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ORGANIZATION OF THE CENTRAL NERVOUS SYSTEM In the brain, the gray matter forms cortex; the white matter forms medulla. The cortex of gray matter in the brain contains nerve cell, bodies, axons, dendrites, and glial cells. The white matter contains only axons of nerve cell plus the associated glial cells and blood vessels. Whereas many of the axons going to or coming from a specific location are grouped into bundles called tracts. CEREBRAL CORTEX LAYERS The cerebral cortex is described as containing six different layers. I. II. III. IV. V. VI. The molecular layer consists largely of fibers, most of which travel parallel to the surface and few cells. The external granular layer contains small pyramidal and numerous stellate neurons. The external pyramidal layer contains small and medium-size pyramidal neurons, as well as non-pyramidal neurons. The internal granular layer contains different types of granule and pyramidal neurons. The internal pyramidal layer contains large pyramidal neurons (the Betz cells). The layer of polymorphic cells contains cells with diverse shapes, many of which have a spindle or fusiform shape. The basic functional and structural unit of cortex is called cortical column or cortical module. Cortical areas that lack a layer IV are called agranular. Cortical areas that have only a rudimentary layer IV are called dysgranular. CEREBELLUM There are three layers to the cerebellar cortex. I. Molecular layer 1. This outermost layer of the cerebellar cortex contains two types of inhibitory interneurons: the stellate and basket cells. II. Purkinje layer 1. The middle layer contains only cell body of Purkinje cells. It is extremely large flask-shaped cell bodies. 2. Purkinje cell dendrites with hundreds of branches go into the molecular layer. 1 3. Purkinje axons have inhibitory synapses with the neurons of the deep cerebellar and vestibular nuclei in the brainstem. 4. Purkinje cells also receive input from the inferior olivary nucleus via climbing fibers. III. Granular layer 1. The innermost layer contains the cell bodies of two types of cells: the numerous and tiny granule cells, and the larger Golgi cells. 2. Incoming (mossy) fibers enter the granular layer and form excitatory synapses with the granule cells and the cells of the deep cerebellar nuclei. 3. The granule cells send their T-shaped axons into the molecular layer. 4. Golgi cells provide inhibitory feedback to granule cells, forming a synapse with them and projecting an axon into the molecular layer. 5. Mossy and climbing fibers carry sensorimotor information into the deep nuclei, which in turn pass it on to various premotor areas. 6. The function of the cerebellar cortex is essentially to modulate information flowing through the deep nuclei. Deep in the granular layer is the white matter. BLOOD BRAIN BARRIER Blood-Brain-Barrier (BBB) prevents materials from the blood to entering the brain. Structure of the BBB 1. Endothelial lining. 2. Basal membrane of endothelial cells. 3. Glial cells (astrocytes). Functions of the BBB 1. Protects the brain from "foreign substances" in the blood that may injure the brain 2. Protects the brain from hormones and neurotransmitters in the rest of the body 3. Maintains a constant environment for the brain General Properties of the BBB 1. Large molecules do not pass through the BBB easily. 2. Low lipid (fat) soluble molecules do not penetrate into the brain. 3. However, lipid soluble molecules, such as barbiturate drugs, rapidly cross through into the brain. 4. Molecules that have a high electrical charge are slowed. The barrier is ineffective or absent in the neurohypophysis, substantia nigra and locus ceruleus. SPINAL CORD 2 The spinal cord is organized into two discrete parts. 1. The outer part contains ascending and descending nerve fibers. These fibers are divided into longitudinal columns or funiculi. They constitute the white matter of the cord. 2. The inner part contains cell bodies of neurons and nerve fibers. This is the gray matter of the spinal cord. Spinal gray matter is butterfly-shaped or H shaped. It extends from the ependymal cells lining the central canal to the surrounding white matter. Spinal neurons within the gray matter are either efferent neurons projection neurons interneurons Functionally related groups of nerve cell bodies in the gray matter are called nuclei. Functionally related bundles of axons in the white matter are called tracts. The dorsal horn marginal nucleus substantia gelatinosa nucleus proprius the nucleus thoracicus is present in thoracolumbar segments The lateral horn intermediolateral nucleus, which is composed of sympathetic preganglionic neurons The ventral horn somatic efferent motor neurons medial motor nuclei innervate muscles of the trunk and are found in all spinal segments lateral collections of motor neurons, which innervate limb muscle, are seen in segments of the cervical and lumbosacral enlargements PERIPHERAL NERVOUS SYSTEM There are two classifications of the PNS: anatomical and physiological. According to the first one, there are nervous, nerve ganglia and nerve endings (terminals) in the PNS. Physiologically, PNS is subdivided into two subsystems: the sensory-somatic nervous system and the autonomic nervous system. ANATOMICAL CLASSIFICATION OF PNS I. NERVES Epineurium is external, dense connective tissue. It contains fibroblast and histiocytes (inactive macrophage), capillaries and blood vessels. 3 Perineurium is the 2nd layer, covers bundle or nerve fibers. Perineurium consists of collagen and elastic fibers and connective tissue cells. Endoneurium surrounds individual nerve fibers, continuous with perineurium. II. NERVE ENDINGS The skin is richly innervated, served by a variety of sensory nerve endings which respond to a variety of modalities (e.g., pressure, vibration, heat, cold, itch, pain) and by motor nerve endings which control blood flow, sweat secretion, and piloerection. Free nerve endings terminate within the epidermis, penetrating almost to the stratum corneum. Merkel's touch corpuscles are nerve endings associated with Merkel cells at the base of the epidermis in thick (glabrous) skin of palms and soles. Meissner's corpuscles are encapsulated endings in dermal papillae, most common in palmar and plantar skin, especially in fingertips. Pacinian corpuscles, located deeper in dermis, are simple nerve endings but are each encapsulated by multilamellar, ovoid structures resembling small onions. Pacinian corpuscles respond to deep pressure. Ruffini endings have numerous fine branches from a single axon within the fluid-filled space of a single thin capsule. They are respond to the permanent pressure. Hair follicle receptors are unencapsulated nerve endings wrapped around hair follicles. Each skeletal muscle fiber is innervated by a single motor axon. The same axon may also innervate other muscle fibers. All the fibers innervated by the same axon are called a motor unit. Muscle action begins at the motor end plate (or neuromuscular junction), which is analogous to a synapse. Skeletal muscles contain specialized proprioceptive sense organs, called muscle spindles, which function to detect muscle stretch. Each muscle spindle consists of an encapsulated cluster of small striated muscle fibers ("intrafusal muscle fibers"). Each fiber has a mechanosensory nerve ending. Proprioceptor endings (Golgi tendon organs) are located at the point where muscle fibers attach to tendon. These sensitively respond to tension (force) exerted by the muscle; activity in these axons inhibits muscle contraction. III. SENSORY GANGLIA Sensory ganglia house cell bodies of sensory neurons. Sensory neurons in the dorsal root ganglia are pseudounipolar. 4 They have a single process that divides into a peripheral segment that brings information from the periphery to the cell body They have a central segment that carries information from the cell body into the gray matter of the spinal cord. The ganglions are surrounded by a connective tissue capsule composed of collagen. PHYSIOLOGICAL CLASSIFICATION OF PNS I. SENSORY- SOMATIC NERVOUS SYSTEM Somatic nervous system is the portion of the peripheral nervous system consisting of the motor neuron pathways that innervate skeletal muscles. The sensory nervous system comprises 12 pairs of cranial nerves and 31 pairs of spinal nerves. All of the spinal neuron pairs are mixed: they contain both sensory and motor neurons. This allows the spinal neurons to properly function as the conduit of transmission of the signals of the stimuli and the subsequent response. The somatic nervous system always acts to excite muscle groups. II. THE AUTONOMIC NERVOUS SYSTEM The Autonomic Nervous System is that part of PNS consisting of motor neurons that control internal organs. The autonomic nervous system (ANS) consists of three subsystems: the sympathetic nervous system the parasympathetic nervous system the enteric nervous system The ANS regulates the activities of cardiac muscle, smooth muscle, endocrine glands, and exocrine glands. The autonomic nervous systems can act to excite or inhibit innervated tissue. Most target organs and tissues are innervated by neural fibers from both the parasympathetic and sympathetic systems. The systems can act to stimulate organs and tissues in opposite ways (antagonistically). THE SYMPATHETIC NERVOUS SYSTEM The nerve fibers of the sympathetic system innervate smooth muscle, cardiac muscle, and glandular tissue. In general, stimulation via sympathetic fibers increases activity and metabolic rate. Accordingly, sympathetic system stimulation is a critical component of the fight or flight response (release of a chemical called noradrenaline). Examples include the acceleration of the heartbeat, raising of blood pressure, shrinkage of the pupils of the eyes, and the redirection of blood away from the skin to muscles, brain, and the heart. THE PARASYMPATHETIC NERVOUS SYSTEM 5 Parasympathetic fibers innervate smooth muscle, cardiac muscle, and glandular tissue. In general, stimulation via parasympathetic fibers slows activity and results in a lowering of metabolic rate and a concordant conservation of energy. Accordingly, the parasympathetic nervous sub-system operates to return the body to its normal levels of function the so-called "rest and digest" state. Examples include the restoration of resting heartbeat, blood pressure, pupil diameter, and flow of blood to the skin. The preganglionic fibers of the parasympathetic system derive from the neural cell bodies of the motor nuclei of the occulomotor (cranial nerve: III), facial (VII), glossopharyngeal (IX), and vagal (X) cranial nerves. With regard to specific target organs and tissues, parasympathetic stimulation acts to decrease heart rate and decrease the force of contraction. THE ENTERIC NERVOUS SYSTEM The enteric nervous system is made up of nerve fibers that supply the viscera of the body: the gastrointestinal tract, pancreas, and gallbladder. 6 EYE The eyes are complex sensory organs that provide us with the sense of sight. The wall of the eye consists of three concentric layers or coats. Corneoscleral coat, the outer or fibrous layer that includes the sclera and the cornea. Uvea, the middle layer or vascular coat that includes the choroid and the stroma of the ciliary body and iris. Retina, the inner layer that includes an outer pigment epithelium, the inner neural retina, and the epithelium of the ciliary body and iris. The cornea The cornea covers the anterior one-sixth of the eye. The cornea is continuous with the sclera. The cornea is transparent. The cornea consists of five layers: three cellular layers and two lamellae. The corneal epithelium is nonkeratinized stratified squamous epithelium. Bowman’s membrane is a homogenous fibrillar lamina on which the corneal epithelium rests. Bowman’s membrane is a barrier to the spread of infections. The corneal stroma constitutes 90% of the corneal thickness. It is composed of about 60 thin lamellae of collagen fibrils between which are found fibroblasts. Descement’s membrane is an unusually thick basal lamina of the corneal endothelial cells. The corneal endothelium is a single layer of flattened cells. It provides metabolic exchange between cornea and aqueous humor. The sclera The sclera is an opaque layer consisting of dense connective tissue. Flat collagen bundles interspersed with elastic fibers and a moderate amount of ground substance. Fibroblasts are scattered among these fibers. The sclera is pierced by blood vessels, nerves, and the optic nerve. Limbus The limbus is the transitional zone between cornea and sclera. It is the limbus region that contains the apparatus for the outflow of aqueous humor.. Iris The iris forms a contractile diaphragm anterior to the lens surface. The iris arises from the anterior border of the ciliary body. The pupil is the central aperture of this thin disc. The layers of the iris, from anterior to posterior, consist of fibroblasts and melanocytes the anterior stromal lamella a loose connective tissue layer that contains many small blood vessels 7 the posterior membrane (the sphincter pupillae and the dilator pupillae) a double layer of pigmented epithelial cells (to absorb light rays and responsible for variation in eye color) Ciliary body The ciliary body is a thickened anterior portion of the tunica vasculosa, located between iris and choroid. The anterior third of the ciliary body has ciliary processes. The layers of the ciliary body are similar to those of the iris, consisting of a stroma and an epithelium. The stroma is divided into two layers: -an outer layer of smooth muscle, the ciliary muscle, that makes up the bulk of the ciliary body -an inner vascular region that extends into the ciliary processes Ciliary processes are ridge-like extensions of the ciliary body from which zonulae fibers emerge and extend to the lens. The ciliary epithelium which covers the ciliary body has three principal functions: secretions of aqueous humor serving as the major component of the blood-aqueous barrier secretion and anchoring of the zonular fibers Choroid The choroid is the portion of the vascular layer that lies between the sclera and the retina and has two layers choriocapillary layer, an inner vascular layer Bruch’s membrane, a thin, amorphous, hyaline membrane Retina It consists of two basic layers: -Neural retina or retina proper, an inner layer that contains the photoreceptors -Retinal pigment epithelium, an outer layer In the neural retina, two regions are recognized: the nonphotosensitive region, located anterior to the ora serrata the photosensitive region located posterior to the ora serrata The fovea centralis is the area of greatest visual acuity. The visual axis of the eye passes through the fovea. The macula lutea surrounds the fovea and characterize as a yellow pigmented zone. There are four groups of cells, which constitute photosensitive region of retina: photoreceptors − the retinal rods and cones conducting neurons − bipolar and ganglion cells association and other neurons − horizontal, centrifugal and amacrine supporting cells − Müllers cells and neuroglial cells The layers of the retina, from outside inward are: 1. Pigment epithelium − the outer layer which consists of cuboidal cells. 