General Physiology
Learning Objectives
By the end of this page, you should be able to:
- Describe the structure of the cell membrane and explain how it controls what enters and leaves the cell
- Distinguish passive transport (diffusion, facilitated diffusion, osmosis) from active transport (primary and secondary)
- Explain homeostasis as a dynamic, feedback-regulated process rather than a fixed state
- Describe how ATP is generated and why cells depend on continuous energy production
- Summarize the core function of each major organ system and how they cooperate to sustain the internal environment
- Predict how failure of a transport or regulatory mechanism produces a recognizable clinical picture
Quick Answer
General physiology is the study of the basic mechanisms — cellular structure, membrane transport, and homeostatic regulation — that every organ system in the body relies on. It matters because the same handful of principles (concentration gradients, ATP-driven pumps, negative feedback loops) explain phenomena as different as nerve conduction, kidney filtration, and drug absorption. Instead of memorizing organ systems as separate silos, general physiology gives you the shared toolkit: how molecules cross membranes, how the body senses and corrects deviations from a set point, and how cells generate the energy that powers everything else. Master this chapter and every subsequent organ-system chapter becomes an application of principles you already know rather than a fresh set of facts to memorize.
Cellular Structure and Function
Every physiological process ultimately traces back to something happening inside or across a cell. Cells are the smallest units capable of independent metabolic activity, and their structure is built to solve one central problem: staying distinct from — while constantly exchanging material with — the environment around them.
Cell Membrane
The cell membrane (plasma membrane) is a phospholipid bilayer studded with proteins, cholesterol, and carbohydrate chains. The phospholipids arrange themselves tail-to-tail, hydrophobic fatty acid chains facing inward and hydrophilic phosphate heads facing the watery environment on both sides. This arrangement makes the membrane selectively permeable: small nonpolar molecules (O2, CO2, steroid hormones) cross easily, while ions and large polar molecules (glucose, Na+, K+) need help.
Substances cross the membrane through two broad strategies:
- Passive transport — no energy required, movement follows the concentration (or electrochemical) gradient:
- Simple diffusion: lipid-soluble or very small molecules move directly through the bilayer (O2, CO2, ethanol)
- Facilitated diffusion: larger or polar molecules move through specific channel or carrier proteins (glucose via GLUT transporters, ions via leak channels)
- Osmosis: water moves across a semipermeable membrane toward the side with higher solute concentration
- Active transport — requires ATP because molecules move against their gradient:
- Primary active transport: ATP is hydrolyzed directly to move the molecule (Na+/K+-ATPase pumps 3 Na+ out and 2 K+ in per ATP consumed)
- Secondary active transport: the gradient built by a primary pump powers movement of a second molecule (Na+-glucose symporter in the intestine and kidney uses the Na+ gradient created by Na+/K+-ATPase)
Why It Matters: Nearly every drug's ability to reach its target, every neuron's ability to fire, and every kidney tubule's ability to reabsorb sodium depends on these transport mechanisms. Local anesthetics work by blocking Na+ channels; cardiac glycosides (digoxin) work by inhibiting Na+/K+-ATPase.
Common Misunderstanding: Students often think "active transport" simply means "faster" transport. It doesn't — the defining feature is movement against a concentration or electrochemical gradient, which is precisely why it costs energy. A transporter can move molecules quickly via facilitated diffusion (no ATP) or slowly via active transport (ATP-dependent); speed is not the distinguishing factor.
Cytoplasm and Organelles
The cytoplasm is everything inside the plasma membrane except the nucleus — a mix of cytosol (the fluid medium) and suspended organelles, each specialized for a task:
- Mitochondria generate ATP through oxidative phosphorylation (the "powerhouse" description is accurate here — roughly 30-32 ATP per glucose molecule under aerobic conditions, versus 2 ATP from glycolysis alone)
- Ribosomes translate mRNA into protein, either free-floating (cytosolic proteins) or bound to rough endoplasmic reticulum (secreted/membrane proteins)
- Lysosomes contain acid hydrolases that digest damaged organelles and engulfed material; lysosomal enzyme deficiencies cause diseases like Tay-Sachs and Gaucher disease
- Endoplasmic reticulum and Golgi apparatus fold, modify, and package proteins for secretion or membrane insertion
Real-World Example: In sepsis, mitochondrial dysfunction impairs ATP production despite adequate oxygen delivery ("cytopathic hypoxia"), which is one reason lactate rises even when tissue oxygenation appears normal — a distinction tested repeatedly in critical care physiology.
