Human Body
The scale at which medicine operates: symptoms are experienced here, diagnoses made here, therapies applied here, outcomes measured here. All seven scales below — from electron orbitals to organ systems — contribute constraints whose emergent behavior is a living person.
Overview — Integrative Biology
The human body is a tightly coupled network of eleven major organ systems operating under constant homeostatic regulation. No system acts in isolation: the cardiovascular system carries oxygen and hormones that every other system depends on; the nervous system encodes and coordinates; the endocrine system broadcasts chemical signals with whole-body reach; the musculoskeletal system houses haematopoiesis and enables movement; the immune system surveils every tissue. Understanding any single disease requires tracing its origins and consequences across multiple scales and systems simultaneously.
This atlas entry serves as the whole-body hub — a navigational and conceptual anchor linking all organism-level parameters (body composition, physiological set-points, homeostatic mechanisms) down to the molecular, atomic, and cellular entries that underpin them.
Body Composition — Reference 70 kg Adult
| Component / Element | % Body Mass | ~Mass (70 kg) | Primary Location / Role |
|---|---|---|---|
| Water (H₂O) | 60% | ~42 L | ICF ~28 L, ECF ~14 L (plasma 3 L, interstitial 11 L) |
| Protein | 17% | ~12 kg | Skeletal muscle (~8 kg), structural collagen, enzymes, antibodies |
| Fat (lipid) | 15% | ~10.5 kg | Adipose (~9 kg), structural membranes, myelin; varies widely |
| Minerals (total) | 6% | ~4.2 kg | Bone (~3.7 kg as hydroxyapatite Ca/P); electrolytes in solution |
| Carbohydrate | <1% | ~500 g | Glycogen (liver ~100 g, muscle ~400 g); glucose in plasma ~5 g |
| • Oxygen (O) | 65% | ~45.5 kg | Dominant element; in water, proteins, lipids, nucleic acids |
| • Carbon (C) | 18% | ~12.6 kg | Backbone of every organic molecule |
| • Hydrogen (H) | 10% | ~7 kg | Most abundant by atom count (~60% of atoms); in water and all C-H bonds |
| • Nitrogen (N) | 3% | ~2.1 kg | All proteins, nucleotides, haem, nitric oxide |
| • Calcium (Ca) | 1.5% | ~1.05 kg | 99% in bone; cytosolic Ca²⁺ is universal second messenger |
| • Phosphorus (P) | 1.0% | ~700 g | 85% in bone; ATP, phospholipids, nucleic acids |
| • Potassium (K) | 0.35% | ~245 g | Principal intracellular cation; resting membrane potential |
| • Sodium (Na) | 0.15% | ~105 g | Principal extracellular cation; osmolality, action potentials |
| • Trace minerals | <0.1% | <70 g | Fe (haemoglobin/cytochromes), Zn (enzymes), Mg (ATP-Mg, 300+ enzymes), I (thyroid hormones), Se (glutathione peroxidase), Cu, Mn, Cr, Mo |
Key Physiological Parameters — Rest vs. Exercise
| Parameter | Rest | Moderate exercise | Maximal exercise (trained) |
|---|---|---|---|
| Heart rate (HR) | 60–80 bpm | 100–140 bpm | 180–200 bpm |
| Stroke volume (SV) | 60–80 mL | 100–130 mL | 160–200 mL (trained) |
| Cardiac output (CO) | ~5 L/min | 12–18 L/min | 20–40 L/min (elite) |
| Mean arterial pressure (MAP) | ~93 mmHg | 100–110 mmHg | 110–120 mmHg |
| Systemic vascular resistance (SVR) | ~1200 dyn·s/cm⁵ | ↓ 50–60% | ↓ 70–75% |
| VO₂ (oxygen consumption) | ~250 mL/min (3.5 mL/kg/min) | 1.5–2.5 L/min | 3–6 L/min |
| Ventilation (VE) | ~6 L/min | 30–60 L/min | 120–180 L/min |
| Respiratory rate (RR) | 12–16 breaths/min | 20–30 breaths/min | 40–60 breaths/min |
| Arterial O₂ saturation (SpO₂) | 97–99% | 96–99% | 93–98% (may fall at elite max) |
| Blood glucose | 4.4–5.6 mmol/L | 4–7 mmol/L | 4–8 mmol/L |
| Core body temperature | 36.5–37.5 °C | 38–39 °C | 39–41 °C |
| Plasma lactate | <1 mmol/L | 2–4 mmol/L (LT1–LT2) | 8–15 mmol/L |
Systems Integration — All 11 Systems
┌─────────────────────────────────────────────────────────────┐
│ NERVOUS SYSTEM (CNS + PNS + ANS) │
│ Coordinates all other systems; ~20% resting energy budget │
└─────┬───────────────────┬───────────────────────┬───────────┘
│ motor/sensory │ autonomic │ HPA axis
▼ ▼ ▼
┌────────────────────┐ ┌────────────────────┐ ┌────────────────────┐
