o s t l n o a s o l u t io n c f p i c r i c a c id i n
dioxan (C a rlo to n , 1 9 3 0 ), vms th e most s a t i s f a c t o r y } w ith th e l a r g e I n t o s t l n o , Susa*8 f i x a t i v e th e b e a t r e s u l t s #
A f t e r ombodding i n p a r a f f i n , tr a n s v e r s e s o o tlo n s were o u t from
th u end p ie c e s and lon^^itiiciinal s o o tlo n s wore c u t from th e c e n t r a l
p o r tio n a t i t s g r o a te o t cHemetor ( F l g # l l ) . ’Iho s e c t lo n e were s ta in e d w ith K rlio h * s a c id liao ratq x ^ /lln and Orange G# T y p ic a l
so o tlo n a from j e ju n a and iloum o f tho r a t a r e shown i n Figs# 3 , 4
, 6
,Af,
? lK . 2 shoTB dl&{^*caxaatioeLLXy how oaoh p o r tio n o f I n t o a t ln e was rou^^ily d iv id e d I n to 3 a eg a en te a f t o r f i x a t i o n I n p lo ro -d io x a n * From th o c e n t r a l p o r tio n lo n ^ iltu d ln a l c e c tlo n s were o u t , w h ile
from th o o th o r two p o r t i o n s , tro n a v e ra e s e c t Iona wero c u t . I n
-C7-To fiïicl th o a ro a o f th o inucouB raombrano th e fo T O ila reo o i^o n d ed
by Warren (1939) waa uaod#
-•>A s f ^ ^ ^
3K SC SL
SA l a th e unknown, th o o a t i m t e d lauooaal area#
&A i s th e s e r o s a l a rea#
lie l.a th o m ucosal olrcuznferonoo#
SO i s th e s e r o s a l olroum foronoa# Ml io th o m ucosal lengrkh*
SL i s th e a e ro s o l len^rth#
To f a c i l i t a t e Bioaaurcnnent, th e s e c tio n s vmro p r o je c te d on t o la r g e sh o o ts o f w h ite p a p e r a t known m a ^ iif lo a t! o n v ary in g ' betw een 70 and 90 d io m e tre s a c c o rd in g t o th e s iz o o f th e s e c tio n # The m ic o sa l and
s o r o s a l o u t li n e s wore drown i n p o n o ll and th e n zoeosured by a ro ta m e te r c a l ib r a t e d in o e n tim a tr o s . The r o lu o s th u s o b ta in e d , a f t e r due
allow ance f o r l a a ^ i i f i c a t i o n , wore th e n i n s e r t e d i n th e form ula end th e
unknown, KA, c a lc u la te d # About 800 s e c tio n s o f g u t i n a l l were o u t
and o taln ed #
I I I . RiSgULTS#
a) H ia to lo fd c o l A m ^aran o ea#
I n th e seeso a n im a l, th o f i n a l m icro aco p io p r e p a r a tio n s showed no s i ^ f i o a n t d if f e r e n c e between th e d ic n o te r o f th e je ju n im and o f th e
lluum# I n th e r a t , th o a v erag e d ia m e te r was 0#5 cm#, i n th e c a t 1#1 cm.
by a iq p lo I n s p e c tio n o f F if^ # 3 , 4 , 5 , 6 , i t i s o bvious t h a t i n th e r a t th e v i l l i aro more nuc*)rous i n th e jejunum th a n i n th e ileum # T h is i s
FlR g, 3 ond 4»
3 shows th o appooraneo o f a tr a n s v o r s e s e o tio n o f a
t y p io a l r e g io n o f th o jojunum o f th e r a t * S in ce th o v llX l o f th e r a t a ro l e a f «shaped « i n tr a n s v o r s e s o o tlo n s th o v l l U
a re r a t h e r l i k e mounds th a n lo n g p ro c e ss e s* jéjunum h a s o b v io u sly moro v l l l l th e n th e Ileum#
ITW îRTW " . '
B' \
P if* # g and 6 .
