Chapter 17

Print ISBN: 978-93-91473-61-7, eBook ISBN: 978-93-91473-85-3

Determination of Histogenesis of Human Kidney in

Spontaneously Aborted Human Fetuses from 14
Weeks to 36 Weeks
Divya Jain Pokarna1, Kasturi Kshitija2* and Seethamsetty Saritha3
DOI: 10.9734/bpi/nfmmr/v2/2963F

ABSTRACT

Aims and Objectives: The development of Kidney is a complex process having two parts the
collecting & excretory part. Due to recent advances in the medical field it is now possible for
premature babies to survive successfully. The original conception of human fetal Kidney morphology
and developmental anatomy is very important for prenatal diagnosis of normal and congenital
disorders such as Wilm’s tumor, Hydronephrosis, Multicystic dysplastic kidney, Autosomal recessive
polycystic kidney disease, Megacystis, Renal dysplasia etc.
Histogenesis of Kidney according to its gestational age gives overview of these congenital anomalies
that are important for a developmental Anatomist , in diagnosing the Genetics aspects, Radiological
and Histopathological diagnosis & finally improvising antenatal screening and forecasting the route of
treatment.
Methods: The study used 40 kidneys obtained from 20 spontaneously aborted foetuses [11 males
and 9 females] ranging in gestation from 14 weeks to 36 weeks. After confirming their age with CRL,
they were grouped and then processed to form slides stained with hematoxylin and eosin. The stained
slides were seen under light microscope.
Results: At an early gestational age, all kidneys were lobulated and fused by 36 weeks. By 18 weeks,
the corticomedullary junction and preformed collecting tubules were plainly visible. By 19 to 23 weeks,
well-differentiated PCT and DCT had formed. Well formed pyramids by 28 weeks and medullary rays
by 29 weeks were clearly distinguished. Loop of Henle developed and distinguished by 28 weeks.
Increased vascularity was seen by 32 weeks to 36 weeks. Nephrogenic zone and undifferentiated
mesenchyme decreased and matured glomeruli increased by 36 weeks.
Conclusion: This present study may help us in understanding various renal disorders. This study can
also emphasizes on the development of each component in medulla and cortex of Kidney, regarding
histological maturity & functional status according to gestational age & gives us an overall panoramic
view.
Keywords: Corticomedullary Junction(CMJ); Proximal Convoluted tubules(PCT); Distal Convoluted
tubules (DCT); Loop of Henle (LOH); Intrauterine growth retardation (IUGR).

1. INTRODUCTION
Prenatal development is a pivotal period for human development and kidneys have long been thought
to play an important part in foetal growth.
To comprehend the origin of numerous pathological disorders associated to the genetic and
congenital domain of this organ, it is necessary to understand the normal developmental anatomy and
histogenesis of the kidney. It has long been known that the formation of kkdney follows an
evolutionary pattern. It develops in a cranio-caudal orientation from the intermediate mesoderm, going
_____________________________________________________________________________________________________
1
Kamineni Academy of Medical Sciences and Research Centre, LB Nagar, Hyderabad (500068), Telangana, India.
2
Department of Pathology, Bhaskar Medical College And General Hospital, Hyderabad, Telangana, India.
3
Department of Anatomy, Kamineni Academy of Medical Sciences And Research Centre, Lb Nagar, Hyderabad (500068),
Telangana, India.
*Corresponding author: E-mail: kshiti80@yahoo.co.in;
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via the pronephros, mesonephros, and metanephric stage. Finally permanent functioning Kidneys
develop from metanephros in the lumbosacral segment. They develop early in 5 th week and start to
function around 9th week [1]. The functioning Kidney has two parts : the collecting part which develops
from ureteric/mesonephric duct and the excretory part which develops from metanephric blastema.
Local mesenchyme migrates into metanephric blastema to form glomeruli and vasa recta. In brief, the
ureteric bud developing from the mesonephric duct dilates to form ampulla which branches itself. The
mesenchymatous tissue epithelializes and forms vesicles which fuse with the branched ampulla to
form a nephron [2].

