Human_Histology

in parts of the cytoplasm near adjacent blood sinusoids. These features become much less prominent in inactive cells. Both active and inactive cells contain glycogen, the amount of which is greater in inactive cells. In the normal parathyroid the number of inactive cells is greater than that of active cells.

The chief cells produce the parathyroid hormone (or parathormone). This hormone tends to increase the level of serum calcium by:

Increasing bone resorption through stimulation of osteoclastic activity;

Increasing calcium resorption from renal tubules (and inhibiting phosphate resorption);

Enhancing calcium absorption from the gut.

Oxyphil Cells

The oxyphil cells are much larger than the chief cells and contain granules that stain strongly with acid dyes. Their nuclei are smaller and stain more intensely than those of chief cells. They are less numerous than the chief cells. The oxyphil cells are absent in the young and appear a little before the age of puberty.

With the EM it is seen that the granules of oxyphil cells are really mitochondria, large numbers of which are present in the cytoplasm. True secretory granules are not present. The functions of oxyphil cells are unknown.

Clinical Correlation

Hyperparathyroidism: Hyperfunction of the parathyroid glands occurs due to excessive production of parathyroid hormone. 0 *

Primary hyperparathyroidism occurs from oversecretion of parathyroid hormone due to disease of the parathyroid glands.

Secondary hyperparathyroidism is caused by diseases in other parts of the body.

Tertiary hyperparathyroidism develops from secondary hyperplasia after removal of the cause of secondary hyperplasia.

Hypoparathyroidism: hormone secretion causes hypoparathyroidism.

SUPRARENAL GLANDS

As implied by their name the right and left suprarenal glands lie in the abdomen, close to the upper poles of the corresponding kidneys. In many animals they do not occupy a “supra” renal position, but lie near the kidneys. They are, therefore, commonly called the adrenal glands.

STRUCTURE OF SUPRARENAL GLANDS

Each suprarenal gland is covered by a connective tissue capsule from which septa extend into the gland substance. The gland is made up of two functionally distinct parts—a superficial part called the cortex, and a deeper part called the medulla. The volume of the cortex is about ten times that of the medulla.

Suprarenal Cortex

Layers of the Cortex

The suprarenal cortex is made up of cells arranged in cords. Sinusoids intervene between the cords. On the basis of the arrangement of its cells the cortex can be divided into three layers as follows (Plate 20.5):

Zona glomerulosa: The outermost layer is called the zona glomerulosa. Here the cells are arranged as inverted U-shaped formations, or acinus-like groups. The zona glomerulosa constitutes the outer one-fifth of the cortex. With the light microscope the cells of the zona glomerulosaareseentobesmall,polyhedralorcolumnar, with basophilic cytoplasm and deeply staining nuclei.

Chapter 20 Endocrine System 259

Zona fasciculata: The next zone is called the zona fasciculata. Here the cells are arranged in straight columns, two cell thick. Sinusoids intervene between the columns. This layer forms the middle three-fifths of the cortex. With the light microscope the cells of the zona fasciculata are seen to be large, polyhedral, with basophilic cytoplasm and vesicular nuclei. The cells of the zona fasciculata are very rich in lipids which can be demonstrated by suitable stains. With routine methods the lipids are dissolved out during the processing of tissue, giving the cells an ‘empty’ or vacuolated appearance. These cells also contain considerable amounts of vitamin C.

Zona reticularis: The innermost layer of the cortex (inner one-fifth) is called the zona reticularis. It is so called because it is made up of cords that branch and anastomose with each other to form a kind of reticulum. The cells in this layer are smaller and more acidophilic than other two layer. With the light microscope the cells of the zona reticularis are seen to be similar to those of the zona fasciculata, but the lipid content is less. Their cytoplasm is often eosinophilic. The cells often contain brown pigment.

Note: With the EM the cells in all layers of the cortex are characterized by the presence of abundant agranular (or smooth) endoplasmic reticulum. The Golgi complex is best developed in cells of the zona fasciculata. Mitochondria are elongated in the glomerulosa, spherical in the fasciculata, and unusual with tubular cisternae (instead of the usual plates) in the reticularis (Fig. 20.7).

