Original Article
STUDY OF HUM AN FETAL KIDNEY
Shalika Sharma *
1, Sunanda Raina
2.
ABSTRACT
Address for Correspondence: Shalika Sharma, Acharya Shri Chander College of M edical Sciences, Jammu, India. E-M ail: [email protected]
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* 1 Lect urer, Acharya Shri Chander College Of M edical Sciences, Jammu,, India.
2 Professor and Head, Depart ment of anat omy, Government M edical College, Jammu,, India.
Background:The know ledge of t he basic hum an m orphology and developm ent al anat om y is very imperat ive for diagnost ic and t herapeut ic procedures. The quest ion of st udy of hum an renal developm ent arose for prenat al diagnosis of congenit al m alform at ions. There ar e few report s regar ding t he m orphological developm ent of hum an kidney, So, our st udy aim s at cont r ibut ing t o t he know ledge of m orphogenesis and hist ogenesis of hum an kidney. At various gestat ions.
M aterials and method: 30 hum an fetal kidneys bet ween 10 t o 34 weeks of gest at ion w ere dissect ed and processed in paraf fin, 7m m t hick sect ions w ere stained w it h Haem at oxylin-Eosin and M asson’s Trichrom e stains. They w er e divided int o 5 gr oups according t o CRL and light m icroscopy exam inat ion done.
Results: M orphogenesis of hum an kidney st art s at 5t h w eek of gest at ion and ext ends upt o last m ont h of last
t rim est er of pregnancy, renal pelvis w as very sm all and undif ferent iat ed at 10 w eeks and f ully different iat ed at 18 w eeks. Zone of t ransit ion bet w een cort ex and m edulla appeared at t he st art ing of 14 w eeks, presence of lobulat ion in kidneys w as observed as early as 10 w eeks, lobules st art fusing w it h each ot her at 15 w eeks of gest at ion. An arcade syst em along w it h w ell-def ined pyram ids w as observed at 16-18 w eeks.
Conclusion: The present w ork m ade an at t em pt t o do det ailed light m icroscopy of hum an kidney at various st ages of gest at ion, t he dat a on w hich is scant y in Indian populat ion.
KEY W ORDS: Kidney, lobules, arcade, pyram id, pelvis.
INTRODUCTION
Int ernat ional Journal of Anatomy and Research, Int J Anat Res 2014, Vol 2(4):785-90. ISSN 2321- 4287 DOI: 10.16965/ ijar.2014.550
Received: 30 Nov 2014 Accept ed: 16 Dec 2014 Peer Review : 30 Nov 2014 Published (O):31 Dec 2014 Revised: 13 Dec 2014 Published (P):31 Dec 2014
Internat ional Journal of Anat omy and Research ISSN 2321-4287
w w w.ijmhr.org/ ijar.ht m
DOI: 10.16965/ ijar.2014.550
Th e em ph asis o n genet i c co un seli n g an d po ssib ilit y of ear ly p r en at al diagnosis h as st imulat ed int erest in fet al kidney anat omy [1]. Definit ive hum an kidney is derived from t he m eso n eph r i c d u ct (u r et er i c bu d ) an d m et anephr ic blast em a. Local m esenchym e m igrat es int o met anephric blast em a t o form glomeruli and vasa recta. In brief, t he ureteric bud developing from t he m esonephric duct dilat es and for m s am pulla. The m esenchy-m at ous t issue epit helises and foresenchy-ms vesicles w hich fuse w it h t he ampulla t o form a nephron.
M et anephric development begins around 5t h
w eek of IUL and t erminat es in t he last mont h of 3rd t r im est er of pregnancy w it h subsequent
int erst it ial grow t h. M any such nephrons are present in fetal kidney due to multiple branching of t he ampullary bud and induct ion of various mesenchymat ous condensat es t o form nephron arcades. This process of renal developm ent begin s at deeper r egions and r eaches t he peripheral part of t he cort ex [2].
-ion of t he organ. Normally, t hese grooves may disappear as a result of fusion of lobules but occasionally may persist int o adult life. By 90 days (90mm C.R.Length) the met anephros shows different iat ion int o a cort ex and a medulla [3].
Since t here are very few report s in regard t o developing human kidney, t he follow ing st udy w as con d u ct ed w i t h an ai m t o st u d y o f hist ological changes during developm ent of kidney and st udy of t ime of different iat ion of cort ex and medulla.