P l g . 5 shc^îB th e Qpi^oarance o f a l o n g itu d in a l s e c t i o n o f a t y p ic a l r e g io n I n th e jo ju n u n o f th o r a t . Cut l o n g it u d i n a l l y $ th e l e a f -
shaped v l l l l found I n r a t g u t appoor t o be g ln g o r - llk e p ro c e s s d s . SixDple In a p o o tio n shoim t h a t th e v l l l l I n th e Jejunun a re more
nuaoroua th a n In th e lle u n *
P i g . 6 aboivs th o appearance o f a t y p ic a l re g io n I n th e Ileum o f
l a th o r a t th o v l l l l oro lo o f-sh a p o d l y in g p a r a l l e l t o one
a n o th e r , th o lo n g luma o f th o v i l l o u s laa v o a ru n n in g a t r l f ^ t a n g le s
to th e le n g th o f tho riut* I n th o e a t th o v l l l l a re lo n g and f in g e r *
lik e »
b) The o f th e Mueono £ioobrapg»
F.feoaupQPïonta were e e r r i e d o u t on o ifÿ it r a t a and f o u r o a ts # I n
•Sable I I flf'tx re s a re givon f o r th o a c t u a l n u o o eal a r e a p e r
c e n tls io tre eorooed len^ith o f th o fpit i n th e fix e d s t a te # Both i n th o r a t ond i n th o o a t th o rmioosal a ro a p o r u n i t le n g th o f g u t i s
ro u g h ly tim oa g r e a t e r i n th o jejunum th an i n th e llo u n # T h is d iffo re n o o oould o b v io u sly be due t o i ^ a t o r <Tut u im a e to r in jejunum th a n i n iloum# B l s t o l o f ^ o a ll y , th e r e was no ev id en o e o f th is #
Bo tween r a t and o a t tlie ro i s a m ost s t r i k i n g d iffo re n o o i n rsuoosal a r e a p e r u n i t len^^th o f t ^ t (T able I I ) . i a r t o f t h i s
d iffo ro n e o i s im doubtedly due t o th o fjro a te r d l w i e t e r o f th e e&t*s
i n te s t i n e # T h is f a c t o r o f g u t d io n o te r can be e lim in a te d by f in d in g th e nuooool a r e a p e r u n i t o o ro s a l a r e a o f th e gut# I h i a h a s been
done i n •fablo I I I by r e c o rd in g th o r a t i o muoooal area# T h is r a t i o
' o m a 1
in d ic a t e s th o S o y isal a ro a dof^roo o f v i l l o u s developm ent b e in g
T
i n th e absoneo o f v i l l i # a s i t I s In th o co lo n end i n o r e e s i w i nm agnitude w ith in c re a s in g ' v lllo u o development#
T able I I I shorn; c l e a r l y t h a t th o d iffo i-eu o e betw een j e j u n a l
end i l e a l m ucosal a re a .b e tw e e n r a t and r a t and o a t and c a t i s a ln o o t w h o lly dependent on th o nu'.bor ond p o s s ib ly le n g th o f th e
[image:39.595.26.573.75.732.2]TABUi I I .
Gocqxirlson b o tv œ n Mweoool Aroa I n J e j u n w and Iloum o f th o R at end Cat* Muoooal Atqb i n S q . Qa p o r 1 csn. S o ro o a l L en g th .
A n l m l .
Jejunum I le tm .
R at
1 7 .7 aq* o^m, 2 .9 s q . c c s .
2 8 .0 s q . o n s . 6 .2 s q . c n s .
3 7 .0 s q . o n s . 5 .7 s q . c n s . ^
4 9 .2 s q . c n s . 4 .9 s q . c n s .
10 1 0 .4 s q . erjs. 6 .0 s q . c n s .
lioan 8 .5 i t 1 .9 0 ) > 5 .1 ( ± 1 .9 6 )
C at
1 5 2 .7 s q . c n s . 4 2 .0 s q . c n s .
2 4 8 .6 s q . c n s . 9 0 .2 s q . c n s .
3 4 7 .2 s q . o n s . 3 4 .4 s q . cms.
A n lm l
fia t
C at
J e ju n u a
6
T
4
TAHLK I I I .
