L04-Histology of digestive glands

Question 1

Major digestive glands

Answer 1

1) Salivary glands
2) Pancreas
3) Liver

Question 2

Salivary glands overview

Answer 2

• Compound tubuloacinar that produces saliva.
• Basic secretory unit is an acinus; can be serous, mucous or mixed serous and mucous
• Divided into 3 pairs of major salivary glands and numerous minor salivary glands

Question 3

Major salivary glands

Answer 3

Paired glands with long ducts emptying into the oral cavity; 3 pairs in total:

1) Parotid (serous, below and in front of the ear)
2) Submandibular (mixed, under the floor of the mouth)
3) Sublingual (predominantly mucous with serous elements, floor of the mouth anterior to the submandibular gland inferior to the tongue)

[Note: Major salivary glands (except sublingual glands) are surrounded by a capsule of moderately dense connective tissue with septa dividing the glands into lobes and lobules

The larger blood vessels and excretory ducts are present in the connective tissue septa.]

Question 4

Minor salivary glands

Answer 4

located in the submucosa of different parts of the oral cavity:

Lingual, labial, buccal, molar, epiglottic and palatine glands

Note: Minor salivary glands are unencapsulated

Question 5

Secretory gland acini

Answer 5

• Definition: a blind sac composed of secretory cells
• organized into lobules
• Three types:
• *1) Serous**
• protein, enzyme secreting
• watery secretion
• generally spherical
• darkly stained in H&E (basophilic)
• *2) Mucous**
• mucin secreting
• thick and slimy secretion
• generally more tubular
• palely stained in H&E (acidophilic)
• *3) Mixed (serous and mucous)**
• presence of both serous and mucous secretory acini and cells
• presence of serous demilunes in traditional fixation

Question 6

serous demilunes

Answer 6

• Artifacts of traditional fixation method
• Seen in mixed (serous & mucous) multicellular secretory acini
• under H&E preparation, mucous acini are capped by serous cells
• Serous demilune not observed in rapidly freezed specimens

Question 7

Myoepithelial cells

Answer 7

Contractile cells present between the gland cells and basal lamina of the epithelium

Question 8

Innervations of salivary glands

Answer 8

Sympathetically and sympathetically:

1) Sympathetic (cervical sympathetic chain) → slow rate of secretion, high consistency, rich in protein
2) Parasympathetic → copious secretion, low consistency, more watery

Question 9

Generic scheme of secretory duct hierarchy

Answer 9

Acinus -> Intralobular duct -> interlobular duct -> Interlobar/ lobar duct -> Main duct

Question 10

Salivary ducts

Answer 10

Three groups: intercalated, striated and excretory:

1) Intercalated duct

• leads from the acinus
• intralobular duct (within parenchyma of glands)
• prominent in serous secretory salivary glands
• short and difficult to identify in mucous secretory salivary glands
• Cl-HCO3 pump for absorption (Cl^-) and secretion (HCO₃^-); thus modify the serous secretiom; hence more commonly associated with serous secretory acini and less with mucous secretory acini
• simple cuboidal

2) Striated duct:

• intralobular duct (within parenchyma of glands)
• presence of “striation” due to extensive infolding of the basal plasma membrane of the ductal cells with longitudinally arranged mitochondria
• diameter of striated duct often exceeds that of secretory acinus
• Na-K pump and the Cl-HCO3 pump to absorption (Na⁺) and secretion (K⁺ and HCO₃^-); thus modify the serous secretiom; hence more commonly associated with serous secretory acini and less with mucous secretory acini
• simple cuboidal or simple columnar

3) Excretory ducts:

• Interlobular and interlobar ducts (travel in interlobular and interlobar connective tissues)
• eventually empty into the oral cavity
• small excretory ducts (simple cuboidal) → gradually change to pseudostratified columnar or stratified cuboidal/squamous as the sizes increase
• Stensen’s duct (parotid duct) and Wharton’s duct (submandibular duct) travel in the connective tissues of the face and neck respectively

