ANATOMY OF PANCREAS , THYMUS & OTHERS

Dr. Sangeeta Kotrannavar Dept. of Anatomy USM-KLE IMP Belagavi

Objectives

• Recall the features of pancreas, thymus gland and testis

• Describe the islets of langerhans of pancreas

• Describe the thymus gland

• Describe the interstitial cells of leydig of the testis

• Describe of the

• Describe the

Testis Introduction

The male reproductive system consists of • Male gonads • Two testes • A system of genital ducts • Epididymis • Vas Deferens • Accessory glands • Seminal vesicles • Prostate • Bulbourethral glands • Penis Coverings of testes

1. Tunica Vaginalis 2. Tunica Albuginea 3. Tunica Vasculosa

Sagittal section of Testis

 Thick connective tissue tunica albuginea surrounds testes and forms mediastinum testis  Thin connective tissue septa from mediastinum testis separate testis into testicular lobules  Each lobule contains 1 to 4 tightly coiled tubules, the seminiferous tubules  The tubules open into rete testis (a network of channels)  Small efferent ductules connect the rete testis to the upper end of the epididymis Testis Microanatomy Seminiferous tubules

Lined by specialised stratified germinal epithelium (Seminiferous) • Spermatogenic cells – involved in spermatogenesis (in different stages -from spermatogonia - spermatocytes - spermatids – mature sperm) • Supporting cells (sertoli cells) Interstitial Tissue & Cells

• Interstitial tissue is a delicate vascular connective tissue that surrounds and supports the seminiferous tubule and is continuous with tunica vasculosa of testes at the periphery. • It contains specialised endocrine cells called Leydig cells, occurs singly or in clumps which secrete testosterone. Leydig cells (interstitial cells) • Are mesenchymal in origin

• Round nucleus at periphery • Are large, polygonal, cells that typically contain lipid droplets.

• Eosinophilic cytoplasm contains smooth endoplasmic reticulum (SER), several mitochondria and crystals.

• Crystals • Rod-shaped known as crystals of Reinke, appears as retractile structures in H&E • Exact nature and function of crystals are remain unknown Functions of Leydig cells • Leydig cells differentiate and secrete testosterone during early fetal life. • Secretion of testosterone is required during embryonic development, sexual maturation, and reproductive function: • In the embryo, secretion of testosterone & other androgens is essential for the normal development of the gonads in the male fetus. • At puberty, secretion of testosterone is responsible for the initiation of sperm production, accessory sex gland secretion, and development of secondary sex characteristics. • In the adult, secretion of testosterone is essential for maintenance of spermatogenesis & of secondary sex characteristics, genital excurrent ducts, & accessory sex glands. Hormonal regulation of

Ref Ross Hormonal regulation • Spermatogenesis dependent on luteinizing and follicle stimulating hormones produced by the • Luteinizing hormone (LH or ICSH) binds to receptors on interstitial cells and stimulates testosterone secretion • Follicle-stimulating hormone (FSH) stimulates Sertoli cells to produce androgen-binding protein(ABP) into seminiferous tubules to bind testosterone • Testosterone is vital for spermatogenesis and accessory gland function • Sertoli cells produce inhibin, which inhibits FSH production from pituitary gland via negative feedback Applied –Leydig cells • Leydig cell tumors represents predominately benign tumors, which occur during two distinct periods (in childhood and in adults between 20 and 60 years old). • Features • They are hormonally active and secrete androgens or combination of androgens and estrogens. • Testicular enlargement, usually is related to abnormal level of hormone production. • In prepubertal boys, this leads to sexual precocity (unexpected pubertal changes in early age), • Whereas in adults it may be observed as feminization (development of female sexual characteristics) and gynecomastia (development of breast in males). Ovary Female Reproductive System Ovary • Female • Location: in ovarian fossa, in post part of broad ligament, & lateral wall of pelvis • Has tubular pole – connected to suspensory ligament • Has uterine pole – connect to uterus via proper ligament of ovary • 2 major functions - production of gamete (oocytes) - production of hormones 1. Estrogen – promotes maturation of internal and external genitalia, and development of mammary gland 2. Progesterone – prepare uterus for pregnancy, and mammary gland for lactation. • Both hormones play key role in menstrual cycle