8 2. Functions: absorption of the light passing through neural retina to prevent reflection isolation of the retinal cells from blood borne substances phagocytosis and disposal of membranous discs from the rods and cones Layer of rods and cones − contains the outer and inner segments of photoreceptor cells. Each rod and cone photoreceptor consists of outer segment, connecting stalk and inner segment. Difference between rods and cones: Amount: 120 million of rods and only 7 million of cones Sensitivity: the rods are more sensitive to light and used during periods of low light intensity but cones are less sensitive to low light Color perception: black and white picture for rods and the red, green or blue colors for cones The visual pigments: rhodopsin present in rods and iodopsin in cones. Outer segment: cylindrical in the rods and conical in the cones. 3. External (outer) limiting membrane − the apical boundary of Müllers cells. 4. Outer nuclear layer − contains the cell bodies (nuclei) of retinal rods and cones. 5. Outer plexiform layer −contains the processes of retinal rods and cones and processes of the horizontal, amacrine and bipolar cells that connect to them. 6. Inner nuclear layer − contains the cell bodies (nuclei) of horizontal, amacrine, bipolar and Müllers cells. 7. Inner plexiform layer − contains the processes, amacrine, bipolar and ganglion cells that connect to each other. 8. Ganglion cell layer − contains the cell bodies (nuclei) of large multipolar ganglion cells. 9. Layer of optic nerve fibers − contains processes of ganglion cells that lead from the retina to the brain. 10.Internal (inner) limiting membrane − composed of the basal lamina of Müllers cells which separating the retina from the vitreous body. Crystalline lens The lens is a transparent, avascular, biconvex structure. It is suspended between the edges of the ciliary body by the suspensory ligament. The lens includes lens capsule, subcapsular epithelium and lens fibers Vitreous humor Vitreous humor is the transparent jelly-like substance that fills the posterior segment (vitreous space) of the eye. The main body of the vitreous is a homogenous gel containing about 99% of water, hyaluronic acid, widely dispersed collagen fibers, and other proteins and glycoproteins. 9 Ear The ear is a three chambered sensory structure that in the auditory system functions in the perception of sound and in the vestibular system functions in the maintenance of balance. The external and middle ear collect and conduct sound energy to the inner ear, where auditory sensory receptors transducer that energy into the electrical energy of nerve impulses. External ear The external ear is composed of an auricle and an external auditory meatus. Thin skin with hair follicles, sweat glands and sebaceous glands covers the auricle. The lateral part of the canal is lined by skin that contains hair follicles, sebaceous glands, and ceruminous glands. Middle ear The tympanic membrane (eardrum) separates the external auditory canal from the middle ear. Structure of the middle ear: An air-filled space that contains three small bones, the ossicles which cross the space of the middle ear in series and connect the tympanic membrane to the oval window. Presence of the vestibular (oval) window and the cochlear (round) window in the medial wall of the middle ear. It contains the auditory tube (Eustachian tube) which connects the middle ear to the nasopharynx. Functions: convert sound waves (air vibrations) arriving from the external auditory meatus into mechanical vibrations that are transmitted to the inner ear equilibrate pressure in the middle ear with atmospheric pressure (due to Eustachian tube) Inner ear The inner ear consists of two labyrinthine compartments, one contained within the other. The bony (osseous) labyrinth is a complex system of interconnected cavities and canals. The membranous labyrinth lies within the bony labyrinth and also form continuous spaces enclosed within a wall of epithelium and connective tissue. There are three fluid-filled spaces in the inner ear. Endolymphatic space contained within the membranous labyrinth. Perilymphatic space lies between the wall of the bony labyrinth and the wall of the membranous labyrinth. 10 Cortilymphatic space lies within the organ of Corti. Bony labyrinth The bony labyrinth consists of semicircular canals, vestibule and cochlea. Structure of the vestibule: It is the central space that contains an elliptical and spherical recess. The semicircular canals extend from the vestibule posteriorly, and the cochlea extends from the vestibule anteriorly. The vestibular (oval) window lies in the lateral wall of the vestibule. Structure of the semicircular canals: They are bony walled tubes that lie in superior, posterior and horizontal planes. Each inner ear has three ampullae which are dilation of the lateral end of semicircular canal. The three canals open into the vestibule through five orifices. Structure of the cochlea: It is a conically shaped helix connected to the vestibule on the side opposite the semicircular canals. Between its base and the apex the cochlea makes about 2,5 turns around a central bony core called the modiolus. One opening of the canal, the cochlear (round) window is covered by the secondary tympanic membrane. Membranous labyrinth The membranous labyrinth consists of membranous semicircular ducts, utricle and saccule, and membranous cochlea (cochlea duct). Structure: Membranous semicircular ducts lie within the bony semicircular canals and are continuous with the utricle. The utricle and saccule are contained in recesses in the vestibule and are connected by the membranous utriculosaccular duct. The membranous cochlear duct is contained within the bony cochlea and is continuous with the saccule. The membranous semicircular ducts, utricle and saccule are components of the vestibular system. The membranous cochlea is part of the auditory system. Specialized sensory cells are located in six regions in the wall of the membranous labyrinth. Three cristae ampullaris located in the ampullae of the semicircular ducts. Two maculae, one in the utricle (macula utriculi) and the other in the saccule (macula sacculi). The organ of Corti that project into the endolymph of the cochlear duct. The three cristae ampullaris are sensitive to angular acceleration of the head (i.e., turning of the head). 11 The maculae of utricle and saccule sense the position of the head (sensors of gravity) and linear movement. The organ of Corti functions as the sound receptor. The hair cell, a nonneuronal mechanoreceptor is the common receptor cell of the vestibulocochlear system. Several important characteristics are common to hair cells: all are epithelial cells each possesses numerous stereocilia, modified microvilli, called sensory “hairs” in the vestibular system, each hair cell possesses a single true cilium called a kinocilium in the auditory system, hair cells have only a residual basal body they are transducers, i.e., they convert mechanical energy to electrical energy function by the bending or flexing of their stereocilia which generates transmembrane potential changes in the receptor cell that are conveyed to the afferent nerve ending(s) there are two types of hair cells and associated nerve endings in the vestibular system Organ of Corti: sensor of sound vibration The cochlear duct divides the cochlear canal into three parallel compartments or scalae: 1. The scala media contains an endolymph and the organ of Corti. The upper wall of the scala media is the vestibular membrane. The lateral wall is the stria vascularis. It is may be the site of synthesis of endolymph. The lower wall is the basilar membrane. 2. The scala vestibuli and the scala tympani contain perilymph. The organ of Corti rests on the basilar membrane and is overlain by the tectorial membrane. The organ of Corti is a complex epithelial layer on the floor of the scala media. It is formed by inner (close to the spiral lamina) and outer (farther from the spiral lamina) hair cells inner and outer phalangeal (supporting) cells pillar cells 12 Integumentary system (skin) The skin and its derivates constitute the integumentary system. The skin consists of 3 layers: epidermis, composed of a keratinized stratified squamous epithelium dermis, composed of a dense connective tissue hypodermis contains variable amounts of adipose tissue The epidermal derivates of the skin contain: 1. hair follicles and hair 2. sweat (sudoriferous) glands 3. sebaceous glands 4. nails 5. mammary glands Functions of integumentary system include: homeostatic function barrier function sensory function ''secretory'' function excretory function Epidermis The epidermis is composed of stratified squamous epithelium in which 5 distinct layers are observed. Beginning with the deepest layer, these are I. The stratum basale provides for epidermal cell renewal and contains the stem cells from which the new cells, the keratinocytes, arise. II. The stratum spinosum has cells which exhibit numerous spinous processes, which gives this layer its name. III. The stratum granulosum has cells that contain numerous keratohyaline granules. IV. The stratum lucidum is a translucent, thin layer of extremely flattened eosinophilic cells. This layer is found only in the skin of the palms of the hands and of the soles of the feet. V. The stratum corneum consists of 15-20 layers of flattened nonnucleated keratinized cells whose cytoplasm is filled with a keratin. Cells of the epidermis Keratinocyte The keratinocyte is predominate cell type of the epidermis. The intermediate filaments, more commonly called tonofilaments in the keratinocytes, represent the essential protein in keratin production. Functions: production of keratin creation of an extracellular water barrier 13 Melanocytes The epidermal melanocyte is a dendritic cell. The ratio of melanocyte to keratinocyte in the basal layer ranges from 1:4 to 1:10 in different parts of the body. Melanocytes have developing and mature melanin granules in the cytoplasm. Function: produce pigment Langerhans Cell The Langerhans cell possesses surface receptors. As an antigen-presenting cell, the Langerhans cell is involved in the initiation of cutaneous contact hypersensitivity reactions, i.e., contact allergic dermatitis, and in other cell-mediated immune responses in the skin. Function: present antigens to T cells Merkel Cell Merkel's cells are modified epidermal cells that are located in the stratum basale. The combination of the neuron and epidermal cell, called a Merkel's corpuscle, is a very sensitive mechanoreceptor. Function: cutaneous sensation Dermis The dermis is composed of two layers. I. The papillary layer consists of loose connective tissue beneath the epidermis and includes the dermal papillae and dermal ridges. It contains blood vessels that serve the epidermis. II. The reticular layer lies deep to the papillary layer. It is characterized by presence of collagen and elastic fibers which form regular lines of tension in the skin. Hypodermis It consists of adipose tissue and its associated loose connective tissue. Functions: energy storage site an important insulating layer SKIN APPENDAGES HAIR Hairs are composed of keratinized cells that develop from hair follicles. Structure of the Hair Follicle: The hair follicle is responsible for the production and growth of a hair. The growing follicle expands on its base to form the bulb. 14 The bulb consists of matrix cells. The outermost part of the hair follicle is the external (outer) root sheath. The dividing cells in the germinative layer of the matrix are the internal root sheath. The hair consists of a medulla, cortex, and cuticle. The internal root sheath consists of a cuticle, Huxley's layer, and Henle's layer. SEBACEOUS GLANDS Structure: Sebaceous gland is simple, branched and acinar, with holocrine type of secretion. It produces sebum. Sebaceous glands secretes into the pilosebaceous canal. The basal cells of the sebaceous gland contain smooth endoplasmic reticulum for lipid synthesis and secretion and few lipid droplets. Functions: secrete sebum that coats the hair and skin surface SWEAT GLANDS Two types of sweat glands are recognized: I. Eccrine Sweat Glands Location in the body: distributed over the entire body surface except for the lips and part of the external genitalia Structure: It is arranged as simple coiled tubular glands with merocrine type of secretion. Secretory segment has clear, dark and myoepithelial cells. Clear cells produce the watery component of sweat. Dark cells secrete glycoprotein. Myoepithelial cells are responsible due their contraction for the expression of sweat from the gland. The epithelium of the duct is stratified cuboidal, consisting of a basal cell layer and luminal cell layer. Function: regulating body temperature serves as an excretory organ (for sodium chloride, urea, uric acid, and ammonia) II. Apocrine Sweat Glands Location in the body: axilla areola nipple of the mammary gland circumanal region 15 the external genitalia the ceruminous glands of the ear canal the glands of Moll of the eyelid Structure: Apocrine glands are coiled tubular glands with apocrine type of secretion. They are associated with hair follicles. The apocrine glands store their secretory product in the lumen, which is very wide. The apical cytoplasm contains numerous small granules, the secretory component within the cells and also includes lysosomes and lipofuscin pigment granules. The duct epithelium is stratified cuboidal. Secretory segment contains secretory and myoepithelial cells Function: secrete protein, carbohydrate, ammonia, lipid, and certain organic compounds NAILS Nails are plates of keratinized cells containing hard keratin. Structure: The nail plate rests on the nail bed. The proximal part of the nail is the nail root. It covers the cells of the germinative zone, the matrix. The crescent-shaped white area near the root of the nail is the lunula. The edge of the skin fold covering the root of the nail is the eponychium or cuticle. A thickened epidermal layer, the hyponychium, secures the free edge of the nail plate at the fingertip. 