Respiratory Pathophysiology PDF

Pathophysiology of the respiratory system primary → Disorder in external respiration Respiratory failure secondary → Pathologies of blood, cardiovascular sys,...

Pathophysiology of the respiratory system primary → Disorder in external respiration Respiratory failure secondary → Pathologies of blood, cardiovascular sys, and other systems RF results Hypoxemic Hypercapnic Manifested by: Damage to lung Parenchyma Airway obstruction Impaired alveolar diffusion Hypoventilation Chronic form is called Dyspnea Cyanosis Types of RF Acute Chronic Bronchial asthma attack Pulmonary fibrosis Pneumothorax Pneumoconiosis Asphyxia Acute RF hypoxemic type Acute RF hypercapnic type Hyperventilation Respiratory alkalosis Hypoventilation Respiratory acidosis Chronic RF Slow compensatory mechanism Hyperventaliation To Prevent hypoxemia, hypocapnia does not occur by the time compensatory depletion, myocardial hypertrophy occur Metabolic acidosis  Rf degrees 1st 2nd 3rd Pa02 > 70 mmHg Pa02 70-50 mmHg Pa02 less than 50 mmHg Dyspnea develops in Dyspnea in Dyspnea and cyanosis physical activity light Physical in rest (mild to moderate) work organs are in deep hypoxia Normal Pa02 is 96-98 mmHg Components of external respiration Lung ventilation Alveolar diffusion Disorders of Pulmonary ventilation: Alveloar hyperventaliation occurs due to hypoxemia Hypocapnia and gaseous alkalosis occur decrease calcium ionization Hypocalcemia Hypocapnia will cause spasm of cerebral vesseles can also cause hypotension indirectly Hypocalcemia will cause Arrhythmia, hypotension oxygen curve shift to the left  Alveolar hypoventaliation Hypoxemia, hypercapain, gaseous acidosis develop oxygen curve shift to the right causes of alveolar hypoventilation Reduced the excitability of the respiratory center reduce Partial Pressure of Co2 in arterial blood, alkalosis, BP Hypoventilation Infants hypoventaliation underdevelopment of Peripheral chemoreceptors and weakness of exciting afferent influences Damage to the respiratory muscle and their nerves Inflammation (Botulism, tetanus) affecting Innervation of respiratory muscles, Autoimmune (myasthenia gravis), dystrophic changes (collagenosis), cramps (tetany, epilepsy) Damage to the Phrenic nerve will cause Paradoxical breathing accompined by an asymmetry movements of the right and left halves of the chest called breathing dissociation (Grocco-frugoni breathing) Thoraco diaphragmatic Pathology: Diseases accompanid by restricting chest and diaphragm movements include Congenital defect of the skeletal cartilaginous apparatus of the chest, Rickets,Kyphosis, lordosis, scoliosis.... Bronchi and lung disease: observed in chronic bronchitis, bronchial asthma, Pneumonia, tuberculosis..... Uneven lung ventilation Combination of Emphysema Impaired bronchial obstruction Exudate formation in (eg. asthma) alveoli (decrease elasticity (e.g. Pneumonia) of alveoli)  Types of hypoventilation Obstructive Restrictive Upper tract Lower tract Pulmonary Extra Pulmonary Fluids (water, sputum) Pathologies affect lower tract Tumor tissues (asthma) Pneumonia Pleural Pathology (pleurisy, pneumo, hydro, hemothorax) Inspiration difficulty Expiration difficulty TB Diaphragm mobility damage Tumors Inspiratory dyspnea Expiration dyspnea (Phernic nerve....) resection of lung tissue Respiratory muscle disorders (myositis....) Pulmonary edema Chest excursion difficulties Pneumosclerosis (kyphosis, lordosis....) Atelectasis Inspiratory dyspnea Hypoxemia, Hypercapnia, Gas acidosis, Hypoxia cerebral edema Hypoventilation will cause Decrease Partia Pressure Increase Pulmonary Pulmonary edema of O2 in the alveolar air Vessels tone reflex (Euler-Lillestrand reflex) Causes of Restrictive type of alveolar ventaliation: Atelectasis Pneumothorax Pneumonia  Disorders of obstructive hypoventilation Chronic bronchitis: Result due to Prolonged regular irritation of the mucous membrane of the respiratory tract Affect upper