Respiratory System (1,24,52)

Alveoli

- 150 million alveoli in each lung, providing about 70m2 of surface for gas exchange. - cells of the alveolus (pneumocytes) -> Squamous (type I) alveolar cells thin, broad cells that are involved with gas exchange and allow for rapid diffusion between alveolus and blood stream, cover 95% of alveolus SA -> Great (type II) alveolar cells- pneumocytes type II round to cuboidal that cover the remaining 5% of alveolar surface, repair the alveolar epithelium when the squamous (type I) cells are damaged • secrete pulmonary surfactant: mixture of phospholipids and proteins that coats the alveoli and prevents them from collapsing when we exhale -> alveolar macrophages (dust cells) most numerous of all cells in the lungs, wander the lumen and the connective tissue between alveoli, keep alveoli free from debris by phagocytizing dust particles, 100M dust cells perish each day as hey ride the mucociliary escalator to be swallowed and digested with their load of debris.

The Lungs

- Autonomic control: regulates smooth muscles, control diameter of bronchioles and airflow resistance in lungs - Bronchoconstriction: constricts bronchi caused by: •parasympathetic ANS activation •histamine release (allergic reactions) - Bronchodilation: • dilation of bronchial airways • reduces resistance

Carbon Monoxide Poisoning:

- Carbon monoxide: competes for the O2 binding sites on the haemoglobin molecule, colourless, odorless gas in cigarette smoke, engine exhausts, fumes from furnaces, space heaters. - Carboxyhemoglobin: CO binds to ferrous ion of hemoglobin • binds 210x as tightly as O2 • ties up hemoglobin for a long time • non-smokers- less than 1.5% of hemoglobin occupied by CO • smokers-10% in heavy smokers • conc. of 0.1% CO in a closed space binds 50% of a persons Hb • atm conc. of 0.2% CO can be quickly lethal

Gas exchange and transport

- Composition of air: 78.6% N, 20.9% O2, 0-4% CO2, water vapor depending on temperature and humidity, and minor gases argon, neon, helium, methane - Dalton's Law: the total atm pressure is the sum of the contributions of the individual gases, partial pressure- the separate contribution of each gas in a mixture. At sea level 1 atm. of pressure 760 mmHg. Nitrogen constitues 78.6% of atm, thus. PN2= 78.6% X 760mmHg = 597 mmHg

FEV1/FVC

- Forced vital capacity (FVC): volume of air can be forcibly blown out after full inspiration (breathing in), measured in litres. - Forced expiratory volume: (FEV1): % of the vital capacity that can be exhaled in one sec, adult healthy reading: 75-85% in 1 sec.

Alveolar Gas exchange:

- Henry's Law: at the air-water interface, for a given temperature the amount of gas that dissolved in the water is determined by its solubility in water and its partial pressure in air, so solubility depends on solute-solvent concentrations. - The solubility of a gas over liquid is proportional to the pressure of that gas. • greater the PO2 in the alveolar air = more O2 blood picks up • since blood arriving at an alveolus has a higher PCO2 than air, it releases Co2 into the air • alveolus: blood is said to unload CO2 and load O2.

Lung pressure

- IntraPULMONARY pressure: Intra-alveolar pressure (in the alveoli) > positive - IntraPLEURAL pressure: pressure in the intrapleural, pressure is negative due to lack of air in the intrapleural space. > negative - Transpulmonary pressure: pressure difference across the wall of the lung. Intrapulmonary-intrapleural pressure (keeps the lungs against the chest wall)

Compliance

- Low compliance: requires GREATER force e.g. Respiratory distress syndrome due to a lack of surfactant causing collapse of alveoli. - arthritis + other skeletal disorders that affect the articulations of the ribs and spinal column also reduce compliance. - High compliance: requires LESS force e.g. emphysema- elastic tissue has been damaged. including alveoli, due to the poor elastic recoil, patients have NO problem inflating lungs, BUT difficulty exhaling air.

