Adrenal Glands and Pancreas

Spec Mapping — OCR H420 Module 5.1.4 — Hormonal communication, content statements covering the histological structure of the adrenal glands and pancreas, including the cortex / medulla distinction, the islets of Langerhans, and the cell types and hormones of each region (refer to the official OCR H420 specification document for exact wording). This lesson provides the anatomical and cellular foundation for the blood-glucose control and diabetes lessons that follow.

Two endocrine organs are particularly important for OCR A-Level Biology A: the adrenal glands, which mount the fight-or-flight response and set long-term metabolic rate, and the pancreas, which together with the liver controls blood glucose. This lesson explores the histology, cell types and hormones of both glands.

The pancreatic islets were first described by the German medical student Paul Langerhans in his 1869 doctoral thesis on pancreatic histology (paraphrase) — he noted clusters of pale-staining cells scattered among the darker exocrine acini, but their function was unknown for half a century. Edward Sharpey-Schafer (1916, paraphrase) proposed that the islets secrete a blood-sugar-regulating substance and proposed the name "insulin" before it was isolated. Frederick Banting and Charles Best (1921, working in Macleod's lab at the University of Toronto, paraphrase) isolated insulin from dog pancreatic islets — by tying off the pancreatic duct to atrophy the exocrine tissue and leave the islets intact — and demonstrated its glucose-lowering effect in diabetic dogs and then humans. The 1923 Nobel Prize in Physiology or Medicine went to Banting and Macleod; Banting shared his portion with Best, and Macleod shared his with the biochemist James Collip, who purified the hormone for clinical use. The discovery of insulin remains one of the most dramatic in the history of medicine — within months of clinical translation, children dying of type 1 diabetes were returned to full health (paraphrase).

Key Definitions:

• Adrenal gland — a paired endocrine gland sitting on top of each kidney; has two distinct regions (cortex and medulla).
• Pancreas — a mixed exocrine–endocrine gland behind the stomach; endocrine cells cluster in islets of Langerhans.
• Islets of Langerhans — clusters of endocrine cells within the pancreas.
• α cells — cells in the islets that secrete glucagon when blood glucose falls.
• β cells — cells in the islets that secrete insulin when blood glucose rises.

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The Adrenal Glands

Each adrenal gland is a pyramid-shaped organ about 5 cm across, sitting on top of a kidney like a cap. In cross-section you can see two distinct regions:

• Outer cortex — pale, derived from mesoderm; accounts for ~85% of the gland by volume.
• Inner medulla — dark brown, derived from neural crest; accounts for ~15% by volume.

The two regions have entirely different embryological origins, entirely different hormones and entirely different control mechanisms. Treating them as "one gland" is a common mistake. The functional reason for this dual organisation appears to be evolutionary cohabitation of the steroid-producing cortex with the modified-sympathetic medulla, allowing rapid coordination of acute (medulla) and sustained (cortex) stress responses through shared blood supply.

The Adrenal Cortex

The cortex makes steroid hormones from cholesterol. It has three histological zones, each producing different hormones. OCR does not require the zone names but expects you to know the three hormone classes produced.

1. Glucocorticoids (chiefly cortisol)

   • Help regulate metabolism; promote gluconeogenesis and lipolysis.
   • Raise blood glucose over the longer term (hours).
   • Suppress inflammation (which is why synthetic cortisol derivatives are used as anti-inflammatory drugs).
   • Secreted under the control of ACTH from the anterior pituitary, which itself is stimulated by CRH from the hypothalamus — the HPA (hypothalamic-pituitary-adrenal) axis.

2. Mineralocorticoids (chiefly aldosterone)

   • Act on the distal convoluted tubule and collecting duct of the kidney.
   • Promote Na⁺ reabsorption and K⁺ excretion.
   • Water follows Na⁺ osmotically, so aldosterone raises blood volume and pressure.
   • Secretion is controlled by the renin-angiotensin system (triggered by low blood pressure) and by plasma K⁺ concentration.

3. Androgens (small amounts of sex steroids such as DHEA)

   • Precursors of testosterone and oestrogen.
   • Of minor importance in healthy adults, but significant in some pathological states.