respiratory tract obstruction is at the level of Trachea, bronchi, bronchioles wall deformation occur Extension occur (bronchiectasis) by the time Emphysema occur Bronchiectasis: Dependent disease Expansion of the lumen of bronchi or bronchioles Two main factors chronic Persistance of the respiratory tract infection obstruction in a certain Part of the bronchi/bronchioles Hyperemia, mucous hyper secretion occur Asthma: characterized by Broncho spasm, airway obstruction and Expiratory dyspnea eg. narrowing bronchial lumen 2 times Increase resistance 16 times (Poissel's law) Hereditary Predisposition allergic components stimulate the Pathogenesis Types of astma 1 Atopic Non-atopic Type I hypersensitivity reaction Allergic (Immune) mechanism is not involved Hereditary Predisposition No hereditary predisposition related to allergic disease Normal IgE synthesis, e.g atopic dermatitis, urticaria High eosinophils synthesis Childhood Bronchial epithelium damage, Increase mucus secretion broncial muscle layer wall hypertrophies Develop due to hyperergic inflammatory reaction chronic irretation decrease irretation threshold of subepithelial parasympathetic receptors  Types of asthma 2 Infections Non-infections Can associate with allergic, Psedo-allergic, non-allergic e.g. aspirin related asthma develop in Pseudo-allergic and non-allergic mechanisms Asthma associated with the Profession develop in non-allergic mechanisms Emphysema: Terminal broncioles obstruction, destructive changes in the wall of the distal Part (acini), Expansion of the alveolar cavities Interalveolar septum undergo atrophy large air bags Expiratory dyspnea occurs  Emphysema Pathophysiology: Imbalance in 1 Protease-Anti Protease sys Oxidant-Antioxidant sys Protease Enzymes break down Ptns oxidants (Ros) (Elastase, collagenase) Antioxidants (glutathione, superoxide Anti protease (α 1 Protease) dismutase) protect lung tissue 2 Chronic irritation of the alveolar wall Leukocytes (neutrophils, macrophages) Release Protease breakdown alveolar Ptn wall Increase Ros Damage Anti Protease defficency Damage Smoking Antioxidant sys Emphysema occur ✗ X Disorders of restrictive hypoventilation Atelectasis: Dependent disease (nosological unit) characterized by wrinkling of the alveoli and close their lumen Three types: Resorption, compression, contraction Resorption atelectasis: Blockage of the bronchi lumen Remaning available air in alveoli is reabsorbed Lumen of alevoli closes Compression atelectasis: Lungs are compressed from outside Results in growth of connective tissue in the lung Parenchyma with Pneumosclerosis contraction atelectasis develops Irrevesible Process If atelectasis is not treated it will cause severe respiratory failure Pneumothorax: Air accumulates in the Pleural cavity Pressure increase in Pleural cavity lungs are compressed Three types: closed, open, valvular Closed Pneumothorax: The air that enters the Pleural cavity loses contact with the external environment Respiratory failure depends on the volume of air that has entered the cavity Open Pneumothorax: Air can enter and leave Pleural cavity freely Disturbance depends on the hole (defect) size  By the time during exhlation Part of the air discharge from the healthy lung enters the compressed lung Volume relatively increases and expels air from the Pleural cavity Valvular Pneumothorax: Air enters while inhlation BUT while Exhlation air cannot escape Soft tissues of the damaged area creats a valve around the wound opens in inhlation close in exhlation Pluera cavity pressure = atmospheric pressure Air flow stops Pneumonia: Is an inflammatory process of various origins that develops in the lung tissue Types of Pneumonia Bactiral (Atypical) Non-bacterial (Atypical) Preamocci Mycoplasma Streptococci chlamydia Staphylococci Adenoviruses Klebsiella Influenza viruses They multiply in the cavity of They Pass from the alveolar cavity to the alveoli Inflammatory process intestition region and