Structure of ovary

1- Germinal Epithelium- Single layer of low cuboidal cells 2- Tunica Albuginea - Dense connective tissue layer beneath epithelium 3- Cortex (Peripheral)- Contains Follicles, collagen and reticular fibers 4- Medulla (Central)- Dense irregular connective tissue. It Contains blood vessels, nerves & lymphatics Stages of Follicular Maturation

1. Primoridal follicle

2. Primary follicle - Unilaminar - Multilaminar

3. Secondary / antral follicle

4. Tertiary follicle / Graafian follicle

5. Atretic follicle

Ovary Maturation of Ovarian follicle

• Primordial follicle - Earliest follicle , contains primary oocyte & is surrounded by a single layer of flat cells • Primary follicle • Unilaminar - covered by a single layer of cuboidal cells. • Multilaminar - on further growth, single layer proliferate & becomes multilayered. Now cells are called granulosa cells.

Maturation of Ovarian follicle • Secondary / antral follicle • Cavities appear between granulosa cells forming an antrum & filled with antral fluid • Mature /Graafian Follicle • A large Antrum - filled with follicular fluid • Primary oocyte is supported by a group of granulosa cells called cumulus oophorus. • The granulosa cells surrounding antrum are named as membrana granulosa • Inner theca interna – Vasular layer • Outer theca externa

Ovulation

• Ovulation – mature follicle ruptures and release secondary oocyte along with corona radiata cells into the peritoneal cavity  capture by the fimbria of fallopian tube • Just before ovulation it completes meiosis 1st division to form secondary oocyte Ovulation Corpus Luteum

• The dominant follicle after releasing the ovum formed as Corpus luteum. • Cells undergo hypertrophy & cytoplasm filled with the yellow pigment called lutein hence corpus luteum. • Theca granulosa  granulosa lutein cells derived from granulosa cells secrets the hormone progesterone acts on endometrium & prepares it to receive & implant the zygote. • Theca interna  theca lutein cells derived from theca interna cells - secrets the hormone oestrogen cause proliferation of endometrium

Corpus luteum

TLC cavity

GLC

Granulosa lutein cells (GLC) - have a large polygonal cells with large amount of eosinophilic cytoplasm & round nucleus. Contains lipid droplets giving yellow colour Theca lutein cells (TLC) have a spherical nucleus, but the cells are considerably smaller than granulosa lutein cells with pale cytoplasm

Corpus Luteum

corpus haemorrhagicum - Bleedingin the cavity Functions • Corpus luteum primarily secrets the hormone progesterone • Responsible for ovulation • secretory phase of endometrium • maintenance of pregnancy Changes in corpus luteum • Fertilization occurs  corpus luteum of pregnancy (survive for 3 months)

• No fertilization  corpus luteum of menstruation (survive for 10-12 days )

• At the end - regress  corpus albicans, white fibrous scar

• Atretic follicles - Most ovarian follicles do not attain maturity and undergo degeneration (atresia) and become atretic follicles (finally replaced by connective tissue) Hormonal regulation of ovarian cycle

This diagram illustrates the relation of the morphologic changes in the endometrium and ovary to the pituitary and ovarian blood hormone levels that occur during the menstrual cycle. The pituitary and ovarian hormones and their plasma concentrations are indicated in arbitrary units. LH, luteinizing hormone; FSH, folliclestimulating hormone. Hormonal regulation of ovarian cycle FOLLICULAR PHASE OVULATION LUTEAL PHASE 10-20 primordial follicles begin to develop in Theca and granulosa cells transform into the corpus response to FSH and LH levels. luteum and secrete large amounts of progesterone. FSH and LH stimulate theca and granulosa cells. No fertilization, corpus luteum degenerates. Production of estrogen and progesterone. If fertilization does occur, HCG released from the embryo Surge of LH induces ovulation. maintains corpus luteum

Polycystic TA ovarian disease

• Characterized by bilaterally enlarged with numerous follicular cysts • Have a smooth, pearl-white surface because of no ovulations hence no scarring • An unusually thick tunica albuginea • Anovulatory cycle characterized by only estrogenic stimulation of the endometrium because of the inhibition of progesterone production. • Progesterone inhibition is caused by failure of the Graafian follicle to transform into a progesterone-producing corpus luteum.

