Block 2 - Healthy heart and lungs

Label the key terms on a spirometry graph.

(Spirometry) Formulas for working out:

• total lung capacity (TLC)

• vital capacity (VC)

• inspiratory capacity (IC)

• functional residual capacity (FRC)

• TLC = VC + residual volume (RV)

• VC = tidal volume (V_T) + inspiratory reserve volume (IRV) + expiratory reserve volume (ERV)

• IC = V_T + IRV

• FRC = ERV + RV

What procedure can be used to measure ventilation? What do we use to measure residual volume (RV) and functional residual capacity (FRC)?

• Ventilation measured using spirometry

• RV and FRC can’t be measured by spirometry, so helium dilution method or plethysmography are used

• helium dilution - the drum is filled with helium

• plethymsography - patient sits in sealed chamber and breath through pneumotach

Physiological functions of residual volume in the lungs and the meaning of elevated RV and decreased RV.

• Residual volume is the amount of air remaining in the lungs after a maximum forceful inhalation

• This air is important as it prevents lung collapse - alveoli open at all times, and maintains a continuous reserve of O₂ and CO₂, preventing sharp, dangerous fluctuations in blood gas levels between breaths

• Elevated RV indicates that air is becoming trapped inside chest, preventing normal complete emptying, e.g. in conditions like COPD

  • Reasons for increased RV include: respiratory muscles have a greater resting length, respiratory movements are less efficient, work required for breathing increases

• Low RV indicates lungs cannot expand or hold a normal volume of air, e.g. in restrictive lung diseases like pulmonary fibrosis

Describe and explain changes in spirometry graph between healthy alveoli and COPD alveoli.

• residual volume has doubled - dead volume has increased - because patients can’t empty their lungs completely before the next breath begins

• total lung capacity is the same

• it takes a similar amount of time to inhale, much longer time to exhale - due to lack of elasticity, stiffer lungs

• reduced functional range - increased exercise increases the breathing rate - small amounts of air that they can inhale and exhale, less room left in chest cavity to draw in fresh breath

• inspiratory capacity has halved - due to dynamic hyperinflation caused by air trapping

Why is alveolar ventilation less than pulmonary ventilation?

Pulmonary ventilation - moving gases into and out of lungs

Alveolar ventilation - volume of air that participates in gas exchange

• alveolar ventilation is less than minute ventilation because a portion of every inhaled breath remains in the anatomical dead space - the conducting airways where gas exchange does not occur

Alveolar ventilation formula

Respiratory rate x (tidal volume (V_T) - dead space (V_D))

Anatomical and alveolar dead space in the respiratory system

• dead space refers to the volume of inspired air that doesn’t take part in gas exchange across respiratory membrane

• anatomical dead space is the volume of air trapped in the conducting airways that lead to the gas-exchange zones - includes nose, pharynx, trachea, bronchi and terminal bronchioles

• alveolar dead space - volume of air that reaches respiratory zone (alveoli) but fails to take part in gas exchange because those alveoli are not perfused with pulmonary capillary blood flow.

• this means air is flowing into the alveoli (ventilation), but blood is not flowing through the surrounding capillaries (perfusion)

What is physiological dead space and the clinical impact of it?

• physiological dead space - sum of anatomical dead space and alveolar dead space, represents total volume of each breath that is ‘wasted’ and doesn’t eliminate CO₂.

• When physiological dead space increases, the body must breathe faster or deeper (increasing minute ventilation) just to clear normal amounts of CO₂.

Define minute volume and tidal volume (V_T) and give equations.

• Minute volume - volume of air entering and leaving lungs each minute (pulmonary ventilation)

• Minute volume (MV) = Respiratory rate (RR) x Tidal volume (V_T)

• Tidal volume - air taken in and out with each breath

• Tidal volume = dead space (V_D) + volume of air entering alveoli (V_A)

Define respiratory rate and give normal rates for newborns, young children and adults.

• Number of breaths per minute

• Newborns: 30-60 breaths/min

• Young children: 20-30 breaths/min

• Adults: 12-20 breaths/min

What are the two airways of the respiratory system? In which part does gas exchange occur?