R a tio
T ^ o a a l Area S e ro s a l Aroa
I l e m 4
T
12“T
Colon
1
T
1
TAÜW IV.
lüueosal Area i n s q . o n . p e r 1 cm. S e r o s a l L en g th .
A n lm l Rot C at
Ileupi 5 .1 s o . cm.* 3 5 .5 a q . o n .
Colon
2mZ s q . o n s . 5 .6 s q . o n s .
-32*
th e in to rcio d lQ te co lo n h a s a isuoh a m a lle r m uoosal a ro a p e r u n i t le n g th
th a n th o a rm ll i n t o s t l n o . "Diis c o n t r a s t i s v e ry s t r i k i n g i n th e e a t (T able IV ). W ithout v i l l i th e r a t i o l u o o aal a r e a sh o u ld be 1
oeroaal area
T
a s was a c t u a l l y found i n th o c o lo n .(Thble I I I )
The n ark ed d iffo re n o o b o teo en m ucosal a r e a i n jejunum and i n iloum mokoa i t e x tre m e ly d l f f i o u l t t o givo a f ig u r e f o r th e t o t a l a b so rb in g su rfo o o o f tho sm all i n t e s t i n e oven u n d er s ta n d a rd c o n d it io n s* lo s t- tio r te m , th e average le n g th o f th e sm a ll i n t e s t i n e o f an
a d u lt r a t i s 100 cm* % o le n g th o f th e s m a ll i n t e s t i n o o f an a d u lt
o a t i s n o t d is s im ila r *
A oeopting th e s e longtlia# and assum ing u n if o m d e c re a s e i n m ucosal
a r e a from je ju m ia t o d i s t a l ilo u m , th o f i g u r e s f o r m udosal a re a p e r cm* le n g t h , Tablo X I, in d ic a te t h a t th e t o t a l m ucosal a r e a o f th o sm e ll
i n t e s t i n e i n th e a d u lt c a t i s i n th o n o lr^b o u rh o o d o f 4 ,3 0 0 sq* cm* The d if f e r e n c e i s m ost s t r i k i n g tilien i t i s romonbored t h a t th e p o s t -
m orton le n g th o f th o sm all i n t e s t i n o i s l i t t l e d i f f e r e n t front t h a t o f
th e a d u lt r a t *
IV Dir^ClSSIOM
a ) A booluto Values*
Tho a b s o lu to v a lu e s in th e p r e s e n t work a ro o b v io u sly v a l i d o n ly f o r
g u t s u b je c te d t o th o p ro ced u re h e re d e scrib e d * N e v e rth e le s s i t i s in te re s tin g ^ t h a t Warron (1939) found th o m ucosal a r e a p o r o e n tim o tre
s o ro a o l lA ngth to bo D4 s q . on i n th e jojunum o f th o dog end 38 s q . cm
3 3
-oxporlinents cm ono dO{| only* Bo adtolto« taoroovoy, t h a t th o d i s t a l lleniQ wfifl i n spaon n o t ovepoooe by th e f i x a t i v e ond th e r e f o r e th e v a lu o s id iich he o b to in o d f o r t h i s sofjnont isopo n o t oom pareble w ith
v a ln e c o b ta in e d f r o n so g o o n te i n which d lm to n eio n was o b ta in e d w ith th o f i x a t iv e *
Aoesptimoe o f suoh d a ta and Indeed o f a l l such f ig u r o a a v a ila b le a t th o p ro e e n t tim e a s a r e l i a b l e b a s i s f o r c a l c u l a t i n g th e t o t a l
m ucosal s u rfa c e o f th e I n t e s t i n o i n v iv o i s g r e a t l y t o be deiirecated * Hot o n ly does h l s t o l o c i c a l tre a tm e n t cause g ro sa d i a t o r t i o n b u t
ovidxmeo I s e e m v iu la tln g t h a t l a l i f e th e e n t i r e g u t i o much s h o r t e r
th a n i t i s poat-m ortcD # (Kspè and Conn o n , 1938;1940)* Bowever# Jo h n sto n (1913) ehotved t h a t d i s te n s io n o f th e s n a i l i n t e s t i n e I n
r:u ln aa-p lg e uado th e lo n g f i n g e r - l ik o v i l l i become stucg^y end tnuoh s h o rto r* Ih u s i t I s j u s t p o s s ib le t h a t th e t o t a l m ucosal a re a may
be l e s s a f f e c te d by a l t e r a t i o n I n g u t le n g th and by d i s t e n s io n th a n ono would a t f i r s t o i ^ t b e lie v e *
i^stlEMitlan o f th o r.iucosal a ro a o f th e s m a ll i n t e s t i n e i n man i s s t i l l f u r t h e r ocxaplloatod by th e o x lsto n c e o f th o v a lv u la r
«34 -B» ItolatlT O V alue#.
