Breathing and Exchange of Gases — NEET notes

Respiratory Organs — How animals breathe, from skin to lungs

Different animals use different respiratory surfaces — body surface (sponges, flatworms), skin (earthworm, frog), gills (fish, prawn), tracheal system (insects), and lungs (reptiles, birds, mammals). In humans, the respiratory tract runs from nostrils → nasal cavity → pharynx → larynx → trachea → bronchi → bronchioles → alveoli. The ~300 million alveoli provide an enormous surface area (~100 m²) for gas exchange.

Respiratory Surfaces in Animals

Respiratory organs evolved based on habitat and body complexity. All share one requirement: a thin, moist surface for diffusion of O₂ and CO₂.

Every respiratory surface must be thin, moist, and richly supplied with blood (or hemolymph). The simpler the animal, the simpler the respiratory organ. As body size and metabolic demands increase, more elaborate structures evolved to maximize surface area.

• Frog uses BOTH skin and lungs — skin for aquatic respiration, lungs on land (also buccal cavity lining)
• Gills work in water, lungs work in air — gills collapse in air because lamellae stick together without water's buoyancy
• All respiratory surfaces follow Fick's law: rate of diffusion ∝ (surface area × concentration gradient) / thickness
• Vascularization maintains the concentration gradient by constantly carrying away absorbed O₂

Human Respiratory System

The human respiratory system consists of the conducting part (nostrils to terminal bronchioles — warms, filters, humidifies air) and the respiratory part (respiratory bronchioles to alveoli — actual gas exchange).

1. Nostrils (External nares) — Two openings that lead into the nasal cavity. Lined with hairs that filter large dust particles.
2. Nasal cavity — Lined with mucus-coated ciliated epithelium. Mucus traps dust/bacteria; cilia sweep trapped particles toward pharynx. Air is warmed to body temperature and humidified here.
3. Pharynx — Common passage for air and food. Connects nasal cavity to larynx (air) and oral cavity to esophagus (food).
4. Larynx (Voice box) — Cartilaginous structure containing vocal cords. Epiglottis prevents food from entering trachea during swallowing.
5. Trachea (Windpipe) — ~12 cm tube with C-shaped cartilaginous rings (incomplete posteriorly, where esophagus lies). Rings prevent tracheal collapse. Lined with ciliated epithelium + goblet cells (mucus).
6. Bronchi — Trachea divides into right and left primary bronchi at the carina. Right bronchus is shorter, wider, and more vertical (why inhaled objects usually enter right lung). Bronchi enter the lungs at the hilum.
7. Bronchioles — Successive branching of bronchi; walls have smooth muscle (no cartilage). Terminal bronchioles are the last part of the conducting zone.
8. Alveoli — Tiny, thin-walled (0.2 μm), balloon-like sacs at the end of respiratory bronchioles. ~300 million per pair of lungs → ~100 m² surface area. This is where gas exchange happens.

• Conducting part: nostrils → pharynx → larynx → trachea → bronchi → bronchioles (up to terminal bronchioles). NO gas exchange here — it's 'anatomical dead space' (~150 mL)
• Respiratory part: respiratory bronchioles → alveolar ducts → alveolar sacs → alveoli. GAS EXCHANGE happens only here
• C-shaped tracheal rings are made of hyaline cartilage — incomplete posteriorly to allow esophagus to expand during swallowing
• Right lung has 3 lobes, left lung has 2 lobes (left has less space because of the heart)
• Each lung is enclosed in a double-layered pleural membrane — outer parietal pleura lines the thoracic wall, inner visceral pleura covers the lung surface

Alveoli

Alveoli are thin-walled, highly vascularized sacs that provide the enormous surface area needed for efficient gas exchange between air and blood.

Each alveolus is a microscopic (0.2-0.3 mm diameter), thin-walled pouch surrounded by a dense network of pulmonary capillaries. The barrier between alveolar air and capillary blood is only 0.2 μm thick — that's 500 times thinner than a sheet of paper. This ultra-thin barrier allows rapid diffusion of O₂ and CO₂.