16 Cardiovascular system The cardiovascular system is a transport system that carries blood and lymph to and from the tissues of the body. The cardiovascular system includes: the heart blood vessels (arteries, arterioles, capillaries, venules and veins) lymphatic vessels Together, the arterioles, associated capillary network, and post capillary venules form a microvascular bed. Arteries Arteries are classified into three types I. Elastic arteries Structure: Tunica intima an endothelial lining with its basal lamina a subendothelial layer of connective tissue not prominent internal elastic membrane Tunica media elastin lamellae between the muscle layers smooth muscle cells collagen fibers and ground substance Tunica adventitia collagen fibers elastic fibers fibroblasts and macrophages blood vessels (vasa vasorum) and nerves (nervi vascularis) II. Muscular arteries Structure: Tunica intima Same structure as in elastic arteries except presence of prominent elastic membrane Tunica media Same structure as in elastic arteries except less amount of elastic fibers Tunica adventitia Same structure as in elastic arteries except presence of: external elastic membrane adipose cells and absence of vasa vasorum and nervi vascularis 17 III. Small arteries and arterioles Small arteries have up to about eight layers of smooth muscle in the tunica media has an internal elastic membrane in the tunica intima the tunica adventitia is a thin, sheath of connective tissue Arterioles one or two layers of smooth muscle in the tunica media this layer may or may not be present the tunica adventitia is a thin, sheath of connective tissue The arterioles have two important functions: 1). Maintain the blood pressure inside the arterial system 2). Control blood flow to the capillary networks. The arterio-venous connections The arterio-venous connections are classified into two main types, namely; 1). Blood capillaries and the vessels regulating their blood flow 2). Arterio-venous anastomosis (A-V shunts) Capillaries Capillaries are the smallest diameter blood vessels, often smaller than diameter of an erythrocyte. They consist of a single layer of endothelial cells and their basal lamina. Capillaries are described as: 1). Continuous or somatic capillaries Location in the body: muscle lung central nervous system (CNS) skin Structure: continuous endothelial lining continuous basal lamina pinocytotic vesicles 2). Fenestrated or visceral capillaries, Location in the body: endocrine glands gallbladder intestinal tract Structure: fenestrae in the walls of endothelial cells continuous basal lamina 18 pinocytotic vesicles 3). Discontinuous or sinusoidal capillaries Location in the body: liver spleen bone marrow Structure: presence of unusually wide gaps (fenestrae) between endothelial cells partial of total absence of basal lamina presence of specialized cells, such as the stellate sinusoidal macrophages (Kupffer cells) and vitamin A storage cells (of Ito) in the liver, among the lining endothelial cells Capillaries have three essential functions: selective permeability synthetic and metabolic activities antithrombogenic function Arteriovenous shunts Direct routes between the arteries and veins that can divert blood from the capillaries are called arteriovenous anastomoses or shunts. Location in the body: in the skin of the fingertips nose lips in the erectile tissue of the penis clitoris Functions: serve in thermoregulation at the body surface (closing an AV shunt in the skin causes increasing heat loss and open it conserving body heat) control the amount of blood passing through the capillary bed How it work: contraction of the arteriole smooth muscle of the AV shunt sends blood to a capillary bed relaxation of the smooth muscle sends blood to a venule, bypassing the capillary bed Difference between veins and arteries 1. Typically, veins have thinner walls than their accompanying arteries. 2. The lumen of the vein is usually larger than that of the artery. 3. The lumen of the vein is often collapsed, whereas the lumen of the artery is often patent. 4. Many veins have valves. 5. Adventitia is the thickest tunica in the veins and media in the arteries. 19 6. The veins have more collagen fibers than elastic. 7. Shape of the wall in the vein is irregular and in the artery is regular. Veins Traditionally, veins are divided into three types on the basis of size. Large veins Structure: The tunica intima an endothelial lining with its basal lamina a small amount of subendothelial connective tissue some smooth muscle cells The tunica media smooth muscle cells collagen fibers some fibroblasts The tunica adventitia bundles of longitudinally disposed smooth muscle cells collagen fibers elastic fibers fibroblasts Medium veins Structure: The tunica intima: an endothelium with its basal lamina a thin subendothelial layer with smooth muscle cells and connective tissue elements a thin internal elastic membrane The tunica media circularly arranged smooth muscle cells collagen fibers The tunica adventitia longitudinally oriented bundles of smooth muscle cells collagen fibers networks of elastic fibers Venules Muscular venules are distinguished from postcapillary venules by the presence of a tunica media. Postcapillary venules receive blood from capillaries and possess an endothelial lining with its basal lamina and pericytes. Muscular venules are located distal to the postcapillary venules in the returning venous network. Whereas postcapillary venules have no true tunica media, the 20 muscular venules have one or two layers of smooth muscle that constitute a tunica media and have a thin tunica adventitia. LYMPHATIC VESSELS Lymphatic vessels convey fluids from the tissues to the bloodstream. In addition to blood vessels, there is a set of vessels that circulates fluid, called lymph, through certain parts of the body. These lymphatic vessels are an adjunct to the blood vessels. Difference between lymph and blood capillaries Lymph capillaries Blood capillaries Wider irregular lumen. Narrower regular lumen. Blind ended, i.e. it begins by a blind end. Has arterial and venous ends. The endothelium is not fenestrated. The endothelium may be fenestrated. It lacks a well-developed basement It has a well-developed basement membrane. membrane. Lacks pericytes. Has pericytes. The outer surface of the endothelium is No anchoring fibers. attached to the surrounding C.T. by anchoring fibers Heart The heart is a pump with four chambers with valves that maintain a one-way flow of blood. General structure: The heart contains 4 chambers (two atria and two ventricles) through which blood is pump. Valves guard the exits of chambers, preventing the backflow of blood. An interatrial septum and an interventricular septum separate the right and left sides of the heart. Structure of the heart wall: I. Epicardium consists of a layer of mesothelial cells on the outer surface of the heart and its underlying connective tissue. The blood vessels and nerves that supply the heart lie in epicardium and are surrounded by adipose tissue. II. Myocardium, the cardiac muscle, is the principal component of the heart. Difference between cardiac and skeletal muscle Cardiac muscle Skeletal muscle formed by individual cardiac muscle formed by muscle fiber cells mononucleated multinucleated location of the nucleus in the center location of nuclei under the plasma membrane (sarcolemma) presence of intercalated disks absence of intercalated disks 21 (attachment between neighboring muscle cells) presence of diad (T tubule and terminal cisternae) presence of juxtanuclear mitochondria presence of cardiac conducting cells (Purkinje cells) III. presence of triad (T tubule and two terminal cisternae) absence of juxtanuclear mitochondria absence of cardiac conducting cells (Purkinje cells) Endocardium consists of an inner layer of endothelium and subendothelial connective tissue (which includes impulse-conducting system), a middle layer of connective tissue and smooth muscle cells, and a deeper layer, also called the subendocardial layer of connective tissue that is continuous with the connective tissue of the myocardium. Intrinsic regulation of heart rate Cardiac muscle is capable of contracting in a rhythmic manner without any direct stimulates from the nervous system. The base of this beating action is initiated at the sinoatrial (SA) node, a group of specialized cardiac muscle cells located near the junction of the superior vena cava and the right atrium. The SA node is referred to as the pacemaker. The SA node initiates an impulse that spreads along the cardiac muscle fibers of the atria and along internodal tracts composed of modified cardiac muscle fibers. The impulse is then picked up at the atrioventricular (AV) node and conducted across the fibrous skeleton to the ventricles by the AV bundle (of His). The bundle divides into smaller right and left bundle branches and then into Purkinje fibers. The AV bundle, the bundle branches, and the Purkinje fibers are modified cardiac muscle cells that are specialized to conduct impulses. 22 Lymphoid system and organs of hematopoiesis and immune response Classification of hematopoiesis and immune defense organs 1. Central organs of hematopoiesis and immune defense are thymus and red bone marrow. 2. Peripheral organs of hematopoiesis and immune defense are spleen, lymph nodes and solitary lymphatic nodules. Thymus Function: Site of the programming, differentiation and proliferation of T lymphocytes Structure: Thymic lobule is the structural and functional unit of the thymus. Connective tissue capsule surrounds the cortex and extends trabeculae to the margin of the cortex and medulla. Cortex is the outer portion of the parenchyma which consists of dense population of so-called thymocytes that are T lymphocytes, and scattered epithelial reticular cells that have multiple processes and partially compartmentalize thymocytes. The connective tissue here contains variable number of plasma cells, granulocytes, T lymphoblasts, mast cells, fat cells and macrophages. Medulla is the inner portion of the parenchyma that contains a lesser number of lymphocytes and T lymphoblasts and more epithelial reticular cells than the cortex. Thymic or Hassall’s corpuscles are concentrically arranged epithelioreticular cells. Blood thymic barrier The blood thymic barrier present only in the cortex. Structure: 1. capillary endothelium 2. endothelial basal lamina 3. thin perivascular connective tissue sheath 4. basal lamina of the epithelioreticular cells 5. epithelioreticular cells sheath Function: Prevents the contact between the high concentrations of antigens circulating in the blood and the developing immature lymphocytes in the thymic cortex. Red bone marrow Structure: developing blood cells in different stages of development network of reticular cells and fibers (supporting framework) 23 blood vessels erythroblastic islands which are clusters of developing erythrocytes surround and receive iron from macrophages Yellow bone marrow In later stages of growth and in the adult, when the rate of blood cell formation has diminished, the tissue in the medullary cavity consists mostly of fat cells; it is then called yellow marrow. Under appropriate stimuli; such as extreme blood loss, the yellow marrow can revert to red marrow. In the adult, red marrow is normally restricted to the spaces of spongy bone in a few locations such as the sternum and the iliac crest. Spleen The spleen is the largest lymphatic organ. In addition to large numbers of lymphocytes, it contains specialized vascular spaces or channels, a meshwork of reticular cells and reticular fibers, and a rich supply of macrophages. Capsule of dense connective tissue from which trabeculae extend into the substance of the organ White pulp is the concentration of lymphatic tissue within the red pulp that surrounds portions of central arteries forming nodules along their lengths. Malpighian corpuscles are enlarged nodules in the white pulp. Nodules consist of reticular mesh with spaces in mesh being filled with lymphocytes, monocytes, plasma cells and macrophages. They have germinal center and marginal zone (separates white pulp and red pulp) where located dendritic cells (macrophages). T-lymphocytes aggregated around the central artery constitute the periarterial lymphatic sheath. B-lymphocytes located at periphery of white pulp. Red pulp consists of splenic sinuses separated by the splenic cords. The splenic cords consist of the loose meshwork of reticular cells and reticular fibers that contain large numbers of erythrocytes, macrophages, lymphocytes, plasma cells and granulocytes. Many of the macrophages are engaged i n the phagocytosis of damaged red blood cells. Present blood sinusoids are site of cellular exchange between spleen and circulatory system. Functions: Immune system functions of the spleen include: proliferation of lymphocytes production of humoral antibodies removal of macromolecular antigen from the blood Hematopoietic functions of the spleen include: formation of blood cells during fetal life 24 removal and destruction of senile, damaged and abnormal red blood cells and platelets retrieval of the iron from red cell hemoglobin storage of blood, especially red blood cells, in some species Lymph Nodes Lymph nodes are small, bean-shaped, encapsulated organs located along the pathway of lymphatic vessels. Structure: Supporting elements (stroma) of lymph node consist of: Capsule is composed of dense C.T. that surrounds the node. The capsule is penetrated at the cortex by the afferent lymphatic vessels and at the hilum by blood vessels, efferent lymphatic vessels and nerves. Trabeculae are composed of dense C.T., which extend from the capsule into the substance of the node, forming a gross framework Reticular C.T., is composed of reticular cells and reticular fibers that form a supporting meshwork throughout the organ. The parenchyma of lymph node consists of: The cortex is composed of cortical lymph nodules surrounded by lymph sinuses. The cortex is divided into an outer and an inner cortex. The outer cortex has lymphatic nodules that mostly contain B-cells. Also they contain small lymphocytes, macrophages, dendritic cells, and some T cells. The inner cortex contains mostly T-cells. There are afferent lymphatic vessels through which lymph enters the subcapsular sinus from which it runs through cortical sinuses into medullary sinuses and leaves through the efferent lymphatic vessels. Main cell type around the sinuses is macrophage. The medulla is composed of medullary cords of lymphoid tissue surrounded by medullary lymph sinuses. Medullary cords contain mainly plasma cells and B cells. Functions: 1) Filtration of lymph: As lymph flows through the sinuses, 99% or more of the antigens and other debris it carries are removed, by the phagocytic activity of macrophages that span the sinuses. 