Homeostasis and Regulation
Homeostasis is the maintenance of a relatively stable internal environment despite continuous external and internal disturbances. It is not a static condition — it is a dynamic equilibrium maintained by continuous sensing and correction.
Every homeostatic control system has three components:
- Receptor (sensor) — detects a change in a regulated variable (e.g., baroreceptors detect blood pressure)
- Control center — compares the detected value to a set point (e.g., the hypothalamus, medulla, or an endocrine gland)
- Effector — produces a response that corrects the deviation (e.g., heart, blood vessels, sweat glands)
Most physiological regulation uses negative feedback: the response moves the variable back toward the set point, shutting off its own stimulus. Examples include thermoregulation, blood glucose control by insulin/glucagon, and blood pressure control by the baroreceptor reflex.
Positive feedback is rarer and amplifies the original change rather than reversing it — used only when a process needs to run rapidly to completion, such as the surge of oxytocin during labor contractions or the clotting cascade.
Homeostatically regulated variables include body temperature, blood pH (tightly held at 7.35-7.45), blood pressure, plasma glucose, plasma osmolarity, and extracellular potassium (a narrow range because even small deviations affect cardiac rhythm).
Why It Matters: Nearly every disease can be reframed as a failure of homeostasis — either the sensor fails to detect the deviation, the control center miscalculates the set point, or the effector cannot mount an adequate response. Fever, for instance, is not a failure of thermoregulation; it is thermoregulation working correctly around a reset, higher set point driven by pyrogens.
Common Misunderstanding: Many students assume homeostasis means the body keeps everything constant. In reality, values like heart rate and blood glucose fluctuate continuously; homeostasis means the body keeps these fluctuations within a functional range and returns them to baseline after a perturbation, not that they never move at all.
Energy Production and Utilization
Cells require a continuous ATP supply to power active transport, muscle contraction, biosynthesis, and cell signaling. ATP is generated mainly through catabolism of carbohydrates, fats, and proteins:
- Glycolysis (cytosol, anaerobic-capable): glucose → 2 pyruvate, net 2 ATP
- Citric acid cycle and oxidative phosphorylation (mitochondria, requires O2): pyruvate is fully oxidized, generating roughly 30-32 ATP per glucose
- Beta-oxidation of fatty acids: yields large amounts of ATP but requires oxygen and cannot sustain rapid, high-intensity effort as quickly as glycolysis
When oxygen delivery cannot keep pace with demand (e.g., sprinting, ischemia), cells fall back on anaerobic glycolysis, producing lactate and only a fraction of the ATP yield — which is why sustained anaerobic metabolism is inefficient and unsustainable.
Nervous System Function
The nervous system coordinates rapid, precise communication throughout the body using electrical and chemical signals.
- Central nervous system (CNS): brain and spinal cord; integrates sensory information and generates coordinated output
- Peripheral nervous system (PNS): cranial and spinal nerves carrying signals to and from the CNS, further divided into somatic (voluntary, skeletal muscle) and autonomic (involuntary, sympathetic/parasympathetic) divisions
Signal transmission depends on the same membrane physiology introduced above: the resting membrane potential (roughly -70 mV in neurons) is set by K+ leak channels and maintained by Na+/K+-ATPase, and an action potential is a rapid, self-propagating reversal of that potential driven by voltage-gated Na+ and K+ channels.
Circulatory System Function
The circulatory system delivers oxygen and nutrients while removing metabolic waste, linking every other organ system together.
