Lecture 11

• Gas exchange is a fundamental reason we have a respiratory system

  • Move oxygen into body tissues and remove carbon dioxide from cells
  • Replenish oxygen and excrete carbon dioxide from the blood
  • Accomplish this by providing extensive surface area
• what are the functions of the respiratory system?

  gas exchange, host defenses, producing sound
• Host defense is important for protecting the respiratory surfaces:

  Muco-ciliary clearance:

  • Cilia on cells line the airway
  • Airways covered by a thin layer of mucous propelled by the cilia
  • Particles/pathogens trapped and coughed out

  engulfment of foreign particles by macrophages
• Upper respiratory system includes: nose, nasal cavity, pharynx, larynx
• Lower respiratory system consists of: trachea, bronchi, bronchioles, alveoli
• The weight of the respiratory system is between 900-1000 g
• In humans, the right lung has 3 lobes, and the left lung has 2 lobes
• Trachea and main bronchi are extra-pulmonary
• Main bronchi divide to form secondary bronchi – one to each lobe
• Right lung has 3 secondary bronchi and left lung has 2 secondary bronchi
• Branching of the respiratory tract gets narrower as you go deeper, with internal diameter decreasing from 18 mm to 0.25 mm
• Bronchi have cartilage while bronchioles do not
• Conducting zone goes from nose to terminal bronchioles and functions to get air into the respiratory zone
• Respiratory zone spans from respiratory bronchioles to alveoli, which is the site of gas exchange
• Respiratory epithelium changes towards the respiratory zone:

  • Pseudo-stratified ciliated columnar epithelium in the nasal area
  • Stratified squamous in the pharynx
  • Pseudo-stratified ciliated columnar epithelium in the larynx
  • Cuboidal in the bronchi
  • Simple squamous in the alveoli
• Histology shows ciliated cells surrounding goblet cells that produce mucus
• Alveoli:

  • Means little cavity
  • Are the basic unit of respiration where gas exchange occurs
  • The thickness of the membrane is very thin, less than 1 micron thick
  • There are 480 million alveoli, approximately the surface area of a tennis court
• Alveoli are made up of:

  • Type I pneumocyte cells:
  • Make up 10% of alveolar cells
  • Cover 90-95% of the internal alveolar surface area
  • Flattened cells used in gas exchange
  • Type II pneumocyte cells:
  • Make up 18% of alveolar cells
  • Cover 5-10% of the alveolar surface area
  • Produce surfactant
  • Endothelial cells
  • Interstitial cells (fibroblasts)
  • Macrophages
• Surfactant is a lipoprotein complex that reduces surface tension in the alveoli
• It is composed of 90% lipid and 10% protein
• Surfactant proteins include SP-A, SP-B, SP-C, and SP-D
• SP-A and SP-D are for innate immunity
• SP-B and SP-C are required for the biophysical function of the lung
• Surfactant prevents atelectasis at the end of expiration, which is alveolar collapse
• Production of surfactant begins between 26-week gestation
• Not enough surfactant is produced before 32 weeks to prevent atelectasis, leading to Respiratory Distress Syndrome (RDS)
• Upper Respiratory System:

  • Reflexes like coughing and sneezing are important
  • Mucociliary clearance propels harmful substances away
  • Filtration removes particles larger than 10 micrometers
  • Production of mucus containing antimicrobial factors (AMF) like enzymes (lysosomes), defensins, and immunoglobulins
• Lower Respiratory System:

  • SP-A and SP-D bind to bacterial or viral surfaces, facilitating phagocytosis by macrophages
  • Alveolar macrophages are found on the tissue layer, make up 3-5% of lung cells, are the 1st line of defence, and maintain tissue homeostasis
  • Alveolar macrophages engulf pathogens/particles, eliminate dead cells, and maintain surfactant homeostasis
  • Interstitial macrophages are found within the tissue layer
  • During steady state, the lung contains both alveolar and interstitial macrophages
  • During inflammation, bone-marrow derived macrophages come into the lung
• Lung Defence Mechanisms:

  • Innate immune defence includes ciliated respiratory epithelial cells, phagocytosis/killing, complement opsonization, and lymph nodes
  • Adaptive immune defence involves immune T-cells, opsonization, and prevention of attachment using immunoglobulins
• The common cold is a mild, self-limiting upper respiratory tract infection characterized by nasal stuffiness and discharge, sneezing, sore throat, and cough
• Symptoms of the common cold include nasal congestion, runny nose, headache, and sore throat
• Risk factors for the common cold include:

  • Crowding
  • Smoking
  • Psychological stress
  • Genetics
  • Age: children are more prone to getting colds than adults
• The common cold accounts for 1/3 to 1/2 of all acute respiratory infections in humans, making it the most frequent human illness
• Colds are responsible for 40% of time lost from jobs and 30% from school
• The most common viral cause of the common cold is rhinoviruses
• Human rhinovirus (HRV) is a single-stranded RNA virus that primarily infects the nasal mucosa
• Rhinoviruses attach to specific receptors on the cell surface, with optimal replication occurring between 33-35°C
• Rhinoviruses have an RNA genome packaged in a protein coat consisting of viral capsid proteins (VP1, VP2, VP3, VP4)
• Rhinoviruses attach to intracellular adhesion molecule 1 (90%) and low-density lipoprotein receptor (10%), leading to increased production of cytokines, bradykinin, prostaglandin, and histamine
• Viral destruction of the respiratory epithelium does not occur with rhinoviruses but does with adenovirus, and cold symptoms are likely due to inflammation and local and systemic responses