Ureteric bud is capped with metanephric blastema. On further sub-division of the ureteric bud, some
parts of the blastema separates from the main mass and forms clusters of cells on each side of the
tubule forming pear shaped hollow renal vesicles. First vesicle is formed at the end of 7th week. Cells
at the proximal pole of the vesicles organize to form C-shaped or comma shaped body followed by
cellular reorganization of tubular cells at distal end to form an 'S' shaped body (S-body). In the cleft of
the S-body at the distal pole, formation of extra cellular matrix and penetration by capillaries targets at
formation of future mesangial region. The proximal limb of the S-body organizes to form distal
convoluted tubule while the intermediate limb enlarges to form loop of Henle and the proximal
convoluted tubule resulting in entire development of a nephron [3].

Due to these sequence of development, macroscopically the Fetal Kidney has about 12 lobes but
these are fused in adults to present a smooth capsulated surface [4]. Microscopically Kidney is
composed of many tortuous closely packed uriniferous tubules bound by little connective tissue in
which runs blood vessels, lymphatics and nerves [5].

The Kidney plays an essential role in maintaining homeostasis in body. It also excretes metabolic
wastes and regulates certain hormones production [6]. The permanent Kidneys become functional in
intrauterine life and urine produced by it is added to amniotic fluid from 10th week of gestation [7].

The present study shows the correlation between histogenesis of Fetal Kidney in particular phases
during fetal development and their respective gestational age. An attempt was made to compare the
findings of our study with that of the other authors in relation with the gestational age of fetus

2. METHODS
The present study was carried out in the Department of Anatomy, KAMSRC, LB nagar; Hyderabad
[Telangana], India. The materials of the present study consists of 20 fetuses of known gestational age
over a period of 1 year.

 Inclusive criteria: The fetuses taken were unclaimed spontaneously aborted or still born
ranging from gestational age 14 weeks to 36 weeks (11males and 9 females).
 Exclusive criteria: The twins and the fetuses with congenital abnormalities were excluded.

These fetuses were obtained from department of Obstetrics and Gynecology, KAMSRC, LB nagar;
Hyderabad [Telangana], India.

Table 1. Textbook of Human Embryology by Hamilton, Boyd and Mossman

Age(in lunar months) Crown rump length in mm

3 55
4 100
5 150
6 200
7 230
8 265
9 300
10 335

The known gestational age of fetuses were then correlated with the respective CRL according to Text
book of Embryology by Hamilton, Boyd and Mossman [8] [Table 1] with an osteometric board having

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mm scale. It helped to confirm their registered gestational age, to rule out any IUGR and conveniently
group them into 5 groups according to their gestational age[Table 2]. The fetuses were embalmed and
then kept in 10% formalin for 24 hours. The Kidneys were then dissected, observed for any gross
abnormalities, cleared and then processed for dehydration. Next after embedding, the paraffin blocks
were prepared. Seven micrometer sections were taken with rotary microtome and stained with
haematoxylin and eosin, observed under microscope and then microphotographed. This process was
followed after taking permission from the Kamineni Institutional Ethics Committee (Registration No.
ECR/58/Inst/AP/2013/RR-16)at KAMSRC and Kamineni hospitals, LB nagar, Hyderabad.
Table 2. Groups of fetuses in study according to their gestational age

Groups Gestational age in weeks Number of fetuses

A 14-18 3
B 19-23 5
C 24-28 3
D 29-32 4
E 32-36 5

3. RESULTS
Group A [14 weeks-18 weeks]: Kidney shows lobulation. Capsule is thin and wavy.
Cortex: Large amount of undifferentiated mesenchyme is seen with nephrogenic zone below capsule.
Zone of transition between cortex and medulla showing CMJ is seen by 16 weeks and well
demarcated by 18 weeks. Hollow structures lined by single layer of cells were seen near the
developing glomeruli, these were nephrogenic vesicle. It also showed many ‘V’ shaped developing
tubules. Many cut sections of tubules not differentiated into PCT and DCT are seen.
Medulla: preformed and developing collecting tubules are seen. Developing renal pelvis had single
layered epithelium at 14weeks and by 16weeks it was multilayered (Fig. 1).
Group B [19 weeks-23 weeks]:
Cortex: S and C shaped tubules are seen in which vascular structure invaginate at its distal pole as
glomeruli. Connective tissue between lobules can be seen. The cut section shows tubules in cortex
have differentiated into PCT and DCT by 19 weeks. They show different characteristic staining
pattern. PCT are more in number with basophilic darkly stained cytoplasm and DCT have pale
eosinophilic cytoplasm. Both are lined by cuboidal epithelium. PCT is lined by brush border and DCT
have clear lumen.

