ToB 2.2 Glands

Gland Definition and Basic Concepts

• Gland Definition

  • An epithelial cell (or collection of epithelial cells) involved in the production and release of secretions.

  • Example: Goblet cell as a single-cell gland.

• Types of Glands

  • A gland is either exocrine or endocrine.

• Classification of Exocrine Glands

  • Morphology.

  • Means of secretion.

  • Nature of secretions.

• Exocrine Gland Illustration (Conceptual)

  • Glands associated with epithelia and secretion into ducts or surfaces.

Destination of Secretions: Exocrine vs Endocrine

• Exocrine Glands

  • Connected to surface epithelium.

  • Have ducts that carry secretions to surfaces or organ lumens.

  • Examples: sweat glands of the skin, salivary glands, glands in stomach & intestines.

• Endocrine Glands

  • Have lost connection to surface epithelium.

  • Secretions released into blood (hormones).

  • No ducts.

  • Examples: pituitary, thyroid, parathyroid, adrenal glands, kidney (regulatory hormones), pancreas (islets of Langerhans).

Means of Secretion

• Merocrine Secretion (the most common)

  • Secretory vesicles fuse with the plasma membrane and contents are released by exocytosis.

• Apocrine Secretion

  • Found mainly in axillae, areolae, and anogenital region.

  • Non-functional before puberty in some glands.

  • Apical part of the cell containing secretion is pinched off.

• Holocrine Secretion

  • Glands such as sebaceous glands of the skin, meibomian glands of the eyelid, and some breast tissue.

  • Whole cell disintegrates to release secretory products.

Nature of Secretion: Mucous vs Serous

• Exocrine Gland Secretions

  • Secrete either mucous or serous secretions.

• Mucous Glands

  • Secretions rich in mucin; mucin is washed out during tissue processing, so they stain poorly and appear pale/foamy.

• Serous Glands

  • Secretions are protein-rich and stain darkly with eosinophilic staining.

Morphology of Glands

• Morphology Terms (Duct Structure)

  • Simple: one duct and one secretory portion.

  • Simple branched: one duct + >1 secretory portion.

  • Compound: >1 duct + >1 secretory portion.

• Secretory Portion Shapes

  • Acinar: rounded sacs.

  • Tubular: straight tubes.

  • Tubuloacinar: combination of tubular and acinar.

• Duct Types (Examples)

  • Simple coiled tubular duct (illustrative for architectural classification).

Classification of Glands – Summary

• Overall Classification Criteria

  • Epithelium surface.

  • Glandular: Exocrine vs Endocrine.

  • Morphology: Simple vs Compound; Acinar vs Tubular vs Tubuloacinar.

  • Secretion: Mucous vs Serous.

  • Destination/Means of Secretion: Merocrine, Apocrine, Holocrine.

Cystic Fibrosis (CF)

• Prevalence

  • CF affects around 11,000 people in the UK.

  • Approximately 1 in 25 Caucasian Europeans are carriers of the CFTR gene.

• Inheritance

  • Autosomal recessive disorder → mutation in the cystic fibrosis transmembrane regulator (CFTR) gene.

• CFTR Function

  • Regulates movement of chloride $(Cl^-)$ across chloride channels against its concentration gradient to the outside of the cell → ATP.

• Consequences of CFTR Mutations (e.g., $\Delta F508$)

  • Impaired $(Cl^-)$ transport.

  • Altered $(Na^+)$ transport leading to increased intracellular $(Na^+)$.

  • Increased water reabsorption by cells.

  • Result: dehydrated and thick mucus in various secretory epithelia.

• Sweat Gland Specifics

  • Mutations in CFTR lead to decreased $(Cl^-)$ and $(Na^+)$ reabsorption into the cell.

  • This is the basis for the sweat test used to confirm CF diagnosis.

Pancreas — Histology and Secretions

• Pancreas Nature

  • A mixed endocrine & exocrine organ.

• Endocrine Component: Islets of Langerhans

  • Generally pale staining.

  • Contain alpha cells (glucagon), beta cells (insulin), delta cells (somatostatin).

• Exocrine Component (~99% of the gland): Secretory Acini

  • Cells are cuboidal to pyramidal with dark, eosinophilic, granular cytoplasm.