• ~300 million alveoli in both lungs combined → total surface area of ~100 m² (size of half a tennis court!)
• Alveolar wall is made of Type I pneumocytes (thin squamous cells — gas exchange) and Type II pneumocytes (secrete surfactant)
• Surfactant — a phospholipid layer that reduces surface tension, preventing alveolar collapse during expiration
• Rich network of pulmonary capillaries wraps around each alveolus like a net around a ball
• The respiratory membrane (alveolar + capillary walls + basement membranes) is the diffusion barrier — only ~0.2 μm thick

Quick recall

Why doesn't the alveolus collapse despite being so thin and small?

Because Type II pneumocytes secrete surfactant — a phospholipid that reduces surface tension of the fluid lining the alveolar walls. Without surfactant, surface tension would cause alveoli to collapse during each expiration (like a wet plastic bag sticking shut).

Mechanism of Breathing — How air gets in and out of your lungs

Breathing (pulmonary ventilation) involves two phases: inspiration (air in) and expiration (air out). The diaphragm and external intercostal muscles contract during inspiration, expanding the thoracic cavity and lowering intrapulmonary pressure below atmospheric pressure — air rushes in (Boyle's law: volume ↑ → pressure ↓). Expiration is largely passive — muscles relax, volume decreases, pressure rises, air is pushed out. Normal respiratory rate: 12-16 breaths/min.

P_1V_1 = P_2V_2 (Boyle's Law)

Inspiration

During inspiration, the diaphragm contracts (flattens) and external intercostal muscles contract (lift ribs up and out), increasing thoracic volume. By Boyle's law, this expansion lowers intrapulmonary pressure below atmospheric pressure, and air flows in.

1. Diaphragm contracts — The dome-shaped diaphragm flattens, pushing abdominal organs down. This increases the vertical dimension of the thoracic cavity.
2. External intercostal muscles contract — They pull the ribs upward and outward (bucket-handle movement), increasing the anteroposterior and lateral dimensions of the thorax.
3. Thoracic volume increases — Both movements combine to expand the thoracic cavity in all three dimensions.
4. Intrapleural pressure becomes more negative — The pleural space pressure drops further below atmospheric (normally about -4 mmHg, drops to about -6 mmHg during inspiration).
5. Lungs expand passively — Since visceral pleura is stuck to the lungs and parietal pleura to the thoracic wall, lung expansion follows chest expansion (thanks to pleural fluid surface tension).
6. Intrapulmonary pressure drops — Expanded lung volume → pressure inside alveoli falls below atmospheric pressure (Boyle's law: P ∝ 1/V). Drops by about 1-3 mmHg below atmospheric.
7. Air rushes in — Air flows from higher pressure (atmosphere, 760 mmHg) to lower pressure (alveoli, ~757-759 mmHg) through the respiratory tract.

• Inspiration is an ACTIVE process — it requires energy for muscle contraction
• The diaphragm is the primary muscle of respiration — responsible for ~75% of air movement in quiet breathing
• External intercostals assist by lifting ribs (the remaining ~25%)
• During forced inspiration (exercise, deep breath), additional muscles help: sternocleidomastoid, scalenes, pectoralis minor

Expiration

During quiet expiration, the diaphragm and external intercostals simply relax. Elastic recoil of the lungs and chest wall reduces thoracic volume, increasing intrapulmonary pressure above atmospheric — air flows out. Forced expiration recruits internal intercostals and abdominal muscles.

1. Diaphragm relaxes — Returns to its dome shape, pushing up and reducing the vertical dimension of the thoracic cavity.
2. External intercostal muscles relax — Ribs move downward and inward due to gravity and elastic recoil.
3. Elastic recoil of lungs — Stretched elastic fibers in lung tissue snap back, further reducing lung volume.
4. Thoracic volume decreases — The combined effect shrinks the thoracic cavity.
5. Intrapulmonary pressure rises — Decreased volume → increased pressure (Boyle's law again). Pressure rises 1-3 mmHg above atmospheric.
6. Air flows out — From higher pressure (alveoli, ~762-763 mmHg) to lower pressure (atmosphere, 760 mmHg).