2) Antibodies production: Antigens carried to the lymph nodes, activate its B-lymphocytes to change into plasma cells which produce the specific antibodies. The antibodies pass with the lymph to the circulation. Memory cells leave the node 25 with the lymph to the circulation. If they are stimulated again by the same antigen, they migrate to the surrounding CT. and change to plasma cells and secrete the antibodies. 3) Site of proliferation of lymphocytes. Lymphatic tissue and the immune response The lymphatic system is specialized form of connective tissue that consists of cells, tissues, and organs that monitor body surfaces and internal fluid compartments and react to the presence of potentially harmful antigenic substances. Immune defenses fall into two categories: I. II. Nonspecific defenses that guard against a wide variety of pathogens Immunity, composed of mechanisms whereby lymphocytes recognize and destroy specific pathogens Nonspecific Body Defenses Surface membranes (skin and mucous membranes) provide mechanical barriers to pathogens. Some produce secretions and/or have structural modifications that enhance their defensive effects. The skin's acidity, lysozyme, mucus, keratin, and ciliated cells are examples. Phagocytes (monocytes, macrophages and neutrophils) swallow up and destroy pathogens that penetrate epithelial barriers. Antigens and antibodies Antigens (Ag) are large, complex molecules (or parts of them) recognized as foreign by the body. Foreign proteins are the strongest antigens. Complete antigens provoke an immune response and bind with products of that response (antibodies or sensitized lymphocytes). Incomplete antigens, or haptens, are small molecules that are unable to cause an immune response by themselves but do so when they bind to body proteins and the complex is recognized as foreign. An antibody (Ab), or immunoglobulin, is a gamma globulin. An antibody is composed of four polypeptide chains (two heavy and two lights) that form a Y-shaped molecule. Immunoglobulins are highly specialized protein molecules, also known as antibodies, fit foreign antigens like a lock and key. Their variety is so extensive that they can be produced to match all possible microorganisms in our environment. Cells of the immune system B-LYMPHOCYTES - These lymphocytes arise in the bone marrow and differentiate into plasma cells which in turn produce 26 immunoglobulins (antibodies). MONOCYTES - A type of phagocytic cell found in the bloodstream which develops into a macrophage when it migrates to tissues. PLASMA CELLS - These cells develop from B-lymphocytes and are the cells that make immunoglobulins. T-LYMPHOCYTES - These lymphocytes arise in the bone marrow but migrate to the thymus where they are instructed to mature into T-lymphocytes. T-EFFECTOR LYMPHOCYTES - These lymphocytes produce chemicals that function in a variety of ways to mediate tissue inflammation and the killing of foreign cells and microorganisms. T-HELPER LYMPHOCYTES - These specialized lymphocytes "help" other T-lymphocytes and B-lymphocytes to perform their functions. T-SUPPRESSOR LYMPHOCYTES - These specialized lymphocytes "suppress" T-helper lymphocytes and thereby turn off the immune response. Two main cell populations, lymphocytes and macrophages, provide for immunity. Macrophages are active in nonspecific resistance. Antibodies Five classes of antibodies exist: IgA, IgG. IgM, IgD, IgE, They differ structurally and functionally. Antibody Main functions IgG Provides resistance against many viruses, bacteria and bacterial toxins. Can cross placenta and provide passive immunity to fetus (80% of antibodies) IgE Found on the surface of basophils and mast cells. Release histamine and other chemicals that promote inflammation reaction. Also active in allergic reaction. IgD Found on the surface of B-cell. Help in the activation of b-cells IgM The first to be secreted after antigen invasion. IgA Found in glandular secretion (mucus, tears and saliva). Attack pathogens before they access the internal tissues. Specific body defenses: the immune system The two arms of immune response are humoral immunity, mediated by antibodies, and cellular immunity mediated by living cells (lymphocytes). 27 Humoral (antibody-mediated) immune response In humoral immunity, the essential stages are recognition, attack, and memory. Primary immune response occurs when antigens bind for the first time to B-cells receptors, causing them to proliferate. Most clone members become plasma cells, which secrete antibodies. Other clone members become memory B cells, capable of mounting a rapid attack against the same antigen in subsequent meetings (secondary immune responses). These memory cells provide immunological "memory." Active humoral immunity is acquired during an infection or via vaccination and provides immunoiogical memory. Passive immunity is conferred when a donor's antibodies are injected into the bloodstream, or when the mother's antibodies cross the placenta. It does not provide immunological memory. Cellular (cell-mediated) immune response. In cellular immunity, lymphocytes directly attack and destroy foreign cells and diseased host cells. 28 Endocrine organs The primary function of two major organ systems, the endocrine system and the nervous system is intercellular communication. The endocrine system communicates through the release of hormones, secretory products of endocrine cells and organs that pass into the circulatory system for transport to target cells that possess receptors for the hormones. Endocrine hormones include three classes of compounds. 1. Steroids are synthesized and secreted by cells of ovaries, testes and adrenal cortex. 2. Small peptides, proteins and glycoproteins are synthesized and secreted by the cells of the hypothalamus, hypophysis (pituitary), thyroid, parathyroid, pancreas and scattered endocrine cells of the gastrointestinal tract and lungs. 3. Amino acid analogues and derivatives, including the catecholamines are synthesized and secreted by many neurons as well as cells of the adrenal medulla. Hypophysis (pituitary gland) The hypophysis has two functional components: I. The adenohypophysis consists of: pars distalis pars intermedia pars tuberalis II. The neurohypophysis consists of: pars nervosa pars infundibulum Pars distalis There are three types of cells according to their staining reaction, such as, basophiles 10%, acidophils 40%, and chromophobes 50%. Basophiles is divided into: the adrenocorticolipotropes (the most common basophiles) which produce adrenocorticotropic hormone (ACTH) and lipotropic hormone (LPH) the gonadotropes (small basophiles) which produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) the thyrotropes (large basophiles) which produce thyroid-stimulating hormone (TSH) Acidophils is divided into: the somatotropes (small acidophils) which produces somatotropin, a growth hormone (GH) the lactotropes (mammotropes) which produce prolactin (PR) or lactogenic hormone (LTH) Chromophobes have undifferentiated cells and follicular cells. 29 Pars intermedia This region made up of cords and follicles of weakly basophilic cells and chromophobic cells. In the basophilic cells are found small amount of melanocytestimulating hormone. Pars tuberalis The endocrine cells are arranged in short clusters or cords in association with the blood vessels. Some functional gonadotropes are present in this region. Neurohypophysis The neurohypophysis is a nerve tract whose terminals store and release secretory product from the hypothalamus. Structure: The neurohypophysis consists of pars nervosa and infundibulum. Pars nervosa contains nonmyelinated axons and nerve endings of approximately 100.000 neurosecretory neurons whose cell bodies lie in the supraoptic and paraventricular nuclei of the hypothalamus. Dilatations of the axons are called Herring bodies. The Herring bodies contain either oxytocin or vasopressin (antidiuretic hormone) which synthesized in the hypothalamus. The neurohypophysis contains pituicytes (about 25% of the volume of organ) associated with the fenestrated capillaries. Functions of hormones: Antidiuretic hormone (vasopressin) increases blood pressure by promoting the contraction of smooth muscle in small arteries and arterioles decreases urine volume by altering the permeability of kidney collecting tubules decreases the rate of perspiration Oxytocin promotes contraction of smooth muscle of the uterus during copulation and parturition promotes contraction of myoepithelial cells of the breast The hypothalamus Structure: The hypothalamus has supraoptic and paraventricular nuclei. Antidiuretic hormone and vasopressin are secreted by these nucleuses. The hypothalamus is the site of production of a number of neurosecretory proteins. The hypothalamic neurons secrete proteins that promote and inhibit the secretion and release of adenohypophyseal hormones. These hormones are 30 called hypothalamic releasing hormones and hypothalamic inhibiting hormones. Function: The hypothalamus regulates hypophyseal function. Pineal gland Structure: The pineal gland contains two basic types of parenchymal cells Pinealocytes are the most common parenchymal secretory cells. They are arranged in clumps within the lobules. They have large, deeply infolded nucleus, contain lipid droplets within their cytoplasm and have expanded club- like endings of their processes. They secrete serotonin and melatonin. The interstitial (glial) cells comprise about 5% of the cells in the gland. They provide support for the pinealocytes. Functions of hormones: Melatonin influences seasonal sexual activity circadian (24 hour) biorhythms slows steroid secretion by the ovaries Serotonin influences hormone of happiness ADRENAL GLANDS Structure: The glands are covered with a thick connective tissue capsule from which trabeculae extend into the parenchyma. The secretory parenchymal tissue is organized in cortical and medullary regions. The cortex is the steroid-secreting portion. It lies beneath the capsule and constitutes nearly 90% of the gland by weight. The medulla is the catecholamine-secreting portion. It lies deep to the cortex and forms the center of the gland. The adrenal cortex is divided into three zones. Zona glomerulosa, the narrow outer zone Zona fasciculata, the thick middle zone Zona reticularis, the inner zone Zona Glomerulosa Structure: The cells are relatively small columnar or pyramidal shaped. They secrete mineralocorticoids mainly aldosterone Functions of hormones: control electrolyte homeostasis (act in distal tubule cells of kidney to increase sodium resorption and decrease potassium resorption) 31 maintain the osmotic balance in the urine control of blood pressure exacerbate inflammatory processes Zona Fasciculata Structure: The cells of the zona fasciculata are large and polyhedral. The cytoplasm contains numerous lipid droplets that are precursors for the steroid hormones secreted by these cells. These cells secrete glucocorticoids mainly hydrocortisone (cortisol), cortisone and corticosteron. Functions of hormones: regulate glucose and fatty acid metabolism depress the immune response depress the inflammatory response inhibit macrophage recruitment and migration stimulate destruction of lymphocytes in lymph nodes provide resistance to stress and suppress some allergic reaction Zona Reticularis Structure: The cells of the zona reticularis are noticeably smaller than those of the zona fasciculata. They are arranged in anastomosing cords, separated by fenestrated capillaries. These cells secrete weak androgens (mostly dehydroepiandrosterone) and glucocorticoids (principle one is hydrocortisone) Adrenal Medulla Structure: It contains large, epithelioid cells, called chromaffin cells connective tissue numerous sinusoidal blood capillaries nerves These cells secrete catecholamines: epinephrine (80%) and norepinephrine (20%) Functions of hormones: Catecholamines increase heart rate blood pressure sweating rate of respiration Catecholamines decreases blood flow to viscera and skin digestion, urine production 32 Thyroid gland Structure: The thyroid is a bilobed endocrine gland located in the neck. The lobes are connected by the isthmus. A thin connective tissue capsule surrounds the gland. It sends trabeculae into the parenchyma to partially outline irregular lobes and lobules. Secretory follicles constitute the functional units of the gland. The lumina of the follicles are filled with a gel-like mass called colloid. Colloid contains thyroglobulin, the inactive storage form of the thyroid hormones. The thyroid hormones are formed by the coupling of two iodinated tyrosine residues to produce thyroxine (T4 and T3 ratio of 20: 1) which cross the basal membrane and enter blood and lymphatic capillaries. Two basic cell types are present in the follicles principal or follicular cells and parafollicular or C cells. Follicular cells secrete T4 and T3. Parafollicular cells secrete calcitonin. Functions of hormones: Thyroxin (tetroidothyronine T4) and triidothyronin T3 regulate cell and tissue metabolism influences body and tissue growth influences development of the nervous system in the fetus and young child responsible for homeostasis Calcitonin lowers blood calcium level suppressing bone resorption Parathyroid glands Structure: They are ovoid and arranged in two pairs, to comprise the superior and inferior parathyroid glands. Each parathyroid gland is surrounded by a thin connective tissue capsule that separates it from the thyroid gland. Septa extend from the capsule into the gland to divide it into lobules and to separate the densely packed cords of cells. Principal (chief) cells which responsible for the secretion of parathyroid hormone (parathormone) and oxyphil cells constitute the epithelial cells of the parathyroid gland. Functions of hormones: increase level of calcium in the blood reduce the concentration of phosphate stimulate bone resorption 33 DIGESTIVE SYSTEM The digestive system consists of alimentary canal and its associated organs, namely, the tongue, teeth, salivary glands, pancreas, liver and gallbladder. The alimentary mucosa is the surface across which most substances enter the body. Functions of the alimentary mucosa: 1. Barrier function: The mucosa serves as a barrier to the entry of noxious substances, antigens, and pathogenic organisms. 2. Immunologic function: Lymphatic tissue in the mucosa serves as a first line of defense of the body by the immune system. 