Joankessler parkland

Male Reproductive System

The testis is the main organ of reproduction in males. It is involved in the production of sperm and testosterone. The accessory organs are the epididymis, ductus deferens (which convey the sperm from the testis to the prostatic part of the urethra) and penis (a copulatory organ).

During the passage of sperm from the testis to the penis, accessory glands like the seminal vesicle, prostate and bulbourethral glands provide a fluid vehicle for sperm and make them more motile.

Testis

The testes lie outside the body cavity in the scrotum. They are ovoid and measure approximately about 5 cm in length and 2.5 cm in diameter. Each testis weighs 10-15 g. The testis has a thick white fibrous connective tissue capsule called the tunica albuginea.

The tunica vasculosa is a highly vascularized connective tissue, which underlies the tunica albuginea.

• On the posterior border of the testis, the dense connective tissue of tunica albuginea projects into its interior and forms the mediastinum of the testis.
• Through the mediastinum, blood vessels, nerves and ducts of the testis enter and leave the organ.
• The connective tissue septa extend between mediastinum and tunica albuginea and divide the testis into about 250 compartments called as lobules
• Each lobule contains one to three tightly coiled tubules, the seminiferous tubules.
• Thus, each testis contains more than 500 seminiferous tubules. Each seminiferous tubule is about 30-70 cm long and about 200 cm in diameter.
• These tubules are sites where sperm are produced. Sperms are produced in these tubules.
• In between seminii- erous tubules, there is the presence of loose connective tissue (interstitial tissue) and blood vessels.
• The interstitial tissue contains endocrine cells, Leydig cells or interstitial cells, which produce testosterone.
• At the apex of the lobule, near the mediastinum, seminiferous tubules open into tubuli recti, which connect the open end of each seminiferous tubule to the rete testis.

Rete testis are epithelial-lined labyrinthine spaces within the mediastinum testis. The spermatozoa after passing through rete tesis travel through 10-20 short tubules known as efferent ducts. These efferent ducts fuse with epididymis.

Testis Remember:

The main function of testes is to produce spermatozoa and synthesize the hormone testosterone.

Microscopic Structure Of Testis

The testis consists of seminiferous tubules, interstitial tissue and blood vessels.

Seminiferous Tubules

Each seminiferous tubule is long and convoluted. It is surrounded by a layer of connective tissue called lamina pro-pria. This layer consists of flattened or spindle-shaped myoid cells arranged in one or more layers. The myoid cells are contractile and help spermatozoon and testicular fluid to move through seminiferous tubules. Deep into lamina propria is basal lamina.

A dense capiUan network surrounds each seminiferous tubule- A dense capillary network surrounds each seminiferous tubule. Deep into lamina propria is basal lamina. On the basal lamina, seminiferous tubules are lined by a complex stratified epithelium.

Which contains two major cell classes.  

1. Supporting cells and
2. Spermatogenic cells.

1. Supporting Cells (Sertoli Cells)

Sertoli cells are tall columnar cells, which extend from the basal lamina to the free surface of the epithelium (lumen of tubule). These cells have irregular outlines as they have lateral cell processes, which surround all spermatogenic cells except those resting on basal lamina. Sertoli cells are non-dividing cells in adults. They have ovoid euchromatic nuclei with one or more prominent nucleoli.

Sertoli cells Ultrastructure:

The Sertoli cells exhibit faint longitudinal striations.

• The cell has a meshwork of thin actin filaments, bundles of intermediate filaments and microtubules arranged parallel to the cell axis.
• These filaments and microtubules are involved in the change of shape of Sertoli cells that help in the movements of the germ cells toward the surface.

Sertoli cells Functions: 

Sertoli cells provide mechanical support to the spermatogenic cells.

• They provide nutrition to the spermatogenic cells.
• Sertoli cells form a blood-testis barrier, thus preventing the movement of extracellular molecules into the seminiferous epithelium.
• They also secrete some components of testicular fluid.

Blood-Testis Barrier:

Complex intercellular tight junctions are present between lateral processes of Sertoli cells over spermatogonia. The inter-sertoli junctions comprise a “blood-testis barrier” to prevent sperm-related proteins from entering the circulation.

The blood testis barrier serves an important role in isolating developing sperm cells and spermatozoa from the immune system. This prevents the formation of sperm-specific antibodies.

• These junctional complexes divide the seminiferous epithelium into two compartments, i.e., basal and luminal.
• The basal compartment is present between basement mem¬brane and junctional complexes. It contains spermatogonia and primary spermatocytes.
• In the luminal compartment, secondary spermatocytes and spermatids are present.
• The movement of primary spermatocytes from the basal com¬partment to the luminal compartment takes place by the formation of new junctional complexes beneath the primary spermatocytes.
• Once the secondary spermatocyte is formed then the junctional complex situated above the dividing pri¬mary spermatocytes break down and spermatocytes move to the luminal compartment.
• Thus, the junctional complexes separate the antigenic haploid germ cells (secondary spermatocytes, spermatids and sperms), which are present in the luminal compartment form the immune system of adults. This prevents the formation of sperm-specific antibodies.

Sertoli cells  Remember:

The Sertoli cells serve many functions, i.e., form the blood testis barrier; secrete androgen-binding proteins and hormones; provide support and protection to spermatoge¬nic cells, and provide nourishment to developing sperm. Sertoli cells also phagocytose cytoplasmic remnants of spermatids

2. Spermatogenic Cells

Besides Sertoli cells, the seminiferous tubules are also lined with spermatogenic cells. The spermatogenic cells are arranged as complex stratified epithelium and consist of stem cells (spermatogonia) at the base of the epithelium.

• The other cells at successively higher levels are primary spermatocytes, secondary spermatocytes, spermatids and spermatozoa. These cells are in different stages of differentiation of sperm.
• Thus seminiferous tubule consists of two different cell populations, i.e., Sertoli cells and a population of germ cells.
• The germ cells (spermatogonia) divide at the base of the epithelium and slowly move upward while they differentiate into spermatozoa.
• The spermatozoa are then released into the lumen of the seminiferous tubule.
• The spermatogenesis is under the control of pituitary hormones, luteinizing hormone (LH, ICSH) and follicle-stimulating hormone (FSH).

Interstitial Tissue and Blood Vessels:

In between the seminiferous tubules are many fenestrated capillaries, lymphatics, loose connective tissue and Leydig (interstitial) cells. The blood vessels apart from the usual function of blood supply, supply cooler blood to the testes.

• The heat of the testicular artery is partly dissipated by its proximity to the pampiniform plexus of veins, which carries cooler venous blood from the testis and surrounds the artery in the spermatic cord.
• The extra-abdominal scrotal position and dartos muscle also regulate the temperature of the testis.
• Leydig cells are 3-8 pm in diameter. They are acidophilic, polyhedral in shape and found in clusters. They secrete testosterone.
• Testosterone stimulates spermatogenesis by influencing the Sertoli cells. It also supports the structure and functions of the accessory sex organs and ducts.
• Testosterone is also responsible for male secondary sex characteristics.

Seminiferous tubules Remember:

Seminiferous tubules consist of complex stratified epithelium surrounded by a thin connective tissue layer, i.e., lamina propria. The epithelium is composed of two different types of cells, i.e., Sertoli cells and spermatogenic cells.

Mature Spermatozoon:

The mature spermatozoon is commonly considered to have a head, neck and tail

1. Head: The nucleus having condensed chromatin is covered in front by the acrosome. The acrosome is later released at the time of fertilization to disperse the corona radiata and digest the zona pellucida of the ovum.
2. Neck: It is a short segment containing the centriole that gives rise to the core of the flagellum (9+2). or axoneme.
3. Tail: The tail has 3 pieces, i.e., midpiece, principal piece and end piece. The mid piece is 5-7 urn in length. Here. 9 coarse fibres form a sheath around the flagellar core. Mitochondria become helically condensed around the sheath, which provides energy for sperm motility. The principal piece is about 45 pm in length. The axoneme and 9 coarse fibres are enclosed in a fibrous sheath. The end piece, 5-7 urn long, consists of axoneme enclosed by plasmalemma.

Spermatozoon Remember:

The spermatozoon consists of the head, neck and tail. The head consists of a nucleus while the tail is divided into three regions, i.e., midpiece, principal piece and end piece. The head is about 5 μm long, while the tail is approximately 55 μm in length.

Sperm Clinical Application

• Immotile Sperm: Sperms are highly motile in the female genital tract.
  • However, in a condition known as immotile cilia syndrome, sperm are unable to move from one place to another.
  • This results in infertility.
  • The immobility of sperm is due to the absence of protein (dynein) required for the motility of cilia and flagella. This also affects the cilia present throughout the body.
  • Thus, immotile cilia syndrome is also associated with chronic respiratory infections because of the presence of immotile cilia on the respiratory epithelium.
• Sperm-specific Antibodies: The secondary spermatocytes, spermatids and spermatozoa possess specific proteins, which are recognized as foreign by the body.
  • Usually, these proteins are isolated by the blood testis barrier.
  • However, in case of breakage of the immune barrier there occurs the formation of sperm-specific antibodies.
  • These antibodies agglutinate the sperms, thus preventing their movements. This leads to infertility.
  • This kind of infertility can be detected by estimating the level of anti-sperm antibodies in the blood serum.

Duct System

The duct system of the male reproductive organ consists of the following tubules or ducts.

1. Straight Tubule (Tubuli Recti)

• Straight tubules are the final portions of seminiferous tubules. The proximal part of the tubules is lined with simple columnar cells and Sertoli cells. The distal part is lined by simple cuboidal cells with microvilli.

2. Rete Testis

It consists of a system of flattened anastomosing channels in the dense connective tissue of the mediastinum that drains the straight tubules. The rete testis is lined by low cuboidal epithelium with microvilli and a single flagellum.

3. Efferent Ducts

• They collect the sperm from the testis. Efferent ducts consist of 12-15 coiled tubes that coalesce to form the head of the epididymis.
• The lumens of ducts are wavy in appearance.
• This is because these ducts are lined by alternating groups of simple ciliated columnar and groups of cuboidal cells. The cilia of columnar cells propel the still non-motile sperm.
• Cuboidal cells are probably absorptive.
• Beneath the base membrane, in lamina propria, a thin layer of circular muscle is present.

Duct system  Remember:

Tubuli recti (straight tubule) and rete testis are present within the testis and both are lined by low cuboidal cells with microvilli. The efferent ducts are interposed between the rete testis and epididymis.

4. Epididymis

Efferent ducts fuse to form this 20-foot-long, highly coiled tube, which can be divided into head, body and tail.

• The epididymis is placed at the posterior border of the testis. The whole organ and individual tubes are surrounded by vascular connective tissue.
• The lining of the tubule is the pseudostratified epithelium. It consists of low basal cells and tall columnar cells. The tall columnar cells are with long stereocilia.
• The function of epithelium is not well understood as stereocilia are non-motile. Probably, the epithelium is involved, both in secretion and absorption.
• The lumen of the tubule may show the collected sperms. Beneath the distinct basement membrane, lamina propria contains circularly arranged smooth muscle fibres.
• The smooth muscle helps to push the sperm along, especially in the proximal segment.

Epididymis  Functions

The epididymis is so long that it may take a month for sperm to make the journey.

• The distal or tail segment stores the sperms, where they mature and lose the last bit of cytoplasm attached to their head and middle piece and become motile, thereby acquiring the capacity to fertilize an ovum.
• Smooth muscle in the wall contracts rhythmically during ejaculation to move the sperm along.
• It also contributes a viscid nutritive substance.
• The epithelial cells of epididymis also phagocytose the degenerated sperms and residual bodies.

Epididymis Remember:

Epididymis is formed by the fusion of efferent ducts. It is a highly coiled tubule divided into head, body and tail. The tail of the epididymis is continuous with ductus deferens. Within the epididymis sperms are stored, mature and thereby acquire the capacity to fertilize an ovum.

5. Ductus Deferens

It is a thick muscular tube extending from the tail of the epididymis to the prostatic part of the urethra. It drains the epididymis.

The ductus deferens consists of the following layers in its wall:

• Mucosa: The lumen of the duct is irregularly star-shaped. The epithe¬lium is pseudostratified columnar with stereocilia and resembles that of epididymis. The lamina propria underlying the epithelium contains collagenous and elastic fibres.
• Muscle Layer: It consists of three layers of smooth muscle, i.e., outer and inner thin layers of longitudinal muscle and a well-devel¬oped thick middle layer of circular muscle. The muscle layer is very thick (1-1.5 mm) compared to the thickness of the mucosa.
• Adventitia: The adventitia is made up of loose areolar tissue, which contains many blood vessels and nerves. The terminal part of the ductus deferens is dilated to form an ampulla. Here, the mucosa is thrown into tall branching folds covered by a low columnar epithelium.

Ductus deferens Functions

1. The ductus deferens does not store sperm.
2. The duct is involved in rapid propulsion during ejaculation because of its strong musculature.

Ductus deferens Remember

The wall of the vas deferens consists of three layers of smooth muscle. This strong musculature helps in the propulsion of sperms from the tail of the epididymis to the ejaculatory duct during ejaculation.

Accessory Sex Glands

1. Seminal Vesicle

The seminal vesicles are elongated sac-like structures with a highly convoluted irregular lumen. Each gland consists of. single tube, about 3-1 mm in diameter, 12-15 cm m light,

Which is folded upon itself to measure about 5 cm in length. It joins with the ductus deferens to form an ejaculatory duct  The wall of the seminal vesicle is composed of the following three layers

• Mucosa: The mucosa is thrown into highly complex folds.
  • These folds join with each other to form many crypts and cavities.
  • The core of these folds is formed by connective tissue derived from lamina propria. The lamina propria is rich is elastic fibres.
  • The epithelium is pseudostratified low columnar or cuboidal. In some places, epithelium is simply columnar or cuboidal.
  • These cells are secretory. The epithelium varies greatly in height and appearance with activity, blood testosterone level and age.
• Muscle Layer: The muscle layer is made up of smooth muscle, which is thinner than that of ductus deferens. The muscle is arranged in two layers, i.e., inner circular and outer longitudinal. The contraction of the muscle at the time of ejaculation expels the secretion of the gland into the ejaculatory duct.
• Adventitia: A thin layer of loose connective tissue surrounds the muscle layer.

Seminal Vesicle Functions

• The gland secretes seminal fluid, which is a yellow viscous fluid containing fructose (an energy source for sperms) and prostaglandin.
• The seminal fluid is alkaline in nature.
• The pale yellow colour of semen is due to lipochrome pigment released by seminal vesicles.
• The gland is under the control of androgen. It helps to flush the sperm out of the urethra.

Seminal Vesicle Remember:

The seminal vesicle is not involved in the storage of sperm. It secretes a yellow viscous fluid that contains fructose and prostaglandin and constitutes about 70% of ejaculate.

2. Prostate Gland

The prostate is the largest of the accessory glands. It is about the size of the chestnut. It surrounds the first part of the male urethra after it emerges from the bladder.

• It is comprised of 20-50 tubulo-alveolar glands, which open by 15-25 ducts into the prostatic urethra. The stroma of the gland consists of fibromuscular tissue in which glandular tissue is embedded.
• Thus, the prostate is known as a fibro¬muscular glandular organ. The prostate gland is surrounded by a thick capsule.
• Three groups of glands surround the prostatic urethra concentrically, i.e., mucosal, sub-mucosal and main prostatic gland. The mucosal glands are small tubular glands situated in the mucosa, which open directly into the prostatic urethra.
• The submucosal glands are situated deep in the mucosa and are tubulo-alveolar type.
• The prostatic glands are situated in the outer zone of the prostate. Both submucosal and main prostatic glands open through long ducts into the prostatic urethra.
• The alveoli of the glands are surrounded by the fibromuscular stroma. The stroma consists of smooth muscle, collagenous and elastic fibres.
• The fibro-muscular stroma runs in different directions and contains blood vessels, lymph vessels and nerves. The glandular alveoli are of variable sizes and irregular lumens.

The epithelium lining the alveoli is secretory. It is either a simple columnar or a pseudostratified columnar.

• However, in some places, the epithelium may be low cuboidal. The variation in the epithelium (low cuboidal to pseudostratified co¬lumnar) is due to its functional state.
• In old people, the lumen of some of the gland alveoli may show the presence of prostatic concretions (corpora amylacea), which are oval-dense bodies of glycoproteins
• This results from to condensation of secretory products, which may become calcified. The significance of these bodies is not known.
• The prostatic urethra, above the opening of ejaculatory ducts, is lined by transitional epithelium. The lower part of the prostatic urethra is lined by stratified columnar epithelium
• . The epithelial lining is surrounded by lamina propria and outside by smooth muscle.

Prostate Gland Functions

• The prostate secretes 10-30% of final ejaculate.
• The fluid is thin and contains acid phosphatase, citric acid, amylase, fibrinolysin and prostate-specific antigen (PSA). Fibrinolysin helps in liquefication of semen.
• Prostatic secretion is facilitated by the contraction of smooth muscles of the stroma at the time of ejaculation.
• Prostatic secretion promotes the mobility of sperm.

Prostate Gland Remember:

Three groups of glands surround the prostatic urethra concentrically, i.e., mucosal, sub-mucosal and main prostatic gland. The prostatic secretion contains acid phosphatase, citric acid, amylase, fibrinolysin and prostate-specific antigen (PSA). Fibrinolysin helps in liquefication of semen.

Prostate Gland Clinical Application

• Enlargement of Prostate:
  • The glandular tissue of the prostate starts proliferating after 40-45 years of age in almost 50% of men. However, 80% of males are affected by 70 years of age.
  • The enlarged prostatic tissue compresses the prostatic urethra, which leads to difficulty in passing urine.
  • The disease is called benign prostatic hypertrophy. It can be treated by surgical removal of a part of the gland.
  • The malignant prostatic tumour is the second most common cancer in men. The tumour arises from glandular tissue of the prostate gland, hence called as adenocarcinoma of the prostate.
  • The level of PSA increases in cancer of the prostate and is used for early detection of cancer. In this case, complete removal of prostate is required.

Bulbourethral Gland

The bulbourethral glands (Cowper’s gland) lie in the urogenital diaphragm and empty into the proximal portion of the penile urethra  The gland is about the size of a pea. It discharges a mucus-like lubricant. It is a compound tubuloalveolar gland. The epithelium of the secretory part varies from simple cuboidal to simple columnar.

3. Bulbourethral Gland Clinical Application

• Semen: The semen contains spermatozoa and secretion of acces¬sory sex glands. The volume of the ejaculate is about 3 mL, 95% of which is secretions from accessory glands. The sperm concentration varies from 50 to 250 million/mL. A male whose sperm count is less than 20 million/mL of ejaculate is considered as sterile.
• The following glands contribute to the formation of semen:
  • Bulbourethral Gland: The secretion is mucus-like fluid, which acts as a lubricant. Secretion starts appearing much before ejaculation begins.
  • Prostate Gland: The secretion of the prostate coagulates the semen, which is later liquefied by fibrinolysin.
  • Seminal Vesicle: The secretion is rich in fructose, which provides energy to sperms.
• Impotence:
  • The inability to achieve an erection is called as impotence.
  • I Impotence may be temporary or permanent. The temporary impotence may be due to drugs or psychological factors.
  • The permanent impotence is due to lesions in the brain, hypothalamus, and spinal cord and injury to autonomic nerves.
  • It may be also due to various systemic diseases such as multiple sclerosis, Parkinson’s disease and diabetes

Bulbourethral Gland Remember:

Secretion of the bulbourethral gland acts as a lubricant and its release in the urethra is due to sexual stimulation.

Penis

The penis is an erectile copulatory organ. It is a common organ through which both semen and urine are discharged. The penis is made up of three cylindrical bodies of erectile tissue

The corpora cavernosa are placed dorsally while a single corpus spongiosum is placed ventrally.

• The urethra passes within the corpus spongiosum and opens at the tip of dilated part of the penis called as glans penis. The glans is covered with a fold of skin called a prepuce.
• In the shaft of the penis, each of the three erectile bodies is covered by a thick connective tissue sheath called the tunica albuginea.
• The tunica albuginea also fonus an incomplete partition between two corpora cavernosa. The tunica albuginea is covered with a layer of loose connective tissue and skin.
• A cross-section of the penis shows the following structures from superficial to deep. The most superficial structure is thin skin, which is devoid of any hair.
• Deep to the skin is the presence of a loose connective tissue layer, which is devoid of fat (adipose tissue). This layer of loose connective tissue is also called Buck’s fascia.
• It binds the tunica albuginea of all three erectile tissues with each other. Deep to this, the tunica albuginea covers all three erectile cylindrical bodies, i.e., two dorsal corpora cavernosa and one ventral corpus spongiosum.

The erectile tissue of the corpora is a sponge-like mass of endothelial-lined vascular spaces. The walls of these spaces are formed by numerous.

• Trabeculae consist of collagen fibres, elastic fibres and smooth muscle. These spaces are supplied by afferent arteries, which are branches of central deep arteries. T
• these spaces are drained to veins on the inner aspect of the tunica albuginea. They penetrate the tunica obliquely to join the deep dorsal vein of the penis.
• During the erection of the penis, blood fills the cavernous vascular spaces because of the vasodilation of arteries due to psychic and afferent sensory input.
• These spaces expand as they are filled with blood under pressure.

The peripheral veins are compressed against the inner surface of tunica albuginea, hence blood outflow diminishes considerably. This causes the erection of the penis. Erection is controlled by the parasympathetic nervous system, while ejaculation is controlled by the sympathetic nervous system

The corpus spongiosum is traversed by the penile urethra throughout its length. The urethra is lined by stratified columnar or pseudostate-tied columnar epithelium. The tip of the urethra, at the glans penis, is lined by stratified squamous non-keratinized epithelium. There are many small mucous glands of Eittre, which are scattered along the length of the urethra. They secrete mucus and have e lubricating function.

Penis Remember:

Filling of cavernous spaces (corpora cavernosa and cor¬pora spongiosum) with blood causes the erection of the penis.

Urinary System

The urinary system consists of two kidneys, two ureters, one urinary bladder and one urethra. Two kidneys produce urine, while ureters conduct urine from the kidneys to the urinary bladder, which stores the urine. The urethra drains the urine from the urinary bladder to the exterior.

Kidney Functions:

1. Excretion: The major function of the kidney is excretory, i.e., it eliminates the waste material (urea) and excess metabolites (electrolytes, water, glucose and amino acids). However, when these metabolites are not in excess it retains them by reabsorption.
2. Endocrine function: Kidney also has an endocrine function, i.e., it secretes renin (involved in the regulation of blood pressure and retention of sodium) and erythropoietin (regulates RBC production) in embryonic life.
3. Conversion of vitamin I) into calcitriol: Proximal convoluted tubules of the kidney are involved in the conversion of vitamin D into active hormone [calcitriol, l,25-(OH)₂
   vitamin DJ that regulates plasma calcium level.

To have a comprehensive understanding of the histological structure of the kidney, readers are advised to learn the gross structure of the kidney structure of nephron and the blood supply of the kidney.

Gross Structure Of Kidney

The naked-eye view of a hemisected kidney shows the outer cortex and inner medulla.

• The cortex lies just beneath the connective tissue capsule. The medulla is made up of 8-12 conical structures called pyramids.
• The cut face of the pyramid displays a striated appearance it consists of numerous parallel tubules and blood vessels.
• The broad base of each pyramid is directed toward the cortex and apex (renal papilla) facing into a minor calyx.
• There are about 8-12 minor calyces, which join to form two or three large extensions called major calyces.
• Major calyces unite to form a funnel-shaped renal pelvis, which is present at the hilus of the kidney. The renal pelvis becomes narrow and forms the ureter.

The cortex at the margin of each pyramid extends inward between the pyramids as renal columns. Some of the striated patterns from the base of the pyramid may extend into the cortex, which are called medullary rays. Each medullary ray is the collection of straight tubules and col¬lecting ducts extending in the cortex. A lobe of the kidney is defined as a renal pyramid with its overlying cortex and part of its laterally associated renal columns 

A kidney lobule is defined as a medullary ray with its laterally associated cortical tissue. Thus, a lobule consists of a col¬lecting duct and all the nephrons draining to it. As there are about 20,000 medullary rays in the cortex, approximately the same number of lobules are estimated to be present. The cortex of the kidney consists of about 2-3 million tubular structures called nephrons.

Kidney Remember:

The lobe of the kidney includes the renal pyramid with its overly¬ing cortex and parts of its later ally-associated renal columns, While on the other hand, the kidney lobule consists of the centrally placed medullary ray with its laterally placed cortical areas. Thus, the number of kidney lobes is equal to number of pyramids present in the kidney (i.e., 8-12). While, the number of kidney lobules is equal to the number of medullary rays present in the cortex (i.e., about 20,000).

General Structure Of Nephron

The functional unit of the kidney is (lie nephron. Bach nephron has several parts, i.e.,

1. Renal corpuscle
2. Proximal convoluted tubules
3. The loop of Henle and
4. Distal convoluted tubule.

1. Renal Corpuscle:

• The blind end of each nephron is expanded in the cortical region into a double-walled cup called Bowman’s capsule made up of an outer parietal epithelium and an inner visceral epithelium. The cup encloses a tuft of capillaries called a glomerulus.
• Bowman’s capsule and glomerulus together constitute the renal corpuscle. The renal corpuscle has two poles, i.e., the vascular pole (where arterioles arc present) and the urinary pole, from where proximal convoluted tubules take origin.
• An ultrafiltrate of the glomerular blood enters the space between two layers of Bowman’s capsule. The filtrate then passes to the proximal convoluted tubules.