• Quiet expiration is PASSIVE — no muscle contraction needed; just relaxation + elastic recoil
• Forced expiration (coughing, blowing, exercise) IS active — uses internal intercostal muscles (pull ribs down and in) + abdominal muscles (push diaphragm up)
• Internal intercostals are OPPOSITE to external intercostals — they pull ribs down and inward
• Normal respiratory rate in adults: 12-16 breaths/minute

Pressure Changes

Three pressures matter: atmospheric (760 mmHg), intrapulmonary (inside alveoli), and intrapleural (between pleural membranes). The interplay of these pressures drives air movement.

Breathing is driven entirely by pressure gradients. Air moves from high pressure to low pressure — that's it. The respiratory muscles don't push or pull air directly; they change the volume of the thoracic cavity, which changes pressure inside the lungs, which creates a gradient with atmospheric pressure.

• Atmospheric pressure = 760 mmHg at sea level (constant, reference point)
• Intrapulmonary (intra-alveolar) pressure = pressure inside the alveoli. Fluctuates during breathing: drops below 760 during inspiration, rises above 760 during expiration. At rest (between breaths) = 760 mmHg
• Intrapleural pressure = pressure in the pleural cavity (between visceral and parietal pleura). ALWAYS negative relative to atmospheric (~756 mmHg = -4 cmH₂O). Becomes more negative during inspiration (~754 mmHg)
• Transpulmonary pressure = intrapulmonary - intrapleural. Always positive → keeps lungs inflated
• If intrapleural pressure equals atmospheric (e.g., chest wound) → lung collapses (pneumothorax)

Quick recall

Why is intrapleural pressure always negative?

Because the elastic recoil of the lungs (pulling inward) and the chest wall's tendency to spring outward create a slight suction in the pleural space. This negative pressure keeps the lungs expanded and prevents collapse. The pleural fluid also creates surface tension that holds the two layers together.

Lung Volumes & Capacities — Measuring what your lungs can really do

Lung volumes are the four non-overlapping air compartments: Tidal Volume (TV ~500 mL), Inspiratory Reserve Volume (IRV ~2500-3000 mL), Expiratory Reserve Volume (ERV ~1000-1100 mL), and Residual Volume (RV ~1100-1200 mL). Capacities are combinations of two or more volumes: Inspiratory Capacity (IC = TV + IRV), Expiratory Capacity (EC = TV + ERV), Functional Residual Capacity (FRC = ERV + RV), Vital Capacity (VC = TV + IRV + ERV, ~3400-4800 mL), and Total Lung Capacity (TLC = VC + RV, ~5000-6000 mL). Measured by spirometry.

VC = TV + IRV + ERV

The 4 Lung Volumes

There are exactly four primary lung volumes that do not overlap. Together they account for all the air the lungs can hold.

Think of your lungs as a container with 4 layers of air stacked on top of each other. Each layer is a 'volume' — and they don't overlap. From bottom to top: Residual Volume (air that never leaves) → Expiratory Reserve Volume (extra you CAN push out) → Tidal Volume (normal breathing air) → Inspiratory Reserve Volume (extra you CAN pull in).

• Only TV is used in normal quiet breathing — the other volumes represent reserves
• During exercise, you dip into both IRV (deeper inspiration) and ERV (more forceful expiration)
• RV cannot be measured by spirometry — it requires helium dilution or body plethysmography
• All values are approximate and vary with age, sex, height, and fitness level

Lung Capacities

Lung capacities are computed by adding two or more lung volumes together. There are five important capacities: IC, EC, FRC, VC, and TLC.