│ MUSCULOSKELETAL │ │ CARDIOVASCULAR │ │ ENDOCRINE │
│ Movement, support │◄─┤ O₂/nutrient │ │ Hormonal broadcast│
│ Haematopoiesis │ │ delivery │ │ Metabolic control │
│ Myokines (IL-6, │ │ CO × (CaO₂−CvO₂) │ │ HPA, HPT, HPG │
│ irisin, BDNF) │ │ = VO₂ (Fick) │ │ Insulin/glucagon │
└─────────┬──────────┘ └──────┬─────────────┘ └──────┬─────────────┘
│ O₂ demand │ transport │ hormones
│ ▼ │
│ ┌────────────────────┐ │
│ │ RESPIRATORY │ │
│ │ O₂ uptake / CO₂ │ │
│ │ elimination │ │
│ │ pH buffering │ │
│ └──────┬─────────────┘ │
│ │ oxygenated blood │
▼ ▼ ▼
┌────────────────────┐ ┌────────────────────┐ ┌────────────────────┐
│ LYMPHATIC / │ │ RENAL │ │ DIGESTIVE │
│ IMMUNE │ │ Fluid/electrolyte │ │ Nutrient absorption│
│ Pathogen defence │◄─┤ homeostasis │ │ Liver: metabolic │
│ GC reactions │ │ RAAS / EPO / │ │ hub; bile; detox │
│ OPSI protection │ │ Calcitriol │ │ Microbiome │
└────────────────────┘ └──────┬─────────────┘ └──────┬─────────────┘
│ fluid/Na⁺ │ nutrients
▼ ▼
┌────────────────────┐ ┌────────────────────┐
│ INTEGUMENTARY │ │ REPRODUCTIVE │
│ Barrier; thermo- │ │ Reproduction; │
│ regulation; UV │ │ HPG axis; sex │
│ vitamin D synth. │ │ steroids systemic │
└────────────────────┘ └────────────────────┘
Central homeostatic variable: MAP, SpO₂, core temp, pH, plasma [glucose], [Na⁺], [K⁺]
All systems contribute effectors; nervous + endocrine systems integrate set-point error signals
Homeostasis Principles
Homeostasis is the maintenance of physiological variables within narrow ranges despite continuously varying external and internal conditions. The key principles governing whole-body homeostasis are:
Negative Feedback Loops
The dominant regulatory mechanism. A sensor detects deviation from set-point; an integrator computes error signal; effectors act to oppose the deviation. Examples: baroreflex (baroreceptors → NTS → sympathetic/vagal → HR/SVR → MAP restored); thyroid HPT axis (TRH→TSH→T3/T4→ negative feedback on pituitary TRβ); glucose homeostasis (hyperglycaemia → β cell insulin → GLUT4 translocation → glucose uptake → normoglycaemia).
Positive Feedback & Set-Point Shifts
Positive feedback amplifies deviation and is used for controlled transitions: the LH surge (oestradiol → GnRH → LH spike → ovulation); platelet aggregation in haemostasis; childbirth oxytocin surges. Set-points themselves shift: circadian rhythms lower core temperature at night; exercise training lowers resting HR set-point; fever elevates temperature set-point via PGE2 at the hypothalamic preoptic area.
Feedforward Control
Anticipatory responses occur before a perturbation is detected by sensors. Examples: cephalic phase insulin release (sight/smell of food → vagal → pre-emptive insulin spike before glucose absorption); anticipatory heart rate rise before exercise begins (central command); shivering initiated before core temperature actually falls during cold exposure. Feedforward improves response speed but requires learned/conditioned circuits.
Redundancy & Hierarchy
Critical variables are regulated by multiple overlapping mechanisms: MAP is controlled by short-term (baroreflex, seconds), medium-term (capillary fluid exchange, minutes), and long-term (RAAS/renal pressure-natriuresis, days) mechanisms in hierarchical sequence. Acid-base pH is buffered by bicarbonate (immediate), respiratory compensation (minutes), and renal compensation (hours-days). Loss of one layer is compensated by others until tipping points are crossed.
Fick Principle and VO₂max
The Fick principle is the quantitative foundation of whole-body oxygen physiology, relating the three measurable variables of oxygen transport:
At maximal exercise, both CO and O₂ extraction increase. VO₂max is primarily limited by cardiac output in health and normoxia (Saltin-Calbet consensus): exercising muscle can extract more oxygen than a healthy heart can deliver, making pump capacity the bottleneck. Endurance training raises VO₂max largely through increased maximal stroke volume (via eccentric ventricular remodeling and expanded plasma volume), not increased maximal HR.