2. Proximal Convoluted Tubule:

The proximal convoluted tubule is quite tortuous and begins at the Bowman’s capsule. It makes many convolutions in the cortex near the Bowman’s capsule from which it arises, it then enters the medullary ray and continues as the descend¬ing thick segment of the loop of Henle.

3. Loop of Henle:

The loop of Henle consists of a descending limb (both thick and thin segments), a hairpin turn and an ascending limb (thin and thick segments).

• The upper part of the descending limb is thick and is in continuation of the proximal convoluted tubule.
• The lower part of the descending limb is a thin segment, which is continuous with the hairpin turn.
• The ascending limb has a lower-thin and upper-thick segment. The thick segment ascends back into the cortex.

4. Distal Convoluted Tubule:

As the ascending thick segment of the loop of Henle comes close to the vascular pole of its originating renal corpuscle, it continues as distal convoluted tubules. After this, it makes many shorter loops in the cortex before it opens in the collecting tubule.

Two different types of nephrons are located in the cortex.

A nephron whose glomerulus is located adjacent to the base of the pyramid is called a juxtamedullary nephron. All other nephrons are called cortical nephrons.

• The collecting tubules are present in cortical tissue and drain into increasingly larger tubules called collecting ducts.
• A collecting duct travels first in the medullary ray and then in the pyramid to its apex.
• At the apex of the pyramid, several large collecting ducts open, which are called as ducts of Bellini. 
• A nephron, its collecting tubule and its collecting duct together form a unit called a uriniferous tubule.
• The nephrons are embryologically derived from metanephros while collecting tubules and ducts from the ureteric bud.

Nephron Remember:

The nephron is the functional and structural unit of the kidney. It consists of renal corpuscle (glomerulus and Bowman’s capsule), proximal convoluted tubule, loop of Henle and distal convoluted tubule that opens in collecting tubule. Each kidney contains about 2 million nephrons.

Relationship between Parts of Nephron and Zones of Kidney:

• Renal corpuscles are located at varying levels in the cortex and only in cortical tissue.
• Renal corpuscles close to the capsule (cortical nephrons) send their tubules down to the outer zone of the medulla.
• Renal corpuscles in the juxtamedullary area send their tubules deep into the inner zone of the medulla.
• Descending and ascending thick limbs occupy the outer zone, while the thin limbs occupy the internal zone almost to the apex of the pyramid.
• Thus, cortical tissue contains renal corpuscles, proximal and distal convoluted tubules and initial parts of collecting tubules.
• The medullary ray contains thick segments of the loop of Henle and collecting ducts. The medulla contains a thick and thin segment of the loop of Henle, vasa recta and collecting ducts.

The cortex of the kidney Remember:

The cortex of the kidney contains renal corpuscles, proxi¬mal and distal convoluted tubules and initial parts of the collecting tubules, while the medulla contains thick and thin segments of the loop of Henle, vasa recta and collecting ducts.

Renal Blood Supply of Kidney

The renal artery after entering the hilus of the kidney divides into a few segmental arteries, which in turn form interlobar arteries. Each interlobar artery runs between two pyra¬mids through the renal column.

• At the cortico-medullary junction (at the base of the pyramid), the interlobar arteries turn to arch over the base of the pyramid. These arteries are known as arcuate arteries.
• The arcuate arteries give off branches, which ascend into the cortex between lobules as interlobular arteries. These arteries are located between medullary rays.
• Many intralobular arteries arise from the interlobular artery and are called as afferent arterioles of glomeruli. They form the capillary network of glomeruli.
• Blood from glomeruli is drained by efferent arterioles. The efferent arterioles give rise to a second network of capillaries, which are called as peritubular capillaries
• The peritubular capillaries of cortical glomeruli surround the local uriniferous tubule and do not go into the medulla.
• However, the peritubular capillaries of juxtamedullary glomeruli descend into the medulla along with loops of Henle. In the medulla, they form capillary loops called recta before returning to the cortex. The ascending limb of the vasa recta forms the arterial limb, while its ascending limb forms the venous limb.
• The venous return from the peritubular capillary networks is via interlobular, arcuate, interlobar and renal veins.

Blood Supply of Kidney Remember:

Both kidneys receive large volumes of circulating blood, i.e., approximately 1000 mL of blood enters two kidneys each minute, from which about 125 mL/min glomerular filtrate is formed. Both kidneys form about 180 L of glomerular filtrate out of which only 2 L is excreted as urine while the remaining 178 L is reabsorbed by the kidneys.

Microscopic Structure Of Kidney

Following is the histological structure of various parts of the nephron i.e., renal corpuscle, proximal convoluted tubules, loop of Henle and distal convoluted tubule

1. Renal Corpuscle

It is also known as the Malpighian corpuscle. It consists of Bowman’s capsule and glomerulus. The Bowman’s cap¬sule has an outer parietal layer and an inner visceral layer  The parietal layer is lined by simple squamous epithelium, while the visceral layer is lined by podocytes. The space between the parietal and visceral layer is the urinary space (Bowman’s space), which receives the ultrafiltrate of blood. At the urinary pole, the space between two layers is continuous with the lumen of the proximal convoluted tubule. The squamous epithelium of the parietal layer at this pole becomes continuous with the cuboidal epithelium of the proximal convoluted tubule. The glomerulus is the tuft of capillaries fed by an afferent arteriole and drained by an efferent arteriole. Both these arterioles are present at the vascular pole of the renal corpuscle.

The visceral epithelium of Bowman’s capsule is closely applied to the endothelial lining of capillaries. The cells of the visceral layer become modified and are called Propodocytes and have many radiating processes, which in turn contain secondary processes, called foot processes or pedicels. The foot processes of neighbouring podocytes interdigitate with each other. These foot processes are separated from each other by narrow intercellular spaces that are called filtration slits. The gap of the filtration slit is occupied with a thin membrane called a filtration slit membrane or slit membrane

Ultrastructure of Filtration Barrier:

The endothelial cell layer and podocyte cell layer (visceral layer of Bowman’s capsule) share a common fused basal lamina. The foot processes of podocytes are closely applied to the common basal lamina.

The filtration barrier is made up of three components

1. Fenestrated Endothelium: The pores of capillary endothelial cells are about 70-90 nm in diameter. These pores are not spanned by a pore diaphragm and allow the passage of molecules up to 70,000 molecular weight. Endothelial cells of glomerular capillaries possess a large number of aquaporin-1 (AQP-1) water channels, which allow fast filtration of water through the endothelium.
2. (Glomerular basement Membrane: It consists of fused basal lamina of endothelium and visceral layers of Bowman’s capsule (podocytes). It is made up of type 4 and 8 collagens, proteoglycan and glycoproteins. It forms the major unit of barrier and serves to retain the necessary plasma proteins from leaking out.
3.  Filtration Slit Membrane (diaphragm): It spans between adjacent foot processes of podocytes and measures 25 nm in width and 4-6 nm in thickness. The slit diaphragm is formed by a transmembrane protein called nephrin. Nephrin proteins emerge from opposite foot processes and form a central density, which has pores. Mutation in the nephrin gene leads to congenital nephritic syndrome which is characterized by proteinuria. This membrane shows the presence of small pores, which prevent the passage of albumin and large molecules from the blood to glomerular filtrate.

Filtration Barrier Remember:

The glomerular filtration barrier is formed by the fenestrated endothelium of glomerular capillaries, glomerular basement membrane and visceral layer of Bowman’s capsule, which consists of epithelial cells that become modified and are called podocytes. The foot processes of neighbouring podocytes interdigitate with each other and contain gaps, which are known as filtration slits. The gap of the filtration slit is occupied with a thin membrane called a filtration slit membrane or slit membrane. This slit membrane acts as a part of the filtration barrier. Thus, the filtration barrier consists of endothelial cells, fused basal lamina and a filtration slit.

Process of Glomerular Ultrafiltration:

Fluid first passes through the pores of capillar}’ endothelial cells then it is filtered by the basal lamina.

• Fluid containing small molecules, ions and macromolecules passes through lamina densa and pores in slit diaphragm of filtration slits.
• If molecules are small (<1.8 nm) and are un¬charged then they pass easily through the slit diaphragm. However, large molecules cannot pass through the slit diaphragm.
• The large molecules, which are unable to cross the barrier are rapidly removed by the intraglomerular mesangial cells, otherwise, the basal lamina will get clogged with these large molecules. The fluid, which after passing through bar¬riers reaches the Bowman’s space is called the glomerular ultrafiltrate.

Mesangial Cells:

The capillaries of the glomerulus are held together by mesangium (mesangium = between vessels). Mesangial cells are of two different types, i.e., extraglomeru lar and intraglomerular. Extraglomerular cells are located at the vascular pole, while intraglomerular cells are located within the renal corpuscle.

Mesangium is a connective tissue consisting of mesangial cells in an extracellular matrix. These cells are most numerous near the vascular pole of the renal corpuscle. Mesangial cells correspond to the pericyte and may be enclosed by the basal lamina of the glomerular capillaries.

They have many functions:

1. Their phagocytic function helps to remove large protein and filtration residues from the glomerular basal lamina. Thus, the integrity of the filter is maintained.
2. They participate in the turnover of basal lamina.
3. Mesangial cells are contractile, thus regulating the glomerular filtration rates.
4. Mesangial cells synthesize and secrete interleukin-1 and platelet-derived growth factor (PDGF).
5. The} provides structural support to podocytes.
6. Mesangial cells proliferate in certain types of nephropathy.

Juxtaglomerular Apparatus:

This is an apparatus present near the vascular pole of a renal corpuscle and helps in maintaining blood pressure. The macula densa, Juxtaglomerular cells and extra mesangial cells constitute the juxtaglomerular apparatus

• Macula Densa: These are specialized cells at the beginning of the distal convoluted tubule that lie adjacent to afferent and efferent arterioles at the vascular pole of the corpuscle.
  • These cells are narrow, columnar and crowded together.
  • Cells of macula densa can sense a low sodium concentration of urine in the distal convoluted tubules and help in the release of renin.
• Juxtaglomerular Cells: The smooth muscle cells in the wall of afferent arteriole (and sometimes in efferent arterioles also), which lie close to macula densa, become modified to form juxtaglomerular cells.
  • These cells contain secretory granules and no myofilaments.
  • They secrete renin hormone, which increases blood pressure. (Renin breaks the angiotensinogen of blood plasma into angiotensin 1, which subsequently is broken down to angiotensin 2 in the lungs. Angiotensin 2 raises the blood pressure by its vasoconstriction activity and controls the glomerular filtration.)
  • It also stimulates the synthesis and release of aldosterone, which in turn acts on collecting ducts to increase the reabsorption of sodium and water.
  • This leads to a further rise in blood volume and blood pressure.
  • Thus, the juxtaglomerular apparatus regulates blood pressure by activating the rennin-angiotensin-aldosterone system.
• Extraglomerular Mesangial Cells: These cells are present in the space between the distal tubule, and afferent and efferent arterioles at the vascular pole of the corpuscle.
  • These cells have receptors for angiotensin 2 and may regulate the glomerular filtration rate.
  • These cells connect the sensory cells of macula densa with the juxtaglomerular effector cells and transmit the signals through gap junctions.
  • They also send signals to the contractile mesangial cells for vasoconstriction within the glomerulus.

Juxtaglomerular apparatus Remember:

The juxtaglomerular apparatus consists of macula dense (which are specialized cells in the beginning of the distal convoluted tubule that lie adjacent to afferent glomerular arterioles), juxtaglomerular cells, (which are smooth muscle cells in the wall of afferent arteriole) and extraglomerular mesangial cells.

The cells of macula densa are specialized to detect the low concentration of sodium and volume of glomerular filtrate in the distal tubule. This leads to the release of renin by juxtaglomerular cells causing the conversion of angiotensinogen to angiotensin 1 which is subsequently converted to angiotensin 2. Angiotensin 2 is a potent vasoconstrictor and helps in the release of aldosterone.

Kidneys Clinical Application

Glomerulonephritis, Filtration Barrier and Proteinuria:

• If kidneys are infected by bacteria, glomeruli are highly affected.
• The urine of a healthy person does not contain protein because the molecules of protein are too large to pass through filtration barrier.
• However, in diseases like glomerulonephritis, the filtration unit (basal lamina of capillaries) may get damaged and large amounts of protein and RBCs can leak into the urine from the blood.
• The presence of protein in urine is known as proteinuria, while the appearance of blood (RBCs) in urine is called haematuria.
• The leakage of protein results in low protein levels in the blood. This causes a collection of fluid in tissue and widespread swelling.
• Proteinuria may also occur in diseases like diabetes mellitus due to damage to the filtration unit of the kidney.

Kidney Failure and Dialysis:

Kidney failure results from the loss of normal function of both kidneys due to a variety of causes, i.e., fall in blood pressure, infection, glomerulonephritis, toxic chemicals, drugs, diabetes mellitus, etc.

• In kidney failure, kidneys are unable to remove waste products and excess water from the blood, thus disrupting the chemical balance of the blood.
• Methods of treatment of kidney failure may include drugs, dialysis or kidney transplant.
• Dialysis is the procedure in which the functions of the kidney (removal of wastes and excess water from the blood) are performed by a machine.
• Each dialysis treatment takes about 3-4 hrs and has to be repeated 3 times a week.

2. Proximal Convoluted Tubule

If starts from the urinary pole of a renal corpuscle and extends up to a thick portion of the descending limb of Henle. This part of the tube is 60 m in diameter and complexly coiled (convoluted). The length of the proximal convoluted tubule is almost double that of the distal convoluted tubule. It is present in the cortex only.

The tube is lined with simple cuboidal or low columnar epithelial cells. These tubules have small uneven lumen (Fig. 17.9 and 17.12). There is the presence of a brush border formed by tall microvilli on the apical surface of cells. Nuclei are round and centrally placed. The cytoplasm stains deeply with eosin. The basal part of the cell may show vertical striations, due to the presence of mitochondria.

Proximal Convoluted Tubule Ultrastructure:

• The electron micrograph of cells of proximal convoluted tubules shows the features that indicate that these cells are involved in absorption and transport.
• The presence of microvilli lateral and basal infoldings of plasma membrane increases the surface area of cell for absorption and transport.
• The presence of mitochondria between basal folds provides for the high-energy requirements needed for active transport.
• Fluid and absorbed substances return to the fenestrated blood capillaries present adjacent to proximal convoluted tubules.

Proximal tubules Functions:

1. In proximal tubules, there occurs reabsorption of 80% of salts (Na and Cl), water (85%)
2. Most amino acids, ascorbic and lactic acid (100%), filtered proteins, glucose and bicarbonate
3. The remaining molecules and fluids are removed in the other portions of the nephron.

3. Loop of Henle

The proximal convoluted tubule continues downward into the medullary ray and medulla as the loop of Henle.

• The histological structure of the thick descending limb of the loop of Henle is similar to that of the proximal convoluted tubule.
• The descending and ascending thin limbs of the loop are about 15 m in diameter and are lined with squamous epithelial cells bearing few microvilli. The cytoplasm is pale staining, nuclei bulge into small lumen.
• The thin limb resembles a venule in cross-section. The histological structure of the thick ascending limb of the loop of Henle is similar to that of the distal convoluted tubule (see below).

Loop of Henle Ultrastructure:

The thin limb of the loop of Henle is lined by squamous epithelium bearing a few’ short microvilli. The presence of very few organelles (including mitochondria) and very few infoldings of plasma membrane indicates that these cells are only involved in the passive transport of fluid and salts.

Loop of Henle Functions:

• The loop of Henle is the essential element in the production of hypertonic urine.
• The thin descending limb is permeable in both water and salt.
• In contrast to this the thin ascending limb is permeable to salt but not to water.

4. Distal Convoluted Tubule

As the distal convoluted tubule is half the length of the proximal convoluted tubule few distal tubules are seen in a microscopic field. The diameter of the distal tubule is less as compared to proximal tubules (15-30 μm). The tubules are lined by cuboidal epithelium.

The cytoplasm of cells stains light eosinophilic. The brush border is not present and the height of cuboidal cells is short (5 μm). These two facts are responsible for the large regular lumen of distal tubules.

Differences between proximal and distal convoluted tubules:

The differences between proximal and distal convoluted tubules are presented in Table

Distal Convoluted Tubule Ultrastructure:

• The cells of distal convoluted tubules show very few short microvilli, but lateral and basal infoldings of the plasma membrane are very prominent.
• The mitochondria are oriented parallel to the long axis of the cell.
• All these features indicate that cells are involved in the active transport of ions.

Distal Convoluted Tubule Functions:

• It is involved in the reabsorption of salt, water and bicarbonate. The distal tubule also secretes potassium and hydrogen ions.
• The distal convoluted tubule is under the control of an antidiuretic hormone, which promotes the reabsorption of water and salts

4. Collecting Tubules

Collecting tubules begin in the cortex and proceed to the medullary ray where they join the larger collecting tubules called as collecting ducts. These ducts in the medulla run toward the apex of the pyramid and join each other to form the duct of Bellini. Collecting tubules are about 40 pm in diameter while ducts are much wider.

Both tubules and ducts are lined by cuboidal to low columnar epithelium. The brush border is not present and cells are lightly stained with eosin. The cell outline is clear and both, tubules and ducts, have a much larger lumen

 Collecting Tubules Ultra Structure:

Collecting tubules and ducts are lined by two kinds of cells, i.e., principal and intercalated cells. Most of the lining cells are principal cells, which are wide, low columnar. They have few organelles, lateral and basal infoldings of the plasma membrane and several mitochondria. Intercalated cells are few and they have microvilli and basal infoldings.

Collecting Tubules Functions:

The function is the concentration of urine by sail-free water re-absorption that occurs under the influence of ADH. The result is hypertonic urine.

• The light microscopic structure of the cortex of the kidney: A section from the cortex of the kidney shows the glomeruli, proxi¬mal and distal convoluted tubules, blood vessels and col¬lecting tubules.
• The light microscopic structure of the medulla of the kidney: A section from the medulla of the kidney shows the thick and thin segment of the loop of Henle, collecting ducts and blood ves¬sels (capillaries).

Ureter

The ureter is a tube with a star-shaped lumen varying in length from 25 to 35 cm. It conducts urine from the renal pelvis to the urinary bladder. The following three layers comprise the wall of the ureter

1. Mucosa
2. Muscle layer
3. Adventitia

The mucosa consists of lining epithelium and lamina pro-pria. The epithelium is transitional and is 4-5 cells thick. The lamina propria is wide and made up of loose connective tissue. Blood vessels and lymphatics are present in it.

The muscle layer consists of an inner longitudinal and outer circular layer of smooth muscle fibres. In the middle and lower partial ureter, a third outer layer of longitudinal smooth muscle is also present.  these three layers of muscle arc are not well defined and are difficult to mark off front of each other. The outermost layer (adventitia) is made up of loose connective tissue and contains many blood vessels, nerves and fat cells.

Kidney Stones Clinical Application

Calcium salts and uric acid are excreted In the glomerular filtrate. These salts are less soluble in water The water is reabsorbed from the glomerular filtrate to concentrate the urine Kidney stones occur when urine is saturated with these salts. These salts tryst into stone-like structures. Kidney stones can take years to form These stones are usually formed in the renal pelvis. A small stone may dislodge from the kidney and may pass to the ureter where it may cause severe pain.

Urinary Bladder

Following are the layers in the wall of the urinary bladder

1. Mucosa
2. Muscle layer
3. Serosa/Adventitia

The mucosa is made up of transitional epithelium and lamina propria. The empty bladder shows many mucosal folds and epithelium increases in thickness up to eight cell layers.

• The superficial cell layer takes dark eosinophilic stains due to the presence of plaques. Plaques are modified areas of the plasma membrane.
• These plaques are more rigid and thicker than the rest of the apical plasma membrane (interplaque region). Plaques give attachment to actin filaments on their inner surface. The functional significance of these plaques is not known.
• Probably, these plaques act as osmotic bar¬rier to water and salts.
• When the bladder is filled, the mucosal folds disap¬pear and the epithelium becomes thin to about 3-4 cells. The lamina propria is made up of moderately dense con¬nective tissue. It may occasionally show small lymphatic nodules among the blood vessels and lymphatics.
• The thick muscle coat is made up of smooth muscle fibres running in all directions. Between the bundles of muscle fibres is loose connective tissue.
• Although the three muscle coats, i.e., transverse, longitudinal and oblique are described, these layers are difficult to distinguish. In the region of trigone, the mucosa is thin and directly applied to the muscle layer.
• The superior surface of the bladder is covered by serosa (peritoneum) while all other surfaces are covered with tu¬nica adventitia.

Urinary Bladder  Clinical Application 

Bladder Tumours and Bladder Stones

• Tumours in the bladder may be either non-cancerous or cancerous.
• The tumour starts growing from the epithelial lining of the bladder and projects into the cavity of the bladder.
• The bladder is also a very common site for the formation of stones.
• Stones are formed because of the crystallization of waste products present in urine.

Urethra

The male urethra is long and consists of prostatic and penile urethra. The male urethra is described along with prostate and penis (see male reproductive system).

The female urethra is short (about 3 cm long) and near the bladder, it is lined by transitional and in the middle portion by pseudostratified columnar epithelium.

• Near the external opening, it is lined by stratified squamous epithelium.
• The submucosa consists of loose connective tissue, which contains many venous plexuses and elastic fibres.
• The muscle coat consists of an inner longitudinal and an outer circular coat of smooth muscle fibres.
• At the terminal end, the urethra is surrounded by skeletal muscle fibres, which constitute the external sphincter.

Female Reproductive System

The female reproductive system comprises the external genitalia and internal organs. The external genitalia consists of labia majora, labia minora, vestibule and clitoris. As the functions of mammary glands are closely associated with the reproductive system, it is considered an accessory reproductive organ.

The internal reproductive organs are listed below :

• Ovaries: These are exocrine organs. They produce maturing ova (secondary oocytes), which are discharged and passed into the uterine tubes where they may be fertilized. The ovaries are also endocrine organs because they produce hormones like progesterone and estrogen.
• Uterine Tubes: The uterine tubes or oviducts transport secondary oocytes where they may be fertilized. The fertilized or unfertilized ova are then transported to the uterus.
• The Uterus: The development of embryo and fetus occurs in the uterine cavity.
• Vagina: It is a fibromuscular organ, which gives passage to the fetus at the time of birth.
• Placenta and Umbilical Cord: These are accessory reproductive organs through which a mother can nurture a fetus until the time of parturition. Placenta is also a major endocrine organ, which produces hormones, i.e… chorionic gonadotrophin and progesterone.
• Mammary Glands: These are also considered to be part of the accessory female reproductive system.

 Female reproductive organs Remember:

The female reproductive organs, under the influence of hormones, undergo regular cyclic changes from puberty to menopause.

Ovary

The ovaries are almond-shaped paired structures, each attached to a broad ligament on either side of the uterus. Each ovary measures about 3 cm in length, 1.5 cm in width, and 1 cm in thickness.

Each ovary consists of the following parts:

• Germinal epithelium: The surface of the ovary is covered with a single layer of low cuboidal or squamous epithelium that is called germinal epithelium. The term germinal epithelium is a misnomer because it does not give rise to germ cells (ova).
• Tunica albuginea: A connective tissue layer lies beneath the germinal epithelium, i.e., the tunica albuginea. A cross¬section of the ovary shows an outer cortex and inner medulla
• Cortex: It is the peripheral portion of the ovary, which lies beneath the tunica albuginea. It contains germ cells (oocytes) in ovarian follicles.
  • The ovarian follicles arc in various stages of development in highly cellular connective tissue (stroma).
  • The connective tissue cells are known as stromal (interstitial) cells.
  • Their structure is like fibroblasts. The primordial follicles are found in large numbers deep into tunica albuginea.
  • The growing follicles (primary and secondary follicles) show stratified follicular cells. Few mature follicles with follicular fluid are also present in the cortex.
  • Theca externa and theca interna surround large-sized follicles.
  • At certain places in the cortex, atretic follicles and corpus luteum can be seen.

• Medulla: It is present deep in the cortex and consists of loose fibroblastic connective tissue, lymphocytes, blood vessels, and nerves. The demarcation between cortex and medulla is indistinct.

Ovary Remember:

The ovary, deep to tunica albuginea, shows an outer cortex and inner medulla. The cortex contains highly cellular connective tissue (stroma) and germ cells (oocytes) in ovarian follicles. The ovarian follicles are in various stages of development.

Ovarian Follicles

A section passing through the cortex of the ovary shows the ovarian follicles in different stages of development. An ovarian follicle consists of centrally placed oocyte and peripherally placed surrounding cells. When an oocyte is surrounded by a single layer of cells, these cells are called as follicular cells. When these cells multiply to form several layers, they are called granulosa cells. The following developmental stages of ovarian follicles are seen in the ovarian cortex of an adult reproductive female.

1. Primordial Follicle:

The primordial follicle consists of a developing ovum (primary oocyte) surrounded by a single layer of flattened epi-thelium (follicular cells). A large number of primordial follicles are found in the stroma of the cortex just beneath the tunica albuginea. The oocyte measures about 25-30 m in size and its plasma membrane is in close contact with follicular cells.