• Ductal System

  • Intercalated duct: simple squamous.

  • Intralobular duct: simple cuboidal.

  • Interlobular duct: simple cuboidal.

  • Main pancreatic duct: simple columnar.

Thyroid Gland

• Function

  • Endocrine gland producing thyroid hormones T3 (triiodothyronine) and T4 (thyroxine).

• Main Functional Components

  • Thyroid follicles.

  • Parafollicular cells (C cells) → produce calcitonin.

• Follicles

  • Lined by simple cuboidal epithelium.

  • Contain colloid between follicular cells.

• Hormone Synthesis (Overview)

  • Iodide uptake: via $(Na^+/I^-)$ symporter.

  • Iodination within colloid: by thyroid peroxidase (TPO) for MIT and DIT formation.

  • Coupling: MIT and DIT formation; coupling to form T3 and T4.

  • Thyroglobulin Storage: Thyroglobulin is iodinated and stored in colloid.

  • Release: Endocytosis of thyroglobulin, proteolysis, and release of T3/T4 into blood.

  • Pendrin Role: Transports iodide into the colloid or into follicular cells as part of the cycle.

  • TSH Stimulation: TSH from the pituitary stimulates these processes.

• Key Reagents and Steps (Synthesis Pathway)

  • Tyrosine-based sequence with MIT/DIT precursors.

  • Oxidation and coupling to form T3 and T4.

  • Endocytosis and proteolytic release from thyroglobulin.

  • Transport into bloodstream via secretion into capillaries.

• Key Structures

  • Colloid, follicular cells, TSH receptor (TSH-R).

• Calcitonin Function

  • From parafollicular (C) cells helps lower blood calcium.

Parathyroid Glands

• Function

  • Secretes parathyroid hormone (PTH) for calcium regulation.

• Cell Types

  • Chief/principal cells: small polygonal cells with large nuclei; secrete PTH.

  • Oxyphil cells: larger, more eosinophilic; function less clear.

  • Adipose cells: increase with aging.

• PTH Function

  • Promotes bone resorption by osteoclasts to raise blood calcium levels.

• Image-based Note

  • Parathyroid hormone is a key regulator of calcium homeostasis.

Adrenal Glands

• Location

  • Atop the kidneys, embedded in perirenal fat; surrounded by a dense connective tissue capsule.

• Structural Division

  • Cortex (outer) and medulla (inner).

• Cortex Zones

  • Zona glomerulosa: aldosterone (mineralocorticoid) production.

  • Zona fasciculata: cortisol (glucocorticoid) production.

  • Zona reticularis: weak androgens production.

• Medulla

  • Made up of chromaffin cells.

  • Produces catecholamines: ~80% adrenaline (epinephrine) and ~20% noradrenaline (norepinephrine).

  • Cells arranged in cords.

Mammary Gland

• Structure

  • Compound tubuloacinar glands.

• Secretory Units

  • Arranged in lobules embedded in adipose tissue.

• Myoepithelial Cells

  • Contractile cells surrounding secretory portions.

  • Facilitate extrusion of secretory contents.

• Type of Secretion

  • Apocrine gland.

• Additional Notes

  • Abundant immune cells (e.g., lymphocytes) within stroma may be present in some slides.

Salivary Glands

• General Classification

  • Exocrine glands → compound tubuloacinar glands.

• Myoepithelial Cells

  • Surround secretory portions.

• Demilunes

  • In mixed mucoserous glands, serous acini often form demilunes (a crescent-shaped serous cap).

• Duct Sequence

  • Intercalated duct → striated duct → excretory duct.

• Specific Glands

  • Parotid gland:

  • Exclusively serous acini; secretes abundant $\alpha$-amylase.

  • Innervation: parasympathetic stimulates saliva release; strong sympathetic innervation reduces saliva leading to xerostomia.

  • Striated ducts important for $(Na^+)$ resorption.

  • Submandibular gland:

  • Mixed mucoserous; predominantly serous; produces about two-thirds of saliva.

  • Also secretes lysozyme for bacterial cell wall hydrolysis.

  • Sublingual gland:

  • Mixed mucoserous but predominantly mucous; contains mucous secretions.

