The Integumentary System

The Integumentary System

This is the skin and its derivatives. It forms the external covering of the body and 15-20% of it's mass.

 

The Skin

Skin is composed of 2 main layers:

1. The epidermis;2. And the dermis.

The hypodermis is deep to the dermis and is the superficial fascia of gross anatomy.

It is a looser form of connective tissue than the dermis. The hypodermis has variable amounts of adipose tissue.

 

Epidermal Derivatives of Skin

The epidermal derivatives of the skin are:

1. Hair and hair follicles;2. Sweat glands;3. Sebaceous glands;4. Nails;5. And mammary glands.

 

Functions of the Integumentary System

There are a number of functions of the integumentary system:

1. A  barrier function, protects against physical, biological and chemical agents;2. A  homeostatic function, to preserve the internal environment by

regulating body temperature;3. A  sensory function, information about the environment, informative and

protective;4. A  secretory function;5. And an excretory function, via sweat glands.

Types of Skin

There are 2 types of skin:

1. Thick skin, which is hairless and on the palms and the soles of the feet;2. And thin skin, which is hairy.

 

The Epidermis

The epidermis is composed of stratified squamous epithelium and is composed of 4 layers in thin skin but 5 in thick skin.

These layers are:

 

Stratum Basale

This is a single layer of cells resting on basal lamina. It has stem cells from which keratinocytes arise. The cells are small and cuboidal to low columnar. It has less cytoplasm than cells above.

 

Stratum Spinosum

This layer is several cells thick and is larger than in the stratum basale. Cytoplasmic processes attach the cells in this layer to other cells

by desmosomes. As they mature, they become flatter and increase in size.

 

Stratum Granulosum

This is the most superficial of the non-keratinised layers. The cells contain numerous keratohyalin granules.

 

Stratum Lucidum

In this layer, the nucleus disappears and cells fill with keratin. This layer is only visible in thick skin.

 

Stratum Corneum

The cells are flattened and coated with a glycolipid to act as a water barrier.

Cells of the Epidermis

The Keratinocyte

This is the predominant cell of the epidermis. On leaving the basal layer has two functions:

1. The production of keratin;2. And creation of an extracellular water barrier.

The keratinocytes are engaged in intermediate filament production (tonofilaments).

This is the protein of keratin production, which are bundled into tonofibrils.

In the upper part of the stratum spinosum they start to make keratohyalin granules and lamellar bodies.

Keratinisation is the conversion of granular cells into cornified cells. It involves the breakdown of the nucleus and the thickening of the plasma

membrane. The lamellar bodies are secreted and coat the cell with a glycolipid forming

a water barrier. Here it is soft keratin compared with the hard keratin of the nails and hair.

 

The Melanocyte

This is a dendritic cell among the basal cells. Its long processes extend into the stratum spinosum between the keratinocytes.

The melanocyte represents a small proportion of the total epidermal cells.

They are also present in dermis where they are stellate cells with long processes and an elongated nucleus.

They are derived from the neural crest and with the keratinocytes form an epidermal-melanin unit.

The melanin granule is called a melanosome. These melanosomes are concentrated near the bases of the cell

processes when they are nearly mature and in the processes or at the ends if they are mature.

Melanosomes are transferred to the keratinocyte through phagocytosis of the ends of the processes.

 

The Langerhan's Cell

This cell doesn't form desmosomes with the neighbouring keratinocytes. Its nucleus is characteristically indented in many places.

It has granules that appear as rods with a striated band. It is involved in the initiation of cutaneous contact hypersensitivity reactions.

 

The Merkel Cell

This is a modified epidermal cell located in the stratum basale. It is most abundant in skin where sensory perception is acute, e.g. the

fingertips.

The Merkel cell is bound to nearby keratinocytes by desmosomes. They have keratin in the cytoplasm and their nucleus is lobed. These cells are characterised by the presence of dense-cored neurosecretory

granules.

The combination of the neuron and epidermal cell is called a Merkel's corpuscle, a very sensitive mechanoreceptor.

The Dermis

This is the layer of skin under the epidermis. It is secured to it via dermal papilla, which are complemented by epidermal

pegs. At areas of increased mechanical stress the epidermal pegs are

much deeper and the dermal papillae are much longer and closely spaced.

Dermal ridges are present in thick skin along with dermal papillae and form fingerprints.

A series of attachment sites called hemi-desmosomes link the basal plasma membrane to the basal laminae and attach to anchoring filaments.

Anchoring fibrils connect the dermis and the basal laminae.

The dermis is composed of 2 layers:

 

The Papillary Layer of the Dermis

This is the more superficial and cellular layer. The collagen fibres are not as thick. The elastic fibres form an irregular network, including the substance of the

dermal papillae and dermal ridges, blood vessels.

Nerve endings are concentrated in the papillae.

 

The Reticular Layer of the Dermis

This layer is considerably thicker and less cellular. It has thick irregular bundles of collagen and more coarse elastic fibres. Collagen and elastic fibres are oriented into Langer's lines.

 

The Hypodermis

This layer contains adipose tissue and individual smooth muscle cells or bundles.

This smooth muscle cells or bundles constitute the arrector pili muscles of the hair.

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Nerve Supply of the Skin.

The most numerous neuronal endings are free nerve endings in the epidermis and the papillary dermis.

They terminate in stratum granulosum.

Networks of free dermal endings surround most hair follicles attached to their outer root sheath.

They are mechanoreceptors and very sensitive.

Other nerve endings in the skin are encapsulated nerve endings; Pacinian corpuscle, Meissner's corpuscle and Ruffini endings.

 

Pacinian Corpuscles

These are deep pressure receptors for mechanical and vibratory pressure. It is found in the deeper dermis and the hypodermis, especially the fingertips.

They are composed of myelinated nerve endings surrounded by a capsule. The myelin is retained for one or two nodes and then lost.

The unmyelinated section is covered by a series of flattened Schwann cell lamellae that form the inner core.

The rest of the corpuscle is composed of concentric lamellae.

 

Meissner's Corpuscles

These are touch receptors, particularly responsive in the papillary layer of hairless skin, e.g., lips and palmar and volar surfaces of the fingers and toes.

They are present at the tip of the dermal papillae. One or two myelinated nerve fibres follow a spiral path in the corpuscle (they

are often described as looking like a "skein of wool").

 

Ruffini Endings

These respond to mechanical displacement of adjacent collagen fibres. Collagen fibres pass through the capsule and the neural element is a single

myelinated fibre.

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Skin Appendages

These include:

1. Hair follicles and hair;2. Sebaceous glands and their product sebum;3. Eccrine sweat glands and their product sweat;4. Apocrine sweat glands and their product serous secretion.

 

Hair

Hairs are composed of keratinised cells that develop from hair follicles. Coloration of the hair is due to the content and type of melanin that the hair

contains.

The base of the follicle is called the bulb. At the base of the bulb there is an invagination; a dermal papilla.

The outermost part of the follicle is the external root sheath. This is a down growth of the epidermis.

Other cells of the bulb are called the matrix and are called matrix cells. The dividing cells of the germinative layer of the matrix differentiate into

the keratin producing cells of the hair and the internal root sheath (multilayered).

Both have 3 layers, the hair having the medulla, cortex and cuticle and the internal root sheath having a cuticle, Huxley's layer and Henle's layer.

Keratinisation occurs at the keratogenous zone. Hair has hard keratin while the internal root sheath has soft keratin.

The arrector pili muscle attaches to outer sheath.

 

Sebaceous Glands

These glands secrete sebum. This is a holocrine-type secretion where both the product and

the cell are discharged from gland. It sebum coats the hair and skin surface.

Sebaceous glands develop as outgrowth of the external root sheath.

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Sweat Glands

There are 2 types of sweat glands:

1. Eccrine sweat glands, all over body except lips and part of external genitalia;2. Apocrine sweat glands, only in axilla, areola, nipple of mammary gland,

and circumanal region and the external genitalia. The ceruminous glands of ear and glands of Moll of eyelid are also apocrine.

Both the eccrine and the apocrine sweat glands are innervated by the sympathetic nervous system.

Eccrine glands respond differently to heat and nervous state. The apocrine glands respond to emotional and sensory stimuli but not heat.

 

Eccrine Sweat Glands

These are simple coiled glands that regulate body temperature. The secretory segment is deep in the dermis or upper hypodermis. Its duct leads to surface.

In the secretory region there are clear cells that produce the watery component of sweat and dark cells that produce a proteinaceous secretion.

There are also myoepithelial cells that are responsible for the expression of sweat from the gland.

Duct cells form the walls from the secretory portion to the area near the surface where the epidermal cells form the wall.

The duct is stratified cuboidal. There is both thermoregulatory sweating and emotional sweating. Resorption of some minerals take place in the duct. Myoepithelial cells are present in the duct.

 

Apocrine Sweat Glands

These are large lumen glands associated with hair follicles. They develop from the same down growths that give rise to hair follicles. The connection is retained and they are coiled tubular glands,

sometimes branched.

The secretory portion is in the dermis or upper hypodermis. The secretory product is stored in the lumen.

Myoepithelial cells facilitate the expulsion of the secretory product from the gland.

The duct has a narrow lumen. This duct has a stratified cuboidal epithelium. Resorption does not take place in the duct. Myoepithelial cells are also not present in the duct.

Apocrine secretions contain protein, carbohydrate, ammonia and lipid.

 

Nails

These are plates of keratinised cells containing hard keratin. The nail plate rests on the nail bed.

The proximal part, called the nail root, covers the germinative zone. This is called the matrix.

The crescent shaped white part near the nail called the lunula.

The fold of skin near the root of the nail is the eponychium. The hyponychium is the thickened epidermal layer that secures the free

edge of the nail plate at the fingertip.

The Gastrointestinal System I

Gastrointestinal System I

The gastrointestinal system consists of the alimentary canal and its associated organs:

1. Tongue;2. Teeth;3. Salivary glands;4. Pancreas;5. Liver and6. Gallbladder

The lumen of the alimentary canal is physically and functional external to the body (the body is topologically a 1-hole donut).

Food is broken down both physically and chemically as it passes through the GIT.

Absorption occurs chiefly through the walls of the small intestine.

Undigested food and other matter are excreted as faeces.

The alimentary mucosa is the surface across which most substances enter the body.

The functions of this mucosa include:

1. Barrier function: barrier to the entry of noxious substances, antigens and pathogenic organisms.

2. Immunologic functions: lymphatic tissue serves as the first line of defence.3. Secretory function: digestive enzymes, hydrochloric acid, mucin and antibodies.4. Absorptive function: absorption of metabolic substrates.

The Oral Cavity

The oral cavity consists of the mouth and its contents. It is divided into the vestibule and the mouth cavity proper.

The vestibule lies between the lips, cheeks and teeth. The oral cavity proper lies behind the teeth and is bounded by the hard and

soft palate superiorly, the tongue and floor of the mouth inferiorly and the entry of the oropharynx posteriorly.

The ducts of the salivary glands empty into the oral cavity. The major salivary glands include the: parotid gland, submandibular gland and

the sublingual gland.

The major salivary glands have relatively long ducts from the secretory portion of the gland.

The minor glands from the submucosa of the tongue and lining of the oral cavity have relatively short ducts.

Lymphatic tissue is organised into a ring of immunologic protection. This consists of the: palatine tonsil (the tonsils), the pharyngeal tonsil (the

adenoids) and lingual tonsils.

 

Oral Cavity Mucosa

The oral cavity is lined by masticatory mucosa, lining mucosa and specialised mucosa.

 

Masticatory Mucosa

It is on the gingivae and hard palate. It is keratinised or parakeratinised stratified squamous epithelium.

Parakeratinised epithelium is similar to keratinised epithelium but the cells of the stratum corneum retain their nucleus, and their cytoplasm does not stain as intensely with eosin.

As in the skin, the depth and number of papillae is dependent on the relative immobility of the masticatory mucosa.

This protects it from frictional and shearing forces.

 

Lining Mucosa

This is on lips, cheeks, alveolar mucosal surface, floor of mouth, inferior surfaces of the tongue and soft palate.

In these sites, it covers striated muscle (lips, cheeks and tongue), bone (alveolar mucosa) and glands (soft palate, cheeks, and inferior surface of the tongue).

The epithelium is generally non-keratinised. In some places it may, however, be parakeratinised (e.g., the epithelium of the

vermilion border of the lip).

The non-keratinised lining epithelium is thicker than the keratinised epithelium.

It consists of 3 layers:

1. Stratum basale;2. Stratum spinosum;3. Stratum superficiale.

The cells of the mucosal epithelium are similar to those of the epidermis of the skin.

They include: keratinocytes, Langerhan's cells, melanocytes and Merkel's cells. The sharp contrast between the alveolar mucosa and the rest of the lining

epithelium is in the numerous deep papillae of the alveolar mucosa compared to the shallow papillae of the rest.

 

Specialised Mucosa

This is restricted to the dorsal surface of the tongue, where it contains papillae and taste buds.

The Tongue

The striated muscles of the tongue are arranged in bundles that generally run at right angles to each other (in 3 planes).

The dorsal surface of the tongue is divided into anterior 2/3 and a posterior 1/3 by a V-shaped depression; the sulcus terminalis.

 

Lingual Papillae

Papillae cover the dorsal surface of the anterior portion of the tongue. Many papillae cover the dorsal surface anterior to the sulcus terminalis. These papillae include: filiform, fungiform, circumvallate and foliate papillae and

some contain taste buds.

The papillae and their associated taste buds constitute the specialised mucosa of the oral cavity.

There are 4 types of papillae described.

 

Filiform Papillae

These are most numerous in humans and are the smallest. They are conical, elongated projections of epithelium and connective tissue. It has keratinised (parakeratinised) stratified squamous epithelium.

This epithelium does not contain taste buds.

They are distributed over the entire dorsal surface, with their tips pointing back. Filiform papillae appear to form rows that diverge from the midline

and parallel to the arms of the sulcus terminalis.

 

Fungiform Papillae

These are mushroom-shaped projections. They tend to be more numerous at the tip of the tongue. Taste buds are present in their stratified squamous epithelium.

 

Circumvallate Papillae

These are large, dome-shaped structures that reside in the mucosa just anterior to the sulcus terminalis.

Each papilla is surrounded by a moat-like invagination of stratified squamous epithelium that contains numerous taste buds.

Ducts to the lingual salivary glands (of von Ebner) empty their serous secretions into the moats.