Principal organs of the respiratory system

- Nose, pharyn, larynx, trachea, bronchi, bronchioles and alveoli incoming air stops in the alveoli, thin walled microscopic air sacs, exchange gases with the blood stream through the alveolar wall and then flows back out - Conducting division of the respiratory system: passagages that serve for airflow, no gas exchange, nostrils through major bronchioles. (actual airway tubules) - Respiratory division: consists of alveoli and other gas exchange regions (air sacs where gas exchange)

Functions

- O2 and CO2 between blood and air - speech and other vocalizations and sense of smell - affects BP by synthesis of vasoconstrictor, angiotension 2 via angiotensin converting enzyme from lungs - breathing creates pressure gradients between thorax and abdomen that promote the flow of lymph and venous blood - breath-holding helps expel abominal contents during urination, defecation and childbirth (valsalva maneuva)

Lung disease affects gas exchange

- Pneuomnia: alveoli walls thickened by edema, fluid and blood cels in alveoli - Emphysema: confluent alveoli

Hb - O2 relationship

- Pressure of Oxygen (PO2) of environment - high PO2 favours loading - low PO2 favours unloading - Hb - Oxygen affinity: • factors affering the affiniting of Hb are: pH/pCO2, temperature and 2,3-bisphosphoglycerate (BPG) • high affinity favours loading • low affinity favours unloading

Measurement of ventilation:

- Spirometer: measures lung function- measures amount (volume) and/or speed (flow) of air that can be inhaled/exhaled - device that recaptures expired breath and records such variables such as rate and depth of breathing, speed of expiration and rate of oxygen consumption - Respiratory volumes: - Tidal volume - volume of air inhaled and exhaled in one cycle during quiet breathing (500 mL) - Inspiratory reserve volume - air in excess of tidal volume that can be inhaled with maximum effort (3000 mL) - Expiratory reserve volume - air in excess of tidal volume that can be exhaled with maximum effort (1200 mL) - Residual volume - air remaining in lungs after maximum expiration (1300 mL)

Respiratory capacities

- Spirometry: measurement of pulmonary function • diagnosis and assessment of restrictive/obstructive lung disorders - Restrictive disorders: reduce pulmonary compliance • limit amount to which lungs can be inflated, disease that produces pulmonary fibrosis e.g. cystic fibrosis, black-lung, tuberculosis - Obstructive disorders: those that interfere with airflow by narrow/blocking airways • make it harder to inhale/exhale given amount of air e.g. asthma, chronic bronchitis, emphysema.

Respiratory capacities (calculations)

- Vital capacity - total amount of air that can be inhaled and then exhaled with maximum effort - VC = ERV + TV + IRV (4700 mL) • important measure of pulmonary health - Inspiratory capacity - maximum amount of air that can be inhaled after a normal tidal expiration - IC = TV + IRV (3500 mL) - Functional residual capacity - amount of air remaining in lungs after a normal tidal expiration - FRC = RV + ERV (2500 mL) • Total lung capacity - maximum amount of air the lungs can contain - TLC = RV + VC (6000 mL

Pleura

- a serous membrane that folds back onto itself to form a two-layered membrane structure - the thin space between the two pleural layers is known as pleural cavity and normally contains a small amount of serous fluid which reduces friction - the outer pleura (parietal) is attached to the chest wall, the inner pleura (visceral) covers the lungs.

Respiratory membrane

- each alveolus surrounded by a basket of blood capillaries supplied by the pulmonary artery - respiratory membrane: barrier between the alveoli air and blood. consists of: • squamous alveloar cells • endothelial cells • their shared basement membrane (collagen fibres) - Important to prevent fluid from accumatiing in alveoli: • except for a thin film of moisture on alveolar wall, alveoli are kept dry by absorption of excess liquid by blood capillaries • lungs have a more extensive lymphatic drainage than any another organ in the body • low capillary BP prevents rupture of the delicate R.M

Pleural pressure

- if one gets stabbed with a knife then the negative pressure becomes atm and more gas will rush in the lungs so they'll collapse, so more molecules fill the pleural space as the pressure are equalized resulting in the lung collapsing. - lungs have a natural tendency to collapse or recoil due to their elasticity. - chest wall has a tendency to expand - what keeps lungs against the chest wall ? Held against chest wall by negative pleural pressure "suction" due to a vacuum seal between the parietal (attached to chest wall) and visceral (attached to lung) pleural players.