3. Secretory function: The lining of the alimentary canal secretes, at specific sites, digestive enzymes, hydrochloric acid, mucin, and antibodies. 4. Absorptive function: The epithelium of the mucosa absorbs metabolic substrates, i.e., the breakdown products of digestion, as well as vitamins, water, electrolytes, and other substances. Oral cavity The oral cavity consists of the mouth and its contents, i.e., the tongue, teeth, salivary glands, and tonsils. Tongue Structure: The tongue is a muscular organ. The striated muscles of the tongue are arranged in bundles that generally run in three planes and usually separated by connective tissue. The dorsal surface of the tongue is divided into an anterior two-thirds and a posterior one-third by a V shaped depression, the sulcus terminalis. Papillae cover the dorsal surface of the anterior portion of the tongue. There are four types: fungiform, circumvallate and foliate papillae have taste buds but filiform don’t have them. Lingual tonsils Structure: Lingual tonsils are located in the lamina propria of the root or base of the tongue. They are found posterior to the sulcus terminalis. The lingual tonsils contain lymphatic nodules. Epithelial crypts usually invaginate into the lingual tonsil. Gingiva Structure: The gingiva is firmly attached to the teeth and underlying bony tissue. It is composed of stratified squamous epithelium and numerous connective tissue papillae. 34 This epithelium is bound to the tooth enamel by means of a cuticle that resembles a thick basal lamina and forms the epithelial attachment of Gottlieb. Between the enamel and the epithelium is the gingival crevice a small deepening surrounding the crown. Teeth and supporting tissues Teeth are embedded in and attached to the maxilla and mandible. Enamel Structure: Enamel covers the crown of the tooth. The enamel layer ends at the neck or cervix of the tooth at the cementoenamel junction. Enamel is the hardest substance in the body It Consists of 96-98% hydroxyapatite. The structural and functional unit of the tooth is rods or prisms. Striations observed on enamel rods (contour lines of Retzius) may represent evidence of rhythmic growth of the enamel in the developing tooth. The enamel in a mature tooth is acellular and nonreplaceable. Cementum Structure: Cementum covers the root of the tooth. Like bone, cementum has a mineral content of 45-50%. The lacunae and canaliculi in the cementum contain the cementocytes and their processes, respectively. Cementum is avascular. The canaliculi in cementum do not appear to form an interconnecting network. A layer of cementoblasts is seen on the outer surface of the cementum, adjacent to the periodontal ligament. Collagen fibers that project out of the matrix of the cementum and embed in the bony matrix of the socket wall form the bulk of the periodontal ligament. These fibers are another example of Sharpey's fibers. Oxytalan fibers that resemble developing elastic fibers are also a component of the periodontal ligament. Dentin Structure: Dentin lies deep to the enamel and cementum. It contains less hydroxyapatite than does enamel, about 70%. 35 Dentin is secreted by odontoblasts that form an epithelial layer over the inner surface of the dentin, i.e., that surface that is in contact with the pulp. Odontoblasts processes embedded in the dentin are narrow channels called dentinal tubules. The rhythmic growth of dentin produces certain "growth lines" in the dentin (incremental lines of von Ebner and the thicker lines of Owen) that can identify significant developmental times such as birth (neonatal line). Study of growth lines has proved useful in forensic medicine. Predentin is newly secreted organic matrix, closest to the cell body of the odontoblasts that has yet to be mineralized. Dental Pulp and Pulp Cavity Structure: The pulp cavity is the space within a tooth that is occupied by pulp, a loose connective tissue that is richly vascularized and supplied by abundant nerves. The pulp cavity has the general shape of the tooth. The blood vessels and nerves enter the pulp cavity at the tip (apex) of the root, at a site called the apical foramen. The blood vessels and nerves extend to the crown of the tooth where they form vascular and neural networks beneath and within the layer of odontoblasts. In teeth with more than one cusp, pulpal horns extend into the cusps and contain large numbers of nerve fibers. Alveolar Process and Alveolar Bone Structure: The alveolar bone proper, a thin layer of compact bone, forms the wall of the alveolus and is the bone to which the periodontal ligament is attached. The rest of the alveolar process is supporting bone. Periodontal Ligament Structure: The periodontal ligament is the fibrous connective tissue joining the tooth to its surrounding bone. Functions: Attachment Support Bone remodeling (during movement of a tooth) Nutrition of adjacent structures Proprioception Tooth eruption Attachment and support are the most apparent functions. 36 Salivary glands Exocrine glands in the mouth produce saliva, which has digestive, lubricating and immunologic functions. Classification of the salivary glands labial buccal molar palatine The minor salivary glands lingual parotid submandibular sublingual The major salivary glands Cells of salivary glands: Serous cells are protein -secreting cells. Mucous cells are mucus-secreting cells. Myoepithelial cells are instrumental in moving secretory products toward the excretory duct. Salivary ducts The lumen of the salivary acinus is continuous with that of a duct system that may have as many as three sequential segments. intercalated duct striated duct excretory duct Parotid gland Structure: The parotid glands are branched acinar and totally serous. The parotid duct travels from the gland, which is located below and in front of the ear, to enter the oral cavity opposite the second upper molar tooth. The secretory units in the parotid glands are serous and surround numerous, long, narrow intercalated ducts. Striated ducts are large. Large amounts of adipose tissue may be one of its distinguishing features. Submandibular gland Structure: The submandibular glands are branched tubuloacinar gland. Its secretory portion contains mainly serous and some mucous cells. The paired, large, mixed submandibular glands are located under either side of the floor of the mouth, close to the mandible. A duct from each of the two glands runs toward and medially to a papilla located on the floor of the mouth just lateral to the frenulum of the tongue. Intercalated ducts are less extensive than in the parotid gland. Sublingual gland Structure: The small sublingual glands are branched tubuloacinar gland; Its secretory portion contains mainly mucous and some serous cells. 37 The sublingual glands are located in the floor of the mouth anterior to the submandibular glands. Their multiple small sublingual ducts empty into the submandibular duct as well as directly onto the floor of the mouth. Intercalated ducts and striated ducts are difficult to locate or may be absent. Alimentary canal structure The wall of the tract is formed by four distinctive layers. 1. Mucosa consists of a lining epithelium, an underlying connective tissue called lamina propria which contains glands, vessels and elements of the immune system, and also of muscularis mucosae, composed of smooth muscle cells arranged as an inner circular and an outer longitudinal layer. 2. Submucosa consists of dense irregular connective tissue which contains the larger blood vessels and the nerve network 3. Muscularis externa consists of the inner layer of circularly oriented smooth muscle cells and the outer one of a longitudinally oriented smooth muscle cells. 4. Serosa or adventitia, a serous membrane consists of a simple squamous epithelium, the mesothelium, and a small amount of underlying connective tissue, where the wall is directly attached to adjoining structures, the outer layer is the adventitia and is composed of connective tissue Esophagus Structure: The esophagus is lined with a nonkeratinized stratified squamous epithelium. The underlying lamina propria and the muscularis mucosae are not unique. The submucosa along with the muscularis mucosae forms a number of longitudinal folds and creates a highly irregular luminal profile. Upper one-third of the muscularis externa is striated muscle, the middle third is striated and smooth muscle and the distal third consists of smooth muscle. The outer layer of esophagus in the thoracic cavity is composed of adventitia. After entering the abdominal cavity it is covered by serosa. Esophageal glands proper occur in the submucosa. They are small compound tubuloalveolar mucous secreting glands. Esophageal cardiac glands occur in the lamina propria of the mucosa. They are simple tubular mucous secreting glands. Functions: The esophagus is a muscular tube that delivers food and liquid from the oropharynx to the stomach. 38 Stomach Structure: The stomach is an expanded part of the digestive tube that lies under the diaphragm. The stomach has mucosae, submucosa, muscularis externa and a serosa. The inner surface of the empty stomach has a number of longitudinal folds or ridges called rugae. In the mucosal surface is present numerous openings. These are the gastric pits or foveolae. The smaller regions of the mucosa are formed by grooves or shallow trenches that divide the stomach surface into bulging irregular areas called mamillated areas. The stomach is divided into three distinct into three distinct parts: the cardia (cardiac region) contains the cardiac glands the pylorus (pyloric region) contains the pyloric glands the fundus (fundic region) contains the fundic or gastric glands. I. Gastric mucosa The epithelium that lines the surface and the gastric pits of the stomach is simple columnar. Fundic glands of the gastric mucosa are simple, branched tubular glands. Fundic glands are composed of 1. Undifferentiated cells that give rise to the mature cells. 2. Mucous neck cells secrete soluble mucus compared with insoluble or cloudy mucus produced by the surface mucous cells. 3. Chief cells secrete pepsin in an inactive precursor form designated pepsinogen and a weak lipase 4. Parietal cells secrete HCL and intrinsic factor. Intrinsic factor, a glycoprotein that is essential for the absorption of vitamin B 12. 5. Enteroendocrine cells secrete gastrin, one of the gastrointestinal polypeptide hormones, is the principal effective agent for stimulating the secretion of HCL. Cardiac glands of the gastric mucosa are simple tubular, and branched. They are composed mainly of mucus-secreting cells, with occasional interspersed enteroendocrine cells. Pyloric glands of the gastric mucosa are branched, tubular glands that are coiled. Enteroendocrine cells are found interspersed within the gland epithelium along with occasional parietal cells. Lamina propria and muscularis mucosae are not unique. II. Gastric submucosa is composed of a dense connective tissue and submucosal (Meissner’s) plexus. III. Gastric muscularis externa consists of an outer longitudinal layer, a middle circular layer, and an inner oblique layer. iV. Gastric serosa is not unique. 39 Functions: Mixing and partial digestion of the food in the stomach by its gastric secretions produces a pulpy fluid mix called chime. The gastric secretions include pepsinogen, hydrochloric acid and intrinsic factor. In addition, the hormone gastrin and other hormones and hormone like secretions are produced by enteroendocrine glands in the gastric epithelium. Small intestine Structure: I. Mucosa consists of: Plicae circulares are permanent transverse folds that contain a core of submucosa. Villi are finger-like and leaf-like projections of the mucosa that extend into the intestinal lumen. Microvilli of the enterocytes give the apical region of the cell a striated appearance, the so-called striated border. The intestinal glands or crypts of Liberkühn are simple tubular structures. They open on to the luminal surface of the intestine of the base of the villi. The lamina propria contains numerous cells of the immune system and nodules of lymphatic tissue that represent a major component of the Gut Associated lymphoid tissue The muscularis mucosae consist of two thin layers of smooth muscle cells, an inner circular and an outer longitudinal layer. Cells of the mucosal epithelium Enterocytes Structure: They are tall columnar cells with a basally positioned nucleus. Microvilli of the enterocytes increase the apical surface area as much as 600 times. Functions: Enterocytes are specialized for the absorption and transport of substances from the lumen of the intestine to the circulatory system. Enterocytes are also secretory cells producing glycoprotein enzymes needed for terminal digestion and absorption. Goblet cells Structure: There are a large accumulation of mucinogen granules in the apical cytoplasm that distends the apex of the cell. An extensive array of flattened Golgi saccules forms a wide cup around the newly formed mucinogen granules near the basal part of the cell. Goblet cells have microvilli that are restricted to a thin rim of cytoplasm. 