Question 11

Parotid glands

Answer 11

- Completely serous (a lot of basophilic serous acini under H&E) *

• Largest of major salivary gland
• Paired

- Large amount of adipose tissue *

• Below and in front of the ear
• Encapsulated by moderately dense connective tissue with septa dividing the glands into lobes and lobules
• More prominent intercalated and striated ducts
• Parotid/ Stenson’s ducts travel in the connective tissues of the face

Question 12

Submandibular glands

Answer 12

• Mixed (high amount of serous demilune *, actually predominantly serous)
• Large major salivary gland
• Paired
• under the floor of the mouth
• Encapsulated by moderately dense connective tissue with septa dividing the glands into lobes and lobules
• Relatively prominent intercalated and striated ducts
• Submandibular/ Wharton’s ducts travel in the connective tissues of the neck

Question 13

Sublingual Glands

Answer 13

• Predominantly mucous * (actually mixed, with few serous acini and serous demilune)
• Smallest of the major salivary gland
• Paired
• Floor of mouth anterior to submandibular glands inferior to the tongue
• Unencapsulated *
• Not prominent intercalated and striated ducts

Question 14

Saliva (features)

Answer 14

Combined secretions of all the major and minor salivary glands

• 1,200 ml produced a day
• Contains water, various types of proteins and electrolytes
• Principal enzymes: lysozymes and α-amylase

Question 15

Saliva (functions)

Answer 15

Both protective and digestive functions:

1) Moistening of oral mucosa

2) Aid swallowing

3) Dissolve food to be chemically tasted

4) pH Buffering (high concentration of bicarbonate ions)

5) Digest carbohydrates (α-amylase)

6) Source of calcium and phosphate ions essential for normal tooth development and maintenance (particularly relevant to patients undergoing radiotherapy e.g. nasopharyngeal carcinoma patients in Hong Kong)

7) Saliva performs immunologic functions

i) Lysozyme controls bacterial flora in the oral cavity
ii) Secretion of secretory IgA:

• IgA (is synthesized by plasma cells in the connective tissue surrounding the secretory acini)
• A secretory glycoprotein (synthesized by the salivary gland) is inserted on the basal plasma membrane which function as dimeric receptor for IgA
• Binding of IgA to the receptor from a secretory IgA complex which is internalized by a receptor-mediated endocytosis into the acini cells and transported to the apical membrane and secreted (similar to the secretory IgA transported across the absorptive columnar epithelial cells of intestines).

Question 16

Pancreas nature

Answer 16

An exocrine and endocrine gland:

• Exocrine - Synthesizes and secretes digestive enzymes into duodenum through pancreatic juice (the proteolytic peptidases: trypsin and chymotrypsin; enzymes that breakdown carbohydrates: α-amylase, maltase; enzyme that breaks down lipids: lipase; and nucleases)
• Endocrine (islets of Langerhans) - Synthesizes and secretes the hormones insulin and glucagons into bloodstream

Question 17

Panceas anatomy

Answer 17

• An elongate gland with a head, body and tail
• Connected to duodennum via the Main pancreatic duct and accessory pancreatic duct

Question 18

Endocrine pancreas

Answer 18

aka Islets of Langerhans (1-2% of the pancreas)

• paler stained than acinar cells in pancreas by H&E
• Usually proximal to blood vessels

Function: regulate blood glucose levels

3 principal islet cell types:

A cells (alpha; 15-20%; glucagon)

B cells (beta; 70%; insulin)

D cells (delta; 5-10%; somatostatin)

Minor cell types:

PP cells (pancreatic polypeptide)

D-1 cells (VIP Vasoactive intestinal peptide)

EC cells (enteroendocrine cells; serotinin aka 5HT, secretin, motilin, substance P)

