GIT

Question 1

1- Structure of the tongue, overview of the salivary glands of the oral cavity

2- Structure of compound salivary glands

LIP

Bulk of lip is made up of orbiculus oris muscle (circumoral striated muscle).
External surface of lip is covered by hairy skin with sebaceous and eccrine (merocrine) sweat glands.

Transitional zone (TZ, red portion of lip): pink-red color derives from the richly vascular papillary layer (prominent rete ridge system) of dermis which is covered by a thin, lightly keratinized epidermis. TZ is highly sensitive due to its rich sensory nerve supply. Since TZ is devoid of sebaceous and sweat glands, it requires continuous moistening by saliva to prevent cracking.

Inner surface of lip is covered by oral lining mucosa. It has a thick nonkeratinized stratified squamous epithelium, lamina propria consists of loose CT and underlying submucosa contains labial glands – compound tubuloacinar seromucous glands

Answer 1

The oral cavity:

• Is the first part of the digestive tract
• Its divided into parts by the dental archades:
  
  • Vestibule:
    
    • Ventrally
    • Cheek, lips
  • Oral cavity Proper:
    
    • Dorsally
    • Teeth, gums, tounge, hard palate, soft palate, palatine tonsils, salivary glands
• Function:
  
  • Ingestion, fragmentation and moistening of food
  • Protective barirer- oral mucosa
  • Mastication (chewing) – process, by which ingested food is made suitable for swalloving.
  • The watery component of saliva moistens and lubricates fragmented food, whilst mucus helps bind the food bolus ready for swalloving.

Dont nesicarilly discuss…

The oral cavity is lined by the oral mucosa that consists of

• Masticatory mucosa
  
  • Location:
    
    • Gingiva and hards plate
    • In sites of friction and stress, regions of matication
  • Structure:
    
    • Epithelium
      
      • Stratified squamous, can be keritinized or parakertinized
    • Lamina propria:
      
      • Loose CT with nerves and vessels
      • Forming thick papillae
    • Deep reticular layer: is composed of more dense CT that is attached to periosteum
• Lining mucosa
  
  • Location:
    
    • Lips, cheeks, alveolar mucosal surface, floor of the mouth inferior surfaces of the tongue and soft palate.
  • Structure:
    
    • Epithelium
      
      • Nonkeratinized stratified squamous epithelium
  • Lamina propria
    
    • Loose CT,
    • Papillae - fewer and shorter; blood vessels and nerves.
  • Submucosa
    
    • EXCEPT IN INF. PART OF TOUNGE
    • Distinct underlies the lining mucosa except on the inferior surface of the tongue
    • Contains bundles of collagen and elastic fibers that bind it to the underlying muscle.
    • Submucosa contains the larger blood and lymphatic vessels, nerves, and minor salivary glands
      
      • in lips, cheeks and tongue.
• Specilized mucosa
  
  • Associated with the sensation of taste
  • Restricted to the dorsal surface of the tounge

Tounge:

General:

• The tongue is a freely movable muscular organ
  
  • Covered by a mucous membrane, parts of which are modified to conform to its function as an organ of mastication and taste.
• The core of the tongue consists of connective tissue and interlacing bundles of skeletal muscle fibers and glands
  
  • Two sheets of connective tissue provide the points for the skeletal muscle: lingual septum and lingual aponeurosis.
  • The distribution and random orientation of individual skeletal muscle fibers in the tongue allows for increased movement during chewing, swallowing, and speaking.

General structure

• Tunica mucosa: specilized oral mucosa, containing taste buds
  
  • Epithelium: non keritanized stratifed squamous epithlium
  • Lamina propria: loose connective tissue, projects into lingual papillae
• Lingual aponeurosis
  
  • plate of sense regular connective tissue
• Tunica muscularis: sleletal muscle
• Varations:
  
  • Inferior surface:
    
    • Covered by covering mucosa (meaning it has a layer of submucosa)
  • Posterior part of dorsal surface:
    
    • Does not contain papillae
    • Contians aggrigation of lymph follicles, the lingual papillae

Dorsal surface of Tounge

• Anterior part (two thirds)
• Posterior part (one third)
• Divided by a V-shaped sulcus terminalis (at its apex - foramen caecum).

1- Anterior part of tounge

• Covered by a specialized mucosa:
  
  • The surface is rough and characterized by numerous mucosal projections called papillae
• Filiform papillae
  
  • Smallest and most numerous, brush shaped
  • They cover the entire dorsal surface of the tongue.
  • The tips of the filiform papillae (2, 6) show partial keratinization.
  • (no taste buds)
• Fungiform papillae
  
  • Mushroom shape, covered with nonkeratinized epithelium
    
    • With a broad, round surface of noncornified epithelium and a prominent core of lamina propria
    • Project above the filiform papillae.
  • More numerous at tip of tounge
  • Taste buds are present in epithelium on the dorsal surface of these papillae
• Cricumvallate papillae
  
  • Large, dome shaped structures (8 – 12) anterior to the sulcus terminalis.
  • The lamina propria exhibits numerous secondary papillae that project into the overlying stratified squamous epithelium of the papilla
  • Each papilla is surrounded by furrow
    
    • Ducts of Ebner ́s glands (serous lingual glands) empty their secretion into base of the furrows.
  • Epithelium of the lateral walls contain numerous taste buds.
• Foliate papillae
  
  • Posterior lateral edge
  • Formed by parallel low ridges separated by deep mucosal clefts,
  • Contain taste buds; less developed in human.

2- Posterior part of tounge

• Separated from anterior part by sulcus terminalis
  
  • Located behind the circumvallate papillae and near the lingual tonsils
• Structure:
  
  • Typically exhibits large mucosal ridges and elevations or folds
    
    • That resemble the large fungiform papillae of the anterior tongue.
    • Stratified squamous epithelium without keratinization: covers the mucosal ridges
  • Filiform and fungiform papillae: absent
  • The lamina propria: similar to anterior
  • Under the stratified squamous epithelium:
    
    • Aggregations of diffuse lymphatic tissue
    • Adipose tissue
    • Nerve fibers
    • Bood vessels
• Between lamina propria and skeletal muscle:
  
  • Mucous acini of the posterior lingual glands
    
    • The excretory ducts: open between bases of the mucosal ridges and folds
• Von Ebners glands: Gustatory glands
  
  • Serous glands
    
    • Open into the grooves of the circumvallate papillae
  • Secretions wash out the are, allawing tatse buds to quickly respond to chaging stimuli
• Posterior lingual glands
  
  • Mucous glands, open into grooves make by lingual tonsil
• Lingual tonsil
  
  • The lingual tonsils are aggregations of small, individual tonsils, each with its own tonsillar crypt
    
    • The tonsillar crypts form deep invaginations on the surface of the tongue and may extend deep into the lamina propria
    • Epithelium of crypts is infiltrated by lymphocytes and is transformed into reticular epithelium
  • Lymphatic nodules in the lamina propria
    
    • Some exhibiting germinal centers
  • Tonsils are not demarcated by capsule from the underlying Weber’s glands and lingual muscle.

Inferior surface of tounge

• Is covered by a lining mucosa
  
  • In contrast to dorsal surface the mucosa of the ventral surface of the tongue is smooth.​
• Anterior lingual gland:
  
  • Seromucous gland at apex of toungue, tubuloacinar,
  • The interlobular ducts, pass into the larger excretory duct of the lingual gland that opens into the oral cavity on the ventral surface of the tongu
• Near apex of tounge

EXTRA:

Taste and taste buds

• Embeded in the stratified lingual epithelium
• Diffrentiated visually by their oval shapes and elongated cells (modified columnar) that are arranged perpendicular to the epithelium
  
  • In histological sections: appear as pale stained bodies in epithlium small opening into epithelium suface at apex of taste bus: taste pore
• Cells found in taste buds:
  
  • Neuroepithelium, taste cells
    
    • Elongated cells, from basal lamina to epithellium- taste pore,
      
      • Contain microvilli
      • lighter cytoplasm and a more oval, lighter nucleus.
    • Form base with afferent sensory neurons of facial, glossopharyneal, and vagus nerve
  • Supporting cells
    
    • Less numerous, from basal lamina to epithellium to taste pore, contain microvilli
      
      • Exhibit a darker cytoplasm and a slender, dark nucleus.
    • Dont connect to nerves
  • Basal cells
    
    • Stem cells
    • Are located at the periphery of the taste bud near the basement membrane.
• Taste:
  
  • Chemical sensation; various substances contained in food interact with receptors located on the membrane of microvilli of sensory cells.
  • These cells react to five basic stimuli:
    
    • sweet,
    • salty,
    • sour,
    • bitter,
    • and unami (taste of certain amino acids – e.g., glutamate, aspartate).
  • Some areas of the tongue are more responsive to certain tastes than others.
    
    • Taste buds (TB) at tip of the tongue detect sweet stimuli,
    • TB immediately posterolateral detect salty stimuli, and
    • TB more posterolateral detect sour stimuli.
    • TB of circum- vallate papillae detect bitter and unami stimuli.
  • The general ability to taste as well as the ability to sense specific testes is genetically determined.
  • Stimulation of taste receptors initiates a cascade of reactions:
    
    • activation of receptor-coupled G proteins generates a second messenger response
    • activation of membrane ion channels –
    • release of neurotransmitter, which generate nerve impulses along postsynaptic sensory nerve

Salivary glands, Exocrine glands of digestive system:

• Classifications:
  
  • Into major and minor salivary glands
  • By character of secretion: mucous, serous, mixed
• General product: Saliva ​​
  
  • The primary functions of saliva include:
    
    • Digestion
    • Protection of the mucosa and teeth
    • Immunological defense
    • Transport of soluble flavors to the taste buds
  • Copontnets:
    
    • Fluid compontnet
      
      • Serous part: water, ions, digestive enzymes
      • Mucous part: mucin- coats and moistens food, easing swallowing
    • Cellular component: lymphocytes and commensal bacteria of the oral cvavity

Serous glands:

• Parotid, Von Ebbers glands

Mucous glands:

• Webers glands: glands of posterior posterior surface

Mixed:

• Submandibular, sublingual, labial, buccal, molar, anterior lingual glands

Major salivary glands:

• Paired glands
• Parotid and submandibular are outside of oral cavity
• Produce saliva apon nervous stimmulation, 90% saliva

Parotid

• Large serous gland
• Classified as a compound tubuloacinar gland
• Structure:
  
  • Surrounded by a capsule from which arise numerous interlobular connective tissue septa:
    
    • That subdivide the gland into lobes and lobules
  • Secretory cells that form the serous acini
    
    • Pyramid-shaped cells are arranged around a lumen.
    • Surrounded by thin, contractile myoepithelial cells that are located between the basement membrane and the serous cells
• Pathway:
  