M ATERIALS AND M ETHODS
The st udy w as conduct ed in t he Depart ment of Anat omy, Govt . M edical College, Jammu, India. St ill born and abort ed fet uses w ere collect ed from t he operat ion t heat re, labour room and Obst et ric wards of Depart ment of Obst et rics and Gynaecology, Gover nm ent M edical College Jam m u, Government Hospit al Gandhi Nagar, Government Hospit al Sarw al and various nurs-ing homes operat nurs-ing in and around Jammu cit y.
TABLE 1:Gestat ional age based on Crow n Rum p Lengt h.
1 53 t o 58 10 t o 11 2
2 75 t o100 12 t o 15 5
3 111 t o 140 16 t o 18 12
4 145 t o177 19 t o 22 6
5 180 t o300 23 t o 34 5
Groups Age No of fetuses
(In w eeks) Crow n-Rump
Length (In mm)
Speci m en s h av in g any t y p e of co ngeni t al malformat ions w ere not taken up for t he st udy. A t ot al of 30 fet uses w ere select ed and grouped int o 5 groups according t o t heir CR lengt h. Youngest fet us w it h CR Lengt h 53 mm and oldest w it h CR Lengt h 300mm as show n in t able 1.
After naked eye examinat ion of fet uses,kidneys w ere dissect ed out and t heir crow n rump lengt h was measured using Vernier Calliber. They w ere immersed and fixed immediately in 10% formalin solut ion. All w ere in excellent condit ion of p r eser v at io n an d no n e o f t h em h ad an y congenit al malformat ion. Ent ire kidneys w ere em bedded en bloc in paraffin using st andard prot ocol.Tissue blocks w ere serially sect ioned t o generat e 5-8 µ t hick sect ions using Rot ary microt ome. The sect ions aft er mount ing w ere st ained w it h H& E and M asson’s Tr ichrom e st ains.
OBSERVATIONS
GROUP 1 – 10 TO 11 W EEKS: Kidney of 10 w eeks old fet us w as very small and lobulat ed. The dist al ends of Prim ary collect ing t ubules dilat ed t o form t he ampulla. Ampulla w as lined by a single layer of cylindrical cells and w as surrounded by double layer of met anephrogenic t issue. Out er layer of t his m et anephrogenic t issue w as seen blending w it h t he surrounding m esenchym at ous t issue.Beneat h am pulla a renal vesicle lined by single layer of columnar cells was seen (Fig 1)
Fig. 1: Am pulla and Renal vesicle in a 10w ks old fet us
in M asson’s t richrom e X 40
No different iat ion is seen bet w een cort ex and medulla at t his st age.
Hilar region show s a developing pelvis lined by single layer of epit helial cells w it h round nuclei. Immediat ely surrounding t he pelvis, t here is a layer of dense mesenchymat ous t issue.
Fig. 2: Show ing pelvis and m ajor Calyces at 11 w ks of
At 11w ks, a larger dilat ed pelvis dividing int o 3 t o 4 M ajor calyces are seen. M ajor calyces w ere seen dividing int o slender and t ubular M inor calyces (Fig2).
GROUP 2 – 12 TO 15 W EEKS: At 12 t o 13 w eeks, kidney w as larger and show ed lobulat ion. These lobules w ere separat ed from each ot her by mesenchymatous t issue.Periphery of t he kidney show ed many branching ampullae.
The mesenchym at ous t issue surrounding t he o ut er l ay er o f m et an eph r o gen i c t i ssu e dif f erent iat ed int o collagen fibr ils and few fibroblast s w it h elongat ed oval nuclei running parallel t o t he long axis of t he kidney (Fig 3). This is t he anlage of fut ure capsule.
Fig. 3: Depict s branching am pulla and developing
capsule in 12 w ks fet us in H& E X 10.
Cort ex and m edulla w ere not different iat ed. Hilar region show ed a larger pelvis w it h a small lum en lined by 2-3 layered t hick epit helium having large rounded nuclei. M esenchymal cells in t he per ipher y w ere loosely ar r anged as compared t o ones immediat ely surrounding t he pelvis (Fig 4).
Fig-4: A sect ion show ing pelvis lined by 2-3 layered
t hick epit helium surrounded by t hick m esenchym e in 12 w ks fet us in M asson’s t r ichrom e X 10.
At 14 w ks – zone of t ransit ion appeared b/ w cort ex and medulla. Here t he pelvis w as lined by same epit helium as in fet us of 12-13 w ks but the mesenchyme surrounding it w as more dense.
At 15 w k s- w el l d if f er en t iat ed co r t ex and medulla w ere seen. Out ermost zone of cort ex w as very darkly st ained know n as t he neogenic zone. Neogenic zone cont ained many glomeruli along w it h PCT and DCT. Numerous collect ing t ubules lined by t all columnar cells w ere seen and t he pelvis w as mult i layered epit helium.
