---

RESPIRATORY PHYSIOLOGY - 5 MARKER ANSWERS

---

1. NON-RESPIRATORY FUNCTIONS OF THE LUNG

1. Filtration: The pulmonary capillary bed acts as a filter, trapping microemboli (small clots, fat emboli, air bubbles) from venous blood before they reach the systemic circulation.
2. Metabolic functions: The lungs metabolize vasoactive substances. Angiotensin I is converted to Angiotensin II by ACE (angiotensin-converting enzyme) located on pulmonary endothelium. Bradykinin, serotonin (5-HT), and prostaglandins (E1, E2, F2α) are inactivated in the lung.
3. Reservoir function: The pulmonary circulation acts as a blood reservoir. Approximately 450-500 mL of blood is held in the pulmonary vasculature at any time and can be rapidly shifted to/from systemic circulation.
4. Immunological defense: Alveolar macrophages phagocytose inhaled particles, bacteria, and debris. IgA secretion and mucociliary clearance protect the airways.
5. Surfactant synthesis: Type II pneumocytes synthesize and secrete surfactant (dipalmitoyl phosphatidylcholine - DPPC), which reduces alveolar surface tension, prevents alveolar collapse, and reduces the work of breathing.
6. Vocalization and thermoregulation (panting in animals).

---

2. TRANSPORT OF O₂ AND CO₂

O₂ Transport:

• O₂ is transported in two forms:
  • Dissolved in plasma: ~1.5% (0.3 mL/dL at PO₂ = 100 mmHg)
  • Bound to hemoglobin: ~98.5% (as oxyhemoglobin)
• Each gram of Hb carries 1.34 mL O₂; normal Hb (15 g/dL) carries ~20 mL O₂/dL blood
• PO₂ in alveoli = 104 mmHg; venous blood entering pulmonary capillary = 40 mmHg → pressure gradient of 64 mmHg drives diffusion
• O₂ rapidly saturates Hb as blood passes through pulmonary capillaries (within 1/3 of capillary length)

CO₂ Transport (three forms):

• In tissues: CO₂ enters RBCs → carbonic anhydrase rapidly converts CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻
• HCO₃⁻ exits RBC into plasma in exchange for Cl⁻ (Chloride shift)
• In lungs: process reverses; CO₂ diffuses out (tissue PCO₂ = 45 mmHg; alveolar PCO₂ = 40 mmHg)
• Hb transports blood CO₂ 15-20 times more than if dissolved alone

---

3. MECHANISM OF INSPIRATION & EXPIRATION

INSPIRATION (Active Process):

1. Inspiratory center (dorsal respiratory group) in medulla fires → activated by apneustic center (lower pons)
2. Nerve impulses travel via phrenic nerve (C3, C4, C5) to diaphragm → contracts, moves downward ~1.5 cm (quiet breathing), up to 10 cm (deep breathing)
3. External intercostal muscles contract → ribs pulled upward and outward → increase in thoracic AP and transverse diameter
4. Thoracic volume increases → pleural pressure falls from -5 to -7.5 cm H₂O
5. Alveolar pressure drops to -1 cm H₂O below atmospheric → air flows in (0.5 L in 2 seconds during quiet breathing)

EXPIRATION (Passive in quiet breathing):

1. At peak inspiration, stretch receptors in lungs send inhibitory impulses via vagus to apneustic center (Hering-Breuer reflex)
2. Pneumotaxic center (upper pons) also inhibits apneustic center
3. Inspiratory center ceases firing → inspiratory muscles relax
4. Lung elastic recoil + chest wall recoil → thoracic volume decreases → pleural pressure returns to -5 cm H₂O
5. Alveolar pressure rises to +1 cm H₂O → air flows out passively
6. Forced expiration: internal intercostals + abdominal muscles contract (active)

---

4. OXYGEN DISSOCIATION CURVE (ODC) & CHLORIDE SHIFT

Oxygen Dissociation Curve:

• The ODC is a sigmoid (S-shaped) curve plotting % Hb saturation (y-axis) against PO₂ (x-axis)
• Sigmoid shape is due to cooperative binding - binding of one O₂ to heme increases affinity of remaining heme groups
• P50 = PO₂ at which Hb is 50% saturated = 26-27 mmHg normally
• Flat upper portion (PO₂ 60-100 mmHg): allows adequate O₂ loading even if alveolar PO₂ drops; Hb still ~90% saturated at PO₂ = 60 mmHg
• Steep lower portion (PO₂ 20-60 mmHg): facilitates O₂ unloading in tissues

Shifts in ODC:

Chloride Shift (Hamburger Shift):

• In tissue capillaries, CO₂ enters RBCs → converted to H₂CO₃ by carbonic anhydrase → H⁺ + HCO₃⁻
• ~70% of HCO₃⁻ formed in RBCs exits into plasma in exchange for Cl⁻ ions (via anion exchanger 1 / Band 3 protein)
• This is the chloride shift: Cl⁻ moves into RBCs, HCO₃⁻ moves out
• Result: Cl⁻ content of venous RBCs > arterial RBCs; venous RBCs are slightly larger (take up water)
• In lungs: process reverses - Cl⁻ exits RBCs, HCO₃⁻ re-enters → reconverts to CO₂ → exhaled
• The shift is complete within 1 second and is essential for efficient CO₂ transport

---

5. SURFACTANT

• ~90% lipids (mainly phospholipids)
• Key phospholipid: Dipalmitoyl phosphatidylcholine (DPPC / dipalmitoyl lecithin) - ~70-80% of lipid mass
• Surface tension: pure water = 72 dynes/cm; alveolar fluid without surfactant = 50 dynes/cm; alveolar fluid with surfactant = 5-30 dynes/cm

1. Reduces surface tension at the air-liquid interface of alveoli → reduces the work of breathing
2. Prevents alveolar collapse (atelectasis) - smaller alveoli would otherwise have greater collapsing pressure (P = 2T/r)
3. Stabilizes alveoli of different sizes by varying surface tension with alveolar radius
4. Prevents alveolar edema (reduces fluid transudation)
5. Has immunological functions (SP-A and SP-D act as opsonins)

---

6. VITAL CAPACITY

VC = IRV + TV + ERV VC = Inspiratory Reserve Volume + Tidal Volume + Expiratory Reserve Volume

Lung Volumes and Capacities (Summary Table):

• Restrictive lung disease (fibrosis, pleural effusion)
• Muscle weakness
• Pregnancy, ascites, obesity (reduced FRC)
• Postural changes (lower in supine)

---

7. LUNG FUNCTION TESTS

A. Spirometry (most common)

B. Interpretation Pattern:

C. Other Lung Function Tests:

• Peak Flow Meter: Simple bedside test; monitors asthma; diurnal variation >20% = asthma
• Body Plethysmography: Measures TLC, FRC, and RV (including gas that cannot be exhaled)
• Helium Dilution Method: Indirect measurement of FRC - patient breathes in/out of a circuit containing known concentration of helium until equilibrium
• Diffusion Capacity (DLCO): Measures lung's ability to transfer gas (CO used as test gas); reduced in emphysema, pulmonary fibrosis, pulmonary hypertension
• Bronchodilator Reversibility Test: FEV₁ measured before and after bronchodilator (salbutamol); >12% or >200 mL increase = significant reversibility (asthma)

D. Flow-Volume Loop:

• Normal: symmetric pattern
• Obstructive: concave (scooped) expiratory limb
• Restrictive: narrow, tall loop (reduced volumes, preserved flow rates)
• Upper airway obstruction: flat plateau on inspiratory and/or expiratory limb

---

---

Important note before reading: Your PDF is titled "Regulation of Respiration" (LRM VI.6, BDS Curriculum, MRDC). It covers nervous and chemical regulation of breathing in detail. However, the following topics from your list are NOT covered in this PDF at all - they appear nowhere in its 65 pages:

• Transport of O₂ and CO₂
• ODC (Oxygen Dissociation Curve) - only 1 MCQ question mentions it
• Chloride shift
• Surfactant
• Vital capacity (only 1 MCQ question mentions it)
• Lung function tests
• Non-respiratory functions of the lung

I will give you exactly what the PDF says for topics it covers, and clearly flag where the PDF is silent.