The suprarenal cortex is essential for life. Removal or destruction leads to death unless the hormones produced by it are supplied artificially. Increase in secretion of corticosteroids causes dramatic reduction in number of lymphocytes.

Hormones Produced by the Suprarenal Cortex

The cells of the zona glomerulosa produce the mineralocorticoid hormones aldosterone and deoxycorticosterone.Thesehormonesinfluencetheelectrolyteand water balance of the body. The secretion of aldosterone is influenced by renin secreted by juxta-glomerular cells of the kidney. The secretion of hormones by the zona glomerulosa appears to be largely independent of the hypophysis cerebri.

The cells of the zona fasciculata produce the glucocorticoids cortisone and cortisol (dihydrocortisone). These hormones have widespread effects, including those on carbohydrate metabolism and protein metabolism. They appear to decrease antibody responses and have an anti-inflammatory effect.

PLATE 20.5: Suprarenal Gland

A

Suprarenal gland. A. As seen in drawing B. Photomicrograph Courtesy: Atlas of Histopathology. Ist Edition. Ivan Damjanov. Jaypee Brothers. 2012. p 292

Fig. 20.7: Some features of ultrastructure of a cell from the adrenal cortex (Schematic representation)

B

% inner medulla

The cortex is divisible into three zones

* +,--

* columns (typically two cell thick). Sinusoids intervene between the columns

* ! branch and form a network

/ !

The zona fascicularis also produces small amounts of dehydroepiandrosterone (DHA) which is an androgen.

The cells of the zona reticularis also produce some glucocorticoids; and sex hormones, both estrogens and androgens.

Suprarenal Medulla

Both functionally and embryologically the medulla of the suprarenal gland is distinct from the cortex. When a suprarenal gland is fixed in a solution containing a salt of chromium (e.g. potassium dichromate) the cells of the medulla show yellow granules in their cytoplasm. This is called the chromaffin reaction, and the cells that give a positive reaction are called chromaffin cells (pheochromocytes). The cells of the suprarenal cortex do not give this reaction.

The medulla is made up of groups or columns of cells. The cell groups or columns are separated by wide sinusoids. The cells are columnar or polyhedral and have a basophilic cytoplasm.

Note: With the EM the cells of the adrenal medulla are seen to contain abundant granular endoplasmic reticulum (in contrast to the agranular endoplasmic reticulum of cortical cells), and a prominent Golgi complex (Fig. 20.8). The cells also contain membrane bound secretory vesicles. In some cells these vesicles are small and electron dense while in others they are large and not so dense. The former contain nor-adrenalin and the latter adrenalin.

The suprarenal medulla is now included in the APUD cell system. In contrast to the suprarenal cortex the medulla is not essential for life as its functions can be performed by other chromaffin tissues.

Hormone Produced by Suprarenal Medulla

Functionally, the cells of the suprarenal medulla are considered to be modified postganglionic sympathetic neurons. Like typical postganglionic sympathetic neurons they secrete nor-adrenalin (nor-epinephrine) and adrenalin (epinephrine) into the blood. This secretion takes place mainly at times of stress (fear and anger) and results in widespread effects similar to those of stimulation of the sympathetic nervous system (e.g. increase in heart rate and blood pressure).

PINEAL GLAND

The pineal gland (or pineal body) is a small piriform structure present in relation to the posterior wall of the third ventricle of the brain. It is also called the epiphysis cerebri. The pineal has for long been regarded as a vestigial

organ of no functional importance. (Hence, the name pineal body). However, it is now known to be an endocrine gland of great importance.

MICROSCOPIC FEATURES

Sections of the pineal gland stained with hematoxylin and eosin reveal very little detail. The organ appears to be a mass of cells amongst which there are blood capillaries and nerve fibers. A distinctive feature of the pineal in such sections is the presence of irregular masses made up mainly of calcium salts. These masses constitute the corpora arenacea or brain sand (Fig. 20.9). The organ is covered by connective tissue (representing the piamater) from which septa pass into its interior.