 

Foliate Papillae

These are parallel low ridges separated by deep mucosal clefts. They are aligned at right angles to the long axis of the tongue.

They occur at the lateral edge of the tongue.

The dorsal surface of the posterior portion of the tongue exhibits smoother bulges that reflect the presence of lingual tonsils.

 

Taste Buds

They appear as oval, pale staining bodies that extend through the thickness of the epithelium.

There is a small opening on the epithelial surface at the apex of the bud. This is known as the pore of the taste bud.

There are 3 principle cells types found in the taste buds:

1. Neuroepithelial cells;2. Supporting (sustentacular) cells;3. Basal cells.

Neuroepithelial cells and supporting cells are mature elongated cells that extend from the basal lamina to the taste pore.

Through the taste pore, the tapered apical surface of each cell extends microvilli.

The basal cells are located near the basal lamina and are believed to be the stem cells of the other two cell types.

The taste buds react to only 4 stimuli; sweet, salty, bitter and acid.

 

Nerve Supply of the Tongue

Anterior 2/3 Posterior 1/3

General Sensation CN V CN IX

Taste CN VII CN IX

The musculature of the tongue is supplied by the hypoglossal nerve (CN XII). There are, in addition, sympathetic and parasympathetic innervation of the

blood vessels and glands.

Teeth and Supporting Tissues

The adult tooth consists of 4 distinct structure components: the enamel and the cementum on the outside, the dentin beneath and the pulp in the central pulp cavity.

 

Enamel

The 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 contains 96-98% hydroxyapatite. Each enamel rod spans the full thickness of the enamel layer.

Striations seen in the enamel (contour lines of Retzius) may represent evidence of rhythmic growth of the enamel in the developing tooth.

 

Enamel Formation (Amelogenesis)

Enamel is produced by ameloblasts. These are narrow, highly polarised columnar cells. They are directly adjacent to the developing enamel.

At the apical pole of the cell is a process, Tome's process, which is surrounded by the developing enamel.

 

Cementum

This covers the root of the teeth. Cementum is thin layer of bone-like material secreted by cementocytes and

their processes.

 

Dentin

This is a calcified substance that forms most of the tooth's substance. It contains less hydroxyapatite than enamel, about 70%, but more than that

found in bone and cementum.

Dentin is formed by odontoblasts which forms an epithelial layer over the inner surface of the dentin.

The layer of odontoblasts retreats as the dentin is laid down. This leaves odontoblast processes embedded in the dentin in narrow tubules

known as dentinal tubules.

Predentin is the newly secreted organic matrix and is closest to the cell body of the odontoblasts.

This substance has yet to be mineralised.

 

Dentinal Pulp and Pulp Cavity

The dental pulp cavity is a connective compartment bounded by tooth dentin. This is occupied by pulp, which is a loose connective tissue that is

richly vascularised and innervated.

 

Alveolar Process and Alveolar Bone

The alveolar processes of the mandible and maxilla contain the sockets or alveoli for the roots of the teeth.

Alveolar bone proper is a thin layer of compact bone. It forms the wall of the alveolus.

 

Periodontal Ligament

This is a fibrous connective tissue joining the tooth to the surrounding bone.

This ligament is also known as the periodontal membrane.

This provides:

Attachment; Support; Bone remodelling (during movement of tooth); Nutrition of adjacent structures; Proprioception; Tooth eruption.

Salivary Glands

The major salivary glands are paired glands with long ducts. These include the: parotid, submandibular and sublingual glands.

The minor salivary glands are located in the submucosa of different parts of the oral cavity.

These include the: lingual, labial, buccal, molar and palatine glands.

The acini of salivary glands contain serous cells (protein secreting), mucous cells (mucin secreting), or both.

Thus, three types of acini are described:

1. Serous acini;2. Mucous acini;3. Mixed acini.

 

Serous Acini

They are generally spherical. Serous cells contain large amounts of rER, free ribosomes, a prominent

Golgi complex and numerous secretory granules. The secretions are stored in zymogen granules found in the apical cytoplasm.

 

Mucus Acini

These are usually more tubular. Most mucous cells contain large numbers of mucinogenic granules in their

apical cytoplasm. Thus, in routine H&E preparations, these cells have an empty appearance.

 

Mixed Acini

Some mucous acini have a cap of serous cells. These caps, or serous demilunes, secrete into the highly

convoluted intercellular space, between the mucous cells.

Salivary Ducts

The lumen of the salivary acini is continuous with the duct system. The duct system can be considered to have 3 sections:

1. Intercalated ducts;2. Striated ducts;3. Excretory ducts.

Serous glands have well-developed intercalated and striated ducts that modify their serous secretions (absorption of specific components and secretion of additional components).

Mucous glands, in which the secretions are not modified, have very poorly developed intercalated ducts and they may not be recognisable in H&E sections.

Moreover, they do not display striated ducts.

 

Intercalated Ducts

There are located between a secretory acinus and a larger duct. They are lined by low cuboidal cells. These cells possess carbonic anhydrase activity.

They secrete the bicarbonate ion and absorb the chloride ion.

 

Striated Ducts

These have numerous infoldings of the basal plasma membrane, which are seen as basal striations.

Their epithelial lining changes from simple cuboidal to simple columnar. These reabsorb sodium and add potassium.

 

Excretory Ducts

These travel in the interlobar and interlobular connective tissue. The excretory ducts connect ultimately with the oral cavity. Their epithelium changes from cuboidal to stratified

cuboidal to pseudostratified columnar.

Parotid Gland

These glands are totally serous. Its duct enters the oral cavity opposite the 2nd  upper molar.

 

Submandibular Gland

These glands are mixed glands that are most serous in humans. Some mucous acini capped with serous demilunes are found among

the predominantly serous acini.

 

Sublingual Gland

The small sublingual glands are mixed glands that are mostly mucous secreting in humans.

Some of the predominant mucous acini have serous demilunes.

The mucous secreting unit may be more tubular than purely acinar.

Liver, Gallbladder and Pancreas

Liver, Gallbladder, and Pancreas

The Liver

This is the largest glandular mass of tissue, and the largest internal organ of the body.

It receives substances from the digestive tract via the portal vein, including metabolites, nutrients, and toxins.

The liver normally conjugates (degrades) toxins, but may be overwhelmed by them.

The liver has both exocrine and endocrine functions:

Exocrine functions include the production of bile from metabolic conversions of substrates from the digestive tract, pancreas and spleen.

Secretion occurs via bile ductules draining into the hepatic duct, the gallbladder, the cystic duct, the common bile duct and, finally, into the duodenum.

Endocrine functions include the release of substances produced by liver cells into blood, including albumin, lipoprotein, globulins, liver glycogen, and T3 (thyroid hormone).

 

Blood supply to the liver

The liver's unique blood supply arises from two sources:

1. 75% of the liver's blood comes from the hepatic portal vein, carrying deoxygenated blood from the small intestine, pancreas and spleen. This blood contains absorbed nutrients and toxins from the intestine, blood products from the spleen, and endocrine secretions of the pancreas.

2. 25% comes from the hepatic artery, a branch of the celiac trunk, carrying oxygenated blood.

Structural organisation of the liver

Structural components of the liver include:

1. Hepatocytes, organised as plates or lamellae2. Connective tissue stroma3. Vessels, nerves, lymphatics and bile ducts4. Sinusoidal capillaries (sinusoids) between plates of hepatocytes

 

Liver lobules

Structural components of the liver are organised into lobules, which can be described in three ways: the classic lobule, the portal lobule and the liver acinus.

 

Classic Lobules of the Liver

These are roughly hexagonal blocks of tissue. They consist of stacks of anastomosing plates of hepatic cells, separated

by anastomosing sinusoids that perfuse the cells with mixed portal and arterial blood.

These plates outwardly radiate from a central vein: the terminal hepatic venule, into which the sinusoids drain.

At the angles of the periphery, connective tissue surrounds portal canals containing portal triads.

 

Portal Lobules of the Liver

These are centred around the interlobular bile ducts of the portal triads. All blood in the portal lobule originates from the portal triad in the centre. This is to emphasise the liver's exocrine functions.

Borders of the portal lobules are formed by the three surrounding central veins, creating a triangular shape.

 

The Liver Acinus

This organisational unit allows description and interpretation of degenerative patterns, regeneration, and toxic effects in liver parenchyma according to vascular perfusion of hepatic cells.

It has a short axis between two portal triads and a long axis between two central veins.

Three zones surround the short axis:

Zone 1 - closest to the axis.

Zone 3 - farthest from the axis, closest to the central veins.

Zone 2 - lies between zone 1 and zone 3.

Hepatocytes

Hepatocytes a large polygonal cells approximately 25 microns wide. They make up the anastomosing plates of the liver lobules.

They have large, central, spherical nuclei, and may be binucleate. Hepatocytes have a life span of about 5 months, although they are capable of

rapid regeneration.

They contain lipid droplets and large deposits of glycogen, along with organelles.

Two surfaces of the cell face the sinusoidal lumen: the basal (free) surfaces. Other surfaces face neighbouring hepatocytes, and may have bile

canaliculi between them, forming lateral and apical surfaces, respectively.

 

Major functions of Hepatocytes

Bile production and secretion; Metabolism (including detoxification) of lipid soluble drugs and steroids as

well as cholesterol synthesis; Lipoprotein synthesis; Carbohydrate synthesis;

Urea formation from ammonium ions.

Portal Canals

These are loose stromal connective tissue (continuous with the fibrous capsule of the liver), at the angles of the periphery of lobules.

They contain portal triads and autonomic nerves, and are bordered by the outermost hepatocytes of the lobules.

The space of Mall, between the connective tissue stroma and the outermost hepatocytes, is thought to be one of the sites where lymph originates in the liver.

 

Portal Triads

These are groups of 4 structures in the portal canals:

1. Branches of the portal vein (the largest structure);2. Branches of the hepatic artery;3. Bile ductules4. Lymphatic vessels (small)

Blood vessels of the parenchyma

Portal and hepatic arterial blood flow through the interlobular vessels of the portal triads, then into distributing branches from the periphery which supply thesinusoids.

From the sinusoids, blood flows centrally to the central vein, which empties into sublobular veins and, eventually, the hepatic veins and inferior vena cava.

The central vein is thin walled, with circularly arranged connective tissue fibres surrounding its endothelium.

 

Sinusoids

Hepatic sinusoids are lined with a thin, discontinuous, fenestrated endothelium containing silver binding reticular fibres and stellate sinusoidal macrophages or Kupffer cells.

Processes of Kupffer cells may span the sinusoidal lumen, and they may be involved in the final breakdown of red blood cells from the spleen.

 

Perisinusoidal Space (Space of Disse)

This space lies between the basal surfaces of the hepatocytes and the basal surfaces of the endothelium lining the sinusoids.

Numerous microvilli extend from the hepatocytes into the space of Disse, where materials are exchanged between blood and liver cells.

This forms the pathway for endocrine secretions of the liver.

Adipocytes with vitamin A are also found here.

Plasma in this space drains to the space of Mall, then enters lymphatic capillaries that travel with components of the portal triads.

Thus, lymph moves towards the portal canals and, eventually the hilum of the liver, draining into the thoracic duct.

The Biliary Tree

This is the conduit system by which bile flows from hepatocytes to the gallbladder, and then to the intestine.

It begins with the canaliculi, grooves between hepatocytes, into which they secrete bile.

These bile canaliculi form a ring about the hepatocytes, and drain into small bile ductules, the canals of Hering.

These drain outwardly, opposite to the flow of blood, from the central vein, into the interlobular bile ducts of the portal canals.

These ductules are lined by cuboidal epithelium, whilst the interlobular (intrahepatic) bile ducts are lined by cuboidal epithelium near the lobules that graduallybecomes columnar nearer to the porta hepatis.

The interlobular ducts then fuse to form left and right hepatic ducts that join at the hilum to form the common hepatic duct.

Extrahepatic ducts now carry the bile to the gallbladder and intestine.

The common hepatic duct fuses with the cystic duct from the gallbladder and becomes the common bile duct (or just "bile duct") which opens into the wall of the duodenum at the hepatopancreatic ampulla (of Vater).

The Gallbladder

The gallbladder is a pear-shaped sac with a volume of about 50 mL, attached to the visceral surface of the liver.

The function of the gallbladder is to store the dilute bile it receives from the hepatic duct, concentrate it, and discharge the concentrated bile into the common bile duct.

 

Mucosa of the Gallbladder

The interior surface of the gallbladder has numerous mucosal folds of simple columnar epithelium, resembling the absorptive cells of the intestine.

The lamina propria of the mucosa is highly vascular, but there are no lymphatic vessels.

It also contains many lymphocytes and plasma cells.

The lamina propria is similar to that of the colon; it is specialised for the absorption of electrolytes and water (thus concentrating the bile).

 

Muscularis Externa, Adventitia and Serosa of the Gallbladder

External to the lamina propria is a muscularis externa containing numerous collagen and elastic fibres, amongst randomly oriented bundles of smooth muscle cells.

The gallbladder does not have a muscularis mucosae or a submucosa.

Contraction of the smooth muscle forces bile out through the cystic duct.

External to the muscularis externa is a thick layer of dense connective tissue, adventitia, containing large blood vessels, lymphatics, autonomic nerves, as well as elastic fibres and adipose tissue.

On the visceral surface of the gallbladder, visceral peritoneum (serosa) consisting of mesothelium and loose connective tissue lines the adventitia.

The Pancreas

The pancreas is an exocrine and endocrine gland, dividing these functions into two structurally distinct components:

1. A  large, serous, exocrine component, continuous throughout the organ, that synthesises and secretes digestive enzyme precursors.

2. A  small, endocrine component, dispersed throughout the organ as islets of Langerhans, that mainly synthesises insulin and glucagon and secretes them into theblood.

 

Exocrine Pancreas

The exocrine pancreas closely resembles the parotid gland. It has serous, secretory acini that are formed by a simple epithelium

of pyramidal cells. These serous cells produce digestive enzyme precursors (proenzymes).

Pancreatic acini are unique, in that the intercalated duct actually begins within the acinus.

The duct cells located inside the acinus are the centroacinar cells.

The acinar cells have acidophilic zymogen granules in their cytoplasm, which contain a variety of digestive proenzymes, including:

Trypsinogen, pepsinogen and procarboxylase for digestion of proteins Amylase for carbohydrates Lipase for lipids Deoxyribonulcease and ribonuclease for nucleic acids

The zymogen granules are released by exocytosis into lumenal spaces between the apical surfaces of the acinar cells.