  • Located in the floor of the mouth; ducts visible as sublingual ducts.

Helpful Notes on Key Concepts and Connections

• Goblet Cells Role

  • Demonstrate that glands can be single cells and contribute to mucous production via rER and Golgi-mediated mucin synthesis.

  • Mucin is hydrated to form mucus and serves protective, lubricative, and antimicrobial roles.

• Exocrine vs Endocrine Organization

  • Illustrates how location and transport pathways shape gland function across organs (e.g., sweat vs pituitary hormones).

• Three Secretory Mechanisms

  • Merocrine, apocrine, holocrine; explain a diversity of glandular products and how secretion is released.

  • Notable gland examples include sweat glands (merocrine), apocrine-containing regions, and sebaceous glands (holocrine).

• Mucous vs Serous Distinctions

  • Influence staining and microscopy interpretation and reflect functional specializations (mucin-rich lubrication vs protein-rich enzymatic activity).

• Gland Morphology

  • Simple/compound; tubular/acinar/tubuloacinar correlates with functional capacity and duct architecture across tissues like pancreas, salivary glands, and others.

• Cystic Fibrosis Significance

  • Highlights how a single gene (CFTR) affects multiple organs via ion transport, mucus hydration, and clinical testing (sweat test).

• Pancreas Function Integration

  • Demonstrates the integration of endocrine and exocrine functions within one organ, including distinct islet cell types (alpha, beta, delta) and a complex duct system that ensures efficient secretion routing.

• Thyroid Hormone Synthesis

  • Involves iodide uptake, organification, coupling, storage in colloid, and regulated release, with critical roles for transporters $(Na^+/I^-)$ symporter, pendrin) and enzymes (TPO).

• Parathyroid and Adrenal Glands Regulatory Role

  • Illustrate endocrine regulation of calcium homeostasis and stress/adaptation hormones, with distinct cortical zones producing mineralocorticoids, glucocorticoids, and androgens, and a medullary chromaffin cell population producing catecholamines.

• Mammary and Salivary Glands Specialization

  • Showcase specialized secretory products and regulatory mechanisms (myoepithelial cell function, demilunes, and ductal maturation).

Key Equations and Quantitative Details

• Cystic Fibrosis Pathophysiology (CFTR mutation effects)

  • $\text{CFTR mutation} \rightarrow \text{impaired Cl}^- \text{ transport} \rightarrow \Delta [\text{Cl}^-]<em>{\text{in}} \rightarrow \Delta [\text{Na}^+]</em>{\text{in}} \rightarrow \Delta \text{water reabsorption} \rightarrow \text{thick dehydrated mucus}$

• CF Carrier and Affected Population Data (from transcript)

  • Approx. affected people in the UK: around 11,000.

  • Carrier frequency: about 1 in 25 among Caucasian Europeans.

Illustrative Pathways in Hormone Synthesis and Secretion (Thyroid Example)

• Iodide Uptake

  • $(Na^+/I^-)$ symporter.

• Transport into Colloid and Iodination

  • TPO (thyroid peroxidase) catalyzes iodination to MIT, DIT.

• Coupling to Form Hormones

  • $\text{MIT} + \text{DIT} \rightarrow \text{T3}$, $\text{DIT} + \text{DIT} \rightarrow \text{T4}$.

• Thyroglobulin Storage and Endocytosis

  • Endocytosis of thyroglobulin from colloid.

  • Proteolysis to release free $\text{T3}, \text{T4}$.

• Transport into Blood

  • Binding proteins (e.g., TBG) and release into circulation.

• Pendrin Role

  • Plays a role in iodide transport within thyroid cells and colloid.

Practical Implications and Diagnostic Cues

• CF Sweat Test

  • Relies on altered chloride reabsorption in sweat glands due to CFTR mutations.

• Parotid Gland Secretion

  • Serous secretion contains abundant $\alpha$-amylase.

  • Xerostomia can be influenced by autonomic tone (parasympathetic promotes secretion; sympathetic reduces it).

• Demilunes

  • In mixed mucoserous glands (e.g., submandibular) reflect the coexistence of mucous and serous secretions and their structural organization.

• Ductal Architecture

  • Intercalated to striated to excretory is a key histological feature in salivary