40 Function: As in other epithelia, goblet cells produce mucus. Paneth cells Structure: The acidophilic secretory granules contain the antibacterial enzyme lysozyme, other glycoproteins, an arginine rich protein and zinc. Functions: Lysozyme digests the cell walls of certain groups of bacteria. This antibacterial action and the phagocytosis of certain bacteria and protozoa by Paneth cells suggest that they have a role in regulating the normal bacterial flora of the small intestine. Enteroendocrine cells Functions: Cholecystokinin, secretin and gastric inhibitory peptide are the most active regulators of gastrointestinal physiology that are released in this portion of the gut. These three hormones increase pancreatic and gallbladder activity and inhibit gastric secretory function and motility. M cells (microfold cell) Structure: The epithelial cells that overlie Peyer’s patches and other large lymphatic nodules are nearly squamous. They have microfolds rather than microvilli on their apical surface. Function: Take up macromolecules of antigens from the lumen in endocytic vesicles and discharge them in the vicinity of lymphocytes. Intermediate cells Structure: . These cells have short, irregular microvilli and small mucin-like secretory droplets which form a column in the center of the supranuclear cytoplasm. Intermediate cells have characteristics of both immature absorptive cells and goblet cells. Function: These cells are still capable of cell division II. Submucosa consists of: A dense connective tissue and localized sites that contain aggregates of adipose cells Submucosal branched tubuloalveolar glands (of Brunner) The secretion of these glands contains neutral and alkaline glycoproteins and bicarbonate ions. 41 Function: Secretion of these glands serves to protect the proximal small intestine by neutralizing the acid-containing chime that is delivered to it Secretion of these glands serves to bring the Ph of the intestinal contents close to the optimal pH for the pancreatic enzymes that are also delivered to the duodenum. III. Muscularis externa consists of: an inner layer of circularly arranged smooth muscle cells an outer layer of longitudinally arranged smooth muscle cells IV. Serosa Serosa is not unique. Large intestine Structure: The mucosa has a smooth surface; neither plicae circulares nor villi are present. The outer longitudinal layer of the muscularis externa exhibits three equally spaced bands. I. Mucosa The mucosa of the large intestine contains numerous straight tubular glands that extend through the full thickness of the mucosa. The glands consist of simple columnar epithelium. The mucosal epithelium of the large intestine contains the same cell types as the small intestine except Paneth cells which are normally absent in the adult human. Absorptive cells of the mucosa are columnar cells with morphology identical to the enterocytes of small intestine. Goblet cells are more numerous in the large intestine than in the small intestine. The lamina propria has: a thick layer of collagen and ground substance just below the free surface elaborate development of GALT absence of lymphatic vessels in the lamina propria Functions of the mucosa: reabsorption of electrolytes and water and elimination of undigested food and waste production of mucin by Goblet cells to lubricate the bowel, facilitating the passage of the increasingly more solid colonic contents epithelial cell renewal from the stem cells II. The submucosa is not unique. III. Muscularis externa 42 In the colon, the outer layer of the muscularis externa is, in the part, condensed into prominent longitudinal bands of muscle that are called the teniae coli. In the rectum, the outer longitudinal layer of smooth muscle is a uniformly thick layer, as in the small intestine. Bundles of muscle from the teniae coli penetrate the inner, circular layer of muscle at intervals along the length and circumference of the colon. These apparent discontinuities in the muscularis externa allow segments of the colon to contract independently, leading to the formation of saccules (haustra) in the colon wall. IV. Serosa and adventitia Where the large intestine is directly in contact with other structures, its outer layer is adventitia; Elsewhere, the outer layer is a typical serosa. Cecum and appendix Structure: The appendix is a thin, finger-like extension of blind pouch of the cecum. The appendix differs from the rest of the colon in having a complete layer of longitudinal muscle in the muscularis externa. The most conspicuous feature of the appendix is the large number of lymphatic nodules that fuse and extend into the submucosa Rectum and anus Structure: The rectum is dilated distal portion of the alimentary tract. Its upper part is distinguished from the rest of the colon by the presence of folds called transverse rectal folds. The most distal portion of the alimentary canal is the anal canal. The upper part of the anal canal has longitudinal folds called anal columns. Depressions between the anal columns are called anal sinuses. The mucosa of the rectum is similar to that of the rest of the distal colon, having straight, tubular intestinal glands with many goblet cells. Anal canal Structure: Anal glands extend into the submucosa and even into the muscularis externa. These are branched, straight tubular glands that secrete mucus onto the anal surface. Large apocrine glands, the circumanal glands, are found in the skin surrounding the anal orifice. 43 The muscularis mucosa disappears at about the level of the rectoanal margin, but at the same level, the circular layer of the muscularis externa thickness to form the internal anal sphincter. Pancreas The pancreas is an exocrine and endocrine gland. Exocrine pancreas Structure: The exocrine portion of the pancreas is a compound acinar gland with serous type of secretion The initial portion of the intercalated duct begins within the acinus. The intercalated duct cells located inside the acinus are called centroacinar cells. Cells which composed pancreatic acini are called acinar cells. They are characterized by acidophilic zymogen granules. Functions: Zymogen granules contain a variety of digestive enzymes in an inactive form. Pancreatic enzymes are capable of digesting most food substances. The intercalated duct cells secrete a large volume of fluid rich in sodium and bicarbonate The bicarbonate serves to neutralize the acidity of the chyme that enters the duodenum from the stomach and to establish the optimum pH for the activity of the major pancreatic enzymes. Duct system 1. The intercalated ducts are short and drain to intralobular collecting ducts. 2. The network of intralobular ducts drains to the larger interlobular ducts. 3. The interlobular ducts, in turn, drain directly into the main pancreatic duct. 4. A second large duct, the ductus choledochus (accessory pancreatic duct) arises in the head of the pancreas. Endocrine pancreas Structure: The islets of Langerhans, the endocrine component of the pancreas, are scattered throughout the organ. The islets constitute about 1-2% of the volume of the pancreas. Principal cell types of the islet The B cells constitute about 70% of the total islet cells They are generally located in its central portion. Functions: They secrete insulin which stimulate: uptake of glucose from the circulation utilization and storage of glucose by all cells 44 The A cells constitute about 15-20% of the human islet population They are generally located peripherally in the islets. Functions: They secrete glucagon which stimulates: release of glucose into the blood-stream gluconeogenesis (synthesis of glucose from metabolites of amino acids) and glycogenolysis (breakdown of glycogen) in the liver The D cells constitute about 5-10% of the total pancreatic endocrine tissue. They are also located peripherally in the islets. Functions: They secrete somatostatin which inhibit: insulin and glucagon secretion The minor islet cells constitute about 5% of the islet tissue. The PP cells secrete pancreatic polypeptide. It stimulates gastric chief cells It inhibits bile secretion and intestinal motility. It inhibits pancreatic enzymes and bicarbonate secretion. The D-1 cells secrete vasoactive intestinal peptide. Its principal effects are similar to those of glucagon. It stimulates pancreatic exocrine secretion. The EC cells secrete secretin, motilin and substance P. Secretin acts locally to stimulate bicarbonate secretion in pancreatic fluid and pancreatic enzyme secretion. Motilin increases gastric and intestinal motility. Substance P function is unclear. Liver The liver is the largest mass of glandular tissue in the body and is also the largest internal organ. Blood supply to the liver 1. The hepatic portal vein (hpv) and the hepatic artery send blood to the liver. 2. Their branches form the interlobular vessels which branch into distributing vessels that are located at the periphery of the lobule. 3. The interlobular vessels that form the smallest portal triads send blood into the sinusoids. 4. In the sinusoids the blood flows centripetally toward the central vein. 5. The central vein courses through the central axis of the classic liver lobule and empties into a sublobular vein. 6. Several sublobular veins converge to form larger hepatic veins that empty into the inferior vena cava. 45 Liver lobules There are three ways of describing the structure of the liver in terms of a functional unit: the “classic” lobule, the portal lobule, and the liver acinus. Classic lobule The classic hepatic lobule is a roughly hexagonal block of tissue which consists of stacks of anastomosing plates of hepatic cells, separated by the anastomosing system of sinusoids that perfuse the cells with the mixed portal and arterial blood. At the center of the lobule is the terminal hepatic venule (central vein) into which the sinusoids drain. The plates of cells radiate from the central vein to the periphery of the lobule, as do the sinusoids. At the angles of the hexagon are the portal areas (portal canals), loose stromal connective tissue characterized by the presence of the portal triads (artery, vein and bile duct). Liver acinus The liver acinus described as diamond shaped, is the smallest functional unit in the hepatic parenchyma. The short axis of the acinus is defined by the terminal branches of the portal triad that lie along the border between two “classic” lobules. The long axis is a line drawn between the two central veins closest to the short axis. The liver acinus provides the best correlation among blood perfusion, metabolic activity, and liver pathology. Portal lobule Its outer margins are imaginary lines between the three central veins that are closest to that portal triad. This defines a roughly triangular block of tissue that includes those portions of three classic lobules that secrete the bile that drains into its axial bile duct. The portal lobule emphasizes the exocrine functions of the liver Sinusoids Hepatic sinusoids are lined with a thin discontinuous endothelium. Hepatic sinusoids have Kupffer cell or the stellate sinusoidal macrophage. The Kupffer cells may be involved in the final breakdown of some damaged or senile red blood cells that reach the liver from the spleen. Perisinusoidal space (space of Disse) The perisinusoidal space is the site of exchange of materials between blood and liver cells. 46 The perisinusoidal space lies between the basal surfaces of the hepatocytes and the basal surfaces of the endothelial cells and Kupffer cells that line the sinusoids. The lypocyte or adipose cell (commonly called an Ito cell) is found in the perisinusoidal space. These cells are storage site for vitamin A. Hepatocytes Hepatocytes make up the anastomosing cell plates of the liver lobule. Hepatocytes are large polygonal cells that constitute about 80% of the cell population of the liver. Liver cells are capable of considerable regeneration when liver substance is lost to disease or surgery. Specific cytoplasmic components include rER, free ribosomes, numerous mitochondria, glycogen, lipid droplets, small Golgi complexes and a lot of peroxisomes. Functions of peroxisomes are metabolism of purines, alcohol and lipids. The sER involved in degradation and conjugation of toxins and drugs as well as enzymes responsible for synthesizing cholesterol and the lipid portion of lipoproteins. Hepatocyte lysosomes may be a normal storage site for iron. Biliary tree The bile canaliculus is small canal formed by grooves in neighboring cells. The bile canaliculi form a ring about the hepatocyte and drains into small bile ducts, the canals of Hering, these in turn, drain into the bile duct of the portal canals. Bile flows in the canaliculi centrifugal. The flow of bile is in a direction opposite to the flow of blood, i.e. from the region of the central vein toward the portal canal. Near the portal canal, but still within the lobule, bile canaliculi join to form small ductules, the canals of Hering that are lined with cuboidal cells that are not hepatocytes. The ductules carry the bile to the interlobar bile ducts that form part of the portal triad. Interlobular duct join to form the right and left lobar ducts that in turn join at the hilum to form the common hepatic duct. Extra hepatic bile ducts carry the bile to the gall bladder and intestine. Bile Structure: About 90% of the bile salts a component of bile is reabsorbed and resecreted by the hepatocytes. 47 Bile also consists of cholesterol, lecithin, bile pigments, water and electrolytes. Functions of the liver: The liver has both exocrine and endocrine functions. Some of the products of metabolic conversions are carried in the exocrine secretion of the liver, called bile. The endocrine secretions of the liver are released directly into the blood that supplies the liver parenchyma. These secretions include substances synthesized by the liver cells, such as albumin, prothrombin, fibronectin and glycogen. Gall bladder The gall bladder concentrates and stores bile. I. Mucosa The empty or partially filled gall bladder has numerous deep mucosal folds. The mucosal surface consists of a simple columnar epithelium. Lamina propria Mucin-secreting glands large number of lymphocyte and plasma cells II. Muscularis externa The smooth muscle bundles are some what randomly oriented. III. Adventitia and serosa External to the muscularis externa is a thick layer of dense connective tissue. Where the gall bladder is attached to the liver surface, this layer is referred to as the adventitia. The unattached surface is covered by a serosa of visceral peritoneum consisting of a layer of mesothelium and a thin layer of loose connective tissue. 48 Respiratory system General structure: The respiratory system consists of the paired lungs and a series of air passages that lead to and from the lungs. The air passages consist of a conducting portion and a respiratory portion. The conducting portion begins at nasal cavities and ends at terminal bronchioles The respiratory portion consists of respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli. Functions: air conduction air filtration warming and moistening of the air gas exchange (respiration) air passing through the larynx is used to produce speech air passing over the olfactory mucosa in the nasal cavities carries the stimuli for the sense of smell Nasal cavities The nasal cavities are paired chambers separated by a bony and cartilaginous septum. Each chamber is divided into three regions: Vestibule (nostril) Respiratory segment Olfactory segment Vestibule of the Nasal Cavity It is lined with stratified squamous epithelium, and contains the hairs that filter out large particulate matter. Sebaceous glands are also present. 1. 2. 3. 4. 5. 1. Respiratory Segment of the Nasal Cavity It is lined by a ciliated, pseudostratified columnar epithelium. It is composed of five cell types: Ciliated cells Goblet cells Brush cells bear short, blunt microvilli Small granule cells contain secretory granules Basal cells stem cells from which the other cell types arise The lamina propria of the respiratory segment has a rich, vascular network and contains mucous glands, many with serous demilunes. Olfactory Segment of the Nasal Cavity The olfactory segment and are lined with olfactory mucosa. The olfactory epithelium is composed of the following cell types: Olfactory cells are bipolar neurons. 