MTF •Regarding testis and ovary

F A Leydigs cells located inside lumen of seminiferous tubules F B FSH stimulates Leydigs cells F E Sertoli cells secrete testesterone F C Corpus luteum develops under the influence of FSH F D Corpus luteum is formed before ovulation

SEQ • Describe the interstitial cells of leydig of the testis • Describe corpus luteum of the ovary Thymus Thymus- Gross features

• Thymus is both immune & endocrine organ • Double embryonic origin: epithelial reticular cells from endoderm & lymphocytes from mesoderm  Lympho-epithelial organ • Well developed in foetus-12-15gm; peak at puberty 30-40gm • Involutes after puberty (10-15gm.) and increases in connective tissue and adipocytes but continues to function in later life • The thymus gland secretes hormones called humoral factors

Thymus- Gross features

Bi-lobe, pear shape. Location - in anterior part of superior mediastinum, just behind manubrium. • Relations: • Anterior- manubrium sternum • Posterior –pericardium, great vessels & trachea • Either sides – lungs with pleura • Arteries - branches from internal thoracic & inferior artery • Veins - drain to the left brachiocephalic, internal thoracic & inferior thyroid veins

Architecture of the Thymus

•Connective tissue frame work or stroma • Thin capsule • Trabeculae • Cellular cytoplasmic reticulum – formed by epithelial reticular cells

•Parenchyma • Cortex • Medulla

Thymic lobule

Cells present in thymus

• T– Lymphocytes T Cells • Epithelial reticular cells(ERC) –endocrine cells • Natural killer cells. • Macrophages • Antigen presenting cells • Others: Fibroblast neutrophils

Thymus: Cortex & Medulla

• Cortex : Densely packed with lymphocytes / thymocytes hence appears, few macrophages and ERC • Medulla: Fewer lymphocytes, lightly stained, More ERC • Hassall’s corpuscles(H): Round lamellated acidophilic bodies, • contain flattened type VI ERC that are arranged concentrically and are filled with keratin filaments • Function is not fully understood, it is thought that it produce interleukins (IL-4 and IL-7) that function in thymic differentiation and education of T lymphocytes Epithelial reticular cells(ERC)

• Forms the cellular supporting frame work • Have pale staining large nucleus, eosinophilic cytoplasm & cytoplasmic processes attached with other cells by desmosomes • Play an important role in development of immunocompetent T cells • Liberates thymosin & thymopoietin hormones

Epithelial reticular cells(ERC)

• Types – 6 • Type I - separates thymus from connective tissue (in Capsule) • Type II –in outer cortex , forms cellular framework , compartmentalize the cortex into isolated areas for the developing T cells & Unlike type I cells, type II cells express MHC I and MHC II molecules, which are involved in thymic cell education. • Type III & IV - Like type I cells, type III & IV create a functional barrier between the cortex & medulla. • Type V – situ in medulla, provide the cellular framework of the medulla • Type VI –in medulla; forms the HC

Blood thymus barrier

1.Endothelium of capillary wall - continuous with occluding junction, major structural component 2. Basal lamina 3. Perivascular connective tissue and cells (eg. pericytes & macrophages) 4. Type I epithelial reticular cells

*Provide protection to developing immature T cells T cell education

Ref – J B Kerr Thymus: Function

• The process of thymic cell education is promoted by substances secreted by the epithelioreticular cells, including interleukins (IL-4 and IL-7), colony-stimulating factors, and interferon. • Supports the proliferation and programming of T lymphocytes. • ERCs secretes the hormone thymosin and thymopoietin  stimulation, proliferation & differentiation of T cells

• Applied • Acute thymic involution – cause metabolic stress w/ pregancy, infection, surgery & malnutrition etc. • Myasthenia gravis Pancreas

• Soft, lobulated, fleshy, highly vascular organ • Location: Posterior abdominal wall, Retroperitoneal at L1 & L2 • Shape-retort shaped flask • Parts - Head, Uncinate process, Neck, Body and Tail • Body has 3 Borders -Ant., sup., inf. & 3 Surfaces - Ant., inf., post