---

5-MARKER ANSWERS - FROM YOUR PDF ONLY

---

1. NON-RESPIRATORY FUNCTIONS OF THE LUNG

---

2. TRANSPORT OF O₂ AND CO₂

---

3. MECHANISM OF INSPIRATION & EXPIRATION

A. Genesis of Inspiration (Page 22)

• The inspiratory centre, although it has its own rhythmicity, is activated by the apneustic centre - i.e., neurons in the lower pons which are tonically active.
• The apneustic centre stimulates the inspiratory centre.
• The inspiratory centre discharges over pathways in the spinal cord to the inspiratory muscles - external intercostals and diaphragm.
• Therefore, inspiration starts.

B. Genesis of Expiration (Page 23)

1. I-neurons in the medulla send excitatory impulses to the pneumotaxic centre, which in turn discharges inhibitory impulses to the apneustic centre.
2. Pulmonary stretch receptors in the lungs, stimulated during inspiration, send inhibitory impulses via the vagus to the apneustic centre.
3. The pneumotaxic centre stimulates the expiratory centre, which reciprocally inhibits the inspiratory centre.
4. The apneustic centre gets inhibited and ceases to activate the inspiratory centre.
5. As a result, the inspiratory centre stops discharging and expiration follows passively.

---

4. OXYGEN DISSOCIATION CURVE (ODC) & CHLORIDE SHIFT

• ODC: Not discussed anywhere in the body of the PDF. The only mention is MCQ 7 (Page 65): "Dissociation curve shifts to the right when - B. CO₂ concentration increases."
• Chloride shift: Not mentioned anywhere in the PDF.

---

5. SURFACTANT

---

6. VITAL CAPACITY

---

7. LUNG FUNCTION TESTS

---

WHAT THE PDF DOES COVER (Fully Answerable Topics)

---

NERVOUS REGULATION OF RESPIRATION

• Composed of several groups of neurons located bilaterally in the medulla oblongata and pons of the brain stem.
• Three major collections:
  1. Dorsal respiratory group - dorsal portion of medulla - mainly causes inspiration
  2. Ventral respiratory group - ventrolateral part of medulla - mainly causes expiration
  3. Pneumotaxic centre - dorsally in the superior portion of the pons - mainly controls rate and depth of breathing

• Located in the ventrolateral medulla
• Neurons show rhythmic discharge and are of two types:
  • I-neurons - discharge during inspiration only
  • E-neurons - discharge during expiration only
• I and E neurons have inhibitory connections to each other (reciprocal innervation)

• Apneustic centre (lower pons) - tonically active neurons that activate I-neurons; inhibited by vagal afferents from lungs. If vagi are cut → apneusis (arrest of respiration in inspiration)
• Pneumotaxic centre (upper pons) - contains both I and E neurons; active in both phases; inhibits apneustic centre, thus preventing apneusis

• Respiration can be modified in rate and/or depth at will (e.g., voluntary hyperventilation, breath holding)
• Pathway: corticospinal tract from cerebral cortex to spinal motor neurons innervating inspiratory muscles
• Bypasses medullary respiratory neurons