Medulla: It shows many cut section of tubules which may later develop into LOH (Fig. 2).

Group C [24 weeks-28 weeks]: There is decrease in connective tissue in between the lobules and
also in the parenchyma of Kidney. Nephrogenic zone is in very less quantity accumulated below the
capsule in the cortex. Undifferentiated mesenchyme is reduced and now compact (Fig. 3B and Fig. 4).

Cortex: ‘C’ shaped tubules encompassing the glomeruli are seen. PCT developed proper brush
border (Fig. 3A).

Medulla: Medulla started to segregate into pyramids by 24 weeks and proper architecture is seen by
29 weeks. LOH have developed from the tubules in medulla and are distinguished into thick
ascending limb lined by cuboidal epithelium and thin descending and a part ascending limb which is
lined by flat epithelium. Medullary rays have started developing.

Group D [29 weeks-32 weeks]:

Cortex: Juxtacortical glomeruli arranged themselves in groups of 2-3. The glomeruli have developed
lobulation. Matured glomeruli are towards centre and immature towards periphery. Medullary rays are
well developed by 29weeks along with development of arteries and renal cortical columns on either
side of developed pyramids (Fig. 5A).

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Medulla: Loops of Henle are surrounded by vasculature which could be Vasa recta (Fig. 5B).

Group E [32-36 weeks]:

Cortex: Well developed compact thick capsule is seen. Lobules have fused by 36 weeks. Connective
tissue, undifferentiated mesenchyme are reduced giving a compact look to the well distinguished
cortex and medulla. Fully matured tubules and lobulated glomeruli are seen (Fig. 6A).

Fig. 1. Medulla and Cortex 14-18 weeks, 1.
Renal Pelvis 2,4. Collecting ducts 3.
Undifferentiated. Mesenchyme 5. Glomerulus
6. Nephrogenic vesicle 7. Convoluted tubules
(H and E, x10)
Fig. 2. Cortex 19-23 weeks, 1. Collecting tubules
2. Corticomedullary junction 3. Glomeruli 4. ‘c’
shaped glomeruli 5. ‘s’ shaped glomeruli 6. ‘v’
shaped glomeruli 7. Connective tissue between
lobules (H and E, x10)

Fig. 3. Cortex 24-28 weeks, 1. Proximal Fig. 4. Cortex 24-28 weeks, 1. Connective
convoluted tubule 2. Glomeruli 3. Distal tissue between lobules 2. Connective tissue
convoluted tubule (Hand E, x40) in kidney parenchyma (H and E, x4).

Fig. 5. Undifferentiated mesenchyme at 14 Fig. 6. Cortex 29-32 weeks, 1. Pyramids 2.

weeks 2. Convoluted tubules 3. Collecting Renal cortical columns 3. Artery development
tubules. (H and E, x10) between two pyramids (h and E, x4).

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Medulla: The magnified visual field is covered with cut section of LOH with interstitial space showing
rich vascularity. Collecting tubules which were scattered are organized in groups forming duct of
Bellini. Renal pelvis is well developed, lined by transitional epithelium and with its own vasculature
(Fig. 6B).

4. DISCUSSION
The Kidney was lobulated in 12-13 lobes and showed signs of fusion as early as 14 weeks to 16
weeks and was fused by term [36 weeks]. The capsule became rigid with increasing gestational age.
Nephrogenic zone which is darkly stained was present beneath the capsule was more marked in early
gestational period and later it decreased with increasing fetal age but remained in accordance with
Kirti Solanki et al and Mamatha Hospatna et al. [9,10]. Sudha Patil et al claimed it to be disappeared
by 38 weeks and Potter Let al claimed it to disappear by 36 weeks [11,12].