• Conducting airways

• Respiratory airways - where gas exchange occurs

What are some tests of ventilatory function? Measuring airflow

• Forced Expiratory Volume in 1 second (FEV₁) and Forced Vital Capacity (FVC) and its ratio FEV₁/FVC expressed as a % - then measured against predicted values

• Peak expiratory flow rate (PEFR) - convenient way of measuring airways obstruction, can be used to monitor asthma or COPD at home

• in obstructive condition, e.g. emphysema - similar endpoint FVC, however it takes a lot longer to reach it. FEV1 is reduced by a lot

• restrictive condition, e.g. pulmonary fibrosis - maximum is reached fairly quickly but FVC is much lower in the restricted condition

Define Boyle’s Law.

At a constant temperature (T) the volume (V) of a given quantity of gas is 1/ to the pressure (P) it exerts.

• basically as volume increases, pressure decreases = they are inversely proportional.

Define Avogadro’s Law. (for gases)

Volume of gas at the same temperature and pressure contain the same number of molecules.

• this means that even with different gases, e.g. hydrogen, helium, contain same number of molecules.

• they are proportional to each other (moles and volume)

Define Charles’ Law.

At a constant pressure the volume of a gas is directly proportional to its absolute temperature.

• this means increasing the temperature increases the volume of a gas at a constant temperature.

What is the Ideal Gas Law?

PV = nRT

pressure x volume = n (moles) x R (gas constant) x T

Define Graham’s Law. (gases)

The rate of diffusion of a gas is inversely proportional to the square root of its molecular weight.

• this means a gas with a lower molecular weight diffuses more quickly

Define Henry’s Law.

The quantity of gas that can dissolve in a fluid is equal to the partial pressure of the gas multiplied by the solubility coefficient.

• some gases are more soluble than others, e.g. oxygen is less soluble in water than other gases

Dalton’s Law of Partial Pressure

• the pressure exerted by a mixture of gases is equal to the sum of the individual partial pressure exerted by each gas in the same volume.

• this means if you add up the partial pressure of each of the individual gases making up a mixture of gases, the pressure exerted by the mixture is the same as the pressure exerted by each one individually

• e.g. pressure exerted by air = 100, made up of one gas pressure 20, another gas pressure 70 and another gas pressure 10.

Describe the pressure gradients that drive ventilation.

• Inspiration: contraction of the diaphragm and external intercostal muscles expands the thoracic cavity. as lung volume increases, intra-alveolar pressure drops below atmospheric pressure. air flows inward down this pressure gradient from the higher pressure outside the body to the lower pressure in alveoli

• Expiration: as the diaphragm and external intercostal muscles relax, the thoracic cavity volume reduces. as lung volume decreases via elastic recoil, the intra-alveolar pressure rises above atmospheric pressure and as a result air is pushed out of lungs into the atmosphere down the pressure gradient.

What are the partial pressures of H₂O, CO₂, O₂ and N₂ in alveolar air, including units? What is the total pressure of alveolar air?

What does the rate of diffusion of gases from the alveoli to the blood depend on?

• partial pressure of the gas

• solubility of the gas in the liquid, e.g. CO₂ ×20> O₂

• area available for gas exchange (e.g. dead space)

• thickness of alveolar membrane

The ability of a gas to diffuse between alveolar air and blood is measured by what?

its diffusing capacity (or transfer factor) D_L

Why is the rate of diffusion of CO₂ in blood faster than oxygen?

• because CO₂ is more soluble, even though it has a higher molecular weight than oxygen

• Oxygen:

• Solubility in water?

• How does it combine with haemoglobin?

• Amount of oxygen carried by blood can be expressed as…

• dissolves slightly in H₂O (greater than N₂ but less than CO₂)

• reversibly combines with haemoglobin (can attach to Hb in places with high O₂ levels and detach in places that need O₂)

• Amount of O₂ carried by the blood can be expressed as:

  • Arterial oxygen content CaO₂ (ml/100ml)

    • Arterial oxygen content (CaO₂) is the amount of oxygen bound to Hb plus the amount of oxygen dissolved in arterial blood

  • % saturation of Hb with O₂, SaO₂ (%)

• the relationship of PaO₂ to SaO₂ and CaO₂ is not linear but forms the oxygen dissociation curve for Hb.