2. Primary Follicle:

After puberty, a few primordial follicles start to grow during each menstrual cycle. The oocyte enlarges and measures about 50 to 80 m.

• The surrounding single layer of lint-tened cells changes to low cuboidal.
• Oocyte and follicle cells now secrete a gel-like glycoprotein layer surrounding the oocyte.
• This is called zona pellucida.
• These single-layer cuboidal-shaped follicular cells divide rapidly to form six to seven layers of cuboidal cells called granulosa cells.
• The outermost cells rest on a well-defined basement membrane, which is separated from the ovarian stroma.

The surrounding stroma now differentiates into two layers:

1. Theca interna, a highly vascular layer of secretory cells and
2. Theca externa is the outer layer of connective tissue cells. It mainly contains smooth muscle cells and collagen fibers.

The follicle is now called as primary follicle

3. Secondary Follicle:

The granulosa cells begin to secrete follicular fluid, thus few small fluid-filled spaces appear between follicular cells. Now diameter of the follicle measures about 0.2 mm and the oocyte measures 125 m. These spaces now coalesce into a single large space (antrum) surrounded by follicular cells. The antrum is filled with a fluid. The follicle is now called a secondary follicle.

4. Graafian Follicle (Mature Follicle):

The follicle now increases in size and its antrum also enlarges. It measures about 10 mm or more. The primary oocyte completes its first meiotic division and becomes a secondary oocyte. The secondary oocyte starts its second meiotic division and reaches the metaphase stage at about the time when the follicle bursts and releases its secondary oocyte. This process is called ovulation. The theca interna further develops and produces estrogen. Similarly, granulosa cells are also involved in the production of ovarian hormones.

The follicle in which the above events are taking place is called as Graafian follicle or mature follicle.

Primordial follicle Remember:

A primordial follicle consists of a developing ovum (pri¬mary oocyte) surrounded by a single layer of flattened epithelium (follicular cells).

• In the development of primary follicles, follicular cells divide rapidly to form 6-7 layers of cuboidal cells called granulosa cells.
• The surrounding stroma now differentiates into two layers, i.e., theca interna and theca externa.
• In the secondary follicle, there occurs the accumula¬tion of liquor folliculi among the granulose cells.
• A mature follicle or Graafian follicle is formed by the continued proliferation of granulosa cells and continued formation of liquor follicle until its size just before ovulation reaches about 1 cm or more. This follicle contains the secondary oocyte.

Corpus Luteum

After ovulation, the wall of the follicle collapses and becomes infolded. The blood vessels and stromal cells now invade the granulosa cells. The granulosa cells and theca interna cells enlarge, accumulate lipids,s and become pale-staining luteal cells. The structure is now called as corpus luteum, which is now a spherical body.

Two kinds of lutein cells are seen in the corpus luteum:

1. Those arising from granulosa cells are called granulosa lutein cells and they form the bulk of corpus luteum and form progesterone.
2. Those arising from theca interna cells are called theca lutein cells.

They are much smaller, less in number, and deeply staining and are found at the periphery. They secrete estradiol. Cells of theca externa form a capsule. If fertilization takes place then the corpus luteum will survive for the next few months. But if fertilization does not take place then corpus luteum will last for only 9 days.

When the corpus luteum degenerates, the lutein cell becomes swollen, thin, and pyknotic and a scar of connective tissue replaces the dead lutein cells. This white scar is called corpus albicans. The corpus albicans persist in the cortex for several months.

Atretic Follicles

For each menstrual cycle usually only one follicle reaches maturity and ovulates. The other maturing follicles, in various stages of development, start to degenerate. This process of regression and ultimate degeneration and disappearance of follicles is called follicular atresia.

After ovulation, the wall of the collapsed follicle undergoes reorganization to form the corpus luteum.

Two kinds of lutein cells are seen in the corpus luteum, i.e.,

1. Granulosa lutein cells (they form progesterone) and
2. Theca lutein cells (they form estradiol).

If fertilization takes place then the corpus luteum will survive for the next few months.

• However, if fertilization does not take place then corpus luteum will last for only 9 days.
• In the process of follicular atresia, the vascular connective tissue from theca invades the membrane granulosa and antrum, the granulosa cells and oocyte degenerate, and wrinkled zona pellucida remains for some time.
• The base membrane under the membrane granulosa and cells of the theca interna enlarge.
• The basement membrane becomes a distinct glossy membrane and theca cells look like theca lutein cells.
• The follicle eventually disappears as the ovarian stroma invades the degenerating follicle.

The primary oocyte is arrested for 12-50 years in the prophase stage of the first meiotic Division. Just before ovulation, the secondary oocyte is also arrested at metaphase in the second meiotic division which is completed only if the oocyte is penetrated by a spermatozoon.

Ovary Clinical Application

• Polycystic Ovary:
  • In this condition, both the ovaries consist of fluid-filled follicular cysts and atrophic secondary follicles that lie beneath the thick tunica albuginea.
  • This condition may result due to excessive production of estrogens; failure of ovulation; and absence of progesterone production due to failure of the follicle to transform into corpus luteum.
  • Females suffering from polycystic ovaries are infertile and have scanty menstruation. These patients can be treated by hormones.

Uterine Tube (Fallopian Tube)

Passing from the open end to the uterine cavity, there are four different regions of the uterine tube: the infundibulum, ampulla, isthmus, and interstitial portion in the wall of the uterus. These regions differ according to the size of their lumina and the relative thickness of their wall. The ovum is received by the uterine tube for fertilization in its ampullary part. From here, it is transported to the uterine cavity.

The uterine tube consists of the following layers :

1. Mucosa

The mucosa of all regions is lined by simple ciliated colum¬nar epithelium and peg-shaped noil-ciliated secretory’ cells. The size and activity of these two types of cells vary depending on the level of estrogen and progesterone (stage of the menstrual cycle).

• The lamina propria is made up of richly vascularized loose connective tissue. Peg cells have secretion functions.
• Their secretion provides nutrition and a protective environment for spermatogonia. The secretion also helps incapacitation of spermatozoa. a process by which spermatozoa become fully mature and capable of fertilizing the ovum.
• It also provides nutrition to fertilize the egg as it travels through the uterine tube, and the cilia of columnar ciliated cells beat towards Lucius. This helps in the movement of the zygote toward the uterus.
• Because of the presence of branching mucosal folds (leaf-like structure). the lumen of the uterine tube is highly irregular. The mucosal foldings are maximum in the ampullary nan and minimal in the interstitial part of the tube.

2. Muscle layer:

This is present in two distinct layers, i.e., inner circular and outer longitudinal. The thickness of the muscle coat increases from the lateral end to the medial end of the tube (from the infundibulum to the interstitial portion).

3. Serosa: It is the peritoneal covering of the broad ligament.

Uterine tube Remember:

The wall of the uterine tube consists of three layers, i.e., mucosa, muscle coat, and serosa. The mucosa is lined by simple ciliated columnar epithelium and peg-shaped non-ciliated secretory cells.

Uterus

The uterus is a pear-shaped organ divided into three parts, i.e.. fundus, body, and cervix. The nulliparous uterus measures 7.5 cm in length, 5 cm in width, and 2.5 cm in thickness. During pregnancy, it increases tremendously in size. The uterine wall of the fundus and body consists of three layers, i.e., perimetrium, myometrium, and endometrium . The histology of the cervical part of the uterus is different and will be described separately.

1. Perimetrium:

This consists of two layers a mesothelial lining and a connective tissue layer rich in blood vessels and elastic fibers. This is the continuation of the peritoneum of the broad ligament.

2. Myometrium: It is the thickest layer of the uterus. It consists of compactly arranged smooth muscle bundles, which are arranged in three ill-defined layers.

• The inner and outer layers of muscle fibers are arranged longitudinally.
• The middle layer is a thick layer of circularly or spirally arranged muscle fibers. This layer contains large blood vessels and interstitial connect-live (issue.
• The myometrium undergoes considerable enlargement of during pregnancy.
• This is due to the hypertrophy of existing muscle lilacs and the addition of new smooth muscle fibers.
• New smooth muscle fibers are produced by the division of existing muscle cells and differentiation of mesenchymal cells.
• These changes occur under the influence of estrogen.

3. Endometrium:

• This is the mucosal lining of the uterine cavity.
• It consists of simple columnar secretory epithelium overlying thick lamina propria.
• Simple tubular glands are present in lamina propria, which open directly to the surface.
• These glands are usually coiled in deep portions. Hence, many cross-sections of glands are seen in the deep part (near the myometrium).
• Coiled (spiral) arteries are present in between the glands.

The endometrium can be divided into two zones:

A narrow 1/3 deep layer is called as basal stratum (stratum basalis) and a wide 2/3 superficial layer called as functional stratum (stratum functionalis).

Uterus Remember:

The uterine wall of the fundus and body consists of three layers, i.e., perimetrium, myometrium, and endometrium. The endometrium is the mucosal lining of the uterus.

• It consists of two layers:  A narrow 1/3 deep layer is called stratum basalis and a wide 2/3 superficial layer is called stratum functionalis. The stratum functionals of endometrium proliferate and then degenerate during each menstrual cycle

Cyclic Changes in Endometrium:

The endometrium undergoes monthly cyclic changes in its thickness and histological appearance. These changes are under the control of ovarian hormones. The cyclic changes of the endometrium are divided into three phases.

• Follicular Phase (Proliferative Phase): It coincides with the secretion of estrogen from developing follicles in the ovary. It extends from day 4 to day 14 of menstrual cycle. It is also known as the pre-ovulatory phase as ovulation occurs on day 14 of the menstrual cycle.
• Secretory Phase: It coincides with the secretion of progesterone by corpus luteum. It correlates with day 15 to day 28 of the menstrual cycle.
• Menstrual Phase (Menses): If the ovum is not fertilized the shedding of the superficial endometrium (functional stratum) occurs along with loss of blood.
  • The stratum basale remains intact.
  • This phase occurs because of the cessation of the selection of progesterone by corpus lutcum.
  • This phase lasts for roughly the first 5 days of the cycle. The first day of menstruation is considered the first day of a new cycle.

Histological Structure of Endometrium in Different Phases

1. The Endometrium of the Proliferative Phase:

This phase begins at the end of the menstrual phase (on about 511 days of the cycle). In this phase, there occurs the repair of damaged endometrium by the proliferation of cells in the stratum basale. There appear new surface epithelium and stroma, and blood vessels and glands begin to grow by numerous mitotic divisions.

At the end of this phase:

• The thickness of the endometrium is about 3-4 mm.
• The stroma is abundant and highly cellular. It consists of fibroblast cells, a few collagen fibers, and a network of reticular fibers.
• The endometrial glands are straight and have narrow lumen with a slightly wavy’ appearance.
• Spiral arteries are now long reaching up to the middle of the endometrium. They are slightly coiled.

2. The Endometrium of the Secretory Phase:

The endometrium now comes under the influence of progesterone secreted by the corpus luteum. The endometrium becomes thicker and measures about 6-7 mm. The increase in thickness is due to the collection of fluid (edema) in the stroma.

• The endometrial glands show increased secretory activities and because of this they become more tortuous and acquire lateral sacculation.
• Thus, in a section, the lumen of glands is dilated because of the accumulation of large quantities of secretory products.
• The spiral arteries are highly coiled and now extend throughout the endometrium, i.e., up to the superficial part.
• The above changes are seen in stratum functionale. Very little change takes place in the stratum basale.

3. The Endometrium of the Menstrual Phase

This phase results because of necrosis of the endometrium secondary to constriction of coiled arteries. These changes occur due to a decline in the ovarian secretion of estrogen and progesterone.

• The epithelium and underlying tissue are lost.
• The fragments of necrotic stroma, spiral arteries, and glands are sloughed off.
• The eroded surface is covered with blood clots.
• The vaginal discharge consists of blood, uterine fluid, and fragments of necrotic endometrial tissue of stratum functional,

Cortex

The cervix is the narrow lower part of the uterus. ‘The lumen of the cervix is narrow and known as a cervical canal. The upper end of the canal communicates with the cavity of the body of the uterus and the lower end with the vagina. The upper and lower openings are referred to as internal and external os, respectively. The lower portion cervix projects into the vagina and is called as portion vaginalis.

The histology of the cervix is different than the fundus and the body of the uterus. The cervix is not lined by endometrium, hence does not show cyclic changes similar to endometrium. The surface epithelium of cervical mucosa is mucus-secreting and lamina propria contains a large branched gland.

There are no spiral arteries in the cervical mucosa.

• The cervical canal is lined by tall columnar mucus-secreting epithelium.
• This type of epithelium also lines the branched tubular cervical glands in lamina propria. They secrete mucus, which is rich in the enzyme lysozyme.
• The secretion of mucus increases many folds during mid-cycle (at the time of ovulation), which helps in the migration of sperms into the uterus.
• The secretion of mucus is under cyclic control of ovarian hormones.
• The lamina propria is made up of loose connective tissue where cells predominate.
• Deep to lamina propria is a muscle layer consisting of smooth muscle and intervening connective tissue.
• The portion of the cervix, which projects in the vagina, is lined by stratified squamous epithelium. At the externals, there is a sudden change from columnar to stratified squamous epithelium.

Cervical canal Remember:

The cervical canal is lined by tall columnar mucous-secreting epithelium. The branched tubular cervical glands are present in lamina propria, which also secrete mucus. At the external os, there is a sudden change from columnar to stratified squamous epithelium.

Cervical and Vaginal Smear Clinical Applications

Examination of Cervical and Vaginal Smear (Pap Smears or Papanicolaou Test)

• As the epithelial cells of the vagina and cervix are constantly shed off. the cervical and vaginal smear is examined to study the characteristics of these cells (cytology).
• This examination gives information of clinical importance. The pap smear can tell us whether the lady is in the first or second half of the menstrual cycle (estrogen or progesterone phase).
• The pap smear is also useful in the detection of early cervical cancer (carcinoma in situ).
• The cancer of cervical (cervical carcinoma) is the most common in males. It is derived from the stratified squamous epithelium of the cervix.

Vagina

The vagina is a fibromuscular tube. It has the following layers

1. Mucosa
2. Muscular Layer
3. Adventitia

1. Mucosa:

The lining epithelium is stratified squamous, which is non-keratinized. although some of the superficial cells may contain keratohyaline.

• The epithelium accumulates glycogen under the influence of estrogen (follicular phase) but diminishes later in the cycle.
• Bacteria act on glycogen to produce lactic acid, which lowers the pH of the vagina and helps in controlling the infection.
• The surface cells are continuously shed off. The vagina has no glands but is kept moist by the secretion of cervical glands.
• The lamina propria is broad and contains many elastic fibers in moderately dense connective tissue.
• Large numbers of small vessels are present throughout the lamina propria.

2. Muscular Layer:

It is made up predominantly of longitudinally and obliquely arranged bundles of smooth muscle fibers. In between the muscle bundles are connective tissue and blood vessels.

3. Adventitia: This layer is made up of connective tissue and contains blood vessels.

Placenta

Readers are advised to read the embryological development of the placenta before reading

The following description of the placenta:

• The placenta is involved in providing the nutrition, hormones, and oxygen to the fetus and removes the metabolic wastes of the fetus. The placenta is formed by both fetal and maternal tissue. The fetal part of the placenta is formed by chorion and the maternal by decidua basalis.  is a diagrammatic representation of various parts of a fully formed placenta.
• From the chorionic plate, there are many stem villi, which branch repeatedly. The core of these villi contains fetal blood vessels and capillaries. The other side of the placenta has a decidual plate. It sends incomplete septa toward the chorionic plate, which divides the placenta into 15- 20 cotyledons.
• The maternal blood comes to intervillous space from the spiral arteries of decidua. It bathes the chorionic villi. The exchange of gases and metabolic products occurs between the blood flowing in the capillaries of the villi and the maternal blood, which bathes these villi.
• A slide of the placenta will show the cross-section of many villi. A villus is lined with the inner layer of cytotrophoblasts and the outer layer of syncytiotrophoblasts. The cytotrophoblasts are cuboidal in shape and lie on the basement membrane.
• The syncytiotrophoblast layer is the layer of multinucleated cytoplasm with indistinct cell margins. The core of the villi contains umbilical blood capillaries.

Placenta Remember:

The placenta is involved in providing the nutrition, hormones, and oxygen to the fetus and removes the metabolic wastes of the fetus. In the third trimester of. pregnancy, the placental barrier is formed by thin syncytiotrophoblastic cells, the basement membrane of the fetal capillary’ and the endothelial cell of the fetal capillary.

Embedded in a thin layer of legal conned tissue. The cross-sections of villi nix’ are surrounded by maternal blood (RBCs)

In earlier stages of pregnancy (3-5 months), the placental barrier between fetal blood (in fetal capillaries) and maternal blood (in intervillous space) consists of:

• Endothelium of fetal capillaries. The endothelium is non-fenestrated.
• The basal lamina of fetal capillaries.
• Fetal connective tissue
• The basal lamina of cytotrophoblasts
• Cvtotrophoblast
• Syncytial trophoblast

As the placenta becomes older, the chorionic villi at full term show the disappearance of the cytotrophoblastic layer. The syncytial trophoblast becomes thin, and fetal capillaries increase in number and abut closely to the syncytial trophoblast. The thickness of the placental barrier reduces from 0.025 mm at the beginning to 0.002 mm at full term.

Now it has the following layers:

• Thin syncytiotrophoblastic cells
• The basement membrane of the fetal capillary
• The endothelial cell of the fetal capillary

The syncytial Imphobliisl produces progesterone, estrogen, human chorionic gonadotrophin, and other hormones.

Umbilical Cord

The umbilical cord extends between the placenta and the fetus. It brings the oxygenated blood from the placenta to the fetus through a single umbilical vein and carries deoxygenated blood to the placenta through two umbilical arteries. A cross-section of the umbilical cord shows the following structures

• The amniotic membrane covers the umbilical cord. Thus, the cord is lined by flattened amniotic epithelial cells.
• Deep to epithelial lining umbilical cord contains mucoid connective tissue (Wharton’s jelly).
• Wharton’s jelly consists of highly branched fibroblasts, collagen fibers, and ground substance.
• The fibroblasts are widely separated from each other because of the ground substance.
• In the connective tissue, there is the presence of two umbili¬cal arteries and one umbilical vein. The umbilical arteries are thick-walled and show wavy internal elastic lamina and narrow lumen. The vein is thin-walled with a wide lumen.

Mammary Glands (Breast)

Two mammary glands are modified sweat glands of the skin that have evolved in mammals to produce milk to nourish the offspring. Breast starts developing in females at puberty under the influence of hormones.

• They reach their greatest development at about age 20. The striking changes in size and functional activity occur during pregnancy and lactation. Atrophic changes start at the age of 40 and increase after menopause.
• Each breast consists of 15-20 individual, radially arranged mammary glands called lobes. A single large lactiferous duct drains each lobe. Therefore, 15-20 large lactiferous ducts converge upon the nipple to open as milk pores.
• Each lobe (in a breast) is surrounded by a dense fi¬brous connective tissue capsule. The capsule in turn is surrounded by abundant adipose tissue. Each lobe consists of several smaller compartments called lobules.
• Each lobule is composed of grapelike clusters of milk-secreting glands termed alveoli, which are embedded in connective tissue.

From alveoli, ducts may be traced as follows:

1. Alveolus to Alveolar Ductule: The ductule drains an alveolus and is lined by low cuboidal epithelium.
2. Intralobular Duct: Many ductules join to form this duct, which is lined by cuboidal epithelium. Both alveolar ductules and intralobu¬lar ducts are present within lobule, in between alveoli.
3. Interlobular Ducts: These are lined by cuboidal to low columnar epithelium and are present in connective tissue septa between lobules.

Lactiferous (Lobar Duct):

It is a large duct with columnar epithelium, terminating at the nipple. The lobar ducts ha ve a dilatation. the lactiferous sinus, under the areola, which may be lined by two layers of cuboidal or pseudostratified columnar epithelium.

Histology of Inactive (Non-lactating) Gland

The inactive mammary gland consists mainly of duets and their branches embedded in connective tissue stroma and fat cells.

• The stroma of the gland is lobulated, although lobules in an inactive mammary gland are poorly defined. Each lobule consists of intralobular ducts and inactive alveoli in the form of solid epithelial spherical masses or cords. The intralobular connective tissue consists of loose vascular connective tissue with numerous fibroblasts.
• Lobules are surrounded by interlobular connective tissue, which is made up of dense collagen fibers, adipose tissue, blood vessels, and interlobular ducts.
• The glandular elements (alveoli) are minimal or absent. The glandular elements may be present in the form of small spherical masses of epithelial cells.
• These masses are present at the terminal end of the smallest branches of the duct system.
• These solid masses of cells do not have a lumen, but under the influence of hormones may develop into functional acini.

Mammary gland Remember:

In an inactive mammary gland, there is the absence of alveoli, and only ducts and their branches are embedded in connective tissue stroma.

Histology of Active (Lactating) Gland

During pregnancy, the increased level of estrogen and progesterone influences the rapid growth and branching of the duct system. There occurs the formation of new acini (alveoli) at the terminal tip of ducts. The pre-existing sphere and cords of glandular cells start proliferating and form true alveoli

• In a lactating breast, the lobule of the gland is full of acini with a minimal amount of connective tissue.
• There is a marked reduction in adipose tissue. New stroma is infiltrated by lymphocytes, plasma cells, and eosinophils.
• Plasma cells secrete antibodies in the milk, which may be some degree of passive immunity to the newborn. Many alveoli me lined with low columnar cells with narrow lumen.
• They lake acidophilic slain, Bill also shows some basophilia near the base. The apical pot lion (d cell shows the presence of lipid droplets.
• The lipid droplets are also seen in the lumen of the alveoli. The secretion of lipids is apocrine, while the protein component of the milk is secreted through merocrine secretion.
• Some alveoli may be in the resting phase, i.e… their epithelium is low cuboidal and their wide lumen is filled with lipid droplets (milk).
• Myoepithelial cells are seen between the basement membrane and secretory cells.
• The intralobular ducts are seen, but they are fewer in number compared to several alveoli.
• They can be easily differentiated from alveoli because they take dark stains compared to alveoli.
• The interlobular ducts may also show the presence of milk in their lumen. The bigger ducts now may be lined with stratified columnar cells.

During pregnancy under the influence of hormones, there occurs the rapid growth and branching of the duct system and the development of secretory units known as alveoli. While in a lactating breast, the lobule of the gland is full of alveoli with a minimal amount of connective tissue.

Mammary Gland (Brest) Clinical Application

1. Breast Cancer: Breast cancers (carcinomas) arise due to the malignant proliferation of epithelial cells lining lactiferous ducts. The early detection of breast cancer by self-examination may reduce the mortality rate.
2. Milk Ejection Reflex: As soon as a child suckles the breast, the sensory receptors in the nipple of the mother get stimulated.
   • This results: In the secretion of oxytocin from the posterior pituitary gland.
   • This hormone causes the contraction of myoepithelial cells 1 in alveoli and ducts, which results in the ejection of milk.
   • The sensory stimulation also inhibits the release of prolactin j inhibiting factor.
   • This leads to the release of prolactin from the anterior pituitary resulting in the secretion of milk from the breast.

Liver

The liver is an accessory digestive gland. It develops as an outgrowth of the entodermal epithelium of the duodenum. The connection between the duodenum and liver develops as a bile duct. The liver is the largest gland in the body weighing about 1500 g.

It has a double blood supply, i.e., the arterial blood from hepatic arteries and venous blood from the veins of digestive tubes and spleen through portal vein.

Blood from both the sources (arterial and venous) passes through liver sinusoids and ultimately drains into hepatic veins that join the inferior vena cava. Thus, the substances absorbed from the intestines first come in contact with the liver cells.

Gross Histological Organization of Liver

The liver is surrounded by a thin connective tissue capsule and is divided into many lobes, i.e., left, right, caudate and quadrate lobes.

• The hepatic artery, bile duct and portal vein enter the liver at the porta (hilus-a short transverse fissure on the inferior surface of the liver). Artery and veins repeatedly branch to supply hepatic lobules.
• Although the bile duct also follows the same course, it carries bile in the opposite direction, i.e., away from liver lobules.
• The connective tissue entering the liver at the porta, along with other structures, branches within the liver to form the partial boundary of liver lobules and to support the branching vessels and ducts.
• In humans, the lobules of the liver are not well defined because their interlobular connective tissue is poorly developed. The interlobular connective tissue is also called interlobular septa.
• The branches of the portal vein, hepatic artery and bile duet course together in the connective tissue interlobular septa as a triad, called as a portal triad.

Microscopic Organization of Liver

1. Liver Lobule

The substance of the liver is made up of liver lobules that form the structural and functional unit of the organ. In cross¬section, the shape of a liver lobule is somewhat similar to a hexagon.

In the human liver, the connective tissue between adjacent lobules is scanty. Hence, no well-defined separation between adjacent lobules is seen. Therefore, the liver tissue of one lobule merges with that of adjacent lobules

At the corners (angles) of the hexagon (lobule) there are small triangular areas of the connective tissue that contain portal triads (branches of the portal vein, hepatic artery and an interlobular bile duct. Thus around the periphery of each lobule, there are several portal triads.