£i\rory o aro vrels ta k e n t o e n su re t h a t th e w hole sm a ll I n t e s t i n e i n each anim al ro a o to d u n ifo rm ly t h r o u ^ o u t i t s len^rth t o th o m a n ip u la tio n s
o f f i x a t i o n and embedding# D is to r tio n s o f th e a b s o lu te v a lu o s sh o u ld
th e n o a n o s l o u t i n making:: oom parleons betw een d i f f e r e n t p o r tio n s o f th e f ^ t i n th o some anim al and th e o o n p a rlso n s sho u ld be v a li d f o r th e
l i v i n g s t a t e .
I t would a p p ea r t h a t th e m usosal e u rfa o e o f th e jejunum p e r u n i t
lo n g th i n b o th r a t s and o a ts i s rou^^ily 1^ tim e s a s g r e a t a s th o m ucosal s u r f a c e o f th o ileum # T h is m ust be a t t r i b u t e d i n b o th
an im als t o g r e a t e r v i l l o u s dovolO]xMint i n th o jejunum s in c e th e
d ia m e te r o f th o m oall i n t e s t i n e rem ained u n if o m t h r o u ^ o u t i t s le n g th # I f vie a sstrie t l i a t th e I n t e s t i n e o f b o th r e t s and o a ts r e t a in e d t h e i r r o l a t i v a dimonoions th ro u c ^ o u t th e p ro c e s s e s o f f i x a t i o n ond embedding th e n i t i s j u s t i f i a b l e to compare th e sm a ll i n t e s t i n e o f th e r a t w ith t h a t o f th o oat#
V illo u s developnont a s a whole m ust be more marked i n th e sm all i n t e s t i n e o f th o o a t th a n i n th o r a t # The m ucosal a r e a p e r sq# cm#
s e r o s a l a r e a was rou(^^ily th r o e tim e s a s éT ^at i n th e c a t#
I t h a s a lre a d y beon n o ted t h a t th e postM aortem le n g th s o f th e sm a ll i n t e s t i n e s i n b o th r a t s ond o a ts wore i n th e noighbourhood o f
100 on# Assuming a u n if o m deci'oaso i n m ucosal a r e a from c r a n i a l t o
c au d a l ond o f th e sm all i n t e s t i n e i t i s p o s s ib le t o f i n d th o ratio ^^
t o t a l m ucosal a re a o f th e sm a ll i n t e s t i n e o f th e r a t t o t a l m ucosal a ro a o f th e s n a i l i n t e s t i n e o f th e c a t
•3S«
o o n tin o tr e lo n ^ th i s 6 .6 oq« m * I n th a r a t and 4 2 .5 a q . om. In th o o n t . dLvaa a r a t i o o f 1 Im plying t h a t th o m uooaal a ro a o f
67s
th e anaXl in to o tln o o f th o o n t i s more th e n 6 tim e s th e n u o o sa l a re a
o f th o s n a i l in to n t l n e i n th e r o t .