Process of gas exchange in alveoli

• O₂: Inhaled air in the alveoli has a higher concentration of oxygen than the deoxygenated blood arriving from the pulmonary artery. Oxygen diffuses across the alveolar epithelium and capillary endothelium into the blood, where it binds to haemoglobin in red blood cells

• CO₂: The blood entering the pulmonary capillaries has a higher concentration of CO₂ (produced by cellular respiration) than the air in the alveoli. CO₂ diffuses out of the blood, across the capillary and alveolar walls and into the alveolus to be exhaled.

Structure of haemoglobin

• composed of four protein globin chains, each surrounding a central heme group

• in most adult haemoglobin, there are two alpha chains and two beta chains

• each heme group consists of a porphyrin ring with an iron atom in the centre

How does haemoglobin help transport more oxygen in the blood? Oxygen content of plasma and red blood cells?

• Oxygen content of plasma normally is 3mL per litre of blood, without haemoglobin, the alveolar pO₂ = arterial pO₂

• Oxygen partial pressure = 100 mmHg

• In blood with haemoglobin: oxygen content of red blood cells = 197 mL per litre of blood + 3mL of oxygen per litre in plasma = total oxygen carrying capacity: 200mL oxygen per litre of blood.

• Red blood cells with haemoglobin are carrying 98% of their max. load of oxygen

Haemoglobin-oxygen dissociation curve: Explain.

• in general, as the dissolved oxygen (pO₂) increases, the haemoglobin saturation increases (% of oxygen bound to haemoglobin)

• its not a linear, it is sigmoidal (S-shaped) due to the change in shape of haemoglobin (positive cooperativity)

• when it binds to the first oxygen, that increases its affinity for the next two oxygen molecules to bind to it

• graph plateaus at pO₂ > 60mmHg - large changes in pO₂ result in very little change in Hb saturation, due to it being harder for fourth oxygen to bind to Hb - there is only one empty site so chances of a free oxygen molecule colliding with and binding to it are significantly lower.

• even if pO2 drops a little (e.g. from 100 down to 60mmHg), Hb stays heavily saturated

• In the steeper phase of the graph (around 40mmHg or less), even a small drop in pO2 causes Hb to rapidly unload large amounts of oxygen to the cells that need it the most.

Explain shifts in the oxyhaemoglobin dissociation curve.

• the curve can shift to the right or the left, which changes how tightly haemoglobin holds onto oxygen (its affinity):

• Right shift:

  • lower affinity for oxygen, easier unloading

  • due to higher temps, higher pCO₂, lower pH (more acidic/acidosis) and higher levels of 2,3-BPG

  • happens in hard-working muscles or active tissues that need more oxygen

  • called the Bohr effect

• Left shift:

  • higher affinity for O₂

  • due to lower temp, lower pCO₂, higher pH and lower 2,3-BPG

  • happens in lungs (or fetal haemoglobin- has higher affinity for O₂, which needs to pull oxygen from the mother’s blood in the placenta)

What is 2,3-BPG in red blood cells?

• 2,3-bisphosphoglycerate - organic phosphate molecule found in RBCs

• it binds to central cavity of deoxygenated haemoglobin, stabilising it

• this binding decreases haemoglobin’s affinity for oxygen, shift the oxygen-haemoglobin dissociation curve to the right

• helps haemoglobin unload oxygen more easily into metabolically active tissues

• levels increase in response to chronic hypoxia or high altitude to help tissues extract more oxygen when air pressure is low

Carbon monoxide binding to haemoglobin + symptoms

• CO combines 200x more readily to Hb than O₂

• combination is almost irreversible

• forms carboxyhaemoglobin

  • decreasing affinity for Hb for O₂

  • impairing release of O₂ at tissues

• symptoms of CO poisoning vary depending of COHb level

  • between 3% and 24% symptoms include acute poisoning, headaches, nausea, blurred vision, dizziness, vomiting

  • 24.3% is the mean level of loss of consciousness

  • 32% is the mean level for fatality

How is carbon dioxide carried in the blood?

• carried in the blood in three forms:

• when cells excrete CO₂, 7% of it dissolves straight into the blood

• the other CO₂: goes through a series of chemical reactions, forming bicarbonate (HCO₃^-) which is in the blood (70% of the CO₂), and some binds to haemoglobin forming carbaminohaemoglobin (23%)

Explain carbon dioxide dissociation curve and Haldane Effect.

