BPK 205 Week 10-11

The Respiratory System - Anatomy

• Air flow:

  • Nasal Cavity

  • Pharynx

  • Larynx

  • Trachea

  • Primary Bronchi (Right/Left)

  • Many smaller bronchi

  • Alveoli

Main Functions of the Respiratory System

• Gas Exchange

  • O2 uptake

  • CO2 release

• Homeostatic regulation of body pH

• Conditioning inspired air

• Protection

  • Filtering & clearing foreign particles

• Vocalization

The Steps of External Respiration

1. Exchange I: atmosphere to lung (ventilation)

2. Exchange II: lung to blood

3. Transport of gases in the blood

4. Exchange III: blood to cells

Muscles used for ventilation

• External intercostals & diaphragm are the only muscles used at rest

  • These muscles contract & the lungs expand → air flows in

• During forceful breathing, other muscles are recruited

The Pleural Membranes

• Like a fluid filled balloon that wraps around the lungs

  • Visceral pleural membrane

  • Parietal pleural membrane

• Each pleural membrane is composed of a thin layer of secretory epithelial cells and a thin layer of connective tissue

The lungs are surrounded by a fluid filled sac

• Protects the lungs

• Pleural fluid lubricates membranes and allows them to slide against each other as lungs move with breathing

• Also “sticks” the lungs tightly to the thoracic wall

  • Important for keeping the lungs inflated

Main Role of the Airways

• Filter out foreign substances

  • Ciliated epithelium lining the trachea & bronchi

• Warm air to body temperature

• Add water vapour

• Help diffusion of O2 in

The Ciliated Epithelium of the Respiratory Tract

• Epithelial cells lining the airways and submucosal glands secrete saline and mucus

• Cilia move the mucus layer toward the pharynx, removing trapped pathogens and particulate matter

  • Watery saline layer allows cilia to push mucus toward pharynx

The Airways create resistance to air flow

• Radius of trachea and bronchi cannot be changed because of cartilage in their walls BUT mucus build up here is a common cause of increased airway resistance

• Bronchioles are collapsible, their radius can be changed by neural, hormonal and paracrine effects on smooth muscle

  • Obstructive lung diseases increase airway resistance

Bronchodilation

• Decreased resistance to air flow

  • Paracrine response to

    • CO2

  • SNS response

    • Norepinephrine/ Epinephrine bind to B2-adrenergic receptors → relaxation of bronchiole smooth muscle

    • GS → AC → cAMP → PKA

Bronchoconstriction

• Increased resistance to air flow

  • Paracrine respond to

    • Histamine released by local mast cells in an immune response

  • PNS response

    • ACh binds to muscarinic receptors (M3) → constriction of bronchiole smooth muscle

    • GQ → PLC → IP3 → IP3R → Ca2+

Alveoli - Site of Gas Exchange

• Make up the bulk of the lung tissue

• Each alveolus is made up of one layer of epithelial cells

  • Type I alveolar cells

    • Gas exchange

    • Make up 95% of alveolar surface area

  • Type II alveolar cells

    • Make & secrete surfactant

Surfactant

• A fluid that lines all the alveoli making them easier to expand & preventing them from collapsing

Alveolar Exchange Surface

• Optimized for diffusion:

  • very thin

  • very little interstitial fluid

  • alveolus and capillary held close together by fused basement membranes

What does surfactant do?

• Surfactant is secreted by type II alveolar cells and lines the inside surface of alveoli. Its function include:

  • Decreasing surface tension inside the alveoli

  • Preventing alveoli from collapsing

  • Making the alveoli easier to expand

Surfactant & Surface Tension

• At an air fluid interface, surface of the fluid is under a tension, due to attractive forces between fluid molecules

  • Results in an inwardly directed pressure that is a function of the surface tension of the fluid

  • Law of Laplace: P = 2T/r

• Surfactant decreases the tension, thus decreasing the pressure and making alveoli easier to expand

Surfactant & The Law of Laplace

• Without surfactant, inward pressure of alveoli would be high, making them difficult to inflate and prone to collapse

  • This effect would be exaggerated in smaller alveoli, making them even harder to inflate

