Lung size is related to body size and O2 demand for metabolism.docx

• Lung size is related to body size and O2 demand for metabolism • Men typically have larger vital lung capacities than women: ~ female < 4 L # male > 4 L ~ difference about 1.5 L • The right lung has 3 lobes, but the left lung has 2 lobes: ~ different shapes due to the cardiac notch on the le...

• Lung size is related to body size and O2 demand for metabolism • Men typically have larger vital lung capacities than women: ~ female < 4 L # male > 4 L ~ difference about 1.5 L • The right lung has 3 lobes, but the left lung has 2 lobes: ~ different shapes due to the cardiac notch on the left • Primary bronchi divide to form secondary, tertiary bronchi etc • Terminal bronchioles divide into respiratory bronchioles which divide into alveolar ducts that supply air to alveoli • Gas exchange takes place in the alveoli: O2 is absorbed for cellular respiration (to form ATP) CO2 is eliminated as a waste product of metabolism • Lungs contains about 500 million tiny alveoli air sacs: • Alveoli are 250 µm wide and are surrounded by capillaries • The alveolar epithelium maximises gas exchange: ~ large surface area (100 – 140 m2) ~ a thin cellular membrane (0.5 - 1 µm) ~ excellent blood supply (5-25L/min) ~ wet surface (alveolar fluid containing surfactant) Red blood cells in the circulatory system transport O2 from lungs to tissues and help remove CO2 Lungs are not used for gas exchange during foetal life but must produce surfactant to be ready to breathe air at birth • Alveolar epithelial Type II cells secrete surfactant to reduce surface tension • Type-II cells mature fully in late pregnancy (week 36) • Premature babies can develop respiratory distress syndrome• Alveolar epithelial Type I cells exchange gasses (O2and CO2) • Breathing (physical ventilation) is required to maintain high O2 levels and low CO2 at respiratory surfaces / arterial blood • Inspiration: ~ inspiration is an active process~ diaphragm and external intercostal muscles contract which expands the thoracic cage~ air flows into lungs by negative pressure (-1 mmHg) • Expiration: ~ expiration is passive ~ external intercostal muscles relax allowing the thoracic cavity to recoil to its resting position ~ air flows out of lungs by positive pressure ( +1 mmHg) High blood CO2 is the main stimulus for inspiration • The medulla monitors falling pH levels in cerebrospinal fluid and blood which directly relate to increasing CO2 levels ~ breathing rate and depth increase as CO2 levels rise • O2 levels have little effect on breathing control except where levels are very low (high altitude & sleep apnoea) ~ low O2 levels stimulate deeper breathing • Exercise can increase breathing from 5 to 100 litres / min~ breathing remains high after vigorous exercise to clear oxygen debts caused by anaerobic metabolism • Breathing air enriched with O2 is used in medical emergencies and chronic illnesses to reduce respiratory distress Pons enables voluntary control and smooths the transition between breathing in and out Medulla detects pH changes (due to increase CO2 levels) and controls the breathing rate – primarily chemoreceptors in the VRG; rhythm is set by neurons in the pre-Botzinger complex (also VRG) Nerves from medulla respiratory groups stimulate the diaphragm and rib muscles to inhale / exhale Sensors in the carotid artery detect blood O2, CO2 and pH levels to help regulated the activity of the medulla Carotid body sensors only stimulate greater breathing when blood 02 levels fall to very low levels (eg below 60%) Lung structure is specialised for its function with a large surface area available for gas exchange • Alveoli are surrounded by a capillary network • Inspiration is active, expiration is passive • Breathing is controlled by the autonomic nervous system (pons and medulla) sensing and responding to changes in blood CO2 and O2 levels • The thoracic cavity is an enclosed cavity: ~ each lung sits inside a pleural cavity~ the cavity is lined by pleural membrane~ space between layers is contains intrapleural fluid which lubricates lung movement • Chest wall muscles including the diaphragm and the intercostal muscles are skeletal muscle ~ voluntary motor neurons stimulate muscle contraction • The lungs and thoracic wall contain elastic tissue ~ this enables the chest to relax and exhale passively Atmospheric Pressure (Patm) • All pressure values are made relative to atmospheric pressure (760 mmHg at sea level) • Alveolar (Intrapulmonary) Pressure (Palv) • determines direction of air flow. • Palv - Patm = +/-1 • Pressure within alveoli, equalizes between breaths • Intrapleural Pressure (Pip) • pressure in intrapleural space that keeps the lungs from collapsing. • respiratory pump • Transpulmonary pressure (Ptp) Ptp = Palv –Pip • Helps the lungs remain inflated • lungs are under tension • they are kept expanded to the thoracic wall by negative pressure in pleural cavity (-4 mm Hg)• pleural fluid and integrity of pleural cavity maintains negative pleural pressure. • Compliance is also important • How elasticated (stretchy) the lungs are• Thickening reduces compliance and requires greater transpulmonary pressure to change lung volumes Surfactant production is also important If pressure differential exists, then air will flow down pressure gradient: Flow = (P1 -P2)/R Flow = (Palv – Patm)/R Airway resistance (R) is determined by airway diameter• Increased diameter = reduced resistance Usually very little resistance but smooth muscle within airways can be contracted Inspiration: • increase thoracic volume • pressure in the lungs decreases • air flows in through airway towards the lower pressure Expiration. • thoracic volume decreases • pressure in the lungs increases • air flows out through airway • Small intra-thoracic pressure changes generate tidal volumes of 500ml per breathing • Tidal volume (Vt) at rest is typically 500ml: ~ 7ml/kg body weight ~ 12 – 14 breaths / min ~ 5 - 7 litres / minute but more with exercise • Inspiratory Reserve Volume (IRV) ~ 3L • Expiratory Reserve Volume (ERV) ~ 1.2 L • Residual Volume (RV) ~1.2L • Vital capacity (VC): ~ 4.8 litres in men ~ 3.4 litres in women • Functional Reserve Capacity (FRC) ~2.4L • Total Lung Capacity: TLC = VC-RV Minute ventilation = total amount of air inspired per minute= Tidal Volume x Respiratory Rate • At rest, tidal volume is about 500 mL and respiratory rate about 12 breaths per minute so minute ventilation = 6000 mL/min • Anatomical dead space = 150ml so Alveolar Ventilation typically more like (500-150) x 12 = 4200mL/min • Determines gas exchange, not minute ventilation • Effected by breathing rate and depth (Vt) • Forced expiratory volume in 1 second (FEV1) • Variant of VC – maximal inspiration then volume expired as fast as possible • Ratio of total volume expired to volume expired in 1 second is a marker of pulmonary function • >80% = healthy • <80% = possible obstructive pulmonary diseases Lungs are delicate and are affected by many serious disorders: • Acid-base disorders caused by insufficient / excess breathing: ~ respiratory acidosis (acidic blood) / alkalosis (alkaline blood) • In restrictive lung diseases total lung capacity is < 80% of normal due to poor lung expansion and lung tissue stiffness: ~ respiratory distress syndromes and pulmonary fibrosis • In obstructive (OLD) and chronic obstructive pulmonary diseases (COPD) forced vital capacity (FVC) is reduced: ~ asthma, cystic fibrosis, emphysema, bronchitis, pneumonia • Lung cancer, emphysema and bronchitis mainly due to smoking Lower airway obstruction- Asthma, chronic bronchitis, emphysema, cystic fibrosis Upper airway obstruction- Epiglottis, foreign body obstruction, upper airway tumour The thoracic cavity and lung pressure changes drive movement of air in and out of the lungs • Air travels down the pressure gradient (Palv - Patm = +/-1) • Spirometry can be used to measure lung volumes and parameters including Minute Ventilation and FEV1 • These parameters can be used to assess lung function • Breathing provides oxygen (O2 ) for metabolism (ATP synthesis) • Metabolic rate is the rate cells use O2 to release energy ~ energy release is about 20 k joules / litre of 02 used ~ at rest = 300 k joules / hour or 4.2 k joules / hour / kg ~ can increase during activity by more than 10x • Oxidation of glucose releases CO2, metabolic H20 and ATP: ~ C6H1206 + 602 → 6C02 + 6H20 + 36 ATP molecules (glycolysis + Citric acid cycle + oxidative phosphorylation) • Metabolism is normally aerobic but during exercise it can be anaerobic which produces lactic acid and much less ATP: ~ glucose → pyruvate + 2 ATP → lactic acid ~ the liver converts lactic acid back to pyruvate • The circulatory system delivers 02 to tissues and removes C02 from tissues • Pulmonary (lung) circulation absorbs 02 from air and removes C02 from the body • Systemic (body) circulation delivers 02 to tissues and removes C02 from tissues • The gases diffuse down partial pressure gradients: P02 / PC02 • Metabolism forms ATP • Partial pressure gradients across epithelial cell membranes in the alveoli cause O2 to be absorbed and CO2 to be expired • Partial pressures (P) are calculated from the total air pressure and the amount of gas in a mixture: ~ sea level air pressure at is 760 mmHg (less at altitude) ~ O2 in air is about 20.9% but CO2 is only 0.03% ~ partial pressure of O2 is 20.9% of 760 PO2 = 159 mmHg ~ partial pressure of CO2 is 0.03% of 760 PCO2 = 0.3 mmHg • Partial pressures of alveolar / expired air are typically: ~ alveolar PO2 = 104 mmHg & expired air PO2 = 130 mmHg ~ alveolar PCO2 = 40 mmHg & expired air PCO2 = 27 mmHg • Blood flow through the upright lung is greatest at the base and least at the apex due to low pulmonary BP and gravity~ pulmonary blood pressures are 25 / 8 mmHg (systolic/diastolic) ~ this effect does not occur when lying down (asleep) • O2 and CO2 are small uncharged gas molecules that diffuse: ~ between air and blood in the lungs ~ between blood and cells in the tissues ~ haemoglobin is essential for efficient transport of O2 and CO2 Oxygen diffusion is driven by partial pressure gradients: ~ high blood flow maintains the pressure gradients for O2to diffuse into red blood cells (RBCs) and tissues~ environmental air pressure is 760 mmHg ~ Po2in environmental air is 160 mmHg (21% of 760) ~ Po2in alveolar air is 100 mmHg (13% of 760) ~ Po2in venous blood & tissues is 40 mmHg (5% of 760) ~ tissue Po2falls below 40 mmHg during exercise • Haemoglobin rapidly becomes 100% saturated with O2 • Carbon Monoxide (CO) is a poisonous gas that displaces O2 from haemoglobin binding sites • O2 molecules bind to all four iron atoms in haemoglobin molecules in red blood cells and are carried to the tissues • Due to the large surface area and high blood flow gas exchanges across alveolar membranes is very fast • O2 and CO2 diffuse rapidly down their partial pressure gradients • Epithelial and endothelial cells are very thin (1-2 micrometres) • Red blood cells (RBCs) contain haemoglobin that carries oxygen bound to an iron atom in a heam / heme group • Adult haemoglobin has 4 protein subunits: ~ 2 a subunits and 2 β subunits in adults (2 γ in a foetus) ~ each subunit has a haem (heme) / iron binding site for O2 During normal metabolism blood is about pH 7.4 • O2 partial pressure (PO2) in the lungs is 100 mmHg and Hb saturation is 96-100%~ O2 pick-up by RBCs • O2 partial pressure (PO2) in tissues is < 40 mmHg and Hb saturation is < 75%~ O2 release to cells • O2 saturation can reduce to < 20% during exercise~ more O2 released Increased metabolism causes blood pH to falls towards 7.2 due to increased CO2/ [H+] .Low pH causes the Bohr shift in Hb / O2 dissociation to release more oxygen to active tissues • Myoglobin is an oxygen binding protein in skeletal / heart muscle. Myoglobin has a very high affinity for O2 and stores O2 for muscle use during anaerobic metabolism due to hypoxia A foetus forms foetal (2a2γ) haemoglobin which has a higher affinity for O2 than its mothers haemoglobin (Hb) • Maternal Hb can unload O2 to the foetus via the placenta. After birth the foetal 2a2γ Hb is rapidly broken down and replaced by adult 2a2β Hb. Rapid breakdown of foetal Hb can cause neonatal jaundice and a risk of brain damage. CO2 is eliminated to prevent acidosis (low