• more linear and steeper than the oxyhaemoglobin dissociation curve - as there is no cooperativity, doesn’t rely on a saturable 4-site binding mechanism the way oxygen does

• more CO₂ in venuous blood than arterial blood as veins carry CO₂ away from respiring cells

• Haldane effect: removing O₂ from Hb increases ability of Hb to pick up CO₂ and CO₂ generated H+ ions.

• venuous curve: deoxyhaemoglobin has a higher affinity for CO₂ and acts as a better buffer for H+ ions - as blood releases oxygen in tissues it shifts upwards to carry more CO₂ at any given pCO₂

• arterial curve: as blood picks up oxygen in the lungs, the curve shifts downwards, displacing CO₂ and forcing it out of the blood to be exhaled

How do the lungs control pH? Normal pH of blood?

• CO₂ is a metabolic waste product that dissolves in blood and combines with water to form carbonic acid (HCO₃^-) and hydrogen ions (H+). More CO₂ means more H+ ions which lowers blood pH (making it more acidic)

• If blood is too acidic (acidosis), brain signals lungs to breathe faster and deeper (hyperventilation), expelling more CO₂ into the air - drops H+ levels in the blood and cerebrospinal fluid.

• If blood is too alkaline (alkalosis), brain signals lungs to breathe slower and shallower (hypoventilation), retaining CO₂ in blood to increase H+ levels and lower pH back to normal

• Normal blood pH range: 7.35 and 7.45

Effect of hyperventilation and hypoventilation on CO₂ levels in the body

• hyperventilation causes low CO₂ (hypocapnia) and alkalosis

• hypoventilation causes high CO₂ (hypercapnia) and acidosis

Henderson-Hasselbalch equation to estimate blood pH given bicarbonate ion concentration and partial pressure of arterial carbon dioxide

What enzyme mediates the conversion of carbon dioxide to carbonic acid in red blood cells?

Carbonic anhydrase

When carbon dioxide enters red blood cell, how is the charge of the cell maintained?

• carbon dioxide forms HCO₃^-

• bicarbonate ions leave the cell, making it more positive

• chloride shift: Cl^- ions enter the cell to maintain charge of cell.

Gas exchange at the tissue

• some CO₂ leaves respiring cells and dissolves into the plasma

• majority of CO₂ combines with water catalysed by carbonic anhydrase to form carbonic acid (H₂CO₃) - then dissociates into bicarbonate ions and H+

• bicarbonate ions leave the cell and chloride ions enter RBC - chloride shift

• some CO₂ binds to amino groups on haemoglobin forming carbaminohaemoglobin inside RBCs

• lower oxygen concentration at tissues causes haemoglobin to unload its oxygen HbO₂ → Hb + O₂

Gas Exchange at the lungs

• bicarbonate ions move back into red blood cells, combing with H+ to form carbonic acid (H₂CO₃) and is converted back into CO_{2 +} H₂O with enzyme carbonic anhydrase inside RBCs

• Carbaminohaemoglobin releases its CO₂

• free CO₂ diffuses out of blood, across the alveolar wall and into the air spaces of the lungs to be exhaled

• air inside alveoli has a high partial pressure of oxygen, so oxygen moves down the concentration gradient into red blood cells, binding to haemoglobin to form oxyhaemoglobin

Causes of pH change in the body and state, in general, physiological responses to it?

• respiratory, e.g. hyperventilation (alkalosis), hypoventilation (acidosis)

• metabolic, e.g. diabetic ketoacidosis (acidosis), vomiting (alkalosis), renal failure (acidosis)

Physiological responses:

• buffering by chemicals including HCO₃^-, Hb and other blood proteins - this is rapid, but limited capacity

• changes in ventilation - rapid, but impossible if primary cause is respiratory

• changes in renal excretion of H+ and HCO₃^- - slower response, limited if primary cause is renal

Physiological response to respiratory acidosis

• caused by low pH and high pCO₂ (lungs retaining CO₂)

• kidney compensates by increasing plasma HCO₃^- and excreting H+ in the urine

• slow - takes 3-5 days

• HCO₃- and pH rise

• this restores pH towards normal

• but HCO₃^- and pCO₂ remain high

Physiological response to respiratory alkalosis

• caused by high pH and low pCO₂ (lungs lose excessive CO₂)

• kidney compensates by retaining plasma H+, excreting HCO₃^- in the urine

• slow - takes 3-5 days

• HCO₃- and pH fall

• this restores pH towards normal

• but HCO₃- and pCO₂ remain low

Equation for dissociation of carbon dioxide equilibrium

(Respiratory) Transfer factor measurement - TLCO meaning and how is it measured

• transfer factor of the lung for carbon monoxide

• measured by breathing a gas containing a small amount of carbon monoxide and helium and looking at the changes between inspired and expired levels. it’s a measure of the quantity of carbon monoxide which is transported across the alveolar-capillary membrane for each kPa of alveolar carbon monoxide (PCO).