• VC = ERV + TV + IRV — does NOT include RV (since you can't voluntarily expire residual air)
• TLC = VC + RV — the only capacity that includes ALL four volumes
• FRC = ERV + RV — air left after normal expiration; clinically important in lung diseases (increased in emphysema)
• VC is higher in males (~4800 mL) than females (~3100 mL), and higher in athletes than sedentary individuals
• VC decreases with age and in diseases like fibrosis, asthma, and restrictive lung disease

Spirometry

Spirometry is a clinical test that measures lung volumes and capacities (except RV, FRC, and TLC which require special methods). The spirometer produces a graph called a spirogram.

A spirometer is a device that measures the volume of air entering and leaving the lungs. The patient breathes into a mouthpiece connected to the device. The resulting graph (spirogram) shows tidal breathing, maximum inspiration, and maximum expiration — from which TV, IRV, ERV, IC, EC, and VC can be directly read.

• Spirometry CAN measure: TV, IRV, ERV, IC, EC, VC — all involve air that moves in/out
• Spirometry CANNOT directly measure: RV (air trapped in lungs), FRC, and TLC — because they include RV
• RV is measured by helium dilution technique or body plethysmography (not by spirometry)
• Once RV is known: FRC = ERV + RV and TLC = VC + RV can be calculated
• Spirometry also measures FEV₁ (Forced Expiratory Volume in 1 second) — crucial for diagnosing asthma and COPD

Quick recall

Which lung volumes/capacities CANNOT be measured by spirometry?

RV, FRC, and TLC — because all three include the Residual Volume, which is the air that can never be exhaled out. Since the spirometer only measures air that moves in and out, it cannot capture RV.

Exchange of Gases — Partial pressures drive O₂ in and CO₂ out

Gas exchange occurs by simple diffusion across the alveolar membrane, driven by partial pressure gradients. O₂ moves from alveoli (pO₂ ~104 mmHg) to deoxygenated blood (pO₂ ~40 mmHg). CO₂ moves from blood (pCO₂ ~45 mmHg) to alveoli (pCO₂ ~40 mmHg). Factors affecting diffusion rate: partial pressure gradient, membrane thickness, surface area, diffusion coefficient, and solubility (Fick's law).

Rate of diffusion Surface area Pressure gradient Solubility Thickness Molecular weight

Partial Pressure

In a gas mixture, each individual gas exerts a pressure proportional to its concentration — this is its partial pressure. Gases diffuse from regions of higher partial pressure to lower partial pressure.

Atmospheric air is a mixture of gases — ~21% O₂, ~79% N₂, ~0.04% CO₂. Each gas in the mixture exerts its own pressure independently, called its partial pressure (Dalton's law). The partial pressure of O₂ in air (pO₂) = 21% of 760 mmHg ≈ 160 mmHg. The partial pressure of CO₂ (pCO₂) is only ~0.3 mmHg in air.

• O₂ diffuses from alveoli (pO₂ = 104) → blood (pO₂ = 40) because of a 64 mmHg gradient
• CO₂ diffuses from blood (pCO₂ = 45) → alveoli (pCO₂ = 40) because of only a 5 mmHg gradient
• Despite CO₂ having a much smaller gradient, it diffuses equally fast because CO₂ is 20 times more soluble in blood than O₂
• Alveolar pO₂ (~104 mmHg) is less than atmospheric pO₂ (~159 mmHg) because alveolar air mixes with residual air and is humidified

Diffusion Across the Respiratory Membrane

The respiratory membrane (alveolar-capillary barrier) is the actual site of gas exchange. Its properties — thinness, large area, and moisture — are perfectly optimized for diffusion.