As the boundaries of hexagonal lobules are touching each other, every portal triad forms a partial boundary for more than one lobule. In the centre of each hepatic lobule is a central vein  The central vein drains blood from lobules into hepatic veins. Radiating from the central vein are hepatic cells (hepatocytes), which are arranged in plates (laminae) that are usually one cell thick. These plates anastomose to form a three-dimensional network.

Between the plates (laminae) are blood passageways called sinusoids. The lateral branches of the small hepatic artery and portal venules, which arise from the portal triads, join to form the hepatic sinusoids. The flow of blood in sinusoids is from the periphery of the lobule to toward the central vein.

The bile canaliculus is a small channel, which occurs at the interphase between an adjacent pair of liver cells in a plate. The walls of the canaliculus are formed by the plasma membrane of the opposite hepatocytes. These canaliculi drain bile, produced by hepatocytes, toward the bile duct at the periphery of the lobule, in the portal triad.

A polygonal hepatic cell is thus exposed on its two or three sides to which blood flows toward the central vein. The same hepatic cell also forms bile canaliculi on its 3 or 4 remaining sides.

Liver Remember:

The structural and functional unit of the liver is the “hepatic lobule” which looks somewhat similar to a hexagon. There is no well-defined separation between adjacent lobules and at the corners (angles) of the hexagon (lobule) there are small triangular areas that contain “portal triads.” In the centre of each hepatic lobule is a central vein.

Three Different Types of Liver Lobules

The following three kinds of structural and functional lobules are described in

1. Classical liver lobule:
   • It has a central vein located in the centre of the lobule and portal triads at the edges of the cross-sectioned lobule.
   • The blood flows from the periphery to cen¬tre and secretion (bile) from the centre toward the periphery (portal triad).
2.  Portal lobule:
   • It is a triangular area of the liver parenchyma around each portal triad. It includes the portions of three neighbouring classical lobules. In this kind of lobule, the portal triad is in the central position and central vein at the edges of the cross-sectioned lobule.
   • This lobule indicates that blood supply to liver parenchyma goes from the centre to the periphery and bile secretion drains into the central duct.
3. Liver acinus:
   • This is the most commonly accepted structural and functional lobule. Liver acinus is elliptical and includes portions of two neighbouring classical lobules.
   • In the centre of the acinus are terminal branches of the hepatic arteriole and portal venule extending laterally from the portal triad, and the central vein at each pole of the cross-sectional structure.
   • It is considered that an acinus has three zones, i.e., zones 1, 2 and 3.
   • Zone 1 is close to blood vessels and zone 3 is close to a central vein.
   • Thus, zone 1 is supplied with blood that is most oxygenated and rich in nutrients and zone 3 gets the least.
   • The cell degeneration as seen in toxic damage to the liver is first observed in the central part (zone 1) as it is exposed to toxin before zone 3, while degeneration secondary to hypoxia is first observed in zone 3.

Lobules liver Remember:

Three different types of lobules are described in the liver, i.e., classical lobule, portal lobule and hepatic acinus. The classical hepatic lobule is a roughly hexagonal mass of tissue. The portal lobule connects three central veins and surrounds a portal triad. The liver acinus is the smallest functional unit of hepatic parenchyma.

Hepatic Sinusoids:

The sinusoids are between the hepatic laminae (plates) and follow their branching and anastomoses Their calibre is larger than capillaries (9-12 pm). Sinusoids are lined by two kinds of cells, i.e., endothelial cells and phagocytic (Kupffer) cells.

• The lining of endothelial cells is not continuous; gaps are seen between neighbouring endothelial cells. The endothelial cells have fenestrations that are not covered by the diaphragm.
• The basal lamina surrounding the sinusoids is either incomplete or absent. The sinusoidal epithelium is separated from the underlying hepatocytes by a small space, called the space of Disse (perisinusoidal space).
• The particulate matter less than 0.5 m in diameter may pass through the lumen of the sinusoid into space of the Disse

The phagocytic Kupffer cells lie by the side of endothelial cells and send cytoplasmic processes (filopodia) between adjacent endothelial cells. They do not form junctions with the neighbouring endothelial cells. Kupffer cells may send their cytoplasmic processes in the space of Disse through fenestrations or the gap between two endothelial cells.

Many microvilli project in the space of Disse from the basal surface of the hepatocytes. They increase the sur¬face area for the exchange of material between blood and liver cells. Blood plasma freely enters the Space of Disse and directly bathes the surface of the hepatic cells.

Ito cells (hepatic stellate cells):

Ito cells (hepatic stellate cells are another type of cells found in perisinusoidal spaces. These cells are involved in the storage of vitamin A and lipids. In chronic inflammation or cirrhosis, they differentiate into cells with characteristics of myofibroblasts, which produce collagen fibres resulting in liver fibrosis.

Hepatic Sinusoids Remember:

Hepatic sinusoids are vascular channels between the plates of hepatocytes. Sinusoids are lined by endothelial and phagocytic (Kupffer) cells. Gaps are seen between neighbouring endothelial cells. The endothelial cells have fenestrations that are not covered by the diaphragm. Perisinusoidal space (space of Disse) is seen between sinusoidal endothelium and hepatocytes.

2. Hepatocytes (Liver Cells)

Each liver cell is polygonal in shape possessing a relatively large nucleus (may be binucleated) and a single nucleolus. Hepatocytes have granular acidophilic cytoplasm but also contain basophilic bodies.

• Hepatocytes constitute about 80% of liver volume. Their life span is of about 5 months and are capable of regeneration.
• The polyhedral liver cells may have 5-12 sides and are about 20-30 cm in width. These cells form hepatic cords, which may branch and anastomose frequently.
• Some sides of the cells are exposed to the sinusoids, and the sides which are not exposed to sinusoids show infolding between adjacent cells to form bile canaliculi. The bile canaliculi form a network within the cell plates.

3. Electron Microscopic Structure of Liver Cells

The electron micrograph of liver cells shows the presence of numerous oval mitochondria with leaf-like cristae. Hepatocytes contain rough and smooth endoplasmic reticulum, free ribosomes, and many small Golgi complexes located near the bile canaliculi. There are many lysosomes and peroxisomes. Peroxisomes are involved in the detoxification of alcohol. Glycogen granules and lipid vacuoles are also seen.

4. Blood Circulation

The hepatic artery and portal vein after entering the porta hepatitis divide repeatedly to lie between hepatic lobules.

• The blood vessels present in portal triads are called interlobular vessels.
• The interlobular vessels of portal triads branch into vessels, which lie at the periphery of the lobules (between the lobules).
• These vessels are called distributing vessels.
• The distributing vessels are branches of the portal vein (which brings deoxygenated blood along with J-absorbed products of digestion) and the hepatic artery (which brings arterial blood) rich in oxygen.
• The distributing vessels send branches to liver sinusoids.
• The flow of mixed blood (arterial and venous) in sinusoids is from the periphery toward the central vein. The central veins join to form hepatic veins, which ultimately drain into the inferior vena cava.

Liver Functions 

• The liver has several functions, most of which are performed by hepatocytes.
• Liver cells produce not only exocrine secretion bile but also perform many endocrine functions.
• It modifies the structure and functions of many hormones.
• The liver produces most of the circulating plasma proteins.
• It is involved in many metabolic pathways, storage of vitamins and detoxification of toxins.
• The liver has several functions, most of which are performed by hepatocytes.
• Liver cells produce not only exocrine secretion bile but also perform many endocrine functions.
• It modifies the structure and functions of many hormones. The liver produces most of the circulating plasma proteins.
• It is involved in many metabolic pathways, storage of vitamins and detoxification of toxins.

Liver Clinical Application

Cirrhosis of the Liver:

• The function of liver cells is to detoxify drugs and toxic chemicals including alcohol.
• Those people who consume alcohol regularly for many years may develop a disease of the liver called cirrhosis.
• In this disease, there occurs the necrosis (death) of liver cells. These dead cells are replaced by fibrous tissue.
• The patient gradually becomes weak and develops jaundice due to the obstruction in the flow of bile.
• The other agents, which may cause cirrhosis are drugs, chemicals, hepatitis virus and autoimmune liver disease.
• Chronic viral hepatitis [^(B or C type) may also lead to cancer of the liver.

Liver Regeneration

The liver has high regenerative power. It can regenerate after toxic damage and even if a portion of it is excised.

Gallbladder

The gall bladder is a temporary storehouse of bile and concentrates it by water reabsorption.

It consists of the following layers:

1. Mucosa
2. Fibromuscular layer
3. Adventitia/Serosa

1. Mucosa:

It consists of simple tall columnar epithelium and lamina propria of loose connective tissue.

• The mucosal glands and muscularis mucosae are absent.
• The mucosa is thrown into small folds when the gall blad¬der is empty. The gall bladder epithelial cells have a basally placed ovoid nucleus and faintly stained eosinophilic cytoplasm.
• These cells have many small microvilli on their apical surface.
• These cells are highly involved in the absorption of water from stored bile. Lamina propria is present but submucosa is absent.

2. Fibromuscular Layer:

• This layer is composed of randomly arranged smooth muscle fibres.
• In between muscle fibres is dense connective tissue that is rich in elastic fibres.

3. Adventitia/Serosa:

• There is a layer of dense connective tissue outside the muscle layer, which contains blood vessels, nerves and lymphatics.
• This layer is called adventitia. On its inferior surface gall bladder is covered by se-rosa, rest of it is covered by adventitia.

 Gall bladder Remember:

The muscularis mucosae and submucosa are absent in the wall of the gall bladder. The release of bile from the gall bladder is controlled by cholecystokinin and vagal stimulation.

Gallbladder Clinical Application

Gallstones and Jaundice:

• Sometimes due to the presence of a higher concentration of bile acids in bile, there may occur the formation of stones in the gall bladder.
• If a gallstone obstructs the bile duct, it causes jaundice.
• Jaundice is a disease where there is the presence of an increased amount of bile pigments in the blood.

Pancreas

The pancreas is an accessory gland of digestion. This lies wholly outside the alimentary tract and is connected to it (duodenum) by an excretory’ duct(s). The pancreas is a mixed gland, i.e., it consists of an exocrine and an endocrine portion.

• The exocrine pancreas secretes pancreatic juice that helps in the digestion of carbohydrates, proteins and fats, while the endocrine pancreas secretes hormones, which regulate the metabolism of carbohydrates.
• The exocrine pancreas shows a similar structural organization as that of salivary glands.
• The secretory units of acini of the exocrine pancreas are tubuloacinar in shape and resemble a bunch of grapes where stems are comparable to the duct system and secretory acini are comparable to grapes.
• The endocrine units are called the islets of Langerhans. These are clusters of pale staining cells situated between the exocrine acini.

Pancreas Remember:

The pancreas is a mixed gland, i.e., exocrine and endocrine. The exocrine pancreas produces serous digestive juices and the endocrine pancreas produces hormones.

Histology of Exocrine Pancreas

The pancreas is covered with a very thin layer of loose con¬nective tissue capsule. Thin septa arise from this to divide the gland into many small lobules. These lobules are not very distinct. The interlobular connective tissue contains large ducts, blood vessels, and nerve fibres. The interlobular loose connective tissue surrounds the acini, small ducts and islets of Langerhans

1. Pancreatic Acini

The pancreatic acini are serous. Their shape is either round or slightly elongated.

• These acini are lined by pyramidal cells and have small lumen. The intercalated duct begins within the acini (see below).
• The acinar cells show all the features of a serous-secreting cell. These cells have centrally placed round nuclei.
• The intranuclear region is intensely basophilic (stains with haematoxylin) because it contains a rough endoplasmic reticulum and many free ribosomes.
• The supranuclear region is filled with secretory granules called zymogen granules The apical portion takes eosinophilic staining or may stain light basophilic. These secretory granules contain the precursors of several digestive enzymes.
• These enzymes are amylase, lipase, ribonuclease, deoxyribonuclease, trypsinogen, chemo-trypsinogen, etc. The release of these enzymes is controlled by cholecystokinin and acetylcholine.
• The cholecystokinin is liberated by the small intestine (mostly duodenum), which acts on the receptors of pancreatic acinar cells.
• Similarly, stimulation of parasympathetic nerves secrete acetylcholine, which facilitates the secretion of enzymes from pancreatic acini.

‘

1. Islets of Langerhans
2. Pancreatic acini
3. Pancreatic lobule
4. Blood vessels
5. Interlobular duct

Islets of Langerhans Present Acini And Intrabular Ducts:

Pancreatic Remember:

The pancreatic acini are lined by pyramidal cells and have small lumen. They are serious in nature and manufacture and release digestive enzymes. Pancreatic exocrine secretion is controlled by hormones (cholecystokinin) and nervous system (acetylcholine).

2. Ducts

The pancreas, like salivary glands, has an extensive duct system, i.e., intralobular (intercalated), interlobular and main duct.

• The intralobular ducts are very small in diameter and lined by squamous to very low simple cuboidal epithelium.
• An intercalated duct commonly begins within the acinus. Therefore, the ends of intercalated ducts are surrounded by acinar cells.
• Cells of intercalated ducts add bicar¬bonate and water to the exocrine secretion. The acinar lumen may show pale staining cells of the intercalated duct. These cells are called centroacinar cells. There are no striated ducts in the pancreas.
• The intercalated ducts are short and open into ’ intralobular collecting ducts’, which are lined by cuboidal or low columnar epithelium.
• The interlobular ducts are lined with simple columnar epithelium and lie in connective tissue septa.
• The main duct is lined with tall columnar cells with occasional goblet cells.

Duct Remember:

The centroacinar cells are part of the intercalated duct. Cells of intercalated ducts add bicarbonate and water to the exocrine secretion.

Histology of Endocrine Pancreas

The endocrine component of the pancreas is in the form of small groups of cells (“islands”), which are scattered among the acini of the exocrine pancreas. These small groups of cells are called “islets of Langerhans.”

• The islets are lightly stained with H&E and thus can be easily differentiated from acini, which are darkly stained.
• The cells of islets are arranged as anastomosing plates or cords and permeated by a rich network of fenestrated capillaries. They pour their secretions directly into blood capillaries.
• The islets contain mainly four kinds of cells, which can be distinguished by special stains, but not by H&E.

These cells are designated as:

• α (alpha) cells: These are 20% of the total population of islet cells and secrete glucagon. Glucagon acts antagonistically to insulin.
• β (beta) cells: These are 70% of the total population and secrete insulin, which promotes the uptake of glucose.
• δ (delta) cells: These are 5% and secrete somatostatin, which suppresses the release of insulin and glucagon.
• PP cells: These cells secrete pancreatic polypeptides, which regulate acinar cell secretion (PP = protein polypeptide).

Pancreas Clinical Application

• Diabetes: Diabetes is caused by to impaired function of beta cells of islets of Langerhans. In this condition, these cells are unable to produce the required amount of insulin.
  • A person suffering from diabetes has high blood levels of glucose. The glucose may also get excreted through urine. The disease if remains untreated may lead to atherosclerosis and partial blindness from degenerative changes in the retina.
  • Diabetes occurs in two forms, i.e., type 1 and type 2:
  • In type 1 the f3 cell of islets are destroyed before the age of 15 years. These patients are dependent on the injection of insulin as no insulin is produced by islets.
  • Type 2 (non-insulin-dependent diabetes) usually occurs after 40 years of age and in.

General Histology Of The Alimentary Canal

The alimentary canal, from the oesophagus to the anal canal, may be identified by its tubular nature and also by the division of its wall into four layers.

These layers from deep to superficial are :

1. Mucosa
2. Submucosa
3. Muscle layer
4. Serosa

1. Mucosa

This is the innermost layer of the alimentary canal and com-prises lining epithelium, lamina propria and muscularis mucosae.

• Epithelium: Different types of epithelium line different parts of the alimentary canal, i.e., the oesophagus and anal canal are lined by protective epithelium (stratified squamous); the intestine and stomach are lined by simple columnar, which is absorptive and secretory.
• Lamina propria: This is a layer of loose connective tis¬sue, which supports the epithelium. It contains the blood and lymphatic vessels through which nutrients are absorbed.
  • Lamina propria also accommodates glands like gastric glands in the stomach and crypts of Lieberkuhn (intestinal glands) in the mucosa of the intestine. These glands develop from the invagination of luminal epithelium.
  • The lamina propria also contains “mucosa-associated lymphoid tissue.” i.e.. lymphocytes and macrophages.
  • These lymphocytes and macrophages are defensive as the alimentary canal is subjected to the entry of foreign substances like bacteria and other microbes.
  • These lymphoid tissues may be in the form of lymphatic nodules (as in the appendix) or the form of diffuse tissue,
• Muscularis mucosae:
• This consists of a thin layer of smooth muscle cells. These are arranged as inner circular and outer longitudinal layers. The muscularis mucosae can change the shape of the mucosa, which helps in absorption and secretion.

Lamina propria Remember:

Lamina propria contains the blood and lymphatic vessels through which nutrients are absorbed. It also contains glands (intestinal glands) and lymphoid tissue. The secretory function of mucosa provides lubrication and delivers digestive enzymes and hormones. Lymphoid tissues are defensive and protect the intestine from foreign substances.

2. Submucosa:

It consists of moderately dense, irregular connective tissue rich in collagen and elastic fibres.

• The submucosa contains blood vessels, lymphatic vessels, nerves and Meissner’s plexus.
• In some parts of the alimentary tract (oesophagus and duodenum), the submucosa contains glands that pour their secretion into the lumen of the gut through ducts.
• This layer may also contain scattered lymphoid nodules, particularly in the large intestine.

3. Muscle Layer:

In most of the parts of the alimentary tract, this layer is made up of an outer sheet of longitudinally arranged smooth muscle fibres and an inner sheet of circularly arranged fibres.

• This layer also contains myenteric plexus (Auerbach’s plexus) between circular and longitudinal sheets of muscle fibres.
• This plexus mostly controls the motility of the tract.

4. Serosa Adventitia:

The serosa is the superficial layer on the parts of the alimentary tract present in the abdominal cavity.

• It is a visceral peritoneum composed of connective tissue and simple squamous epithelium.
• The oesophagus part of the alimentary tract, which is outside the abdominal cavity, has a superficial layer called adventitia that consists of areolar connective tissue.

 Serosa Remember:

Contraction of the muscle layer mixes and propels the contents of the digestive tract. The serosa or adventitia is the outermost layer of the alimentary canal.

Oesophagus

The oesophagus is a straight muscular tube extending from the pharynx in the neck to the stomach in the abdomen. Most of it lies in the thoracic cavity.

Its wall is made up of four layers:

1. Mucosa
2. Submucosa
3. Muscle layer
4. Serosa

1. Mucosa

• Epithelium: It consists of thick non-keratinized strati¬fied squamous epithelium.
• Lamina propria: It consists of a thin layer of loose con¬nective tissue
• Muscularis mucosae: It is unusual in two respects; firstly, it is thicker compared to other parts of the alimentary canal. Secondly, it is single-layered and formed by longitudi¬nally running smooth muscle fibres. Sometimes, the mucosa of the oesophagus may contain mucous glands in its uppermost (near the laryngopharynx) and lower (near the stomach) regions.

2. Submucosa

It is a wide layer of irregular, moderately dense connective tissue composed of bundles of collagen and elastic fibres.

• Due to the presence of elastic fibres, the submucosa is thrown into folds.
• Hence, the lumen of the oesophagus appears star-shaped. The submucosa contains blood vessels and branched tubuloalveolar mucous glands.
• Ducts arising from these glands run through lamina propria to open into the lumen of the oesophagus.

3. Muscle Layer

The muscle layer is different in different parts of the oesophagus.

• In the upper third portion, the muscle is skeletal.  It consists of both skeletal and smooth muscles in the middle portion.
• In the lower third, it consists of purely smooth muscle.

These muscles are arranged in two layers, i.e… an outer longitudinal and an inner circular. A well-formed myenteric plexus of nerve fibres and ganglion cells exists between the two muscle layers. It controls the peristaltic movements.

4. Serosa/Adventitia

The superficial layer, adventitia, consists of loose areolar connective tissue, which merges with the connective tissue of surrounding structures. The adventitia surrounds most of the oesophagus, except for the lowest 1 inch where it is covered by serosa.

Oesophagus Functions

• The oesophagus has neither digestive nor absorptive functions.
• It is involved in the transport of food and water from phar¬ynx to the stomach. The bolus of the food travels in the oesophagus at the rate of 50 mm per second.
• It secretes mucus that lubricates the lumen of the oesopha¬gus to facilitate the transport of food.

Oesophagus Remember:

The glands of the mucosa and submucosa of the oesophagus secrete the mucus to facilitate the transport of food and protect the mucosa of the oesophagus. The muscle layer in the upper part of the oesophagus consists of skeletal muscle, while in the lower part it consists of smooth muscle. However, in the intermediate part, it is mixed.

Stomach

Based on histological structure, the stomach is divided into three distinct regions

1. Cardiac region: This part of the stomach is about 2-3 cm wide at the junction of the oesophagus.
2. Fundic region (or body): This region consists of fun¬dus and body.
3. Pyloric region: This region connects the stomach to the duodenum

In an empty stomach, the mucosa and submucosa are thrown into longitudinal folds called rugae. These rugae disappear when the stomach is distended with food. The epithelial lining of gastric mucosa contains many depressions called gastric pits.

From the bottom of each gastric pit, several tubular gastric glands extend into the lamina propria A section through the wall of the stomach shows the usual four layers, i.e., mucosa, submucosa, muscle layer and serosa

1. Cardiac Region

1. Mucosa:

• The epithelial lining, at the cardio-oesophageal junction, changes from stratified squamous epithelium to simple columnar epithelium. The columnar epithelium of the cardiac region shows basal, oval nuclei.
• These cells are involved in the secretion of mucus and arc called mucous surface cells.
• The goblet cells are not present in this epithelium. The lamina propria contains small tubular glands that open in gastric pits.
• These glands are lightly stained with ll&E and arc called mucus-secreting cardiac glands. The muscularis mucosae contain smooth muscle fibres arranged in two layers.

2. Submucosa:

The submucosa is a broad layer of connective tissue. It consists of blood vessels and nerve plexus (Meissner’s plexus).

3. Muscle Layer:

It is composed of three thickened layers of smooth muscle bundles inner oblique, middle circular and outer longitudinal. The inner oblique layer is not always apparent. The myenteric plexus may be seen in connective tissue between muscle layers.

4. Serosa:

Serosa is our most covering formed by simple squamous epithelium resting on a layer of connective tissue.

2. Fundic or Body Region

Following lour layers mo observed in this region.

1. Mucosa:

Lining Epithelium:

• The epithelium, which lines the surface and the gastric pits, is a simple columnar mucous epithelium.
• These cells are involved in the secretion of mucus. The mucus protects the epithelial lining from damage due to the presence of acid in the stomach.
• These cells are replaced every few days (3 5) with the proliferating cells of gastric pits.

Lamina propria:

Simple tubular glands arc present in lamina propria, which extend from the bottom of the gastric pit to the muscularis mucosae. They are called gastric glands or fundic glands and several may open at the bottom of a gastric pit. The isthmus is a small segment between the gastric pit and the fundic gland.

The cells of the isthmus divide and migrate upwards and downwards. These cells give rise to the cells of the surface epithelium and various cells of the gastric gland. In H&E sections.

The following types of cells can be identified in fundic glands:

• Mucous neck cells:
  • These cells are located just below the gastric pit. They are columnar and have mucinogen granules in apical cytoplasm, while nuclei arc basally situated.
  • They produce mucus of a different nature than that of surface epithelium.
  • They produce soluble mucus compared to insoluble mucus produced by surface mucous cells. The parietal cells are seen located with mucous neck cells.
  • Mucous neck cells also contain few regenerative (stem) cells. These cells proliferate to replace all of the specialized cells lining the gastric gland, gastric pit and surface. The mucous neck cells are replaced every 5-7 days.
• Parietal or oxyntic cells:
  • They produce HCl and intrinsic factors. These cells are mostly found in the upper half of gastric glands.
  • The parietal cells are large, rounded or pyramidal. These cells are wedged against the basement membrane.
  • In H&E preparation, they are stained dark pink. The electron micrographs, show the presence of a deep infolding of the apical membrane forming an “intracellular canaliculus” into which many microvilli. The cytoplasm contains tubulovesicular structures under the microvilli and many mitochondria.
  • The tubule-vesicular structures are involved in HCI secretion.
  • The synthesis of HCl takes place by the combination of Cl ions inside the intracellular canaliculi (outside cell). Both H⁺ and Cl^– ions are secreted by parietal cells. The life span of parietal cells is 150-200 days.

HCI Remember:

HCI is produced outside the parietal cell, be, in the lumen of the intercellular canaliculus.

• Chief or zymogenic cells:
  • Most of these cells are located in the lower third of gastric glands.
  • They usually take basophilic stains and thus are easily differentiated from parietal cells, which are strongly eosinophilic.
  • The chief cells contain a rough endoplasmic reticulum near the base, secretory granules near their apex and a small Golgi apparatus.
  • These cells are typical protein-secreting cells and secrete pepsinogen, which is converted to a proteolytic enzyme pepsin in an acid environment.

0

• Enteroendocrine and APUD cells:
  • These cells are located in the basal portion of gastric glands.
  • In the H&E section, the cells appear unstained. They contain secretory granules, which stain only in special preparations.
  • They are thought to produce serotonin, histamine and gastrin.
  • As these cells are endocrine cells, they release their products into the blood vessels.