• the helium is used to assess alveolar volume

(Respiratory) KCO diffusion coefficient meaning and how is it measured?

• it is TLCO divided by the alveolar volume to which the gas has access

• measured by breathing a gas containing a small amount of carbon monoxide and helium and looking at the changes between inspired and expired levels. it’s a measure of the quantity of carbon monoxide which is transported across the alveolar-capillary membrane for each kPa of alveolar carbon monoxide (PCO).

• the helium is used to assess alveolar volume

Davenport diagram - identify the 6 acid-based disorders given pH, pCO₂ and bicarbonate concentration.

• metabolic acidosis = decrease in arterial pH, usually due to a decrease in plasma bicarbonate concentration (bicarbonate in plasma acts as a base that keeps blood pH normal)

• metabolic alkolosis = increase in arterial pH, usually due to an increase in plasma bicarbonate concentration

• respiratory acidosis = when your lungs cannot get rid of carbon dioxide causing CO₂ to build up in your blood and drop blood pH below normal

• respiratory alkalosis = hyperventilation causes body to exhale too much carbon dioxide, driving blood pH above normal

• when acidosis/ alkolosis is chronic, the body has time to adapt - renal compensation - kidneys have time to reabsorb/excrete (alkolosis) and generate more bicarbonate (acidosis)

Structural divisions of the respiratory system

Upper respiratory

• nose, nasal cavity and paranasal sinuses

• pharynx

• larynx

Lower respiratory

• trachea

• bronchi

Describe the external anatomy of the nose (simple)

• nasal bone and cartilage covered by facial muscles and skin

• apertures (openings) are the nostrils

Functions of the nasal cavity

• warms and humidifies inspired air

• removes and traps pathogens and particulate matter from inspired air

• responsible for sense of smell

• drains and clears the paranasal sinuses and lacrimal ducts

• resonating chamber

Describe the anatomy of the nasal cavity.

• entered anteriorly through the nostrils

• opens posteriorly into the nasopharynx through the choanae

• mucosa lines the nasal cavity, except for the nasal vestibule which is lined with skin

• roof of the nasal cavities is curved and narrow, except at its posterior end where the body of the sphenoid bone forms the roof

• floor of nasal cavities is formed by the palatine processes of the maxilla and the horizontal plates of the palatine bone

• medial wall of the nasal cavities is formed by the nasal septum

• lateral walls of the nasal cavities are made up of the nasal conchae

• nasal conchae (superior, middle, inferior) project medially from the lateral wall of the nasal cavity, and meatus (superior, middle, inferior) underlies each concha

• sphenoethmoidal recess superior to the superior concha

Function of the conchae (turbinate bones)

• scrolled shape increases surface area, warming and moisturising air before it reaches lungs

• middle and superior conchae guide air currents toward the olfactory epithelium at top of nasal cavity to help process smells

• filter impurities - trap dust, pollen and debris in the mucus lining

Histology of the nasal vestibule and respiratory region of the nasal cavity

Nasal vestibule:

• keratinising and non-keratinising stratified squamous epithelium, contains hair follicles that trap large particles

Respiratory region:

• ciliated pseudostratified columnar epithelium

• goblet cells produce and secrete mucus to humidify air + trap particles

• ciliated columnar cells move mucus and trapped debris toward the pharynx

What are the paranasal sinuses?

sinus = hollow space within bone

Where do the paranasal sinuses drain?

• frontal sinus drains into middle meatus

• maxillary sinus drains into middle meatus

• anterior and mid ethmoid air cells drain into middle meatus

• posterior ethmoid air cells drain into superior meatus

• sphenoid sinus drains into sphenoethmoidal recess

What is sinusitis? symptoms?