The respiratory membrane (also called the diffusion membrane or alveolar-capillary membrane) consists of multiple layers, but together they're incredibly thin:

1. Thin squamous alveolar epithelium (Type I pneumocytes) — the alveolar wall
2. Alveolar basement membrane — thin ECM layer
3. Interstitial space — extremely thin (or absent in places)
4. Capillary basement membrane — thin ECM layer
5. Capillary endothelium — single-cell-thick blood vessel wall
6. Total thickness: only ~0.2 μm — gases cross all these layers by simple diffusion in a fraction of a second

• Total surface area of respiratory membrane: ~100 m² (alveoli + capillary network)
• Membrane is extremely thin (~0.2 μm) — minimizes diffusion distance
• Membrane is always moist — gases dissolve in the fluid layer before diffusing
• Rich blood supply ensures blood is continuously replaced — maintaining the partial pressure gradient
• In diseases like pulmonary fibrosis (thickened membrane) or emphysema (reduced surface area), gas exchange is severely impaired

Fick's Law Factors

The rate of gas diffusion across the respiratory membrane depends on: surface area, partial pressure gradient, membrane thickness, and the diffusion coefficient (which depends on solubility and molecular weight).

Rate of diffusion A P S T MW

Where A = surface area, ΔP = partial pressure difference, S = solubility of gas, T = membrane thickness, MW = molecular weight. This is essentially Fick's law of diffusion applied to the respiratory membrane.

• ↑ Surface area → ↑ diffusion rate. Alveoli provide ~100 m² — massive surface area. Emphysema reduces this.
• ↑ Pressure gradient (ΔP) → ↑ diffusion rate. Exercise increases gradient by increasing O₂ consumption in tissues.
• ↑ Solubility → ↑ diffusion rate. CO₂ is 20× more soluble than O₂ → diffuses fast despite small gradient.
• ↑ Membrane thickness → ↓ diffusion rate. Fibrosis thickens the membrane → impairs gas exchange.
• ↑ Molecular weight → ↓ diffusion rate. CO₂ (MW 44) is heavier than O₂ (MW 32), but CO₂'s higher solubility more than compensates.

Quick recall

A patient with pulmonary fibrosis has difficulty breathing. Which factor in Fick's law is affected?

Membrane thickness (T) is increased due to scar tissue deposition. Since rate ∝ 1/T, the thicker membrane slows diffusion of both O₂ and CO₂, leading to hypoxemia.

Transport of O₂ — Hemoglobin is the delivery truck, the S-curve is the route map

About 97% of O₂ is transported bound to hemoglobin (Hb) as oxyhaemoglobin (HbO₂), and ~3% is dissolved in plasma. Each Hb molecule (Hb₄) has 4 heme groups, each carrying 1 O₂ → max 4 O₂ per Hb. Binding shows cooperative kinetics → sigmoid (S-shaped) oxygen-hemoglobin dissociation curve. The Bohr effect: ↑H⁺, ↑CO₂, ↑temperature, ↑2,3-BPG shift the curve RIGHT → easier O₂ unloading at tissues. Opposite conditions shift LEFT → tighter O₂ binding at lungs.

Hb_4 + 4O_2 leftharpoons Hb_4(O_2)_4

Hemoglobin Structure

Hemoglobin is a quaternary protein with 4 polypeptide chains (2α + 2β in adult HbA), each containing an iron-bearing heme group that reversibly binds one O₂ molecule.

Hemoglobin (Hb) is a metalloprotein found in RBCs. Each Hb molecule consists of 4 subunits — 2 alpha (α) chains and 2 beta (β) chains (in adult hemoglobin, HbA). Each subunit has a heme group at its core — an iron-porphyrin complex where Fe²⁺ binds O₂ reversibly.

• Each Hb has 4 heme groups → can bind 4 O₂ molecules (one per heme)
• Iron must be in Fe²⁺ (ferrous) state to bind O₂. If oxidized to Fe³⁺ (ferric), it forms methemoglobin — cannot carry O₂
• Normal Hb concentration: 12-16 g/dL in women, 14-18 g/dL in men
• Each gram of Hb can carry 1.34 mL O₂ → 100 mL blood with 15 g Hb carries ~20 mL O₂
• ~97% of O₂ is carried as HbO₂ (oxyhaemoglobin); only ~3% dissolved in plasma
• Fetal hemoglobin (HbF) has 2α + 2γ chains — binds O₂ more tightly than HbA (helps fetus extract O₂ from maternal blood)

Oxygen-Hemoglobin Dissociation Curve

The O₂-Hb dissociation curve plots % saturation of Hb against pO₂. It's S-shaped (sigmoid) due to cooperative binding. At the lungs (high pO₂), Hb is ~97% saturated. At tissues (low pO₂), Hb releases O₂ efficiently.