The Adrenal Medulla

The medulla is really modified sympathetic nervous tissue. It contains chromaffin cells, which are essentially specialised postganglionic sympathetic neurones without axons. When the sympathetic nervous system is activated (fight or flight), preganglionic sympathetic fibres release ACh onto nicotinic receptors on the chromaffin cells, which depolarise and release their hormones into the blood:

1. Adrenaline (~80% of medullary secretion)
2. Noradrenaline (~20%)

Both are catecholamines derived from the amino acid tyrosine through the biosynthetic pathway: tyrosine → L-DOPA → dopamine → noradrenaline → adrenaline. The final step (adrenaline formation) requires the enzyme phenylethanolamine N-methyltransferase (PNMT), which is uniquely expressed in chromaffin cells and is dependent on local cortisol concentrations from the surrounding cortex — a paracrine link between the two adrenal regions. These hormones act within seconds to produce the classic fight-or-flight response:

• Heart rate and stroke volume increase (β1-adrenergic on cardiac muscle).
• Vasoconstriction in the skin and gut (α1-adrenergic); vasodilation in skeletal muscle and cardiac muscle (β2-adrenergic).
• Bronchioles dilate (β2-adrenergic on bronchial smooth muscle, easier breathing).
• Pupils dilate (α1-adrenergic on dilator pupillae muscle).
• Liver glycogenolysis is activated (β2-adrenergic via cAMP) raising blood glucose.
• Piloerection (hairs stand up — α1-adrenergic on arrector pili muscle).
• Energy is mobilised from fat stores (β3-adrenergic on adipocytes; lipolysis).

Because adrenaline is a hormone in the blood rather than a neurotransmitter at a synapse, its effects last longer than a direct sympathetic nerve stimulation — minutes rather than seconds. The combined sympathetic + adrenal-medullary response is sometimes called the SAM axis (sympathetic-adrenal-medullary), to distinguish it from the longer-lasting HPA axis.

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Summary of Adrenal Hormones

Region	Hormone	Class	Target	Main effect
Cortex	Cortisol	Steroid	Many	Raises blood glucose; anti-inflammatory
Cortex	Aldosterone	Steroid	Kidney	Na⁺ reabsorption, water retention
Cortex	Androgens	Steroid	Many	Precursors of sex steroids
Medulla	Adrenaline	Catecholamine	Liver, heart, vessels, airways	Fight or flight
Medulla	Noradrenaline	Catecholamine	Heart, vessels	Fight or flight

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The Pancreas

The pancreas lies in the abdomen behind the stomach. It has both endocrine and exocrine tissue, arranged intimately together.

Exocrine Function

Most of the pancreas is exocrine: ~98% of cells form clusters called acini, which secrete pancreatic juice containing digestive enzymes (amylase, trypsinogen, chymotrypsinogen, lipase and many others) and bicarbonate ions, which neutralise the acid from the stomach. This juice drains via the pancreatic duct into the duodenum. Although not the focus of this lesson, OCR expects you to recognise that the pancreas is a dual-function organ.

Endocrine Function — The Islets of Langerhans

Scattered through the exocrine tissue are about a million islets of Langerhans, small clusters of endocrine cells each containing several types:

• α (alpha) cells — secrete glucagon when blood glucose is low (~20% of islet cells).
• β (beta) cells — secrete insulin when blood glucose is high (~70% of islet cells).
• δ (delta) cells — secrete somatostatin, which inhibits both insulin and glucagon (not required by OCR but useful context; ~5% of islet cells).
• PP cells — secrete pancreatic polypeptide (again, not required; ~5% of islet cells).

β cells are more numerous and lie centrally in each islet, surrounded by α cells on the periphery — an arrangement that allows paracrine interactions between cell types. The islets are richly supplied with capillaries, allowing rapid detection of blood glucose and rapid release of hormones. Each islet behaves as a "miniature sensor-effector unit", with β cells acting as the glucose sensor (via GLUT2 transporters and downstream KATP-channel signalling) and the entire islet acting as a coordinated secretory unit.