Muscularis mucosae:

It consists of two thin layers of smooth muscles, i.e., outer longitudinal and inner circular.

Lamina propria Remember:

Lamina propria of the fundic or body region contains fundic (gastric) glands, which secrete gastric juice of the stom¬ach. Gastric juice contains hydrochloric acid (HCI) and intrinsic factors, pepsin and mucus. Parietal cells produce HCI and gastric intrinsic factor, while chief cells produce pepsinogen, reninin and gastric lipase. Mucus neck cells produce mucus.

2. Submucosa:

The submucosa is the same as described under general histol¬ogy of the alimentary canal.

3. Muscle Layer:

It has three layers of smooth muscle, i.e., in the outermost layer muscle fibres are oriented longitudinally, in the middle layer Fibres are circular and in the inner layer are obliquely arranged. The outer longitudinal layer is not very complete.

4. Serosa:

It is the outermost layer of the stomach and consists of loose connective tissue covered by mesothelium.

Fundic Or Body region Functions

• Mixing, partial digestion and storage of food.
• Production of gastric juice, i.e., pepsin, HC1, renin, in¬trinsic factor, hormones and mucus.
• Absorption of water and salt (slight). Alcohol and aspi¬rin enter the lamina propria by damaging surface epithelium.

3. Pyloric Region

1. Mucosa:

• The surface epithelium is the same as present in the fundic part of the stomach. The pyloric glands occupy the lamina propria (Fig. 14.8 A and B).
• The gastric pits of these glands are deeper and extend through half the thickness of the mucosa. These glands are short, tortuous and branched. They are lined by one-cell
• Type, which is similar to mucous neck cells. They produce mucus and gastrin. Muscularis mucosae is same as in fundic part.

2. Muscle Layer: The circular muscle is much thickened and forms a pyloric sphincter.

3. Submucosa and Serosa: Same as in the fundic part.

Pyloric Region Clinical Application

Pernicious Anaemia:

The parietal cells also serve as the source of intrinsic factors. The intrinsic factor is a must to absorb vitamin Br from the small intestine. In the absence of parietal cells (due to disease or surgery), the vitamin Bn is not absorbed, which leads to a condition known as pernicious anaemia. Parietal cells may also decrease in old age. The pernicious anaemia is treated by giving injections of vitamin B12.

Small Intestine

The small intestine is about 5 m in length and consists of three parts, i.e., duodenum (about 12 cm in length), jejunum (2 m) and ileum (3 m). This long tube extends from the stomach to the colon and is highly coiled. The major function of the small intestine is digestion and absorption. Most of the nutrients are absorbed by the small intestine.

 Intestine Remember:

The absorptive surface area of the intestine is increased by the formation of plicae circularis, villi and microvilli. The plicae circularis (valves of Kerckring) are permanent mucosal folds. These structures do not disappear on distension as they contain the core of the submucosa. Besides increasing the absorptive surface area, they also decrease the velocity of movement of contents.

1. Duodenum

It consists of four layers, i.e.,

1. Mucosa
2. Submucosa
3. Muscle layer and
4. Serosa/adventitia.

1. Mucosa:

• In the duodenum, the mucosa and submucosa are thrown into circular folds called plicae circularis. These mucosal folds are permanent structures and do not disappear on distension. This is because they contain the core of submucosa.
• The function of plicae circularis is to slow the passage of contents and to increase the surface area of mucosa.
• The surface area of the mucosa is further increased because of the presence of mucosal villi. The plicae are covered with villi. Villi are fingerlike mucosal projections about 0.5 mm in length.
• The core of each villus is formed by loose connective tissue of lamina propria containing fenestrated capillaries, smooth muscle fibres and lymphatics (blind-end lacteals).
• The surface of the villi is covered by epithelium consisting predominantly of columnar cells with striated borders (microvilli). In between the columnar cells, a few goblet cells are also present.

Mucosa Remember: 

• The mucosa of the intestine consists of villi, intestinal glands along with lamina propria, lymphocytic collections and muscularis mucosae.
• In between the bases of two intestinal villi, the epithelium is invaginated in lamina propria to form intestinal glands (crypts of Lieberkuhn). These glands are short tubular glands that open into the lumen of the intestine at the base of the intervillous space. These glands are lined by columnar cells, goblet cells, Paneth cells and enteroendocrine cells.
• The lamina propria, in between tubular intestinal glands, consists of loose connective tissue, reticular cells and diffuse lymphoid tissue. Occasionally, lamina propria may also contain submucosal Brunner’s glands. The muscularis mucosae sends smooth muscle fibres towards the core of the villi.

2. Submucosa:

The submucosa is almost completely occupied by highly branched, tubuloacinar duodenal glands. Brunner’s glands. The ducts of these glands pass through muscularis mucosae and open into the lumen of the duodenum. The acini of duodenal glands secrete mucus, hence taking light stain.

• These acini are lined with cuboidal or low columnar cells.
• Duodenal glands secrete alkaline mucus with high concentrations of bicarbonates that protect the duodenal mucosa from acid secreted by the stomach.
• Brunner’s gland also secretes “human epidermal growth factor,” which increases the mitotic activity of epidermal cells.
• This factor also inhibits the secretion of HCl.

3. Muscular Layer: It is made up of outer longitudinal and inner circular layers of smooth muscle.

4. Serosa/Adventitia: As most of the duodenum is retroperitoneal, some parts of its surface may show serosa. Otherwise, it is covered by adventitia.

Brunner’s gland Remember:

Brunner’s gland secretes “human epidermal growth factor” (which increases the mitotic activity of epidermal cells) besides producing mucous and alkaline fluid to neutralize the acidic chyme.

2. Jejunum

It also consists of four layers.

1. Mucosa:

Similar to the duodenum, the mucosa and submucosa of the jejunum are also thrown into permanent circular folds (plicae circularis), which bear tongue-shaped villi of different heights.

• Each villus is covered with tall columnar cells having a striated border. The core of each villus is formed by lamina propria containing diffuse lymphatic tissue, blood vessels, smooth muscle fibres and central lacteal.
• The crypts of Lieberkuhn (intestinal glands) are present in lamina propria below the bases of villi.
• These glands contain four different types of cells, i.e., absorptive columnar cells, goblet cells, enteroendocrine cells and Paneth cells
• Paneth cells play an important role in controlling the bacterial flora of the small intestine by producing antibacterial agents lysozyme and defensin.

Following are the main hormones secreted by gastric and intestinal enteroendocrine cells glucagon, serotonin, endorphin, histamine, gastrin, somatostatin, secretin, cholecystokinin (CCK), gastric inhibitor.’ peptide (GIP), noradrenaline and vasoactive intestinal peptide (VIP). The muscularis mucosae are in the usual two layers.

2. Submucosa

It is made up of connective tissue, blood vessels, nerve plexus (Meissner’s plexus) and lymphatics. Although no Peyer’s patches are seen, occasionally a lymph nodule may occur. No Brunner’s glands are seen.

3. Muscular Layer

It is the same as in the duodenum.

4. Serosa

It covers the jejunum to form an outermost layer.

Jejunum Remember:

Crypts of Liberkuhn or intestinal glands: These are simple tubular or branched tubular glands present in lamina pro-pria below the bases of villi. They increase the surface area of the intestinal lining. These glands consist of surface absorptive cells, goblet cells, enteroendocrine and Paneth cells.

Enterocytes are tall columnar and have elongated nuclei situated at the base. They are absorptive cells and transport water and substances from the lumen of the Intestine to the blood capillaries. They are also secretory cells, producing enzymes, which help In digestion and absorption.

3. Ileum

The ileum also has the usual four layers in its wall, i.e., mucosa, submucosa, muscle layer and serosa.

1. Mucosa

The epithelial lining of villi consists of the same absorptive columnar cells as present in the jejunum. The villi arc is few, short and finger-like. Lamina propria contains intestinal glands and aggregation of lymphatic nodules called Peyer’s patches. The number of lymphatic nodules increases in the distal ileum where they are covered with rudimentary villi.

In the ileum where Peyer’s patches are much larger they extend into the submucosa after disrupting the museularis mucosae. The muscular mucosae is thin or absent whereas Peyer’s patches are large.

Submucosa, Muscle Layer and Serosa

These layers are the same as in the jejunum.

Peyer’s Patches and “M” Cells

The mucosa intestine is exposed to toxins and microorganisms. To protect the gut from this invasion, there is the presence of lymphocytes, plasma cells and macrophages in the connective tissue of lamina propria. In the terminal portion of the ileum, there are aggregations of lymphatic nodules (Peyer’s patches).

• Overlying these lymphatic nodules, there are specialized “M” cells in between the columnar cells of the epithelium.
• These cells are broad and have few micro folds on their apical surface.
• The base of these cells is invaginated and occupied by lymphocytes and macrophages of underlying lymphoid tissue.
•  The formation of a deep recess in the M cell facilitates the lymphocytes to come in close contact with the bacteria and macro-molecules present on the apical surface of M cells.
• The M cells are capable of attracting bacteria and transporting their antigen across the cell to macrophages. The macrophages present the antigen to the surrounding lymphocytes.
• These lymphocytes then migrate to the lym¬phatic nodules in lamina propria. Mere, these lymphocytes then differentiate into plasma cells and produce the specific antibody.
• The antibodies (IgA) then pass from lamina propria to the surface of the epithelium through epithelial cells.
• Where (hey sil in the glycocalyx to neutralize toxins and microorganisms. Antibodies produced in lamina propria arc also re-circulated through the liver and gall bladder to the lumen of the intestine.

Ileum Remember:

M cells transport bacteria and other macromolecules from the lumen to cells of the immune system in Peyer’s patches and other large lymphocytic nodules. Thus, the M cell is considered an antigen-transporting cell

Large Intestine

The large intestine consists of the colon, rectum and anal canal.

Similar to the small intestine, the large intestine also has a mucosa, submucosa, muscle layer and serosa.

1. Colon

Mucosa:

The mucosal folds (plicae circularis) and villi are absent. Hence, the mucosal surface is smooth. The surface epithe¬lium principally consists of columnar cells and a few goblet cells. The columnar cells are absorptive and bear microvilli (striated border). These cells are involved in the absorption of lipids, water and salts.

• The lamina propria is occupied with tubular glands, which extend from surface to mus-cularis mucosae. The glands are straight and much longer than the glands of the small intestine.
• Glands are lined with few absorptive columnar cells and widely scattered enteroendocrine cells, but goblet cells now become Iho principal cells.
• Paneth cells may occur occasionally. In the lower third of the gland, the epithelium consists almost entirely of goblet cells. The lamina propria contains rinse lymphatic tissue and sometimes lymph nodules. The muscularis mucosae is typical.

Submucosa:

Its histological structure is typical.

Muscle Layer:

The outer longitudinal muscle layer is very thin. It is arranged in thick bands (taenia coli) only at three places. The inner circular layer of muscle is also thin compared to the small intestine.

Serosa:

It covers the transverse colon but parts of ascending and descending colon are covered by adventitia.

Colon Remember:

The mucosal surface of the colon is smooth as it has no villi or mucosal folds. The lining cells of mucosa consist predominantly of surface absorptive cells, which are involved in the absorption of lipids, water and salts. The number of goblet cells increases from the ascending colon to the sigmoid colon.

The lamina propria is occupied with tubular glands (crypts of Luberkhun), which extend from the surface to muscularis mucosae.

2. Rectum

Mucosa:

• The rectum is structurally similar to the colon. The intesti¬nal glands are straight like test tubes. The surface epithe¬lium and glands are lined predominantly with goblet cells.
• Entero-endocrine cells may be found, but Paneth cells are absent. Toward the termination of the rectum, the long intestinal glands decrease in length.
• The temporary longitudinal folds may be present in the upper rectum that has a core of submucosa.
• The permanent longitudinal folds of the rectum (rectal columns) appear in the lowermost rectum. The muscularis mucosae, in the lowermost rectum, appears as a thin layer.

Submucosa: It has a typical structure.

Muscle Layer:

In the rectum, the taenia coli are absent and a complete longi¬tudinal external muscle coat is present. The inner muscle coat is circular.

Serosa/Adventitia:

As the rectum is retroperitoneal, the serosa is present only

Functions of Colon and Rectum

• Absorption or remaining lipids, which are not absorbed by the small intestine.
• Absorption of water and salts that results in concentra¬tion of faeces.
• Secretion of mucus that facilitates the movement of intestinal contents.
• The mucus also protects the epithelium against abrasions by the concentrated faeces.

3. Anal Canal

Mucosa:

The mucosa of the anal canal has different histological structures in its upper, middle and lower parts.

• The upper part of the anal canal (the longitudinal anal columns) is covered by simple columnar epithelium similar to the rectum. There are few short intestinal glands in lamina propria, which gradually disappear as traced distally.
• The mucosa in the middle part is covered by stratified squamous non-keratinized epithelium.
• The uppermost portion of the middle part sometimes may show stratified cuboidal or columnar epithelium.
• The mucosa in the lowest part of the anal canal is covered with true skin and contains associated sebaceous and large apocrine glands. The muscularis mucosae disappear at the level of the middle part of the anal canal.
• The submucosa contains large thin-walled veins. These vessels are prime targets of varicosities or dilatations and are known as haemorrhoids.
• A thin layer of muscularis mucosa is present that disappears at the junction of the upper ar middle parts of the anal canal

Muscle Layer:

The circular muscle coat gets thickened to form an internal anal sphincter. The longitudinal muscle coat extends up to the middle part of the anal canal and then disappears.

Adventitia: It is the outermost layer.

Anal Canal Function

• Retention and elimination of wastes.

Diarrhoea Clinical Applications 

Diarrhoea is the production of stools that are more watery, more frequent or greater in volume than normal. Sometimes, diarrhoea is accompanied by abdominal pain, loss of appetite and vomiting.

• Severe diarrhoea can lead to dehydration and may be life-threatening, especially in infants.
• Diarrhoea, which starts all of a sudden is mostly caused by food poisoning. Diarrhoea may also be caused by viral or bacterial infections.
• Persistent diarrhoea may be due to chronic inflammation of the intestine due to disorders such as ulcerative colitis (inflammation of the large intestine) or malabsorption.
• Lactose intolerance (in this condition person can not digest the milk, i.e., lactose of milk) can also cause diarrhoea.
• If dehydration is treated properly by taking plenty of fluids then diarrhoea clears up within a day or two.
• If it lasts longer than 3-4 days, specific treatment is needed.

4. Appendix

The vermiform appendix is the appendage at the base of the caecum. It is the narrowest part of the large intestine. Its wall contains all four layers typical of the intestinal tract

Mucosa:

The epithelial lining of the mucosa is made up of absorptive 5 columnar cells, goblet cells and M cells.

• The M cells are antigen-transporting cells, which are present among the columnar cells of the epithelium overlying the lymphatic nodules.
• The lamina propria contains a few short intestinal glands. Enteroendocrine cells may be present in the intestinal glands, particularly those that secrete serotonin.
• The lamina propria is occupied with many large and small lymphatic nodules that may also extend into the submucosa.
• Lymphatic nodules with germinal centres can increase in size to such a degree that the narrow lumen of the appendix may be occluded.
• The muscularis mucosae are disrupted at places where lymphatic nodules extend into the submucosa.

Submucosa:

The submucosa is typical and may show the extension of lymphatic nodules.

Muscle Layer and Serosa:

The muscle layer consists of usual circular and longitudinal smooth muscle coats. The serosa forms the outermost layer covering the appendix completely.

• Innervation of Alimentary Canal The alimentary canal (from the oesophagus to the anus) is supplied by the enteric nervous system.
• This system consists of ganglia known as Meissner’s submucosal plexus and Auerbach’s myenteric plexus.
• These ganglia contain a large number of neurons (about 100 million). The enteric nervous system controls the mobility and secretion of the alimentary canal.
• Although the enteric nervous system is self-sufficient, its functions are modified by sympathetic and parasympathetic components of the autonomic nervous system.

Cancers of Intestine Clinical Application

Cancers of the intestine may arise from either surface epi- j thelium or glandular epithelium. Malignant tumours of the stomach and small intestine usually arise from surface 1 epithelial cells. However, in the case of the large intestine, malig¬nant tumours usually arise from the epithelium of intestinal glands. These tumours are called adenocarcinomas. Adenocarcinoma of the colon is the second most common cancer in humans.

Microscopic Structure of, mucosa of the gastrointestinal tract:

The Digestive System 1 Oral Cavity

The digestive system consists of two groups of organs

1. The gastrointestinal tract or alimentary canal: This is in the form of a tube that extends from the oral cavity to the anus. The parts of the gastrointestinal tract are: oral cavity, pharynx, oesophagus, stomach, small intestine, co¬ lon, rectum and anal canal.
2. The accessory digestive organs: These are teeth, tongue, salivary glands, liver, gall bladder and pancreas. In this chapter, we shall learn about the organs of the oral cavity and salivary glands pouring their secretion in the oral cavity.

Oral Cavity

In the oral cavity, food is broken into small pieces by the teeth, moistened and mixed with the secretions (which also contain hydrolytic enzymes) of salivary glands, for its passage through the oesophagus to the stomach

The oral cavity is lined by mucosa composed of stratified squamous epithelium, and a lamina propria of loose areolar connective tissue containing many mucus and serous secreting small glands. As this mucosa is subjected to friction of food, the epithelium at certain places in the oral cavity may show some degree of keratinization or it is para keratinized.

The para-keratinized epithelium is similar to the keratinized epithelium. Here, superficial cells do not lose their nuclei. The nuclei remain in these cells until cells are exfoliated

The lymphatic tissues (diffuse lymphatic tissue, nodules and tonsils) are present beneath the oral epithelium and provide a defence mechanism against infection as the oral cavity is the site of entry of foreign material.

The Lip

The lip consists of an external surface lined by skin, an internal surface lined by mucous membrane and the centrally placed skeletal muscle called orbicularis oris. The external and internal surfaces meet at the free border of the lip, which is also called as “red margin” of the lip.

• The skin ofthe lip is lined by the epidermis, which is keratinized stratified squamous epithelium. In the dermis, there is the presence of hair follicles, sweat glands and sebaceous glands.
• The inner surface flip is lined by non-keratinized stratified squamous epithelium. The lamina propria is present beneath the epithelium and contains labial mucous glands and blood vessels. The secretion of these glands keeps the oral mucosa moist.
• The free border (red margin) ofthe lip is the site of the mucocutaneous junction. It shows the transition ofthe epi¬ dermis ofthe skin to the epithelium of mucosa.
• Beneath the epithelium large number of blood vessels are present. which are responsible for the pink colour ofthe red margin of the lip

The lip Remember:

The external and internal, surfaces of the are lined by the skin and mucous membranes) respectively. These surfaces meet at the free border rof the margin or vermilion zone of the lip. The central core of the lip is formed.

Teeth

The teeth are accessory digestive organs located in the sockets of alveolar processes of the mandible and maxilla. The alveolar processes are covered by the gum. The root of the tooth is attached to the alveolar socket by periodontal ligaments, which consist of dense fibrous connective tissue

General Structure of a Tooth:

The parts of a typical tooth are. The crown is the part of the tooth above the level of the gum. The part of the tooth that lies embedded in the socket is called as root. The neck is the junction of the crown and root near the gum line

The central portion of a tooth is called as dentine. It is a calcified connective tissue that is harder than bone Dentine encloses a cavity called as pulp cavity. This cavity is filled with pulp, which consists of connective tissue containing blood vessels, nerves and lymphatic vessels. The pulp cavity continues down into the root as the root canal.

Each root canal has an opening at its base, the apical foramen, through which blood vessels, lymphatic and nerve enter. The dentine of the crown is covered by enamel. Enamel is the hardest substance in the body and consists of calcium salts. The dentine ofthe root is covered by cementum, which is a bone-like tissue. The cementum attaches the root to the periodontal ligament

Detailed Structure of Tooth:

1. Dentine:

Dentine forms the wall of the root and roof of the pulp cavity. It is composed of 80% inorganic salts (crystals of hydroxyapatite) and 20% inorganic matter (type 1 collagen and other proteins). It is a hard material similar to bone.

• Dentine is characterized by dentinal tubules radiating outward from the pulp cavity to the outer wall of the tooth.
• These tubules, in a living state, are occupied by the processes of odontoblasts. These cells line the pulp cavity and are tall columnar.
• The apical portion of the cell gives rise to a slender odontoblast process. The dentinal tubules, containing processes of odontoblasts, are parallel to each other.
• The dentine is laid down in layers that lie parallel to the pulp cavity. The layer of newly formed dentine near the apical end of odontoblasts, which is yet to be mineralized, is called dentine.
• Formation of dentine is a continuous slow process, which occurs throughout life and the pulp cavity is gradually narrowed with advancing age.
• The layers of dentine may be separated by less mineralized tissue that forms the incremental lines of Von Ebner. These lines reflect the cyclic pattern of cellular activity during the formation of dentine.

Dentine Remember:

Dentine consists of alcified tubules which are occupied by the processes of odontoblasts. the dentine of the root is covered by cementum, which is a bone-like tissue.

2. Enamel:

Enamel is made up of 99% of inorganic salts (hydroxyapatite crystals). Hence, it is considered to be the hardest substance in the body.

• Histologically, the enamel consists of enamel rods or prisms that radiate from the dentin enamel junction towards the enamel surface.
• The enamel rods are bound together by a thin layer of organic matrix called the prismatic rod sheath
• Enamel is an extracellular product of enamel organ cells. It is produced by a layer of columnar cells called ameloblasts, which covers the crown as an epithelial membrane.
• Following completion of enamel deposition (before the eruption) the ameloblasts wear off and never return.
• Thus no further deposition of enamel is possible. Therefore, this layer of ameloblasts is not present in mature teeth. Enamel is produced in waves, producing growth lines.
• These lines are at a right angle to the direction ofthe enamel rods.
• These lines are called contour Lines of Retzius and reflect the wave of enamel formation. Any erosion in enamel (caries) must be repaired through filling.

Enamel Remember:

Enamel is composed of enamel rods, which are made up of calcium hydroxyapatite crystals. Enamel is the hardest substance in the body.

3. Cementum

The enamel at the neck (from the cementoenamel junction) to the apical pore

• The cementum is bone-like tissue. It is mineralized. The main organic component is collagen and proteoglycan.
• The cementum contains cementocytes in lacunae.
• Similar to an osteocyte, a cementocyte also contains many processes within canaliculi, which radiate from lacunae.
• Cementum is an avascular tissue in contrast to the bone which is vascular.
• The collagen bundles of the periodontal membrane are anchored to the cementum.

4. Periodontal Ligament:

The periodontal ligament connects the cementum to the bone of the alveolar socket.

• It is made up of both loose and dense connective tissue.
• The dense connective tissue is found in the bulk of the periodontal ligament.
• The loose connective tissue provides passage to the blood vessels and nerves.
• Besides providing attachment and support to the tooth the periodontal ligament also helps in bone remodelling during the eruption of teeth

5. Dental Pulp:

The dental pulp is present in the pulp cavity, which is bounded by mineralized dentine. The pulp on its periphery has a layer of odontoblasts.

• The central portion of the pulp consists of fibroblasts, macrophages, mast cells, collagen fibrils and a large amount of ground substance.
• The neurovascular bundles form a network in the crown portion of the pulp, just beneath the layer of odontoblasts.
• The nerve fibres forming this network contact the cell body of odontoblasts and may also travel in dentinal tubules.
• Because of this reason, dentine is highly sensitive to pain.
• The capillary loops that form the network also enter the layer of odontoblasts.

Tooth Clinical Application

• Dental Caries: If the hygiene of the oral cavity is not maintained properly, the bacteria present in the oral cavity may destroy the enamel and dentine.
  • Bacteria when act on sugar present In the oral cavity produce acid. This acid gradually de-mineralizes the enamel and dentine leading to their destruction.
  • The resulting condition is called dental caries. If infection is not controlled, it may reach up to the pulp cavity.
  • The infection of the pulp is painful as it has sensory nerve endings
• Orthodontic Treatment: With the help of orthodontic treatment, the disposition of teeth can be gradually changed.
  • As the periodontal ligament is plastic, it allows the change in the disposition of teeth in the mouth.
  • Similarly, cementum has lower metabolic activity because it is not supplied by blood vessels.
  • Both the above facts help in the movement of teeth by orthodontic appliances.

Tongue

The tongue is an accessory digestive organ composed of skeletal muscle covered with mucous membranes. The lining mucosa consists of stratified squamous epithelium and a lamina propria.

An inverted V-shaped groove, the sulcus terminalis, divides the dorsal aspect of the tongue into anterior 2/3 (body of the tongue) and posterior 1/3 (the root of the tongue) The dorsal aspect of the root of the tongue (posterior 1/3) contains many oval or rounded elevations, which are due to the lingual tonsils.

These elevations may contain lymph nodules and may show the presence of germinal centres in. Elsewhere, where lymph nodules are not present, the mucosa shows the general properties of lining mucosa. The lingual salivary glands of the posterior 1/3 of the tongue are mostly mucous and are located in the muscular layer. These glands open into the recesses of the mucosa.

1. Lingual Papillae

The body of the tongue (anterior 2/3), on its dorsal surface, is covered with the specialization of epithelium called the lingual papillae. The lingual papillae are projections of lamina propria covered with stratified squamous epithelium, which may be keratinized. Many papillae contain taste buds.