The basophilic cytoplasm of the acinar cells have extensive rough endoplasmic reticulum (rER) and free ribosomes, indicating high levels of protein synthesis.

 

Duct system

This begins with squamous, centroacinar cells, which are intercalated duct cells located in the acinus.

These cells are continuous with the short intercalated duct lying outside the acinus.

The intercalated ducts drain into intralobular collecting ducts.

There are no striated ducts in the pancreas.

The intralobular collecting ducts drain into the larger interlobular ducts which, in turn, drain directly into the main pancreatic duct.

This runs the length of the gland and opens into the hepatopancreatic ampulla (of Vater) with the common bile duct.

The accessory pancreatic duct also arises in the head of the pancreas, opening into the minor duodenal papilla.

 

Hormonal control of exocrine secretion

Acidic chyme in the duodenum stimulates the release of the following hormones:

1. Secretin, which stimulates the duct cells to secrete large volumes of fluid with little or no enzyme content.

2. CCK, which causes acinar cells to secrete their proenzymes.

Endocrine Pancreas

The endocrine pancreas is a diffuse organ. The islets of Langerhans, most numerous in the tail, comprise about 1-2% of

the volume of the pancreas.

They secrete hormones that regulate blood glucose. Islets contain varying numbers of polygonal cells arranged in short, irregular

cords, profusely invested with fenestrated capillaries (for hormonal release), and stain less intensely than the surrounding serous acini.

Three principal cell types are found in the islets of Langerhans:

1. A Cells, about 15-20% of the islet population, found in the periphery. They stain red with the Mallory-Azan method, and secrete glucagon from densely packedcytoplasmic granules.

2. B Cells, about 70% of the islet population, located in the central portion. They stain brownish-orange with the Mallory-Azan method, and secrete insulin from large secretory granules.

3. D Cells, about 5-10% of the islet population, located in the periphery. They stain blue with the Mallory-Azan method, and secrete somatostatin from the largest secretory granules in the islet.

Other pale staining cells, about 5% of the islet population, also secrete hormones, including pancreatic polypeptide (PP).

 

Functions of Hormones

Hormones secreted by the endocrine pancreas regulate metabolic functions.

Insulin, the major hormone secreted by the islet tissue, stimulates the uptake, utilisation, and storage of glucose.

Glucagon, the second largest secretion, stimulates the mobilisation of glucose.

Somatostatin, when released from the hypothalamus, inhibits growth hormone (GH or somatotropin) release from the anterior pituitary gland.

In the islets, it inhibits both insulin and glucagon secretion.

 

Blood Supply of the Pancreas

The blood supply of the pancreas provides a cascading perfusion of the islets and acini.

Blood from arterioles at the periphery of the islets, will perfuse by A and D cells before reaching B cells in the centre.

Larger vessels invading the islets are accompanied by A and D cells, so that blood reaching B cells has always perfused the A and D cells (for the self-regulatory mechanisms of, say, somatostatin).

The Endocrine System

The Endocrine System

The endocrine system parallels the nervous system; their primary function is intracellular communication.

It produces a slower, more prolonged response than the nervous system.

Hormones are typically released into fenestrated capillaries, and reach receptors of target cells via the circulatory system.

The endocrine system includes pituitary gland, adrenal glands, thyroid and parathyroid glands, the pineal gland, and other endocrine centres.

The Pituitary Gland (Hypophysis)

This is a pea sized, compound endocrine gland lying within the sella turcica of the sphenoid bone at the base of the skull.

It is joined to the hypothalamus by the stalk-like infundibulum.

There are two functional components of the pituitary:

1. The anterior pituitary (adenohypophysis): glandular epithelial tissue derived from the ectoderm of the oropharynx (Rathke’s pouch).

2. The posterior pituitary (neurohypophysis): neural secretory tissue derived from the neuroectoderm of the diencephalon.

 

The Anterior Pituitary (Adenohypophysis)

This is the master gland of the endocrine system, regulating other endocrine glands.

It has the typical arrangement of endocrine tissue, consisting of cords of cells separated by large, fenestrated sinusoidal capillaries.

Upon signalling from the hypothalamus, these cells synthesise and secrete tropic hormones that regulate the activity of other endocrine tissues in the body.

These regulatory hormones are either releasing or inhibiting.

The anterior pituitary has 3 parts, the pars distalis, the pars intermedia and the pars tuberalis.

 

The Pars Distalis

The pars distalis comprises most of the anterior pituitary. Its has 3 types of cells based on their staining:

1. Basophils2. Acidophils3. Chromophobes

Many hormones are secreted from this region include:

1. Adrenocorticotropin (ACTH), that stimulates the adrenal cortex to produce cortisol and aldosterone.

2. Lipotropic hormone (LPH), which may be cleaved to form melanocyte stimulating hormone and endorphins which have analgesic effects.

3. Luteinizing hormone (LH), which stimulates ovulation in the ovaries and the production of testosterone from the Leydig cells in the testis.

4. Follicle-stimulating hormone (FSH), that stimulates follicle development in the ovaries and the Sertoli cells in the testis.

5. Thyroid-stimulating hormone (TSH), causing release of T4 and T3 from the thyroid gland.

6. Somatotropin, or Growth hormone (GH), that causes release of insulin-like growth factors (IGFs) in the liver, and inhibits the effects of insulin on carbohydrate and fat metabolism.

 

The Pars Intermedia

This is a thin zone of tissue between the pars distalis and the posterior pituitary.

It includes:

1. Basophils2. Chromophobes3. Colloid-filled cysts, representing the residual lumen of Rathke’s pouch.

Hormones produced in this region include:

Melanotropin (MSH), stimulating the production of the pigment melanin by melanocytes in the skin.

 

The Pars Tuberalis

This is a highly vascular region surrounding the infundibulum and forming a collar around the pars intermedia.

It contains:

1. Squamous cells;2. Small follicles lined with cuboidal cells;3. Veins of the hypophyseal portal system.

The Posterior Pituitary (Neurohypophysis)

This is a storage site for neurosecretions from the neurons of the supraoptic and paraventricular nuclei (SON & PVN) of the hypothalamus.

It is not an endocrine gland.

The posterior pituitary has 2 parts, the pars nervosa and the infundibulum.

 

The Pars Nervosa

This is the neural lobe of the pituitary, containing non-myelinated axons and nerve endings of many neurosecretory neurons.

These cells’ cell bodies lie in the supraoptic and paraventricular nuclei. They convey neurosecretions to the pars nervosa, where they

are stored and released.

These neurons have 2 unique features:

1. They end close to fenestrated capillaries in the pars nervosa;2. And they contain membrane bound secretory granules in all parts of the cells,

not just the cell body.

The membrane bound granules come in 3 sizes:

10-30 nm neurosecretory granules, accumulating in axon terminals and forming Herring bodies, which are dilations in the axon near the terminals.

30nm terminal vesicles containing acetylcholine.

The larger 50-80nm terminal vesicles.

Hormones contained in membrane bound Herring bodies are direct acting and include:

1. Antidiuretic hormone (ADH) or vasopressin, produced in the SON, which affects blood pressure and increases water resorption in the kidney tubules.

2. Oxytocin (OT), produced in the PVN, promotes contraction of the smooth muscle of the uterus and the myoepithelial cells of the breast (releasing milk).

 

The Infundibulum

This connects the pars nervosa to the hypothalamus.

Pituicytes

These cells are unique to the neurohypophysis, found amongst the fenestrated capillaries.

They are irregular in shape, with many branches, and resemble glial cells. They have round or oval nuclei and pigmented granules in their cytoplasm. They often have processes terminating in the perivascular space, and may

have a similar role to that of the astrocyte in the rest of the CNS.

 

Blood Supply of the Pituitary

The blood supply of the pituitary arises from 2 sets of vessels:

1. The superior hypophyseal arteries, from the internal carotid arteries and circle of Willis. This supplies the pars tuberalis, median eminence, and infundibular stem.

1. The inferior hypophyseal arteries, from the internal carotid arteries alone. This supplies the pars nervosa.

Most of the anterior lobe of the pituitary has no direct arterial supply.

 

The Hypophyseal Portal System

Arteries supplying the pars tuberalis, median eminence and infundibular stem give rise to the primary capillary plexus of fenestrated capillaries.

These capillaries drain into the hypophyseal portal veins running along the pars tuberalis and give rise to the secondary capillary plexus.

This system carries neuroendocrine secretions from hypothalamic nerves to the cells in the pars distalis.

Most blood then drains into the cavernous sinus via the hypophyseal veins, but some blood may flow into the pars nervosa, and then back to the hypothalamus.

This provides a direct feedback mechanism to the brain that bypasses the greater circulation.

The Adrenal Glands (Suprarenal glands)

These are flattened triangular glands embedded in perineal fat on the superior poles of the kidneys.

 

Structure of the Adrenal Glands

There is a thick connective tissue capsule from which trabeculae extend into the parenchyma, carrying blood vessels and nerves.

 

The Cortex of the Adrenal Glands

The outer cortex of the parenchyma is beneath the capsule. This comprises 90% of the gland, and is the steroid secreting portion. Its cells are derived from mesodermal mesenchyme, and are controlled by the

pituitary and function in regulating metabolism and maintaining electrolyte balance.

It is divided into 3 zones, the zona glomerulosa, zona fasciculata and zona reticularis.

 

The Zona Glomerulosa

This is a narrow outer zone, 15% of cortical volume.

It has small, densely staining, columnar or pyramidal cells with spherical nuclei.

They are closely packed into clusters and columns that are continuous with the cords of the next zone.

It secretes mineralocorticoids, of which aldosterone functions to control blood pressure.

The renin-angiotensin system provides feedback control of this zone.

 

The Zona Fasciculata

This is the thick middle zone, 80% of cortical volume.

It consists of pale staining cells are large and polyhedral with spherical nuclei and lipid droplets in an acidophilic cytoplasm.

They are arranged in long, straight cords 1 or 2 cells thick that are separated by sinusoidal capillaries.

It secretes glucocorticoids that regulate glucose and fatty acid metabolism. The most important of which is hydrocortisone (cortisol) that acts to mobilise

glucose and fatty acids for energy.

This zone is under feedback control of the hypothalamic-hypophyseal corticotropin-releasing factor-adrenocorticotropic hormone (CRF-ACTH) system.

 

The Zona Reticularis

This is the inner zone, 5% of cortical volume, but is thicker than the glomerulosa due to its central location.

It has small cells with darker nuclei, arranged in narrow, anastomosing cords between fenestrated capillaries.

It secretes weak androgens (sex hormones), mostly dehydroepiandrosterone (DHEA), as well as a small amount of glucocorticoids, namely cortisone.

This zone is also under the CRF-ACTH system.

 

The Medulla of the Adrenal Glands

The inner medulla forms the centre of the gland. It is derived from neural crest origin, and its parenchyma contains chromaffin

cells: modified neurons.

These large, epithelioid cells are characterised by membrane-bound secretory granules of 100-300nm, and are organised as clusters and short interconnecting cords.

They are innervated by preganglionic sympathetic neurons. Upon the release of acetylcholine they are stimulated to release

the catecholamines epinephrine and norepinephrine. Sinusoidal capillaries are intimately related to these, originating from

either cortical capillaries or branching from cortical arterioles.

Ganglion cells are also present.

Blood Supply of the Adrenal Glands

The adrenal glands are supplied by the superior, middle and inferior adrenal arteries.

These branch before and inside the capsule, producing 3 distribution systems:

1. Capsular capillaries, supplying the capsule;2. Fenestrated cortical sinusoidal capillaries, supplying the cortex and draining

"venous blood" into the medullary capillary sinusoids;3. Medullary arterioles traversing the cortex within trabeculae and

bringing arterial blood to the medullary capillary sinusoids.

Thus the medulla has a dual arterial and "venous" blood supply.

Venules from cortical and medullary sinusoids drain into medullary veins, the large medullary (adrenal) vein, and the IVC.

The Thyroid Gland

This is a bi-lobed endocrine gland located in the neck. Its lobes (about 25g each) are on either side of the larynx and trachea, and are

connected by the isthmus. It is fully functional from 10 weeks, required for embryonic and neural

development.

 

Hormones Produced by the Thyroid Gland

It produces 3 hormones, each essential to normal metabolism and homeostasis, as well as foetal development.

1. Thyroxine (tetraiodothyronine - T4) and triiodothyronine (T3), which regulate cell and tissue metabolism, growth and differentiation.

2. Calcitonin, which lowers blood calcium levels, stimulates osteoblasts, inhibits osteoclasts and stimulates calcium excretion from the kidney.

Thyroid hormone deficiency in foetal development leads to irreversible damage called cretinism.

 

Structure of the Thyroid Gland

The structure of the thyroid gland includes:

 

Capsule of the Thyroid Gland

There is a thin connective tissue capsule, sending trabeculae into the parenchyma, creating irregular lobes and lobules.

 

Secretory Follicles of the Thyroid Gland

This constitutes the structural and functional units of the gland.

These are spheroidal compartments with a wall of simple cuboidal follicular epithelium.

The follicular lumen is filled with gel-like colloid containing the iodinated glycoprotein thyroglobulin.

There are 2 basic cell types in the follicles:

1. Follicular (principal) cells that secrete T4 and T3, derived from the endoderm of the pharyngeal part of the foregut;

2. Parafollicular (C) cells that secrete calcitonin, of neural crest origin. These are solitary or a small cluster of pale staining cells, also found in the interfollicular space. They are characterised by membrane bound secretory granules (0.1-0.5 um diameter).

The follicles are surrounded by many fenestrated capillaries, from the superior and inferior thyroid arteries.

Lymphatic capillaries are also present in the interfollicular connective tissue, providing a secondary route for hormonal secretions from the gland.

 

Thyroid Hormone Synthesis

Thyroglobulin is synthesised and glycosylated in the follicular epithelial cells and secreted into the colloid.

Tyrosine residues on thyroglobulin are iodinated in the colloid, and then coupled to form T3 and T4 residues.

Thyroglobulin is endocytosed into the follicular cells, where T4 and T3 are released by lysosomal enzymes.

This uptake and release is subject to feedback control. Low levels of T3 and T4 cause the release of thyroid releasing

hormone (TRH) from the hypothalamus, stimulating the pituitary to release thyroid stimulating hormone(TSH).

This increases the uptake and release of T3 and T4. Conversely, high T3 and T4 levels inhibit the release of TSH, along

with somatostatin from the hypothalamus.