pH) • CO2 diffusion is driven by partial pressure gradients: ~ Pco2 in venous blood is 45 mmHg (6% of 760) ~ Pco2 in alveolar air is 40 mmHg (5% of 760) ~ Pco2 in fresh air is 0.23 mmHg (0.03% of 760) • CO2 enters RBCs and is carried to the lungs • Some CO2 binds haemoglobin forming carbamino-haemoglobin and is carried to the lungs in RBCs where release occurs• Most CO2 forms carbonic acid and then HCO3- and H+ • H+ reversibly binds to haemoglobin to be carried to the lungs • O2 and CO2 are taken up by RBCs according to the partial pressure gradients Lung structure is specialised for its function with a large surface area available for gas exchange • Alveoli are surrounded by a capillary network• Inspiration is active, expiration is passive• Breathing is controlled by the autonomic nervous system (pons and medulla) sensing and responding to changes in blood CO2 and O2 levels Feedforward • Limits change • Anticipatory behaviour – acts to minimise disruption to set points • Appropriate clothing for weather • Homeostasis – relatively stable internal environment • Negative feedback most important • Feedforward anticipates change • Loss of homeostasis results in disease What is anatomy? ~ scientific description of the physical structure of organism parts • What is physiology? ~ branch of science concerned with functioning of organisms~ processes and functions of all or part of an organism • What does physiological mean? ~ normal healthy functioning (not pathological) • What is pathology / pathological? ~ branch of medicine concerned with the cause, origin and nature of disease as well as changes in tissues and organs • The body is composed of several Internal fluid compartments: TBV = total body volume (60 - 80 litres) TBV is subdivided: TBW = total body water (40 - 45 litres) ICF = Intracellular fluid (28 - 30 litres) ECF = extracellular fluid (14 - 15 litres) ECF is subdivided: Plasma = fluid in blood (3 litres) ISF = interstitial fluid (11 litres) The body has over 200 cell types that can be divided into 4 types: 1) Neural cells: ~ excitable signalling cells 2) Muscle cells: ~ excitable contractile cells 3) Epithelial cells: ~ sheet-like external body covering (skin) ~ internal cavity linings & renal tubules ~ specialised endocrine cells (hormones) 4) Connective tissue cells: ~ cells found in: blood, lymph, fat, tendons, bone • What are Tissues? ~ a collection of similar cells that carry out a specific function • What are organs? ~ contain 2 or more tissues ~ perform a particular function ~ eg: heart chambers and valves • What are organ systems? ~ contain 2 or more organs that work together ~ eg: cardiovascular system • Food processing, gas exchange, distribution / excretory systems: ~ Gastrointestinal, Respiratory, Cardiovascular, Renal • Movement / Support systems: ~ Muscular and skeletal Homeostasis is maintenance of a relatively constant internal environment • Control systems: ~ Nervous and Endocrine (neuroendocrine) • Protective systems: ~ Skin (integumentary) and immune • Reproductive systems: ~ Gender specific systems The maintenance of the of the composition, temperature and volume of the internal environments at relatively constant levels negative feedback mechanisms maintain homeostasis ~change detected: increase in glucose ~a response (insulin secretion) is generated to correct the change back to the ‘set point’ Failure of homeostasis causes many disorders: ~diabetes (insulin failure) ~neuroendocrine disorders ~hypertension (high blood pressure) ~obesity ~heat stroke homeostasis = steady state ~ keeps an internal dynamic equilibrium for optimal function ~ ECF, Interstitial Fluid, Plasm ~ pH, temp, hormone levels, BP e.g., Normal plasma K+ levels 3.5-4.5 mM; Hyperkalaemia >5.0mM. Above 6.5MM is a medical emergency. Positive and negative feedback: ~ negative feedback – a change in a variable initiates response which serve to cancel the change ~ positive feedback – a change in a variable initiates further disruption which amplifies the initial change ~ Feedforward – limits change. Anticipatory behaviour that acts to minimise disruption to set points