Exercise demand↑ → CO must rise 4–5× (5 → 20–25 L/min) Step 1: Central command (motor cortex) → anticipatory HR↑ before muscles contract Step 2: Active muscle metaboreflex (H⁺/K⁺/adenosine → group III/IV afferents → ↑SNS) Step 3: Venous return augmentation (skeletal muscle pump + respiratory pump + venoconstriction) Step 4: Frank-Starling mechanism (↑EDV → ↑SV) — primary CO augmentation at moderate intensity Step 5: Sympathetic-mediated redistribution: muscle β2-AR vasodilation; splanchnic/renal α1 constriction → MAP maintained At peak: SV near-maximal → further CO rise = HR-dependent Cardiac output ceiling → VO₂max ceiling
Levine (2008) provides the definitive analysis: central (CO) and peripheral (muscle oxidative capacity, mitochondrial density, capillarization) factors both matter, with CO dominant in sedentary individuals and peripheral capacity becoming limiting in highly trained states.
RAAS — Multi-Organ Volume/Pressure Regulator
The renin-angiotensin-aldosterone system is the body's primary long-term, multi-organ mechanism for blood pressure and extracellular volume regulation, integrating kidney, liver, lung, adrenal cortex, pituitary, and hypothalamus:
Trigger stimuli:
↓ Renal perfusion pressure ─┐
↑ Sympathetic (β1-AR) ├──→ JG cells (juxtaglomerular apparatus) → RENIN secretion
↓ Macula densa [Na⁺/Cl⁻] ─┘
Renin (kidney) + Angiotensinogen (liver) → Angiotensin I (inactive decapeptide)
↓ ACE (lung + vascular endothelium)
Angiotensin II (Ang II) ──→ AT1 receptor effects:
├── Vascular smooth muscle → vasoconstriction → ↑SVR → ↑MAP
├── Adrenal cortex (zona glomerulosa) → ALDOSTERONE → Na⁺/H₂O retention → ↑blood volume
├── Posterior pituitary → ADH (vasopressin) → renal aquaporin-2 → ↑water retention
├── Hypothalamus → thirst centre → ↑fluid intake
└── Heart/vasculature (chronic) → fibrosis, hypertrophy (maladaptive in HFrEF)
Negative feedback: ↑MAP → ↓renin secretion; atrial stretch → ANP/BNP → ↓renin/aldosterone
Drug targets:
ACE inhibitors (enalapril) → ↓Ang II ARBs (losartan) → block AT1 receptor
ARNi sacubitril/valsartan → ↑ANP/BNP + AT1 block Spironolactone → aldosterone antagonist
Autonomic Regulation & Heart Rate Variability
The autonomic nervous system modulates all visceral organs on a beat-to-beat basis through two opposing limbs. Sympathetic fibres release norepinephrine at β1-AR (heart: ↑HR, ↑contractility, ↑AV conduction) and α1 (vasculature: vasoconstriction). Epinephrine from the adrenal medulla amplifies the response during stress. Parasympathetic fibres release acetylcholine at M2 muscarinic receptors (SA node: ↓HR via IKAch activation; AV node: ↓dromotropy). Vagal tone dominates at rest, suppressing intrinsic SA rate (~100 bpm) to typical resting HR of 60–80 bpm.
Heart rate variability (HRV) — beat-to-beat variation in R-R intervals — is a non-invasive whole-body readout of sympathovagal balance. The high-frequency component (HF-HRV, 0.15–0.4 Hz) reflects vagal tone. High HRV correlates with better cardiovascular outcomes, lower all-cause mortality, and greater cardiac reserve. HRV declines with ageing, heart failure, diabetes, and autonomic neuropathy; it increases with endurance training and improves with vagal neuromodulation therapies.
Whole-Body Pathological Phenotypes
Shock
Failure of cardiac output or systemic vascular resistance to maintain MAP ≥ 60 mmHg → inadequate tissue O₂ delivery → anaerobic metabolism → lactic acidosis → multi-organ dysfunction. Types: distributive (septic, anaphylactic — ↓SVR); hypovolaemic (haemorrhage, burns — ↓preload); cardiogenic (MI, HFrEF — ↓CO); obstructive (PE, tamponade — ↓venous return). Universal endpoint if untreated: MODS (multi-organ dysfunction syndrome) and death.
Heart Failure Syndrome
↓CO → ↓renal perfusion → RAAS activation → Na⁺/H₂O retention → ↑blood volume → pulmonary and peripheral oedema (right/left HF). Simultaneously, ↓CO reduces O₂ delivery to exercising muscle → exertional dyspnoea and fatigue (HFrEF: EF <40%). Maladaptive RAAS and sympathetic activation drives cardiac remodelling, worsening function. Key biomarker: BNP/NT-proBNP (released by stretched myocytes). Treatment: ACE-i/ARB/ARNi + β-blocker + MRA + SGLT2 inhibitor.