 

The Parathyroid Glands

These are small, superior and inferior laterally paired glands on the posterior aspect of the thyroid gland.

They receive their blood supply from the thyroid arteries and contain fenestrated capillaries.

 

Structure of the Parathyroid Glands

There is a thin connective tissue capsule, separating it from the thyroid, with small septa extending into the gland.

This poorly defines the lobules and separating densely packed cords of cells.

The parenchyma contains 2 types of cells, the chief cells and the oxyphil cells.

 

Chief (Principal)Cells

These are small, polygonal cells with central nuclei and a pale staining cytoplasm that secretes parathyroid hormone (PTH).

This has the reciprocal effect of calcitonin, and increases calcium resorption from bone and urine, and from the G.I. tract via the production of 1,25-dihydroxycholecalciferol.

 

Oxyphil Cells

These are only a minor portion of the parenchymal cells. They are larger and more rounded than chief cells, with a very acidophilic

cytoplasm.

The Pineal Gland

This is a small, flattened, cone-shaped structure weighing between 100-200mg.

It is attached to the brain by a short stalk. Its function is not yet clearly defined.

The pineal gland has 2 basic parenchymal cell types:

Pinealocytes are the most common cell type, arranged in clumps or cords within lobules formed by septa extending from the gland’s surrounding pia mater.

They have large, infolded nuclei with prominent nucleoli, and lipid droplets in their cytoplasm.

Interstitial (glial) cells constitute about 5% of the gland. These cells closely resemble astrocytes.

The human pineal gland also has calcified concretions called corpa arenacea or brain sand.

Other endocrine centres

Endocrine subsystems are also found in:

1. The kidney

2. The gastro-intestinal system3. The liver and pancreas4. The testes and ovaries

The Urinary System

The Urinary System

The urinary system consists of the kidneys, ureters, bladder and the urethra.

 

The Kidney

This is a highly vascular organ receiving about 25% of cardiac output. It produces ultrafiltrate that is converted to urine by selective

resorption and secretion by kidney cells.

 

Endocrine Functions of the Kidney

These include:

1. Production of erythropoietin, a growth factor regulating red blood cell formation, secreted by interstitial cells;

2. Production of renin, a hormone controlling blood pressure and volume, secreted by juxtaglomerular cells in response to low blood pressure, blood volume or sodium ion concentration;

3. Hydroxylation of vitamin D to its active form: 1,25-dihydroxycholecalciferol.

 

Kidney Structure

This consists of:

1. A  thin, lining capsule, consisting of an outer layer of fibroblasts and collagen, and an inner layer of myofibroblasts;

2. An outer, reddish-brown cortex. This contains spherical, renal corpuscles, each bounding a glomerulus; tubules of nephrons, collecting tubules, and an extensivevascular supply.

Straight collecting tubules and straight tubule components of the nephrons make up medullary rays that project into the cortex from the pyramid.

Between the medullary rays, convoluted tubules of the nephrons and renal corpuscles form the cortical labyrinths.

3. An inner, paler medulla. This contains straight tubules of nephrons and collecting ducts, accompanied by a capillary network called the vasa recta.

The tubules form pyramids, with their apices or papilla projecting into a minor calyx.

These minor calyces form major calyces and, eventually, the renal pelvis.

Cortical tissue surrounding the pyramids form renal columns. Each pyramid constitutes a lobe of the kidney, and each lobe divides

into lobules that consist of a medullary ray and the nephrons it drains.

The Nephron

This is the functional unit of the kidney, producing urine. The parts of the nephron include:

1. The renal corpuscle;2. The renal tubule, including the proximal segment, the loop of Henle, the distal

segment.

There are 3 types of nephron:

3. Juxtamedullary nephrons, which have their renal corpuscles close to the base of the medullary pyramid.

These have long loops of Henle and long thin segments that extend well into the inner region of the pyramid.

4. Cortical nephrons, which have their renal corpuscles in the outer part of the cortex.

These have short loops of Henle and the hairpin turn occurs in the distal thick segment.

5. Intermediate nephrons in the mid-region, which have intermediate length loops of Henle.

 

The Renal Corpuscle

The renal (Malpighian) corpuscle consists of a tuft of capillary loops, the glomerulus, surrounded by a Bowman's (renal) capsule.

The glomerular capillaries are supplied by an afferent arteriole and drained by an efferent arteriole.

These penetrate the Bowman's capsule at its vascular pole.

At the opposite end, the proximal convoluted tubule begins at the urinary pole.

The Bowman's capsule has an outer parietal layer of simple squamous epithelium, continuous with the cuboidal epithelium of the proximal convoluted tubule.

The inner, visceral epithelial layer, enclosing the filtration apparatus of the kidney, is formed by podocytes.

Between these layers, the Bowman's (renal) space collects filtrate that has perfused from the high-pressure capillary lumen.

This space is continuous with the lumen of the proximal convoluted tubule.

Mesangial cells are phagocytic, modified smooth muscle cells that produce mesangium.

Intraglomerular mesangial cells are found at the stalk of the glomerulus and the interstices of adjoining glomerular capillaries, enclosed by their basal lamina.

Extraglomerular mesangial cells of the juxtaglomerular apparatus (lacis cells) lie along the vascular pole.

The Filtration Apparatus

This is a semi-permeable barrier with 3 parts:

1. The discontinuous endothelium of the glomerular capillaries;2. The podocytes forming the discontinuous visceral layer of Bowman's

capsule;3. The continuous basal lamina between them.

Podocytes extend around the fenestrated glomerular capillaries, with foot processes that interdigitate with their neighbours.

Narrow filtration slits between the foot processes with a filtration slit membrane allow blood to enter the Bowman's space.

The glomerular basement membrane (GBM, basal lamina) is the principal filtration barrier and an ion selective filter.

It has 3 parts:

1. The lamina rara interna, on the capillary side;2. The lamina rara externa, next to the podocytes;3. The lamina densa, a thick, fused portion between the other 2 layers.

The GBM has an overall negative charge. This restricts the movement of large proteins in the blood. Proteins that do pass through are reabsorbed in the proximal convoluted

tubule.

 

The Proximal Segment

This begins as the proximal convoluted tubule of cuboidal cells with a brush border invading the lumen.

It enters a medullary ray, continuing in its thick segment as the descending straight tubule, and in its thin segment as the descending limb of the loop of Henle.

The proximal convoluted tubule reabsorbs about 80% of the primary filtrate.

 

The Loop of Henle

This U-shaped part consists of squamous cells. It includes the loop and the descending and ascending limbs of

the proximal and distal segments respectively.

Cortical nephrons have short loops of Henle and juxtamedullary nephrons have very long loops of Henle.

 

The Distal Segment

This part of the tubule has fewer microvilli than the proximal segment.

It ascends through the pyramid and medullary ray in thin, then thick segments towards the vascular pole of the renal corpuscle.

Modified epithelial cells next to the afferent arteriole form the macula densa.

The tubule then becomes the distal convoluted tubule, emptying into a connecting tubule, then straight collecting tubule in the medullary ray.

The straight collecting tubules form cortical collecting ducts that continue into the apex of the pyramid, emptying into ducts of Bellini that open into the calyx.

The Juxtaglomerular Apparatus

This structure next to the vascular pole regulates blood pressure. It includes the macula densa, juxtaglomerular cells and extraglomerular

mesangial cells.

Juxtaglomerular cells are modified smooth muscle cells of the afferent arteriole.

They have spherical nuclei that secrete renin from secretory granules.

Renin catalyses the conversion of angiotensinogen to angiotensin I, which is then converted to angiotensin II in the lung.

Angiotensin II, acting via the central nervous system, is a potent vasoconstrictor, but also causes the release of aldosterone from the zona glomerulosa of theadrenal gland.

This causes increased distal tubal resorption of sodium and water. This in turn increases blood volume and thus blood pressure.

 

Interstitial cells

The connective tissue parenchyma of the kidney cortex has macrophages and cells resembling fibroblasts.

Cells resembling myofibroblasts are present in the medulla.

 

Vasa Recta

The efferent arterioles form capillary networks around the renal tubules, known as peritubular capillaries.

In cortical nephrons, the peritubular capillaries anastomose with those of other nephrons.

In juxtamedullary nephrons, they descend with the loop of Henle as arterioles.

They then loop and ascend as venules back to the cortex. These are the vasa recta, forming fenestrated capillary plexuses at various

levels in the pyramid.

 

Countercurrent Exchange

This occurs between the collecting system and the vasa recta. In the cortex, the interstitium is hypotonic, along with the distal convoluted

tubule. In the medulla, the interstitium becomes hypertonic.

Thus, as the vasa rectae descend, water is drawn from them and salts enter, making them hypertonic at the loop.

As the vasa rectae ascend, however, the process is reversed, with blood losing salt and gaining water.

This countercurrent exchange system occurs passively along ion gradients.

Blood Supply

This begins with the renal artery dividing anteriorly and posteriorly, sending interlobar branches between the pyramids.

At the cortex they divide into arcuate arteries that follow the base of the pyramid.

These arcuate arteries give interlobular arteries that ascend into the cortex.

The interlobular arteries branch into afferent arterioles that form the glomerular capillaries.

The glomerular capillary bed reunites as efferent arterioles.

These give rise to the peritubular capillaries. Peritubular cortical capillaries and the vasa rectae drain into arcuate

veins, interlobar veins, and the renal vein.

 

Lymphatics

Lymphatic vessels drain into 2 major networks:

1. The larger capsular lymphatic vessels;2. And the larger lymphatic vessels in the renal sinus.

Excretory Passages

These include the calyces, renal pelvis, ureter, bladder and urethra. Except for the urethra, their structure consists of:

1. A  mucosa;2. A  muscularis;3. An adventitia (or serosa in some regions);

All these passages are lined with transitional epithelium, allowing distension.

Plaques are present on the luminal surface of the plasma membrane. When the bladder is undistended, the plaques fold inward, but in

the distended bladder, they unfold as the transitional epithelium flattens.

The lamina propria is dense and collagenous. There is no muscularis mucosae or submucosa.

In the ureters and urethra, bundles of smooth muscle below the lamina propria spiral downward with differing curvature.

This gives the appearance of 3 layers of smooth muscle:

1. An outer longitudinal layer;2. A  middle circular layer;3. And an inner longitudinal layer.

Peristaltic contractions move the urine toward the bladder.

 

The Ureters

The ureters follow an oblique path into the bladder wall. As the bladder distends, the openings of the ureters are

thus compressed, preventing reflux of urine into the ureters. This protects the kidney from the spread of infection from the bladder.

 

The Urinary Bladder

The smooth muscle within the bladder wall forms an internal sphincter around the opening of the urethra.

The trigone, formed from the openings of the ureters and urethra, remains smooth and constant in thickness, regardless of the state of filling of the bladder.

 

Innervation of the Bladder

Sympathetic fibres form a plexus in the adventitia of the bladder wall.

Parasympathetic fibres in ganglia in muscle bundles and the adventitia form the efferent fibres of the micturition reflex.

Sensory fibres going to the sacral spinal segments form the afferent fibres of the micturition reflex.

 

The Urethra

In the male, the urethra is about 20 cm long. It has 3 segments:

1. The prostatic urethra (4cm), from the neck of the bladder through the prostate gland. Seminal vesicles and prostatic ducts open into this segment. The epithelium here is transitional.

2. The membranous urethra (1cm), from the apex of the prostate gland through the pelvic and urogenital diaphragms. The surrounding skeletal muscles form theexternal sphincter of the urethra. The epithelium becomes pseudostratified columnar here.

3. The penile urethra (15cm), through the penis to open at the glans penis. Here, the epithelium becomes stratified squamous, continuous with the skin of the penis. Ducts of the bulbourethral glands and mucous-secreting glands of Littre open into this portion.

In the female, the urethra is about 4 cm long. The epithelium also changes from transitional to stratified squamous.

Many small paraurethral and periurethral glands, producing an alkaline secretion, open into the female urethra.

The Respiratory System

The Respiratory System

This consists of the lungs and the air passages that lead to and form the lungs. The air passages branch as they enter the lungs to finally form alveoli. This system has 3 functions:

1. Air conduction;2. Air filtration;3. Gas exchange (respiration).

Also air passing through the larynx gives rise to speech and air passing over the olfactory mucosa leads to our sense of smell.

Air passages consist of a conducting portion and a respiratory portion. The conducting portion is the air passages that lead to the sites of

respiration so gas exchange can occur. The passages external to the lungs are:

1. Nasal cavities;2. Nasopharynx and oropharynx;3. Larynx;4. Trachea;5. Paired primary bronchi.

Bronchi within the lungs branch extensively to form bronchioles, which are the terminal part of the conducting system.

The respiratory portion is the part of the tract where gaseous exchange takes place and includes:

1. Respiratory bronchioles;2. Alveolar ducts;3. Alveolar sacs;4. Alveoli.

Capillaries within the lungs come into intimate contact with the alveoli and are the structural basis of gas exchange in the lung parenchyma.

Conditioning of the air before it reaches the respiratory portion occurs and consists of warming, moistening, and removal of particulate material.

Mucous and serous secretions are very important in the conditioning process and also stops dehydration of the underlying epithelium.

Mucous is produced from goblet cells and mucus-secreting glands. Cilia push mucous into the pharynx. Vibrissae are small hairs that trap particulate material.

Nasal cavities

The nasal cavities have 3 regions:

1. Vestibule;2. Respiratory segment;3. Olfactory segment.

The paranasal sinuses are filled with respiratory epithelium.

 

The Vestibule of the Nasal Cavity

The vestibule communicates anteriorly with the environment and is lined by stratified squamous epithelium and contains vibrissae.

Sebaceous glands are present and also assist in the entrapment of particulate matter.

Posteriorly, the epithelium changes to ciliated pseudostratified columnar epithelium of the respiratory portion.

 

The Respiratory Portion of the Nasal Cavity

The respiratory portion has its lamina propria attached to the underlying bone.

The medial wall is the nasal septum. The lateral wall contains conchae. The conchae increase the surface area and cause turbulence in the airflow to

allow more efficient conditioning of air and also the removal of particulate matter viaturbulent precipitation.