The papillae are of four types:

1. Filiform
2. Fungiform
3. Circumvallate and
4. Foliate.

The foliate papillae are not well-developed in humans

1. Filiform Papillae:

These are most numerous ofthe lingual papillae, covering most of the anterior 2/3 of the tongue. These are conical projections about 2-3 mm in length. Their tips are keratinized. These papillae are distributed in parallel rows. Filiform papillae contain no taste buds: the increase the friction between the tongue and food

2. Fungiform Papillae:

They are found distributed among the filiform papillae. Their shape is like a mushroom (narrow base with globular upper end) and they project above the filiform papillae. They have highly vascularized connective tissue cores: hence, visible on as red dots. The taste buds are present in the epithelium on its dorsal surface

3. Circumvallate Papillae:

• Circumvallate papillae are situated just in front of the sulcus terminalis.
• They are about 8- 16 and each one measures about 1- 2 mm in diameter.
• Each papilla is surrounded by a circular sulcus (trench). The stratified squamous epithelium, covering the free surface, is smooth while the epithelium covering the walls of the sulcus (trench) contains many taste buds.
• At the bottom of the trench, there are openings in the ducts of serous glands on Ebner, which are situated in the submucosa. The secretion of these serous glands keeps the sulcus rinsed.
• A core of connective tissue, supporting vessels, lymphatics and nerves fills the papillae

Papillae Remember:

Three common papillae found in humans are filiform fungiform, and circumvallate. Taste buds are present in fungi form and circumvallate papillae. The foliate papillae are not well-developed in humans

2. Taste Buds

Taste buds are neurosensory epithelial structures embedded in the surface epithelium of the tongue.

• The taste buds are also present in the epiglottis, soft palate and oropharynx. Tongue, they are present in the epithelium of fungiform and circumvallate papillae
• Taste buds appear as onion-like, oval, pale staining epithelial structures.
• 50-80 pm in length and 30-50 pm in width. The length of the taste bud extends through the full thickness of the epithelium vertically.
• The cells of taste buds are long and vertically oriented. Their tapering apical ends converge on a small depression (opening) on the surface of the epithelium. This depression (operating) js ca|iecj as taste pore

Three different types of cells are present in the taste blends:

1. Neuroepithelial cells or Receptor cells
2. Supporting cells and
3. Basal (stem) cells

These are

1. The neuroepithelial (receptor) cells:
   • The neuroepithelial and supporting cells are elongated and extend from the basal lamina to the taste pore.
   • Both kinds of cells send their microvilli in the taste pore.  Nerve axons form a plexus around each taste bud.
   • Their branches penetrate the basal lamina of the taste bud and make contact with the receptor cells. It is believed that this cell type is the principal taste receptor
2. Supporting cells:  The supporting cells besides providing support to receptor cells, also secrete an amorphous dense material at the taste pore.
3. Near the basal lamina:  Near the basal lamina there are small dark cells called basal or stem cells. The function of basal cells is to provide new receptors and supporting cells by their mitotic activity.

Taste is a chemical sensation. Various types of chemicals (tastants) stimulate neuroepithelial (receptor) cells of taste buds. We can feel sweet, salty, bitter, sour and delicious tastes through our receptor cells.

The tastants, which are with salt and sour taste act by opening and passing through ion channels of neuroepithelial cells. The sour tastants act by closing ion channels while bitter, sweet and delicious
tastes act by acting on specific taste receptors present in neuroepithelial cells.

Taste buds Remember:

Taste buds appear as onion-like, oval, pale staining epithelial structures. Three different types of cells are present in the taste buds: receptor cells, supporting cells and basal (stem) cells. We can feel sweet, salty, bitter, sour and delicious tastes through our receptor cells

3. Muscles of the Tongue

The core of the tongue (beneath the mucous membrane) contains striated muscle. The muscle fibres are arranged in transverse, longitudinal and vertical bundles. In between the muscle bundles, variable amounts of loose connective tissue, adipose tissue and lingual glands are found.

Salivary Glands

The salivary glands are accessory glands of digestion and pour their secretion (saliva) into the oral cavity.

There are two kinds of salivary glands:

1. Minor salivary glands: These are small salivary glands situated in the mucous membrane ofthe lip (labial), cheeks (buccal), soft palate (palatine) and tongue (lingual).
2. Major salivary glands: These are parotid, submandibular and sublingual glands. Each of these glands lies completely outside the alimentary tract and is connected to it by an excretory duct. These glands are classified as compound alveolar or tubuloalveolar.

Salivary Glands Functions

Salivary glands secrete saliva, which is composed of water, mucus, proteins, salts, salivary amylase (ptyalin immunoglobulins (particularly IgA), and lactoperoxidase

• It serves to moisten food
• Lubricates and moistens oral mucosa and lip.
• It initiates the digestion of carbohydrates.

Basic Organization of Salivary Glands

As stated earlier, the major salivary glands are compound glands that consist of multiple acini at the end of the highly branched duct system.

• An acinus is defined as a group of secretory cells that are arranged around a narrow lumen.
• The duct and acini of the salivary gland resemble a bunch of grapes in which ducts represent the branching stem and acini represent the grapes.
• Acini are made up of either serous or mucous cells.
• There may be a mix of both serous and mucous acini these are called mixed salivary glands.
• In addition, some of the mucous acini may have a cap of serous cells called the parotid gland is chiefly a serous, while submandibular and sublingual are mixed glands.
• A salivary gland contains branching ducts, which are classified as in intralobular (intercalated and striated), interlobular, lobar and main excretory ducts.
• These ducts are lined by cuboidal (intercalated), columnar (striated), pseudostratified columnar (interlobular), stratified cuboidal (lobar) and major excretory ducts are lined by stratified columnar epithelium.

Salivary glands Remember:

Major salivary glands consist of multiple acini at the end of the highly branched duct system. Acini are of three types: serous, mucous or mixed. Some of the mucous acini may have a cap of serous cells called serous demilune. Ducts are classified as intralobular (intercalated and striated), interlobular, lobar and main excretory ducts

Salivary glands other Details Of Basic Organization:

A salivary gland consists of two components

1. Connective tissue component
2. Parenchymal components (ducts and acini)

The parotid and submandibular glands are surrounded by a well-developed connective tissue capsule. Septa arising from the capsule enter the parenchyma of the gland and divide the gland into lobes and lobules.

The acini and intralobular ducts are enveloped by delicate connective tissues. The connective tissue septa form a medium through the parenchymal component of the salivary gland consisting of acini and ducts.

The acini are composed of pyramidal secretory cells, which are arranged around a narrow lumen and surrounded by myoepithelial cells. The myoepithelial cells are present between secretory cells and basal lamina The lumen of acini is continuous with the duct system

Duct System

The main excretory duct of a salivary gland divides to give lobar and interlobular ducts. The interlobular ducts further divide to give intralobular ducts. The intralobular ducts are of two types, i.e., intercalated and striated. The lumen of the intercalated duct opens directly into the acinus.

1. Intercalated Ducts:

The intercalated ducts arc of short length and serve to connect acini with the striated ducts.

• These ducts are lined by short cuboidal ceils or sometimes by simple squamous epithelium.
• The cells of intercalated ducts, similar to acini may also be surrounded by myoepithelial cells.
• Intercalated ducts are prominent in the serous glands. They secrete HCO₃^– into the acinar product and absorb Cl^– from the product.

2. Striated Ducts:

The striated ducts connect interlobular ducts to intercalated ducts. These ducts are lined by simple columnar epithelium.

• These cells are stained bright pink in H&E preparation and have nuclei located near the lumen.
• These cells also show basal striations, which are due to the vertical orientation of mitochondria lodged between basal infoldings of the plasma membrane.
• This characteristic is typical of cells engaged in salt and water transport.

The intercalated and striated ducts are predominantly present in serous glands. These ducts are involved in the modification of the serous secretion (by absorbing certain constituents and secreting others, i.e., secretion of K⁺ and HCO₃^– and absorption of Na⁺).

As the mucus secretion is not modified while passing through the duct, the intercalated ducts are poorly developed and striated ducts are absent in mucous glands.

Striated duct Remember:

The basal plasma membrane of striated duct cells is highly folded. The longitudinally oriented, elongated mitochondria are enclosed in these foldings. Striated ducts are the sites of reabsorption of sodium and secretion of potassium

3. Interlobular, Lobar and Main Excretory Ducts:

These larger ducts are lined by epithelium that ranges from simple columnar to pseudostratified columnar (interlobular ducts) to stratified columnar or stratified cuboidal (lobar and main excretory ducts) At its opening in the oral cavity, it may be lined by stratified squamous epithelium. These ducts are surrounded by a large amount of connective tissue.

The Secretory Acinar System

The acini are described as

1. Serous
2. Mucous and
3. Mixed

1. Serous Acini:

Serous acini have a small lumen and produce a clear watery secretion. Serous cells are usually pyramidal and have rounded nuclei located near the base.

• A large amount of rough endoplasmic reticulum and free ribosomes are present near the base.
• Because of this acini are stained with haematoxylin (basophilic) near the base.
• Above the nucleus and Golgi complex, apical secretory granules (zymogen granules) are present.
• The presence of secretory granules is responsible for the staining of the apical portion by eosin.

2. Mucous Acini:

The mucous acini arc is usually tubuloalveolar and has relatively wide lumens.

• Mucous cells arc roughly pyramidal or columnar and have flattened nuclei situated near their base.
• The apical portion of the cell contains mucus, which is stored in the form of mucinogen granules.
• Because the mucus is lost in the preparation of H&E-stained paraffin sections,
• The apical portion ofthe cell is not stained and shows an empty appearance

3. Mixed Acini:

Submandibular and sublingual salivary glands contain both (serous and mucous) types of acini. In addition, some ofthe mucous acini may have the cap of serous cells called serous demilune.

Differences between serous and mucous acini:

Myoepithelial Cells (Basket Cells):

These star-shaped (branched) cells are present between the epithelium and basal lamina of the acinus and the proximal part of the duct. They contain actin filaments and hence are contractile. Their contraction is thought to help in expelling the secretion from the lumen facing.

Parotid Gland

The parotid gland is the largest salivary gland. It has a well-defined capsule. Septa divide the gland into lobes and lobules.

1. Secretory acini: The acini are purely serous The gland has abundant myoepithelial (basket) cells that help to expel the secretory product from the lumen of the acinus
2. Ducts: The interlobular ducts are present in the connective tissue septa. These ducts may be lined by simple columnar or pseudostratified columnar epithelium. The intralobular ducts are seen between acini. The intercalated ducts are lined by simple squamous to low cuboidal epithelium.

They are long and branching in the parotid gland. The striated ducts are lined by simple low columnar epithelium and show basal striations. The striations are responsible for the bright eosinophilic (acidophilic) staining reaction of these ducts The adipose tissue may be seen among acini and smaller ducts.

Parotid gland Clinical Applications

Mumps:

The infection of the parotid gland by mumps virus (Myxovirus) is called mumps. In this disease, there is swelling and enlargement of the parotid gland and severe pain in the throat. The infection may also spread to other salivary glands. The disease is self-limiting

Submandibular Gland

The submandibular gland is a mixed gland. It has a well-defined capsule and septa, which divide the gland into lobules.

• Secretory acini: It consists of both serous and mucous acini However, sometimes the serous acini are more than mucous. At certain places, mucous acini are capped by a layer of serous cells, which may present a half-moon appearance in some sections; hence, they are called serous demilunes.
• Ducts: The epithelial lining of the main, interlobular and intralobular ducts are the same as in the parotid gland. However, the striated ducts of the submandibular gland are large and branching; hence, many are seen between acini.

Serous demilunes are, not the true histological structures:

The serous demilunes are observed in the mixed salivary gland (both under light and electron microscopes) after the tissue is fixed by the routine fixation method. However, when

• The tissue is preserved by the rapid freezing method and observed under the transmission electron microscope, a different kind of histological structure of the gland is observed.
• Here, the acini of mixed glands consists of both serous and mucus-secreting cells.
• One end of these cells rests on the basal lamina and the other end projects into the lumen of acini. Both the serous and mucous cells arc almost of the same size.
• The serous cells arc pyramidal in shape and the shape of mucous varies from short columnar to pyramidal.
• The mucous cells contain centrally located rounded nuclei and many mucinogen granules in the apical region.
• Both types of cells pour their secretion into the lumen of acinus. This appearance ofthe mucous cells seems to be the real one as the rapid freezing method preserves the tissue with minimal alteration in its morphological structure and chemical composition.

The acini, as seen in resembles the above description of tissue preserved with the rapid freezing method.

• However, when the tissue slides are prepared by using routine chemical fixative (usually formaldehyde), then the fixative causes the swelling of mucinogen granules in the mucous-secreting cells.
• This pushes the nucleus ofthe cell towards the basal lamina, which under the pressure of mucinogen granules becomes flattened. These swollen mucous cells also push the pyramidal-shaped serous cells towards the periphery of the acinus.
• It appears as if mucous acinus has having crescentic-shaped cap of serous cells, which is traditionally described as serous demilune

The tissue was obtained from an adult goat and preserved in formaldehyde.

Even though this tissue was not preserved by the rapid freezing method, its ducts showed similar features as described for rapid freezing fixed tissue.

Question 1. Why we must have found these kinds of mixed acini after routine fixation?
Answer:

The possible explanation for this may be that the goat is a ruminating animal as partially digested cud comes back in its mouth at intervals. As these animals constantly chew, the saliva is also produced constantly in large quantities.

This may be the reason for the nonaccumulation of a large quantity of mitogen granules in the mucous-secreting cells in a goat. During chemical recreation, though these granules swell they may not exert much pressure on the neighbouring serous cells. Thus, in most ofthe mixed acini serious demilunes fail to form

The above description indicates that not only the serous demi lunes but also the large size of mucous cells, the basal position and the flattered shape of its nuclei are also the artefacts of chemical fixation.

Chemical fixation Remember:

Serous demilunes and mucous cells as observed in histological slides after chemical fixation, are not the true histological structure but are artefacts of chemical fixation.

Differences between serous and mucous cells

Sublingual Gland

It has no definite capsule. The septa divide the gland into lobules

• Secretory acini: The sublingual gland is made up predominantly of mucous-secreting acini  Some mixed acini with serous demilunes are also io seen. The pure serous acini are rarely seen. Thus, it is classified as a mixed salivary gland.
• Ducts: The main and interlobular ducts are present. Very’ few striated ducts are seen in this section. Intercalated ducts are difficult to find (rarely seen).

Respiratory System

The respiratory system consists of the nose, pharynx larynx, trachea and lungs.

Respiratory System is concerned with the following functions:

• Perception of smell: The olfactory mucosa of the nasal cavity contains receptors for the sense of smell
• Filtration of inhaled air: The upper respiratory mucosa of the nasal cavity contains receptors for the sense of smell.
• Phonation: The Larynx helps in the production of sounds. The larynx also prevents the entry of solid food, liquid and foreign bodies into the trachea and lungs
• Respiration: Exchange of gases, i.e., intake of O and elimination of ofCOr This process of exchange of gases is called respiration.
• Maintenance of blood pH: It participates in the regulation of blood pH.

Functionally, the respiratory system consists of two factors:

1. Conducting part: It conducts the air from nose to lung and consists of the nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles. The trachea bronchi and bronchioles are branching systems of tubes The conducting part also filters, warms and moistens the while passing through it
2. Respiratory part: It is located strictly within the lungs and consists of spongy respiratory tissue of the lungs across which blood and air exchange their gases.It consists of respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli

The Conducting Part Of The Respiratory System

The conducting part of the respiratory system consists of the

1. Nasal cavity,
2. Nasopharynx
3. Larynx
4. Trachea and Primary bronchi
5. Intrapulmonary bronchi and
6. Bronchioles.

Histology of Nasal Cavity, Nasopharynx and Larynx:

1. Nasal Cavities

The nasal cavities repaired chambers separated by septum. Each nasal cavity is a hollow organ composed of bone, cartilage and connective tissue covered by mucous membrane. The nasal cavity chamber is divided into three regions, i.e., nasal vestibule, respiratory region and olfactory region.

Nasal vestibule:

This is the most anterior dilated part. the nasal cavity. It is situated inside the nostril and lined by hair skin These hair filter large particles from in Spired air

Respirators- region:

It is the largest part of the nasal cavity. It is occupied by the lower 2/3 part of the nasal cavity. The respiratory portion of the nasal cavity is lined with pseudostratified ciliated columnar epithelium with goblet cells.

• Underlying this epithelium, aminapropria contains ser°us mucus-secreting glands, large venous plexus, lymphatic tissue collection, plasma cells and macrophages
• Cilla on tall colour cells act as filter and their beatings carry foreign matter and mucus towards the oropharynx where they are swallowed’ The goblet cells Produce mucus to trap foreign particles and keep the membrane moist
• The cells in lamina propria (lymphocytes, plasma cells macrophages, etc) serve aprotective function.
• The large venous plexus warms the air, and seromucous glands provide the moisture and mucus.
• Thus, while passing through the nasal cavity, the air is conditioned, i.e., it is wanned, moistened and freed of dust particles.
• The upper respiratory tract is exposed to a wide variety of pathogens in the process of warming, humidifying and filtering the inspired air.
• These organisms may lodge and grow in the host This may lead to an upper respiratory infection (sore throat tonsillitis and infection of paranasal air sinuses)

Respiratory system Remember:

The inhaled air is conditioned before reaching the lung alveoli. This is achieved by warming, humidifying and filtering the inspired air while it is passing through the conducting part of the respiratory system.

 Olfactory region:

It is occupied by the upper 1/3 part of the nasal cavity near its apex. It is lined by specialized olfactory mucosa. The total area of olfactory mucosa is only about 1 0 cm² area. The epithelium of olfactory mucosa is pseudostratified.

Composed of the following types of cells:

1. Olfactory receptor cells: These are modified bipolar neurons that send axons to the olfactory nerve. Their apical portion bears cilia (hair).
   • These cilia are involved in olfactory transduction pathways.
   • Cilia have numerous odour receptor molecules.
   • The molecules of odoriferous substance dissolved in serous fluid bind to the specific receptor molecules.
   • This generates the action potential and information is passed to the brain
2. Supporting cells: These are long columnar cells which provide mechanical support to olfactory receptor cells
3. Basal cells: These are present near the basement membrane. They differentiate into receptor and supporting cells
4. Olfactory glands (Bowman’s glands): These are present in the lamina propria. They deliver their proteinaceous secretion via ducts onto the olfactory surface

Olfactory Remember:

The olfactory mucosa is pseudostratified and composed of olfactory receptor cells, supporting cells and basal cells. Olfactory glands (Bowman’s glands) are present in the lamina propria.

2. Nasopharynx

It lies between the nasal cavity and the oropharynx. The nasopharynx is also covered with pseudostratified ciliated columnar epithelium goblet cells.

3. Larynx

It begins with the epiglottis and ends at the trachea. Most ofthe parts ofthe larynx are also covered by pseudostratified ciliated columnar epithelium with goblet cells. Lamina propria at places may contain seromucous glands and lymphatic tissue.

Epiglottis:

The epiglottis consists of a plate of elastic cartilage in the middle. On both the sides of cartilage, there is the presence of lamina propria. Lamina propria contains seromucous glands. The anterior surface (facing tongue) and upper part of the posterior surface of the epiglottis are lined by stratified squamous epithelium.

The remaining pan of the posterior surface is lined by pseudostratified ciliated columnar epithelium with goblet cells.

4. Trachea and Primary Bronchi

The histological structures of the trachea and primary bronchi are essentially the same. The trachea is a flexible tube measuring about 11 cm in length and 2 cm in diameter. Its wall contains 1 6-20 C-shaped hyaline cartilages, which keep the lumen of the tube patent. The gap between the free ends of a C is bridged by a muscle called the tracheal

The trachea divides into two principal (or primary) bronchi The trachea and primary bronchi consist of four layers.

• Mucous membrane (epithelium and lamina propria): The epithelium is a pseudostratified ciliated columnar with goblet cells. The epithelium rests on thick basal lamina. Three different types of common cells of epithelium are ciliated cells (30%), goblet cells (28%) and basal cells (29%).
  • The ciliated cells propel the mucus upwards and their percentage increases from the upper to the lower trachea.
  • The goblet cells produce mucus. The basal cells are small pyramidal cells situated near the basal lamina.
  • They act as stem cells that can divide and differentiate to replace other cell types
  • The other two less common cells are granule cells Kulchitsky cells) and brush cells.
  • The small granule cells are situated at the base ofthe epithelium and contain dense secretory granules in an intranuclear position.
  • These cells discharge their contents in response to hypoxia. The brush cells contain large microvilli with an actin filament core extending down into the cytoplasm.
  • The nerve terminals are seen in these cells. These cells contain no secretory granules and may have sensory functions
  • The lamina propria of the trachea and principal bronchi is made up of loose connective tissue, which is rich in elastic fibres.
  • It may also contain lymphatic tissue, in both diffuse and nodular forms.
•  Submucosa: In the trachea, it is difficult to distinguish the boundary between lamina propria and submucosa.
  • At the junction of the two, there is a dense layer of elastic fibres, which is seen with a special stain.
  • The submucosa contains mixed seromucous glands whose ducts open onto the surface epithelium
• Cartilage and smooth muscle layer: This layer consists of a hyaline cartilaginous ring separated by interspaces bridged by fibroblastic connective tissue.
  • The rings of cartilage are incomplete posteriorly.
  • The gap is filled by smooth muscle (tracheal) and by fibroblastic tissue.
• Adventitia: External to the cartilaginous ring, there is a layer of connective tissue that is rich in elastic fibres.

Trachea and primary branch Remember:

The trachea and primary bronchi consist of four layers, i.e., mucosa (lined by pseudo-stratified ciliated columnar epithelium with goblet cells resting on lamina propria) submucosa (contains mixed seromucous glands, cartilage and srn°°th muscle layer and adventitia.

5. Intrapulmonary Bronchi

The primary bronchi enter the lung through the hilum. In the lung, primary bronchi branch into lobar bronchi, which in turn divide into segmental bronchi. The segmental bronchi branch many times as they penetrate further into the lung, resulting in many orders of decreasing diameter.

Following are the layers observed in the intrapulmonary bronchi:

• Mucosa: The epithelium is pscudoslrati tied ciliated columnar with goblet cells. The lamina propria contains many clastic fibres and seromucous glands
• Smooth muscle layer: The smooth muscle layer is present in lamina propria beneath the epithelium Smooth muscle is arranged in bundles, which run spirally. Elastic fibres arc intermixed with muscle
• Submucosa: It consists of the loose connective tissue in which glands are embedded.
• Cartilage layer: In contrast to C-shaped cartilage present in the trachea, the intrapulmonary bronchi contain irregular plates of cartilage. These cartilaginous plates surround the bronchi and keep them open. Therefore, intra-pulmonary bronchi are always cylindrical rather than flattened on one side as arc the trachea and primary bronchi.
• Adventitia: Outside the cartilage layer adventitia is made up of the connective tissue layer

As the bronchi divide repeatedly and become smaller in size each component of the wall becomes thinner and sparser, except the layer of smooth muscle, which remains distinct The submucosal glands gradually decrease in number and end at the level ofthe bronchiole.

Intrapulmonary Bronchi Remember:

In contrast to the trachea, bronchi contain circumferentially arranged smooth muscle layers in lamina propria and irregular plates of cartilage

6. Bronchioles

Bronchioles are defined as conducting tubules that are less than 1 mm in diameter and their wall no longer contain The bronchioles further divide to end in the terminal bronchioles, which are the terminal segments ofthe conducting portion of the respiratory tract. Terminal bronchioles subdivide into microscopic branches called respiratory bronchioles.

Following are the layers observed in bronchioles:

• Mucosa: The type of epithelium varies with the size of the bronchiole. Large bronchioles have simple ciliated columnar cells with very few goblet cells.
  • The smaller bronchioles have simple cuboidal ciliated cells with no goblet cells. The Clara cells replace the goblet cells.
  • These cells are non-ciliated but have many microvilli on their apical surface.
  • They first appear in small bronchi but greatly increase in number of terminal bronchioles.
  • Clara cells are considered to secrete a lipoprotein, which forms a protective layer of surface active agents throughout the lower respiratory tract.
  • Surface active agent reduces the surface tension of the alveolar fluid, which reduces the tendency of alveoli to collapse. It also prevents the adhesion between walls forming a lumen of air passage, especially during expiration.
  • Clara cells also produce a 16-kilodalton protein known as Clara cell secretory protein (CC16). Seromucous glands are not present in the lamina propria of bronchioles.
• Smooth muscle layer: It is a prominent layer and a major component of the wall. The smooth muscles are supplied with sympathetic and parasympathetic nerves.
  • Normally, the muscle layer regulates the passage of air through it.
  • But sometimes the hyperirritability of the respiratory tract may lead to the excessive contraction of smooth muscle
  • This results in the constriction of bronchi and bronchioles and may cause difficulty in breathing. This condition may arise in a person suffering from asthma
• The connective tissue layer:
  • Outside the muscle coat, the bronchioles are surrounded by lung alveoli.
  • The bronchioles and lung alveoli are connected with the connective tissue layer, which is rich in elastic network

Bronchioles Remember:

Bronchioles are less than 1 mm in diameter. Cartilage plates and glands are absent. However, Clara cells are present in their epithelial lining.

