Lecture: When Things Go Wrong with the Respiratory System 2024

Lecture topic 21. When things go wrong with the respiratory system  Part 1: Introduction & overview (type and airway resistance recap) When things go wrong Part 2: Obstructive respiratory disease – COPD with the [chronic...

Lecture topic 21. When things go wrong with the respiratory system  Part 1: Introduction & overview (type and airway resistance recap) When things go wrong Part 2: Obstructive respiratory disease – COPD with the [chronic bronchitis, emphysema], asthma respiratory system Part 3: Restrictive lung lecture disease – fibrosis (focus) learning Part 4: Infection - objectives upper/lower respiratory tract, pneumonia, tuberculosis, COVID-19  Part 1: Introduction & overview (type and airway resistance recap) When Part 2: Obstructive things go respiratory disease – COPD [chronic bronchitis, wrong with emphysema], asthma the Part 3: Restrictive lung respiratory disease – fibrosis (focus) system (Part 1) Part 4: Infection - upper/lower respiratory tract, pneumonia, tuberculosis, COVID-19  Obstruction Airway resistance increased Types of Outflow pressure reduced respirator Restriction y disease Reduced compliance Infection & inflammation Measuring airway resistance Forced expiratory volume in 1 sec (FEV1) by spirometry Reduced FEV1 FEV1 is normally 80 % of vital capacity ↑ airway resistance 1 sec Types of Respiratory Disease obstructive - conditions which impede the rate of flow into and out of the lungs ↑ airway resistance – narrowing of airways ↓ outflow pressure – elastic recoil of lungs lost restrictive – conditions which cause reduced lung volume - reduced compliance ↓ vital capacity (VC) infection and inflammation  Part 1: Introduction & overview When Part 2: Obstructive things go respiratory disease – COPD [chronic wrong with bronchitis, emphysema], asthma the Part 3: Restrictive lung respiratory disease – fibrosis (focus) system Part 4: Infection - (Part 2) upper/lower respiratory tract, pneumonia, tuberculosis, COVID-19  Chronic Obstructive Pulmonary Diseases (COPD) - Narrowing of airways → ↑airway ↓ resistance FEV1 - Elastic recoil of lungs lost → ↓ outflow pressure ↑ Residual Volume (RV) → appearance of chest over-inflation Main diseases: Chronic bronchitisNarrowing Emphysema Recoil - In 2021, COPD caused approx. 3.5 million people deaths globally [5% of all global deaths] (WHO) - 4th leading cause of death worldwide Chronic Bronchitis - inflammation of the bronchi – mucus hypersecretion Acute bronchitis: due to: bacteria / virus Lasts: days / Chronic bronchitis: weeks Due to: smoking (80%), environmental irritants Lasts: at least 3 consecutive months in 2 consecutive years  irritants cause inflammation in bronchi  abnormal mucus secretion  plugs airways  prone to infection  further inflammation 20% of adult males have chronic bronchitis Result airway obstruction shortness of breath / wheezing, chest pain, chronic (productive - sputum) cough Treatment Stop smoking Bronchodilators Antibiotics Emphysema  Mechanism Elastase normally Smoking inactivated by 1 antitrypsin Neutrophils & macrophages X Genetic 1 antitrypsin deficiency (2% COPD patients) release elastase elastase destroys alveolar walls Emphyse ma Emphysema Normal Lung - compliance significantly ABOVE normal - ↑RV → ↑ FRC: chronically OVER- INFLATED lung Emphysema Lung Symptom s: - shortness of breath on exertion - hyperventilation - expanded chest  20% of smokers will develop COPD Lifelong smokers Loss of Enzyme alveoli is supplements in 1 permanent & antitrypsin irreversible deficiency - Stop smoking!! - Supplemental O2 Asthma Symptoms Bronchoconstriction Airway Oedema of airway mucosa resistance Mucus- secretion Causes / Precipitating factors… Hypersensitivity reaction to allergens Air pollution Exercise and cold air Emotional stress ?Genetics Causes?? Tristan da Cuhna: Allergy island – EXTRA FOR INTEREST https://vimeo.com/17786462 Mechanism Mast cell activation Histamine and cytokine release Oedema, mucus, smooth muscle contraction - bronchoconstriction Treatment Bronchodilators e.g. salbutamol (β2 adrenoceptor agonist) Anti-inflammatories - Approximately 5.4 million people in the UK are currently receiving treatment for asthma. - This includes more than 1.1 million children. - This is equivalent to 1 in 11 children. - However….  