Physiology: The Queen of Medicine — Understanding Health, Disease and the Action of Drugs
by: lim ju boo
There is an old expression in medical education that has always appealed to me: “Physiology is the queen of medicine.” I believe there is considerable truth behind this statement.
Before explaining why I hold this view, however, it is useful to understand how medical education has traditionally been organised and where physiology fits into the larger picture.
From the Foundations of Medicine to Clinical Practice
The expression “Institutes of Medicine” has had different meanings at different periods of medical history. In older nineteenth-century medical education, the term could refer to the foundational principles of medicine, the scientific knowledge of the normal body and the principles underlying disease rather than to the modern American organisation now known as the National Academy of Medicine.
Today, medical education is generally divided broadly into foundational or pre-clinical sciences and clinical training, although the exact organisation differs from one medical school to another.
During the early years of medical school, students normally encounter subjects such as anatomy, physiology, biochemistry and pathology. Anatomy teaches them the structure of the body, including gross anatomy, histology and embryology. Physiology then asks a different but fundamental question: How do these structures actually work?
Biochemistry explains the chemical processes taking place within living organisms. Pathology examines the causes and mechanisms of disease and the structural and functional changes that result. Pharmacology introduces the student to drugs, how they act on the body and how the body handles them.
Many medical schools also teach microbiology and immunology, which deal with infectious organisms and the body's defence mechanisms. Behavioural sciences, ethics, psychology, communication and aspects of medical law may also be introduced.
The later clinical years bring the student into hospitals and clinics, where these foundational sciences are applied to real patients under supervision.
Students learn internal medicine, surgery, paediatrics, obstetrics and gynaecology, psychiatry and emergency medicine. They may also study family and community medicine, social medicine and preventive medicine.
I personally regard preventive and social medicine as particularly important because, as the old saying reminds us, prevention is better than cure.
Yet if you were to ask me which subjects are most crucial for understanding what happens to the human body in health, disease and treatment, I would immediately think of physiology and pharmacology.
Let me explain why.
Physiology and Pharmacology: Two Disciplines That Work Hand-in-Hand
Firstly, a deep understanding of pharmacology requires a solid foundation in physiology.
The relationship is almost self-evident.
Physiology is the study of how the normal living body and its parts function. Pharmacology is the study of how drugs interact with and alter biological systems.
We cannot fully understand how a drug changes a physiological process unless we first understand how that process normally works.
This distinction becomes particularly clear when we consider two fundamental concepts in pharmacology.
Pharmacodynamics — What the Drug Does to the Body
Pharmacodynamics concerns the effects of a drug on the body.
Drugs may bind to specific receptors, mimic naturally occurring hormones or neurotransmitters, block receptors, inhibit enzymes, alter ion channels or otherwise modify normal biological pathways.
To understand why a drug lowers blood pressure, changes heart rate, alters brain activity or affects hormone action, we need to understand the normal physiology of the cardiovascular, nervous and endocrine systems.
Without that foundation, pharmacology can become little more than a collection of drug names and memorised effects.
Pharmacokinetics — What the Body Does to the Drug
Pharmacokinetics concerns what happens to a drug after it enters the body, how it is absorbed, distributed, metabolised and eliminated.
Again, physiology is fundamental.
The movement of drugs through the body depends upon organ function. We need to understand gastrointestinal absorption, blood flow, plasma protein binding, liver metabolism and kidney filtration and excretion in order to understand how drugs are processed and cleared.
A patient with impaired kidney function, for example, may not eliminate a drug normally. The same dose that is appropriate for a person with normal renal function may therefore produce a much greater exposure in someone whose kidneys are failing.
This is physiology directly influencing pharmacology and, ultimately, clinical practice.
Why the Pharmaceutical Industry Needs Physiologists
When I was a student in the early 1960s, I used to buy a popular scientific magazine called New Scientist. Among the professional advertisements I regularly noticed were vacancies for physiologists and pharmacologists in major drug-development organisations.
This made a strong impression on me.
Pharmaceutical and biotechnology companies employ scientists with expertise in physiology, pharmacology and many related disciplines. In drug development, pharmacologists and physiologists often work closely together, although they approach the problem from somewhat different directions.
One important modern concept is translational physiology—the effort to take findings from basic biological research and understand how they translate into the function of cells, organs and whole living organisms, including humans.
Physiologists can contribute at several stages of the development of a new medicine.
1. Target Identification and Disease Modelling
Before a drug can be developed, scientists need to understand what biological process is disturbed in a disease.