  • Secretory serous acini empty their product →
  • Into narrow channels, the intercalated ducts:
    
    • Simple squamous →
  • Drains into larger striated ducts
    
    • Simple columnar cells that exhibit basal striations →
  • Into the intralobular excretory ducts
    
    • ​That are located within the lobules of the gland, stratified columnar →
  • These ducts join larger interlobular excretory ducts
    
    • In the connective tissue septa: stratified squamous

Submandibular

• Also a compound tubuloacinar gland.
• However, the submandibular gland is a mixed gland,
  
  • Containing both serous and mucous acini
  • With serous acini predominating.
• ​The serous acini are similar to those in the parotid gland
• The mucous acini
  
  • Are larger than the serous acini
  • Have larger lumina
  • Exhibit more variation in size and shape.
  • The mucous cells
    
    • are columnar with pale or almost colorless cytoplasm after staining.
    • Nuclei: flattened and pressed against the base of the cell membrane.
  • Mixed acini (serous and mucous),
    
    • The mucous acini are normally surrounded or capped by one or more serous cells,
    • Forming a crescent-shaped serous demilunes
  • Myoepithelial cells
    
    • ​Surround the serous (I) and mucous (II) acini and the intercalated​ ducts (III).
• The duct system of the submandibular gland is similar to that of the parotid gland.
• The salivary duct (Wharton duct) ends in the sublingual caruncle

Sublingual

• Compound, mixed tubuloacinar gland
  
  • Resembles the submandibular gland
  • Because it contains both serous and mucous acini
• Predominating mucous acini and serous demilunes
• Pathway:
  
  • The intercalated ducts are short or absent
  • The main salivary duct also ends in the Wharton duct (salivary duct of the submandibular gland)
• Function:
• secrete salivary amylase, lysosyme, lactoferrin and a secretory component, which complexes with IgA (produced by plasma cells in the connective tissue), forming a complex that is resistant to enzymatic digestion in the saliva?????

Question 2

Structure of compound salivary glands

Answer 2

Salivary glands

• Part of exocrine glands of digestive system
• Arrises from developing oral cavity epithelium
• Divided into
  
  • major and minor glands
    
    • minor:
      
      • labial, buccal, moral, palatine, lingual (ant, post: gustatory of von ebner, webers glands)
      • in submucousa
  • by secretion: serous, mucous, mixed

​Saliva:

• secretion controlled bu autonomic system
• Fluid compontent:
  
  • serous: water, ions, digestive enzymes
  • mucous: mucin- coats and mositens food,
• Cellular compontent: epithelial cells, lympohocytes, commensal bacteria
• Function:
  
  • moisten oral mucosa
  • moisten dry food
  • medium for dissolved food
  • buffering content of oral cavity
  • digest carbohydrates
  • control bacterial flora of oral caivty
  • sourse of clacium and phosphate ions essentail for tooth development and maintainece
  • immunologic function
    
    • contain IgA, (produced by plasma cells in the connective tissue), forming a complex that is resistant to enzymatic digestion in the saliva
  • Secrete salivary amylase, lysosyme, lactoferrin and a secretory component,

Division according to secretion:

• Serous: parotis, pposterior lingual, gustatoey, (von ebners glands)
• Mucous: root of tounge (webners gkands)
• Mixed: submandibular, sublingual, labial, buccal, molar, ant lingual glands
  
  • mucous accinin have a cap of serous cells that are thought to secrete into highly convuluted intercellular spaces= serous demilunes
    
    • ​depends on the types of fixation- rapid freexing vs conventional fixation

Structure:

• Secratory component
  
  • serous acinus: more spherical
    
    • zygomen granules
  • mucus tubule: more tubular shaped
    
    • mucinogen granules
    • duing fixation usually most, appical portion appears emty
  • (myoepithelial cells)
    
    • contractile, woth numerous processes
• Ducts
  
  • Intercalated ducts: from acinus
    • simple cuboidal epithelium
    • more prominent in salivary glands that produce watry secretion
    • can modify secretory product
  • Striated ducts: (intralobular)
    
    • cuboidal—> columnar epithelium
    • basal striations- numroud infoldings containing mitrochondria
    • Na reabsorbtion
    • K and HCO3 secretion
  • Interlobular ducts:
    
    • columnar gladually changes to pseudostratified stratified cuboidal
  • Main duct: non-k stratified squamous epithelium
    
    • parotid (stensen’s) and submandibular (Wharton’s) duct travel in the CT of the face and neck before penetrating oral mucosa

Parotid

• Largest, serous glands
• facial nerve travels though it

Submandibular

• compound, mixed
• serous acini
• mucinous tubules with serous demilunes

Sublingual

• compound, mixed
• mucinous tubules with serous demilunes - no intercalated ducts

Minor salovary glands:

• in submucosa, enter via short duct and are called by their location: buccal, labial, lingual, palatine

Question 3

Structure of the tooth

Answer 3

General:

• Essential for beggining of digestive process
• Embedded in maxialla and mandible, attached by alverolar porcesses
• Deciduous teeth
  
  • 1st to errupt, 20 overall
• Perminate teeth
  
  • 32
• Tooth type:
  
  • incisors
  • canine
  • premolar
  • molar
• Macrostructure:
  
  • crown
  • neck
  • root
    
    • apical foramen
  • pupl cavity

Microstructure

The three mineralized components of the tooth:

• Enemal
  
  • Hardest sustance in body, ~97% calcium hydroxapatite
  • Acellular minerlized tissue (from epithelium)
    
    • but it is influenced by the salivary glands- substances in saliva
  • Cant be replaced
  • Composed of enemal rods, keyhole shape
    
    • Formed by paralelly arranged hydroxyapatite crystals: enemal crystals
    • interrod enamel – different orientation of HA crystals
    • striation of enamel:
      
      • rythmic growth enamel during development - lines of Retzius, concentric rings
      • different orientation in the course of rods (radial, spiral, radial): lines of Hunter – Schreger??????
  • Produced by inner ameloblasts of enamel organ (ectodermal origin)
    
    • Consists of hexagonal enamel rods (prisms) extended through the entire thickness of enamel, formed by paralelly arranged hydroxyapatite crystals
  • Enamel can be decalcified by acid produced by bacteria. Fluoride added to the hydroxyapatite complex makes enamel more resistant.
  • Mature enamel contains very little organic component, and water
  • *
• Dentin
  
  • 70% hydroxyapatite, 50% dentin
  • secreted by odontoblasts that form an epithelial layer over inner surface of dentine
    
    • odontoblasts- neural crest cells that miagrate into pulp cavity
    • tomes fibers
      
      • cytoplasmic projections running in dential canals twards dentoenimal junstion in the tooths crown and dentino- cementum junction in corwns root ????
  • Dentinal tubules:
    
    • processes of odontoblasts embedded in secreted dentine due to retraction
    • creates “growth lines”
      
      • von ebner
      • and thicker lines of owen
  • is hard CT produced by odontoblasts, their process – Tomes fibers is located in the dentinal tubule (peritubular dentin is highly mineralized)
• Cementum
  
  • Covers the root of the tooth, part that fills into alveolus
  • thin layer of bone like material secreted by cementocytes
  • 65% mineral
  • lacunae and canaliculi contain cementocytes and their processes
  • unlike bone: it is avascular and the canaliculi do not form a netwerk
  • Sharpeys fibers ​
    
    • form a bulk of the peridontial ligament
    • bundles of collagen fibers embedded on the one side in the cementum and on the other side into alveolar bone (plasticity of collagen of periodontal lig. allows orthodontic intervention)
  • Cementum is highly resistant tissue, during corrective tooth movements the alveolar bone is resorbed (action of the pressure) and resynthesized (action of the pull), but the cementum is not

Odontoblasts

• diffrenciate from cells in the periphery of the dental papilla
• secrete organic matric of dentin (more correctly- predentine) , after minirilization- dentine

Other:

gingiva:

periodonteum

Enamel

98% mineral salts, crystals of hydroxyapatite, enamel rods

Dentin

a calcified connective tissue, 72% of mineral component, organic component – collagen fibrils, glycosaminoglycans
is formed by odontoblasts in the pulp cavity, the odontoblast processes (Tomes’s fibers) running in the dentinal tubules
predentin unmineralized dentin

Cementum

has a structure similar to bone covers dentin
cementocytes and cementoblasts

Question 4

General structure of the digestive tube, structure of esophagus

• Function:
  
  • Protection: seperating lumen of alimentary canal from rest of organism
  • Absorption: allows movment of digested nutients, water, electrolytes into blood and lymph
  • Secretion: lubrication, as well as buffering of tract lining and substance

*

Answer 4

GENERAL STRUCTURE OF DIGESTIVE TUBE

• The digestive (gastrointestinal) tract is a long hollow tube that extends from the esophagus to the rectum.
• It includes the:
  
  • Esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (colon), and rectum.
• The wall of the digestive tube exhibits four layers that show a basic histologic organization.
  
  • The layers are:
    
    • The mucosa
    • Submucosa
    • Muscularis externa
    • Serosa or adventitia.
• Because of the different functions of the digestive organs in the digestive process, the morphology of these layers exhibits variations.

1- Mucosa

• Innermost layer of the digestive tube.
• The mucosa has three principal functions:
  
  • Protection, absorption, and secretion.
• It consists of a covering epithelium and glands that extend into the underlying lamina propria (loose connective tissue)
• Epithelium
  
  • Squamous stratified non-keratinizing or simple columnar
  • Glands:
    
    • Types of glands:
      
      • Mucosal: extend into lamina propria
      • Submucosal glands: deliver their secretions directly to the lumen of mucosal glands or via ducts
      • Extramural glands: lie outside the digestive tract and deliver their secretions via ducts that pass through the wall of the intestine to enter the lumen.
        
        • liver and the pancreas
    • The various secretory products
      
      • Provide mucus for protective lubrication,
      • Buffering of the tract lining
      • Bubstances that assist in digestion: including enzymes, hydrochloric acid, peptide hormones, and water
      • Also secretes antibodies that it receives from the underlying connective tissue.
• Lamina propria:
  
  • Loose connective tissue
  • Containing
    
    • Glands, vessels that transport absorbed substances, and components of the immune system.
  • Lympahtic tissue:
    
    • Diffuse lymphatic tissue consisting of numerous lymphocytes and plasma cells
      
      • Gut-associated lymphatic tissue (GALT).
      • In the distal small intestine, the ileum, extensive aggregates of nodules, called Peyer’s patches, occupy much of the lamina propria and submucosa.
    • Lymphatic nodules with well-developed germinal centers.
    • Eosinophils, macrophages, and sometimes neutrophils.
• Muscularis mucosae: smooth muscle
  
  • Arranged in an inner circular and outer longitudinal layer Contraction of this muscle produces movement of the mucosa, forming ridges and valleys that facilitate absorption and secretion.

