Adrenaline (also known as epinephrine) is a catecholamine hormone responsible for the “fight or flight” response. It is produced by the chromaffin cells in the medulla (middle part) of the adrenal glands. Adrenaline helps the body respond to a potential threat. It has a short duration of action, helping with an intense burst of physical activity (fight or flight), after which the effects dissipate.
Noradrenaline (also known as norepinephrine) is a closely related catecholamine that mainly functions as a neurotransmitter throughout the central nervous system and peripheral nervous system. Neurotransmitters are used at synapses to deliver a nerve signal from one cell to the next. This might be:
- From one neurone to the next neurone
- From a neurone to another type of cell (called a neuroeffector junction), for example, from a neurone to a muscle
Noradrenaline is also produced by the adrenal medulla and released into the general circulation as a hormone, but in smaller amounts and with a smaller role than adrenaline.
Adrenaline Release
Adrenaline is released in response to a potential threat. Various sensory inputs (e.g., sight, sound, smell and touch) collect information about the potential threat. These inputs are processed in their relevant brain areas (e.g., the visual cortex for sight). This information is relayed to the:
- Prefrontal cortex, which processes and understands the information
- Amygdala, which is responsible for emotional responses (e.g., fear and anxiety)
The prefrontal cortex and amygdala alert the hypothalamus to danger. The hypothalamus responds by:
- Activating the sympathetic nervous system, which stimulates adrenaline release from the adrenal glands
- Releasing corticotropin-releasing hormone (CRH), which stimulates cortisol release from the adrenal glands
The signal from the hypothalamus is transmitted down the spinal cord to the sympathetic nervous system. The sympathetic nervous system originates with the cell bodies of the preganglionic neurones, found in the spinal cord at levels T1 to L2. These preganglionic neurones carry the signal to networks of sympathetic ganglia, which are nodules of postganglionic neurone cell bodies that run vertically on either side of the spine, called the sympathetic chain or paravertebral ganglia. The sympathetic trunk refers to the nerve fibres that connect the ganglia. The sympathetic ganglia are where the preganglionic neurones synapse with the postganglionic neurones.
The preganglionic sympathetic neurones use acetylcholine as the neurotransmitter when communicating with the postganglionic sympathetic neurones. The postganglionic sympathetic neurones carry the signal from the sympathetic ganglia to the tissues. The postganglionic neurones primarily use noradrenaline as a neurotransmitter to communicate with the tissues.
The sympathetic nervous system stimulates the adrenal medulla to release adrenaline into the blood.
Action of Adrenaline
The actions of adrenaline and noradrenaline include:
- Increase heart rate
- Increased cardiac output
- Increased blood pressure (via vasoconstriction and increased renin-angiotensin-aldosterone activity)
- Increasing alertness
- Bronchodilation (expanding the airways in the lungs)
- Increasing blood sugar
- Reducing digestive activity
- Pupil dilation
Adrenergic Receptors
Adrenaline and noradrenaline exert their effects by stimulating adrenergic receptors (also called adrenoceptors). These receptors can be divided into alpha (α) receptors and beta (β) receptors.
Alpha receptors are further divided into:
- Alpha-1 (α1) receptors (increase vasoconstriction, pupil dilation and urethral sphincter contraction)
- Alpha-2 (α2) receptors (inhibit sympathetic nervous system activity and cause sedation and pain relief)
Beta (β) receptors are further divided into:
- Beta-1 (β1) receptors (increase heart rate, contractility and blood pressure)
- Beta-2 (β2) receptors (increase bronchodilation, vasodilation and glucose production)
- Beta-3 (β3) receptors (increase lipolysis, the breakdown of fat tissue into fatty acids for energy)
Beta-1 (β1) receptors are primarily found in the heart. They increase the heart rate and the contractility of the heart muscle (myocardium). They increase how fast and hard the heart pumps.
Beta-1 (β1) receptors are also found in the juxtaglomerular cells of the kidneys, and stimulate renin production. Increased renin leads to increased angiotensin II and aldosterone, which increase the blood pressure.
CLINICAL RELEVANCE
Beta-blockers can be non-selective (blocking all the types of beta receptors) or selective (blocking only specific types of beta receptors).
Bisoprolol is a cardioselective beta-blocker. It selectively targets beta-1 receptors, helping to reduce heart rate, contractility, and blood pressure without stimulating beta-2 and beta-3 receptors.