• inflammation of tissue lining paranasal sinuses

• blocked with fluid

• symptoms include:

  • pain, pressure around cheeks, eyes or forehead

  • blocked or stuffy nose

  • thick, discoloured mucus from nose or down back of throat

  • reduced sense of smell/taste

  • fever, headache, toothache

Function of the nasolacrimal duct

• when lacrimal gland secretes tears, eyelids sweep tears towards the lacrimal sac

• this drains tears down the nasolacrimal duct to the inferior meatus

• nasolacrimal duct drains into inferior meatus

Epistaxis

• nosebleed

• originate from Kiesselbach’s plexus (or Little’s area) on the lower nasal septum

• Kiesselbach’s plexus - lots of blood supply to it as many arteries supply the area, e.g. ethmoidal artery, palatine artery

• common causes: local irritation and trauma (nose blowing, picking nose), dry air, medications

Anatomical position of the pharynx + overview

• muscular tube

• posterior to the nasal cavity, oral cavity and larynx

• base of the skull superiorly

• cricoid cartilage of larynx inferiorly

• 3 constrictor muscles: superior, middle, inferior

• 3 parts: nasopharynx, oropharynx, laryngopharynx

Parts of the pharynx and regions

• nasopharynx: from base of the skull to the uvula and soft palate

• oropharynx: from soft palate to epiglottis

• laryngopharynx: from epiglottis to cricoid cartilage

Structures of nasopharynx

• from base of skull to uvula and soft palate

• tubal opening (eustachian tube), tubes drain and equalise pressure in middle ear

• pharyngeal tonsil (adenoids) and tubal tonsil

• tonsils are collections of lymphoid tissue and immune system’s first line of defense

Tonsils in the oropharynx

palatine and lingual tonsils

Anatomical position of the larynx and its functions

• superiorly - laryngeal inlet

• inferiorly - cricoid cartilage

• anteriorly - trachea

• posteriorly - oesophagus

• functions:

  • phonation (arytenoid cartilages and vocal ligament)

  • cough reflex

  • protection of the lower respiratory tract

What cartillages are within the larynx?

• Unpaired: epiglottis, thyroid and cricoid

• Paired (one on either side): arytenoids (vocal folds), cuneiform and corniculate

false vocal cords also known as ventricular cords

What is phonation? What produces changes in pitch?

process where airflow from lungs is converted into sound by making the vocal folds vibrate inside the larynx

rima glottidis (aperture between vocal folds) changes shape as vocal folds move

muscles stretch and tense or relax the vocal ligament, and abduct or adduct the vocal folds - these movements permit changes in pitch

Cause of dysphonia

dysphonia - abnormal functioning of voice

impairment of the vocal vibrations

inflammation of the vocal folds - hoarse voice

What is the vertebral level of the arch of cricoid cartilage, superior end of oesophagus and superior end of trachea?

vertebral level C6 (CVI)

Describe the trachea. At what vertebral level does it bifurcate?

• main airway

• anterior to the oesophagus

• has c-shaped cartilage rings bridged by trachealis

• it bifurcates (splits into two) into the two primary bronchi at T4/T5 (manubriosternal angle)

Functions of the thoracic cage.

• organ protection - encloses and shields vital organs in the chest cavity from external trauma and impact

• respiration support - facilitates breathing, rhythmically expanded by the respiratory muscles to create a vacuum that draws air into the lungs

Rib numbers of the true ribs and the false ribs

• true ribs: 1-7

• false ribs: 8-12

• floating ribs: 11, 12

What are the muscles involved in inspiration?

• sternocleidomastoid

• scalenes

• external intercostals

• parasternal intercostals

• diaphragm

What are the muscles involved in expiration?

• internal intercostals

• external abdominal oblique

• internal abdominal oblique

• transversus abdominis

• rectus abdominis

Diaphragm

• floor of the thoracic cavity and roof of the abdominal cavity - partition between these two regions

• dome shaped muscle

• when it contracts, the top of the dome flattens down

Process of inspiration

• diaphragm contracts and descends

• external intercostals contract to raise ribs

• volume of thoracic cavity increases

• intrathoracic pressure drops below atmospheric pressure

• air moves in down the pressure gradient

Process of expiration

• expiration can be passive (quiet breathing) or active (forced breathing)

• quiet breathing - relies on natural relaxation of diaphragm and external intercostals, combined with the elastic recoil of the lungs

• forced expiration - internal intercostals pull the ribs down and in to reduce chest volume, abdominal muscles compress the abdominal organs upward against the diaphragm and pull the lower ribs down, sharply decreasing thoracic volume

What are the blood and nerve supply to the intercostal spaces?