The epithelium consists of 5 types:

1. Ciliated cells;2. Goblet cells;3. Brush cells (have short blunt microvilli);4. Small granule cells (contain secretory granules);

5. Basal cells (stem cells).

The lamina propria of the respiratory segment has a rich vascular network. This allows inhaled air to be warmed, and also contains mucus glands, many

with serous demilunes. It is directly contiguous with the periosteum of the underlying bone. The laminae propria also contains blood and lymphatic vessels, unmyelinated

olfactory nerves, myelinated nerves and the olfactory glands (Bowman's glands).

 

The Olfactory Portion of the Nasal Cavity

The olfactory segment is lined by the olfactory mucosa. It is also pseudo-stratified but contains very different cells:

1. Olfactory cells, bipolar neurons;2. Supporting or sustentacular cells (columnar cells providing mechanical and

metabolic support of olfactory cells, and microvilli);3. Basal cells;4. Brush cells (have short blunt microvilli and are columnar, they appear to be

involved in the transduction of general sensory stimulation of the mucosa to CNV).

Olfactory cells are bipolar neurons that possess an apical projection called the olfactory vesicle bearing cilia.

The olfactory glands are tubuloalveolar serous glands, which deliver secretions via ducts to the surface.

The serous secretions remove odours so that new scents can be smelt.

Pharynx

This part connects the nasal and oral cavities to the larynx and the oesophagus.

It provides a resonating chamber for speech. This is divided into nasopharynx, oropharynx and laryngopharynx.

 

Larynx

This is the passageway of air between the oropharynx and the trachea. It serves as the organ of speech.

The vocal folds are 2 folds of mucosa that project into the lumen of the larynx in an anteroposterior direction.

In each are the vocal ligament and the vocalis muscle.

Intrinsic skeletal muscles join cartilage plates and generate tension in the vocal folds and open and close the glottis.

This is important for pitch.

Extrinsic laryngeal muscles move larynx during swallowing.

Above the vocal folds is the laryngeal ventricle, an elongated recess. Above this are the false vocal cords, or the vestibular folds. These are important for resonance.

The larynx lined by ciliated, pseudostratified columnar epithelium, but the luminal surface of the vocal fold is lined by stratified squamous epithelia.

Trachea

This extends from larynx to the middle of the thorax and divides into two primary bronchi.

The wall of the trachea has 4 layers:

1. Mucosa (ciliated, pseudostratified epithelium and elastic fibre-rich lamina propria);

2. Submucosa (denser connective tissue);3. Cartilaginous layer (C-shaped cartilages);4. Adventitia (binds trachea to other structures).

The trachealis muscle bridges the gap in the cartilage.

 

Mucosa of the Tracheal Wall

The epithelium is similar to respiratory epithelium in other parts of the conducting system.

1. Ciliated cells (remove small inhaled particles from the lungs);2. Mucous cells (lack cilia and look like goblet cells);3. Brush cells (columnar cells that bear microvilli, and the basal surface is in

synaptic contact with an afferent nerve ending so is a receptor cell);4. Small granule cell;

5. Basal cell (serve as a reserve population by maintaining individual cell replacement in the epithelium).

A  thick basement membrane is characteristic of tracheal epithelium. The lamina propria appears as typical loose connective tissue. It is very cellular and contains many lymphocytes,

which infiltrate the epithelium. Furthermore, there are also plasma cells, mast

cells, eosinophils and fibroblasts.

The lymphatic tissue in diffuse and nodular forms.

 

Submucosa of the Tracheal Wall

There is an elastic membrane that marks the boundary between the lamina propria and the submucosa.

The submucosa is loose connective tissue. Diffuse lymphatic tissue and nodular lymphatics are found.

The submucosa also has mucous-secreting acini with serous demilunes. These have ducts that extend to the epithelium (simple cuboidal). This layer ends when the connective tissue blends with the perichondrium of

the cartilage.

 

Adventitia of the Tracheal Wall

The adventitia lies peripheral to the tracheal rings and the trachealis muscle. It contains large blood vessels and nerves supplying the tracheal wall and

also the lymphatics draining it.

Bronchi

The trachea divides into the primary bronchi (extrapulmonary, left and right). The right is wider and shorter than the left. The primary bronchi enter the lung and

become intrapulmonary and branch to give lobar bronchi.

The left lung has 2 lobes and the right lung has 3 lobes. Each lobe receives a lobar bronchus.

The left lung is further divided into 8 bronchopulmonary segments and the right into 10.

Each segment gets a segmental bronchus.

Bronchi have the same structure as the trachea but where they becomes intrapulmonary, the cartilage rings become cartilage plates of irregular shape.

These cartilage plates are arranged to give the circular shape of the bronchi.

As branching occurs plates become smaller and less. Smooth muscle appears upon entering the lung and increases as cartilage

decreases. As there is smooth muscle in the wall of the bronchus, it can be considered to

have 5 layers:

1. Mucosa;2. Muscularis;3. Submucosa;4. Cartilage layer;5. Adventitia.

At 1 mm diameter, the cartilage plates disappear and it becomes a bronchiole.

 

Bronchioles

The bronchopulmonary segments are further subdivided into pulmonary lobules; each supplied by a bronchiole.

Lobules are composed of pulmonary acini. Each pulmonary acinus is made up of a terminal bronchiole, and

the respiratory bronchioles and alveoli it aerates. The respiratory bronchiolar unit consists of a single respiratory

bronchiole and alveoli.

The epithelium changes from ciliated, pseudostratified columnar to simple cuboidal as the size decreases.

The number of glands decreases. Clara cells increase as the ciliated cells decrease in number. These cells produce a lipoprotein (a surfactant) that prevents luminal

adhesion should airway fold on itself. There are small amounts of connective tissue.

Outpocketings of the respiratory bronchiole are the alveoli.

It is here that the gas exchange occurs.

 

Alveoli

Each alveolus is confluent with a respiratory bronchiole by means of an alveolar duct (elongated airways with almost no walls only alveoli) and an alveolar sac(spaces surrounded the alveolus).

Alveoli are separated from one another by a thin connective tissue layer (alveolar septum) with many capillaries.

Alveolar epithelium is composed of:

1. Type I pneumocytes (squamous, 95 % of surface area);2. Type II pneumocytes (secretory, cuboidal cells, 5% of surface area, they bulge

into the lumen and are filled with granules called lamellar bodies which contain asurfactant that is secreted onto the surface of the alveoli to reduce surface tension);

3. The occasional brush cell.

Components of the alveolar septum:

1. Alveolar epithelial cells;2. Basal laminae of alveolar epithelium;3. Basal laminae of the capillary endothelium;4. Endothelial cells;5. Fibroblasts, macrophages, collagen fibres and elastic fibres.

The air-blood barrier is the cells and cell products across which gases may diffuse between the alveolar compartment and the capillary compartment.

The thin portion is for most of the gas exchange and the thick portion is a site in which tissue fluid can accumulate, which is drained by lymphatics of the terminal bronchiole.

Alveolar macrophages remove inhaled particulate matter from the air spaces and red blood cells from the septum.

Collateral air circulation through alveolar pores allows air to pass between alveoli.

Blood Supply

The pulmonary circulation supplies the capillaries of the alveolar septum and is derived from the pulmonary artery.

The bronchial circulation, via bronchial arteries, branches from the aorta and supplies the whole lung.

The 2 circulations anastomose at the level of the junction between the conducting and respiratory passages.

 

Lymphatic Vessels

One set of lymphatic vessels drains the parenchyma of the lung and follows the air passages.

The second set drains the surface of the lung and travels in the connective tissue of the visceral pleura.

 

Nerves

There are parasympathetic and sympathetic divisions of the ANS. These mediate reflexes that moderate the dimensions of the air

passages and blood vessels by contraction of smooth muscle.

Gastrointestinal System II

Gastrointestinal System II

Structural organisation of the alimentary canal

The wall of the alimentary canal is formed by 4 distinct layers:

1. Mucosa2. Submucosa3. Muscularis externa4. Serosa or adventitia

Mucosa

The mucosa of the G.I. tract has a barrier function, secretory function, and an absorptive function.

It is composed of epithelium, lamina propria, and a muscularis mucosa. The epithelium differs throughout the alimentary canal, adapting specifically for

one or more of these functions. The lamina propria has glands, lymphatic and fenestrated vascular vessels to

receive the absorbed substances and an immunologic barrier consisting of:

Diffuse lymphatic tissue, including lymphocytes and plasma cells, which, together with lymphatic nodules, are called gut-associated lymphatic tissue (GALT)

Eosinophils and macrophages

The muscularis mucosa has smooth muscle cells in inner circular and outer longitudinal layers.

There are 4 basic mucosal types in the G.I. tract:

1. Protective - stratified squamous epithelium found in the oral cavity, pharynx, oesophagus and anal canal.

2. Secretory - found in the stomach, where the mucosa consists of long, closely packed tubular glands which may be simple, or branching, depending on the region of the stomach.

3. Absorptive - found in the small intestine, where the mucosa has finger like projections called villi, with intervening short glands called crypts (of Lieberkuhn).

4. Absorptive/Protective - in large intestine, where the mucosa is arranged as closely packed, straight tubular glands with cells specialised for water absorption and mucous-secreting goblet cells for lubrication of the intestine.

Submucosa

This is composed of dense connective tissue, containing larger blood vessels, lymphatics, and sensory, parasympathetic, sympathetic and enteric nerves.

ganglion cells of postganglionic parasympathetic neurons and enteric neurons form the submucosal plexus (Meissner’s plexus)

Glands are present in this region in the oesophagus and duodenum.

Muscularis externa

This is generally arranged as 2 thick layers of smooth muscle, with an inner spiral layer of circular fibres and outer, looser spiral layer of longitudinal fibres.

Between these layers lies the myenteric plexus (Auerbach’s plexus) of the enteric nervous system.

Synchronised rhythmic contractions of these layers, controlled by the enteric nervous system, forms waves of peristalsis, propelling the gut contents distally.

The circular muscle layer thickens along several points of the G.I. tract to form sphincters or valves, including:

The pharyngeoesophageal sphincter The pyloric sphincter The ileocaecal valve The internal anal sphincter

Serosa and Adventitia

The serosa, consisting of mesothelium and loose connective tissue, is the visceral peritoneum of the abdominal cavity, continuous with the mesentery.

Those portions of the tract that are retroperitoneal or lie outside the abdominal cavity attach to adjacent structures via loose connective tissue called adventitia.

The oesophagus

This is a muscular tube extending from the oropharynx to stomach, lined by stratified squamous nonkeratinising epithelium.

The dense lamina propria has diffuse lymphatic tissue and lymph nodules, as well as oesophageal cardiac glands in the terminal part, and are similar to the cardiac glands of the stomach.

Their mucous secretions protect the oesophagus from gastric reflux juices. The muscularis mucosa is composed of longitudinal smooth muscle.

The submucosa forms loose, longitudinal folds, allowing for distension during swallowing, and has oesophageal glands proper along its length, mostly found in the upper half.

These small, compound tubuloalveolar glands are invaginated from the epithelium, and their mucous secretions lubricate the lumen.

The muscularis externa is composed of striated muscle in the upper third, striated and smooth muscle in the middle third, and smooth muscle in the distal third.

It is innervated by both somatic and visceral motor fibres of the vagus (X) nerve. Most of the oesophagus is covered by adventitia, but the abdominal portion is

covered by serosa.

Gastro-oesophageal junction

Here the epithelium undergoes abrupt change from protective, stratified squamous epithelia to tightly packed, glandular secretory mucosa

Other layers are continuous, although there is a physiological sphincter mechanism that helps prevent reflux of gastric juices.

The stomach

This is a very distensible organ with rugae on its internal surface in the collapsed state.

It has a scant lamina propria, between gastric glands. Its muscularis externa is described as having an extra inner layer of oblique

fibres.

It is histologically divided into 3 portions, based on the nature of the glands present in its mucosa:

1. The cardia, near the oesophageal orifice, with cardiac glands2. The fundus (including the fundus and body as defined in gross anatomy),

containing fundic glands3. The pylorus, proximal to the pyloric sphincter, with pyloric glands.

The secretory gastric mucosa consists of simple columnar epithelial cells, called surface mucous cells.

These cells have apical cups of mucinogen granules, and their cloudy mucous forms a thick, protective coating against acid and abrasion.

Gastric secretions come from gastric glands that empty into gastric pits opening onto the mucosal surface, including:

Pepsinogen, the inactive precursor of pepsin Hydrochloric acid (HCl) Intrinsic factor, which is essential to the absorption of Vitamin B12

Hormones such as gastrin, that stimulates HCl secretion

Fundic glands (Gastric glands)

These simple, branched, tubular glands produce the digestive juice of the stomach.

Several glands may extend from one gastric pit to the muscularis mucosa, with a relatively long neck segment and a shorter, wider base.

Cells of the fundic glands include:

1. Mucous neck cells, localised to the neck region, with less prominent mucous cups, that secrete a more soluble mucous compared to that of the surface mucous cells.

2. Chief cells, located deep within the glands, with round, basophilic, basal nuclei and apical zymogen granules containing their secretory product, pepsinogen.

3. Large parietal (oxyntic) cells, mostly in the middle and upper portions of the gland, with round nuclei and an eosinophilic cytoplasm with an intracellular canalicular system, secreting HCl and Intrinsic Factor.

4. Small enteroendocrine (APUD) cells, mostly at the base, with a clearer staining cytoplasm, that secrete the hormone gastrin into the lamina propria.

5. Undifferentiated stem cells.

Cardiac glands

These tubular, somewhat tortuous glands, occasionally branched, are composed mainly of mucous secreting cells, with occasional enteroendocrine cells.

They have a short duct segment, entering into relatively shallow gastric pits.

Pyloric glands

These coiled, branched tubular glands lie in the pyloric antrum and the pylorus, composed of mucous cells, enteroendocrine cells, and occasionalparietal cells.

They empty into very deep gastric pits, half the size of the thickness of the mucosa.

 

Cell replacement is rapid at the epithelial surface, with the mucous secretory sheet being replaced over 3-5 days.

Cells of the gastric glands are renewed at a much slower rate of about once a year.

The APUD cells are endocrine cells found throughout the gastrointestinal mucosa, secreting hormones that act on the same or functionally related parts of the GI Tract.

Food in the stomach leads to secretion of gastrin into blood, causing secretion of pepsin and acid from the gastric glands and increasing gastric motility.

Gastro-duodenal junction

The pyloric sphincter is a notable increase of circular smooth muscle in muscularis externa

The mucosa changes from the secretory glandular arrangement of stomach to the absorptive, villous arrangement of the small intestine with plicae circulares.