Atenolol is relatively cardio-selective, mainly targeting beta-1 receptors at lower doses. However, at higher doses it starts to affect beta-2 receptors as well.
Propranolol is non-selective and blocks beta-1 and beta-2 receptors. This leads to side effects of bronchospasm (particularly affecting patients with asthma or COPD), fatigue and hypoglycaemia (low blood sugar).
Beta-2 (β2) receptors stimulate:
- Bronchodilation in the lungs
- Vasodilation in the vessels that supply the skeletal muscles, heart and lungs (to improve physical performance)
- Glucose production in the liver and muscles (converting glycogen and other energy sources to glucose)
- Potassium uptake into cells (reducing the potassium concentration in the blood)
CLINICAL RELEVANCE
Beta-2 agonists (e.g., salbutamol) are used to treat asthma and chronic obstructive pulmonary disease (COPD). In these conditions, the bronchial smooth muscles contract, causing the airways to narrow, resulting in shortness of breath. In this scenario, beta-2 agonists relax the bronchial smooth muscles, causing bronchodilation.
Beta-2 agonists can cause side effects such as hyperglycaemia (raised blood sugar) and hypokalaemia (low potassium). They are rarely used as a short-term treatment for hyperkalaemia (high potassium).
Phaeochromocytoma
A phaeochromocytoma is a tumour of the chromaffin cells that secrete unregulated and excessive amounts of adrenaline.
About 30-40% of patients have a genetic cause. They are associated with specific genetic disorders:
- Multiple endocrine neoplasia type 2 (MEN 2)
- Neurofibromatosis type 1
- Von Hippel-Lindau disease
The adrenaline tends to be secreted in bursts, giving intermittent symptoms. Typical symptoms include:
- Anxiety
- Sweating
- Headache
- Tremor
- Palpitations
- Hypertension
- Tachycardia
Measuring serum catecholamines or adrenaline is unreliable as the levels fluctuate, and they have a very short half-life of only a minute or so. Metanephrines (a breakdown product of adrenaline) have a longer half-life, resulting in more stable levels. High levels of plasma-free metanephrines can indicate a phaeochromocytoma.
Measuring 24-hour urine catecholamines gives an idea of how much adrenaline is being secreted by the tumour over a 24 hour period.
Management of a phaeochromocytoma involves:
- Alpha blockers (e.g., phenoxybenzamine or doxazosin)
- Beta blockers, only when established on alpha blockers
- Surgical removal of the tumour
Medications
Intramuscular adrenaline is used to treat anaphylactic reactions. Anaphylaxis is a life-threatening allergic reaction involving bronchoconstriction (airway narrowing), hypotension (low blood pressure) and angioedema (swelling). Adrenaline helps reverse these effects by causing bronchodilation and vasoconstriction, opening the airways, increasing the blood pressure and reducing the oedema.
Noradrenaline is a vasopressor. Vasopressors cause vasoconstriction (narrowing of blood vessels), increasing systemic vascular resistance and blood pressure. They are commonly used in intensive care to improve blood pressure and, therefore, tissue perfusion. Septic shock is a common example of a condition where noradrenaline may be used.
Dobutamine and isoprenaline are inotropes. Dobutamine works by selectively stimulating beta-1 receptors. Isoprenaline non-selectively stimulates beta-1 and beta-2 receptors. Inotropes increase the heart muscle (myocardium) contractility, increasing cardiac output (CO) and blood pressure. They are used in patients with a low cardiac output, for example, due to heart failure, recent myocardial infarction or following heart surgery.
Beta blockers are used to treat cardiac arrhythmias, heart failure and hypertension. Cardioselective beta blockers (e.g., bisoprolol) only block beta-1 receptors, targeting the heart more than other organs. Non-selective beta blockers (e.g., propranolol) block beta-1 and beta-2 receptors.
Inhaled beta-2 (β2) agonists (e.g., salbutamol) are used to treat asthma and chronic obstructive pulmonary disease (COPD). By stimulating beta-2 (β2) receptors, they relax the bronchial smooth muscle and expand the airways (bronchodilation).
Alpha-1 blockers (e.g., tamsulosin or doxazosin) are used to treat hypertension and benign prostatic enlargement.
Alpha-2 agonists (e.g., clonidine) are used to treat hypertension (it is a vasodilator) and menopausal flushing.
Last updated August 2024
Now, head over to members.zerotofinals.com and test your knowledge of this content. Testing yourself helps identify what you missed and strengthens your understanding and retention.