• Surfactant reduces surface tension and inward pressure; reduces work to inflate alveoli

  • Smaller alveoli have more surfactant

  • Equalization of the pressure between large and small alveoli

  • Air flow equalized to all alveoli

Alveolar and Intrapleural Pressures at rest

• At the end of normal expiration, volume of air left in lungs = functional residual capacity (FRC):

  • Pressure inside the alveoli (Palv) = Pressure of outside air (Patm) = 0 mmHg

  • Elastic recoils of lungs inward equals elastic recoil of chest wall outwards

    • Result: negative intrapleural pressure (Pip) and lungs pulled towards chest wall due to resultant forces on pleural membranes

  • Positive transpulmonary pressure (=distending pressure) is the force inflating the lungs

Pneumothorax

• Air enters the pleural sac; intrapleural pressure is no longer negative. The bond holding the lung to the chest wall is broken, and the lung collapses, creating a pneumothorax (air in the thorax)

Pressure Changes during Quiet breathing

• Chest expansion causes low Pip

• High transpulmonary pressure (Palv - Pip)

• High in pressure forces pulling lungs towards chest wall

  • Lung/alveoli expand and Palv decreases

  • Air flows into alveoli until Palv = Patm

Compliance

• Ability of the lung to expand

  • The change in volume for a given change in pressure exerted on the lung

  • Decreased in restrictive pulmonary diseases, e.g. fibrosis

Elastance

• Ability of the lung to spring back after being stretched

  • Due to the presence of elastin fibers throughout the lung interstitial space

  • Decreased in emphysema (loss of elastin)

Mechanical changes of the thoracic cavity create pressure gradients that drive ventilation

• During quiet inspiration:

  • Diaphragm contracts and flattens

  • Muscles of inspiration contract and pull ribs up and out; sternum lifts up

  • thoracic and lung volumes increase, Pip and Palv decreases → Patm > Palv

  • air flows in

• During passive expiration:

  • Diaphragm relaxes and moves upward

  • Muscle of inspiration relax; ribs and sternum “fall” back down

  • thoracic and lung volumes decrease, Pip and Palv increases → Patm < Palv

  • air flows out

Lung volumes and capacities

• Tidal volume (Vt) → 500mL

• Inspiratory Reserve Volume (IRV) → 3000 mL

• Expiratory Reserve Volume (ERV) → 1100 mL

• Residual volume (RV) → 1200 mL

• Inspiratory capacity (Vt + IRV)

• Vital capacity (VC) (Vt + IRV + ERV)

• Total lung capacity (Vt + IRV + ERV + RV)

• Functional Residual Capacity (ERV + RV)

  • Total pulmonary ventilation = ventilation rate x tidal volume ~ 6 L/min

Ventilation

• Volume of air moved into/out of respiratory system per minute = 6 L/min

• But because gas exchange does not occur in the conducting airways, they are anatomical dead space (~150 mL)

• Better indicator of ventilation efficiency is alveolar ventilation, i.e. the volume of air moved in/ out of alveoli per minute

• Alveoli ventilation = ventilation rate x (Vt - dead space volume Vd)

Alveolar Ventilation and Anatomical Dead Space

1. At the end of inspiration, dead space is filled with fresh air

2. Exhale 500 mL

• The first exhaled air comes out of dead space. Only 350 mL leaves the alveoli

• PO2 in the lungs will never be equal to the PO2 of inspired atmospheric air (ALWAYS LESS)

3. At the end of expiration, the dead space is filled with “stale air from alveoli

4. Inhale 500 mL of fresh air (tidal volume)

• Dead space is filled with fresh air. Only 350 mL of fresh air reaches alveoli. The first 150 mL of air into the alveoli is stale from the dead space

The Air We Breathe

• A mix of gases

  • 78% N2, 21% O2, 0.003% CO2

• Dalton’s Law: The total pressure exerted by a mixture of gases is the sum of pressures exerted by all individual gases

  • The pressure exerted by an individual gas is called the partial pressure of that gas