Question 19

Exocrine pancreatic acinar cells

Answer 19

• Serous glands
• Secretory units: acinar or tubuloacinar
• Distinct basophilia in the basal cytoplasm
• Extensive array of rER and free ribosomes
• Correlates to high level of protein synthesis
• Acidophilic zymogen granules in the apical cytoplasm
• Proenzymes of protease (e.g. trypsinogen, chymotrypsinogen)
• Pancreatic proteases are activated only in small intestine by enterokinases at the microvilli (typsinogen to trypsin); trypsin then converts other inactive enzymes into active enzymes as well as digestion of protein
• lipase, amylase are released in active form
• Well-developed Golgi apparatus
• Opens to intercalated duct (simple cuboidal)

Question 20

Centroacinar cell

Answer 20

• Centroacinar cells are spindle-shaped cells only found in the exocrine pancreas
• smaller and more palely stained than acinar cells
• Centroacinar cells are an extension of the intercalated duct cells into each pancreatic acinus
• mucin, HCO₃^- secreting
• Stimulated by secretin to add bicarbonate and water to the exocrine secretion

Question 21

Pancreatic ducts

Answer 21

Ductal system:

• Intercalated ducts (squamous, more accurately low simple cuboidal) → intralobular ducts (simple cuboidal; no striated duct) → larger interlobular ducts (low columnar) → main pancreatic duct (along the long axis of pancreas) or accessory pancreatic duct (arises in head of pancreas)

* The intercalated ducts begin within the acinus (uniques feature of pancreas), these duct cells within the acinus are referred to as centroacinar cells (palely stained)

* Intercalated ducts add bicarbonate and water to the exocrine secretion

Question 22

Control of exocrine pancreas

Answer 22

Pancreatic exocrine secretion is under hormone and neural control:

1) Hormones: secretin and CCK; stimulated by the acidic chyme in duodenum
2) Parasympathetic fibres stimulates the activity of acinar and centroacinar cells
3) Sympathetic fibres regulates pancreatic blood flow

Question 23

Liver overview

Answer 23

• Largest gland in the body (1.5 kg and 2.5% of body weight)
• Develops from endodermal evagination from the wall of the foregut
• Hepatocytes are arranged into cellular cords

Question 24

Functions of liver

Answer 24

• Produce and secrete many circulating plasma proteins (Albumins, lipoproteins (e.g.VLDL, LDL, HDL), glycoproteins (e.g. transferrin), prothrombin, fibrinogen, non immune α- and β-globulins (osmotic pressure of plasma and carrier proteins).
• Uptake, storage and distribution of both nutrients and vitamins from the bloodstream, e.g. Vitamin K and Vitamin A (Ito cells)
• Maintains the blood glucose level
• Regulates circulating levels of VLDLs (metabolism and transport of lipids)
• Degrades and conjugates numerous toxic substances and drugs (e.g. detoxification by sER, bilirubin removal)
• Storage, metabolism and homeostasis of iron
• Synthesis and secretion of bile (exocrine functions); about 1.1 litre per day
• Endocrine-like functions
• Convert vitamin D to 25-hydroxycholecalciferol
• Convert of T₄ to T₃

Question 25

Hepatocyte

Answer 25

Histogical features of hepatocytes • Make up the anastomising cell plates of the liver lobule (one cell thick) * Binucleation is common * Long live (average life span: 5 months) * Hepatocyte cytoplasm is generally acidophilic * Extensive smooth ER (contains enzymes involved in degradation and conjugation of toxin; enzymes for synthesizing cholesterol and lipid; sER undergo hypertrophy induced by alcohol and drugs) * Basophilic regions represent rough ER * Numerous mitochondria * Multiple small Golgi complex * Large number of peroxisomes (contain hydrogen peroxide, H2O2, catalase etc. - for alcohol detoxification) * Deposits of glycogens * Lipid droplets, lipoprotein (llipid transport and metabolism) * Lipofusin pigment

Question 26

Liver blood supply

Answer 26

• entering at the porta hepatic together with the bile duct and lymphatic): - 75%: Hepatic portal vein (venous), from intestines - 25%: Hepatic artery (arterial); from celiac trunk; oxygenated • Blood from hepatic portal vein and hepatic artery flows into the sinusoids between hepatocytes leading eventually to the central vein, then to sublobular vein and leaving the liver through the hepatic veins and empty into inferior vena cava.