Physiologists help map normal biological pathways and determine how those pathways change during disease.
In conditions such as diabetes or neurodegenerative diseases, for example, researchers need to understand not merely that something has gone wrong, but where and how normal physiological regulation has been disturbed.
Scientists may then develop experimental models, including cell-based in vitro systems and appropriate in vivo models, in which potential treatments can be investigated.
Thus, once again, a deep understanding of normal physiology provides the foundation for understanding abnormal physiology.
2. Preclinical Safety and Off-Target Effects
A drug might successfully kill a cancer cell in a laboratory dish. But what happens when the same compound interacts with a living heart, brain, kidney or liver?
This is where pharmacology and physiology overlap particularly closely.
Cardiovascular physiologists and safety pharmacologists may investigate whether a compound affects the electrical activity and rhythm of the heart, helping to identify potentially dangerous arrhythmias.
Neurophysiological studies can examine whether a drug alters brain activity, nerve conduction or behaviour.
Renal and hepatic specialists can investigate whether a compound adversely affects kidney function or produces liver injury. A medical doctor does not study these areas very much. Their job is to make use of the drugs developed by a team of multi-disciplinary scientists who then tested them extensively before giving them to the doctor with instructions how to prescribe them safely to the patients.
The important point is that a drug does not act in isolation. It enters an extraordinarily interconnected physiological system.
3. Physiologically Based Pharmacokinetic Modelling
Modern drug development also makes extensive use of mathematical modelling and computer simulation to predict how a drug may behave in the human body before it is administered to volunteers.
One example is physiologically based pharmacokinetic (PBPK) modelling.
These models incorporate physiological information such as blood-flow rates, organ volumes, tissue characteristics and other biological parameters to simulate how a drug may be absorbed, distributed, metabolised and excreted.
Such modelling can be particularly useful when researchers and scientists need to consider populations in whom drug handling may differ, including children, older adults and pregnant women.
The pharmacologist may focus intensely on the chemical entity—how a drug molecule binds to a receptor and what molecular or cellular cascade it triggers.
The physiologist looks at the larger picture and asks:
“How does this change ripple through the organ and ultimately alter the function of the living body?”
This systems-level way of thinking is one of the great strengths of physiology.
There are also specialised branches of physiology, such as neurophysiology and cardiovascular physiology, whose knowledge can contribute to the development and understanding of important medicines, including cardiovascular drugs and modern therapies that act on metabolic pathways such as those involving GLP-1.
Why I Call Physiology the Queen of Medicine
In older medical textbooks and teaching traditions, physiology has sometimes been described as “the queen of medicine.”
The analogy also reminds me of the famous description of mathematics as the “queen of the sciences.”
There is an interesting parallel between the two.
1. They Provide a Foundational Language
Mathematics provides a language through which we can express relationships in physics, chemistry and many other sciences.
Likewise to me, physiology provides a fundamental language for medicine.
We cannot properly understand disease, drug action or many aspects of surgical and medical treatment without understanding how the human body normally functions.
Physiology gives us the fundamental rules of the living system.
2. They Shift Our Attention from “What” to “How”
Early scientific study often involved observing and cataloguing what existed.
Mathematics allowed science to move towards quantitative relationships, logical deduction and prediction.
Medicine underwent a somewhat similar transformation.
Anatomy tells us what structures exist. Physiology asks how those structures function.
Pathology tells us what has gone wrong and examines the structural and functional consequences of disease. Pharmacology tells us how drugs can modify biological processes. Surgery may repair, remove or reconstruct structures.
But underlying all of these is the question:
What is the normal physiological function, and what has happened to it?
3. Other Medical Disciplines Ultimately Interact with Physiology
A cardiologist, neurologist, anaesthesiologist, endocrinologist or pharmacist may work in very different areas of medicine, but each ultimately deals with living physiological systems.
The cardiologist is concerned with cardiovascular physiology.
The neurologist deals extensively with nervous-system physiology.
The endocrinologist studies hormonal regulation.
The anaesthesiologist must understand respiration, circulation, consciousness and the body's responses to physiological stress.
The pharmacist and clinical pharmacologist must understand how drugs interact with these systems.
Thus, the branches of medicine may appear increasingly specialised, but beneath them lies a common physiological foundation.
Without mathematics, much of modern science would be reduced to qualitative observation and guesswork.
Without physiology, medicine would lose much of the framework that allows us to understand why a patient becomes ill and how an intervention changes the patient's condition.
Pathology: Physiology Gone Wrong?
This brings me to what I consider one of the most profound ideas in medical science.