Plot pO₂ on the x-axis and % saturation of Hb on the y-axis. The resulting curve is S-shaped (sigmoid) — not a straight line. This shape is critical: it means Hb loads O₂ efficiently at the lungs AND unloads it efficiently at the tissues.

• At pO₂ = 104 mmHg (lungs): Hb is ~97-98% saturated → maximum loading
• At pO₂ = 40 mmHg (resting tissues): Hb is ~75% saturated → releases ~25% of its O₂
• At pO₂ = 20 mmHg (active tissues/exercise): Hb is ~35% saturated → releases much more O₂
• The steep middle portion of the curve is where small changes in pO₂ cause large changes in O₂ release — this corresponds to tissue pO₂ ranges
• The flat upper portion means that even if pO₂ drops a bit at the lungs (e.g., at moderate altitude), Hb still loads almost fully — a safety margin

Quick recall

At resting tissue pO₂ (~40 mmHg), what percentage of Hb's O₂ is released?

Hb is ~75% saturated at 40 mmHg and ~97% at the lungs → it releases about 25% of its O₂ to resting tissues (the difference). During exercise, when tissue pO₂ drops further, Hb releases up to 60-70% of its O₂.

Bohr Effect & Curve Shifts

The Bohr effect: increased CO₂ and H⁺ (lower pH) decrease Hb's affinity for O₂ → right shift of the dissociation curve. This ensures O₂ is released more readily at active tissues. Temperature and 2,3-BPG also shift the curve.

Active tissues produce lots of CO₂, lactic acid (H⁺), and heat. All of these signal Hb: 'We need more O₂ here — drop your load!' Hb obeys by changing its shape slightly, weakening its grip on O₂. This is the Bohr effect — the shift in O₂-Hb dissociation curve caused by CO₂ and pH changes.

• Bohr effect specifically refers to the effect of CO₂ and H⁺ on O₂-Hb affinity
• CO₂ lowers affinity by two mechanisms: (1) direct binding to Hb (forms carbaminohaemoglobin, changes shape), (2) CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻ (lowers pH)
• 2,3-BPG (2,3-bisphosphoglycerate) is produced in RBCs; it binds to deoxy-Hb and stabilizes the T-state (low-affinity state). ↑ at high altitude → helps O₂ release
• Fetal Hb (HbF) binds 2,3-BPG poorly → LEFT-shifted curve → higher O₂ affinity → extracts O₂ from maternal blood efficiently
• CO (carbon monoxide) binds Hb 250× more tightly than O₂ → shifts curve LEFT and blocks O₂ binding → deadly because it doesn't let go

Transport of CO₂ & Regulation — Three rides for CO₂ and the brain's breathing control room

CO₂ is transported in three forms: dissolved in plasma (~7%), as carbaminohaemoglobin bound to Hb (~23%), and as bicarbonate ions HCO₃⁻ (~70%). The bicarbonate pathway involves carbonic anhydrase in RBCs and the chloride shift. Breathing is regulated by the respiratory centre in the medulla oblongata, with input from pneumotaxic centre (pons), chemoreceptors (central in medulla, peripheral in carotid/aortic bodies), and stretch receptors in lungs (Hering-Breuer reflex).

CO_2 + H_2O carbonic anhydrase H_2CO_3 leftharpoons H^+ + HCO_3^-

Three Forms of CO₂ Transport

CO₂ produced by tissues enters the blood and is transported to the lungs in three ways. The bicarbonate pathway dominates (70%), followed by carbaminohaemoglobin (23%), and dissolved CO₂ (7%).