Question 27

Sinusoids

Answer 27

* Venous channels between cords of hepatocytes * Carrying blood from portal areas (from hepatic portal vein and hepatic artery) to central vein * Lined by incomplete walls formed by endothelium and Küpffer cells — phagocytic (mononuclear phagocytotic system) * Facilitate exchange of materials between sinusoid and hepatocytes via sinusoidal lumens

Question 28

Küpffer cells

Answer 28

**Location**: Liver (e.g. endothelial lining of sinusoids) **Function**: - antigen presnetation - phagocytosis (mononuclear phagocytotic system) **Histology**: - essentially macrophages - difficult to distinguish - Can be visualized with Indian ink/ Carbon particle injection (Küpffer cells will perform phagocytosis on foreign materials, as a result the phagocytic vesicles will be stained and marked, labelling Küpffer cells) - see img below

Question 29

Ito cells

Answer 29

- aka Hepatic stellate cells (HSC) or perisinoidal cells - located in perisinoidal space **Functions**: - Store vitamin A - Antigen presenting - Involved in liver fibrosis: Differentiate into myofibroblasts in pathological conditions and synthesize collagen type I and III

Question 30

Space of Disse

Answer 30

- aka Perisinoidal space - between a hepatocyte and a sinusoid - It contains the blood plasma, Ito cells and microvilli of hepatocytes - Site of exchange of materials between blood and liver cells

Question 31

Bile canaliculi

Answer 31

- a thin tube that collects bile secreted by hepatocytes - formed by grooves on some of the lateral faces of hepatocytes - surrounded by zonula occludens - bile canaliculi merge and form bile ductules, which eventually become common hepatic duct

Question 32

Liver unit classification

Answer 32

Can be classified into three types: 1) Classical lobule (Structural) 2) Portal lobule (Functional - bile drainage) 3) Liver acinus (Functional - blood supply)

Question 33

Portal area

Answer 33

Contains the portal triad (hepatic artery, hepatic portal vein, bile duct) and lymphatic vessels embedded in connective tissues (that surrounds a classical liver lobule) [note: hepatic triad refers to types of vessels found in portal area, not number. So there might be more than one of each kind of vessels in a portal area, still considered as triad]

Question 34

Classic lobule

Answer 34

- Structural in nature - Theoretical hexagonal (or pentagonal) structures consists of stacks of anastomosing plates of hepatocytes - More easily recognized in pig’s liver (delineated by connective tissues) but less prominent in human liver - central vein located at the center of the classic lobule - anastomosing plates of hepatocytes (one cell thick) radiate out from central vein and are separated by sinusoids - 6 portal areas at the angles of the hexagon of the classic lobule - Blood flows from periphery towards central; Opposite for bile

Question 35

Portal lobule

Answer 35

- Based on the exocrine function of liver (bile secretion) - Portal area at the center of the lobule (bile drainage) - Border (imaginary lines between two central veins forming triangular structure)

Question 36

Liver acinus

Answer 36

- Provides the best correlation between blood perfusion, metabolic activity and liver pathology - Diamond-shape - Smallest functional unit of liver - Two portal areas and two central vein reside on the angles of liver acinus - Can be devide into zone 1, zone 2, zone 3 - Perfusion, nutrients and metabolism (from greatest to least): zone 1\> 2\> 3 - pathophysiological events like poisoning, (from most affected to least): zone 1\> 2\> 3 - Under ischaemic condition, most affected (i.e. most prone to shock): zone 3\> 2\> 1

Question 37

Gall bladder

Answer 37

* Concentrate and store bile * Mucosa, much folded (Simple columnar epithelium) * Lack of muscularis mucosae and submucosa