Pancreas Visceral relation Duct system

Mixed gland : Pancreatic glands forms digestive secretions passes through duct system forms - Exocrine part Islets of Langerhans secrets hormones passes through blood , forms - Endocrine part Pancreas – Histology

• Gland covered by capsule – dense connective tissue • Septa divides into smaller lobules • Lobules contain compound tubuloalveolar acini forms exocrine part • Secretary part- Alveolus • Conducting part- Ducts • Islets of Langerhans forms - Endocrine part

T.S. of Pancreas (H&E) ( showing exo and endocrine part)

Serous acinous Inetrca lated duct

Connective tissue

Arteriole Pancreas – Islets of Langerhans

Lightly stained area

• Endocrine part of the pancreas made up of numerous collections of polyhedral group of cells embedded within the exocrine part of the pancreas, called as islets of Langerhans. • One million or more in number, more abundant in the tail of the pancreas. • Each islet is surrounded by thin layer of reticular tissue they are rich in its blood capillaries and nerve supply. Cells of Islets of Langerhans A D

B • Mallory Azan stain – • Alfa cells- stained with brilliant red , granules are dense, many, homogenous & round of size 300nm in diameter, lies at periphery. • Beta cells- brownish orange stained cells granules are less numerous, smaller, round & homogeneous of size 200nm, lies at center. • Delta cells- granules are round, homogeneous, larger than other cells. Cytoplasm is stained with blue color • PP cells- have no granules or very few granules

Islets of Langerhans

H&E stain. Gomori's trichrome stain islet of Langerhans showing alpha (A) cells and beta (B) cells. Cells of Islets of Langerhans

Cell Type Quanti Position Hormone Hormonal Function ty Produced Alpha 20% Usually in Glucagon • Increases blood glucose content periphery • Acts on several tissues to make energy stored in glycogen and fat available through glycogenolysis and lipolysis Beta 70% Central Insulin • Promotes decrease of blood glucose region content • Promotes glucose uptake by cells & muscle tissue • Is essential for normal cell growth & functions. Delta <5% Variable Somatostatin • Inhibits the activity of both alpha and beta cells Pancreatic Rare Variable Pancreatic • Inhibit enzymatic and alkaline pancreatic polypeptide polypeptide secretions Control of pancreatic hormones

Normal Blood sugar = 80-120 mg/ml Applied • Insulin-dependent or type I diabetes (juvenile diabetes) - results from partial or total destruction of B cells due to an autoimmune disease, the individual susceptibility to which is controlled by several genes. • Insulin-independent diabetes or type II diabetes - occurs at a later stage in life and is frequently associated with obesity.

• Tumors of islet cells may produce insulin, glucagon, somatostatin, and pancreatic polypeptide. Some pancreatic tumors produce two or more of these hormones simultaneously, generating complex clinical symptoms.

Pineal Gland Pineal Gland

• The pineal gland (pineal body, epiphysis cerebri) is neuroendocrine gland that regulates daily body rhythm. • Is a flattened, pine cone–shaped structure • Develops from neuroectoderm of the posterior portion of the roof of the diencephalon and remains attached to the by a short stalk. • Located at the posterior wall of the third ventricle near the center of the brain. • Photosensitive organ • Function: MELATONIN–amino acid derivative, have connection with regulating sleep cycle.

Microanatomy • • Modified neuron, arranged in clumps or of pineal gland. cords within lobules • large nucleus with prominent nucleoli • Cytoplasm contains melatonin granule • Interstitial (glial) cells - 5% of the cells • Supporting cells • closely resemble astrocytes and • Brain sand – • characterized by the presence of basophilic calcified concretions of , called corpora arenacea or brain BV sand • Number increases with age • Used as landmark in skull X ray brain sand Functions

• Melatonin may inhibit gonadotrophin release until puberty, preventing the onset of precocious gonadal function (precocious puberty).

• Melatonin regulates circadian rhythm MTF Regarding pancreas & thymus

F A Hassal corpuscles are seen in cortex F B Thymocytes secrete thymulin F C Alpha cells secrete somatostatin F D Insulin deficiency causes diabetes insipidus T E Islets contain abundant capillary networks

SEQ • Describe the islets of langerhans of pancreas

• Describe the microscopic structure of thymus gland

Thank You