multiply leading to strong exudation (fluids) Alveolar infiltration is NOT observed and alveolar infiltration occur lung tissue is damaged exudation Either alveolar or interstitial edema Hering-Breuer reflex is enhanced Dyspnea occurs * Pneumonia can also be acute and chronic OR community-accuired and nosocomial Pneumonitis (allergic alveolitis): occurs due to hypersensitivity reaction of the alveoli, intestitial tissue to exogenous antigen Type 3 and 4 of allergic reaction, manisisted by damage and gradual fibrosis of the alveolar wall and interstitial tissue Pleurisy: It's an iflammatory disease of the Pleura Develop for many reasons (e.g. Pneumonia, HF, Quincke edema) Two types are available Dry Pleurisy, Exudative Pleurisy Exudative Pleurisy: fluid accumulates in the Pleural cavity (Hydrothorax) leading to atelectasis, respiratory and heart failure Important terms in Plural cavity: Fluid accumulation Hydrothorax Blood ← Hemothorax Lymp = Chylothorax Alveolar diffusion: In norm alveolar diffusion provides the transition of oxygen from the alveolar cavity to the Pulmonary capillaries and carbon dioxide in the opposite direction Pa 02 in the blood is less than in the alveolar air Blood flowing to the lungs the Po 2 is 40mm Hg, blood returning from the lungs to the heart is 100 mmHg Pco2 of blood in the initial Part of the Pulmonary capillaries is 46 mmHg, final Part is 40mm Hg Disturbance of alveolar diffusion: Difference in gas gradiants Surface diffusion area of the lung normal 180-200 m² Pneumonia, allergic alveolitis, Pulmonary edema-.. the area of the diffuse surface and the volume of alveolar diffusion are reduced Thickness of the alveolar capillary membranes (ACM) Norm is 0.2-2 microns. e. g. in respiratory distress syndrome of newborns the thickness of the Acm increase Gas diffusion throng the membrane decrease Molecular weigh of diffused gases and their solubility: CO2 is able to diffuse in the alveolar capillary 20 times higher than of oxygen Hypoxemia develops while normocapria is preserved deeper damage to the ACM (e.g. adult respiratory distress syndrome hypercapnia and hypoxemia occur * Alveolar diffusion also depends on the condition of Pulmonary circulation e. g. increase blood flow velocity in the Pulmonary capillaries RBCs doesn't have time to connect with oxygen Disturbance of lung Perfusion: Decreased Pressure in the right ventricle (e.g. Shock, collapse) Increase Pressure in the left atrium (e.g. mitral stenosis) Increased resistance in the Pulmonary vessels (e.g. reflex spasm, thromboemboli in Pulmonary arterioles) Disturbance in lung Perfusion can lead to Pulmonary hypertension Causes of Pulmonary hypertension: 6 1- Euler-Lillestrand reflex 2- Kitayev reflex 3- Increase intra-alveolar pressure 4- Decrease total area of capillary network of the lungs (e.g. Pneumo sclerosis) 5- Increase norepinephrine levels 6- Thickening of the blood  Types of Pulmonary hypertension Precapillary Mixed Postcapillary Compression of Pulmonary arteriols start in one form then Progress Compression of Pulmonary veins In Pulmonary hypertension hypertrophy of the right Part of the heart develops Called a corpulmonary. Long Pulmonary hypertension will lead to Pulmonary edema Mechanisms of Pulmonary edema Hydrostatic Membrane Exogenous and endogenous intoxications, cardiogenic Pulmonary edema Type one allergic reactions, Infections and inflammatory oncotic process In nephoretic syndrome Stages of Pulmonary edema 1 2 Plasma Passes from the Plasma enters the lament of the Pulmonary capillaries into alveoli (alveolar edema) interstitial space (Inerstital edema) Dyspnea at rest cause compression of the bronchi and alveoli from the outside Asphyxia may develop decrease in the volume of the respiratory surface Hypoxemia occurs dyspnea in normal Physical activity  Ventiation Perfusion index (V/P): Reflects the effectiveness of respiration based on the ventilation of the lung alveolar diffusion and Perfusion of the