- Heart: a dual pump — the right side drives pulmonary circulation (oxygenation), the left side drives systemic circulation (delivery)
- Blood vessels: arteries carry blood away from the heart under high pressure, veins return blood at low pressure, and capillaries are the site of actual exchange because their walls are only one cell thick
Cardiac output (heart rate × stroke volume) is itself under homeostatic control via the baroreceptor reflex, illustrating how organ-system physiology is built directly on general regulatory principles.
Respiratory System Function
The respiratory system exchanges O2 and CO2 between the atmosphere and the blood, and it plays a direct role in acid-base homeostasis by controlling how quickly CO2 (a volatile acid precursor) is exhaled.
- Lungs: site of gas exchange across the alveolar-capillary membrane
- Trachea and airways: conduct air to and from the alveoli
- Diaphragm and intercostal muscles: generate the pressure gradients that drive inspiration and expiration
Digestive System Function
The digestive system breaks food down into absorbable units and relies heavily on the transport mechanisms discussed earlier — most nutrient absorption in the small intestine uses secondary active transport (e.g., the Na+-glucose symporter, the physiological basis of oral rehydration therapy).
- Stomach: mechanical churning and acid/pepsin digestion of proteins
- Small intestine: primary site of digestion and absorption
- Liver and pancreas: produce bile and digestive enzymes, and the pancreas additionally regulates blood glucose via insulin and glucagon
Endocrine System Function
The endocrine system achieves slower, longer-lasting regulation than the nervous system by releasing hormones into the bloodstream. Glands such as the thyroid, pancreas, adrenal cortex/medulla, and pituitary secrete hormones that act on distant target cells bearing the appropriate receptor. Because hormone action depends on binding to specific receptors (many of which are membrane proteins), endocrine physiology is another direct extension of the cell membrane principles covered above.
Key Terms
| Term | Definition | Related Concept |
|---|---|---|
| Cell membrane | Selectively permeable phospholipid bilayer that separates the cell interior from its environment | Passive/active transport, fluid mosaic model |
| Passive transport | Movement of molecules across a membrane down their concentration gradient, without ATP | Simple diffusion, facilitated diffusion, osmosis |
| Active transport | Movement of molecules against their concentration gradient, requiring ATP | Na+/K+-ATPase, secondary active transport |
| Osmosis | Diffusion of water across a semipermeable membrane toward higher solute concentration | Tonicity, osmotic pressure |
| Homeostasis | Dynamic maintenance of a stable internal environment via feedback regulation | Negative feedback, set point |
| Negative feedback | A regulatory response that opposes and corrects the original stimulus | Homeostasis, baroreceptor reflex |
| Positive feedback | A regulatory response that amplifies the original stimulus until a process completes | Labor contractions, blood clotting |
| Mitochondria | Organelle responsible for producing most of the cell's ATP via oxidative phosphorylation | Cellular respiration, cytopathic hypoxia |
| Resting membrane potential | The stable voltage difference (~-70 mV) across a neuron's membrane at rest | Na+/K+-ATPase, K+ leak channels |
| Set point | The target value a control system tries to maintain (e.g., 37°C for body temperature) | Homeostasis, fever |
Common Mistakes
Misconception: Facilitated diffusion requires ATP because it uses a protein transporter.
Why it's wrong: Students often equate "needs a protein" with "needs energy." The defining feature of active transport is movement against a concentration gradient, not the mere presence of a transport protein.
Correct understanding: Facilitated diffusion still moves solutes down their concentration gradient — the protein channel or carrier simply provides a path for molecules (like glucose or ions) that cannot cross the lipid bilayer directly. No ATP is consumed.
Misconception: Homeostasis keeps physiological variables perfectly constant at all times.
Why it's wrong: Real physiological variables (heart rate, blood glucose, temperature) fluctuate continuously in response to activity, meals, and stress. If homeostasis meant "never changing," physical exertion or eating a meal would be pathological events.
Correct understanding: Homeostasis is a dynamic equilibrium — the body tolerates fluctuation but actively works to keep the variable within a functional range and returns it to baseline once the disturbance passes.
Misconception: ATP is only produced in the mitochondria.