2- Submucosa

• Contains:
  
  • The larger blood vessels that send branches to the mucosa, muscularis externa, and serosa.
  • Lymphatic vessels and a nerve plexus.
• Enteric nervous system:
  
  • Innervating the smooth muscle layers of the alimentary canal
  • Meissner’s plexus:
    
    • Network of unmyelinated nerve fibers and ganglion cells constitute the submucosal plexus
• Glands occur occasionally
  
  • Present in the esophagus and the initial portion of the duodenum.

3- Muscularis externa:

• Mostly:
  
  • Consists of two concentric and relatively thick layers of smooth muscle.
    
    • Inner layer: circularly oriented layer (tightly arranged)
      
      • Located between the two muscle layers is a thin connective tissue layer.
        
        • Myenteric plexus (also called Auerbach’s plexus)
        • Blood vessels and lymphatic vessels.
    • Outer layer: longitudinally (loose spiral)
  • Contractions of the muscularis externa mix and propel the contents of the digestive tract: peristalsis
• The circular smooth muscle layer forms sphincters at specific locations along the digestive tract.
• Variations:
  
  • Esophagus
    
    • both smooth and skeletal muscle
  • Stomach
    
    • inner oblique, middle circular, outer longitudinal
  • Large intestine
    
    • Part of longutidinal smooth muscle layer is thickened to form 3 disticnt equally spaced longitudinal banks- tenae coli

4- Adventitia OR Serosa

• Serosa
  
  • Serous membrane
  • Consisting:
    
    • Layer of simple squamous epithelium:called the mesothelium,
    • Small amount of underlying connective tissue.
  • It is equivalent to the visceral peritoneum described in gross anatomy
  • The serosa is the most superficial layer of those parts of the digestive tract that are suspended in the peritoneal cavity.
  • As such, the serosa is continuous with both the mesentery and the lining of the abdominal cavity.
• Adventitia
  
  • Parts of the digestive tract do not possess a serosa.
    
    • Lies outside of the peritoneal cavity and is called retroperitoneal.
  • These structures are attached to the abdominal and pelvic wall by connective tissue, the adventitia, which blends with the connective tissue of the wall.
  • Includes:
    
    • Thoracic part of the esophagus
    • Part of the duodenum,
    • Ascending and descending colon,
    • Rectum, and anal canal.

EXTRA:

• Absorption of digested nutrients, water, and electrolytes
  
  • Surface projections greatly increase the surface area available for absorption
    
    • Plicae circulares:
      
      • are circumferentially oriented submucosal folds present along most of the length of the small intestine.
    • Villi:
      
      • are mucosal projections that cover the entire surface of the small intestine, the principal site of absorption of the products of digestion.
    • Microvilli:
      
      • are tightly packed, microscopic projections of the apical surface of intestinal absorptive cells.
      • They further increase the surface available for absorption.

Eosophagus​

• The esophagus is a fixed muscular tube that delivers food and liquid from the pharynx to the stomach.
  
  • Cervical part: in viseral space of neck
    
    • Adventita
  • Thoracic part:
    
    • It is located posterior to the trachea and in the mediastinum
    • Adventitia
  • Abdominal part:
    
    • After descending in the thoracic cavity, the esophagus penetrates the muscular diaphragm.
    • Serosa
• The wall is composed of 4 main layers:
• Tunica mucosa:
  
  • Lamina epithlialis: Stratified squamous epithelium
  • Lamina propria:
    
    • Loose connective tissue
      
      • Containing interwoven fine collagen and elastic fibers, as well as fibroblasts and macrophages.
    • Invaginates the epithelium as papillae
    • Rich in blood vessels and lymphatic vessels.
      
      • Diffuse lymphatic tissue is often seen in this layer
    • Esophageal cardiac glands:
      
      • Small, branched tubular mucous glands
      • At the level of the cricoid cartilage, near the junction with the stomach.
      • They are structurally identical to the cardiac glands in the stomach
  • Muscularis mucosae:
    
    • Consists of bundles of longitudinal smooth fibers.
• Tunica submucosa
  
  • ​Loose CT
    
    • Esophageal glands
      
      • Which are tubular glands of mucous type
      • Secreting an acid mucus to lubricate the epithelial lining of the esophagus.
      • Numerous in the upper part of the eosophagus
• Tunica muscularis
  
  • General organization:
    
    • Inner circular
    • Myenteric plexuses (Auerbach’s plexus
    • Outer longitudinal
  • Upper 1/3: Skeletal muscle from mesenchyme of pharyngeal archs
  • Middle 1/3: Skeletal and smooth
  • Lower 1/3: Smooth
• Tunica adventitia/ serosa

***When the esophagus is empty, the lumen exhibits numerous but temporary longitudinal folds of mucosa.

Question 5

Mucous layer of the stomach

​

Answer 5

Opening:

• Stomach is an expanded part of the digestive tube
• It lies beneath the diaphragm.
• It receives the bolus of macerated food from the esophagus.
• Function:
  
  • Production of chyme= pulpy fluid mix of food
  • By mixing and partial digestion of the food in the stomach by its gastric secretions
• The chyme then passes into the small intestine for further digestion and absorption.

Contains the 4 basic layer of the GIT

• Mucosa
  
  • Epithelial lamina: simple columnar epithelium
    
    • Glands
  • Lamina propria: Loose connective tissue
    
    • Glands, vessels that transport absorbed substances, and components of the immune system.
    • Inner surface: rugae, accomadation of expansion of stomach
  • Muscularis mucosae: smooth muscle
    
    • Inner circular, outer longitudinal
• Submucosa
  
  • The larger blood vessels that send branches to the mucosa, muscularis externa, and serosa.
  • Meissner’s plexus
• Muscularis externa:
  
  • Variartion:
    
    • Inner oblique
      
      • The oblique layer is not complete and is not always seen in sections of the stomach wall
    • Middle circular
    • Outer longitudinal
    • Myenteric plexus (also called Auerbach’s plexus)
    • Peristalsis
  • The middle circular and outer longitudinal layers are continuous with the two muscle layers of the esophagus. At the pylorus, the middle circular layer thickens as the pyloric sphincter
• Serosa
  
  • Serous membrane: Layer of simple squamous epithelium:called the mesothelium

The stomach is divided histologically into three regions based on the type of gland that each contains, the composition of the mucosa layer varries

• Cardia
• Fundus
• Pyloric part
• The esophageal-stomach junction
  
  • Characterized by an abrupt transition from:
    
    • The stratified epithelium of the esophagus
    • To the simple columnar epithelium of the stomach.
      
      • The surface of the stomach also exhibits numerous gastric pits into which open the gastric glands
  • The lamina propria of the stomach, in contrast to that of the esophagus, is seen as thin strips of connective tissue between the tightly packed gastric glands

Mucosa

• Longitudinal submucosal folds, rugae, allow the stomach to distend when filled.
• inner surface of the empty stomach reveals a number of longitudinal folds or ridges called rugae

Gastric glands

• Mucosal surface of the stomach is a simple columnar epithelium that invaginates deeply into the lamina propria.
• The invaginations form millions of gastric pits, each with an opening to the stomach lumen
• The gastric pits lead to long, branched, tubular glands that extend through the full thickness of the lamina propria.

Cells of the gastric glands:

• Mucous neck cells
  
  • Location:
    
    • Present in the neck of gastric glands
    • Interspersed with parietal cells
  • Structure:
    
    • The nucleus is basally located
    • Cubic shape
    • Basal cytoplasm is basophilic,
    • And the apical cytoplasm contains secretory granules.
  • Secretions:
    
    • Mucous neck cells produce an acid mucus.
• Chief cells
  
  • Location:
    
    • Predominant in the fundus of the gland and intermingle with parietal and mucous neck cells toward the neck region.​
  • Structure:
    
    • Low columnar cells
    • Round nucleus
    • Have the typical appearance of protein-producing cells,
      
      • With a spherical nucleus located toward the base,
      • basophilic basal cytoplasm,
      • Apical ectoplasm filled with acidophilic zymogen granules
  • Secretions:
    
    • Secrete inactive pepsinogen
      
      • Which, in the acid medium of the stomach, is converted into the highly active proteolytic enzyme pepsin that is able to hydrolyze protein into smaller peptides
    • Weak gastric lipase (protien)
• Parietal cell
  
  • ​Location:
    
    • Mainly in the isthmus and neck regions, but are also scattered in the fundic region.
  • Structure:
    
    • Characteristically they are large, rounded, or pyramidal cells
    • Central spherical nuclei
    • Extensive eosinophilic cytoplasm.
    • Electron microscopy has shown:
      
      • that the cytoplasm contains numerous mitochondria and intracellular canaliculi, deep invaginations of the luminal surface with associated microvilli.
    • Canalicular system appears as an irregular, pale area.
  • Secretions:
    
    • Formation of hydrochloric acid
      
      • secrete hydrogen and chloride ions seprately which join together in the lumen of the gland to from hydrochloric acid
    • Intrinsic factor (pernicious anemia)
      
      • Castel: for absorbrion of B12 in ileum
    • Produce bicarbonate, which is secreted into blood
• Enteroendocrine cells
  
  • ​Location:
    
    • ​Scattered throughout the stomach and small and large intestines.
    • located between the basement membrane and the epithelial cells of the gastric glands
  • Structure:
    
    • They are usually small pyramidal cells with dense granules in the cytoplasm,
  • Secretion
    
    • Produce gastrin, ghrelin, VIP (vasoactive intestinal peptide), somatostatin
      
      • Regulation function of the digestive tract
  • Closed cells
    
    • Their secretion is regulated by luminal content through neural and paracrine mechanism.
  • Open cells
    
    • Chemoreceptors on the apical membrane (taste receptors for sweet, bitter and umami);
    • Their secretion is regulated by luminal content. thin cytoplasmic extensions with microvilli that is exposed to gland lumen
• Undiffrienciated adult stem cells
  
  • ​Location:
    
    • Isthmus region, bordering on the mucous neck cells or scattered between the parietal cells.
  • Structure:
    
    • Undifferentiated cells have a large, spherical nucleus and pale cytoplasm.
    • They are thought to be precursors of surface epithelial cells in the gastric pits and mucous neck cells.

Types of gastric glands:

• Cardiac
  
  • At junction between eosphagus and stomach, in area of eosophogal orifice
  • Simple, or branched tuboal alveolar mucous gland
  • Connected to shallow pits
  • Contributes to gastric juice and helps prevent eosphageal epithelium against gastric reflux
    
    • Mainily mucous secreting cells with enteroendocrine cells occasionally
    • Dosent contain cheif and parietal cells
• Gastric glands proper/ fundic glands
  
  • In body and fundus
  • Simple, or branched tuboal alveolar mucous gland
• Pyloric glands
  
  • Pyloric glands are branched coiled tubular.
  • They open into deep gastric pits.
  • Secretory epithelium contains mucous cells, interspersed enteroendocrine cells and occasional parietal cells

Question 6

Mucous layer of the small and large intestines

IMPORTANT PARTS GOT DELEATED!!!!!!!!