GROUP 3 – 16 W KS TO 18 W KS: By 16 w ks, kidney increased in size. Lobulat ion w as st ill vis-ible. Capsu le w as w ell d if f er en t iat ed w it h numerous collagen fibrils running parallel t o t he long axis of t he kidney. Beneat h t he capsule many developing glomeruli w ere seen in t he neogenic zone w hich w ere now com pact ly arr anged due t o decrease in t he int erst it ial t issue. Anot her import ant finding in t his group w as t hat t he parenchyma of t he t w o adjacent lobules w as separat ed by t he neogenic zone. This zone is similar t o t he neogenic zone seen u n der t h e cap sul e an d ext end s f r o m t h e subcapsular area t o t he pelvis of t he kidney. It gives t he appearance of a column or sept um and is know n as t he prim ary columna Bert ini (Fig 5).This column marks t he junct ion of primary lobules. Pelvis becam e ext ended and m any m inor calyces open int o it . The epit helium lining t he pelvis at t his st age w as mult i-layered.
Fig. 5: Depict s Pr im ary colum na Bert ini bet w een 2
adjacent lobules in 16 w ks fet us in M asson’s t richrom e X 4.
are t ow ards t he juxt a medullary region and t he most immat ure are seen t ow ards t he periphery of t he cort ex.
Som e of t he col l ect i n g t u bu l es sh ow ed st rat ificat ion. Well defined arcades i.e m any nephrons at t ached t o a single collect ing t ubule, and pyramids w ere seen in t he cort ical region. Cone shaped pyramids w ere seen w it h apex t ow ards pelvis and base t ow ards cort ex. Pelvis w as lined by t ransit ional epit helium.
By 18 w ks –w ell defined pyramidal syst em w as delineat ed. M inor calyx also appeared t o be lined by t ransit ional epit helium (Fig 6).
Fig. 6: Presence of Renal pyram id in 18 w ks in
M asson’s t richrom e X 4.
GROUP 4 – 19 W KS TO 22 W KS: Kidney size increased. Thick compact capsule w as seen at periphery w it h increase in t he collagen fibrils and cellular component s. In t he cort ical region, t he int erst it ial t issue had reduced t o a minimum w hich has result ed in crow ding of glomeruli. .
Arcade system was w ell developed .W it hin t he cort ex collect ing t ubules w ere seen aligning t h em selves i n o ne dir ect i on f r o m base of pyram id t ow ards periphery of cort ex. These regions w ere know n as t he medullary rays. In bet w een t w o medullary rays, areas cont aining glomeruli along w it h convolut ed t ubules w ere seen know n as t he cort ical labyrint h.
M ajorit y of t he collect ing t ubules appeared t o be lined by st rat ified epit helium. Lobules w ere st ill in t he process of fusion w it h t he column of Ber t i ni b/ w t h em (Fig 7). Well d evelo ped t ransit ional epit helium lined t he pelvis (Fig 8).
Fig. 7: Prim ary colum na Bert ini in fet us of 22 w ks in
H& E X 4.
Fig. 8: Show ing w ell defined t ransit ional epit helium
lining t he pelvis in fet us of 22w ks in M asson’s t richrom e X 40.
GROUP 5 – 23 W KS TO 34 W KS: Kidneys w ere l ar ger w i t h l ob ul at io n st i ll p r esen t . Th e collagen fibrils w it hin t he capsule w ere arranged in w avy pat t ern. Almost negligible int erst it ial t issue w as seen in t he cort ex. Subcapsular area or t he neogenic zone show ed met anephrogenic t issue (Fig 9).
Fig. 9: Depict s alm ost negligible int erst it ial t issue in
In t he region of cort ical labyrint h of cort ex t he most mat ure glomeruli w ere seen t ow ards t he m edu ll a an d m o st i m m at ur e t o w ar d s t h e capsule. M edullary rays w ere now composed of elongated collect ing t ubules (Fig 10).
In t he longit udinal sect ions of kidney of t his group, in bet w een adjoining lobules, the primary columna Bert ini w as seen. This finding show ed t hat t he process of fusion of lobules w as st ill go in g on . Pel vi s w as l in ed by t r an si t i on al epit helium around w hich dense mesenchyme is seen.
Fig. 1 0: sh o w s co r t i cal l ab yr i n t h i n b e t w e e n 2
m edullary rays. M edullary r ays com prising of elongat ed collect ing t ubules and Cort ical labyr int h com pr ising of m at ure glom eruli in fet us28 w ks in M asson’s t richrom e X 4.