Respiratory epithelium

- lines rest of nasal cavity except vestibule: ciliated pseudostratified columnar epithelium with goblet cells, cilia are motile, goblet cells secrete mucus and cilia propel the mucous posteriorly toward pharynx.

Pleura & Pleura fluid

- reduces friction - creates pressure gradient: • lower pressure than atm and assists lung inflation - compartmentalization: • prevents spread of infection from one organ in the mediastinum to others.

Trachea

- rigid tube 12cm long, 2.5 cm in a diameter - supported by 16-20 C-shaped rings of hyaline - found anterior to esophagus - reinforces the trachea and keeps it from collapsing when you inhale - opening rings faces posteriorly towards esophagus - trachealis muscle spans opening in rings: - gap in C allows room for the esophagus to expand as swallowing food, muscle contracts or relaxes to adjust air flow e.g. during coughing constricts to allow air to move faster and propel substances that are making you cough

Nasal cavity

- vestibule: small dilated chamber inside nostril lined with stratified squamous epithelium, vibriaaW (guard hairs block insects and debris from entering) - posterioly nasal cavity expands into a larger chamber wuth not much open space. - occupied by 3 folds of tissue (nasal conchae, mucous membranes), superior, inferior nasal conchae (turbinates): - project from lateral walls towards septum - meatus: narrow air passage beneath each concha - narrowness/turbulence allows most air contact mucous membranes, cleans moistens and warms air - flat/curved projections inside the nose that moistens and warm air as well as creating turbulence, prevent air from damaging alveolu by being too cold/dry.

Bronchial Tree

-> Lobar (secondary): supported by crescent-shaped cartilage plates. Three right lobar: superior, middle, inferior Two left lobar bronchi: Superior/inferior -> Segmental (tertiary): supported by crescent-shaped cartilage plates (10 on right, 8 on left) -> Bronchioles: - lack cartilage - 1mm < in diameter - pulmonary lobule, portion of ling ventilated by one bronchiole - have ciliated cuboidal epithelium - divides into 50-80 terminal bronchioles.

Bronchioles

-> Terminal bronchioles: - final bronches of conducting division - measures 0.5 < in diamete - limited number of ciliated cells and have no goblet/ mucuous glands - epithelium contain clara cells: produce protein like compound similar to surfactant that keeps the tubes open and prevent from collapse - each terminal bronchiole gives off 2 > smaller respiratory bronchioles. -> Respiratory bronchioles: - have alveoli budding from their walls, beginning of respiratory division since alveoli participate in gas exchange - end in alveolar sacs: grape-like clusters of alveoli arranged around a central space called the atrium, also covered in capillaries allowing for gas exchange.

Respiratory Distress Syndrome

-Surfactant: oily secretion, contains phospholipids and proteins, coats alveolar surfaces and reduces surface tension, prevents alveoli from collapsing -lack of surfactant: infants not strong enough to inflate their alveoli - protein-rich fluid leaks into the alveoli forming a membrane which further blocks oxygen uptake - treatment with mechanical ventilation may cause bronchopulmonary dysplasia and chronic respiratory insufficiency over time. - surfactants are suspended in saline and administered into airways through an endotracheal tube. • w/o surfactant: H2 bonds pull the water molecules together and the alveolus collapses • with surfactant: H2 bonds disrupted and the alveolus remains inflated

Broncial tree

A system of air tubes in each lung. - from main bronchus to 65,000 terminal bronchioles -> Main (primary): supported by c-shape hyaline cartilage rings, right main bronchus is a 2-3 cm branch arising from fork of trachea, right bronchus is slightly wider and more vertical than left, aspirated (inhaled) foreign objects lodged right bronchus more than left. ->Left main bronchus about 5cm long, slightly narrower and more horizontal than the right