NEED TO REDO

FUCK

Answer 6

Small intestines:

• Characteristics
  
  • Middle portion of the gastrointestinal tract situated between the pylorus proximally and the ileocecal junction distally
  • Subdivisions:
    
    • Duodenum, jejunum, and ileum
  • Embryology:
    
    • Develops from the distal foregut and midgut
• Function
  
  • Enzymatic breakdown of chyme into monosaccharides, amino acids, and fatty acids (predominantly in the duodenum)
  • Absorption of nutrients and water (predominantly in the jejunum and ileum)
  • Innate immune system and adaptive immune system function

Large intestines:

• Characteristics
  
  • Terminal portion of the gastrointestinal tract
  • Divided into:
    
    • The cecum and appendix, the ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and anal canal.
• Function
  
  • Absorbs water and electrolytes
  • Absorbs vitamins
  • Eliminates feces

Contain the general layers of the GIT:

General overview, before focusing on the mucosa

• Mucosa
  
  • Epithelial lamina: simple columnar epithelium
  • Lamina propria: Loose connective tissue
  • Muscularis mucosae: smooth muscle, inner circular, outer longitudinal
• Submucosa
  
  • Loose CT, Meissner’s plexus
    
    • In duodenum: brunners glands, mucous gland in the extire thickness of submucosa
• Muscularis externa:
  
  • Inner circular
  • Myenteric plexus (also called Auerbach’s plexus)
  • Outer longitudial
    
    • Large intestines: very thin apart from taeniaw coli
• Serosa/Adventita
  
  • Serous membrane
    
    • intraperitoneal parts
  • Adventita:
    
    • Retroperitoneal parts: part of duodenum, addending and desending colon, lower part of rectum

Small intestines: mucosa

*divided into 3 parts:

1- Duodenum

• shortest and widest
• containins openings to pancriatic and bile ducts
• ligment of treitz??
  
  • Circular folds: largest
  • Villi: multiple, leaf shaped
  • Lymph nodules: solitary
  • submucosal glands: Brunner
• Jejunum
  
  • duodenaijejunal flexture
    
    • Circular folds: decreasing in size and number
    • Villi: multiple, long finger like
    • Lymph nodules: solitary
• Ileum
  
  • final segment
  • communication with cecum with illiocecal valve
    
    • Circular folds: massivly reduced in size and number, may be absent
    • Villi: small in number, short and thread like
    • Lymph nodules: solitary and aggregated (peyer’s patchs), located on the side opposite to the mesenteric attachment
      
      • Aggregated lymphatic nodules (200-400, in adulthood the number sinks in about 30-40) located in the submucosa of ileum opposite insertion of the mesentery.
      • Nodules of PP interrupt muscularis mucosae, penetrate lamina propria, erase intestinal villi, and bulge into the intestinal lumen. M-cells are scattered in the epithelium covering PP.

Absorbtion structures:

• Circular folds/ valves of kercking
  
  • perminate transverse folds that contain a core of submucosa
  • circullarly arranged, about 1/2-2/3 around circumfrence of lumen
  • most numerous in distal part of duodenum
• Villi
  
  • projections of mucosa
  • loose CT core
  • covered by simple columnar epithelium, extention of lamina p
  • contains a central binding lymphatic capilary- lacteal
• Microvili of enterocytes with brush border
  
  • give apperance of straighter border

Microstructure

• Tunica mucosa
  
  • Epithelium
    
    • simple columnar
    • 6 types of cells
  • Lamina p
    
    • lymph nodules (GALT component)
      
      • intestinal glnds/ crypts of lieberkuhn
        
        • simple tubular structures
        • extend into lamina p
      • 2 thin layers of smoothe muscle
        
        • inner circular
        • outer longitudinal
        • extend into lamina p of villi
• Submucosa
  
  • submucosal glands: brunners glands
    
    • IN DUODENUM
    • branched tubular
    • alkaline secretions neutralizes acidic chyme released from stomach
• Tunica muscularis
  
  • inner circular, outer longitudinal smooth muscle
  • auernach plx
  • contactions: segmentation and peristalsis
• Serosa

Cells

• Enterocyte
  
  • Enzyme production for terminal digestion and absorption
  • Absorvative cell
  • with microvilli forming straited brush border
    
    • ​core of actin microfillaments ancored to villin “cap: at tip
    • myosin I moclecules connect the actin to the plasma membrane
    • actin ectens into apical cytoplasm and insert into terminal web: network od horizontally orientated contactile microfillaments
    • contaction of terminal web causes spreading of micrivilli, increasing spaces for abdorption
    • enzymes of brush border:
      • Disaccharidases
      • Dipeptidases
      • Aminopeptidases
      • Alkaline phosphatase
      • Enterokinase (activates trypsinogen)
• Goblet cell
  
  • unicellular glands, produce mucus
• M (microfold cell)
  
  • Specialized antigen-presenting epithelial cells.
  • have microfolds rather than microvilli that take up miccroprganisms to
    • Body and lateral surfaces are deeply invaginated by intraepithelial lymphocytes.
    • Endocytose antigens and transport them to the underlying macrophages and lymphocytes, which then migrate to lymph nodes where immune response is initiated.
• Enteroendoctine cell
  
  • Secrete various peptides and represent part of the diffuse neuroendocrine system.
  • Upon stimulation these cells release their secretory granules and their hormones may then exert paracrine (local) or endocrine (blood-borne) effect.
  • Rounded nucleus and clear cytoplasm, their cell body is triangular with its larger side on basal lamina. In the basal cell pole are located secretory granules, which may be detected by specific methods (mainly by immuno- cytochemical) or by use of TEM.
    
    • “closed” in lowe portion, “open” at all levels.
    • activation of taste receptors found on apical membrane of open cells acrivates G protien signaling cascade- resulting the relase of peptides
• Paneth cell
  
  • in base of intestinal glnads
  • basophillic cytoplasm, appilacy numerous secratory granules that are eosinophillic
  • produce antibacterial enzyme lysosomes, phaopholipase A2 and defensins
• Stem cell

Large intestines:

General:

• Last section of digestive tract
• Reabsorption of electrolytes and water and elimination of undigested food and waste
• Divided into colon and rectum
  
  • Cecum: opening of illeum
    
    • illeocecal valve/ bauhins valve
    • veriform appendix- transverse section.
  • Colon:
    
    • assending
    • transverse
    • desending
    • sigmoid
  • Rectum
    
    • rectal ampula
    • anal canal
    • anus

Features of large intensine

• Teniae coli
  
  • 3 narrowed, thick bands of outer longitudinal layer of muscularis externa
• Haustra coli
  
  • outpockets of colonic wall, bwteween adjacent semilunar folds
• Semilunar folds:
  
  • cresent shaped mucosal folds caused by contractions of tunica muscularis
• Omental appendices:
  
  • small pouchs of serosa containing fat

Microstructure:

• Tunica mucosa: smooth surface, without circular folds and no villi; contain long crypts without Paneth cells
  
  • Ep
    
    • Colomnar absorbative cells predominate (4:1) over goblet cells, in rectum it is 1:1
  • Lamina P
    
    • Same as rest of digestive tract, distinctive features:
      
      • GALT, extensivly developed, large lymphatic nodules
  • Lamina muscularis: smooth muscle
• Submucosa: meissner plx
• Tunica muscularis
  
  • segmentation and peristalsis
  • inner circular
  • aurebach plx
  • Outer longitudinal
    
    • teniae coli
      
      • rectum, anal canal and viriform appendix: the outer longitudinal layer of smooth muscle is uniformly thick. w/o teniae
• Serosa

Rectum

• General:
  
  • Rectal ampula
    
    • Transverse folds
      
      • houstons folds
      • missdle transverse folds fo kohlrausch
    • supreatransitional line
  • Anal canal
    
    • Anal transitional zone
      
      • Anal columbs and sinuses
        
        • longitudinal mucosal folds ectending in lowe protion of transitional zone
  • anus

Microstructure:

• T mucosa
  
  • • Rectum is divided into zones according to epithlial lining:
      
      • Coleorectal zone: upper 1/3
        
        • simple colomnar epithelium
      • Supratransitional line: border..
      • Anal transitional zone:
        
        • from simp colum. to stratified to stratified squamous
        • with anal columbs and sinuses
      • Pectinate line:
        
        • border bwtween endiderm of hindgut and ectoderm of protodeum/ rectal amuplla and anal canal
      • Anal squamous zone
        
        • stratified sq non k
      • Ano-cut line: between anal canal and orifice
      • Anal skin:
        
        • stratified sq. keritinized, with hair follicles and openings of glands
• Submucosa
  
  • zona haemorrhoidalis (deep venous plexus)
• T muscularis
  
  • inner circular
    
    • internal anal sphincter
      
      • where circular layer thickens to from internal anal sphincter- from straigted muscle of pelvic floor, at level fo anal transitional zone
  • outer longitudinal layer
    
    • at this level no teniae coli
• T externa
  
  • serosa: superior part of rectum
  • adventita:lower part of rectum
• Ex. anal sphincter
  
  • skeltal muscle fibers, seperated from rectum by a thin layer of adventita
• anal glands
  
  • (extened into submucosa and even muscularis ex), branched, straight tubular glands
• circumanal glands:
  
  • in skin surrounding anal orifice
  • (apocine sweat glands)

Question 7

Pancreas and gall bladder, biliary ducts

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Answer 7

The liver, gallbladder, and pancreas are accessory organs of the digestive tract that deliver their secretory products to the small intestine by excretory ducts.

General Pancreas

• Secondary retroperitoneal organ
• Has endorine and exocrine functions
  
  • Exocrine: creates pancreatic juice
  • Endocrine: islet of langerhan, produce hormones into bloodstream (insulin, glucagon)
• Macro:
  
  • Head (surrounded by duodenum)
    
    • Located within the C-shaped duodenal curvature; contains the pancreatic duct and distal common bile duct.
  • Neck, body
  • Tail (intrapertioneal)
  • Pancreatic duct: empties to the duodenal paillae of vater
  • Acssesory pancreatic duct of santorini

Exocrine pancreas

• > 90% of the pancreas
• Function:
  
  • Produces digestive enzymes that are secreted into the gastrointestinal tract

Structure:

• Capsule:
  
  • Thin, made of loose connective tissue.
  • Interlobular connective tissue septa project from the capsule into the pancreatic parenchyma, organising it into lobules
    
    • Interlobular septa contain:
      
      • Interlobular ducts, blood vessels, nerves, and lamellar (Pacinian) corpuscles
• Parenchyma
  
  • Consists of pancreatic acini
  • Sparsely scattered pancreatic islets surrounded by stroma of loose connective tissue.