Ih e r o t s usod In t h i s work hod an a v e ra f^ w e l ^ t o f 299 g p e ,, tlio c a t s an ctrora^se body wolfiht o f 1*990 0Rb. The r a t i o *
body woirbtt o f r a t a l a th e r o f o r e % body w oic^ t o f c o ts 6%6
W ithout stro a e ln G unduly* i n view o f th o assumptiKme involved* th o c lo s e a^Puemont botwoon th eo e two r a t i o s * I t l a y e t obvious
t! ia t th o muoosal o u rfnco o f th o e n a l l i n t e s t i n e h as an in tim a te
r o l a t ic n a h lp t o th e body woi{j(ht oven vdion coraparlnc two suoh d i f f e r e n t o ro n tu ro s a s th e r a t and th e o a t . T his r e l a ti o n s h i p * i f e x p re sse d i n th e form*
auooogl s u rfa c e o f th e s n a i l i n to o t l x ^
body w o ié^t i s a
o o D sto n t, Im io d la to ly b r in g s to mind a s i m i l a r g e n e r a l i s a ti o n by C orl (1 9 2 5 ). I n h ie oaae* tho r e s u l t was p e rh a p s n o t so
unexpected s in c e ho :;orkad o n ly on r e t s o f d i f f e r e n t w o i ^ t s . Frcm
th e q u a n t i t i e s o f v a rio u s a u ^ ^ s absorbed from th e i n t e s t i n o he concluded tîm t i n t o s t i n a l a b so rb in g s u r f a c e i s a c o n s ta n t body
Thus* p u r e ly m o rp h o lo g ical o b so rv a tio n s I n t h l e t h e s i s su g g e st t h a t
on iia p o rta n t g o n o r a lis a tio n may bo s t i l l f u r t h e r e x te n d e d .
V. ÜU.11/JBY.
3 6
-R cpld f i x a t i o n and unlfosm d l a to n a l on o f th o g u t i n r a t a and
i n c a t s 1908 onçurod by ru n n in g f i x a t i v e th ro im ^ th e lumen a t a
c o n a ta n t hoad o f p re a a u ro . A f te r embedding i n p a r a f f i n , tr a n s v e r s e and l o n g it u d i n a l s e c tio n s o f tlic (jut wore o u t and s ta in e d * From m easurem ents on th e s e s o c tlo n o , m o ^ ^ f le d and p r o j e c te d , th e a r e a o f
th e nucoos membrano v iq b o a lc u la to d i n jejunum , iloum and colon*
Both i n th e r a t and o a t th e muoosol a re a p e r u n i t g u t le n g th l a
much g r o a te r i n th o jejunum th a n i n th e Ileum* Ih o r a t i o
muoosol a r e a l a (?% ater i n th o jejunum th a n I n th e ileton i n b o th so ro a o l a r e a
ap o cies* I n th e e a t t h i s r a t i o i s n e a r ly 3 tim e s a s g r e a t aa th e r a t i o i n th e r a t in d ic a t i n g a g r e a t e r dov elo p n o n t o f v l l l l In th o c a t*
I n s p i t e o f n ark ed d lffercm o o i n s i z e and i n h a b i t , th e t o t a l a ro a o f th e mucous nw ibrano i n th o e n t i r e sm all i n t e s t i n e b e a rs a
--►30*
Itelativ Q Hatoa o f A boon)tion o f lonoouoo ^ciride# ftrgp ead Il#um
o f Bttta UPÛoy Urothmw A n a ea tlio ala »
I . I n tr o d u c tio n . I I . P e s t Work. I l l l ^ s o n t Wogk.
a) Method.
b) XZssuXto. o) DlaotJission.
—30«*
I . HmtODDCTICH
I t rtao p o s tu la te d by Vorz&r (1936) t h a t th o d if f e r o n o e I n th e r a t e c f a b s o r p tio n o f hoxooos e . g . glucoso» and p e n to s o s , e*g« x y lo s e .
I n th o a n a l l i n t o s t l n o o f th e r a t I s due t o a s p o c ia l a c t i v i t y o f
th e I n t e s t i n a l icucosa, namely p h o sp h o ry la tio n o f th e hexoses* He a ls o s t a t e d t h a t t h i s s p o o la l a c t i v i t y wheroby g lu c o se was
p r e f e r e n t i a l l y a b so rb ed , was p a r t i c u l a r l y marked In c r a n i a l r e g io n s o f th o ST« I I I n t e s t i n e i n com parison w ith c a u d a l re g io n s (VorzAr and Viinz, 1 9 3 7 ).