Alveolar Gas exchange:

Alveolar gas exchange - the back-and-forth traffic of O2 and CO2 across the respiratory membrane: - air in the alveolus is in contact with a film of water covering the alveolar epithelium. - for O2 to get into the blood is MUST dissolve in this water. - pass through the respiratory membrane separating the air from the blood stream - for CO2 to leave the blood it MUST pass the other way - diffuse out of the water film into the alveolar air. **Gases diffuse down their conc. radient until the PP of each gas in the air is equal to its PP in water.

Alveolar ventilation:

Amount of air reaching alveoli each minute - Calculated as: (Tidal Volume - Anatomical Dead Space) x RR - a person inhales 500mL of air, and 150mL stays in anatomical dead space, then 350mL reaches alveoli. - alveoli ventilation rate (AVR): - air that ventilates alveoli (350mL) X RR (12bpm) = 4200mL/min - of all the measurements, this one is the most relevant to the bodies ability to get oxygen to the tissues and dispose of CO2 - residual volume: 1300mL is the volume of air left in the lungs that cannot be exhaled with max effort using forced exhalation.

Inspiration:

Another force that expands the lungs is warming of inhaled air- Charle's Law - Charle's Law: the given quantity of a gas is directly proportional to its absolute temperature. V≈T - on a cool day, 16˚C air will increase its temperature by 21˚C - inhaled air is warmed to 37°C by the time it reaches the alveoli - inhaled volume of 500 mL will expand-> 536 mL and this thermal expansion contributes to the inflation of the lungs - Quiet breathing: dimensions of the thoracic cage increase only a few millimeters in each direction: enough to increase its total volume by 500 mL, thus, 500mL of air flows into the respiratory tract

a) changes in ventilation (alveolar PO2) -> changes in perfusion

Changes in alveolar ventilation lead to changes in perfusion, so blood flow is directed to areas with MOST O2 or better ventilated. - low PO2 in alveolus-> pulmonary arteriole constricts - high PO2 in alveolus-> pulmonary arteriole dilates

b) changes in perfusion (alveolar PCO2) -> changes in ventilation

Changes in efficiency of perfusion lead to changes in the amount of ventilation so air flow is directed to areas with the most blood flow. - low PCO2 in arteriole-> bronchiole constricts - high PCO2 in arteriole-> bronchiole dilates

Pulmonary ventilation:

Compliance: an indicator of expandability i.e. how easily lungs expand. factors that affect compliance: - connective tissue structure of the lungs - level of surfactant production - mobility of the thoracic cage. (in some disease compliance limits how expansion occurs)

Henry's Law:

Example: soda in a can (closed lid) - when a gas under pressure contacts liquid the pressure tends to force gas molecules into solution, at a given pressure the number of dissolved gas molecules will rise until an equilibrium is established = At equilibrium: gas molecules diffuse out of the liquid as quickly as possible as they enter it, so total # gas molecules in solution remains constant. Example: when can is opened, internal pressure falls, gas moelules begin to come out, the volume of the can is so small vs. volume of atm great, within 30min all CO2 comes out and drink is 'flat' - If PP is reduced, gas moelcules will come out of solution = eventually new equillibrium estabilshed.

Respiration 2

Gas exchange: Three processes of external respiration 1. Pulmonary ventilation: (breathing) 2. Gas diffusion: across membrane and capillaries 3. Transport of O2 and CO2: between alveolar capillary beds in other tissues.