The duodenum has unique mucosal glands extending into submucosa called submucosal (Brunner’s) glands.

The Small Intestine

This is the longest component of the digestive tract, whose main function is absorption, and is comprised of the duodenum, jejunum and ileum.

The characteristic feature of the small intestine is the absorptive mucosa, whose surface area is increased by:

Transverse folds of mucosa and submucosa called plicae circulares, most prominent in the duodenum and jejunum.

Finger like projections of mucosa, villi, with a core of lamina propria that contains a blind ending lymphatic capillary, a lacteal, surrounded by myofibroblasts.

Many, many microvilli of the enterocytes, the intestinal absorptive cells, creating a striated border in their apical regions.

The duodenum has a unique feature of branched, tubuloalveolar submucosal (Brunner’s) glands.

Intestinal glands (crypts of Lieberkuhn) are simple, tubular glands, lined with simple columnar epithelium, extending from the muscularis mucosa and opening into the lumen at the bases of the villi.

The lamina propria surrounds the glands, containing cells of the immune system as part of the GALT.

Aggregated lymph nodules are also found in the lamina propria, and are especially prominent in the ileum, called Peyer’s patches.

Strands of smooth muscle extend from the muscularis mucosae into the lamina propria of the villi.

Cells of the mucosal epithelium are found both on the mucosal surface and in the crypts, including:

1. Tall columnar enterocytes, with basal nuclei and a striated border on the apical surface, reflecting their primary function of absorption.

2. Mucous secreting goblet cells, most numerous in the terminal ileum, with basal nuclei and mucinogen granules in the apical cytoplasm.

3. Paneth cells, found in the bases of the intestinal glands, characterised by strongly eosinophilic secretory granules containing the antibacterial enzyme lysozyme.

4. Enteroendocrine cells, mainly in the lower parts of the crypts, with their main secretions being cholecystokinin (CCK), secretin and gastric inhibitory peptide (GIP), that increase pancreatic and gallbladder activity and decrease gastric secretion and motility.

5. M  (Microfold) cells, modified enterocytes covering the lymphatic nodules, characterised by microfolds instead of microvilli, that discharge their absorptions basolaterally, presenting their contents to intraepithelial lymphocytes to aid stimulation of GALT.

6. Intermediate cells, the majority of cells in the lower half of the crypts, that are still undifferentiated, with characteristics of absorptive and goblet cells.

The inner circular layer of the muscularis externa produces local contractions deemed segmentation, whilst the outer longitudinal layer producesperistalsis.

Serosa of the peritoneum lines the small intestine.

All of the mature cells of the intestinal epithelium are derived from stem cells in the lower half of the intestinal crypts, called the zone of cell replication.

Epithelial cells migrate from the crypt onto the villus, with the absorptive and goblet cells lasting about 5-6 days, whilst Paneth cells can last for up to 4 weeks.

Gut Associated Lymphatic Tissue (GALT)

Up to 25% of the gut mucosa consists of lymph nodules, lymphocytes, macrophages, plasma cells and eosinophils in the lamina propria, as well as intraepithelial lymphocytes, as part of the GALT.

Diffuse lymphatic tissue, in co-operation with epithelial cells (especially M cells) samples the antigens in the epithelial spaces, then migrates to the nodules, undergoing transformation into plasma cells and secreting antibodies.

Ileo-caecal junction

The mucosa changes from the villiform pattern of the small intestine to the glandular form of the large intestine.

A thickened extension of the muscularis forms a cone shaped valve emptying into the caecum, the dilated first part of the large intestine.

The large intestine

The large intestine includes the caecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum and anal canal.

The main functions of the colon are reabsorption of electrolytes and water and the elimination of undigested food and waste.

Distinctive features of the large intestine include:

The absence of villi or plicae circulares The outer longitudinal layer of muscularis externa divided into 3 bands,

called taeniae coli

The mucosa has closely packed straight tubular glands, (crypts of Lieberkuhn), extending down to a prominent muscularis mucosa, with thin strands of lamina propria between them.

The glands consist of simple columnar epithelium, invaginated from the lumen, and have 2 main cell types:

1. Columnar absorptive cells, identical to the enterocytes of the small intestine, are the predominating cell type.

2. Goblet cells, more numerous than in the small intestine, and are most prominent in the distal part of the large intestine, as they lubricate the increasingly solid faeces.

Other cells of the small intestine are also found, although Paneth cells are normally absent.

As with the small intestine, epithelial cell turnover times are about 6 days for the absorptive cells and goblet cells, and about 4 weeks for theenteroendocrine cells.

The lamina propria has a thick collagen layer between the epithelium and its fenestrated capillaries that is secreted by pericryptal fibroblasts forming a pericryptal fibroblast sheath.

There are many lymph nodules in the lamina propria, extending into the submucosa, but there are no lymphatic vessels between the colonic crypts.

The muscularis externa consists of the outer, longitudinal taeniae coli, and inner circular fibres at irregular intervals, creating saccules (haustra).

Adventitia attaches the colon retroperitoneally, whilst serosa covers those parts of the colon with a mesentery.

Caecum and Appendix

The caecum is a small blind pouch just distal to the ileocaecal valve. The appendix is a small finger-like extension, with characteristic features of:

Diffuse lymphatic tissue diffusely infiltrating the mucosa and submucosa.

Lymph follicles bulging into the lumen. A  complete outer longitudinal layer of muscularis externa.

Recto-anal junction

The rectum is a short dilated terminal portion of the large intestine, characterised by transverse rectal folds in its upper part.

The rectal mucosa is similar to rest of large bowel, with straight tubular glands, but with even more goblet cells.

The mucosa then changes from simple columnar, to stratified columnar, and finally, stratified squamous epithelium of the anal canal.

The anal canal has longitudinal folds called anal columns.

Branched, straight tubular anal glands in the anal canal can extend into the muscularis externa.

The submocusa contains the anastomosis between branches of the superior rectal artery and the rectal venous plexus, which may enlarge to form internalhaemorrhoids.

The circular layer of the muscularis externa thickens to form the internal anal sphincter.

The stratified squamous epithelium changes to skin, containing sebaceous glands, hair follicles and large apocrine circumanal glands.

The Lymphatic System

The Lymphatic System

The lymphatic system is a specialised form of connective tissue consisting of cells, tissues and organs that react to the presence of potentially harmful (including foreign) antigenic substances.

It includes the thymus, spleen, lymph nodes, lymphatic nodules and diffuse lymphatic tissue, and may be collectively referred to as the immune system.

It is our 2nd  line of defence, after the epithelial covering of the body.

 

Primary Lymphatic Organs and Tissues

The primary (central) lymphatic organs and tissues include the thymus, bone marrow and gut associated lymphatic tissue (GALT).

They are sites of antigen-independent proliferation and differentiation into cells pre-programmed to recognise specific antigens.

These immunocompetent cells then enter the blood and lymph to be dispersed in the connective tissue and penetrate into the epithelia that line the mucosal surfaces.

 

Secondary Lymphatic Organs and Tissues

These are the effector lymphatic tissues. They include the lymphatic nodules, lymph nodes, tonsils and the spleen.

Here lymphocytes undergo antigen-dependent proliferation and differentiation into effector lymphocytes and memory cells.

Lymphocytes

These are immunocompetent cells that have the ability to:

1. Distinguish between molecules of an organism and foreign bodies;2. Inactivating or destroying foreign organisms or toxins, thus providing the

protective response known as immunity.

There are small, medium and large lymphocytes. The medium and mostly small size lymphocytes are found in circulation.

Larger, activated lymphocytes may be found in lymph nodes.

Lymphocytes originate from stem cells in bone marrow. They differentiate, by different routes, into two functional types: T

Lymphocytes (T Cells) and B Lymphocytes (B Cells).

B Cells, T Cells and the Response to Antigens

The immune system responds to antigens in 2 ways:

1. A  cell mediated response;2. And an antibody-mediated or humoral response.

 

B Lymphocytes

These evolve in bone marrow and GALT, and are part of the humoral response.

They will only react with the antigen they have been genetically programmed for.

Once activated by this antigen, they may differentiate and proliferate into either:

Plasma cells, that produce antibodies. The antibody binds, forming an antibody-antigen complex, that may

be phagocytosed by macrophages.

It may also activate a complement system of proteins that bind to foreign cells for lysing or phagocytosis.

Memory cells, which, after exposure to the specific antigen, will be able to participate in a rapid, secondary response with the same antigen.

They do not participate in an initial or primary response.

 

T Lymphocytes

These evolve in the thymus and are part of the cell-mediated or thymus-dependent response to antigens.

Upon interaction with an antigen, they will differentiate and proliferate into memory cells, and 3 types of effector T lymphocytes:

Cytotoxic lymphocytes (killer T cells), the primary effector cells in cell-mediated immunity.

These cells scan the surface of other cells for signs of viral infection or abnormality, killing them if necessary by causing them to lyse.

Helper T lymphocytes, which recognise foreign antigens presented by macrophages.

After this, they release interleukin hormones to stimulate ‘processed’ B cells to produce antibodies.

Suppresser T lymphocytes, that suppress the activity of B cells.

 

Lymphokines and Interleukins

Lymphokines are substances release by lymphocytes on contact with a specific antigen.

These stimulate the activity of monocytes and macrophages in the cell-mediated immune response.

 

Macrophages

These are involved in both types of immune response. They can process and present the antigen to the B cells or helper T cells. Or they can destroy the antigen by digestion after it has been processed by

other cells of the immune system.

Lymphatic Vessels and Lymphocyte Circulation

Lymphatic vessels begin as a network of capillaries in the loose connective tissue, most numerous under the epithelium of the skin and mucous membranes.

Lymphatic capillary walls are more permeable than those of blood capillaries, and thus more readily drain substances from the extracellular spaces of connective tissue.

Lymph vessels pass through lymph nodes in the lymphatic circulation. Here antigens in the lymph are concentrated by dendritic cells and presented

to lymphocytes, leading to the immune response.

These vessels ultimately drain into the thoracic duct, and thence to the bloodstream at the junction of the internal jugular and subclavian veins in the neck.

Lymphocytes reach sites of the body via the lymphatic circulation and enter the lymph nodes.

B cells will migrate to the medulla and the lymphatic nodules of the cortex. T cells migrate to the paracortex.

Lymphocytes are conveyed to and from the lymphatic tissues via the blood vessels.

They recirculate in all tissues except the thymus.

Diffuse Lymphatic Tissue

The alimentary canal, respiratory passages and genitourinary tract are guarded by accumulations of diffuse lymphatic tissue, which are not encapsulated.

Cells of this tissue are found in the lamina propria of these tracts.

They are strategically placed to intercept the entry of antigens, travel to regional lymph nodes, and undergo proliferation and differentiation, with effector lymphocytes, plasma cells and memory cells returning.

Large numbers of plasma cells and eosinophils can be found in the lamina propria of the GIT.

 

Lymphatic Nodules (follicles) and GALT

These are random, localised concentrations of lymphocytes. They are sharply defined, but not encapsulated, and are found mainly in the

walls of the alimentary canal, respiratory passages and genitourinary tract.

There are notable aggregations of these nodules in the alimentary canal, including:

1. The tonsillar ring (of Waldeyer) in the oropharynx, including the pharyngeal, palatine and lingual tonsils;

2. Peyer’s patches in the ileum;3. Aggregations in the caecum and appendix.

The diffuse lymphatic tissues and their aggregations of the alimentary canal form the gut associated lymphatic tissue (GALT).

Lymphatic nodules are also the basic structural unit of the lymph node.

 

Features of a lymphatic nodule include:

1. A  germinal centre. This region develops when a lymphocyte has recognised an antigen, and is an indicator of lymphatic tissue response to antigen. It stains less intensely than;

2. The marginal zone containing smaller lymphocytes.

Lymph Nodes

These are small, encapsulated organs located along the pathway of lymphatic vessels.

They range in size from 1mm - 2cm.

They are filters for lymph on its way to the blood and phagocytose any particulate matter.

Lymph nodes are concentrated in regions such as the axillae, groin, mesenteries, neck, cubital and popliteal fossae.

 

Structure of Lymph Nodes

There is a dense connective tissue capsule surrounding the node. Trabeculae, invade the substance of the node from the capsule.

Reticular tissue, composed of reticular cells and their fibres, forms a supporting meshwork throughout the organ.

Afferent lymph vessels bring lymph to the node, entering at various points on the convex surface of the capsule.

A  single efferent lymph vessel conveys lymph away from the node. It leaves at the hilum, a depression on the concave surface of the node and

gateway for blood vessels and nerves.

The parenchyma of the lymph node consists of:

The core, medulla. It consists of cords of lymphatic tissue separated by lymphatic or medullary sinuses.

These sinuses converge toward the hilum, draining into the efferent lymphatic vessel.

The outer cortex, contain many reticular fibres, lymphocytes, macrophages, plasma cells, and lymphatic sinuses.

Lymphocytes in the outer part of the cortex are organised into nodules. The paracortical zone or deep cortex, adjacent to the medulla, is free of

nodules. Development of this region depends on the supply of T cells, and is thus also

known as the thymus-dependent cortex.

B lymphocytes are mainly in the cortex and medullary cords.

Just under the capsule of the node, there is a subcapsular sinus. This is for the drainage of afferent vessels.

Trabecular sinuses extend through the cortex with the trabeculae, draining into the medullary sinuses.

Within these sinuses, macrophage and reticular cell processes span the lumen of the sinus, forming a criss-crossing meshwork, retarding and filtering the lymph, and trapping any materials for phagocytosis.

Most lymphocytes enter the node via postcapillary venules in the deep cortex. The venules are lined by cuboidal or columnar endothelial cells. It allows lymphocytes to cross the endothelium from the bloodstream, but

prevents the passage of fluid into it.

Lymphocytes may leave the node via the sinuses, and the efferent lymphatic vessel.

The Thymus

The thymus is a bi-lobed organ in the superior mediastinum, anterior to the heart and great vessels.

It develops bilaterally, out of epithelial invaginations from the third oropharyngeal pouch.

The thymus is where stem lymphocytes proliferate and differentiate into T lymphocytes.

The function of the thymus is as the site of maturation of T cells.

The parenchyma of the thymus consists of epithelioreticular cells. These are epithelial cells that have a stellate shape and form a cytoplasmic

reticulum: a framework for the thymic lymphocytes. These epithelioreticular cells correspond to the other reticular cells in

lymphatic tissues, but there are no reticular fibres in the thymus.