Secretory units

• Serous acinar (tubuloacinar) glands= pancreatic acini
  
  • Pyramidal-shaped acinar cells
    
    • Have a broad basal portion and a narrow apical surface that surround a small central lumen.
    • Basal cytoplasm
      
      • With distinct acidophilic zymogen granules in their apical poles.
  • Zymogen granule
    
    • Storage of inactive enzymes: called zymogens or proenzymes.
    • Upon stimulation, the zymogens are activated and the acinar cells release their secretions by way of exocytosis.
    • During exocytosis, the granules merge with the cell membrane and expel their contents into the lumen of the acinus.
  • Centro-acinar cells
    
    • Present in the acinar lumen
    • Flattened epithelial cells with ovoid nuclei and pale-stained cytoplasm
    • Secrete bicarbonate ions into the pancreatic fluid
    • Represent the beginning of the duct system
• Production
  
  • Digestive enzymes
    
    • proenzymes (e.g., trypsinogen, chymotrypsinogen)

Duct system​

• Intercalated duct: simple sq
  
  • Initially lined by centroacinar cells→
  • Longitudinal section, the intercalated duct can be seen as two rows of nuclei
• Intralobular duct: simple cuboidal →
  
  • With a large lumen, is composed of simple columnar epithelium
  • Surrounded by a thin layer of loose connective tissue.
• Interlobular ducts:
  
  • Low columnar epithelium that becomes taller and more stratified as the size of the ducts increases
  • Located within the interlobular connective tissue septa.
    
    • Drain into the main pancreatic duct (of Wirsung),
      
      • Sometimes into the accessory pancreatic duct (of Santorini).
• →Main pancreatic duct
  
  • Travels from the tail to the head of the pancreas:
    
    • Collecting secretions from all the interlobular ducts
  • Hepatopancreatic ampulla (of Vater),
    
    • Merge of pancreatic duct and with the gallbladder’s common bile duct
    • which empties into the descending part of the duodenum at the major duodenal papilla.
      
      • Surrounded by a thickened smooth muscle layer called the sphincter of ampulla (hepatopancreatic sphincter of Oddi).
      • This controls the flow of both the pancreatic secretions and bile into the duodenum.
      • The accessory pancreatic duct (of Santorini), when present, drains the head of the pancreas and empties into the duodenum through the minor duodenal papilla.

EXTRA PANCREAS

• In response to the presence of acidic chyme in the small intestine (duodenum), the release of the hormone secretin stimulates exocrine pancreatic cells to produce large amounts of a watery fluid rich in sodium bicarbonate ions.
  
  • This fluid, which has little or no enzymatic activity, is primarily produced by centroacinar cells in the acini and by cells that line the smaller intercalated ducts.
  • The main function of this bicarbonate fluid is to neutralize the acidic chyme, stop the action of pepsin from the stomach, and create a neutral pH in the duodenum for the action of the digestive pancreatic enzymes.
• In response to the presence of fats and proteins in the small intestine, CCK is released into the bloodstream.
  
  • CCK stimulates the acinar cells in the pancreas to secrete large amounts of digestive enzymes:
    
    • Pancreatic amylase for carbohydrate digestion,
    • Pancreatic lipase for lipid digestion,
    • Deoxyribonuclease and ribonuclease for digestion of nucleic acids,
    • Proteolytic enzymes trypsinogen, chymotrypsinogen, and procarboxypeptidase.
• Pancreatic enzymes:
  
  • are first produced in the acinar cells in an inactive form and are only activated in the duodenum by the hormone enterokinase secreted by the intestinal mucosa.
  • This hormone converts trypsinogen to trypsin, which then converts all other pancreatic enzymes into active digestive enzymes.

Gallbladder

• General:
  
  • Small, hollow organ attached to the inferior surface of the liver.
    
    • When the gallbladder is empty, the mucosa exhibits deep folds.
  • Not a gland
    
    • ​Function:
      
      • Store and concentrate bile produced by liver
    • Bile is released into the digestive tract as a result of hormonal stimulation after a meal.
  • Bile general:
    
    • Bile is produced by liver hepatocytes and then flows to and is stored in the gallbladder.
    • Bile leaves the gallbladder via the cystic duct and enters the duodenum via the common bile duct through the major duodenal papilla, a fingerlike protrusion of the duodenal wall into the lumen.

Wall of gallbladder

• The gallbladder is a muscular sac.
  
  • Tunica mucosa
  • Tunica muscularis
  • Tunica externa: adventitia or serosa.
    
    • Does not contain a muscularis mucosae or submucosa.
• Tunica mucosa
  
  • Simple columnar epithelium
  • Lamina propria:
    
    • Containing collagen and elastic fibers, fibroblasts, and a vascular plexus, some diffuse lymphatic tissue
  • Temporary mucosal folds:
    
    • that disappear when the gallbladder becomes distended with bile.
    • The deep epithelial invaginations can be seen in sections as crypts, called Rokitansky-Aschoff sinuses.
• Tunica muscularis
  
  • Bundles of randomly oriented smooth muscle fibers
  • Interlacing elastic fibers
• Adventitia: covers in places the gallbladder is attached to the liver surface
• Serosa: covers the entire unattached gallbladder surface.

Biliary tract

• The biliary tree is divided into the intrahepatic and extrahepatic bile ducts.
  
  • Intrahepatic Bile canaliculi →intrahepatic bile ductules (canals of Hering) → segmental bile ducts → sectional ducts
  • Right posterior duct/ right anterior duct
• Right posterior and anterior duct connect and form the right hepatic duct (RHD)
• Bile ducts from segment II to IV connect and form the left hepatic duct (LHD)
• The right and left hepatic ducts form the common hepatic duct (CHD).
• ExtrahepaticThe common bile duct is formed by
• Common hepatic duct
• Cystic duct
• Hepatobiliary triangle (Calots triangle)
• An anatomical space formed by the common hepatic duct, the cystic duct, and the lower border of the liver.
• The Calot triangle contains the cystic artery and the cystic lymph node (Lund’s node).
• During cholecystectomy, the Calot triangle must be carefully identified to prevent damage to the cystic artery and extrahepatic biliary system.
• Common bile duct
• Travels in the free edge of the lesser omentum, in the hepatoduodenal ligament
• Posterior to the duodenum and the pancreas
• Connects with the main pancreatic duct
• Drains into the hepatopancreatic ampulla (ampulla of Vater).

Question 8

Liver

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• Adult are normally one cell thick and are separated by sinusoidal capillaries.
• In young individuals up to 6 years of age, the liver cells are arranged in plates two cells thick.

Answer 8

The liver, gallbladder, and pancreas are accessory organs of the digestive tract that deliver their secretory products to the small intestine by excretory ducts.

Liver

• General
  
  • The liver is the largest mass of glandular tissue in the body and the largest internal organ
• Location:
  
  • Under the diaphragm in the right upper abdomen
  • It is divided into right and left lobes by the line of attachment of the gastrohepatic and falciform ligaments.
• Function:
  
  • The liver produces most of the body’s circulating plasma proteins:
    
    • Albumins, lipoproteins, lipoproteins…
  • Several vitamins are taken up from the bloodstream and are then stored or biochemically modified by the liver.
    
    • They include: vitamin A (retinol), vitamin D (cholecalciferol), vitamin K
  • Storage, metabolism, and homeostasis of iron
  • Detoxification of metabolic waste products
    
    • Exocrine function: bile production: is an eof the liver.
  • The endocrine: -like functions of the liver are represented by its ability to modify the structure and function of many hormones pathways.

Structure:

• It is able to filter and process nutrient rich blood from the digestive tract because of its intricate histological arrangement.

Structural Organization of the Liver

• Parenchyma:
  
  • Consisting of organized plates of hepatocytes,
  • Snusoidal capillaries (sinusoids)
    
    • Vascular channels between the plates of hepatocytes.
    • Fenestrated endothelial cells that also exhibit fenestrations and discontinuous basal lamina.
    • Without diaphragms, are present within the endothelial cells (E).Large gaps are present between neighboring endothelial cells
  • Perisinusoidal spaces (spaces of Disse)
    
    • Which lie between the sinusoidal endothelium and the hepatocytes.
    • Contain Ito/ hepatic stellate cells.
      
      • Mesenchymal origin.
      • Function:
        
        • Storage of hepatic vitamin A inside lipid droplets, which is subsequently released as retinol.
        • Also responsible for hepatic fibrosis, since they are the ones secreting large amounts of collagen during liver injury.
        • Production of ECM components deposited in perisinusoidal space and central vein. During cirrhosis IC transform into myo- fibroblasts and become the main collagen-produing cells.
• Stroma:
  
  • Connective tissue, continuous with the fibrous capsule of Glisson.
  • Blood vessels, nerves, lymphatic vessels, and bile ducts travel within the connective tissue stroma.
  • The connective tissue of the stroma is type III collagen (reticulin), which forms a meshwork that provides integrity for the hepatocytes and sinusoids.

Hepatocytes

• Large (20-30 μm) polyhedral polarized cells,
• Rounded nucleus
  
  • Fine chromatin structure and distinct nucleoli
  • (binucleated cells are common)
• Organells:
  
  • Many mitochondria,
  • rER (synthesis of the plasma proteins),
  • Multiple Golgi complexes,
  • Extensive sER (enzymes for degradation and conjugation of toxins and drugs, synthesis of cholesterol and the lipid portion of lipoproteins ),
  • Peroxisomes
    
    • which contain oxidases and catalases. These enzymes are responsible for detoxification reactions taking place in the liver, for example, that of alcohol.
  • Deposits of glycogen, lipid droplets.
• Lifespan of hepatocytes:
  
  • About 5 months; cells are capable of considerable regeneration.
• Basolateral surface of hepatocytes faces sinusoids
• Apical surface of hepatocytes faces bile canaliculi

The adjacent hepatocytes leave a very small space between them known as bile canaliculi which are almost 1.0-2.0 μm in diameter. The cell membranes near these canaliculi are joined by tight junctions.

Liver Lobules

• There are three ways to describe the structure of the liver in terms of a functional unit:
  
  • Classic lobule,
  • Portal lobule,
  • Liver acinus.

1- Classic lobule,

• Six-sided polyhedral prism with portal triads (hepatic artery, portal vein, and bile duct) at each of the corners.
• The blood vessels of the portal triads send distributing branches along the sides of the lobule, and these branches open into the hepatic sinusoids.
• Center of the lobule:
  
  • Terminal hepatic venule (central vein) into which the sinusoids drain.
• The plates of cells radiate from the central vein to the periphery of the lobule

2- Portal lobule

• Emphasizes the exocrine functions of the liver.
  