• intercostal vein

• intercostal artery

• intercostal nerve

• present in each intercostal space

• collateral vein, artery and nerve

Explain the physiological mechanism of a cough

Cough has three phases: inspiratory, compressive and expiratory.

1. Inspiratory phase - vocal cords (glottis) open wide (abduct). Diaphragm and external intercostal muscles contract to draw a deep breath into lungs, increasing lung volume

2. Compressive phase - vocal cords snap shut (adduct) to close the glottis, abdominal wall and internal intercostal muscles contract forcefully. Glottis is closed, so air cannot escape, causing pressure (subglottic and thoracic) to build up rapidly in lungs

3. Expiratory phase - glottis suddenly opens and trapped high-pressure air bursts outwards at extremely high speeds, creating a high-velocity airflow 'spike' that shears mucus and debris off the airway walls and expels them.

Describe the cough reflex arc

Caused by irritation of respiratory tract by gases, smoke and dust

The cough reflex arc:

• (afferent pathway) - Chemical or mechanical stimuli activate sensory nerve endings (receptors) in larynx, trachea, bronchi or upper airways. Signals travel via vagus nerve to nucleus tractus solitarius (NTS) in brainstem

• (central pathway) - 'cough centre' in pons and medulla processes input.

• (efferent pathway) - output signals trave down vagus, phrenic and spinal motor nerves to coordinate respiratory and laryngeal muscles.

• in trachea, output is a cough, in lower airways leads to hyperpnoea (deep or fast breathing to match demand for oxygen)

• also causes reflex bronchial & laryngeal constrictions

• results in expulsion of irritants from respiratory tract

Why is a cough clinically significant?

Indication to diseases such as rhinitis (acute), or from cigarette smoke, pulmonary diseases, and asthma (chronic)

Could also be side effects from medication (ACE inhibitors like ramipril)

Role of opiate receptors in cough and respiration

• Opioid receptors are specialised receptors on surface of cells in the brain, spinal cord and digestive tract.

• They inhibit pain signals and influence mood, stress, respiration, and digestion.

• Opiates suppress the cough reflex primarily by binding to mu-opioid receptors (MOR) and kappa-opioid receptors (KOR) located on presynaptic neurons in the brainstem (medullary cough centres). This inhibits transmission and processing of cough signal.

Label each structure of respiratory system.

What types of epithelium are in the conducting zone of the respiratory system?

• pseudostratified with 3 cell types:

  • ciliated epithelial cells - mucociliary escalator

  • goblet cells (secretory, non-ciliated)

  • basal cells (act as stem cells, may contribute to structure)

• columnar in nasal cavities, trachea, bronchi

• more cuboidal in bronchioles with Clara cells replacing goblet cells

What are the defence mechanisms of the nose and oropharynx?

• nasal hairs of the nose filters large particles from inspired air

• nose warms and humidifies the air - prevents epithelium drying out

• mucosal layer lined with different types of epithelial cells:

• respiratory epithelium - bathed in aqueous viscous and sticky mucus to trap particles

• ciliated epithelium have a coordinated beat - ‘mucociliary escalator’ push material towards the nasopharynx and oropharynx

• irritant particles stimulate irritant receptors and provoke sneezing and coughing to remove material

• smell is also a defence mechanism!

Histology of the bronchus

• presence of plates of hyaline cartilage

• smooth muscle and goblet cells are also present

• lined with ciliated pseudostratified columnar epithelium

Histology of terminal bronchiole

• terminal bronchioles are smallest and final segments of the conducting portion of the respiratory system, mark end of air transport before respiratory gas-exchange airways begin

• no cartilage or glands

• epithelium in initial portion is ciliated columnar but becomes cuboid with cilia

• absence of goblet cells

• final portion un-ciliated smooth muscle - allows autonomic control of airway diameter

• contain club cells (clara cells)

What are Club Cells (Clara cells)?