---

FACTORS AFFECTING RESPIRATORY CENTRES

1. Afferents from higher centres (Page 25):
   • Cerebral cortex
   • Hypothalamus and limbic system
2. Pain and emotional disturbances (Page 25): Act through hypothalamus and limbic system to stimulate respiration.
3. Fever (Page 25): Acts via anterior hypothalamus → acts on respiratory centre → produces tachypnoea (rapid, shallow respiration).
4. Vagal afferents from inflation and deflation receptors (Page 26):
   • Stretch receptors located in smooth muscles of airways; relay in medulla via myelinated afferents in the vagi
   • Steady inflation of lungs stimulates stretch receptors → impulses via vagi → inhibit apneustic centre → inhibiting inspiration → prolonged expiration = Hering-Breuer Inflation Reflex
   • Determines the pattern of breathing when respiration is increased (e.g., during exercise)
   • Hering-Breuer deflation reflex: decrease in duration of expiration produced by marked deflation of lungs
5. Afferents from proprioceptors (Page 27): Active or passive movement of joints stimulates proprioceptors in muscles, tendons, and joints → afferent impulses stimulate inspiratory neurons → increase rate and depth of respiration. Helps increase ventilation during exercise.
6. Afferents from pharynx, trachea, and bronchi (Page 28): Irritant receptors - endings of myelinated vagal afferents throughout airways from trachea to respiratory bronchioles. Stimulation → coughing or sneezing.
7. Afferents from baroreceptors (Page 29): Cause inhibition of respiration. Physiologically insignificant.

---

CHEMICAL REGULATION OF RESPIRATION

• A. Peripheral chemoreceptors
• B. Medullary (central) chemoreceptors

• Carotid bodies (near common carotid artery bifurcation) and aortic bodies (near arch of aorta)
• Each body (glomus) contains Type I and Type II cells, surrounded by fenestrated sinusoidal capillaries
• Type II cells are glial cells that support Type I cells
• Respond to: oxygen (greatest response when PO₂ < 100 mmHg), CO₂ and H⁺
• Stimulated by:
  1. Hypoxia - when arterial PO₂ decreases, dissolved O₂ decreases in carotid bodies
  2. Vascular stasis - amount of O₂ delivered per unit time decreases
  3. Asphyxia - combination of O₂ lack and CO₂ excess
  4. Drugs (cyanide, nicotine) - prevent O₂ utilization at tissue level
  5. Increase in plasma K⁺ - during exercise (contributes to exercise-induced hyperpnoea)

• Located on the ventral surface of the medulla, near but separate from the respiratory centre
• Stimulated by H⁺ concentration of CSF and brain interstitial fluid
• Magnitude of stimulation is directly proportional to local increase in H⁺ concentration, which increases linearly with arterial PCO₂
• Inhibited during: anaesthesia, sleep, cyanide poisoning

• Decrease in PO₂ of inspired air → decreases arterial pO₂ → stimulates respiratory centre via peripheral chemoreceptors → increases pulmonary ventilation
• If IpO₂ falls to 60 mmHg: only slight increase in ventilation
• If IpO₂ falls below 60 mmHg: increase is marked

• Arterial pCO₂ kept constant at 40 mmHg
• CO₂ increases pulmonary ventilation by stimulating central chemoreceptors primarily; also stimulates peripheral chemoreceptors

• Acidosis (increased H⁺) → pronounced respiratory stimulation → hyperventilation
• Alkalosis (decreased H⁺) → depresses respiratory centre → hypoventilation
• These effects are mediated via central chemoreceptors

---

LUNG RECEPTORS (Page 50)

---

Transparency note: Both PDFs combined cover: Transport of O₂, ODC, Chloride Shift, CO₂ transport, and Genesis of Inspiration/Expiration/Regulation. The topics Non-respiratory functions, Surfactant, Vital Capacity, and Lung Function Tests are absent from both PDFs. I will state this clearly for each.

---

5-MARKER ANSWERS - FROM YOUR PDFs ONLY

---

1. NON-RESPIRATORY FUNCTIONS OF THE LUNG

---

2. TRANSPORT OF O₂ AND CO₂

TRANSPORT OF OXYGEN

• For each 100 mL of inspired air, 5 mL of O₂ is extracted by blood.
• For each 100 mL of arterial blood, 5 mL of O₂ is extracted by tissues.