The β-cell glucose-sensing mechanism is itself worth understanding: glucose enters β cells via the GLUT2 transporter (a high-Km transporter, so glucose entry scales with blood concentration); intracellular metabolism raises the ATP/ADP ratio; this closes ATP-sensitive K⁺ channels (KATP), depolarising the cell; voltage-gated Ca²⁺ channels open; Ca²⁺ influx triggers insulin granule exocytosis. The same KATP channel is the molecular target of sulfonylurea drugs (e.g. gliclazide) used in type 2 diabetes — they bind the sulfonylurea-receptor subunit of KATP and close it, mimicking the glucose-stimulated state and forcing insulin release.

Glucagon and Insulin — Opposing Actions

Glucagon and insulin act antagonistically on the liver. Together they keep blood glucose within the narrow range of 4–8 mmol dm⁻³. This range is non-negotiable for survival: hypoglycaemia below ~2.5 mmol dm⁻³ causes confusion, seizures and ultimately coma because the brain depends almost exclusively on glucose as its fuel (it cannot use long-chain fatty acids, and only uses ketones in prolonged starvation). Hyperglycaemia above ~10 mmol dm⁻³ for extended periods causes glycation of proteins (advanced glycation end-products, AGEs) that damage vascular endothelium, glomerular basement membrane, nerve sheaths and retinal capillaries — the molecular basis of the long-term complications of poorly controlled diabetes.

Feature	Insulin (β cells)	Glucagon (α cells)
Secreted when	Blood glucose high	Blood glucose low
Effect on liver	Increases glucose uptake; activates glycogen synthesis (glycogenesis)	Activates glycogen breakdown (glycogenolysis) and gluconeogenesis
Effect on muscle	Increases glucose uptake (via GLUT4); promotes glycogenesis	No significant effect
Effect on fat	Promotes fat storage	Promotes fat breakdown
Receptor type	Tyrosine kinase receptor	G-protein-coupled; cAMP second messenger
Net effect on blood glucose	Decreases	Increases

The next lesson (Blood Glucose Control) traces this in full detail.

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Histological Staining of the Pancreas

OCR sometimes asks about recognising pancreatic tissue under the microscope. Using haematoxylin and eosin (H&E) stains, you can distinguish:

• Dark pink acinar cells with prominent nuclei — these are the exocrine cells, packed with rough ER and zymogen granules (digestive enzyme precursors).
• Pale-staining rounded clusters in between — these are the islets of Langerhans, with smaller, less basophilic cells than the acini.
• Within the islets, special immunostains (or aldehyde fuchsin) can differentiate α and β cells, but in a standard H&E stain you cannot tell them apart without further staining.
• Capillaries are abundant in islets — much denser than in surrounding exocrine tissue, reflecting the rapid blood-glucose-sensing and hormone-release functions.

The histological appearance of the pancreas in type 1 diabetes is dramatically different — islets are largely empty of β cells, with lymphocytic infiltrates around the remaining ones (insulitis), reflecting the autoimmune destruction underlying the disease. In type 2 diabetes, islets initially appear hypertrophied (compensating for insulin resistance) but show progressive amyloid deposition (islet amyloid polypeptide, IAPP) and β-cell apoptosis over decades.

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The Pancreas in Homeostasis

The pancreas sits right in the bloodstream leaving the gut (via the portal vein towards the liver). This is strategically perfect: glucose absorbed from food reaches the pancreas within seconds, where β cells detect it and respond with insulin. The hormone then travels to the liver — the very next organ — through the portal circulation, where it exerts its strongest effects. This means that hepatic insulin concentrations are several-fold higher than systemic insulin concentrations, allowing the liver to be exquisitely sensitive to insulin even at low systemic levels. This anatomical arrangement (gut → portal vein → pancreas → liver → systemic circulation) is sometimes called the enterohepatic axis and is why the liver is the dominant insulin-target organ, with muscle and adipose tissue receiving lower, systemic concentrations.

flowchart LR
    FOOD[Food digested] --> GUT[Glucose absorbed in ileum]
    GUT --> PV[Hepatic portal vein]
    PV --> PAN[Pancreas: β cells detect glucose]
    PAN --> INS[Insulin released]
    PV --> LIVER[Liver: takes up glucose]
    INS --> LIVER
    LIVER --> SYS["Systemic circulation<br/>regulated glucose"]

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