49 2. Supporting cells provide mechanical and metabolic support to the olfactory cells 3. Basal cells are stem cells from which new olfactory cells and supporting cells differentiate 4. Brush cells The lamina propria of the olfactory segment has connective tissue with numerous blood and lymphatic vessels. Pharynx Structure: The pharynx connects the nasal and oral cavities to the larynx and esophagus. The pharynx is divided into the nasopharynx and oropharynx The auditory tubes connect the nasopharynx to each middle ear. Diffuse lymphatic tissue and lymphatic nodules are found in the wall of the nasopharynx. The concentration of such nodules in the posterior wall is called the pharyngeal tonsil. Larynx Structure: The passageway for air between the oropharynx and trachea is the larynx. It is formed by irregularly shaped plates of hyaline and elastic cartilage. The vocal folds are two folds of mucosa that project into the lumen of the larynx. A supporting ligament and skeletal muscle, the vocalis muscle, is contained within each vocal fold-ligament. The ventricular folds located above the vocal folds are the "false vocal cords". The luminal surface of the vocal cords is covered with stratified squamous epithelium. The rest of the larynx is lined with the ciliated, pseudostratified columnar epithelium. The connective tissue of the larynx contains mixed mucoserous glands that secrete through ducts onto the laryngeal surface. Function: Vocal folds control the flow of air through the larynx and vibrate to produce sound Trachea The trachea is a short tube. The wall of the trachea consists of four layers: 1. Mucosa composed of ciliated, pseudostratified epithelium which has same cell types as respiratory portion of the nasal cavity and an elastic fiber-rich lamina propria (typical loose connective tissue). Basement membrane appears as a glassy or homogeneous layer. 50 2. Submucosa is a relatively loose connective tissue. Submucosal glands composed of mucus-secreting acini with serous demilunes. 3. Cartilaginous layer composed of C-shaped hyaline cartilages. Fibroelastic tissue and smooth muscle bridge the gap between the free ends of the Cshaped cartilages. 4. Adventitia, which binds the trachea to adjacent structures. It consists of loose connective tissue. Bronchi The trachea divides into two branches forming extrapulmonary bronchi. On entering the lungs the bronchi become the intrapulmonary bronchi, which branch immediately to give rise to the lobar bronchi. The lobar bronchi divide to give rise to segmental bronchi. Bronchial Structure The wall of the bronchus consists of five layers. Mucosa is composed of a pseudostratified epithelium having the same cellular composition as the trachea. Muscularis is a continuous layer of smooth muscle in the larger bronchi. It may appear discontinuous in smaller bronchi. Submucosa remains as a relatively loose connective tissue. Cartilage layer consists of discontinuous cartilage plates that become reduced in size as the bronchial diameter diminishes. Adventitia is dense connective tissue. Bronchioles large bronchioles terminal bronchioles respiratory bronchioles Structure: Bronchioles are air-conducting ducts. Cartilage and glands are not present in bronchioles The larger diameter bronchioles initially have a ciliated, pseudostratified columnar epithelium. Thick layer of smooth muscle. The terminal bronchioles are lined with a simple cuboidal epithelium in which Clara cells are found among the ciliated cells. Clara cells are nonciliated cells secrete a surface-active agent which prevent luminal adhesion during expiration. A small amount of connective tissue underlies epithelium. A circumferential layer of smooth muscle underlies the connective tissue. Respiratory bronchioles are the first part of the bronchial tree that allows gas exchange to occur. They are lined by a cuboidal epithelium. Scattered, thin-walled outpocketings, alveoli, extend from the lumen of the respiratory bronchioles. 51 ALVEOLI Alveoli are the terminal air spaces of the respiratory system and are the actual site of gas exchange between the air and the blood. At some point, each alveolus is confluent with a respiratory bronchiole, by means of an alveolar duct, and an alveolar sac. Alveolar epithelium is composed of type I and II alveolar cells and occasional brush cells. Type I alveolar cells, also known as type I pneumocytes, are extremely thin squamous cells that line most of the surface of the alveoli. Type II alveolar cells are secretory cells. Their apical cytoplasm is filled with granules which rich in phospholipids, among which is the surface active agent surfactant. Without adequate secretions of surfactant, the alveoli would collapse on exhalation. The alveolar septum is the site of the air-blood barrier which consists of: Alveolar epithelial cells Basal lamina of the alveolar epithelium Basal lamina of the capillary endothelium Endothelial cells of the rich capillary network Other connective tissue elements, including fibroblasts, macrophages, collagen fibers, and elastic fibers Function of air-blood barrier: It is place across which gases must diffuse between the alveolar compartment and capillary compartment. 52 Urinary system The urinary system consists of the paired kidneys, the paired ureters, which lead from the kidneys to the bladder, and the urethra, which leads from the bladder to the exterior of the body. Functions of kidneys: Production of urine Synthesis and secretion of erythropoietin Synthesis and secretion of renin KIDNEY STRUCTURE 1. Capsule The kidney surface is covered by a thin connective tissue capsule. 2. Cortex It has renal corpuscles with their tubules and medullary rays. Each medullary ray contains straight collecting tubules and straight tubule components of the nephrons. 3. Medulla It has straight tubules, collecting ducts, and a special capillary network. The tubules in the medulla form a number of conical structures called pyramids. Usually 8— 12 pyramids may occur in the human kidney. The bases of the pyramids face the cortex and the apices face the renal sinus. The caps of cortical tissue that lie over the pyramids form the renal columns. Nephron The nephron is the basic functional and structural unit of the kidney. They are responsible for the production of urine and correspond to the secretory part of other glands. The renal corpuscle represents the beginning of the nephron. It consists of the glomerulus, a tuft of capillaries, surrounded by a doublelayered epithelial cup, the renal or Bowman's capsule. The glomerular capillaries are supplied by an afferent arteriole and are drained by an efferent arteriole that then branches, forming a new capillary network to supply the kidney tubules. This is then an arterial portal system. Continuing from Bowman's capsule, the remaining segments of the nephron, namely, the tubular parts, are: Proximal thick segment, consisting of the proximal convoluted tubule and the proximal straight tubule. Thin segment, which constitutes the thin limb of the loop of Henle. Distal thick segment, consisting of the distal straight segment and the distal convoluted tubule. 53 The distal convoluted tubule connects to the collecting tubule, often through a connecting tubule, thus forming the uriniferous tubule, i.e., the nephron plus collecting tubule. Types of Nephrons The types of nephrons are based on where their renal corpuscles are located in the cortex: Cortical or subcapsular nephrons have their renal corpuscles located in the outer part of the cortex. Juxtamedullary nephrons have their renal corpuscles in proximity to the base of a medullary pyramid. Intermediate nephrons have their renal corpuscles in the midregion of the cortex. Renal (Malpighian) Corpuscle Structure: The renal corpuscle consists of the glomerular capillary tuft and the surrounding visceral and parietal epithelial layers of Bowman’s capsule. The outer layer of Bowman's capsule, called the parietal layer, is a simple squamous epithelium The inner layer of Bowman's capsule, called the visceral layer, constitute podocytes cells The space between the visceral and parietal layers of Bowman's capsule is called the urinary or Bowman's space. The renal corpuscle contains group of cells called mesangial cells. The renal corpuscle contains the filtration apparatus of the kidney. The filtration apparatus consists of three components: 1. endothelium of the glomerular capillaries with numerous fenestrations 2. basal lamina (the glomerular basement membrane) 3. visceral layer of Bowman’s capsule Functions: Bowman's capsule is the initial portion of the nephron where blood flowing through the glomerular capillaries undergoes a filtration process to produce the initial urine filtrate (I filtration phase of urine production). Filtration apparatus restricts the movement of albumin and hemoglobin. Mesangial cells are phagocytic; they can remove trapped residues and aggregated proteins from the glomerular basement membrane. Mesangial cells and their matrix provide structural support for the podocytes where the epithelial basement membrane is absent or incomplete. Juxtaglomerular Apparatus Structure: The juxtaglomerular apparatus includes the macula densa, the juxtaglomerular cells, and the extraglomerular mesangial cells. 54 Lying directly adjacent to the afferent and efferent arterioles of the renal corpuscle is the terminal portion of the distal thick segment of the nephron. It contains cells that collectively are referred to as the macula densa. The smooth muscle cells of the adjacent afferent arteriole are modified. These smooth muscle cells are referred to as juxtaglomerular cells. The granules of the juxtaglomerular cells contain renin that is synthesized, stored, and released into the blood. Some extraglomerular mesangial cells are located along the vascular pole where they are also designated as lacis cells Functions: Renin increases blood pressure, stimulates the release of the hormone aldosterone which raising blood volume and pressure. The cells of the macula densa monitor the NaCl concentration in the afferent arteriole and regulate the release of renin by the juxtaglomerular cells. KIDNEY TUBULE FUNCTION Proximal Thick Segment Structure: The proximal convoluted tubule receives the primary filtrate from the urinary space of Bowman's capsule. The cuboidal cells of the tubule have the following features: A brush border, composed of numerous, relatively long microvilli A terminal bar apparatus, consisting of a narrow tight junction and a zonula adherens Extensive interdigitation of basal processes of adjacent cells Basal striations, consisting of elongate mitochondria concentrated in the basal processes Functions: reabsorption of 80% of the primary filtrate (II phase of urine production) reabsorption of fluid is driven by active transport of Na + into the lateral intercellular space and into the peritubular capillary network reabsorption of amino acids, sugars, and proteins Proximal Straight Segment The cells of the straight segment of the proximal tubule, i.e., the thick descending limb of the loop of Henle, are not as specialized for absorption as are those of the convoluted segment. Thin Segment Structure: The thin segment has four types of epithelial cells which possess few organelles. Functions: 55 The descending portion of the thin segment is permeable, permitting free passage or equilibration of salt and water between the lumen of the nephron and the peritubular connective tissue. Distal Thick Segment Structure: The straight segment of the distal tubule, like the ascending thin segment, transports ions from the tubular lumen to the interstitium. The large, cuboidal cells of the distal tubule have extensive basal-lateral plications and numerous large mitochondria associated with these basal folds. They have considerably fewer and less well-developed microvilli than proximal tubule cells. Functions: Reabsorption of Na+ and secretion of K+ in order to conserve Na+ Continued reabsorption of bicarbonate ion Antidiuretic hormone can act on the terminal portion of the distal convoluted tubule to increase the permeability of the tubule to water, thereby producing more concentrated urine. Collecting Tubules and Collecting Ducts Structure: Both the collecting tubules and ducts are composed of a simple epithelium. The arched and cortical collecting tubules have flattened cells, somewhat squamous to cuboid in shape. The medullary collecting ducts have cuboidal cells, with a transition to columnar cells as the ducts increase in size. Cytologically, two distinct types of cells are present in the collecting system: Light cells have basal infoldings, true infoldings rather than processes that implicate with those of adjacent cells. They possess a single cilium and have relatively few short microvilli. Dark cells, occur in considerably smaller numbers. They have many mitochondria. Numerous vesicles are present in the apical cytoplasm. Functions: Final III secretory phase of urine production occurs in the collecting tubules H+ ions are secreted in the cortical and medullary collecting tubules. The collecting tubules responsible for the final concentration of the urine. INTERSTITIAL CELLS The connective tissue of the kidney parenchyma, called interstitial tissue, surrounds the components of the nephrons, the ducts, and the blood and lymphatic vessels. 56 In the medulla, the principal interstitial cells resemble myofibroblasts. These cells may secrete a hormone-like material that reduces blood pressure. Prostaglandins and prostacyclin are synthesized in the interstitium. Excretory passages All excretory passages except the urethra have the same general structure, namely, a mucosa, a muscularis, and an adventitia (or in some regions serosa) Transitional epithelium lines all of the excretory passages. Transitional epithelium is essentially impermeable to salts and water. The apical surface of the cell is very irregular, with deep clefts. In the ureters and urethra there are usually two layers of smooth muscle longitudinal inner layer and circular outer layer The smooth muscle of the urinary passages is mixed with connective tissue, so that it forms parallel bundles rather than pure muscular sheets. The smooth muscle of the bladder wall is more random mixing of muscle and collagen bundles. Ureters The ureters conduct urine from the renal pelvis to the bladder and follow an oblique path through the wall of the bladder. The terminal portion of the ureters is a thick outer layer of longitudinal muscle. Urinary Bladder The bladder is a distensible reservoir for urine; its size and shape change as it fills. The smooth muscle of the bladder wall forms an internal sphincter, a ring-like arrangement of muscle around the opening of the urethra. The triangular region defined by these three openings the trigone, is relatively smooth. Urethra In the male, the urethra is about 20 cm long and serves as the terminal duct of both the urinary and genital systems. It has three distinct segments: Prostatic urethra extends for 3-4 cm from the neck of the bladder through the prostate gland Membranous urethra extends for about 1 cm from the apex of the prostate gland through the body wall Penile urethra extends for about 15cm through the length of the penis to open the body surface at the glans penis. 