As shewn i n th e p re v io u s s e c tio n th e mucosal a r e a I s l e s s In th o d i s t a l th a n I n th o c r a n i a l re^^o n o f th e sm a ll I n t e s t i n e . T h is
f a c t o r w i l l n a t u r a l l y n o t be w ith o u t in flu e n c e cm ab so rp tlcm r a t e s m easured by th o u s u a l tu c lm lq u e . TerzAr to o k no p r e c a u tio n s t o allo w f o r t h i s f a c t o r . The g r e a t e r p h o s p h o ry la tio n a c t i v i t y
o ro n iad I n th e g u t may sim p ly be an e x p ro sa lo n o f (ppoater m ucosal absorbing; n u rfa o e .
Hormvor, sh o u ld VArzar’ s p o s tu la te d g r e a t e r p h o s p h o ry la tln g
a c t i v i t y r e a l l y e x i s t I n th e c r a n i a l re g io n s o f th o sm a ll é ^ t , th en
th o a b s o rp tio n r a t e s o f (^lucoso and o f r^alaotose p e r u n i t a re a o f
n u c o sa l s u rfa c e should d e crea so from je ju n u n to l l e u n . On th e o th e r band, x y lo a o , s a id n o t t o bo p h o sp h o ry la te d i n th e p ro c e s s
o f a b s o r j tl o n (V o rz â r, 1936) sho u ld have th e ecsno r a t e o f a b s o rp tio n p e r u n i t a re a m ucosal su rfn o o b o th In jojunum and ileu m s in c e x y lo se
i s bollQ ved t o be ab so rb ed by sim ple d i f f u s i o n . Any s l ^ l f l c a n t
—40^
th o r o f o r e , to V e r s a r 'e h y p o th o ala 11© w ith Glucoee
end cplnetoe© r a t h a r th e n w ith xylooe#
II. P/.
3T
m m ,IlDbor (1898, 1899, 1903) found t h a t I n th o I n t o s t i n a l loojpo o f a n ao o th o tla o d ûO{^ some su co ro wero abaorbod I n p ro p o r tio n t o t h o l r
d lfT u o lo n v e lo c it l o o i*o* nonooacchîïrides nor© q u io k ly th e n
dloaeohf^rldos* Ile Aid n o t toko i n t o noooimt tiw p r o b a b i l i t y t h a t th o slow or r a t e o f a b s o rp tio n o f th o d lo ao o ^ arld o o vms duo t o th e tira©
tokon by h y d ro ly s is o f tho»© mioors in to slrn p lo r m m osaoW iarldos b e fo re a b s o rp tio n üould occur# Ho n lo o d isco y o ro d t h a t g lu co se and t^ la o to o o , In enaeothcrtlBod d o g s, wero a b so rb ed s t e q u a lly r a p id
rato G frcci th o sm a ll i n to s tin e # Hêdcm (1900) t e s t e d th e a b s o rp tio n r a t e o f a u g ers fro E th e em ail i n t e s t i n e o f u n a n e e s th e tis o d r a b b its #
Ik) used lo o k s o f g u t a e p a ra to d f r o n th o s n a i l i n t e s t i n e le a v in g th e
laeoontorlo oonnoctlons in ta c t # Oluooso v as found t o be ab so rb ed moro r a p id ly th e n c a ln o to o e whloh i n t u r n was n c ro r a p i d l y ab so rb ed
th a n fiTfiblnooe. I n 1908, Hagano, com paring s o l u t io n s o f d i f f e r e n t
c o n o o n tra tio tis I n rin a e sth o tlso d d o g s, found t h a t g a la c to s o was absorbed
laoro r a p id ly t?um f r u c to s e # F ru c to se was found t o be ab so rb ed a t a
(5?oator rat© tVmn x y lo se and arab in o eo #
I W i t t (1084) found I n u n o n a e o th e tise d r a b b i t s and p ith e d o a t s ,
t h a t gluooso i a noro r a p i d l y abaorbod th an o o la e to s e o r fru c to s e #
By fe e d in g d i f f é r e n t ougnr so lu tio n © t o u n o n a e s th e tls e d r a t s by j,loans o f Q stomach tu b e C orl (1985) e s ta b lis h e d th e r e l a t i v e r a t e s
o f a b s o rp tio n I n th o in to s tln o # C o r i’ o work l e so fundam ental t h a t