Respiration 3

Gas transport: The process of carrying gases from the alveoli to the systematic tissues and vice versa. - O2 transport: 98.5% bound to haemoglobin, 1.5% dissolved in plasma - CO2 transport: 75% as bicarbonate ion, 20% bound to haemoglobin, 5% dissolved in plasma

Oxygen Transport

Haemoglobin: molecule specialized in O2 transport - four protein (globin) portions: •each with a heme group which binds one O2 to the ferrous ion Fe2+ • one haemoglobin molecule carries up to 4O2 • oxyhaemoglobin (HbO2)- O2 bound to haemoglobin • deoxyhaemoglobin (HHb)- haemoglobin with NO - O2 • 100% saturation of Hb with 4 oxygen molecules • 50% saturation Hb with 2 oxygen molecules

Respiration

Has 3 meanings: 1. ventilation of the lungs (breathing) 2. The exchange of gases between the air and blood, between blood and tissue fluid 3. The use of oxygen in cellular metabolism

The flow of air into and out of the lungs in response to changes in air volume/pressure within the TC

Inhalation: volume increases pressure outside > pressure inside - pressure inside falls, so air flows in Exhalation: volume decreases pressure outside < pressure inside - pressure inside rises, so air flows in

Inspiration and Expiration

Inspiratory effect causes: - fall in intrapleural and alveolar pressure - pressure gradient from mouth to alveoli - gas flow down the pressure gradient Expiration causes: (relaxed breathing) - passive process mainly achieved by the elastic recoil of the thoracic cage, recoil compressed lungs, volume of the thoracic cavity decreases, raises intrapulmonary pressure to about +3mm Hg. air flows down the pressure gradient -> and out of lungs. Forced breathing: - accessory muscles raise intrapulmonary pressure as high as +30mm Hg, massive amounts of air moves out of the lungs.

Oxyhemoglobin Dissociation Curve

It is usually a sigmoid plot. The shape of the curve results from the interaction of bound oxygen molecules with incoming molecules. The binding of the first molecule is difficult. Once this happens a change in the structure of the Hb molecule occurs which facilitates the binding of the second and third molecules very easily, and it is only when the fourth molecule is to be bound that the difficulty increases, partly as a result of crowding of the haemoglobin molecule, partly as a natural tendency of oxygen to dissociate Partial pressure of oxygen (PaO2). This measures the pressure of oxygen dissolved in the blood and how well oxygen is able to move from the airspace of the lungs into the blood Partial pressure of carbon dioxide (PaCO2). This measures how much carbon dioxide is dissolved in the blood and how well carbon dioxide is able to move out of the body

Factors affecting gas exchange:

Membrane thickness: only 0.5µm - presents little obstacle to diffusion - pulmonary edema in left side ventricular failure causes edema and thickening of the respiratory membrane - pneumonia causes thickening of respiratory membrane - farther to travel between blood and air - cannot equilibrate fast enough to keep up with blood flow Membrane SA: 100 ml blood in alveolar capillaries, spread thinly over 70 m2. - emphysema, lung cancer, and tuberculosis decrease surface area for gas exchange Ventilation-perfusion coupling: the ability to match ventilation and perfusion to each other - gas exchange requires both good ventilation of alveolus + perfusion of the capillaries - ventilation-perfusion ratio of 0.8 - a flow of 4.2 L of air and 5.5 L of blood per minute at rest

Structure of respiratory epithelium at different sites within respiratory tract:

Nasal cavity & superior portion of pharynx: mucous cells and escalator inferior portion of the pharynx: stratified sqamous epithelium, protecting it from abrasian and chemical attack conducting portion of lower R.T: typical respiratory mucosa finer bronchioles: cuboidal epithelium gas exchange surface: delicate simle squamous epithelium

Alveolar Ventilation

Only air that enters the alveoli is available for gas exchange - Not all inhaled air gets there and ONLY a part of respiratory minute volume reaches alveolar exchange surfaces- Volume of air remaining in conducting passages is called Anatomical Dead Space (about 150 ml) - conducting division of airway where there is no gas exchange - can be altered somewhat by sympathetic and parasympathetic stimulation - In pulmonary diseases, some alveoli may be unable to exchange gases because they lack blood flow or there respiratory membrane has been thickened by edema/fibrosis - sum of anatomic dead space and any pathological alveolar dead space

oxyhemoglobin dissociation

Point A: Hemoglobin (Hb) is almost 100% saturated n systematic arterial blood, as no O2 has been unloaded to the tissues. Point B: When a person is resting, Hb unloads ONLY about 25% of its O2 to the tissues, therefore, Hb in systematic venous blood is about 75% Point C: when a person exercises vigorously, HB unloads MOST of its O2 in the tissues, in such cases, the Hb entering venous blood is ONLY about 25% saturated.