• Amount is 0.3 mL per 100 mL of blood per 100 mmHg PO₂
• Amount of dissolved O₂ increases in linearity with arterial PO₂

• Each Hb molecule has 4 haem groups, each with iron in ferrous (Fe²⁺) form
• Therefore, 4 moles of O₂ combine with one mole of haemoglobin
• The reaction is rapid, requiring less than 0.01 sec
• Each gram of Hb combines with 1.34 mL O₂
• With normal Hb levels, each dL of blood contains about 20 mL O₂

• Human blood carries O₂ at 14 vol%
• Iron deficiency anaemia reduces O₂ carrying capacity considerably

• Decreases when inspired air PO₂ decreases
• Remains unaltered even during exercise, as velocity of blood flow increases

• Varies according to degree of body activity
• Active tissues utilise more O₂, so venous PO₂ decreases

---

TRANSPORT OF CO₂

• Tissue activity produces CO₂ which enters blood due to a pressure difference:
  • Arterial blood PCO₂ = 40 mmHg
  • Tissue PCO₂ = 46 mmHg
• CO₂ has a high diffusion coefficient - 20 times more than that of O₂
• Therefore, a small pressure gradient of 6 mmHg is sufficient for CO₂ transport

• Arterial blood = 48 mL/dL
• Venous blood = 52 mL/dL
• Each 100 mL of arterial blood passing through tissues picks up 4 mL of CO₂
• CO₂ first gets accommodated in plasma; when plasma is fully saturated, it is accommodated in RBCs
• Of the 4 mL/dL transported: 60% in plasma, 40% within RBCs

• In plasma: goes into solution as CO₂; small amounts form carbonic acid (H₂CO₃)
• In RBCs: CO₂ is rapidly hydrated to form H₂CO₃ due to enzyme carbonic anhydrase (CA)

• In plasma: CO₂ combines with plasma proteins → carbamino protein
• In RBCs: CO₂ combines with amino group of haemoglobin → carbamino haemoglobin (fast reaction)

• In plasma: CO₂ carried as sodium bicarbonate (NaHCO₃)
• In RBCs: CO₂ carried as potassium bicarbonate (KHCO₃)
• Haemoglobin is a strong H⁺ acceptor
• RBCs are rich in carbonic anhydrase (CA) → irreversible reaction takes place within 1-2 seconds

---

3. MECHANISM OF INSPIRATION & EXPIRATION

A. Genesis of Inspiration (Page 22):

• Inspiratory centre, although it has its own rhythmicity, is activated by the apneustic centre - neurons in the lower pons which are tonically active
• Apneustic centre stimulates the inspiratory centre
• Inspiratory centre discharges over pathways in the spinal cord to the inspiratory muscles - external intercostals and diaphragm
• Therefore, inspiration starts

B. Genesis of Expiration (Page 23):

1. I-neurons in medulla send excitatory impulses to the pneumotaxic centre, which in turn discharges inhibitory impulses to the apneustic centre
2. Pulmonary stretch receptors stimulated during inspiration send inhibitory impulses via the vagus to the apneustic centre
3. Pneumotaxic centre stimulates the expiratory centre, which reciprocally inhibits the inspiratory centre
4. Apneustic centre gets inhibited and ceases to activate the inspiratory centre
5. As a result, the inspiratory centre stops discharging and expiration follows passively

---

4. ODC (OXYGEN DISSOCIATION CURVE) & CHLORIDE SHIFT

OXYGEN HAEMOGLOBIN DISSOCIATION CURVE

• Shows the relationship between percentage O₂ saturation of haemoglobin and PO₂
• Has a characteristic sigmoid (S-shaped) shape

• Due to shifting affinity of haemoglobin for O₂
• All 4 atoms of Fe²⁺ do not combine with O₂ simultaneously
• Combination of 1st haem-haemoglobin molecule with O₂ increases affinity of the 2nd haem for O₂
• Oxygenation of 2nd increases affinity of the 3rd, and so on
• Affinity of haemoglobin for the 4th O₂ molecule is maximum
• At maximum PO₂ of approx. 120 mmHg, haemoglobin gets saturated to full capacity
• 1 gm of haemoglobin can combine with 1.34 mL of O₂

• Acidity increases (pH decreases) → affinity of Hb for O₂ decreases → increasing acidity enhances unloading → shifts curve to right
• Rise in PCO₂ → Hb unloads oxygen more easily → shifts curve to right
• Low blood pH can result from high PCO₂