Hypertension
Sustained MAP elevation (systolic ≥ 130 mmHg and/or diastolic ≥ 80 mmHg, ACC/AHA 2017). Multi-scale origin: ↑Na⁺ retention (kidney; genetic variants in NCC, ENaC), ↑RAAS activation, ↑SNS tone, ↑vascular smooth muscle tone, arterial stiffness (collagen cross-linking, reduced NO). Consequence: left ventricular hypertrophy, stroke, MI, CKD, retinopathy. Primary HTN: >95% of cases — polygenic. Secondary causes: renal artery stenosis, phaeochromocytoma, primary aldosteronism, OSA.
Exercise Intolerance
↓VO₂max from ↓COmax (HFrEF, coronary disease), ↓skeletal muscle oxidative capacity (deconditioning, mitochondrial disease, sarcopenia), ↓haemoglobin O₂-carrying capacity (anaemia), or pulmonary limitation (COPD, ILD). CPET (cardiopulmonary exercise test) with VO₂max measurement distinguishes cardiac vs. ventilatory vs. peripheral causes — the Fick equation disaggregated into components.
Orthostatic Hypotension
↓MAP ≥ 20/10 mmHg within 3 min of standing. Mechanisms: ↓baroreflex sensitivity (ageing, autonomic neuropathy in diabetes/Parkinson's), ↓venous return (hypovolaemia, vasodilation from medications), ↓cardiac reserve. Can cause syncope, falls, and cognitive impairment from cerebral hypoperfusion. Treatment: volume expansion, compression garments, fludrocortisone, midodrine (α1 agonist).
Metabolic Syndrome
Cluster of whole-body metabolic dysregulation: central obesity (waist ≥ 102 cm men / ≥ 88 cm women), hyperglycaemia (fasting ≥ 5.6 mmol/L), hypertriglyceridaemia (≥ 1.7 mmol/L), low HDL-C, hypertension. Prevalence ~30–40% in Western populations. Pathophysiology: insulin resistance → adipocyte-driven ectopic lipid deposition → hepatic lipogenesis → VLDL ↑ + HDL-C ↓; visceral adipose IL-6/TNF-α → systemic inflammation → endothelial dysfunction → atherosclerosis. Highly amenable to lifestyle intervention.
Physiological Variation
| Variable | Key determinants | Physiological effect |
|---|---|---|
| Sex | Testosterone (muscle mass, RBC mass, LV size); oestrogen (lipid profile, coagulation, bone) | Women: higher resting HR, lower VO₂max/kg (~10–15%), higher HDL-C, lower haemoglobin; men: higher SVT/MI risk pre-menopause |
| Age | VO₂max falls ~10%/decade after 25; arterial stiffness ↑ (collagen cross-linking); HRV ↓; baroreflex sensitivity ↓ | Reduced exercise capacity; orthostatic hypotension risk; impaired immune response; sarcopenia after 50 |
| Athletic training | Eccentric LV hypertrophy; plasma volume expansion (~10–20%); ↑mitochondrial density | ↑SV at rest and exercise; ↓resting HR; ↑VO₂max; ↑HRV; altered Fick equation both sides |
| Altitude | ↓PO₂ → ↓SaO₂ → ↓CaO₂ | Acute: ↓VO₂max, ↑HR, ↑VE. Adaptation (weeks): ↑EPO → ↑RBC mass → restored O₂ delivery; ↑2,3-DPG shifts HbO₂ curve right |
| Obesity | ↑Adipose mass → ↑mechanical load, ↑inflammatory cytokines, insulin resistance, OSA | ↓VO₂max (relative), ↑BP, ↑risk metabolic syndrome, ↓HRV, impaired immune function |
All-Scales Connections
The whole body contains and integrates all eleven major organ systems and all scales beneath them:
References
- Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. 14th ed. Elsevier; 2020. ISBN 978-0-323-59712-8. elsevier.com
- Saltin B, Calbet JA. Point: in health and in a normoxic environment, VO2max is limited by cardiac output. J Appl Physiol. 2006;100(2):744–748. doi:10.1152/japplphysiol.01431.2005 · PubMed 16428358
- Levine BD. VO2max: what do we know, and what do we still need to know? J Physiol. 2008;586(1):25–34. doi:10.1113/jphysiol.2007.147629 · PubMed 17855754
- Bianconi E et al. An estimation of the number of cells in the human body. Ann Hum Biol. 2013;40(6):463–471. doi:10.3109/03014460.2013.807878
- Task Force of the European Society of Cardiology and the North American Society. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation. 1996;93(5):1043–1065. PMID 8598068.