It is not possible to understand fully why we fall ill, or how diseases disturb the functions of the body, unless we first understand how the healthy body normally works.
In this sense, pathology is not an entirely separate world from physiology.
It can often be understood as physiology disturbed, dysregulated, overwhelmed or pushed beyond its normal limits.
The French physiologist Claude Bernard, one of the great pioneers of modern physiology and experimental medicine, emphasised the continuity between the laws governing health and those governing disease.
The modern discipline of pathophysiology expresses this relationship particularly well.
I shall write a separate paper on pathophysiology later.
Disease is therefore often a story of normal physiological mechanisms becoming excessive, inadequate, misdirected or unable to compensate any longer.
The Breakdown of Homeostasis
One of the central concepts of physiology is homeostasis.
The body is constantly making adjustments to maintain its internal environment within a range compatible with life. Body temperature, blood glucose, blood pressure, acid-base balance, oxygenation and many other variables are continuously regulated.
Homeostasis does not mean that everything remains absolutely fixed. Rather, it is a dynamic process of constant adjustment.
Pathology often develops when these regulatory mechanisms fail, become overwhelmed or become maladaptive.
For example, when the body can no longer maintain glucose regulation appropriately, persistent hyperglycaemia can develop and diabetes may result.
The disease is not a completely new biological system unrelated to normal physiology. It develops from disturbances in the physiological mechanisms that normally maintain metabolic balance.
The Body's Compensatory Mechanisms
Another important principle is that the body does not simply break down when it is injured or stressed.
It attempts to compensate.
Ironically, some of the body's normal protective responses can themselves contribute to the symptoms or complications of disease when they become excessive or persist for too long.
Inflammation
When we suffer an infection or tissue injury, the body increases blood flow and recruits immune and inflammatory cells to the affected area.
The physiological purpose is protection, containment and healing.
But the consequences of inflammation include redness, heat, swelling and pain. Fever may also occur as part of the body's systemic response.
Thus, a response that is fundamentally protective can itself produce many of the symptoms we experience as illness. Symptoms are not diseases. They are just the cries of the body in distress. Disease is just the body in dis -ease (not at ease).
Heart Failure
Consider heart failure.
When cardiac output falls, the kidneys detect changes in renal perfusion and activate mechanisms, including the renin-angiotensin-aldosterone system that help maintain blood pressure and circulating volume.
Under ordinary circumstances, retaining sodium and water can be an appropriate physiological response to reduced effective circulation.
But in a failing heart, continued fluid retention can become harmful. The increased volume places additional stress on the weakened heart and can contribute to congestion and fluid accumulation in the lungs.
Again, a physiological mechanism designed to preserve circulation can become maladaptive when the underlying disease persists.
Health and Disease Are Often a Continuum
Health and disease are not always two completely separate rooms with an impenetrable wall between them.
They can represent points along a physiological continuum.
As physiological regulation becomes increasingly disturbed, compensatory mechanisms may initially maintain apparent health. Eventually, however, those mechanisms may no longer be sufficient.
Normal blood pressure, for example, can gradually move into a range associated with elevated blood pressure and eventually into persistent hypertension.
Normal cellular proliferation is tightly controlled by numerous regulatory mechanisms. When these safeguards become disrupted, cells may proliferate abnormally, contributing to the development of cancer.
Understanding this continuum transforms pathology from a frightening list of symptoms and diseases into a logical story of a living system attempting to maintain itself under increasing stress.
Let me give three examples that illustrate this transformation from normal physiology to pathophysiology.
1. Asthma: When a Protective Airway Response Becomes Excessive
The Normal Physiology
Our lungs are continuously exposed to the outside world.
The airways therefore possess defensive mechanisms designed to protect the deeper parts of the respiratory system from inhaled particles, irritants and potentially harmful organisms.
Airway smooth muscle, mucus production and the cough reflex all participate in airway defence and clearance.
Mucus can trap particles, while coughing helps remove them.
These mechanisms are normally tightly regulated.
The Pathophysiological Shift
In asthma, the airways become abnormally sensitive and hyper-responsive.
Triggers such as allergens, cold air, exercise or respiratory infections can provoke excessive airway narrowing.
The airway smooth muscle contracts, the airway walls become inflamed and swollen, and mucus production may increase.
The result is that mechanisms intended to protect the airways become excessive and obstruct airflow.
The very system designed to defend the lungs therefore contributes to wheezing, chest tightness and shortness of breath.
This is a beautiful example of how understanding normal physiology helps us understand disease.