• Increased PCO₂
• Increased temperature
• Increased 2,3-DPG
• Decreased pH

• O₂ content decreases → "unloading" of O₂

1. Fall in blood pH due to: (i) increased CO₂, (ii) presence of any acid in blood (Bohr's effect)
2. Increase in body temperature
3. Increase in concentration of 2,3-diphosphoglyceric acid (2,3-DPG)

• All these decrease affinity of haemoglobin for O₂ → help in unloading of O₂ to the tissues

• Affinity of haemoglobin for O₂ increases → less release of O₂ to tissues

1. Carbon monoxide
2. Foetal haemoglobin (HbF)
3. Decrease in body temperature
4. Decrease in hydrogen ion concentration of blood

• Has a higher affinity for oxygen than adult haemoglobin
• Can carry 30% more oxygen
• Maternal blood's oxygen is readily transferred to fetal blood

• Byproduct of glycolysis
• RBCs contain no mitochondria - rely on glycolysis
• 2,3-DPG increases with intense exercise and may increase due to training
• Helps deliver O₂ to tissues; helps unload oxygen by binding with Hb

• Iron-containing globular protein in skeletal and cardiac muscle
• Stores O₂ intramuscularly; contains only 1 iron atom
• O₂ is released at low PO₂
• Acts as muscle's O₂ store

---

CHLORIDE SHIFT (HAMBURGER SHIFT)

1. Bicarbonate content of RBCs in tissue is much greater than that in plasma due to carbonic anhydrase (CA). So HCO₃⁻ from RBCs enters plasma along its concentration gradient. This disturbs the electrical equilibrium within RBCs.
2. To maintain electrochemical neutrality, diffusion of Cl⁻ from plasma into RBC occurs - this is called the Chloride Shift.
3. The Cl⁻ content of RBCs in venous blood is significantly greater than arterial blood. As a result, RBCs take up water and increase in size - there are larger RBCs in venous blood compared to arterial blood. Haematocrit of venous blood is greater than arterial blood.
4. In lungs: as blood is oxygenated, Cl⁻ moves out of RBCs and they shrink.

• HCO₃⁻ accumulates inside RBCs as they pick up carbon dioxide
• Some HCO₃⁻ diffuses out into plasma
• To balance the loss of negative ions, Cl⁻ moves into RBCs from plasma
• Reverse happens in lungs - Cl⁻ moves out as HCO₃⁻ moves back into RBCs

---

5. SURFACTANT

---

6. VITAL CAPACITY

---

7. LUNG FUNCTION TESTS

---

---

5-MARKER ANSWERS - FROM YOUR PDFs ONLY

---

1. NON-RESPIRATORY FUNCTIONS OF THE LUNG

• Conducting zone warms and humidifies inspired air to 37°C and saturates with water vapour
• Mucus (secreted by goblet cells and mucus glands) traps particles
• Mucus and particles are moved by cilia to be expectorated

• Humidification, particle expulsion (coughing, sneezing)
• Particle trapping (clots, fat cells, detached cancer cells)
• Immunoglobulins from tonsils and adenoids
• Alpha-1 antitrypsin, lysozyme, interferon, complement system
• Pulmonary vessels trap fat cells, small clots and detached cancer cells - preventing their entry into systemic circulation

• Lungs synthesize certain prostaglandins, histamine, heparin and kallikrein
• Also forms prostacyclin, bradykinin, serotonin
• Pulmonary capillary endothelial cells contain Angiotensin Converting Enzyme (ACE) - converts Angiotensin I to Angiotensin II

• Lungs synthesize surfactant (by alveolar Type II cells / granular pneumocytes)

• Lungs act as a reservoir of blood

• Homeostatic regulation of body pH
• Changes in ventilation help balance e.g., acute acidosis of exercise

• Lose heat and water
• Liquid reservoir for blood
• Force generation for lifting, vomiting, defaecation and childbirth