Why it's wrong: This overlooks glycolysis, which occurs entirely in the cytosol and produces ATP (net 2 per glucose) without any mitochondrial involvement or oxygen requirement.
Correct understanding: Mitochondria are responsible for the majority of ATP yield through oxidative phosphorylation (~30-32 ATP per glucose), but glycolysis in the cytosol is an essential ATP-generating step that can proceed even under anaerobic conditions.
Comparison and Connections
| Feature | Passive Transport | Active Transport |
|---|---|---|
| Direction of movement | Down concentration/electrochemical gradient | Against concentration/electrochemical gradient |
| Energy requirement | None | ATP (directly or via a stored gradient) |
| Examples | Simple diffusion of O2, facilitated diffusion of glucose, osmosis of water | Na+/K+-ATPase, Na+-glucose symporter, Ca2+-ATPase |
| Saturation with high substrate | Only facilitated diffusion saturates (carrier-limited); simple diffusion does not | Saturates once all transporters are occupied |
| Clinical relevance | Impaired GLUT4 function contributes to insulin resistance | Digoxin toxicity from Na+/K+-ATPase inhibition |
| Feature | Negative Feedback | Positive Feedback |
|---|---|---|
| Effect on stimulus | Reduces/reverses it | Amplifies it |
| Purpose | Maintain stability around a set point | Drive a process rapidly to completion |
| Frequency in the body | Common — most homeostatic loops | Rare — reserved for specific events |
| Examples | Thermoregulation, blood glucose control, baroreceptor reflex | Labor contractions (oxytocin), clotting cascade, action potential depolarization phase |
Practice Questions
Recall
-
Name the three components of every homeostatic feedback loop. Answer guidance: Receptor (sensor), control center, and effector.
-
What ion does the Na+/K+-ATPase pump out of the cell, and how many ATP molecules does it consume per cycle? Answer guidance: It pumps 3 Na+ out and 2 K+ in per ATP hydrolyzed.
Understanding
-
Explain why facilitated diffusion is considered passive transport even though it requires a specific membrane protein. Answer guidance: The defining criterion for "passive" is movement down the concentration gradient without ATP expenditure. The carrier protein only provides a pathway across the lipid bilayer for molecules that cannot diffuse through it directly; the driving force is still the concentration gradient, not cellular energy.
-
Why is fever considered a regulated response rather than a failure of thermoregulation? Answer guidance: Pyrogens act on the hypothalamus to raise the temperature set point itself. The body then generates heat (shivering, vasoconstriction) to reach this new, higher set point — the feedback system is functioning normally, just around a different target value.
Application
-
Oral rehydration therapy for cholera-induced diarrhea includes both glucose and sodium in the solution. Using membrane transport physiology, explain why glucose is included even though the patient is not calorically deficient. Answer guidance: The intestinal Na+-glucose symporter (secondary active transport) couples glucose uptake to sodium uptake, and water follows osmotically. Glucose is included specifically to drive sodium (and therefore water) absorption, not primarily for calories.
-
A patient takes a high dose of digoxin and develops arrhythmias. Which specific transport protein is affected, and what happens to intracellular ion concentrations as a result? Answer guidance: Digoxin inhibits Na+/K+-ATPase. Intracellular Na+ rises, which slows the Na+/Ca2+ exchanger, causing intracellular Ca2+ to accumulate — this increases cardiac contractility but at toxic levels disrupts normal electrical rhythm.
Analysis
-
Compare how the body would respond to a drop in blood glucose (negative feedback) versus the hormonal surge during labor (positive feedback) in terms of loop behavior and biological purpose. Answer guidance: Falling glucose triggers glucagon release, which raises glucose back toward the set point and then shuts off the stimulus for further glucagon release — a self-limiting negative feedback loop. In labor, uterine stretch triggers oxytocin release, which increases contractions, further stretching the uterus and triggering more oxytocin — an escalating positive feedback loop that only terminates with delivery, illustrating that positive feedback is reserved for processes that need to reach a decisive endpoint rather than a stable equilibrium.