Differences between bronchus and bronchiole:

Conducting part of respiratory system Clinical Applications

Asthma

Asthma is an acute, episodic, airway obstruction that results from an allergy to a variety of substances (such as pollen, house dust, mites, moulds or a particular food).

• A person suffering from asthma tends to develop bronchospasm, which leads to obstruction of airways and air trapping.
• The bronchospasm (airway obstruction) may be due to smooth muscle spasm in the wall of smaller bronchi and bronchioles, increased secretion of mucus and swelling of mucosa
• A person suffering from asthma has difficulty in breathing, tightness in the chest, cough and anxiety.
• Asthma is treated with drugs, which relaxes smooth muscles in the bronchioles and opens up the airways.

The Respiratory Part Of Respiratory System

Respiratory Bronchioles, Alveolar Ducts and Alveolar Sacs and Alveoli

1. Respiratory Bronchioles

• Respiratory bronchioles are the site of transition from the conducting part to the respiratory part.
• It is called respiratory bronchiole because it is partly respiratory in function
• A respiratory bronchiole usually measures less than 0.5 mm in diameter
• The respiratory alveoli are present in its wall as outpouching.
• The epithelium is simple cuboidal with cilia, which are gradu¬ ally lost and are replaced by non-ciliated low cuboidal cells
• The Clara cells are also present in between cuboidal cells
• A smooth muscle layer is still present outside the epithelium
• Outermost covering is ofdelicate connective tissue.

2. AlveolarDucts and Alveolar Sacs

Each respiratory bronchiole ends by dividing into 2 or 3 alveolar ducts. Many alveoli and alveolar sacs open into the alveolar duct. At the end of the alveolar duct, the clusters of alveoli share a common opening to the alveolar duct. This cluster of alveoli is called as alveolar sac.

3. Alveoli

These are thin-walled polyhedral sacs, one side of which is always lacking. Alveoli are round or polygonal in shape and about 200 pm in diameter.

• They consist of pure respiratory surfaces across which gaseous exchange occurs.
• Alveoli are closely packed, so the alveolar wall is a partition 2 present in their epithelial lining.
• Remember or septum between two alveoli. The interalveolar septa contain a network of capillaries, supported by reticular and elastic fibres, and occasionally fibroblasts and macrophages between the squamous epithelium of adjacent alveoli.

There may be openings in septa, which are called pores. These pores help in the circulation of air from one alveolus to another, thus equalizing the pressure in the alveoli. The alveolar pores play another important role in case of blockage of air passage.

The alveoli distal to the blockage may get air from the alveoli of neighbouring lobules. Wherever the endothelium of the capillary comes in contact with the alveolar epithelium no connective tissue lies in between the two.

Respiratory bronchioles Remember:

Respiratory bronchioles are partly respiratory in function where the exchange of gases occurs. Alveolar duct, atria and alveoli are supplied by rich capillary network and are the site of gas exchange

The blood-air barrier:

The air in the alveolus is separated from the blood in the capillary by following three structures

• Continuous non-fenestrated endothelium of capillary.
• Squamous epithelium lining the alveolus.
• The fused basal lamina of endothelium and epithelium

This thin (1.5 – 2μm) blood-air barrier facilitates the diffusion of oxygen and carbon dioxide.

4. Cells of Alveolar Wall (septum)

The alveolar wall (septum) is covered with the following types of epithelial cells

Type 1 alveolar cells (squamous epithelial cells/pneumocyte 1):

These are very thin squamous cells. These cells cover over 95% ofthe alveolar surface

Type 2 alveolar cells (great alveolar cells/ pneumocyte):

These are large rounded cells, which bear microvilli on their apical surface. These cells are placed in between type 1 cells and the remaining 5% surface area of alveoli.

• Type 2 alveolar cells are secretory and secrete the pulmonary surfactant, which lowers surface tension and prevents alveoli from collapsing during expiration.
• When viewed under electron microscope an electron microscope the secretory granules of these cells show a peculiar appearance.
• These granules contain membrane-like layers arranged parallel one upon the other.
• These layers are made up mainly of phospholipids and proteins (precursors of surfactants). The surfactant is secreted continuously by cytosis.
• This kind of secretory granules is called s. Type 2 alveolar cells also give origin to type 1 alveolar cells. After lung injury, they give origin to type 1 and type 2 cells within lung alveoli.
• Besides secreting lipoprotein surfactant, type 2 cells also produce various types of proteins (surfactantprotein A, B, C and D). These proteins modulate alveolar immune responses.

Type 3 alveolar cells (brush cells):

• These cells are found only occasionally in the alveolar epithelium. These cells serve as receptors to monitor the quality of air entering the lung
• All cells forming the alveolar epithelium are joined to each other by zonula occludens.

Alveolar Remember:

95% of the alveolar wall is covered by type 1 pneumocytes, which are involved in the exchange of gases. The remaining 5% of the alveolar wall is covered by type 2 pneumocytes involved in the secretion of surfactant. Brush cells are also found occasionally in the alveolar epithelium. Brush cells serve as receptors to monitor the quality of air entering the lungs.

5. Alveolar Macrophage

These cells are found in the connective tissue of interalveolar septa. Some of these cells enter the connective tissue from blood and pass through the alveolar epithelium to reach into the lumen alveoli. Alveolar macrophages are the first line of defence against pulmonary infection.

They act in the following way:

• They phagocytose dust particles, which may be seen in their cytoplasm.
• Hence, sometimes they are also called dust cells.
• In cigarette smokers, they engulf carbon and tar
• They are also capable of phagocytosing bacteria In patients of heart failure (here pulmonary capillaries are overloaded with blood), erythrocytes may accumulate in alveoli.
• These erythrocytes are phagocytosed by macrophages, which acquire a brick-red colour because of the presence of haemosiderin (a product of haemoglobin degradation and are then called as heart failure cells.

The respiratory part of the respiratory system Clinical Application

Pneumonia

• It is an acute infection of the lung alveoli. Pneumococcal pneumonia is the most common bacterial pneumonia and represents a threat to the aged and chronically.
• When microorganisms enter the lungs, they produce toxins which in turn stimulate inflammation and immune response.
• This leads to a collection of exudates, plasma proteins, RBCs, fibrin and leucocytes in the alveoli.
• This interferes with ventilation and gas exchange.
• The clinical signs include fever, cough, chest pain, blood-streaked sputum and difficulty in breathing. Pneumonia is treated with antibiotics

Cigarette Smoking and Cancer of Lung

The association between cigarette smoking and cancer of the lung is well known.

• Although the bronchial tree is mainly lined by pseudostratified ciliated columnar epithelium, it changes to stratified squamous epithelium in chronic smokers because of the presence of toxic elements in smoke. (The epithelial alteration from one kind to another is known as metaplasia.)
• This transformation is the first step in the development of squamous cell carcinoma, which is the main type of cancer of the lung.

Different Types of Ceils ofRespiratory System and their functions

1. In the epithelium of the trachea, bronchus and bronchiole:

• Ciliated cells: Beating oftheircilia moves the mucus upward
• Goblet cells: These cells produce mucus, which traps the dust particles
• Basal cells: They multiply and give rise to another type of cell
• Granule cells: They are believed to be endocrine cells.
• Brush cells: Sensory
• Clara cells: Produce secretion, which reduces the surface tension in alveoli

2. In the epithelial lining of lung alveoli:

• Type 1 alveolar cells (pneumocytes 1/squamous cells): Exchange of gases occurs through these cells
• Type 2 alveolar cells (pneumocytes 2): These cells produce pulmonary surfactant, which prevents collapse ofthe alveolus during expiration.
• Brush cells: They are considered to be sensory cells.

3. About the lumen of lung alveoli:

Macrophages: They phagocytose dust particles (dust cells) or erythrocytes (heart failure cells).

Distribution of epithelium in various parts of respiratory passage:

Integumentary System (Skin) Introduction

The skin is the outer covering of the body. The hair, sebaceous glands, nails and sweat glands are considered as derivatives or appendages of skin. Skin is the largest organ of the body. It consists of 16% of the body weight. The skin and its appendages constitute the integumentary system.

1. Skin Functions

• It acts as a protective shield for the body and protects us from injury, microorganisms, ultraviolet irradiations and chemical injuries.
• It provides a water barrier. Water cannot be absorbed or lost through superficial layers of epidermis, i.e., stratum corneum
• Sweat glands and unique vascular supply help in heat regulation. Sweat glands also excrete waste like urea
• Skin is an important sense organ for sensations like pain, touch, temperature and pressure
• It helps in the absorption of ultraviolet radiation from sun for the production of vitamin D

Skin Remember:

The skin along with its accessory structures is considered an important body system, which serves many important functions

2. Thick and Thin Skin

The skin on the surface of the palm and sole is thick. Here, the epidermis is much thicker than elsewhere. Thick skin is hairless skin in other places in the body, skin is thin and hairy, for details on thick and thin skin.

Differences between thin and thick skin:

Microscopic Structure Of Skin

The skin consists of two layers

1. Epidermis
2. Dermis

1. Epidermis:

It consists of stratified squamous (keratinized) epithelium. Following live layers can be distinct-guessed in thick skin from deep to superficial surface.

1.  Stratum hostile: It consists of a single layer of cuboidal cells, which are situated on the dermis. A thin basement membrane is situated between the stratum basale and der¬ mis. Basally located hemidesmosomes attach the cell to the basal lamina. Cells of this layer show high mitotic activity. The newly produced cells move towards the superficial layer
2. Stratum spinas am: It consists of several layers of polygonal cells, which are held together by desmosomes. These cells contain tonofilaments and tonofibrils in their cytoplasm. The presence of tonofibrils causes the cytoplasm to become eosinophilic. The artefact of fixation causes shrinkage of the cell membrane except at the desmosomes, giving the cell a spiny appearance. Because of this reason, this layer is called stratum spinosum
3. Stratumprumdusunr: This layer is made up of 3 5 layers of flattened polygonal cells. These cells are filled with keratohyalin granules
4. Stratum lucidum: This layer is seen only in thick skin. Cells in this layer are flattened, translucent, eosinophilic and without any organelles including the nucleus. These cells are filled with proteins called keratin and eleidin (a product of keratohyalin)
5. Stratum corneum: It is the most superficial layer of the epidermis. It is composed of structureless dehydrated dead cells. The interior of the cell is filled with keratin. The thickness of the stratum corneum is much higher in thick skin compared to thin skin. The superficial layer ot the stratum corneum is continuously sloughed oil. This process takes 20- 30 days

Stratum  Remember:

The appearance of the cells of stratum spinosum is due to their shrinkage during fixation in formaldehyde during the preparation of the slide. In living conditions, cells are almost rounded and without spines. Students should also remember that layer “stratum lucidum” is only present in thick skin. They should not try to find this layer while observing a slide of thin skin

2. Dermis

The dermis is predominantly made up of collagen bundles.It also contains elastic fibres, connective tissue cells, nerves, lymphatics and blood vessels. Dermis is usually divided into two layers

• Papillary layer: It is a narrow band of loose connective tissue in contact with the basement membrane of the stratum basale. This layer shows finger-like processes projecting into the undersurface of the epidermis. These projections are called as dermal papillae and serve to interlock the dermis and epidermis. The papillae contain type 3 collagen and elastic fibres, nerves, blood vessels and various types of connective tissue cells
• Reticular layer: The reticular layer of skin is an example of dense irregular connective tissue. It contains coarse bundles of type 1 collagen, thick elastic fibres, nerves, and blood vessels, but few connective tissue cells (fibroblasts, mast cells, lymphocytes, macrophages and fat cells

Skin Pigmentation: 

The colour of the Skin depends on the following factors:

• The pigment carotene of epidermal cells is responsible for the yellow colour of skin.
• Carotene is an exogenous or ange pigment taken up from food and concentrated in tissue containing fat
• The pigment melanin of epidermal cells gives a black colour to the skin
• The blood vessels of the dermis are responsible for the pink colour of the skin

The colour of the skin of an individual depends on a combination of the above factors.

Cells of Epidermis

The following types of cells are seen in the epidermis

• Keratinocytes: ‘Ninety per cent of cells in the epidermal layer arc epithelial cells, which are sometimes called keratinocytes (because of their capacity to produce protein keratin). The process of formation of keratin filaments is a continuous process, while the keratinocytes pass from stratum basale through st. spinosum and st. granulosum to the st. corneum
• Melanocytes:  The melanocytes are rounded cells with dendrite-like branches. These cells are present in the stratum basale. Melanocytes produce melanin pigment, which is responsible for the colour of skin.
  • They transfer melanin pigment to epidermal cells by “cytocrine secretion” (cell-to-cell transfer, i.e.„ it is a process in which keratinocytes phagocytosis the tip of melanocyte process) through their long dendrite-like branches.
  • These cells are derived from neural crest cells.
  • In white people, melanin is degraded by lysosomes, while in black people this pigment is more stable.
  • Melanin saves the nuclei from the ultraviolet rays of the sun
  • The melanin pigments arc present in the supranuclear region to protect the nucleus from ultraviolet rays from the sun

• Langerhans Cells: These cells are also called non-pigmented granular dendrocytes.
  • These cells are present in the stratum spinosum and normally constitute 2 to 4% of the epidermal cell population (their number may reach up to 800 per mm²).
  • They possess dendritic processes similar to melanocytes. Its nucleus is indented in many places and the cytoplasm contains rod-shaped granules.
  • Langerhans cells are phagocytic and belong to the mononuclear phagocytic system.
  • These cells protect the skin from foreign invasions, i.e., antigens, micro-organisms etc.
  • Therefore Langerhans cells are also known as antigen-presenting cells
• Merkel Cells: Merkel cells are sensory cells of the epidermis.
  • They are present in stratum basale and innervated by sensory nerves. Merkel cells are abundant in the fingertips, oral mucosa and hair follicles.
  • It is believed that Merkel cells function as mechanoreceptors. These cells are derived from the neural crest.

Cells of the epidermis Remember:

The cells of the epidermis are also known as keratinocytes The 90% of the cells of the epidermis are keratinocytes, while the remaining are melanocytes, Langerhans and Markel cells. Melanin saves the nuclei from the ultraviolet rays of the sun. Langerhans cells are known as antigen-presenting cells, while Merkel cells function as mechanoreceptors.

Skin Clinical Applications

• Albinism: Albinism is a kind of inborn error of metabolism. Here, melanocytes are unable to synthesize melanin pigments due to the absence of the enzyme tyrosinase. Thus, skin remains unprotected from sunlight and may develop skin cancers (basal and squamous cell carcinoma).
• Vitiligo: In vitiligo, there occurs the degeneration and disappearance of already existing melanocytes. This results in patchy de-pigmentation of the skin
• Warts: Warts are small round growths from the epidermis caused due to infection of epidermal cells by papillomaviruses. The virus invades skin cells and forces them to multiply, resulting in thickened areas of skin. Warts usually occur on hands and feet and mostly are harmless. Warts may also occur on the sole
• Skin Cancer:
  • Chronic exposure to excessive solar ultraviolet radiation may damage the DNA leading to basal cell carcinoma or malignant melanoma
  • In adults, most of the skin tumours are derived from basal cells, squamous cells of the stratum spinosum and melanocytes. They produce basal cell carcinoma, squamous cell carcinoma and melanomas, respectively
  • Malignant melanoma is an invasive tumour of melanocytes. This tumour may penetrate the basal lamina to enter the dermis. From here it may invade the blood and lymph vessels to gain wide distribution throughout the body

Question 1. Why does skin become wrinkled in old age?
Answer:

The suppleness of the skin, in young and adults, depends on the adequate presence of collagen and elastic fibre in the dermis. However, in old people there occurs the loss of these fibres due to decreased production. The overexposure to the sun also causes the degeneration of these connective tissue fibres. Both these conditions result in the wrinkling of the skin

Derivatives Of Skin

The following are the derivatives of the skin:

1. Nails
2. Hair
3. Sebaceous glands
4. Sweat glands and
5. Mammary glands

1. Nails

Various parts of nails are the inferior surface of the nail sits on a nail bed, which is made up of the stratum basale and stratum spinosum ofthe epidermis. The germinal matrix is the portion of the nail bed involved in the growth of the nail. The body and root ofthe nail are modified stratum corneum. The body of the nail corresponds to the upper cornified layer of the skin

2. Hair

A hair has a shaft, which projects above the surface of the skin, and a root which is enclosed by a hair follicle. The hair follicle is a tubular invagination that is partly epidermal and partly dermal origin

1. Structure of Shaft and Root of Hair: The structure of the shaft and root of hair consists of epidermal cells that are for the most part keratinized. These cells contain hard keratin and melanin granules. In a cross-section, various layers are seen such as the medulla, cortex and cuticle
2. Structure of Hair Follicle: The hair follicle is a tubular invagination of the epidermis and dermis in which the hair root resides Epithelial root sheath is derived from the epidermis. It has two parts
   1. Outer epithelial root sheath: This layer is the continuation of the skin and corresponds to the stratum basale and stratum spinosum
   2. Inner epithelial root sheath: This is a keratinized sheath that arises from cells in the hair matrix

Connective tissue root sheath:

• The connective tissue root sheath is derived from the dermis. It contains nerves vessels, etc. The arrector pili muscle (smooth muscle) extends from the papillary layer of the dermis to the connective tissue sheath surrounding the hair follicle. The contraction of the muscle depresses the skin and elevates the hair shaft and skin around the hair shaft. This leads to the
• Formation of “goosebumps” on the surface of skin. The Goosebumps are seen when a person is frightened (sympathetic overactivity) or chilled.

Hair bulb:

• The lower end of the hair follicle is expanded and this expansion is called a hair bulb. The cells of the hair bulb correspond to those of the stratum spinosum and form a germinal matrix or hair matrix. These cells are concerned with the growth ofthe hair.
• The cells of the germinative layer make up a single layer that rests directly on the dermis (the hair papilla). New cells are produced here and push older cells up. Cells acquire melanin and become keratinized.

Hair papilla (dermal papilla):

• The dermal papilla fills the indentation at the base ofthe hairbulb.
• It consists of highly cellular connective tissue, which is rich in cells, capillaries, and nerves and contains melanocytes.

Hair Remember: Hairs consist of keratinized cells that develop from hair follicles

3. Sebaceous Glands

These glands are present in the dermis in association with hair follicles.

• It secretes oily substances called sebum, which consists of cellular debris and various types of lipids.
• The sebum functions as a lubricant of the skin and hair shaft (prevents their dryness).
• The sebaceous gland is a solid mass of cells (thus no lumen is present).
• The basal cells undergo mitosis and polyhedral daughter cells are pushed towards the centre ofthe glands. The centrally located cells are degenerating.
• As the cells of sebaceous glands contain lipids they are either unstained or stained lightly with eosin in
• H&E preparation. The gland has a short and wide duct, which opens into a hair follicle The mode of secre¬ tion is holocrine, i.e.,
• The entire cell is lost in the process of secretion. The contraction of arrector pilgrim helps in the exudation of secretion’

Sebaceous Remember:

The sebaceous gland secretes sebum that functions as a lubricant of skin and hair shaft (prevents their dryness)

Sebaceous Clinical Applications

• Acne Vulgaris: At puberty, under the influence of sex hormones, sebaceous glands grow In sire and increase their production of sebum.
  • If the normal secretion of sebum is obstructed, then it may result in acne.
  • Acne Is the inflammation of sebaceous glands due to Infection by bacteria.
  • Acnes are small elevations of skin (pimples) that may contain pus and are usually confined to the face.
  • This occurs predominantly in teenagers. The disease is self-limiting and dis¬ appears after some time.

4. Sweat Glands

It is a simple (unbranched) tubular gland of epidermal origin. Sweat glands extend from the surface of the epidermis to the subcutaneous layer. It has two parts, i.e., the secretory portion and the excretory duct

The secretory portion is present in the deep dermis or subcutaneous tissue in the form of a twisted coil. The epithelium is simply cuboidal or columnar. It has three types of cells, i.e., clear cells, dark cells and myoepithelial cells In H and E preparation, clear cells look light due to abundant glycogen in their cytoplasm and dark cells contain large amounts Of RER.

Clear cells secrete watery components and dark cells secrete glycoprotein of sweat. The contractile myoepithelial cells are located between the base of secretory cells and basal lamina. Contraction of these cells helps in the expulsion of secretory products to Duct

The excretory duct is long and extends From the secretory portion to the surface of the epidermis. The epidermal portion is spiral and has no lining of its own it is bordered by epidermal cells of epidermis. The portion of duct lying in the dermis is lined by stratified cuboidal epithelium. These cells are involved in the reabsorption of sodium from the sweat. The secretion of the sweat gland is clear and watery and may contain electrolytes, urea lactic acid and some drugs etc, the mode of secretion is merocrine

Sweat glands are of two types:

1. Eccrine and
2. Apocrine

Eccrine sweat glands are widely distributed throughout the skin, but are present most densely in the skin of palms and soles (up to 450 glands per square centimetre) Apocrine glands are found in the skin ofaxilla, groin, areola of the breast, labia minora and perianal region.

• The secretion of eccrine glands is watery, while apocrine glands secrete viscous secretion containing protein and lipids ceruminous glands are modified apocrine sweat glands. These glands are present in the skin ofthe external acoustic meatus (external car canal) and produce a wax secretion.
• This secretion is called cerumen, which along with the hair of the ear canal provides a sticky barrier for foreign bodies. Sometimes, cerumen may accumulate in the ear canal and prevent the sound waves from reaching the tympanic membrane.
• The modified apocrine glands of eyelashes are called as glands of Moll Similarly, the modified sebaceous glands of fluid are known as Meibomian glands (tarsal glands). These glands are large and embedded in the tarsal plate

5. Mammary Glands

Mammary glands are modified (specialized) sweat glands that secrete milk in females, for histology of mammary glands.

Lymphatic System

The lymphatic system is also sometimes called as immune system. (Readers are advised to refer to the functions of the immune system from a textbook of physiology.)

Lymphatic System  system consists of the following structures:

• Lymphatic vessels: The thin-walled vessels collect the tissue fluid (lymph) and drain it into veins.
• Specific lymphatic organs: These are made up of accumulation of lymphatic tissue and are surrounded by capsule, e.g., lymph node, spleen and thymus
• Lymphatic tissue found within the tissues of other organs: Examples of this are lymphatic tissue found within the bone marrow, GI tract (tonsils, Peyer’s patches, appendix), urinary tract, respiratory tract, etc. These lymphatic tissues are not surrounded by a capsule

Question 1. What is lymph?
Answer: 

The tissue fluid drained by lymphatic vessels is called as lymph. It consists of tissue fluid, large molecules of proteins, fat droplets and particulate matters

Question 2. What is lymphatic tissue?
Answer:

It is a specialized form of connective tissue. The supporting framework of lymphatic tissue is a meshwork formed by reticular cells and reticular fibres. The spaces within the meshwork are occupied by a large number of lymphocytes. The other cells present in lymphatic tissue are plasma cells and macrophages. (In the thymus, the supporting framework is not formed by reticular cells and fibres, but by star-shaped epithelial cells called as epithelioreticular cells

Question 3. What are the General Functions of the Lymphatic Tissue?
Answer:

Defence of body. This is achieved by lymphocytes and macrophages, which protect the body from foreign cells (bacteria, viruses and cancer cells). Lymphocytes are capable of identifying foreign entities (antigens) at the molecular level and responding to them immuno-logically. Phagocytosis of foreign cells such as bacteria, viruses and cancer cells by macrophages. Lymphatic tissues are also involved in the production of lymphocytes and plasma cells.

Question 4. What are diffuse lymphatic tissue and lymphatic nodules?
Answer:

The accumulation of lymphatic tissue is seen in the mucous membrane of the gastrointestinal, respiratory, urinary and reproductive tracts. Here, lymphocytes are disposed of randomly beneath the epithelium. This kind of lymphatic tissue is called diffuse lymphatic tissue. These kinds of lymphatic tissues are also known as mucosa-associated lymphatic tissue (MALT). These collections of lymphatic tissues are located in areas where they come in direct contact with antigens and may initiate the immune response

A lymphatic nodule is a circumscribed concentration of lymphatic tissue (lymphocytes and related cells) that is not surrounded by a capsule ). The lymphatic nodules are found both in scattered lymphoid tissue infiltration ofthe connective tissues (as in lamina proper of appendix, tonsil, etc) as well as in the encapsulated lymphoid organs such as spleen and lymph nodes.

The lymphatic nodule may show a lighter stained area in the centre (germinal centre) surrounded by a darkly stained zone of densely packed small lymphocytes. The lighter staining of the germinal centre is because it contains large euchromatic lymphoblasts and plasmoblasts, which are involved in the production of lymphocytes and plasma cells. In a lymphatic nodule, the germinal centre develops only when a nodule is exposed to an antigen (for example, Infection, or foreign cells).

Lymphocytes Remember:

Lymphatic nodules are a circumscribed collection of lymphocytes within the meshwork of reticular cells. This kind of collection of lymphatic tissue is seen In the mucous membrane of gastrointestinal, respiratory, urinary and reproductive tracts

The Lymphatic System Acts as the Immune System:

It should be noted that various lymphatic organs and lymphatic tissues constitute the immune system. The cells of the immune system consist of lymphocytes and various supporting cells.