  • The major exocrine function of the liver is bile secretion.
• Centrer of the portal lobule:
  
  • The interlobular bile duct of the portal triad of the classic lobule.
    
    • Its outer margins are imaginary lines drawn between the three central veins that are closest to that portal triad
• These lines define a roughly triangular block of tissue that includes those portions of three classic lobules that secrete the bile that drains into its axial bile duct.

3- The liver acinus

• Structural unit that provides the best correlation between:
  
  • blood perfusion, metabolic activity, and liver pathology.
• Smallest functional unit of the hepatic parenchyma.
  
  • The short axis:
    
    • is defined by the terminal branches of the portal triad that lie along the border between two classic lobules.
  • The long axis:
    
    • Line drawn between the two central veins closest to the short axis.
  • The hepatocytes in each liver acinus are described as being arranged in three concentric elliptical zones surrounding the short axis
    
    • Zone 1
      
      • Closest to the short axis and the blood supply from penetrating branches of the portal vein and hepatic artery.
      • This zone corresponds to the periphery of the classic lobules.
    • Zone 3
      
      • Farthest from the short axis and closest to the terminal hepatic vein (central vein).
      • This zone corresponds to the most central part of the classic lobule that surrounds the terminal hepatic vein.
    • Zone 2
      
      • Lies between zones 1 and 3 but has no sharp boundaries.
  • The zones, marked 1, 2, and 3, are supplied with blood that is most oxygenated and richest in nutrients in zone 1 and least so in zone 3.

SCHEME OF THE FLOW OF BLOOD AND BILE IN THE HEPATIC LOBULE

• The liver, as an organ, receives blood from two different sources.
  
  • The major one is via the hepatic portal vein (75%)
    
    • Which carries venous blood from the intestines, pancreas and spleen.
      
      • All nutrients and liquids that are absorbed in the intestines enter the liver through the hepatic portal vein, except the complex lipid products, which are transported by the lymph vessels
    • Despite the lack of oxygen, this blood contains high amount of nutrients, endocrine secretions, broken down erythrocytes, but also ingested toxins.
  • The second major source is via the hepatic artery (25%),
    
    • Which brings oxygenated blood to the liver.
• In the sinusoids, the mixed blood flows centripetally toward the central vein
  
  • Hepatic sinusoids: contain Kupffer cells
    
    • Cells of mononuclear phagocyte system.
    • They break down aged erythrocytes
      
      • (iron is used for Hb synthesis)
    • Remove bacteria or debris that may enter the portal blood from the gut
    • Act as antigen-presenting cells in adaptive immunity.
• Bile secreted by hepatocytes goes into bile canaliculi
  
  • Near the periportal space the BC transform into the short canals of Hering interconnected with the interlobuar bile ducts.

Question 9

Hypophysis, structure and function, hypophyseal portal system

Answer 9

ENDORINE SYSTEM

• The endocrine system is a collection of glands.
• These glands secrete a variety of hormones, which travel to specific target organs via the bloodstream.
• Hormones have specific functions such as regulating growth, metabolism, temperature and reproductive development.
  
  • Acts as a signaling pathway,
    
    • Although hormones are slower acting than nerve impulses.

Extra general info for opening:

• The hypothalamus controls the endocrine system
  
  • via several pathways.
  • Direct projections to the posterior pituitary (neurohypophysis),
  • Indirect control over the anterior pituitary (adenohypophysis)
    
    • via projections to the median eminence and via the autonomic nervous system.
• The hypothalamus carries out its control by producing releasing or inhibiting hormones, known as neurohormones.
• The neurohormones produced by the hypothalamus to manipulate hormone production by the pituitary gland include:
  
  • Anti-diuretic hormone (ADH): This increases water absorption in the kidneys.
  • Corticotropin-releasing hormone (CRH): This stimulates the release of corticosteroids by the adrenal glands, regulating metabolism and immune response.
  • Gonadotropin-releasing hormone (GnRH): GnRH stimulates the production of follicle stimulating hormone (FSH) and luteinizing hormone (LH), which combine to maintain ovary and testes functioning.
  • Growth hormone-releasing hormone (GHRH) or growth hormone-inhibiting hormone (GHIH): GHRH prompts the release of growth hormone (GH), whilst GHIH has the opposite effect. In children, GH is essential to maintaining a healthy body composition. In adults, it ensures healthy bone and muscle mass and is involved in fat distribution.
  • Oxytocin: This is involved in the release of breast milk, orgasm, and smooth muscle contraction. It also regulates body temperature by helping to redistribute heat, and sleep cycles as increasing levels of oxytocin are thought to help induce sleep.
  • Prolactin-releasing hormone (PRH) or prolactin-inhibiting hormone (PIH): PRH stimulates the production of breast milk, whilst PIH inhibits it. This can also be seen in males too, although it is a sign of significant health issues.
  • Thyrotropin releasing hormone (TRH): TRH triggers the release of thyroid stimulating hormone (TSH), causing the release of thyroid hormones which regulate metabolism, energy, growth, and development.

Hypophysis (pituitary gland)

• Located in a midline depression of the sphenoid bone (sella turcica) in the middle cranial fossa
• Its a pea size, compound endocrine gland
  
  • The endocrine system is a collection of glands that secrete a variety of hormones, which travel to specific target organs via the bloodstream.
  • Hormones have specific functions and acts as a signaling pathway
    
    • Slower acting than nerve impulses.
  • Hypothalamus=Regulates hormonal pathways and autonomic functions
• Divided into two parts:
  
  • Anterior pituitary gland (= adenohypophysis)
    
    • Rathke ́s pouch (ectoderm of oropharynx)
    • develops from the ectoderm at the roof of the oral cavity of the embryo. These cells migrate dorsally and form Rathke’s pouch.
  • Posterior pituitary gland (= neurohypophysis)
    
    • Actual downgrowth of the diencephalon directly connected to the hypothalamus
    • Neuroectoderm of the floor of the 3rd venticle)

Functional components of pituitary gland

1- Anterior lobe (adenohypophysis), (glandular portion

• Contains typical granular tissue
• Organized in clumps and sepertated by fenestrated sinusoidsl capilarries
• ​Divided by the residual lumen of Rathke’s pouch into two unequal parts.
  
  • The pars distalis is anterior to the lumen, and the pars intermedia is posterior to the lumen.
  • The pars tuberalis is an extension of the pars distalis, enveloping the neural stalk (infundibulum)
• Distal part
  
  • Glandular cells that are arranged in irregular clusters or cords, surrounded by a thin network of connective tissue rich in reticular fibers.
  • Between the clusters or cords are sinusoids, in which the endothelial lining is characteristically fenestrated.
  • Cells: ​
    
    • Descriptions of the cells within the pars distalis were based solely on the staining properties of secretory vesicles within the cells
    • Chromophobe cells, 50%
      
      • Have a light-staining, homogeneous cytoplasm
      • Degranulated cells: either cells that lost their granules or stem cells_​_
      • Are normally smaller than the chromophils.
    • Chromophils
      
      • Secretory cells, store hormones in granules:
      • The cytoplasm of chromophils
        
        • Stains reddish in the acidophils, 40%
          
          • large and round or ovoid in shape. The cytoplasm is packed with small pink or red
          • specific granules, the secretory granules, which are readily stained by acid dyes such as eosin, acid fuchsin, orange G, and azocarmine.
        • And blueish in the basophils 10%​
          
          • Slightly larger in size than the acidophils.
          • The cytoplasm is crowded with small bluish secretory granules when stained with basic dyes (hematoxylin, aniline blue, methylene blue, resorcin fuchsin).
          • These secretory granules also give a PAS-positive reaction.
  • Five functional cell types are identified in the pars distalis on the basis of immunocytochemical reactions:
    
    • Basophils
      
      • Corticotrophs (ACTH)
        
        • Adrenocorticotropic hormone (ACTH): This is involved in the body’s stress response and causes the production of cortisol in the adrenal cortex.
      • Gonadotrophs (LH, FSH)
        
        • Follicle-stimulating hormone (FSH): This causes estrogen production in females, as well as the development of oocytes (immature egg cells). FSH also stimulates sperm production in the testes
        • Luteinizing hormone (LH): LH stimulates estrogen and progesterone production in females, and testosterone production in males.
      • Thyrotrophs (TSH)
        
        • Thyroid-stimulating hormone (TSH): TSH causes hormone production by the thyroid gland.
    • 40% acidophils
      
      • Somatotrophs (GH, eosinophillic granules)
        
        • Growth hormone (GH): Stimulates growth and has an anabolic effect on the body
      • Mammotrophs (prolactin)
        
        • Prolactin (PRL): This stimulates milk production in the mammary glands.
• Intermediate part
  
  • Arranged around vesicles filled with eosinophilic “colloid”, which contains no iodine. (Follicles)
  • Around the vesicles is a thin loose connective tissue that contains blood vessels and fibroblasts.
  • Corticotrophs, basophil (ACTH)
  • Chromophobes, (melanocyte-stimulating hormone)
    
    • Promotes the synthesis of melanin by skin melanocytes, resulting in an increase in skin pigmentation.
• Tuberal part
  
  • An extension of the anterior lobe along the stalklike infundibulum.
  • It is a highly vascular region containing veins of the hypothalamohypophyseal system.
  • predominantly gonadotrophs???
  • The parenchymal cells are arranged in small clusters or cords in association with the blood vessels.
  • Nests of squamous cells and small follicles lined with cuboidal cells are scattered in this region.

2- Posterior lobe (neurohypophysis)

• Neural secretory tissue, NOT ENDOCRINE GLAND!
  
  • Extension of CNS that stores and releases secratory products from hypothalamus
• Infundibulum-
  
  • Continuous with median emincnce
  • Contains neurosecretory axons froming hypothalamo-hypophyseal tracts
• Nervous part
  
  • 1- ​Contains unmyelinated, light-staining axons of secretory cells, whose cell bodies are located in the hypothalamus.
  • 2- Pituicytes (branched glial cells)
    
    • Small cells with rounded or ovoid nuclei
    • Specilized glial cells, similar to astrocytes
    • 3D support network
    • Contain pigmented granules: they are characterized by their cytoplasmic pigment
    • Most of the red-staining nuclei in the pars nervosa are the supportive cell pituicytes
  • Fenestrated capillaries
  • Herring bodies
    
    • Accumulations of neurosecretory material at the end of the axon terminals in the pars nervosa
    • Irregular-shaped, red-staining structures
    • Are closely associated with capillaries and blood vessels
    • Store oxytocin and antidiuretic hormone (vasopressin)
• Functions:
  
  • Involved in the release of two hormones;
    
    • Oxytocin and antidiuretic hormone (ADH).
      