lungs normal V/P = 0.8-1 V/P > 1 when alveolar ventilation increase and Perfusion decrease it occurs during the increase of the volume of the alveolar dead space (e.g. obstruction or the Pulmonary arterioles with a thrombus or embolus) V/P < 0.8 blood flow is more than air (ventilation is less than Perfusion) e.g. Atelectasis atreiovenous shunt occur * Sometime even with Pulmonary disease V/P index can remain within the normal range even with the presence or uneaven ventilation of the lung due to compensatory mechanisms Disturbance in regulation of respiratory system: Respiratory center in medulla the center of inspiration and expiration receive impulses from Pneumotoxic and apneustic centers located in the Pons as well as from Peripheral chemo, baro and mechanoreceptors and from the cerebral cortex Pneumotaxic center inhibits inhalation and enhance exhalation Apneustic center enhance inhlation Neurons of exhlation center does not Participate in normal breathing (active during heavy Physical work..). Peripheral receptors: In the synocarotid region (chemo, baroreceptors) Mechanoreceptors Irritant receptors (Between the epithelial cells of the respiratory tract) J-receptors (interstitial regions Peripheral chemoreceptor irretated by decrease in the blood pH Peripheral baroreceptors regulate respiration according to BP (increased BP decrease respiratory rate) Hering Breuer reflex When Pressure in the alveoli is high Vagus nerve trigger exhlation to prevent over inflation of the lung namely HBV in infirmation reflex become more sensitive rapid, shallow breathing Irritant receptors cause narrowing of the airway (Protecting the lung from exposure to toxic substances) J-receptor Is irritated in lung congestion causing superficial, rapid breathing  Impaired respiration central (medulla oblongata) Efferent Slow down inhibition of the impulse Organic changes (edema, tumors....) Functional (Psychosis...) Involuntary breathing is disturbed Voluntary Anemia.... breathing occur respiratory arrest occurs while sleeping (curse of Undine) P. 3 4 0 Afferent Increase decrease impulses Normal respiratory rate (euponea) at rest is 16-20 Per minutes Types of respiratory rhythm disturbance: 1 Tachypnea or Polypnoea Rapid, superficial Observed with Pulmonary Hering-Brener reflex is accelerated respiration Pathology (e.g. Pneumonia, Pulmonary edema) Hyperpnea 2 Rapid, deep Observed in increased Severe hypercapria leading to breathing Oxegyn demand Kussmaul breathing (e.g. workout, anemia...) Deep, rapid noisily breathing occurs due to acidosis that irritates respiratory center  3 Bradypnea Decrease respiratory Narrowing of the Steatonic breathing lumen of the upper rate, deep breaths Due to increased resistance respiratory tract due to to air flow, inflation difficulties (tumor, edema, foreignbody..) complete opening of the alveoli is delayed (delayed Hering-Brier reflex) Apnea 4 Temprory respiratory occurs due to severe hypocapain Pickwick' syndrome arrest Apnea while sleeping due to obesity Periodic breathing: Normal respiratory rhythm is accompanied by regularly recouring apnea Two forms are available Cheyne stokes, Biot breathing B r a in t r a u m a s , H e at s t ro k e s D e c o m p e n s a t e d h e a r t d e f e c t s Cheyne stokes breathing: Inspiration gradually deepens and accelerates reaching certain maximum level Amplitude of respiration decrease gradually and respiration stops Apnea lasts 30-40 Seconds Biot breathing: suddenly accelerated with deep breath replaced by periods of apnea Pathogenesis of Periodic breathing: weakness or the excitability or the respiratory center carbon dioxide cannot irritate respiratory center apnea occur Increased CO2 levels Stimulates respiratory center Terminal breathing: The body is between life and death Two forms are available Apneustic breathings, Gasping breathings Apneustic breathing: Characterized by single short term acts of exhlation occurring through the Prolonged acts of