DISCUSSION
Th e r enal pel v is app ear s t o b e li n ed b y t ransit ional epit helium by 18 w eeks of gest ation in consonance w it h Sabit a M et al [6] w ho also observed t hat t he pelvis is lined by t ransit ional epit helium by 18-20 w eeks of gest at ion.
The capsule of t he kidney develops from t he m esenchym at ous t issue. This finding agrees w it h Huber, G.C [7] w ho also visualised t hat t he m esenchym at ous t issue is t he anlage of t he fut ure capsule of t he kidney.
In t he pr esent st udy, a zon e o f t ransi t i on appeared bet w een cort ex and medulla at t he start ing of 14 weeks of gest at ion w hereas Sabit a M et al [6] observed t his t ransit ional zone at 16 w eeks of gestat ion. Well different iated cortex and medulla w ere first observed in t his st udy by the end of 14 w eeks of gestation. Hamilt on, Boyd and M ossman [5] observed t his different iat ion bet w een cort ex and medulla by t he end of 12 w eeks of gest at ion. Sabit a M et al found a w ell-different iat ed cort ex and medulla in a fet us of 18-20 w eeks of gest at ional age.
St r at i f i cat i o n o f co l l ect i n g t u bu l es i n t h e medullary region is observed by t he 18t h w eek o f gest at io n , Sabi t a M et al [ 6] o bser ved st r at if icat ion of collect ing t ubules at 18-20 w eeks of gest at ion.
In t his st udy, renal pyram ids and arcades app ear ed by 16-18 w eek s of gest at i on i n accordance w ith the previous observat ions made by Osat hanondh, V and Pot t er, E.L [2-4] and Huber, G.C [ 7] . But , Sabit a M et al [ 6] t oo observed t hem in t heir st udy by 18-20 w eeks old fet us.
This st udy out lines t he presence of lobulat ion at 10 w eeks in ut ero t ill 33 w eeks, w hich is in accordance wit h Osat hanondh, V and Potter, E.L [2-4], Ham ilt on, Boyd and M ossm an [5] and Sabit a M et al [6]. Fusion of lobules is evident at 15 w eeks of gest at ion. But Huber, G.C [7] observed fusion at 11 w eeks of gest at ion. Sabit a M et al [6] observed t hat t he fusion of lobules occurs in a fet us of 16 w eeks of gest at ion. M orphogenesis of human kidney begins at 5t h
w eek of gest at ion and ext ends upt o t he last month of t hird t rimest er of pregnancy [5]. M ost of t h e r esu lt s in t h e pr esen t st ud y ar e in accordance w it h t he previous aut hors w hile some are not . Thus, an at t empt has been made t o compare t he findings of ot her aut hors w it h t hose made in t his st udy.
In t he present st udy, a very small undifferent-iat ed kidney is seen at 10 w eeks of gest at ion. In t his kidney t he development of pelvis is seen in t he hilar region. This developing pelvis is in t he form of a circular st ruct ure lined by a single layer of epit helium w hich is in accordance w it h Ham i l t o n , Bo y d an d M o ssm an [ 5] an d Osathanondh V and Potter, E. L, [2-4]. But , Sabita M et al [6] observed t he developing pelvis at a lit t le lat er st age of 14 w eeks of gest at ion.
CONCLUSION
Lobulat ion of t he kidney appears at 10 w eeks and can be seen t hr oughout t he f et al lif e. Arcades syst em is observed at 16 t o 18 w eeks along w it h w ell defined pyramids.
In a 10 w eeks old fet us, t he kidney is in an undifferent iat ed form. There is a large amount of int erst it ial t issue in bet w een t he developing glom eruli and t he collect ing t ubules in early st ages of development but as t he age advances t here is decrease in t his int erst it ial t issue w hich result s in increased crow ding of glomeruli and collect ing t ubules t hat in t urn result s in coiling of t hese t ubules. A zone of t ransit ion appears bet w een cort ex and medulla at 14 w eeks of gestat ion. Well-different iated cortex containing large number of glomeruli, proximal convolut ed t ubules and dist al convolut ed t ubules and medulla cont aining port ions of collecting tubules and t he loop of Henle, are seen in a fet us at t he end of 14 w eeks of gest at ion.
ACKNOW LEDGEM ENT
I am ver y gr at ef u l t o Dr. Su n an d a Rai na, Professor and Head of Depart ment of Anat omy, Governm ent M edical College, Jam mu for her valuable suggest ions and comment s during t he course of t he present t ask.
Conflicts of Interests: None
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