• Carbonic anhydrase — the key enzyme, found in HIGH concentration inside RBCs (not in plasma). Catalyzes CO₂ + H₂O ⇌ H₂CO₃ extremely fast (~600× normal)
• H₂CO₃ (carbonic acid) immediately dissociates → H⁺ + HCO₃⁻
• The H⁺ released is buffered by deoxy-Hb (which is a better buffer than oxy-Hb) → prevents blood from becoming too acidic
• HCO₃⁻ exits the RBC via band 3 protein (anion exchanger) → enters plasma for transport
• Cl⁻ enters the RBC to maintain electrical neutrality → this is the chloride shift (Hamburger phenomenon)

Chloride Shift

As HCO₃⁻ is produced inside RBCs and moves out to plasma, Cl⁻ ions move IN to maintain electrical neutrality. This exchange is called the chloride shift or Hamburger phenomenon. At the lungs, the entire process reverses.

1. At the tissues: CO₂ diffuses into RBCs from tissue capillaries.
2. Carbonic anhydrase converts CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻.
3. HCO₃⁻ moves OUT of RBC into plasma via band 3 protein (anion exchanger).
4. To balance the charge, Cl⁻ moves INTO the RBC from plasma → chloride shift.
5. H⁺ is buffered by deoxygenated Hb (Hb acts as a buffer).
6. In plasma, HCO₃⁻ is carried to the lungs as the primary CO₂ transport form.
7. At the lungs: The entire process REVERSES — Cl⁻ exits RBC, HCO₃⁻ re-enters, carbonic anhydrase reforms CO₂ + H₂O from H₂CO₃, CO₂ diffuses out into alveoli.

• Chloride shift is mediated by band 3 protein (also called AE1 — anion exchanger 1)
• Venous blood RBCs have MORE Cl⁻ and MORE water (slight swelling) than arterial blood RBCs
• The entire process is reversible — at lungs, HCO₃⁻ re-enters RBCs, Cl⁻ exits, CO₂ is regenerated and exhaled
• This shift happens very rapidly — within the ~0.75 seconds blood spends in a tissue capillary

Quick recall

Why do RBCs in venous blood contain more Cl⁻ than in arterial blood?

Because of the chloride shift. At tissues, HCO₃⁻ produced from CO₂ exits the RBC → Cl⁻ enters to maintain charge balance. So venous RBCs accumulate Cl⁻. At the lungs, the process reverses — Cl⁻ exits again.

Regulation of Respiration

Breathing is controlled by the respiratory centre in the medulla oblongata, fine-tuned by the pneumotaxic centre in the pons, and modulated by chemoreceptors that detect CO₂, H⁺, and O₂ levels in the blood.

You don't have to think about breathing — it's automatic, controlled by neural centres in the brainstem. But you CAN override it voluntarily (hold your breath, breathe faster). This dual control makes respiration unique — part involuntary, part voluntary.

• Respiratory centre — located in the medulla oblongata. Contains the inspiratory area (dorsal respiratory group) and expiratory area (ventral respiratory group). Generates the basic breathing rhythm.
• Pneumotaxic centre — located in the pons (above medulla). Sends inhibitory signals to the inspiratory area → controls the duration and depth of inspiration. More signals from pneumotaxic centre → shorter inspiration → faster breathing rate.
• Apneustic centre — also in the pons. Stimulates inspiration (opposes pneumotaxic centre). Less clinically important for NEET.
• Central chemoreceptors — in the medulla. Detect ↑H⁺ / ↑CO₂ in cerebrospinal fluid. MOST sensitive regulators of breathing.
• Peripheral chemoreceptors — in carotid bodies (at bifurcation of common carotid artery) and aortic bodies (near aortic arch). Detect ↓O₂, ↑CO₂, and ↑H⁺ in arterial blood.