inspiration (Inspiration is more the exhlation) occurs due to barbiturates Poisoning, brain injures, infarction of the brain stem vagus nerve and brainstems are the key Players Gasping breathing (agonal breathing): characterized by separate (rare) acts of inspiration trying to swallow air all muscles are working (cant continue for long time) occurs in the agonal stage of terminal state Inhibition in central and Peripheral respiratory system Dyspnea: Felling Lack of air Doesn't occur in unconscious state Main sign of respiratory failure occurs due to increase the activity of the inspiration center or weakning the inhibition system Rapid and deep breath may be slow and superficial Types of dyspnea Inspiratory Expiratory Mixed Restrictive diseases Obstructive diseases Pneumothorax, Asthma, Pneumonia, Emphysema, Pneumo sclerosis, Bronchiectasis Atelectasis Coughing: Reflexogenic zones of coughing reflex are located in the wall Respiratory tract, lung tissue, Pluera, diaphragm Extraordinary excitation of the inspiratory center cause deep short inhlation while lungs are filled with air Epiglottis Closes and Preassure increase in the lung, In exhlation strong air opens the epiglottis and Vocal cords, the soft Palate Closes the nasal cavity Air explodes outward Protective function (by removing mucus, foreign substances from the respiratory tract) Induced cough from reflexogenic zones located outside of the respiratory system Is not Protective Prolonged cough will damage the inter alveolar septa and cause gradual development of emphysema, by the time it will also impair general circulation Vagus nerve mediated Sneezing: Protective reflex Receptors in nasal mucosa signals mediated by trigeminal nerve Pharynx is squeezed Not epiglottis Prolonged sneezing will cause dyspnea Hiccups: Intense act of inspiration results from the contraction of the diaphragm, stomach and glottis occurs due to irritation of the receptors located directly in the diaphragmatic muscle itself, irritation of the diaphragmatic nerves, damage to the central nervous system Yawning: Deep, long breathing while the non functioning alveoli (at rest) stretch and more air enters the lungs, then energetic exulation occurs Aim to improve the oxygen supply in the body can be observed in Pathological conditions (brain hypoxia) Disturbance of internal (tissue) respiration: Internal respiration involves the transport of oxygen from the lungs to the tissues and carbon dioxied from tissues to the lungs oxygen transport depends on: 1- oxygen capacity of the blood Is the content of the oxygen in 100mL of blood (16.5-20.5 Vol) Depends on the Partial Pressure of oxygen in the alveoli and blood, body 2- Ability of oxygen to bind to hemoglobin temperature blood PH, levels 2,3diphosphoglycerate (2,3 DPH) and ATP in erythrocytes 3- Dissociation of oxyhemoglobin 4- Level of blood circulation and the micro circulatory network Dissociation curve of oxyhemoglobin is shifted to the left, oxygen is more able to combine with hemoglobin in the Pulmonary capilarie BUT in tissue capillaries it is difficult to separate oxygen from Hbo2 Carbon dioxide: is transported in a form of compounds with bicarbonate and hemoglobin (carbhemoglobin) Hypercapnia expaned cerebral vessels increase intercranial pressure, impaired cerebral circulation Hypocapria Spasm of cerebral Vessels and brain hypoxia Oxygen utilization index: The amount of oxygen that is absorber by the tissues Expressed as a Percentage the ratio between arteriovenous oxygen to arterial blood 02 Decrease blood flow velocity decrease in the content of oxygen in arterial blood index Disturbance of biological oxidation include: 1- Deficiency of vitamine B1, B2, PP....) 2- cytochrome oxidase inhibition (e.g. in cyanide Poisoning, alcohol....) 3- Imbalance between oxidation and Phosphorylation (e.g. in thyrotoxicosis, nitrate Poisoning....) 