      • Oxytocin
        
        • is involved in childbirth, milk production, and orgasm.
      • ADH, antidiuretic hormone: (vasopressin)
        
        • is important in reducing water loss by decreasing urination and sweating, therefore increasing blood pressure.
  • These hormones are transported down the hypothalamohypophyseal tract to thempars nervosa in association with carrier proteins known as neurophysins.

Hypophyseal portal system: Blood supply

Anterior lobe

• Because the adenohypophysis does not develop from neural tissue, its connection to the hypothalamus of the brain is via a rich vascular network.
• Internal carotid artery → Superior hypophyseal arteries
  
  • Supply the pars tuberalis, median eminence, and infundibulum.
• →These arteries form a fenestrated primary capillary plexus
  
  • In the median eminence at the base of the hypothalamus.
    
    • Secretory neurons that are located in the hypothalamus synthesize hormones that have a direct influence on cell functions in the adenohypophysis.
    • The axons from these neurons terminate on the capillaries of the primary capillary plexus, into which they release their hormones.
• Small venules then drain the primary capillary plexus→
  
  • hypophyseal portal system.
• And deliver the blood with the hormones to a secondary capillary plexus:
  
  • That surrounds the cells in the pars distalis of the anterior lobe.
  • The venules that connect the primary capillary plexus of the hypothalamus with the secondary capillary plexus in the adenohypophysis form the hypophyseal portal system.
• To ensure efficient transport of hormones from the blood to the cells, the capillaries in the primary and secondary capillary plexuses are fenestrated (contain small pores).
• From secondary capillary network→ hypophysial vien →venous flow to cavernous sinus

Posterior lobe

• Has a direct neural connection with the brain.
• As a result, there are no neurons or hormone-producing cells in the neurohypophysis, and it remains connected to the brain by a multitude of unmyelinated axons and supportive cells, the pituicytes.
• CONNECTION WITH HYPOTHALAMUS
  
  • N1: supraoptic and paraventricular nuclei of the hypothalamus→
  • The unmyelinated axons that extend from the hypothalamus into the posterior lobe form the hypothalamo-hypophysial tract
    
    • Neurons in the hypothalamus first synthesize the hormones
    • Hormones transported in neurosecratory vesicles, (herring body is an accumliation of these vesicles)
  • When needed, hormones from the neurohypophysis are directly released into the fenestrated capillaries of the pars nervosa by nerve impulses from the hypothalamus.
  • Inferior hypophyseal arteries→ capillary network → hypophysial vein

Question 10

Structure and function of the thyroid gland and parathyroid gland

↑↑↑↑↑ → ↓

Answer 10

Opening

• Thyorid galnd is apart of the endocrine system
• The endocrine system is a collection of glands.
  
  • These glands secrete a variety of hormones, which travel to specific target organs via the bloodstream.
  • Hormones have specific functions such as regulating growth, metabolism, temperature and reproductive development.
  • The endocrine system acts as a signaling pathway,
    
    • Although hormones are slower acting than nerve impulses.
    • Endocrine signals can last from a few hours to a few weeks.
    • The main control center for the organs in the endocrine system is the hypothalamus in the brain.

Thyroid General:

• Location: Anterior neck region, anterior surface of neck at levels C5-T1
• Structure: left lobe, right lobe, isthmus (connects the lobes)
  
  • pyramidal lobe often extends upwards
  • Thyroid follicle is the functional unit of the glands
• Function: regulates metabolysm (by enhancing it)
• Hormones: thyroxine (T4), triiodthyronine (T3), calcitonine
• Embyology
  
  • Develops from endoderm of the
  • Follicular cells: endodermal base, floor of primitive pharynx.
  • Parafollicular cells: endoderm 4th pharyngeal arch, neural crest

Structure:

• The thyroid gland is encapsulated by:
  
  • Pretracheal fascia (false/surgical capsule)
  • The gland is highly vascularised. The arteries supplying it are the superior and inferior thyroid arteries, which lie between the fibrous capsule and the sheath of fascia. Venous drainage of the gland is via the superior, middle and inferior pairs of thyroid veins, which form the thyroid plexus of veins. Innervation is from the cervical sympathetic ganglia, as well as parasympathetic fibers from the vagus nerves.
• True capsule: (Internal capsule):
  
  • An inner connective tissue covering that cannot be separated from the gland
  • Forms septae, dividing the gland into lobes and lobules.
  • Attached to the cricoid cartilage and tracheal rings by dense connective tissue
• Stroma: Interfollicular spaces are filled by
  
  • Reticular connective tissue,
  • Fenestrated capillaries (facilitate the release of hormones into the blood),
  • Lymphatic vessels, adipocytes, and sympathetic nerves.
• Paranchyma:
• Lobules of thyroid gland
  
  • Further subdivide the gland into irregular lobular units
  • Each lobule contains a cluster of follicles, which are the structural and functional units of the thyroid gland.
• Thyroid follicles
  
  • Smallest functional units
  • Function: hormone production and storage
  • Spheric, vesicular components of the thyroid gland lined with epithelium
  • Follicular lumen (central cavity)
    
    • Filled with colloid: storage of the thyroid hormone precursor thyroglobulin
  • Cells in epithlium: follicular epithlium, and C cells

1: Thyroid epithellial cells: follicular cells

• Resting on basal lamina
• Simple epithelium
• Low columnar, cuboidal or squamous cells
  
  • Depending on the level of activity of the follicle.
  • When they are active, they appear cuboidal to low columnar, but when they are inactive the cells are squamous.
• Function
  
  • Synthesize, secrete, and store thyroglobulin and thyroid peroxidase
    
    • Stored in iodine-rich, gelatinous thyroid colloid
  • Produce hormones thyroxine (T4) and tri-iodothyronine (T3): thyroid hormones
    
    • Transport iodine and amino acids from blood: on their basolateral side from blood
    • Iodination of thyroglobulin in colloid
    • Formation of T3 and T4 by oxidative coupling reaction
  • Regulate basal metabolism of cells and are necessary for normal intrauterine development

2: C (clear) cells, parafollicular cells

• Originate in the neural crest.
• Occurrence:
  
  • Along the basement membrane of the thyroid epithelium
  • Or between thyroid follicles in the interfollicular space,
  • No direct contact with the follicular lumen
• Function: Hormone production and storage in granules
  
  • Calcitonin
    
    • Regulates calcium metabolism and inhibits bone resorption
    • Antagonist to parathyroid hormone
    • This hormone aide in the regulation of blood calcium levels by downregulating bone resorption (breakdown of bone and subsequent release of minerals into the blood) and limiting calcium reuptake in the kidneys.
  • Also secretes several neuroendocrine peptides in smaller quantities such as serotonin, somatostatin, dopamine, TRH, and motilin

***Colloid:

• Substance which is secreted and stored by the follicular cells.
• In H.E.-stained preparations, the colloid appears pink and structureless, often showing spaces between colloid and epithelium, and vacuoles within the colloid; these are artifacts of fixation.
• Thyroglobulin
  
  • ​Principal component, inactive storage form of tyroid hormones
  • ionated glycoprotien, 120 thyrosine resisues
    
    • active thyroid hormones are liberated from thyroglobulin and released into capillaries

EXTRA:

Thyroid hormone production

1. Synthesis of thyroglobulin: Thyrocyte → follicular lumen

• Thyroglobulin (TG) is produced in the rough ER of the follicular cells.
• TG is packed in vesicles in the Golgi apparatus.
• TG is released into the follicular lumen via exocytosis.

2. Uptake of iodide: Blood vessel → thyrocyte → follicular lumen

• Basolateral transport
• Na+/I−-symporter: Uptake of iodide by thyrocytes
• Apical transport
• Pendrin: Iodine diffuses to the apex of the cell and is transported into the follicular lumen via the Pendrin transporter.

3. Iodination of thyroglobulin: In follicular lumen

4. Storage: Bound to thyroglobulin in lumen

5. Release: Thyrocyte → fenestrated capillary network

• Reuptake of iodinated TG in thyrocytes via endocytosis
• Fusion of endocytosis vesicles with lysosome
• Proteolytic enzymes cleave TG to release T3, T4, DIT, and MIT
• T3 (∼ 20%) and T4 (∼ 80%) are released into the blood (via the MCT8 transporter)
• Deiodinase removes the iodine from the MIT and DIT
• Iodine is then redistributed to the intracellular I- pool (iodine salvage).

Physiological effects of thyroid hormones

• ↑ Basal metabolic rate (↑ oxygen consumption, and ↑ body temperature)
• Stimulation of carbohydrate metabolism
• Anabolism of proteins
• lipolysis or liponeogenesis depending on metabolic status
• Permissive effect on catecholamines (particularly via β receptors)
• In children: stimulation of bone growth
• CNS effects
  
  • Perinatal period: maturation of the brain (therefore, hypothyroidism screening is very important!)
• Adulthood:
  
  • Hyperthyroidism: hyperexcitability, irritability
  • Hypothyroidism: somnolence, slowed speech, impaired memory
• Reproductive effects
  
  • Fertility
  • Ovulation and menstruation

Parathyroid

• Characteristics
  
  • There are four, oval-shaped endocrine glands embedded in the posterior surface of the thyroid gland
    
    • Two superior parathyroid glands: located near the superior pole of the thyroid gland at the junction of cricoid and thyroid cartilages.
    • Two inferior parathyroid glands: located in the area between the inferior poles of the thyroid lobes and the superior mediastinum.
• Function:
  
  • Secretion of parathyroid hormone (PTH) in response to low calcium serum levels
  • Development:
    
    • Endodermal cells from 3rd and 4th pharyngeal pouchs
    • Principal cheif cells diffenciate during embryonic development and are functionally actuve in regulating fetal calcium metabolism
    • Oxyphy cells diffrenciate later at puberty

Structure:

• Fibrous capsule: merges with fibrous capsule of thyroid gland
  
  • From the capsule, delicate connective tissue strands pass into the parenchyma carrying blood vessels and nerve fibers.
  • The glandular cells do not form definite lobules, but form cords that are supported by delicate reticular connective tissue.
• Stroma:
  
  • CT, blood and lymph vessels, fibrocytes,
  • lipid droplets which increase in age
    
    • ​At adulthud consits about 1/3
• Parenchyma: 2 types of cells arranged to form trabecula/ small nodules
  
  • Oxyphil cells
    
    • Red/pink cytoplasm; function not clear
      
      • Minor
      • Scattered among the chief cells as single cells or small groups.
      • Acidophillic cytoplasm: Contain more cytoplasm than cheif cell
    • No secratory vessicles
    • Only beggin to appear aound puberty
  • Chief cells/ Principal cells
    
    • More numerous
    • Polyhedral in shape, and have a spherical nucleus and a pale-stained, light cytoplasm.
      