Pinealocytes

The organ is made up mainly of cells called pinealocytes. Each cell has a polyhedral body containing a spherical oval or irregular nucleus. The cell body gives off long processes with expanded terminal buds that end in relation to the walls of capillaries, or in relation to the ependyma of the third ventricle.

The cell bodies of pinealocytes contain both granular and agranular endoplasmic reticulum, a well developed Golgi complex, and many mitochondria. An organelle of unusual structure made up of groups of microfibrils and perforated lamellae may be present (canaliculatelamellar bodies). The processes of pinealocytes contain numerous mitochondria. Apart from other organelles the terminal buds contain vesicles in which there are monamines and polypeptide hormones. The neurotransmitter gamma- amino-butyric acid is also present.

262Textbook of Human Histology

Hormone Produced by Pinealocytes

The pinealocytes produce a number of hormones (chemically indolamines or polypeptides). These hormones have an important regulating influence (chiefly inhibitory) on many other endocrine organs. The organs influenced include the adenohypophysis, the neurohypophysis, the thyroid, the parathyroids, the adrenal cortex and medulla, the gonads, and the pancreatic islets. The hormones of the pineal body reach the hypophysis both through the blood and through the CSF. Pineal hormones may also influence the adenohypophysis by inhibiting production of releasing factors.

The best known hormone of the pineal gland is the amino acid melatonin (so called because it causes changes in skin color in amphibia). Large concentrations of melatonin are present in the pineal gland. Considerable amounts of 5-hydroxytryptamine (serotonin), which is a precursor of melatonin, are also present. The presence of related enzymes has been demonstrated.

Interstitial Cells

The pinealocytes are separated from one another by neuroglial cells that resemble astrocytes in structure. They lie in proximity to blood vessel and pineolocytes.

Added Information

Cyclic Activity of Pineal Gland

The synthesis and discharge of melatonin is remarkably gland being most active in darkness. The neurological pathways concerned involve the hypothalamus and the sympathetic nerves. Because of this light mediated response, the pineal gland may act as a kind of biological clock which may produce circadian rhythms (variations following a 24-hour cycle) in various parameters.

The suprachiasmatic nucleus of the hypothalamus plays an important role in the cyclic activity of the pineal! it projects to the tegmental reticular nuclei (located in the" # $ neurons reach the superior cervical ganglion from where the nervus conarii arises and supplies the pineal gland.

It has often been stated in the past that the pineal gland degenerates with age. The corpora arenacea were considered to be signs of degeneration. Recent studies show that the organ does not degenerate with age. The corpora arenacea are now regarded as by-products of active secretory! exist in the form of complexes with a carrier protein called neuroepiphysin. When hormones are released from the complex the carrier protein combines with calcium ions and is deposited as brain sand.

SOME OTHER ORGANS HAVING ENDOCRINE FUNCTIONS

PARAGANGLIA

Aggregations of cells similar to those of the adrenal medulla aretobefoundatvarioussites.Theyarecollectivelyreferred to as paraganglia because most of them are present in close relation to autonomic ganglia. The cells of paraganglia give a positive chromaffin reaction, receive a preganglionic sympathetic innervation, and have secretory granules containing catecholamines in their cytoplasm.

Like the cells of the adrenal medulla paraganglia are believed to develop from cells of the neural crest. Paraganglia are richly vascularized. They are regarded as endocrine glands that serve as alternative sites for the production of catecholamines in the foetus, and in early postnatal life, when the adrenal medulla is not yet fully differentiated. Because of their histochemical and ultrastructural features the cells of paraganglia are included in the APUD cell system. Most of the paraganglia retrogress with age, but some persist into adult life.

Cells similar to those of paraganglia are also present within some sympathetic ganglia. (They are called SIF or small intensely fluorescent cells). Here they are believed to act as interneurons.

Note: Some workers include the para-aortic bodies and carotid bodies amongst paraganglia.