• Total air pressure, Patm = PN2 + PO2 + PCO2

• In humid air, Patm = PN2 + PO2 + PCO2 + PH2O

Gas Composition in the Alveoli

• In the atmosphere:

  • PO2 = 160 mmHg

  • PCO2 = 0.25 mmHg

• Alveolar partial pressures remain relatively constant during quiet breathing

  • PO2 = 100 mmHg

  • PCO2 = 40 mmHg

• Can vary with hypo- or hyperventilation

• Match perfusion with ventilation

  • As alveolar ventilation increases, alveolar PO2 increases and PCO2 decreases. The opposite occurs as alveolar ventilation decreases (Normal ventilation = 4.2 L/min)

Pulmonary Gas Exchange and Transport

1. Oxygen enters the blood at alveolar-capillary interface

2. Oxygen is transported in blood dissolved in plasma or bound to hemoglobin inside RBCs

3. Oxygen diffuses into cells

4. CO2 diffuses out of cells

5. CO2 is transported dissolved, bound to hemoglobin, or HCO3-

6. CO2 enters alveoli at alveolar-capillary interface

Diffusion of a gas is governed by Fick’s Law

• Rate of diffusion is directly proportional to:

  • Surface area (A)

  • Membrane permeability (D = diffusion constant)

  • Concentration (partial pressure) gradient

• Rate of diffusion is inversely proportional to:

  • Diffusion distance (T)

    • Membrane thickness

    • Interstitial fluid

• Diffusion rate proportional A x D x (delta Pgas)/ T²

Gases Diffuse Down their “Partial Pressure” Gradients

1. Air moves by bulk flow down pressure gradients between atmosphere and alveoli

2. Pulmonary Circulation

• Alveolar PO2 > Venous Blood PO2

• Alveolar PCO2 < Venous Blood PCO2

3. Systemic Circulation

• Arterial PO2 > Tissue PO2

• Arterial PCO2 < Tissue PCO2

  • Diffusion reaches equilibrium under normal circumstances

Factors that Affect Gas Exchange

• Inefficient exchange can lead to low O2 content in the blood

• Hypoxia = not enough O2 to meet body’s needs

  • O2 reaching alveoli

  • Gas diffusion between alveoli and blood

  • Adequate perfusion of alveoli

Factors that decrease he amount of O2 reaching the alveoli

• Low O2 Content in the atmosphere

• Low alveolar ventilation

  • decreased lung compliance (how easily they can expand)

  • Increased airway resistance

  • CNS depression (drugs, alcohol overdose)

Emphysema

• Destruction of alveoli by e.g. cigarette smoke

  • Less surface area for gas exchange and low partial pressure gradient

Asthma

• Increased airway resistance decreases alveolar ventilation

• Partial pressure gradient low

Fibrotic lung disease

• Thickened alveolar membrane slows gas exchange. Loss of lung compliance may decrease alveolar ventilation

• Build up of scare tissue around alveoli by particulate irritants, e.g. asbestos

• Low distance and partial pressure gradient

Pulmonary edema

• Fluid in interstitial space increases diffusion distance. Arterial PCO2 may be normal due to higher CO2 solubility in water

• Increase in interstitial fluid in lungs; often a result of heart failure

• low distance

Hemoglobin

• Found in RBC, erythrocytes cells

• Reversibly binds O2

• Each Hb molecule has the ability to bind 4 O2 molecules

• Cooperativity (binding is reversible & can have affinity → 1 bind, the other 3 will)

O2 Hb Dissociation curve

• Plateau portion: 60-100 mmHg

  • Max (close to 100%)

  • In the pulmonary capillaries of the lungs

• Steep portion: 0-40 mmHg

  • Rest of. the body (tissues, muscle, etc.)