Part 1: Introduction & overview When Part 2: Obstructive things go respiratory disease – COPD [chronic bronchitis, wrong with emphysema], asthma the Part 3: Restrictive lung respiratory disease – fibrosis (focus) system (Part 3) Part 4: Infection - upper/lower respiratory tract, pneumonia, tuberculosis, COVID-19 Restrictive lung disease Causes - intrinsic or extrinsic to the lung parenchyma Intrinsic o long term exposure to dust: pneumoconiosis (asbestosis) o Drugs, e.g. methotrexate o Rheumatoid arthritis o ARDS, IRDS o Many no known cause, idiopathic pulmonary fibrosis Extrinsic o Non muscular disease of upper thorax  Fibrosis (development of excess connective tissue) - lungs STIFFER “Honeycomb lung” alveoli replaced by fibrotic tissue → DECREASED lung compliance IRREVERSIBLE decrease in oxygen diffusion capacity Causes - Inhaled environmental and occupational pollutants - Cigarette smoke - Autoimmune disease Treatment - no effective treatments  Part 1: Introduction & overview When Part 2: Obstructive things go respiratory disease – COPD [chronic bronchitis, wrong with emphysema], asthma the Part 3: Restrictive lung respiratory disease – fibrosis (focus) system Part 4: Infection - (Part 4) upper/lower respiratory tract, pneumonia, tuberculosis, COVID-19  Respiratory tract infections UPPER Respiratory tract UPPER respiratory tract infections Nasal Cavity Common but minor Pharynx Average adult ~ 2- 4 URTI /year Larynx LOWER Respiratory tract LOWER respiratory tract infections Trachea Less common but serious Primary bronchi e.g. bronchitis, Lungs pneumonia, tuberculosis...  Pneumonia Caused by bacteria: Streptococcus pneumoniae, Staphylococcus aureus or Klebsiella pneumoniae Affects bronchi & alveoli Inflammatory exudate fills alveoli Leads to ‘consolidation’ Lung tissue becomes firm and airless  Tuberculosis (TB) 2023 – 8.2 million newly diagnosed cases (Global Tuberculosis Report 2024) One quarter of world’s population thought to have latent TB infection Approx 1.25 million deaths Caused by inhalation of Mycobacterium tuberculosis – highly contagious - stained red in sputum Two phases: latent versus active disease - Latent – asymptomatic, non-infectious, granuloma in lung tissue - Active (~10%) - spreads to bronchioles and circulation  Replicate in alveoli alveolar macrophage (Ghon focus – site of primary infection) Initial infection – ineffective immune response Bacteria moved to lymph nodes Collagen deposited around bacteria  Lymph node erodes releasing bacteria Drainage into Drainage into blood bronchioles vessels Destructio n of alveoli Treatment: difficult due to antibiotic resistance  COVID-19 Virus - severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) World Health Organization (WHO) named the new epidemic disease Coronavirus Disease (COVID-19). Coronaviruses - Coronaviridae family in the Nidovirales order “Corona” = crown-like spikes on the outer surface of the virus 65-125 nm in diameter Contain a single-stranded RNA (26 to 32 kilobases (kb) in length) Believed to be of zoonotic origin  This Photo by Unknown Author is licensed under CC BY-SA-NC primarily via direct contact or through droplets spread by coughing or sneezing Transmission Binding of a receptor expressed by host cells is the first step (person to of viral infection and is the followed by fusion with the cell membrane. person) Lung epithelial cells thought to be primary target Receptor = Angiotensin-converting enzyme 2 (ACE2).Journal of autoimmunity, 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433. Variants of concern lineages under monitoring Alpha, Beta, Delta, Gamma and Omicron (WHO labels) Variant of concern lineages under monitoring Feb 2022: over 98% of all sequenced samples belonged to Omicron family – significant evolution September 2024: the WHO lists BA.2.86 and JN.1 as "circulating variants of interest" and 7 others "under monitoring" 1st vaccine in UK: 8th December 2020 September 2024: Current Autumn vaccination programme: - people aged 65 and over, are pregnant, residents in care homes for older people, anyone aged 6 months and over in a clinical risk group, and health and social care staff. - Vaccine used: Pfizer/BioNTech, or Spikevax (previously Moderna).  Part 1: Introduction & overview: types and airway resistance When things go wrong Part 2: Obstructive with the respiratory disease – COPD respiratory [chronic bronchitis, system: emphysema], asthma revisiting Part 3: Restrictive lung what have disease – fibrosis (focus) you learned in this Part 4: Infection - lecture? upper/lower respiratory tract, pneumonia, tuberculosis, COVID-19  Overall Recap: what have you learned about the respiratory system (lecture topics 18-21)? How we breathe – mechanics and forces we have to overcome? Lung compliance and air resistance O2 and CO2 – transport How levels of the different gases are detected and changes then effected in the way in which we breathe? What happens in some common respiratory diseases/conditions? This Photo by Unknown Author is licensed under CC BY-SA-NC