PARA-AORTIC BODIES

These are two elongated bodies that lie, one on each side of the aorta, near the origin of the inferior mesenteric artery. The two masses may be united to each other by a band passing across the aorta.

These bodies have a structure similar to that of the adrenal medulla. The cells secrete nor-adrenalin. The aortic bodies retrogress with age.

CAROTID BODIES

These are small oval structures, present one on each side of the neck, at the bifurcation of the common carotid artery (i.e. near the carotid sinus).

The carotid bodies contain a network of capillaries in the intervals between which there are several types of cells.

Cells of Carotid Bodies

The most conspicuous cells of the carotid body are called glomus cells (or type I cells) (Fig. 20.10). These are large cells that have several similarities to neurons as follows:

They give off dendritic processes.

Their cytoplasm contains membrane bound granules which contain a number of neuropeptides. In the human carotid body the most prominent peptide present is encephalin. Others present include dopamine, serotonin, catecholamines, vasoactive intestinal peptide (VIP), and substance P.

The cells are in synaptic contact with afferent nerve terminals of the glossopharyngeal nerve. Chemoreceptor impulses pass through these fibers to the brain. Some glomus cells also show synaptic connections with the endings of preganglionic sympathetic fibers, and with other glomus cells.

The organization of endoplasmic reticulum in them shows similarities to that of Nissl substance.

They are surrounded by sheath cells that resemble neuroglial elements.

Because of these similarities to neurons, and because

of the possibility that the cells release dopamine (and possibly other substances) they are sometimes described as neuroendocrine cells (and are included in the APUD cell category).

The exact significance of the glomus cells, and of their nervous connections, is not understood at present. They

could possibly be sensory receptors sensitive to oxygen and carbon dioxide tension. Dopamine released by them may influence the sensitivity of chemoreceptor nerve endings. They may also serve as interneurons.

Apart from the glomus cells other cells present in the carotid bodies are as follows:

Sheath cells (or type II cells) that surround the glomus cells.

A few sympathetic and parasympathetic postganglionic neurons.

Endothelial cells of blood vessels, and muscle cells in the walls of arterioles.

Some connective tissue cells.

Nerve Supply of Carotid Bodies

The carotid body is richly innervated as follows:

Afferent nerve terminals from the glossopharyngeal nerve form synapses with glomus cells.

Preganglionic sympathetic and parasympathetic fibers end on the corresponding ganglion cells. Some preganglionic sympathetic fibers end by synapsing with glomus cells.

Postganglionic fibers arising from the sympathetic and parasympathetic nerve cells within the carotid body innervate muscle in the walls of arterioles.

264Textbook of Human Histology

Functions of Carotid Bodies

The main function of the carotid bodies is that they act as chemoreceptors that monitor the oxygen and carbon dioxide levels in blood. They reflexly control the rate and depth of respiration through respiratory centers located in the brainstem. In addition to this function the carotid bodies are also believed to have an endocrine function.

Note: The precise mechanism by which the carotid bodies respond to changes in oxygen and carbon dioxide tension is not understood. It is not certain as to which cells, or nerve terminals are responsible for this function.

Added Information

Diffuse Neuroendocrine or APUD Cell System

$ art from the discrete endocrine organs considered in this chapter there are groups of endocrine cells scattered in various parts of the body. These cells share some common characteristics with each other, and also with the cells of$ precursor substances from the circulation and process them (by decarboxylation) to form amines or peptides. They are, therefore, included in what is called the APUD cell system. These peptides or amines serve as hormones. Many of& $'*+ cell system is also called the diffuse neuroendocrine system. The cells of this system contain spherical or oval membrane bound granules with a dense core. There is an electronlucent halo around the dense core.

/ $'*+ -- tion. They were earlier referred to as cells of the chromaf-. However, they appear to be closely related tendency is to consider all these cells under the common category of diffuse neuroendocrine cells.

Contd…

Contd…

The diffuse neuroendocrine system is regarded as representing a link between the autonomic nervous system on the one hand, and the organs classically recognized as endocrine on the other, as it shares some features of both. The effects of the amines or peptides produced by the cells of the system are sometimes “local” (like those of neurotransmitters) and sometimes widespread (like those of better known hormones).