2. Kidney Failure: When Filtration and Regulation Become Harmful
The kidneys are remarkable physiological filtering and regulatory organs.
Blood passes through microscopic structures called glomeruli, where filtration takes place. The amount of filtration depends on carefully regulated pressures and blood flow within the renal circulation.
The kidneys also regulate electrolytes, fluid balance, acid-base balance and blood pressure.
The Pathophysiological Shift
Chronic hypertension and diabetes can progressively damage the delicate structures of the kidneys.
In chronic hypertension, prolonged high pressure can contribute to vascular injury and changes such as nephrosclerosis. Diabetes can damage the glomerular and vascular structures through several interacting mechanisms.
As kidney function declines, the remaining functional nephrons may undergo adaptive changes, including increased workload and altered intraglomerular pressure.
At the same time, reduced renal perfusion or impaired renal sensing can activate hormonal systems such as the renin-angiotensin-aldosterone system, contributing to further blood-pressure elevation and fluid retention.
These compensatory responses may initially help preserve filtration and circulation. But when the underlying disease persists, the adaptations can contribute to further renal and cardiovascular damage.
Eventually, the kidneys may lose their ability to maintain the body's internal chemical and fluid environment, resulting in chronic kidney failure.
Once again, normal physiology and pathology are deeply intertwined.
3. Ischaemic Stroke: When Cellular Survival Mechanisms Become Destructive
The brain provides perhaps one of the clearest demonstrations of the importance of physiology.
Brain cells require a continuous supply of oxygen and glucose to generate the energy needed to maintain their electrical gradients and cellular integrity.
Membrane ion pumps, particularly the sodium-potassium pump, continuously maintain the concentration gradients necessary for normal neuronal function.
The Pathophysiological Shift
When a blood clot blocks an artery supplying the brain, an ischaemic stroke occurs.
The affected brain tissue is deprived of oxygen and glucose.
Energy production falls, ATP levels decline and the ion pumps begin to fail. Sodium accumulates inside cells, and water follows, producing cellular swelling known as cytotoxic oedema.
At the same time, injured neurons may release excessive amounts of the excitatory neurotransmitter glutamate.
Glutamate is a normal and essential neurotransmitter involved in processes such as learning and memory. But when released excessively during severe ischaemic injury, it can produce excitotoxicity.
Excessive activation of glutamate receptors allows too much calcium to enter neurons. The resulting calcium overload activates damaging intracellular processes, including oxidative and enzymatic injury, mitochondrial dysfunction and several pathways leading to cell death.
Depending on the severity and circumstances of the injury, both necrotic and programmed forms of cell death can contribute.
Thus, once again, a normal physiological molecule—glutamate can become part of a destructive cascade when the normal physiological system is overwhelmed.
The Same Principle Runs Through Medicine
In all these examples I have illustrated, the disease is not caused by a completely foreign biological process unrelated to normal physiology.
Rather, normal physiological mechanisms have been pushed beyond their limits, become dysregulated, or have responded inappropriately to a persistent pathological stimulus.
This is why I believe that physiology deserves its special place in medical education.
If we know only the names of diseases, we may memorise a catalogue of disorders.
If we understand physiology, we can begin to understand why those diseases develop, why particular symptoms appear, why the body responds as it does, and why particular treatments work.
And if we then understand pharmacology, we can appreciate how medicines deliberately intervene in these physiological and pathophysiological processes.
The pharmacologist asks what the drug molecule does.
The physiologist asks what happens to the living system when that molecular change takes place.
The clinician must ultimately understand both.
Physiology as the Foundation
Medicine has expanded enormously over the decades.
New specialties and subspecialties have appeared as medical research has opened previously unknown frontiers. We now have molecular medicine, genetics, immunology, interventional cardiology, oncology, transplantation medicine, advanced neuroscience and many other highly specialised fields.
This expansion is a sign of the extraordinary progress of medicine.
But beneath all these increasingly sophisticated branches remains the same living human organism.
The heart must still pump.
The lungs must still exchange gases.
The kidneys must still regulate the internal environment.
The nervous system must still communicate.
Hormones must still coordinate organs.
Cells must still obtain energy, maintain their membranes, repair damage and reproduce under controlled conditions.
These are physiological processes.
When they become disturbed, we call the resulting changes pathophysiology and disease.
When we deliberately alter them with medicines, we enter the realm of pharmacology.
That is why, despite the enormous number of medical specialties that have evolved, I still personally regard physiology as the queen of medicine.
It teaches us the language of the living body.
And before we can understand what has gone wrong, we must first understand what right looks like.
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