      • 7-10 um diamerter, small
      • Pale, slighlty acidophillic cytoplasm
      • Contains lipofusin vessicles, large accumlation of glycogen and lipid droplets
    • Function:
      
      • Synthesis and storage of PTH

PTH: causes levels of calcium in blood to increase

• Action on bone tissue
• Kidney:
  
  • reabsorbtion at distal tubule
  • conservation of vitamin D?

See calcium homeostasis (PTH increases serum calcium and decreases serum phosphate)

• High extracellular calcium → activation of calcium-sensitive receptors → ↓ PTH excretion
• Low extracellular calcium → inhibition of calcium-sensitive receptors → ↑ PTH excretion

Question 11

Structure and function of the adrenal gland and pancreatic islets

→ δ

Answer 11

Overview

• The adrenal gland is a paired retroperitoneal organ located on the upper pole of each kidney.
• They have a flattened triangular shape and are embedded in the perirenal fat at the superior poles of the kidneys.
• Have separate and distinct embryologic origin, structure, and function
• Embryology: Parenchymal cells of the cortex and medulla are of different embryologic origin.
  
  • Adrenal cortex: derived from mesoderm, mesodermal mesenchyme
  • Adrenal medulla: derived from the neural crest cells that migrate into the developing gland
• Function
  
  • Adrenal cortex: outer layer that produces steroid hormones
  • Adrenal medulla: inner part of the gland that produces catecholamines

The parenchymal cells of the adrenal cortex are controlled in part by the anterior lobe of the pituitary gland and function in regulating metabolism and maintaining normal electrolyte balance

• The adrenal glands are covered with a thick connective tissue capsule from which trabeculae extend into the parenchyma, carrying blood vessels and nerves.
• The secretory parenchymal tissue is organized into two distinct regions
  
  • The cortex is the steroid-secreting portion. It lies beneath the capsule and constitutes nearly 90% of the gland by weight.
  • The medulla is the catecholamine-secreting portion. It lies deep to the cortex and forms the center of the gland.

Structure:

1- Adrenal cortex: *originates in mesodermal epithelium*

• Surrounded by a fibrous capsule: dense connective tissue.
• Steroid secreting portion
  
  • Secretory epithelium is organized in cords surrounded by dense capillaries.

Layers of the cortex

• Zona glomerulosa
  
  • Description:
    
    • Pyramidal cells arranged in irregular, ovoid clumps
    • Surrounded by delicate connective tissue surrounded by numerous sinusoidal capillaries
    • The cytoplasm of these cells stains pink and contains few lipid droplets.
  • Function:
    
    • Mineralocorticoid synthesis, (principally aldosterone)
    • Which control water and electrolyte balance by the regulation of the sodium and potassium ion level.
    • secretion of aldosterone is independent of ACTH????​
• Zona fasciculata
  
  • Description:
    
    • Widest cell layer
    • Large, polyhedral cells arranged in long, radial cords usually two cells wide.
      
      • Round, centrally located nuclei
      • Well developed SER, mitochondria with tubular crists
      • Numerous lipid droplets (spongiocytes), pale-stained cytoplasm ​
    • These cords are perpendicular to the surface of the gland, and separated from one another by parallel capillaries.
  • Function:
    
    • Glucocorticoid synthesis (hydrocortisone and cortisone).
    • Secretion of this class of hormones is controlled by the hypothalamus via the anterior pituitary hormone ACTH.
    • Glucocorticoids have wide-ranging effects, such as those on the metabolism of carbohydrates, proteins, and lipids, as well as on suppressing the immune response.
• Zona reticularis
  
  • Description:
    
    • Arranged in an irregular netlike formation surrounded by connective tissue and capillaries
      
      • form anastomosing cords surrounded by sinusoidal capillaries.
    • Smaller and darker than those of the adjacent zona fasciculata
    • Cytoplasm has accumulations of lipofuscin pigment granules.
  • Function:
    
    • Androgens and some glucocorticoids
      
      • Seroid sex hormones, including both female sex honnones (estrogen and progesterone) and several androgenic hormones that are not of physiological significance.

2- Adrenal medulla

• At the center of the organ
• The medulla is not sharply demarcated from the cortex.
• Chromaffin cells
  
  • Originate in the neural crest and migrate to the paraganglia and adrenal medulla during embryonic development.
  • Contain granules
  • Are arranged in clusters or cords.
  • Function:
    
    • They synthetize and relase catecholamines adrenaline and noradrenaline (epinephrine and norepinephrine).
    • Noradrenaline producing cells
      
      • Contain electrondense secretory granules
    • Adrenaline producing cells
      
      • Secretory granules in are smaller and contain fine moderately eosinophilic material.
• Sinusoidal capillaries drain the contents of the medulla into the prominent medullary blood vessels
• Ganglion cells
  
  • Are also present in the medulla.
  • Their axons extend peripherally to the parenchyma of the adrenal cortex to modulate its secretory activity and innervate blood vessels, and extend outside the gland to the splanchnic nerves innervating abdominal organs.
• Hormones of the adrenal medulla: catecholamines
  
  • General
    
    • Catecholamines: norepinephrine, epinephrine, dopamine
  • Site of synthesis
    
    • Regions of the CNS
    • Chromaffin cells of the adrenal medulla
    • Postganglionic adrenergic neurons
• Stimuli
  
  • Sympathetic activation (“fight and flight”)
  • Cortisol from the adrenal cortex
• The cytoplasm of the secretory cells of the medulla appears clear.
  
  • After tissue fixation in potassium bichromate: called the chromaffin reaction,
    
    • Fine brown granules become visible in the cells of the medulla.
    • These granules indicate the presence of the catecholamines epinephrine and norepinephrine in the cytoplasm.

Blood supply:

• Superior suprarenal artery (from the inferior phrenic artery)
• Medial suprarenal artery (from the abdominal aorta)
• Inferior suprarenal artery (from the renal artery)
• Branch before entering the capsule into capsular capilaries →
  
  • Cortical arteries→ subscapular plexsus: in glomerulosa zone, and fasculata zone→ adrenocortical sinusoids →adrenomedullary collecting viens, reticularis zone→ central vien →
  • Perforating arteries (medullary arteries)→ medullary capillaries →central vien→
• →Suprarenal vien
  
  • Fernestrated cortical sinusoidal capillaries
    
    • Supply cortex and drain into fenestrated medullary capilary sinusoids

Pancreatic islets

Pancreas general:

• The pancreas is a glandular organ located in the retroperitoneum between the duodenal curvature and the splenic hilum.
• Has two functional structures:
  
  • The exocrine acinar glands
    
    • Produce digestive enzymes, which are secreted into the duodenum
    • Produces bicarbonate, which neutralizes chyme
  • The endocrine: pancreatic islets.
    
    • Produce blood glucose-regulating hormones such as insulin and glucagon, which are secreted into the blood.

Endocrine pancreas: is called the pancreatic islet

• Because it is separated from the cells of the exocrine pancreas by a thin connective tissue capsule.
  
  • Does not contain excretory ducts.
  • Instead, it is highly vascularized, and all of the secretory products leave the pancreatic islet via numerous blood vessels (capillaries)

Cells of endocrine pancreatic islet

• General structure: filled with reticular connective tissue and fibers, and fernistrated capillaries
• Highest concentration in tail
• Islet of Langerhans stained by the VPL
  
  • (Victoria blue, phroxin, and light green) method,
  • Highlighting cells of three types: alpha, beta, and delta celis, which possess 20%, 75%, and 5% of the islet cell population, respectively.
  • All the nuclei are stained pink.

1- Alpha cells, 15-20%

• Staining:
  
  • Pink and are usually located in the peripherally of the islet.
  • Their granules are more uniform in size,
• Secrete:
  
  • Glucagon:
  • Raises the plasma glucose concentration by stimulating the release of glucose from the liver via glycogenolysis.
    
    • Catabolic effect (opposes the effects of insulin)
    • ↑ Gluconeogenesis
    • ↑ Glycogenolysis
    • ↑ Lipolysis
    • ↑ Ketogenesis

Beta cells, 70%

• Staining:
  
  • With this method are filled with blue secretory granules in their cytoplasm.
  • Most commonly located in the central part of the islet.
• Secretion:
  
  • Insulin
  • Promotes glucose uptake from the blood and the conversion of glucose to glycogen by cells, especially hepatocytes and skeletal myocytes. The effect of insulin is thus to lower plasma glucose levels.
    
    • Anabolic effect
      
      • ↑ Glucose uptake in skeletal muscle and adipose tissue
      • ↑ Glycogenesis
      • Lipid synthesis
      • Protein synthesis in skeletal muscle
      • K+ uptake into cells
      • Renal Na+ retention
      • ↓ Lipolysis (adipose)

Delta cells, δ-cells, 5-10%

• Staining
  
  • Pale-staining appearance, without any granules.
  • Located diffusely throughout the islet but most commonly in the periphery
• Secretion:
  
  • Somatostatin, which may inhibit the secretion of both glucagon and insulin, and diminish the mobility of the stomach, small intestine, and gallbladder.
    
    • ↓ Insulin and glucagon secretion
      
      • ↓ Growth hormone secretion
      • ↓ Gastric acid and pepsinogen secretion
      • ↓ Pancreatic and small bowel fluid secretion
      • ↓ Gallbladder contraction → ↓ Biliary drainage
      • Splanchnic vasoconstriction
      • Analog: octreotide

PP cells, (pancreatic polypeptide) cells, <5%

• They are mostly located within the head of the pancreas.
• Secretion
  
  • Pancreatic polypeptid
    
    • ↑ Gastric secretion of gastric acid
    • ↓ Pancreatic exocrine secretions
    • Promotes satiety
  • Stimulation: fasting
  • Inhibition: intake of food

Endocrine Gland: Pancreatic Islet

An example of an endocrine gland is illustrated as a pancreatic islet from the pancreas. The pancreas

is a mixed gland, containing both an exocrine portion and endocrine portion. In the pancreas,

the exocrine acini surround the endocrine pancreatic islets (A and B).

The structure and function of other endocrine organs (glands) are presented in greater

detail in Chapter 18.

Endocrine and Exocrine Pancreas

A photomicrograph of pancreas shows a mixed gland with both endocrine and exocrine portions.

The exocrine pancreas (3) consists of numerous secretory acini that deliver their secretory material

into the excretory duct (1), which is lined by simple cuboidal epithelim and surrounded by a layer

of connective tissue. The endocrine pancreas (5) is called the pancreatic islet (5) because it is separated

from the cells of the exocrine pancreas (3) by a thin connective tissue capsule (4). The

endocrine pancreatic islet (5) does not contain excretory ducts. Instead, it is highly vascularized, and

all of the secretory products leave the pancreatic islet via numerous blood vessels (capillaries)