$'*+$ some discrete endocrine glands are now included under this heading. Some cells are enumerated:

Various cells of the adenohypophysis.

Neurons in the hypothalamus that synthesize the hormones of the neurohypophysis (oxytocin, vasopressin); and the cells that synthesize releasing factors controlling the secretion of hormones by the adenohypophysis.

The chief cells of the parathyroid glands producing parathyroid hormone.

The C-cells (parafollicular cells) of the thyroid, producing calcitonin.

Cells of the adrenal medulla (along with some outlying" 6 nalin. These include the SIF cells of sympathetic ganglia.

Cells of the gastro-entero-pancreatic endocrine system which includes cells of pancreatic islets producing insulin, glucagon and some other amines. It also includes endocrine cells scattered in the epithelium of the stomach and intestines producing one or more of the following: 5-hydroxytryptamine, glucagon, dopamine, somatostatin, substance P, motilin, gastrin, cholecystokinin, secretin, vasoactive intestinal polypeptide (VIP), and some other peptides.

Glomus cells of the carotid bodies producing dopamine and noradrenalin.

Melanocytes of the skin producing promelanin.Some cells in the pineal gland, the placenta, and modi-

myoendocrine cells.Renin producing cells of the kidneys.

The eyes are peripheral organs for vision and are located in the bony orbit. Each eyeball is like a camera. It has a lens that produces images of objects that we look at. The images fall on a light sensitive membrane called the retina. Cells in the retina convert light images into ner­ vous impulses that pass through the optic nerve, and other parts of the visual pathway, to reach visual areas in the cerebral cortex. It is in the cortex that vision is actually perceived.

STRUCTURE OF EYEBALL

The wall of an eyeball consists of three layers:

Outer fibrous coat that includes sclera and cornea

Middle vascular coat that includes choroid, ciliary body and iris

Inner retina.

The space between the iris and the cornea is called the

anterior chamber, while the space between the iris and the front of the lens is called the posterior chamber. These chambers are filled with a fluid called the aqueous humor. The part of the eyeball behind the lens is filled by a jelly­ like substance called the vitreous body. The main parts of eyeball (as seen in section) are shown in Figure 21.1.

OUTER FIBROUS COAT

Sclera

The outer wall of the eyeball is formed (in its posterior five­sixths) by a thick white opaque membrane called the sclera. The sclera consists of white fibrous tissue (collagen). Some elastic fibers, and connective tissue cells (mainly fibroblasts)arealsopresent.Someofthecellsarepigmented.

Externally, the sclera is covered in its anterior part by the ocular conjunctiva, and posteriorly by a fascial sheath (or episclera). The deep surface of the sclera is separated from the choroid by the perichoroidal space. Delicate connective tissue present in this space constitutes the suprachoroid lamina (or lamina fusca).

Fig. 21.1: Section across the eyeball to show its main parts (Schematic representation)

Anteriorly, the sclera becomes continuous with the cornea at the corneoscleral junction (also called sclero­ corneal junction or limbus). A circular channel called the sinus venosus sclerae (or canal of Schlemm) is located in the sclera just behind the corneoscleral junction (Fig. 21.2). A triangular mass of scleral tissue projects toward the cornea just medial to this sinus. This projection is called the scleral spur.

The optic nerve is attached to the back of the eyeball a short distance medial to the posterior pole. Here the sclera is perforated like a sieve, and the area is, therefore, called the lamina cribrosa. Bundles of optic nerve fibers pass through the perforations of the lamina cribrosa.

Functions

The sclera (along with the cornea) collectively forms the fibrous tunic of the eyeball and provides protection to delicate structures within the eye.

266 Textbook of Human Histology

Fig. 21.2: Some features of the eyeball to be seen at the junction of the cornea with the sclera (Schematic representation)

It resists intraocular pressure and maintains the shape of the eyeball.