Classification of Lymphocytes:

Three different functional types of lymphocytes are found in the body, i.e., B lymphocytes, T lymphocytes and natural killer(NK) lymphocytes

1. T Lymphocytes (T cells)
   • These lymphocytes although originate in the bone marrow, get differentiated in the thymus gland, hence called as T lymphocytes
   • T lymphocytes constitute about 60-80% of total blood lymphocytes.
   • Three different types of lymphocytes are known, i.e., helper T, cytotoxic T and memory T cells
   • The T lymphocytes are involved in cell-mediated immunity in which, cytotoxic T lymphocytes bind to the surface of parasites and virally infected cells and kill them
2. B Lymphocytes (B Cells)
   • These cells originate and mature in the bone marrow.
   • B lymphocytes constitute about 20-30% of total circulating lymphocytes.
   • They are responsible for the production of various antibodies.
   • B lymphocytes are of two types, i.e., plasma cells (which produce antibodies) and B memory cells.
   • B lymphocytes are responsible for humoral immune response in which B lymphocyte produces antibodies, which combine with antigens to form antigen-antibody complexes.
   • These are removed by macrophages and neutrophils
   • B cells also express major histocompatibility complex 2 (MHCH) on their surface.
3. NK Cells
   1. These cells also originate in the bone marrow.
   2. They are genetically programmed to recognize those cells, which are viral Infected or tumour cells. Alter recogni¬ tion they kills these cells.
   3. NK cells constitute about 5- 10% of circulating lymphocytes

Question 5. How different types of lymphocytes are identified
Answer:

Various types of lymphocytes are similar in appearance, hence, cannot lie differentiated morphologically even under an electron microscope. However, both B and T lymphocytes are distinguished by immunocytochemical methods.

Different types of lymphocytes possess different types of unique molecules on the surface of their cell membrane. These molecules arc culled cluster ol’dilTcrenliation (CD) molecules. These CD molecules can be visualized by immuno-histochemical methods using monoclonal antibodies. This method has helped to identify various subtypes of lymphocytes. These CD markers are designated as numbers according to an international system

T cells express CD2, CD3, CD4, CD7 and CD8 markers. T cells expressing CD4 markers are called helper T cells. While T cells expressing CD8 markers are also known as cytotoxic T lymphocytes. B cells express CD9, CD19 CD20 and CD24 markers. Similarly, CD markers for NK cells are CD16, CD56 and CD94.

Supporting Cells of the Immune System:

The supporting cells of the immune system consist of reticular cells, macrophages, follicular dendritic cells, Langerhans cells and epithelioreticular cells

Lymphocytes Clinical Application

Acquired Immunodeficiency Syndrome (AIDS) The disease is caused due to infection of the human Immunodeficiency virus (HIV). The infection destroys the defence system (immune system) of the body. The virus binds to CD4 molecules of T helper lymphocytes and destroys their capability to fight infection, not only with HIV but also infections due to other viruses and bacteria.

The HIV multiply rapidly within the T lymphocytes and infects other lymphocytes so that their number is reduced significantly. As a result, the infected person ultimately becomes incapable of fighting against any bacteria or virus. Death usually occurs due to secondary infections.

Lymphatic Vessels

In addition to the blood vascular system, there exists a lymphatic system to assist in draining tissue fluid to the blood circulation. The lymphatic system consists of lymph vessels and lymph nodes. The tissue fluid leaves the blood capillaries at its arteriolar end and re-enters at its venule end The excess of tissue fluid, containing particulate matter colloidal material, is absorbed through lymphatic capillaries because these capillaries are more permeable than blood capillaries

Lymphatic vessels begin as a network of blind capillaries in the tissues of the body. The lymphatic capillaries unite to form progressively larger lymph vessels. The largest of these vessels are known as the thoracic duct and right lymphatic duct.

These vessels pour their lymph into venous blood at the root ofthe neck. While the lymph is travelling through lymphatic vessels, it passes through lymph nodes where it gets filtered. The foreign substances (antigens) being conveyed by the lymph are exposed to lymphocytes of lymph nodes, which ultimately leads to an immune response

Histology of Lymph Vessels

1. Lymph Capillaries:

The lymphatic capillary networks accompany the networks of blood capillaries. The histological structure of lymph capillaries is similar to blood capillaries. However, lymph capillaries are more dilated and irregular in cross-section compared to blood capillaries and lack a continuous basal lamina

Lymph Capillaries Remember:

In the lymph capillaries, endothelial cells overlap and act as a one-way valve, which permits only the passage of tissue fluid into lymphatic capillaries but prevents its escape.

2. Small size Lymph Vessels

Their histological structure is almost similar to lymph capillaries. but they are more dilated than capillaries A lymph vessel can be differentiated from a blood vessel by staining it with an immuno-histochemical method (using D2-40 as a marker). This stains only lymphatic endothelial lining

3. Medium Size Lymph Vessels

These vessels consist of three layers. In tunica intima. the endothelial cells rest on the basal lamina. In subendothelia! layer, connective tissue fibres are arranged longitudinally. In tunica media, the connective tissue and muscle fibres are circularly disposed. The tunica externa of lymph vessels is similar to that of veins.

4. Large Size Lymph Vessels:

Although the histological structure of large size lymph vessels resembles that of comparable size veins, it differs in two characteristics: the muscle tissue is more abundant than in veins and their tunicae are more difficult to distinguish. In the thoracic duct, muscle is arranged longitudinally

Lymphatic Organs

Lymphatic organs are made up of an accumulation of lymphatic tissue and are surrounded by capsules, i.e.,

1. Lymph nodes
2. Spleen and
3. Thymus

1. Lymph nodes

Lymph nodes are kidney-shaped structures measuring from a millimetre to one or two centimetres. Lymph nodes serve as filter of lymph and hence are placed in the pathway of lymphatic vessels. Several afferent lymphatic vessels enter the lymph node at its convex surface and a single lymph vessel leaves through the hilus as an efferent lymphatic vessel

The hilus also serves for the entry and exit of blood vessels and nerves  A section through the lymph node shows an outer darkly stained zone cortex and an inner medulla. The dark staining is due to densely packed lymphocytes in the cortex while the medulla is lightly stained because it contains fewer lymphocytes. The cortex has several lymph nodules, which may show a germinal centre (see above).

The Supporting Elements of Lymph Node:

• The connective tissue capsule surrounds the bean-shaped lymph node. It is made up of dense connective tissue (collagenous, elastic and a few reticular fibres).
• The trabeculae extend from the capsule into the substance ofthe lymph node
• Besides the capsule and trabeculae, the supporting elements in the organ are formed by reticular cells and reticular fibres, which form a meshwork throughout the cortex and medulla.
• Reticular cells synthesize reticular fibres (type 1 collagen) and ground substance. These cells also produce substance which attracts T and B lymphocytes and dendritic cells
• Dendritic cells, which are present in the parenchyma of lymph nodes are of bone marrow origin and they present the antigen t0 specific T cells
• This meshwork is not seen, in a histological section, as the spaces within this meshwork are occupied by densely packed iymph0cytes.
• This meshwork can be demonstrated by special staining

Passage of Lymph Through Lymph Node:

• Afferent lymphatic vessels pour their lymph into the subcapsular sinus, which is placed just under the capsule between the capsule and cortical lymphocytes.
• From here the lymph flows deep inside the cortex in the secular sinuses and reaches the medullary sinuses.
• The sinuses within the medulla are in the form of
• Interanastomosing channels between cords of lymphocytes.
• The medullary sinuses then drain into an efferent lymphatic vessel at the hilum through which lymph passes through the lymph node.
• The sinuses are lined by endothelium, but their wall allows passage of lymphocytes into and out of sinuses

The Parenchyma of Lymph Node:

The parenchyma of the lymph node is present in the form of the cortex and medulla. The cortex is darkly staining the outer portion of the node deep to the capsule. The cortex is further divided into the outer and deep cortex. Lymphocytes are the most numerous cells of parenchyma.

These lymphocytes’ outer cortex are organized in the form of nodules, which may be in the form of primary nodules (nodules is made up of small lymphocytes with heterochromatic nuclei with very little cytoplasm and thus is deeply stained) or secondary nodules (nodules possessing germinal centre,

Germinal centre stains lightly because there are few dark staining small lymphocytes, but there are more light staining large lymphocytes (lymphoblasts, with euchromatic nucleus and clear rim of cytoplasm), macrophages and young plasma cells.

The lymphocytes in the deep cortex are not organized in the form of nodules, but they are diffusely arranged. B lymphocytes are predominantly present in the outer cortex but T lymphocytes are present in the deep cortex

Cortex Medulla Remember:

The cortex of the medulla is rich in B lymphocytes, while the cortico-medullary junction of the lymph node is rich in T cells.

The medulla is the inner part ofthe node and consists of lymphocytic tissue arranged in the cords called as medullary cords.

Besides lymphocytes both the cortex and medulla also contain the following types of cells:

• Reticular cells: These cells along with reticular fibres serve as the framework of the lymph node.
• Plasma cells: B lymphocytes mature into antibody-producing plasma cells. These cells are mainly present in medullary cords
• Macrophages: These cells are mainly present in the medulla but are also common in the germinal centres. These cells are phagocytic, which hold and present antigens to lymphocytes to aid the immune response
• The antigen-presenting cells (APCs) like dendritic and follicular dendritic cells are also present in the lymph node.
• The Parenchyma of the cortex and medulla is traversed by blood vessels and lymph sinus both of which are lined by endothelial cells.

Functions of Lymph Node:

It serves as filter of lymph. Filtration occurs in two different ways, i.e., the reticular meshwork (meshwork formed by reticular fibres and reticular cells) obstructs The foreign bodies (antigens), while these foreign bodies are phagocytosed by macrophages.

The foreign bodies are presented to lymphocytes by reticular cells and macrophages, which aid in immunological reactions.

• Both B and T lymphocytes are produced by lymph nodes. Thus, both humoral and cellular immune functions oc¬ cur here.
• B lymphocytes mature to form plasma cells in lymph nodes, which produce antibodies.
• Re-circulation of B and T lymphocytes takes place here through lymph nodes, i.e., the circulating B and T lymphocytes may enter the lymph node through postcapillary venule and may pass in lymph via the efferent lymphatics, draining to the thoracic duct

Lymph node Remember:

The lymph node is an important site where foreign bodies are phagocytosed by macrophages. The immune response is initiated when foreign bodies are presented to lympho¬ cytes by reticular cells and macrophages.

The Circulation of Lymphocytes Through Lymph Node:

In addition to lymph, lymphocytes also circulate through the lymph node. The lymphocytes enter the lymph node from two different sources.

Few lymphocytes enter the lymph node through afferent lymphatic vessels and reach into the network of lym¬ phatic sinuses. From the sinus, they enter into the cortex of the lymph node where they engage in immunosurveillance. This lymphocyte now comes back to the sinuses and migrates out of the lymph node through efferent lymph vessels.

• Many lymphocytes enter the deep cortex lymph node through the wall of postcapillary venules.
• Postcapillary venules are specialized blood vessels because they are lined by cuboidal or columnar endothelial cells, hence, also called as high endothelial venules. These endothelial cells have receptors to identify specific types of lymphocytes.
• They signal lymphocytes to leave the postcapillary venule (by passing between endothelial cells) and migrate into the deep cortex of lymph node.

From here lymphocytes migrate in the entire cortex and after performing their function of immunosurveillance they mi¬grate in lymph sinuses to come out of the lymph node through efferent lymph vessels.

Lymph node Clinical Applications

Lymphadenitis (Enlargement of Lymph Nodes) Lymph nodes are located along the path of lymph ves¬ sels. Lymph flows from one node to the next. Lymphad¬ enitis is the name given to the enlargement of lymph nodes, which is usually secondary to the infection in the area of drainage of lymph.

The most common infection causing lymphadenitis is due to streptococcal and staphylococcal bacteria. Common symptoms of acute lymphadenitis are swollen and tender nodes, fever and gen¬ eral weakness. Lymph nodes are also enlarged secondary to cancer (malignancy) in the region of drainage

2. Spleen

The spleen, similar to the lymph node, is an encapsulated lymphatic organ. Lymph nodes filter the lymph while blood is filtered through the spleen (thus blood is monitored immunologically by the spleen). In humans, the spleen is a single large organ present in the upper abdomen and covered by the peritoneum.

A cut section through the spleen shows the substance of the spleen arranged in the form of limited pulp and red pulp. In a fresh section of the spleen (unstained), the white pulp is seen as circular grey areas scattered randomly throughout the substance of the spleen.

The white pulp is surrounded by red pulp. In the hematoxylin-stained section, the white pulp appears as basophilic due to the presence of small lymphocytes with heterochromatic nuclei. The red pulp appears red because it contains many blood sinuses filled with RBCs.

The Supporting Elements of Spleen:

The spleen is covered by a capsule made up of dense connective tissue. The capsule contains elastic fibres. From the capsule, trabeculae extend into the substance ofthe organ where they repeatedly divide to form a network. Small spaces within the trabecular network are occupied by the delicate meshwork formed by reticular cells and reticular fibres.

• Macrophages are also present in this delicate meshwork. The spaces of this meshwork are filled by lymphocytes, macrophages and blood cells.
• In red pulp, these cells are arranged in the form of cords, which itself forms a network
• These cords are called splenic cords. Spaces between cords are occupied by blood sinusoids.
• The hilus of the organ gives passage to the splenic artery, vein, nerves and efferent lymphatic vessels.
• The spleen has no afferent lymphatic vessels and efferent vessels originate in the white pulp through which lymphocytes go out of the spleen

Circulation of blood Through the Spleen:

• The splenic artery enters at hilum and its branches travel in the trabeculae.
• After repeated branching within trabeculae, the final branch enters the pulp where it is covered by the aggre¬ gation oflymphocytes.
• This peri-arteriolar lymphatic sheath is called the white pulp. At the centre of the white pulp is the central artery. The central artery then enters red pulp and terminates by branching into straight vessels that are called penicillin.
• Penicilli shows localized thickening called as an ellipsoid. Penicillin continues as arterial capillaries. The mode of flow of blood between arterial capillaries and splenic sinuses is yet not clear. Two different theories (open and closed circulation theories) have been proposed.
• According to the ‘closed circulation theory,’ arterial capillaries open directly into splenic sinuses that drain into tributaries of splenic veins that are present in trabeculae.

The splenic vein thus formed comes out from the hilus of the spleen.

According to the “open circulation theory,” the arterial capillaries open and pour their blood into splenic cords of pulp,

The blood cells from here (splenic cords) then enter the blood sinuses by passing between endothelial cells lining the wall of the sinus.

Pulps of Spleen:

The substance of the spleen consists of two different types of 2 1 pulp, i.e., white pulp and red pulp S The white pulp is the lymphatic tissue sheath that surrounds * the central artery. It contains lymphocytes and macrophages P in a reticular connective tissue meshwork.

This peri-area rial lymphatic tissue sheath may also contain lymphatic nodules with germinal centres. These nodules are called splenic & nodules or Malpighian corpuscles. Most of the lymphocytes in while pulp are T lymphocytes while nodules predominantly contain B lymphocytes.

The red pulp consists of a network of inter-anastomosing splenic cords. The splenic cords are made up of reticular cells and reticular fibres containing B and T lymphocytes, macrophages, plasma cells, RBCs and granulocytes. These splenic cords are also called “cords of Billroth.” In between the splenic cords, spaces are filled with branch¬ ing venous sinuses.

The macrophages and lymphocytes come in contact with the antigens present in circulating blood. This leads to the initiation of an immune response against blood-borne antigens

 Spleen Remember:

The periarterial lymphatic sheath of white pulp contains T cells, while the lymphoid nodule of white pulp contains B cells. The red pulp of the spleen consists of blood sinuses and splenic cords

Spleen Functions

• Filtration of blood.
• Immune response against antigens circulating in the blood. Site for production of B and T lymphocytes.
• Aged and abnormal RBCs are detained and destroyed in the red pulp by the macrophages of the splenic cord.
• Macrophages also remove bacteria by phagocytosis. Storage of blood.
• Formation of blood cells during fetal life.
• The spleen may enlarge secondary to malaria and leukaemias.
• The spleen is not an essential organ and can be surgically removed if required (as in the case of profuse bleeding alter injury to the spleen).

Spleen Clinical Application

Rupture of Spleen:

The spleen is a fragile organ and presents relatively superficial in the abdomen, therefore trauma to the spleen may lead to its rupture. As it is a highly vascular organ, rupture leads to rapid and massive bleeding, which may result in the death of a person soon after injury. In some cases, the spleen can be removed surgically without affecting the life of a person because its function of removal of aged red blood cells is taken over by macrophages present in the liver and bone marrow.

3. Thymus

It is an encapsulated lymphatic organ, which neither filters lymph (like a lymph node) nor blood (like a spleen). This is the only lymphatic organ, which is fully developed at birth, while organs such as lymph nodes, tonsils and spleen are underdeveloped and require the migration of B and T cells for their development.

Supporting Elements of Thymus:

Both the lobes of the thymus are completely covered by a thin layer of connective tissue capsule from which trabeculae extend into the substance of the organ. These trabeculae partially subdivide the lobe of the thymus into thousands of lobules, each of which has a cortical cap over inner medullary tissue.

• The medullary tissues are partly divided by the trabeculae, hence the medullary tissue of adjacent lobules are continuous with each other.
• Thus, the medulla is a continuous branching mass surrounded by the cortex. Through these trabeculae pass the blood vessels, nerves and lymphatics.
• The thymus has only efferent lymphatic
• The delicate supporting stroma of the organ, within a lobule, is formed by epithelial-reticular cells. These cells are stellate in shape and their cytoplasmic processes are joined with the processes of neighbouring cells with the help of desmosomes.
• Thus, epithelioreticular cells form a cytoplasmic reticulum within the thymus. This reticulum is different from the reticulum present in the spleen and lymph nodes.
• In the spleen and lymph node, the reticulum is formed with the help of reticular cells and reticular fibres.

The epithelioreticular cells envelope the thymic blood capillaries to form a “blood-thymic barrier.”It is believed that the blood-thymic barrier does not allow any antigen to enter the thymus where T lymphocytes are maturing, which otherwise may influence the development of T lymphocytes

MicroscopicStructure of Thymic Lobule:

Each lobule of the thymus is surrounded by connective tissue stroma and contains an outer cortex and inner medulla

The cortex contains a higher concentration oflympho¬ cytes than the medulla. The cortex is darkly stained because of densely packed small lymphocytes with heterochromatic nuclei.

The outer cortex receives stem cells from bone marrow”‘ which divide repeatedly to form small lymphocytes. These cells form the cellular framework for the entire 1 – These small, maturing lymphocytes then move towards the medulla. The mature lymphocytes leave the thymus via veins and lymphatics.

This entire process takes about 24 hrs The medulla stains lightly compared to the cortex because here lymphocytes are less densely packed. Because of this reason, epithelioreticular cells are more obvious. The ta i medulla also contains thymic or Hassall’s corpuscles. !lu; These are masses of concentrically arranged type 6 l epithelioreticular cells around a central degenerated homogeneous mass.

The Hassall’s corpuscles stain pink with acid |u dyes and their number increases with increasing age. The macrophages are found in large numbers both in the cortex and medulla. They engulf antigens and also remove the lymphocytes, which might have been produced in excess.

Thymic Remember:

In the thymic cortex, immunologically incompetent T cells acquire the immunological competency (site of maturation of T lymphocytes), while the medulla consists of all immune-competent T cells.

Thymic Epithelioreticular Cells:

Epithelioreticular cells provide a skeletal framework of the thymus, which is similar to the reticular cells and their associated fibres in the spleen and lymph node

Epithelioreticular cells show some features of epithelial cells such as the presence of intercellular junction and intermediate filaments. The thymus exhibits six different types of epithelioreticular cells, i.e., types 1,2,3,4, V and 6. Out of these six types, types 1,2 and 3 are present in the cortex and the remaining three in the medulla. It is believed that epithelioreticular cells are derived from the endoderm of third and fourth pharyngeal pouches.

The epithelioreticular cells provide an isolated and protective environment to developing (immature) lymphocytes.

The following functions can be attributed to various kinds of reticuloendothelial cells:

1. Type 1: They isolate lymphocytes from neighbouring connective tissue (capsule and trabeculae) and blood vessels of the cortex. These cells form occluding junctions with each other, thus isolating the thymic cortex from the remainder of the body
2. Type 2: These cells are present in mid cortex and form an isolated compartment for developing T cells
3. Types 3 & 4: These cells are present at the cortico-medullary junction. They form a functional barrier between the cortex and medulla
4. Type 5: These cells form the cellular framework for entire medulla lymphocytes. and form compartments for various groups of
5. Type 6: They form thymic corpuscles. Thymic cor¬ puscles are isolated masses of closely packed concentrically arranged type 6 epithelioreticular cells. They contain flattened nuclei and their number increases with the increase in age.

Though the function of the thymic corpuscle is not known it is believed that type 6 cells are involved in the production of interleukins (IL-4 and IL-7) that help in the differentiation and education of T lymphocytes. Some believe that thymic corpuscles are the site for the death ofT lymphocytes

Thymic (Hassall’s) Corpuscles:

The type 6 epithelioreticular cells form thymic corpuscles. These cells of the thymic corpuscle show keratohyalin granules, intermediate filaments and lipid droplets in their cytoplasm. The centre of the corpuscle shows the keratinization of epithelioreticular cells. Thymic corpuscles are functionally active multicellular components of the medulla that are capable f producing hormones like thymosin and thym opoietin.

Blood-Thymic Barrier:

Further Details The thymic barrier helps to protect the developing immature lymphocytes in the thymus from exposure to the external environment (antigens).

The following are the constituents of blood thymic barrier:

• Capillary endothelium with basal lamina and pericytes
• Perivascular connective tissue space containing macrophages
• TypeI epithelioreticular cells with their basal lamina

Thus, the perivascular connective tissue space is located between the basal laminar capillary endothelium and basal lamina ofepithelioreticular cells. The macrophages present in perivascular connective tissue phagocytose the antigenic molecules that may come out from the capillary lumen. Thus,the layers of the blood-thymus barrier provide necessary protection to the developing immature T lymphocytes and separate them from mature lymphocytes, which are circulating in the bloodstream

Blood Thymic Barrier Remember:

Blood-thymus barrier protects the developing T cells in the cortex form the macromolecules present in the blood

Thymus Functions:

• The thymus receives immunologically incompetent stem cells from bone marrow and provides the environment where they can divide and mature into T lymphocytes.
• The mature T lymphocytes are then carried from thymus, via blood, to the lymph nodes, spleen and other lymphatic tissues.
• T cells are important for both cellular and humoral immunological responses.
• Epithelioreticular cells secrete many factors.
• Thymopoietin induces T cell production and maturation.
• Thymosin supports T cell activities throughout the body.
• Thymus is essential till puberty. After puberty, the other lymphatic tissues ofbody are fully developed; hence, the thymus gets atrophied

Thymus Remember:

The thymus is a primary lymphoid organ where T lymphocytes are immunologically matured.

Thymus Clinical Application:

1. Myasthenia Gravis: Myasthenia gravis is a rare autoimmune disorder in which the immune system produces antibodies that attack and slowly destroy the receptors in muscles that receive nerve impulses.
   • As a result, the affected muscle fails to respond or responds only weakly to nerve impulses. The muscles of the throat, face and eye are most commonly affected.
   • The other muscles may also be affected.
   • The cause of the autoimmune disorder is not known, but about 70% of people suffering from this disorder have an abnormality of the thymus gland.
   • The most common abnormality of the thymus gland associated with this disorder is thymoma (a noncancerous tumour of the thymus
2. DiGeorge’s Syndrome: This syndrome is characterized by the congenital absence of the thymus gland.
   • The patient is unable to produce T lymphocytes, thus cell-mediated immune response is not functional.
   • Patients may die at a young age due to infection. Since the thymus is absent, the parathyroid gland also fails to develop.
   • In the absence of a parathyroid, death may be caused due to tetany.

Lymphatic Tissue In Other Organs

As stated earlier, the mucosa-associated lymphoid tissue (MALT) consists of localized lymphocyte infiltration and lymphoid nodules in the mucosa of GIT (tonsil, Peyer’s patches of intestine, appendix), respiratory (bronchus), re¬ productive and urinary tracts.

Palatine Tonsil:

• Palatine tonsils are collections of lymphoid tissue in the mucosa of oropharyngeal isthmus.
• Each tonsil consists of an aggregation of lymphatic nodules within the diffused lymphoid tissue
• This lymphoid tissue is present just beneath the stratified
  squamous epithelium ofthe oropharynx.
• This epithelium at places may go deep into the substance of the tonsil. This invagination epithelium within the lymphoid tissue is called as epithelial crypt.

Tonsil has only efferent lymphatic vessels. Infection of the tonsil is called tonsillitis

Tonsil Functions:

• Production of lymphocytes.
• Immunological responses against the antigens and organisms coming in contact with epithelium

Tonsil Clinical Application

Tonsillitis: The infection of the tonsil may be caused either by virus or by bacteria. The tonsillitis is common in children because their tonsils are exposed to infections for the first time. Tonsils become smaller with increasing age and hence tonsillitis is also less common in adults. Surgical removal of tonsils (tonsillectomy) is performed on children who have recurrent tonsillitis.