---

2. TRANSPORT OF O₂ AND CO₂

Transport of O₂:

• For each 100 mL inspired air → 5 mL O₂ extracted by blood
• For each 100 mL arterial blood → 5 mL O₂ extracted by tissues

• 0.3 mL per 100 mL of blood per 100 mmHg PO₂
• Increases in linearity with arterial PO₂

• Each Hb molecule has 4 haem groups with iron in ferrous form
• 4 moles of O₂ combine with 1 mole of haemoglobin; reaction requires < 0.01 sec
• Each gram of Hb combines with 1.34 mL O₂
• Normal Hb levels → each dL of blood contains ~20 mL O₂
• Relationship shown by the oxygen-haemoglobin dissociation curve (sigmoid shape)

Transport of CO₂:

• Arterial blood PCO₂ = 40 mmHg; Tissue PCO₂ = 46 mmHg
• CO₂ has high diffusion coefficient - 20 times more than O₂
• Small pressure gradient of 6 mmHg is sufficient

• Arterial blood = 48 mL/dL; Venous blood = 52 mL/dL
• Each 100 mL arterial blood picks up 4 mL CO₂ from tissues
• 60% transported in plasma; 40% within RBCs

---

3. MECHANISM OF INSPIRATION & EXPIRATION

Mechanism of Inspiration (Page 67):

1. Contraction of diaphragm → increase in vertical dimension of thorax
2. Contraction of chest-elevating muscles → increase in anteroposterior and transverse dimensions of thorax
3. Lungs are pulled outward and downward → expansion of lungs
4. Decrease in intrapulmonary pressure
5. Pressure gradient established: atmosphere to alveoli
6. Air flows in → inspiration starts
7. Intrapulmonary pressure becomes equal to atmospheric → end of inspiration

Mechanism of Expiration (Page 69):

1. Relaxation of inspiratory muscles
2. Decrease in size of thorax
3. Compression of lungs → decrease in size of lungs
4. Increase in intrapulmonary pressure
5. Pressure gradient established: alveoli to atmosphere
6. Air flows out → expiration starts
7. Intrapulmonary pressure becomes equal to atmospheric → end of expiration

Genesis of Inspiration and Expiration (from regulation PDF, Pages 22-23):

• Inspiratory centre activated by apneustic centre (lower pons, tonically active)
• Discharges via spinal cord to external intercostals and diaphragm
• Inspiration starts

1. I-neurons send excitatory impulse to pneumotaxic centre → inhibits apneustic centre
2. Pulmonary stretch receptors stimulated during inspiration → inhibitory impulses via vagus to apneustic centre
3. Pneumotaxic centre stimulates expiratory centre → reciprocally inhibits inspiratory centre
4. Apneustic centre inhibited → ceases activating inspiratory centre
5. Expiration follows passively

---

4. ODC (OXYGEN DISSOCIATION CURVE) & CHLORIDE SHIFT

Oxygen-Haemoglobin Dissociation Curve:

• Due to shifting affinity of haemoglobin for O₂
• All 4 atoms of Fe²⁺ do not combine with O₂ simultaneously
• Binding of 1st O₂ to haem → increases affinity of 2nd haem for O₂
• Oxygenation of 2nd → increases affinity of 3rd, and so on
• Affinity for 4th O₂ molecule is maximum
• At PO₂ of ~120 mmHg, Hb gets saturated to full capacity
• 1 gm Hb combines with 1.34 mL O₂

• Acidity increases (pH decreases) → affinity of Hb for O₂ decreases → enhances unloading → shifts curve to right
• Rise in PCO₂ → Hb unloads oxygen more easily → shifts curve to right
• Low blood pH can result from high PCO₂

1. Fall in blood pH due to: (i) increased CO₂; (ii) presence of any acid (Bohr's effect)
2. Increase in body temperature
3. Increase in 2,3-diphosphoglyceric acid (2,3-DPG)

• All decrease affinity of Hb for O₂ → help unloading of O₂ to tissue

1. Carbon monoxide
2. Foetal haemoglobin (HbF) - higher affinity, carries 30% more O₂
3. Decrease in body temperature
4. Decrease in H⁺ concentration