Structure of the Thymus

An outer cortex, densely populated with lymphocytes, thus very basophilic. Also, there are many macrophages present for the phagocytosis of 80% of

lymphocytes which are self reacting (programmed for their own antigens).

An inner medulla that stains less intensely, containing larger lymphocytes with more cytoplasm.

Epithelioreticular cells can also be seen here. A distinctive feature of the thymic medulla are thymic or Hassall’s corpuscles,

masses of concentrically arranged epithelioreticular cells, that may be partlykeratinised.

An external capsule of connective tissue which extends trabeculae into the margin of the cortex and medulla.

It contains blood vessels, efferent lymphatic vessels, and nerves. The trabeculae create thymic lobules, which are just cortical caps over

the medullary tissue.

 

Changes of Thymic Structure with Age

The thymus is fully functional at 20 weeks of foetal life. Its features change over time, however, with the progressive

involution of adipose tissue.

Starting in the juvenile, there is isolation of cortical compartments, reduction of cortical and medullary volume, and the appearance of more, larger blood vessels, until the adult thymus is mainly dominated by fat.

 

The Blood-Thymic Barrier

Blood vessels enter the substance of the thymus from the trabeculae, carrying a perivascular connective tissue sheath with them.

This sheath is covered by a basal lamina and another sheath of epithelioreticular cells.

This blood-thymic barrier prevents molecules from passing to the tissue spaces.

The layers of this barrier, from the lumen outwards, are:

1. Capillary endothelium2. Endothelial basal lamina3. A thin perivascular connective tissue sheath containing many macrophages4. Basal lamina of the epithelioreticular cells5. Epithelioreticular cell sheath

The Spleen

The spleen is the largest lymphatic organ, located in the upper left quadrant of the abdominal cavity.

The spleen functions to filter the blood, and react immunologically to blood-borne antigens.

 

Functions of the Spleen

Immune functions include the proliferation of B and T lymphocytes. Also, there is the production of humoral antibodies and

the removal of macromolecular antibodies from blood.

Haemopoetic functions include the formation and removal of blood cells and platelets.

Also, there is the retrieval of iron from red cell haemoglobin, and the storage of blood in some species.

The spleen, however, is not essential.

Structure of the Spleen

There is an external capsule of dense connective tissue. From here, trabeculae extend into the substance of the organ.

This connective tissue also contains myofibroblasts, and is thus contractile.

On the medial surface of the spleen, the hilum allows passage of the splenic vessels, nerves and lymphatic vessels.

The substance of the spleen is known as the splenic pulp. This pulp is divided into white pulp areas, surrounded by red pulp.

 

The White Pulp

This mainly consists of lymphocytes. Branches of the splenic artery course through the trabeculae and then enter

the white pulp, known as the central artery in this region. The lymphocytes aggregated around the central artery in a cylindrical fashion

constitutes the periarterial lymphatic sheath (PALS) of the artery. Lymph nodules in the PALS may displace the central artery from its central

position in the white pulp.

 

The Red Pulp

This has large numbers of red blood cells (RBCs). It consists of splenic sinuses, separated by splenic cords (of Billroth).

The splenic cords are a loose meshwork of reticular cells and fibres, containing blood cells and immunological cells.

Iron is recycled from the phagocytosis of RBCs.

The venous splenic sinuses are special sinuses, lined by extremely long endothelial cells, longitudinally arranged along the vessel, with spaces between them for the passage of blood cells.

Splenic Circulation

The splenic artery branches into the trabecular, the central arteries. The central arteries of the white pulp then branch into penicillar arterioles in

the red pulp. These are actually capillaries, and may be sheathed by aggregations

of macrophages. Blood from these penicilli leaves the vascular system to populate the splenic

pulp, before re-entering the red pulp.

Two theories of circulation through the splenic arterioles exist.

 

Closed Circulation Model

In this model, the splenic arterioles are a "continuous vascular channel". They only empty into the splenic sinuses of the red pulp. The blood then leaves the sinuses before re-entering them.

 

Open Circulation Model

In this model, the arterioles empty directly into the splenic cords. Thus, blood percolates through the reticular meshwork of the pulp. It then only enters the splenic sinuses from the extravascular side.

This model has more supporting evidence than the former.

The Female Reproductive System

The Female Reproductive System

The female reproductive system consists of internal organs, including the ovaries, oviducts, uterus and vagina; external genital structures, and the breasts.

Menarche, the beginning of menstruation in females after puberty, occurs at about age 15.

In the reproductive phase of female life, the menstrual cycle, taken between each menses (the start of bleeding), lasts about 28 days.

Menopause occurs when this cycle eventually ceases, between the ages of 45 and 55.

 

The Ovary

These are paired organs lying on either side of the uterus, next to the lateral pelvic wall.

There are 2 main functions of the ovary:

1. Gametogenesis: the production of gametes. Oocytes are female gametes developing into mature ova; thus this process is known as oogenesis in the female.

2. The production of steroid hormones, including:

  o Oestrogens, that promote growth and maturation of the sex

organs and mammary glands giving mature female characteristics;o Progestogens, that prepare the sex organs (mainly the uterus)

for pregnancy, and the mammary glands for lactation.

These hormones have an important role in the menstrual cycle by preparing the uterus for implantation of a fertilised ovum.

 

Ovarian Structure

The ovary consists of:

 

The Medulla of the Ovary

The medulla, in the central portion It contains loose connective tissue, large blood

vessels, lymphatics and nerves.

 

The Cortex of the Ovary

The cortex, in the peripheral portion. It comprises the bulk of the tissue.

It is lined by a layer of cuboidal germinal epithelium, over a dense connective tissue layer called the tunica albuginea.

The primordial germ cells, however, are of extragonadal origin. The cortex contains ovarian follicles in richly cellular connective tissue stroma. Scattered smooth muscle fibres are present.

At the hilum, the peritoneal fold of mesovarium is continuous with the medulla.

Follicle development

Click here for a diagram of follicular development.

The early stages of oogenesis occur during foetal development. All potential eggs are present at birth, arrested in their development at the first

meiotic division.

During the menstrual cycle, follicular maturation and ovulation continues, but only one oocyte will be released from the ovary.

Most oocytes present at birth are lost through atresia: the death and resorption of immature oocytes.

Thus, although there are some 400,000 follicles at birth, only 400 eggs will be ovulated in the reproductive life span.

Basic types of ovarian follicle include:

1. Primordial follicles, the earliest stage of development;2. Growing follicles, including preantral (primary) and small antral (secondary)

follicles.3. Mature, pre-ovulatory (Graafian) follicles.

 

Primordial follicles

These appear in the third month of foetal development. They are found in the stroma of the cortex just below the tunica albuginea.

They are surrounded by a single layer of squamous follicular cells. The oocyte has a large, eccentric nucleus.

 

Preantral (Primary) Follicles

This is the first stage of the growing follicle. The oocyte enlarges, and the surrounding follicular cells proliferate,

becoming cuboidal.

The zona pellucida, a deeply staining, acidophilic glycoprotein layer is deposited next to the follicular cells by microvilli from the oocyte.

The follicular cells then stratify with an outer columnar layer, becoming known as granulosa cells.

During this proliferation, surrounding stromal cells form the theca folliculi: a connective tissue sheath with 2 layers:

1. The theca interna, an inner, vascular layer of cuboidal secretory cells with luteinising hormone (LH) receptors, that, upon response to LH, synthesise and secrete androgens; the precursors of oestrogen;

2. The theca externa, an outer layer of connective tissue cells, smooth muscle cells and collagen fibres.

A  basal lamina separates the granulosa cells from the theca folliculi. In the process of atresia, this membrane thickens and hyalinises to become

the glassy membrane. The follicle, about 0.2 mm wide, moves deeper into the cortical stroma.

Factors required for oocyte and follicular growth include:

1. Follicle stimulating hormone (FSH);2. Epidermal growth factor (EGF);3. Insulin-like growth factor I (IGF-I);4. Calcium ions (Ca2+ ).

 

Antral (Secondary) Follicles

These follicles have a fluid filled, crescent shaped cavity, the antrum, containing liquor folliculi.

The oocyte, positioned eccentrically, grows no further after reaching a diameter of about 125 micrometres.

The granulosa cells surrounding the oocyte form the corona radiata. This is located in the cumulus oophorus, a mound of granulosa cells

projecting into the antrum.

 

Pre-ovulatory (Graafian) Follicles

The mature follicle has a diameter of about 10 mm.

Near this size, the stratum granulosum becomes thinner.

Spaces between the granulosa cells widen, and the oocyte with its cumulus cells loosens from the others, preparing for ovulation.

The thecal layers become more prominent, with lipid droplets appearing in the cytoplasm of theca interna cells.

LH stimulates these cells to release androgens that are transported to the granulosa cells.

Here, upon the response to FSH, they are converted to oestrogens. This stimulates the granulosa cells to proliferate, increasing the size of

the follicle.

Ovulation

This is a hormone-mediated process resulting in the release of the secondary oocyte from the pre-ovulatory follicle.

This is due to hormonal changes and enzymatic effects occurring in the middle of the menstrual cycle (day 14).

A  surge in the release of FSH and LH is induced in the pituitary about 24 hours before ovulation.

This triggers resumption of the first meiotic division in the primary oocyte, producing two daughter cells:

1. The secondary oocyte, receiving half the chromatin and most of the cytoplasm;

2. The first polar body, which receives little cytoplasm and degenerates.

The granulosa and theca cells then undergo luteinisation and produce progesterone.

The second meiotic division begins immediately.

The macula pellucida (stigma) is the site of rupture of the follicle, and the secondary oocyte with its granulosa cells is expelled, in the process of division.

The oocyte, arrested at metaphase, is transported to the oviduct, where it remains viable for about 24 hours.

If fertilisation occurs, the second meiotic division completes, producing:

1. A  mature ovum with the maternal pronucleus containing a set of 23 chromosomes;

2. The second polar body, which degenerates.

If fertilisation fails to occur, the oocyte then degenerates.

The Corpus Luteum

After ovulation, the follicle collapses, forming the corpus luteum. Connective tissue eventually invades the follicular lumen, and

the granulosa and theca interna cells (luteal cells) become larger, filled with yellow lipid droplets.

There are now 2 types of luteal cells:

1. Large, centrally located granulosa lutein cells, from the granulosa cells;2. Smaller peripherally located theca lutein cells, from the theca interna.

This structure becomes highly vascularised, secreting progesterone and oestrogens, preparing the endometrium of the uterus for implantation.

If fertilisation occurs, the corpus luteum forms the corpus luteum of pregnancy.

If fertilisation does not occur, the corpus luteum of menstruation remains active for 14 days before degenerating and forming a white scar called the corpus albicans.

 

The Ovarian Cycle

This consists of 3 phases:

1. The follicular phase (days 1-14), where follicles develop under the influence of oestrogen;

2. Ovulation (day 14): rupture of the follicle;3. The luteal phase, where the corpus luteum produces progesterone before

degenerating.

The Oviduct

These are paired tubes, also known as Fallopian or uterine tubes. They extend bilaterally from the uterus to the ovaries.

It carries the ova from the ovary to the uterus.

There are 4 parts to the oviduct:

1. The funnel-shaped infundibulum opening into the peritoneal cavity next to the ovary with fringed extensions, called fimbriae, extending towards it;

2. The ampulla, the main part of the tube, which is the site of fertilisation;3. The narrow isthmus, adjacent to the uterus;4. The uterine or intramural part within the uterine wall;

 

The Wall of the Oviduct

This is composed of 3 layers:

1. An external serosa or peritoneum, consisting of mesothelium and loose connective tissue;

2. The intermediate muscularis, consisting of thick, inner circular and thin, outer longitudinal muscle;

3. The inner mucosa, with thin longitudinal folds projecting into the lumen of the oviduct, numerous in the ampulla, but smaller in the isthmus.

There is no submucosa. The simple, columnar epithelial mucosal lining has 2 types of cells:

1. Ciliated cells whose wave is directed toward the uterus;2. Non-ciliated peg cells that secrete oviductal fluid, providing nutrients for the

ovum.

 

Oviduct Transport

At ovulation, the fimbriae are closely apposed to the ovarian surface where rupture will occur.

As the egg is released, ciliated cells in the infundibulum sweep it towards the oviduct, to prevent it from passing into the peritoneal cavity.

The egg is transported to the uterus for about 3 days by both peristaltic muscular activity and ciliary movement.

The Uterus

This is a hollow pear-shaped organ with a thick muscular wall. It is divided into:

1. The large upper body, with the fundus above the uterine tubes;2. The lower, barrel-shaped cervix is separated from the body by the isthmus.

The uterine wall is composed of a mucosa, the endometrium; a muscularis, the myometrium; and an external serosa of visceral peritoneum called the perimetrium.

There is no submucosa.

The myometrium and endometrium undergo cyclic changes each month, constituting the menstrual cycle.

 

The Myometrium

This is the thickest layer of the uterine wall. It consists of 3 indistinct layers of muscle:

1. A  middle muscle layer, the stratum vasculare, containing large blood vessels, with spiralling, interlacing smooth muscle fibres;

2. Outer and inner layers with smooth muscle fibres running down the long axis of the uterus.

In pregnancy, these muscle fibres hypertrophy and divide, and there is an increase in connective tissue.

There are elastic fibres in the outer layer.

 

The Endometrium

This layer proliferates, then degenerates during the menstrual cycle. It has 2 layers:

1. The thick stratum functionale. It is lined with simple columnar epithelium that invaginates into the endometrial stroma to form simple, tubular uterine glands. This layer is sloughed off at menstruation;

2. The basal stratum basale, retained during menstruation, serves as a source for regeneration of the stratum functionale.

 

Endometrial Vasculature

Arcuate arteries in the myometrium, from the uterine artery, branch to radial arteries entering the basal layer of the endometrium.

These branch into straight arteries supplying this layer, and spiral arteries supplying capillaries in the stratum functionale.

This capillary bed contains dilated segments called lacunae. The vasculature in this layer proliferates under the influence of oestrogen,

and degenerates under the influence of progesterone.

The Menstrual Cycle

Click here for a diagram of the menstral cycle.

This 28 day cycle has 3 continuous phases:

1. Menstrual phase (days 1-5), when the corpus luteum degenerates and ovarian hormone production declines. In the stratum functionale, arteries constrict and rupture,surface epithelium is disrupted, constituting vaginal discharge;

2. Proliferative phase (days 5-14), influenced by oestrogen from the ovaries, occurring with follicular maturation. Cells and spiral arteries of the stratum basale proliferate rapidly.