4- Mitochondrial damage and ATP deficiency (eg, in cachexia, sepsis, radiation sickness....) In these condition Normal oxygen content in arterial blood BUT oxygen is not used in tissues leading to histotoxic hypoxia  Impairment of non respiratory functions of lungs: Metabolic functions Hemostasis functions Protective functions Lymphatic drainage 1- synthesis of coagulation 1- Air Purification 1- Remove accumulated 1- formation of angiotensin 2, in and anticoagulant factors substances in the endothelial cells of the Pulmonary Such as 2- Alveolar macrophages lungs during Pathological capillaries ACE convert angiotenin 1 to 2 (active) collagenase process Thromboplastin Elastase 2- Inactivation of substances such as Heparin catalase Bradykinin A Phospholipase Plasminogen activator 3- Mucociliary apparatus Norepinephrine Prostacyclin 4- Blood filtration Serotonin Thromboxane A2 by the help of alveolar macrophages Acute lung injury (Acute respiratory distress syndrome * ARDS *): Characterized by diffuse lessions to the alveolar capillaries and alveolar epithelium Lead to Pulmonary edema and acute respiratory failure ARDS form Adults Newborns (Prematures) Diffuse damage to the lung tissue known as hyaline membrane disease Alveolar epithelium undergoes necrosis, Permability of the Main cause is surfactant deficiency alveolar capillaries increase alveolar edema develops Alveoli are closed Atelectasis develops Result due to direct injury of the lungs (infections, capillary Permability increase, exudation increase allergic, inflammatory processes) OR extra pulmonary Hyaline settles on the alveoli wall Pathologies (Sepsis, Pancreatitis, Peritonitis, traumatic and burn shock, disseminated intravascular coagulation DIC) severe hypoxia, acidosis develop in the body Damage to the alveolar capillary membrane is due to dysregulation of the acute inflammatory response (Imbalance Surfactant synthesis may also decrease due to between Pro and anti inflammatory mediators) Hypoxia, Hypothermia, weakning of blood flow in the lungs, acidosis Neutrophils that are activated by macrophages secrete excessively inflammatory mediator Leukotrines, PAF, Protease, IL-1, I L-8, TNF....) damaging and necrotizing alveolar epithelium Destruction of Type 2 epithelial cells synthesis of surfactant stop Alveoli are closed Atelectasis develops Neutrophils cannot be inhibited by anti-inflammatory mediators (IL-10, endogenous, Protease, antioxidants) Hyaline membrane forms leading to hypoxemia Asphyxia: Severe form of respiratory failure Transfering oxygen to the blood and removing carbon dioxide from body become impossible * severe cases * can occur for many reason squeezing airway from outside, drowning, Laryngeal edema, severe broncho spasm Respiratory muscle Paralysis, glottis spasm... P. 347 Stages of asphyxia First stage Second stage Third stage Fourth stage weakining of the Breathing stops for Reflexes are lost Acute increase in respiratory respiratory center 1-2 minutes center activity mydriasis Inspiratory dyspnea Expiratory dyspnea Respiratory arrest due Very severe hypotension to delay in the activity Increase sympathetic tone increase Parasympathetic of the respiratory center Gasping breathing tone explained by increase CO2 level Explained by the effect severe hypotension Respiratory center but not reaching the inhibition of acute hypercapria on paralysis and and very slow Pulse effect the Parasympathetic death occurs Consciousness is system 5-15 minutes after lost respiratory arrest rare heart rate continue within this time life can be saved During asphyxia, rising carbon dioxide levels and falling oxygen levels initially stimulate the respiratory and vasomotor centers, increasing breathing, heart activity, and blood pressure. However, as carbon dioxide continues to rise, it eventually inhibits these centers. At the same time, worsening oxygen deprivation (hypoxemia) leads to brain hypoxia, further weakening the cardiovascular and respiratory systems, ultimately paralyzing the respiratory center and stopping breathing.