57 Male reproductive system The male reproductive system consists of the testes, epididymides and genital ducts, accessory reproductive glands, and penis. TESTIS Functions: The testes produce sperm and androgens. They influence embryonic development, reproductive function. sexual maturation, and Structure: The testes have a thick connective tissue capsule, the tunica albuginea. Each testis is divided into approximately 250 lobules by incomplete connective tissue septa that project from the capsule. Each lobule contains several highly convoluted seminiferous tubules which produce the sperm. They continuous with tubuli recti which connect with the rete testis. Tubuli recti are lined only by Sertoli cells. Near their termination, the tubuli recti are lined by simple cuboidal epithelium. A simple cuboidal or low columnar epithelium lines the channels of the rete testis. Interstitial or Leydig cells are found in a connective tissue stroma. They are large, polygonal, acidophilic cells that typically contain lipid droplets and secrete testosterone. The seminiferous tubules consist of a seminiferous epithelium which composed of two basic populations of cells: Spermatogenic cells Sertoli cells The tunica propria is a multilayered connective tissue that lacks typical fibroblasts. It consists of three to five layers of myoid cells and collagen fibrils external to the basal lamina of the seminiferous epithelium. Rhythmic contractions of the myoid cells help move spermatozoa and testicular fluid to the excurrent duct system. Sertoli cells Structure: The Sertoli cells are columnar cells with complex apical and lateral processes. They surround the adjacent spermatogenic cells and fill the spaces between them. Functions: 58 The Sertoli cells give structural organization to the tubules. They divides the seminiferous epithelium into basal and luminal compartments. They exchange metabolic substrates and wastes between the developing spermatogenic cells and the circulatory system. They phagocytized and break down any spermatogenic cells that fail to differentiate completely. The Sertoli-Sertoli junctional complex is the site of the blood-testis barrier. They secrete androgen-binding protein. EXCURRENT DUCT SYSTEM Efferent Ductules The efferent ductules connect the rete testis to the epididymis. They are highly coiled and form 6-10 conical masses. The efferent ductules are lined with a pseudostratified columnar epithelium. Interspersed among the columnar cells are a few basal cells and intraepithelial lymphocytes. The smooth muscle forms a circular sheath in the wall of the ductule. Ductus Epididymis Structure: The ductus epididymis is a highly coiled tube which lies along the posterior surface of testis. It consists of the ductus epididymis and its associated vascularized connective tissue, smooth muscle, and a fibrous connective tissue tunic. The ductus epididymis is divided a head (caput), a body (corpus), and a tail (cauda). The ductus epididymis is lined with a pseudostratified columnar epithelium. It contains principal cells (tall) and basal cells (short). In the head of the epididymis and most of the body, the smooth muscle coat consists of a thin layer of circular smooth muscle. In the tail, inner and outer longitudinal layers are added. These three layers are then continuous with the three smooth muscle layers of the ductus deferens. Functions: Epididymal cells function in both absorption and secretion. Maturation of the sperm cells. Ductus deferens The ductus deferens is a direct continuation of the epididymis and connects to the prostatic urethra. The distal end of the ductus deferens enlarges to form the ampulla. The ampulla has branched mucosal folds. The ductus deferens is lined with a pseudostratified columnar epithelium. The tall columnar cells also have long microvilli that extend into the lumen. The rounded basal cells rest on the basal lamina. 59 The lumen of the duct appears to be thrown into deep longitudinal folds throughout most of its length, probably due to contraction. Accessory sex glands Seminal vesicles Structure: The seminal vesicles are paired, elongate tubular glands that have a muscular and fibrous coat. The pseudostratified columnar epithelium contains tall, nonciliated columnar cells and short round cells. Functions: Prostaglandins are synthesized in large amounts in the seminal vesicles. Secrete the fluid that is rich in fructose. Prostate Gland Structure: The prostate consists of a collection of 30—50 tubuloalveolar glands that surround the proximal urethra. The glands are arranged in three concentric layers: a mucosal layer, a submucosal layer, and the most peripheral layer containing the main prostatic glands. The epithelium is generally columnar but may have patches that are cuboidal, squamous, or pseudostratified. Prostate has fibromuscular tissue. Functions: It secretes protein enzymes, acid phosphatase, fibrinolysin, and citric acid. Bulbourethral Glands Structure: The paired bulbourethral glands are pea-sized structures located in the urogenital diaphragm. They are compound tubuloalveolar glands. They are lined by simple columnar epithelium. Functions: Produce the major portion of the preseminal fluid Serves as a lubricant of the penile urethra. Penis The urethra, which originates at the bladder and extends through the penis, carries both semen and urine to the exterior. The penis consists principally of two corpora cavernosa, and the corpus spongiosum, in which the urethra is embedded. A dense fibroelastic layer, the tunica albuginea, binds the three together and forms a capsule around each one. The skin of the penis is thin and loosely attached to the underlying loose connective tissue except at the glans, where it is very thin and tightly attached. The Female Reproductive System 60 The female reproductive system consists of internal sex organs and external genital structures OVARY Functions of the ovary: Production of the estrogen and progesterone Production of gametes. Structure: The ovaries are paired structures covered by tunica albuginea. The ovary is composed of a cortex and a medulla. 1. Medulla located in the central portion of the ovary. It contains loose connective tissue, blood vessels, lymphatic vessels, and nerves. 2. Cortex found in the peripheral portion of the ovary. It contains the ovarian follicles. Types of follicles 1. Primordial follicles 2. Growing follicles (primary and secondary) follicles 3. Mature or Graafian follicles The Primordial Follicle The primordial follicles are found in the stroma of the cortex. A single layer of squamous follicular cells surrounds the oocyte. The Primary Follicle Follicular cells proliferate and become cuboidal. Zona pellucida appears between the oocyte and the adjacent follicular cells. Follicular cells undergo stratification to form the granulosa layer of the primary follicle. Connective tissue cells form the theca interna and externa layers of the primary follicle. Under the plasma membrane the oocytes exhibit cortical granules. The Secondary Follicle In the secondary follicle begins to form a single cavity called the antrum, which contain liquor with estrogen. The granulosa cells form the cumulus oophorus. The Graafian follicle The mature follicle, also known as a Graafian follicle, has a diameter of 10 mm or more. The cells of the cumulus oophorus which surround the oocyte are called corona radiata. Ovulation Ovulation is the process by which an oocyte is released from the Graafian follicle due to increasing volume and pressure of the follicular fluid and enzymatic proteolysis of the follicular wall. Corpus Luteum 61 At ovulation, the follicular wall, composed of the remaining granulosa and thecal cells, is transformed into the corpus luteum (yellow body), which produces progesterone. 1. If fertilization and implantation do occur, the corpus luteum forms the corpus luteum of pregnancy. It remains active 12 weeks. 2. If fertilization and implantation do not occur, the corpus luteum forms the corpus luteum of menstruation. It remains active 14 days. 3. The corpus luteum degenerates after pregnancy or menstruation. A white scar forms the corpus albicans. Most ovarian follicles are lost by atresia. OVIDUCT The oviducts (Fallopian tubes) are paired tubes that extend bilaterally from the uterus toward the ovaries. The oviduct wall consists of next layers. The serosa. The muscularis. The mucosa is lined with simple columnar epithelium composed of ciliated and nonciliated cells. Uterus The human uterus is a hollow, pear-shaped organ. The uterine wall is composed of three layers. 1. Endometrium, the mucosa of the uterus which consists of stratum functionale and stratum basale. The stratum functionale is lined with a simple columnar epithelium with secretory and ciliated cells and contain uterine gland (simple tubular). 2. Myometrium, the thick muscular layer which is composed of three indistinctly defined layers of smooth muscle. 3. Perimetrium consists of a mesothelium and a thin layer of loose connective tissue. The perimetrium covers the entire posterior surface of the uterus but only part of the anterior surface. The remaining part of the anterior surface consists of connective tissue or adventitia. The endometrium undergoes cyclic changes each month that prepare it for the implantation of the embryo. The discharge of tissue and blood from the vagina, which usually continues for a period of 3-5 days, is referred to as menstruation. Menstrual cycle The menstrual cycle has 3 phases: 1. Proliferative phase, occurring concurrently with follicular maturation and influenced by ovarian estrogen secretion 62 2. Secretory phase, coinciding with the functional activity of the corpus luteum and primarily influenced by progesterone secretion 3. Menstrual phase, commencing as hormone production by the ovary declines with the degeneration of the corpus luteum I. The proliferative phase of the menstrual cycle is regulated by estrogen. Following changes can be seen: 1. Epithelial cells in the basal portion of the glands reconstitute the glands 2. Spiral arteries lengthen as the endometrium is reestablished. 3. Thickness of endometrium is about 3 mm. 4. Duration of this phase is from 5 up to 14 days of menstrual cycle. II. The secretory phase of the menstrual cycle is under the control of progesterone. Following changes can be seen: 1. The endometrium becomes edematous. 2. Thickness of endometrium is about 5-6 mm. 3. The glands enlarge and become corkscrew shaped. 4. The lumen of the glands is filled with secretory products (glycogen). 5. The spiral arteries lengthen and become more coiled. 6. Stromal cells undergoing transformation into decidual cells. III. The menstrual phase results from a decline in the ovarian secretion of progesterone and estrogen. Following changes can be seen: 1. As the hormone levels rapidly decline, periodic contraction of the walls of the spiral arteries cause the stratum functionale to become ischemic and than sloughed off. 2. At the end of the menstrual phase, thickness of endometrium is about 1 mm. This layer is the stratum basale; the layer that was sloughed off was the stratum functionale. Vagina The vagina is a fibromuscular tube lined by nonkeratinized stratified squamous epithelium The vaginal wall consists of: 1. Inner mucosal layer (without glands) consists of lamina propria and submucosa. 2. Intermediate muscular layer is smooth muscle layers, an outer longitudinal and an inner circular layer. 3. Outer adventitial layer consists of an inner dense connective tissue and an outer loose connective tissue. MAMMARY GLANDS Mammary glands are modified apocrine sweat glands that develop under the influence of sex hormone. 63 Structure: It is composed of 15-20 irregular lobes of branched tubuloalveolar glands which radiate from the mammary papilla or nipple and are further subdivided into numerous lobules. Abundant adipose tissue is present in the interlobular spaces. The epidermis of the adult nipple and areola is highly pigmented and somewhat wrinkled. Deep to the areola and nipple, bundles of smooth muscle fibers are arranged radially and circumferentially in the dense connective tissue and longitudinally along the lactiferous ducts. The areola contains sebaceous glands, sweat glands, and modified mammary glands and fewer sensory nerve endings. Each tubuloalveolar gland ends in a lactiferous duct that opens through a constricted orifice onto the nipple. Beneath the areola, the pigmented area surrounding the nipple, each duct has a dilated portion, the lactiferous sinus. The morphology of the secretory portion of the mammary gland varies with the menstrual cycle. Mammary glands undergo dramatic proliferation and development during pregnancy 1. Decreasing of the amount of connective and adipose tissues. 2. Infiltration of plasma cells, lymphocytes, and eosinophils of fibrous component of the connective tissue. 3. Branching of ducts and developing of alveoli. 4. Hypertrophy of the secretory cells and accumulation of secretory product in the alveoli. Both merocrine and apocrine secretion are involved in production of milk. The secretory cells produce two distinct products that are released by different mechanisms: 1. Merocrine secretion: The protein component of the milk is synthesized in the rER and released from the cell by fusion of the granule's limiting membrane with the plasma membrane. 2. Apocrine secretion: The lipid coalesces to form large droplets that pass to the apical region of the cell and project into the lumen of the acinus. The droplets are invested with an envelope of plasma membrane as they are released. A thin layer of cytoplasm is trapped between the plasma membrane and lipid droplet and is released with the lipid, but the cytoplasmic loss in this process is minimal. The secretion released in the first few days after childbirth is known as colostrum. 64