3. Secretory phase (days 15-28). This stage begins with ovulation, with the endometrium swelling under the influence of progesterone from the corpus luteum.

 

The Cervix

The cervix has 2 constricted openings:

1. The internal os at the uterine end2. The external os at the vaginal end. This is the site

of transition between vaginal stratified squamous epithelium in the porto vaginalis, and the mucous secreting simple columnar epithelium of the cervical canal.

The cervical mucosa differs from the rest of the uterine endometrium. It:

1. Lacks spiral arteries;2. Has little change in thickness over the menstrual cycle, and is not sloughed in

the menstrual phase;3. Have large, branched, mucous secreting cervical glands (Nabothian glands).

Normally in the menstrual cycle, the mucous inhibits sperm migration, but duringmidcycle, a lot less viscous mucous is produced, providing a more favourable environment for the passage of sperm and fertilisation.

The cervical epithelial cells are constantly exfoliated into the vagina. These cells can be prepared on a Papanicolaou cervical smear for screening

of lesions related to cervical cancer.

The Vagina

This is a fibromuscular tube extending from the cervix to the vestibule. The vaginal wall consists of:

1. The vaginal mucosa internally, lined by non-keratinised stratified squamous epithelium, with many rugae. Connective tissue papillae from the lamina propria project into this layer. There are no glands here, as the vagina is lubricated by mucous produced by the cervical glands.

2. The intermediate vaginal muscularis, with inner circular smooth muscle and outer longitudinal fibres.

3. The outer vaginal adventitia, with an inner layer of dense fibroelastic tissue, and an outer layer of loose connective tissue.

 

The Mammary Glands (Breasts)

These are modified apocrine sweat glands that develop during puberty.

It is composed of lobes of branched (lobulated) tubuloalveolar glands in subcutaneous tissue, radiating from the nipple.

Each lobule drains into ducts that carry milk to lactiferous sinuses beneath the areola, where it pools before being secreted through the nipple via lactiferous ducts.

The intralobular connective tissue is loose. The dense interlobular connective tissue contains adipose tissue.

The areola becomes pigmented during puberty, increasing after pregnancy. It contains sebaceous glands, sweat glands, and modified mammary

glands (of Montgomery).

Underlying smooth muscle fibres are arranged circumferentially and radially, and longitudinally along the lactiferous ducts.

This facilitates lactation from, and erection of the nipple.

The nourishing, yellow pre-milk released temporarily after childbirth, colostrum, contains many antibodies that provide the newborn with some passive immunity.

The Male Reproductive System

The Male Reproductive System

This consists of the testis, epididymis, genital ducts, accessory glands and the penis.

 

The Testis

These are small, paired, oval structures in the scrotum, weighing about 15 g.

Like the ovary, the functions of the testes are:

1. Gametogenesis. This equates to the production of sperm in the male, and is called spermatogenesis. The optimum temperature for spermatogenesis is about 2 degrees below body temperature. Factors contributing to temperature control include:

o The dartos muscle of the scrotum that pulls the testis closer to the body when it is cold;

o The pampiniform plexus of veins surrounding the testicular artery, providing a countercurrent heat exchange system whereby cooler venous blood returning from the scrotum and testis cools the incoming arterial blood.

The production of androgens, namely the steroid hormone testosterone. These steroid hormones are essential for development of the male foetus, development of secondary sex characteristics in puberty, and the maintenance of sperm production in the adult male.

 

Structure of the Testis

The structure of the testes consists of:

1. A thick connective tissue capsule: the tunica albuginea, with inwardly projecting septa, creating about 250 lobules.

Posteriorly, it thickens and projects inwards to form the mediastinum testes, through which structures enter and leave the testes.

Beneath this layer, a looser tunica vasculosa contains blood vessels. The tunica albuginea is a visceral peritoneal layer that is surrounded

anteriorly by a parietal layer called the tunica vaginalis, with a peritoneal sac between them.

Inner lobules containing long, highly convoluted seminiferous tubules, surrounded by interstitial (Leydig) cells in the stroma.

The tubules straighten out into tubuli recti (straight tubules) before joining an anastomosing channel system in the mediastinum called the rete testis.

 

Leydig (interstitial) Cells

These are large, polygonal, acidophilic cells in the stroma of the lobules.

They may contain lipid droplets and cytoplasmic crystals (of Reinke).

Leydig cells secrete the androgen testosterone that will act inside the seminiferous tubule.

 

Seminiferous Tubules

These tubules are about 50 cm long.

They have a complex, stratified, seminiferous epithelium with 2 cell types:

1. Spermatogenic cells organised as patches of cells in different stages of evolution throughout the tubule. As they mature, they move inwards from the basal lamina(spermatogonia) to the lumen (spermatids).

2. Sertoli cells. These are columnar, non-dividing, sustentacular cells on the basal lamina, with an ovoid or triangular nucleus.

Sertoli cells maintain the overall structure of the tubules and each support a small colony of developing sperm, surrounding them with cytoplasmic processes.

They are bound to each other by Sertoli-Sertoli junctional complexes that form tight junctions.

This divides the seminiferous epithelium into 2 compartments:

1. A  basal compartment containing immature spermatogonia and primary spermatocytes;

2. A  luminal compartment containing mature spermatocytes and spermatids.

It is also the site of the blood-testis barrier, protecting the antigenically foreign haploid sperm from an autoimmune response by circulating antibodies.

The Sertoli cells have an exocrine function, secreting fluid for the passage of sperm, and an endocrine function, including the secretion of:

1. Androgen Binding Protein (ABP), that concentrates testosterone in the tubular lumen for the developing sperm;

2. Inhibin is involved with feedback inhibition of FSH from the anterior pituitary.

Sertoli cells themselves are stimulated by FSH and testosterone.

The seminiferous epithelium is surrounded by lamina propria called tunica propria.

This contains peritubular contractile cells (myoid cells). These cells create peristaltic waves that propel spermatozoa and testicular

fluid toward the excurrent ducts and epididymis.

There are 6 different stages or phases of differentiation of human spermatogonia, called the cycle of the seminiferous epithelium.

The total time required for spermatogonia to reach the stage where they are released as sperm is 74 days.

The patch-like distribution of the stages of differentiation along the tubule is called the wave of the seminiferous epithelium.

Spermatogenesis

This is the process by which 1 spermatogonia develops into 4 spermatozoa (sperm).

It has 3 distinct phases, the spermatogonial phase, the spermatocyte phase, and the spermatid phase.

 

The Spermatogonial Phase

Spermatogonia lie in the basal region of the seminiferous tubule with the Sertoli cells, and have large, rounded nuclei.

Dark type A (Ad) spermatogonia give rise to pale type A (Ap) spermatogonia that are connected by cytoplasmic bridges.

This ensures synchronous development of each clone.

After several divisions, type A cells differentiate into type B spermatogonia.

 

The Spermatocyte Phase (Meiosis)

Type B spermatogonia divide into primary spermatocytes by mitosis. Spermatocytes are characterised by prominent nucleoli, due to cell division.

The primary spermatocytes undergo meiosis, forming diploid, secondary spermatocytes upon the first meiotic division.

Haploid spermatids are formed upon the second meiotic division.

 

The Spermatid Phase (Spermiogenesis)

Spermatids lie in the luminal region of the tubule, and may have elongated nuclei.

They develop into mature spermatozoa by the process of spermiogenesis, as follows:

1. The acrosomal vesicle forms next to the nucleus at the anterior pole.2. The acronemal complex (9+2 microtubule arrangement in the tail) begins to be

synthesised at the posterior pole.3. The acrosomal vesicle spreads over the anterior pole, forming the acrosomal

cap.4. Now the nucleus elongates, moving to the front of the cell whilst

the cytoplasm extends backwards into the tail.5. Finally, the cytoplasm is lost into the tubule, becoming a residual body that

is phagocytosed by Sertoli cells.

6. The sperm, now free of the Sertoli cell, has a head (5 micrometres), neck (5 micrometres) and tail (50 micrometres).

7. Final maturation of the sperm occurs in the tail of the epididymis.

Sperm are stored in the distal portion of the ductus epididymis before ejaculation.

They can live in the male excurrent system for several weeks, but will only survive for 2-3 days in the female reproductive tract.

During this time, they will acquire the ability to fertilise the ovum via capacitation.

This involves the removal and replacement of the glycocalyx components on the sperm membrane.

Intratesticular Ducts

Terminal sections of the seminiferous tubules straighten into tubuli recti (straight tubules), lined only by Sertoli cells.

The tubuli recti then narrow, and become lined with simple cuboidal epithelium that is continuous with the rete testis of the mediastinum.

Cells in the rete testis have a single apical cilium and few apical microvilli.

 

Excurrent Duct System

This consists of :

1. Efferent ductules (ductuli efferentes);2. The ductus epididymis;3. The ductus deferens.

 

Efferent Ductules

About 20 efferent ductules join the rete testis to the proximal portion of the ductus epididymis.

Outside the rete testis, these ducts are highly coiled, forming coni vasculosi that drain into the ductus epididymis.

Efferent ductules are lined by a pseudostratified columnar epithelium, with tall columnar ciliated cells and short, non-ciliated cells with numerous microvilli.

This gives the lumen a "cog-wheel" appearance.

 

Ductus Epididymis

This is the duct of the epididymis, lying posterior to the testis. It has a head, body and tail. Sperm acquire motility and

undergo capacitation here. It is lined by pseudostratified columnar epithelium, containing 3 types of cells:

1. Tall principal cells with numerous, long stereocilia;2. Small, round stem cells on the basal lamina, called basal cells;3. Intraepithelial lymphocytes called halo cells.

The epididymal cells in the proximal portion reabsorb fluids and residual bodies that were not collected by the efferent ductules.

They also secrete substances aiding the maturation of sperm.

A  thin circular smooth muscle layer in the head of the epididymis thickens towards the tail, adding inner and outer longitudinal layers.

Mature sperm are stored in the tail. In ejaculation, the 3 smooth muscle layers force the sperm into the ductus

deferens.

 

Ductus Deferens

This is the terminal portion of the excurrent duct system. It is continuous with the tail of the epididymis.

It ascends in the spermatic cord through the scrotum and inguinal canal and enters the abdomen.

It then descends to the pelvis and ends in the prostatic urethra. Here it enlarges, forming the ampulla, and is joined by the duct of the seminal

vesicle, continuing as the ejaculatory duct through the prostate gland.

This opens into the urethra. Like the ductus epididymis, it is lined by pseudostratified columnar

epithelium with tall columnar cells and rounded basal cells. Its lumen is dwarfed by a very thick muscular coat that contracts

during ejaculation.

Accessory Sex Glands

These include:

1. The seminal vesicles;2. The prostate gland;3. And the bulbourethral glands.

 

The Seminal Vesicles

These are paired, highly folded tubular glands with a muscular and fibrous coat.

Mucosal folds create many sac chambers in the lumen.

They have pseudostratified columnar epithelium that is similar to that of the excurrent ducts.

Its secretory products, under the control of testosterone, include fructose, which is the principal metabolite for sperm.

During ejaculation, contraction of the smooth muscle coat discharges the secretions into the ejaculatory ducts and helps flush sperm into the urethra.

 

The Prostate Gland

This is the largest accessory gland, consisting of 30-50 tubuloalveolar glands arranged in 3 concentric layers:

1. A  mucosal layer, secreting directly into the urethra;2. A  submucosal;3. And peripheral layer.

The last two layers, with the main prostatic glands, open into prostatic sinuses on either side of the urethral crest in the prostatic urethra.

The epithelium of the prostate is generally columnar, although it contains cuboidal, squamous and pseudostratified compartments.

It is under the control of testosterone.

It secretes acid phosphatase, fibrinolysin and citric acid. During ejaculation, these secretions are pumped into

the urethra by contraction of the fibromuscular wall. In older men, prostatic alveoli may contain prostatic concretions (corpora

amylacea). These are precipitated secretory materials appearing as concentric

lamellated bodies.

 

Bulbourethral Glands

The bulbourethral glands (Cowper's glands) are pea-sized, paired structures. They are compound tubuloalveolar glands in the urogenital

diaphragm, resembling mucous secretory glands.

Their ducts pass through the inferior fascia of the urogenital diaphragm (superficial fascia) to join the initial portion of the penile urethra.

Its simple columnar epithelium, also under the control of testosterone, secretes a mucoid fluid that lubricates the penile urethra.

Semen

Semen is the combined product of all the glandular elements of the male reproductive system. It:

1. Contains fluid and sperm from the testis;2. Contains secretions from the epididymis, ductus deferens, prostate, seminal

vesicles and bulbourethral glands;3. Is alkaline, contrasted with the acidic environment of the female vagina.

The average volume of ejaculate is about 3 mL.

 

The Penis

Structure of the Penis

1. Erectile tissue, including 2 dorsal corpora cavernosa (singular = corpus cavernosum), and a ventral corpus spongiosum in which the penile urethra is embedded;

2. A  fibroelastic layer called the tunic albuginea, encapsulating the erectile tissues;

3. An outer layer of loose connective tissue, to which thin skin is loosely attached, except at the glans penis where it attaches tightly;

4. Smooth muscle and many sensory and autonomic nerves are also present.

The corpora cavernosa (and, to a lesser extent, the corpus spongiosum) contain many vascular sinuses.

In the flaccid penis, helicine (spiral) arteries coil outwards from the centrally located deep arteries of each corpus cavernosum.

Blood drains into peripherally located veins.

 

Erection

Erection requires 2 conditions:

1. Increased arterial inflow;2. Decreased venous outflow.

The process of erection occurs as follows:

1. Parasympathetic stimulus causes relaxation of the smooth muscle surrounding the vascular endothelium, causing vasodilation of the helicine arteries;

2. The vascular sinuses of the erectile tissue become engorged with blood from increased arterial inflow, and the penis becomes rigid;

3. The transmural pressure rises, compressing the peripheral veins, thus decreasing venous outflow and amplifying the erectile response.

 

Ejaculation

Ejaculation occurs via sympathetic stimulus. It involves:

1. Intense contraction of the smooth muscle of the epididymis, ductus deferens, seminal vesicles and prostate;

2. Contraction of the striated muscle in the pelvic and urogenital diaphragms (sphincter utherae) to prevent the passage of urine, and the bulbospongiosus;

3. Emission of the seminal fluid.