Fig. 7. Medulla 29-32 weeks, 1. Medullary rays 2.
Mature glomeruli towards center than immature
glomeruli 3. Thick ascending Loop of Henle 4.
Thin descending Loop of Henle 5. Vasa recta (H
and E, x4)
Fig. 8. Cortex 32-36 weeks, 1. Increased
vasclarity 2. Group of juxta cortical glomeruli
3. Cortex under capsule (H and E, x10)

Fig. 9. Medulla 32- 36 weeks, 1. Tightly packed Loop of Henle 2. Grouping of collecting ducts 3.
Renal pelvis (H and E, x10)

Undifferentiated mesenchyme was till 36 weeks in accordance with Kirti Solanki et al and Sadiq Ali
Syed et al. [9,13].
The CMJ was observed by 16 weeks and was well demarcated by 18weeks .KhayatiSantRam et al
found the differentiation after 18 weeks. but it was in accordance with Sabita M et al. [7,14].
The evolution of renal corpuscle observed was as follow:
‘v’ shaped at 14weeks to 18 weeks.;‘s’ shaped at 19weeks to 23 weeks.;‘c’ shaped at 24weeks to
32 weeks and matured lobulated glomeruli at 29weeks to 32 weeks.
These were similar to the findings of Bhattam Narsinga Rao et al and Takano k. et al. [15-17]. Though
all the different developmental stages were found in almost all the gestational ages.

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Many cut section of tubules were seen in cortex by 14 weeks to 18 weeks. By 19 weeks the tubules
have differentiated into PCT and DCT. Tank KC et al found it by 17weeks and Kirti Solanki et al first
observed at 20 weeks. Mamatha Hospatna et al found the differentiation as early as 16weeks [1,9,10].

Medullary rays were found well developed by 29 weeks in cortex in accordance with Kirti Solanki et al.
[9].

Medullary pyramids and renal cortical columns have started developing by 24 weeks and were distinct
in accordance with Bhattam Narsinga Rao et al. [15] but Shallika Sharma et al found renal pyramids
by 16 weeks to18 weeks [2].

The proper architecture and arrangement of pyramids and renal columns are seen by 29 weeks.By 19
weeks to 23weeks medulla was filled with cut section of tubules. Few being preformed and still
forming collecting tubules and the others giving rise to LOH and vasa recta. It could be completely
distinguished into thick and thin ascending and thin descending LOH by24-28weeks. The surrounding
vessels developed to give rise to vasa recta by 29 weeks. By 36 weeks it became the major
component of medulla. This was is in accordance with Mamatha Hospatna et al and Laura Vinci et al
[10,16] . Takano K et al found the differentiation by 17weeks [17].

The developing renal pelvis showed single layer of cells at 14 weeks in accordance with Sabita M et
al. [14]. By16 weeks to 20 weeks showed stratification in accordance with Shallika Sharma et al. [2].

In the interstitial spaces, huge number of blood vessels were found showing increase in Kidney’s
vasculature with time, in accordance with Laura Vinci et al. [16].

The arrangement of matured Glomeruli towards centre and immature towards periphery was in
accordance with Khayati Sant Ram et al. and Maria H et al. [7,18].

The emphasis on genetic counseling and possibility of early prenatal diagnosis has stimulated interest
in Fetal Kidney Anatomy [19].

The current study was done on 20 fetuses (11 males and 9 females) with gestational age ranging
from 14weeks to 36 weeks. The findings of this study were found to be within the ranges of findings of
other authors and also in the literature.

5. CONCLUSION
This study helps us to know the sequence of development of various parts of histogenesis of Kidney
and its correlation with the fetal gestational age.

It focused mainly on morphological and histological changes during renal development in fetuses,
both in the architecture of the medulla and cortex for understanding of congenital and pathogenesis of
Kidney

ACKNOWLEDGEMENTS
We express our sincere thanks to the department of Anatomy, Obstetrics and Gynecology and
Pathology KAMSRC, for the help and moral support .Lastly we show our gratitude to all editors and
publishers of all the Articles, Journals & Books from where needful information for this Research was
taken.

ETHICAL APPROVAL
It is not applicable.

COMPETING INTERESTS
Authors have declared that no competing interests exist.

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Biography of author(s)

Ms. Divya Jain Pokarna

Kamineni Academy of Medical Sciences and Research Centre, LB Nagar, Hyderabad (500068), Telangana, India.

EDUCATION QUALIFICATION:
 Procured a merit seat for undergraduation{MBBS} at KAMINENI ACADEMY OF MEDICAL SCIENCES AND RESEARCH
CENTRE in 2016.
 Passed final year in 2021.