-
A patient in septic shock has adequate blood oxygen levels but rising lactate. Using cellular energy production physiology, explain a mechanism other than tissue hypoxia that could cause this. Answer guidance: Mitochondrial dysfunction ("cytopathic hypoxia") caused by inflammatory mediators can impair oxidative phosphorylation even when oxygen delivery is adequate, forcing cells to rely more on anaerobic glycolysis and produce lactate despite normal tissue oxygenation — illustrating that lactate reflects cellular energy failure, not oxygen delivery failure alone.
FAQ
What's the real difference between diffusion and osmosis?
Diffusion refers to any solute moving from high to low concentration; osmosis is a special case describing water movement across a semipermeable membrane toward the side with higher solute concentration. Every osmosis question is really asking you to track where the solutes are, because water follows solute concentration, not the other way around.
Why does the body bother with both nervous and endocrine regulation instead of just one?
They are optimized for different timescales. The nervous system uses electrical signals and synapses for rapid, millisecond-to-second responses (withdrawing your hand from heat). The endocrine system uses hormones traveling through blood for slower but longer-lasting and more widespread regulation (growth, metabolic rate, the menstrual cycle). Many physiological responses, like the stress response, use both simultaneously.
Is the resting membrane potential the same in every cell?
No. Resting membrane potential varies by cell type based on the density and type of ion channels present, though most excitable cells (neurons, muscle) sit around -70 to -90 mV. What is constant across cells is the underlying mechanism: an unequal distribution of ions maintained by Na+/K+-ATPase and shaped by resting ion channel permeability.
How does understanding transport mechanisms help with pharmacology later?
Many drugs are named for or act directly on transport proteins: proton pump inhibitors block the H+/K+-ATPase in gastric parietal cells, loop diuretics block the Na+-K+-2Cl symporter in the kidney, and SSRIs block serotonin reuptake transporters. If you understand the normal transporter's job, the drug's mechanism and side effects become predictable rather than memorized.
Why do organ systems get their own chapters if physiology is supposedly unified?
Because each organ system applies the same underlying principles (membrane transport, feedback regulation, energy metabolism) to a specialized problem — gas exchange, filtration, digestion, and so on. Learning general physiology first means you are not re-learning transport and feedback concepts from scratch in every organ chapter; you are seeing familiar tools applied to a new context.
Quick Revision
- Cell membrane = phospholipid bilayer; selectively permeable via channels, carriers, and pumps
- Passive transport (diffusion, facilitated diffusion, osmosis): no ATP, moves down gradient
- Active transport (primary, secondary): requires ATP, moves against gradient
- Na+/K+-ATPase: 3 Na+ out, 2 K+ in, per ATP — sets up gradients used throughout the body
- Homeostasis = dynamic equilibrium maintained by receptor → control center → effector loops
- Negative feedback (common) opposes the stimulus; positive feedback (rare) amplifies it to completion
- Glycolysis (cytosol, 2 ATP net) vs. oxidative phosphorylation (mitochondria, ~30-32 ATP per glucose)
- Anaerobic metabolism produces lactate when oxygen delivery cannot meet demand
- Fever = regulated upward shift of the hypothalamic set point, not a failure of regulation
- Resting membrane potential (~-70 mV) underlies all electrical signaling in nerve and muscle
- Each organ system (cardiovascular, respiratory, digestive, endocrine) is a specialized application of shared transport and feedback principles
- Oral rehydration therapy and drug mechanisms (digoxin, PPIs, diuretics) are direct clinical applications of membrane transport physiology
Related Topics
Prerequisites: Introduction to Physiology, basic cell biology, general chemistry (concentration gradients, pH)
Related Topics: Biochemistry (ATP-generating pathways), Neurophysiology (action potentials, synaptic transmission), Endocrinology (hormone-receptor signaling), Renal Physiology (transport-dependent filtration and reabsorption)
Next Topics: Blood and Body Fluids, Nervous System Physiology, Cardiovascular System Physiology
This page is for educational purposes. Always verify with current clinical guidelines.