• Byproduct of glycolysis; RBCs have no mitochondria - rely on glycolysis
• Increases with intense exercise
• Helps unload oxygen by binding with Hb; helps deliver O₂ to tissues

---

Chloride Shift / Hamburger Shift (Pages 35, 37):

1. Bicarbonate content of RBCs in tissue is much greater than plasma due to carbonic anhydrase (CA) → HCO₃⁻ from RBCs enters plasma along concentration gradient → disturbs electrical equilibrium within RBCs
2. To maintain electrochemical neutrality, Cl⁻ diffuses from plasma into RBCs - this is the Chloride Shift
3. Cl⁻ content of RBCs in venous blood is significantly greater than arterial blood → RBCs take up water and increase in size → larger RBCs in venous blood → haematocrit of venous blood > arterial blood
4. In lungs: blood is oxygenated → Cl⁻ moves out of RBCs → they shrink → HCO₃⁻ moves back into RBCs

---

5. SURFACTANT

• A mixture of protein-lipid complexes
• Made up of dipalmitoyl phosphatidyl choline (DPPC) lipid along with other lipids

• Granular pneumocytes = alveolar lining epithelial type II cells
• Also stated as: Alveolar type II cells secrete surfactant (RESPIRATORY PHYSIOLOGY PDF, Page 35)

• A layer of fluid and air lining alveoli causes surface tension
• Surfactant reduces surface tension by forming a layer between the fluid lining the alveoli and the alveolar air

1. Reduces the tendency of alveoli to collapse
2. Reduces the work of breathing
3. Prevents pulmonary oedema
4. Alveolar stabilization - maintains almost uniform size of alveoli

• Hyaline Membrane Disease / Infant Respiratory Distress Syndrome (IRDS)
• Serious disease of newborn infants due to deficiency of surfactant
• Surface tension in the lungs is very high
• Many areas of alveoli are collapsed (Atelectasis)
• Pulmonary oedema occurs
• Infants die of pulmonary insufficiency

---

6. VITAL CAPACITY

• Males: 4.8 litres
• Females: 3.2 litres

• Provides useful information about the strength of respiratory muscles
• Maximum inspiratory and expiratory effort can be assessed
• Gives useful information about other aspects of pulmonary functions through FEV₁

1. Physical dimensions - VC more in males due to: (a) large chest size, (b) more muscle power, (c) more BSA
2. Age - VC decreases in old age due to loss of elasticity of lungs
3. Strength of respiratory muscles - VC more in swimmers and divers
4. Posture - VC more in standing position because: (a) decreased venous return reduces pulmonary blood flow, (b) diaphragm descends down increasing inspiration
5. Pregnancy - VC decreases as diaphragm is pushed up, reducing thoracic capacity

• VC decreases in diseases of the respiratory apparatus

---

7. LUNG FUNCTION TESTS

A. Timed Vital Capacity / Forced Vital Capacity (FVC) (Page 20):

• Maximum volume of air breathed out forcefully and rapidly as possible following maximum inspiration
• Special stress on "rapid, forcible and complete exhalation"

B. Components of FVC (Page 21):

C. Clinical Significance of FVC (Page 23):

D. Minute Ventilation / Pulmonary Ventilation (Page 24):

• Volume of air expired or inspired by lungs in one minute
• PV = TV × RR = 500 × 12 = 6 L/min normally

E. Maximum Breathing Capacity (MBC) / MVV (Page 25):

• Largest volume of air moved into and out of lungs in one minute by maximum voluntary effort
• Normal: 90-170 L/min (average 100 L/min)

F. Pulmonary Reserve / Breathing Reserve (Page 26):

• Maximum amount of air above pulmonary ventilation that can be breathed in one minute
• Formula: MVV - PV
• Expressed as Dyspnoeic Index (DI) = (MVV - PV) × 100 / MVV
• Normal DI > 60-70% (usually 90%)
• If DI < 60% → dyspnoea is usually present

---