  • PO2 = 100 in lungs

  • PO2 = 40 in tissues

The O2 Hb dissociation curve is sigmoidal because of cooperative binding

• O2 binding is cooperative, NOT independent

  • i.e. the binding of O2 molecule(s) INCREASES binding affinity of the remaining site(s)

  • Cooperative binding underlies the sigmoidal shape of the O2 Hb dissociation curve

    • Functionally important:

      • In the steep region, a small change in PO2 can result in large change in %Hb saturation

P50 is the oxygen partial pressure at which hemoglobin is 50% saturated with O2. As the P50 increases, hemoglobin’s affinity for oxygen

• decreases

Oxygen Binding by Hb - Effect of Changing pH

• Low pH reduces O2 carrying capacity of Hb

• O2 dissociates more readily at tissues where pH is lower

Oxygen binding by Hb - Effect of Changing PCO2

• High PCO2 shifts O2 carrying capacity of Hb

• O2 dissociates more readily at tissues where PCO2 is higher

O2 Transport in the blood

• Total blood O2 = dissolved O2 + HbO2

  • In lungs, PO2 is high

    • Drives O2 exchange into plasma

    • High plasma PO2 drives O2 binding to Hb

  • In tissues, PO2 is low

    • Drives O2 exchange out of plasma

    • Low plasma PO2 drives O2 release from Hb

Carbon Dioxide (CO2) Transport in the Blood

• 7% transported as dissolved gas in plasma

• 23% transported as HbCO2

• 70% transported as bicarbonate dissolved in plasma

  • Normally the H+ is buffered by Hb in rbcs

  • Excess H+ present = respiratory acidosis

Chemoreceptors

• Sensory receptors convert chemical signals to action potentials

• Central chemoreceptors located in the medulla

  • Increased activity in response to elevated PCO2

    • Results in increased rate and depth of respiration

• Peripheral chemoreceptors located in the carotid sinus and aortic arch

  • Increased activity in response to elevated PCO2 and [H+], or decreased PO2

  • Afferent signals back to respiratory control center of medulla oblongata

    • Results in increased rate and depth of respiration

General functions of the Kidney

• Regulation of extracellular fluid volume and blood pressure

• Regulation of osmolarity

• Maintenance of ion balance → Na+, K+, Cl-, Ca2+, PO3 4-

• Homeostatic regulation of pH → variable excretion of H+ and HCO3-

• Excretion of wastes → e.g. creatinine, urea, hormones, ubrililinogen

• Production of hormones

  • Erythropoetin: stimulates RBC synthesis

  • Renin: important regulator of blood pressure

Anatomy of Nephron

• AA

• EA

• Bowman’s capsule

• Proximal tubule

• Descending limb

• Ascending limb

• Loop of Henle

• Distal tubule

• Collecting duct

The nephron is made up of epithelial cells

• Epithelial cell structure differs between regions of the nephron. The reflects the different functions of the various parts of the nephron

Urinary excretion depends on filtration, reabsorption and secretion

• Amount filtered - amount reabsorbed + amount secreted = amount of solute excreted

Filtration

• The filtration fraction: the % of total plasma volume that filters into the tubule

1. Plasma volume entering afferent arteriole = 100%

2. 20% of volume filters

3. >99% of filtrate is reabsorbed

4. >99% of plasma entering kidney returns to systemic circulation

5. <1% of volume is excreted to external environment

The Renal Corpuscle

• Substances filtered cross 3 filtration barriers

1. Glomerular capillary endothelium

2. Basal lamina

3. Epithelium of Bowman’s capsule (podocyte)

Main substances that are filtered out of the blood plasma at the renal corpuscle

• Na, K, Cl, Ca

• PO3 4, H, HCO3. NH4

• H2O

• Urea

• Glucose

• Creatinine, Urobilinogen

• Some proteins (trace amounts), amino acids

Glomerular Filtration Rate (GFR)

• The volume of fluid that filters into Bowman’s Capsule per unit time

  • 180 L/day or 125 mL/min

• Influenced by pressure

  • Hydrostatic pressure

  • Colloid Osmotic pressure gradient

  • Fluid pressure within Bowman’s capsule

Osmotic pressure

• The driving force for osmosis, which can be measured as the force that must be applied to prevent osmosis

Colloid osmotic pressure gradient

• Osmotic pressure gradient due largely to the presence of proteins in the plasma, but not in the filtrate

Someone with cirrhosis has lower than normal levels of plasma proteins and higher than normal GFR. Why?

• Colloid osmotic pressure is lower