• dome-shaped, non-ciliated secretory cells found in bronchioles of the lungs

• secrete lipoproteins and glycoproteins to protect the bronchiole epithelium and prevent luminal collapse

• act as local stem cells in the bronchiolar epithelium, multiplying and differentiating into ciliated cells to repair and regenerate the airway lining after injury

Cell types present in alveoli

• Type I pneumocytes (epithelial cells)

• Type II pneumocytes (epithelial cells)

• Alveolar macrophages

• Neighbouring alveoli interconnected by ‘Pores of Kohn’ - small openings in the walls of adjacent pulmonary alveoli that allow air, fluid and cells to pass between them

What are Type I pneumocytes?

• 90 - 95% of alveolar surface

• highly flattened

• simple squamous epithelium

• cannot replicate/ divide - if damaged, they’re replaced with Type 2 cells

• form occluding junctions with one another

  • barrier to extracellular fluid into alveolus

• type I cells forms thin diffusion barrier - fused with pulmonary capillary endothelium: the blood-gas interface, allows rapid diffusion of oxygen into blood and CO₂ out of blood

What are Type II pneumocytes?

• more numerous than type I but only about 5-10% of the alveolar surface

• cuboidal with apical microvilli

• capable of rapid cell division

• dispersed among type I pneumocytes and form occluding junctions with them

• produce surfactant - reduces surface tension, prevents alveoli from collapsing during exhalation

Sneezing reflex

• caused by irritation of nasal mucous membrane due to dust particles, debris and excess fluid accumulation

• characterised by deep inspiration followed by forced expiration with open glottis

• results in expulsion of irritant from airways

• irritation of nasal mucous membrane, olfactory receptors and trigeminal nerve endings in nasal mucosa

• afferents from trigeminal and olfactory nerves pass to sneezing centre in medulla

• efferent fibres pass from medulla via trigeminal, facial, glossopharyngeal, vagus and intercostal nerves

• results in activation of pharyngeal, tracheal and respiratory muscles

Swallowing reflex

• initiated by stimuli to dorsum of tongue, soft palate and epiglottis

• during swallowing, respiration is inhibited - deglutition reflex

• prevents inhalation of food

What is the mucociliary escalator? How does it work? What can damage it?

• defence mechanism of the airways

• two layers of mucus coating cilia of epithelium - thin sol layer and gel layer on top

  • sol layer - more fluid and less viscous than gel layer - enables the cilia to beat, if it was more thick, cilia would be inhibited and wouldn’t beat properly

  • gel layer - thicker layer of mucus, acts as a trap for particulate matter, dust, bacteria

• creates semipermeable barrier and allows exchange of nutrients, H₂O and gases - it is impermeable to most pathogens

• cilia beat in coordinated fashion to removed unwanted particles via ‘escalator’ towards the mouth

• mucus from large bronchi to reach pharynx takes about 40 min

• from respiratory bronchi it takes several days

• escalator can be damaged by inflammation, smoking, pollution, infections

What is the mucus and how does it provide non-specific immunity?

• produced by goblet cells

• main component of airway mucus are mucins, which are high molecular weight glycoproteins - give it gel-like nature

• fluidity and ionic composition of sol phase controlled by epithelial cells

• mucus contains:

  • anti-proteases, e.g. a1-antitrypsin - inhibits proteases released from bacteria and neutrophils, which can be destructive to us

  • lysozyme - has anti-bacterial and anti-fungal properties (enzyme that targets bacterial cell walls)

  • anti-microbial properties from lactoferrin (glycoprotein that binds to free iron), peroxidases and neutrophil-derived defensins (disrupt pathogen membranes)

  • these provide non-specific immunity

What are the main roles and characteristics of pulmonary immune responses?

• multifaceted - protective (prevents infections with non-specific immunity) and reactive roles (responds when infection, injury or inflammation occurs)

• lungs are immunologically active

• healthy lungs - contain relatively few leukocytes

• when there are pathological conditions - increased influx and diversity of leukocytes

• involves a large number of receptors, cytokines and chemokines

• vital in immune homeostasis, infection and inflammation

What are cytokines and chemokines?

• cytokines - signalling proteins that activate and regulate immune responses

• chemokines - chemoattractant proteins that recruit immune cells to specific locations

• both help coordinate immune responses in the lungs (as well as other body parts)

Give examples of innate immune cells and adaptive immune cells.

• Innate (general): neutrophils, eosinophils, basophils/mast cells, natural killer cells, dendritic cells, monocytes and macrophages

• Adaptive (specialised): T-helper cell, cytotoxic T-lymphocyte, B cell, plasma cell