Its smooth external surface allows eye movements to take place with ease.

The sclera also provides attachment to muscles that move the eyeball.

Cornea

In the anterior one­sixth of the eyeball the sclera is replaced by a transparent disc called the cornea. The cornea is convex forwards. It is colorless and avascular but has a very rich nerve supply. The cornea is made up of five layers (Plate 21.1).

Corneal epithelium: The outermost layer is of non­ keratinized stratified squamous epithelium (corneal epithelium). The cells in the deepest layer of the epithe­ lium are columnar; in the middle layers they are poly­ gonal; and in the superficial layers they are flattened. The cells are arranged with great regularity.

With the EM the cells on the superficial surface of the epithelium show projections either in the form of microvilli or folds of plasma membrane. These folds are believed to play an important role in retaining a film of fluid over the surface of the cornea. The corneal epithelium regenerates rapidly after damage.

Bowman’s membrane: The corneal epithelium rests on the anterior limiting lamina (also called Bowman’s membrane). With the light microscope this lamina appears to be structureless, but with the EM it is seen to be made up of fine collagen fibrils embedded in matrix. It gives great stability and strength to the cornea.

Corneal stroma: Most of the thickness of the cornea is formed by the substantia propria (or corneal stroma). The substantia propria is made up of type 1 collagen fibers embedded in a ground substance containing sulphated glycosaminoglycans.

They are arranged with great regularity and form lamellae. The fibers within one lamellus are parallel to one another, but the fibers in adjoining lamellae run in different directions forming obtuse angles with each other. The transparency of the cornea is due to the regular arrangement of fibers, and because of the fact that the fibers and the ground substance have the same refrac­ tive index.

Fibroblasts are present in the substantia propria. They appear to be flattened in vertical sections through the cornea, but are seen to be star­shaped on surface view. They are also called keratocytes or corneal corpuscles.

Descemet’s membrane: Deep to the substantia propria there is a thin homogeneous layer called the posterior limiting lamina (or Descemet’s membrane). It is a true basement membrane.

At the margin of the cornea the posterior limiting membrane becomes continuous with fibers that form a network in the angle between the cornea and the iris (irido­corneal angle). The spaces between the fibers of the network are called the spaces of the irido­corneal angle. Some of the fibers of the network pass onto the iris as the pectinate ligament (Fig. 21.2).

Endothelium: The posterior surface of the cornea is lined by a single layer of flattened cells that constitute the endothelium of the anterior chamber. This layer is in contact with the aqueous humor of the anterior chamber.

The endothelial cells are adapted for transport of ions. They possess numerous mitochondria. They are united to neighboring cells by desmosomes and by occluding junctions. The cells pump out excessive fluid from cornea, and thus ensure its transparency.

VASCULAR COAT OR UVEA

Deep to the sclera there is a vascular coat (uvea) that consists of the choroid, the ciliary body and the iris.

1.Stratified sqaumous corneal epithelium

2.Anterior limiting membrane (Bowman's)

3.Substantia propria

4.Posterior limiting membrane (Descemet's)

5.Posteriorcuboidalepithelium

Choroid

The choroid consists of

Choroid proper

Suprachoroid lamina that separates the choroid proper from the sclera

Basal lamina (membrane of Bruch) which intervenes between the choroid proper and the retina (Fig. 21.3).

Choroid Proper

The choroid proper consists of a network of blood vessels supported by connective tissue in which many pigmented cells are present, giving the choroid a dark color. This color darkens the interior of the eyeball. The pigment also

prevents reflection of light within the eyeball. Both these factors help in formation of sharp images on the retina.

Added Information

The choroid proper is made up of an outer vascular lamina containing small arteries and veins, and lymphatics; and an inner capillary lamina (or choroidocapillaris). The connective tissue supporting the vessels of the vascular lamina is the choroidal stroma. Apart from collagen fibers it contains melanocytes, lymphocytes, and mast cells. The capillary lamina is not pigmented. Nutrients diffusing out of the capillaries pass through the basal lamina to provide nutrition to the outer layers of the retina.