Resistance to Airflow

Pressure + Resistance are determinants of air flow: greater the resistance, slower the flow Three factors influencing airway resistance: - diameter of the bronchioles - pulmonary compliance - surface tension

Resistance to airflow

Pulmonary compliance: the ease with which the lungs can expand- - the change in lung volume relative to a given pressure change - compliance reduced by degenerative lung diseases in which the lungs are stiffened by scar tissue - compliance increased in emphysema due to poor elastic recoil Surface tension: of the alveoli and distal bronchiole- - surfactant - reduces surface tension of water - infant respiratory distress syndrome (IRDS) - premature babies

Pulmonary Ventilation:

Respiratory Rates and Volumes; - Respiratory system adapts to changing oxygen demands by varying - The number of breaths per minute (respiratory rate) - The volume of air moved per breath (tidal volume) The Respiratory Minute Volume: - Amount of air moved per minute - Is calculated by: Respiratory rate × Tidal volume -Measures pulmonary ventilation

Pulmonary Ventilation:

Respiratory airflow is governed by the same principles of flow, pressure and resistance as blood flow. - Boyle's Law: at a constant temperature, pressure of a given quantity of gas is inversely proportional to its volume. - if the lungs contain a quantity of a gas and the lung volume increases, internal pressure falls. - if lung volume decreases, intrapulmonary pressure rises, if pressure rises above atm then air moves out of the lungs

Lungs

Right: - shorter than left because liver rises higher on right Left: - taller and narrower because the heart tilts towards the side and occupies more space on side of mediastinum - has indentation: cardiac impression

Pressure in/out the thoracic cavity:

The pressure inside and outside the thoracic cavity at the start of the breath. > P outside = P inside - so no air movement occurs - the thin layer of pleural fluid produces a bond between the parietal pleura and the visceral pleura, preventing the collapse of the lungs.

Upper and Lower RS

Upper: head, neck, nose through larynx Lower: organs of the thorax trachea through lungs

Pneumothorax

a collapsed lung which occurs when the chest cavity and the lung itself fills with air, causing all or a portion of the lung to collapse. Air usually enters this space, called the pleural space, through an injury to the chest wall or a hole in the lung e.g. stabbing or gun shot

Diameter of the bronchioles:

bronchodilation: increase in diameter of bronchus/bronchiole - epinephrine and sympathetic stimulation stimulate bronchodilation-> increase air flow bronchoconstristion: decrease in diameter of bronchus/bronhiole - histamine, parasympathetic nerves, cold air, chemical irritants stimulate bronchoconstriction-> suffocation from extreme bronchoconstriction brought about by anaphylactic shock and asthma

Composition of Inspired and Alveoli air

composition of inspired air and alveolar air is different because of 3 influences: 1. Air is humidified by contact with mucous membranes: alveolar PH20 is more than 10x higher than inhaled air 2. Freshly inspired air mixes with residual air left from previous respiratory cycle: oxygen is diluted and enriched with CO2 3. Alveolar air exchanges O2 and CO2 with the blood: PO2 of alveolar is about 65% that of inspired air, PCO2 is more than 130x higher

Functions of the nose

warms, cleanses and humidifies inhaled air, detects odours in airstream, serves as resonating chamber that amplifies voice - Erectile tissue in nasal cavity: extensive venous plexus in inferior concha. - every 30-60min, erectile tissue on one side swells with blood, restricts air flow throuhg that nostril, most air directed through other nostril - allowing engorged side time to allow time for drying - flow of air shifts between R and L nostrils once or twice an hour