ACADEMIC ACCOLADES:

 State topper in ophthalmology and received university gold medal for it.
College topper in second year.
College topper for microbiology, ophthalmology and community medicine and received gold medals for it.
First research paper published in the “INTERNATIONAL JOURNAL OF RESEARCH IN MEDICAL SCIENCES.” In the year
2019. “HISTOGENESIS OF HUMAN FETAL KIDNEY FROM 14 WEEKS TO 36 WEEKS: A STUDY.”
Received a momento in appreciation for presenting research paper at CME 2019, by department of Anatomy.

ACADEMIC ACTIVITIES

 Indulgent participant in PULSE POLIO PROGRAMME organized nationally and also in College debates and integrated
programs.
Participated as a speaker in “CME 2019: LIMBIC SYSTEM AND

CLINICAL CORRELATION.” by department of anatomy and also participated as a volunteer in “CME 2017: CYTOKINES AND
TUMOR MARKERS: A BIRD’S EYE VIEW.” by department of biochemistry and oncology.

Dr. Kasturi Kshitija

Department of Pathology, Bhaskar Medical College and General Hospital, Hyderabad, Telangana, India.

A)Education Qualification
i) MBBS: J.S.S Medical College, Mysore, Karnataka , 1998 batch
ii) MD Pathology: Sri Ramachandra Institute of Higher Education & Research, Chennai, Tamil Nadu, 2005 batch
iii) Advance course in medical education (Fellowship degree): Sri Ramachandra Institute of Higher Education &
Research, Chennai, Tamil Nadu, 2021 ongoing batch
iv) Completed Basic Course in Biomedical research March 2021
v) Completed Revised Basic Course Workshop in Medical Education Technologies & AET-COM Sensitization
Programme by MCI regional Centre, Gandhi Medical College at Bhaskar Medical College & General Hospital on Sept 17th to
19th 2018

B) Teaching Experience:
i)Assistant professor : 3years in Apollo Institute of Medical Sciences & Research, Hyderabad.
1year 8months in Bhaskar Medical college & General Hospital, Hyderabad
ii)Associate Professor : 1yr and 6months in Bhaskar Medical college & General Hospital, Hyderabad

C) Associate member of Indian Association of Pathologists and Microbiologists - IAPM/A/2006/94

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D)Publications
1)Original/Research Article: Six in indexed journals
2)Case reports : Four in indexed journals

E) Histology text & Power Point Presentation(January 2018) CBS Publishers & Distributors- Editor

F)Academic activities at Bhaskar Medical College & General hospital

i) Co-ordinator & Resourse person at Hands on Training in Basic Blood Banking conducted at Blood Bank, on 14 th June, The
World Blood Donor Day.
ii) Talk on “Significance of March 24th in Medical History” on World Tuberculosis Day ,March 24th 2019.
iii) Talk on “Du Variant” at CME on Transfusion Medicine organized by ISBTI on June 26 th 2019.
iv) Talk on “Safe Blood For All” A Sensitization progamme for New PG Batch ,on June 26th 2019.
v)Resourse Faculty for Foundation Course in the Competency Based undergraduates Curriculum in
August 2019

G) Attended forty CME Programs, Workshops & Conferences in my career

Dr. Seethamsetty Saritha

Department of Anatomy, Kamineni Academy of Medical Sciences and Research Centre, Lb Nagar, Hyderabad (500068),
Telangana, India.

Research and Academic Experience:

30 Years experience in Academic (Teaching)
Guided Number Postgraudates in Anatomy

Research Area: Interested In Research of Congenital Anamolies in Fetuses

Number of Published papers: Published Scientific Papers around: 52 (in State, National & International journals.)

Special Award:
1. Conducted three CME Programmes & as an Organizing Chairperson & speaker.
2. Invited as Guest speaker for CME in number of Medical colleges

Any other remarkable point(s):

1. Conducted Second National wide competition for
First and Second MBBS students on awareness of “Legal Rights of a Woman”
2. Member, Editorial board International Journal of Research in Medical Sciences.
3. Reviewer -Journal of the Anatomical Society of India
_________________________________________________________________________________
© Copyright (2021): Author(s). The licensee is the publisher (B P International).

DISCLAIMER
This chapter is an extended version of the article published by the same author(s) in the following journal.
International Journal of Research in Medical Sciences, 7(11):4330-4334, 2019.

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