Pneumonia: Pathophysiology and Overview

• A 43-year-old female with fever, chest pain, shortness of breath, and a productive cough with rusty sputum likely has pneumonia.
• Auscultation reveals a bronchial breath sound, and an X-ray shows consolidation (pulmonary infiltrate) in the lung parenchyma.

Pneumonia Overview

• Pneumonia is an acute pulmonary infection where bacterial invasion of the lung causes consolidation of the lung tissue.
• Consolidation is the solidification of lung tissue due to exudative infiltration (fluid instead of air) into the lung parenchyma..

Pathophysiology of Pneumonia

• Damage to the muco-ciliary apparatus allows bacterial invasion.
• Bacteria (1-3 micrometers) enter the alveoli and multiply.
• Bacterial replication leads to acute inflammation.
• Acute inflammation leads to capillary congestion (dilation).
• Cytokines released by inflammatory cells increase capillary permeability.
• Fluid infiltrates the alveolar spaces, resulting in solidification (consolidation).

Risk factors for Pneumonia

• Age
• Alcohol
• Smoking
• IV drug use
• Underlying respiratory diseases like Cystic Fibrosis, bronchiectasis, COPD, viral infections.
• Immunosuppressive drugs.
• These factors damage muco-ciliary clearance mechanisms.
• Individuals over 65 and under 16 are at the highest risk.

Diagnosis of Pneumonia

• Requires cough, fever, and new radiological infiltrate.
• Symptoms (cough and fever) are essential.
• Pneumonia classification is based on:
  • Site of acquisition.
  • Etiologic agent.
  • Morphology.

Pneumonia Classification by Acquisition Site

• Community-acquired pneumonia.
• Hospital-acquired pneumonia.

Pneumonia Classification by Etiologic Agent

• Typical pneumonia is caused by typical organisms with fever.
• Atypical pneumonia is caused by atypical organisms without fever.

Causative Agents of Typical Pneumonia

• Streptococcus Pneumoniae
• Hemophilus Influenzae
• Staphylococcus aureus
• Streptococcus pyogenes
• Klebsiella pneumoniae

Causative Agent of Atypical Pneumonia

• Mycoplasma pneumoniae

Morphological Classification of Pneumonia

• Lobar pneumonia
• Bronchopneumonia (lobular pneumonia)
• Interstitial pneumonia
• Lobar and bronchopneumonia are typical.
• Interstitial pneumonia is atypical.

Lobar Pneumonia

• Involves an entire lobe or a large portion.

Causative Agent for Lobar Pneumonia

• Streptococcus Pneumoniae (Pneumococci).
• The most common cause of meningitis.

Stages of Lobar Pneumonia

• Congestion
• Red Hepatization
• Gray Hepatization
• Resolution
• These stages are for untreated lobar pneumonia.

Congestion Phase

• Capillary dilation leads to exudative fluid infiltration into alveolar spaces
• Replication and spread of Pneumococci.
• Acute inflammation.
• Pleural effusion possible.
• No significant infiltration on X-ray.

Diagnosis Without X-Ray Findings (Congestion Phase)

• Patients are febrile.
• Sputum culture can diagnose bacteria (S. Pneumoniae/Pneumococci).

Red Hepatization Phase

• Capillaries widely dilate, RBCs are seen.
• Radiographic findings (consolidation).
• Acute Inflammation.
• Bronchial breath sounds.
• This is the severe stage for the patient.

Grey Hepatization Phase

• Congestion subsides.
• Exudate remains.
• Fever subsides.

Resolution Phase

• Exudate is removed.

Bronchopneumonia

• Patchy consolidation of one or more lobes.
• Typical pneumonia.

Organisms Causing Bronchopneumonia

• Hemophilus Influenzae
• Staphylococcus aureus
• Streptococcus pyogenes
• Klebsiella pneumoniae

Interstitial Pneumonia

• Patchy inflammatory changes of the pulmonary interstitium
• Atypical pneumonia.
• Capillaries and alveolar spaces widen
• Leads to Ventilation/Perfusion mismatch and low V/P ratio.
• Mild disease with slow progression (walking pneumonia).
• Patients are afebrile.

Causative Agent of Interstitial Pneumonia

• Mycoplasma pneumoniae
• Influenza viruses
• Respiratory syncytial virus (RSV).
• Atypical organisms/viruses
• Q-fever is caused by Coxiella burnetii from cattle/sheep or unpasteurized milk.

Pneumonia in AIDS Patients

• Pneumocystis jiroveci (fungus).
• The most common opportunistic infection in AIDS.

Community-Acquired vs. Hospital-Acquired Pneumonia

• Hospital-acquired pneumonia occurs in hospitalized patients, usually with serious diseases.

Organisms Causing Hospital-Acquired Pneumonia

• Gram-negative bacteria like:
  • Pseudomonas aeruginosa
  • Escherichia Coli
  • Klebsiella pneumonia
  • Legionella
  • Staph aureus

Presentation of Pneumonia

• Cough (dry or productive)
• Fever
• Shortness of Breath
• Chest pain (pleuritic)
• Bronchial breath sound
• Possible non-pulmonary symptoms (headache, fatigue, muscle pain).
• Elderly may present with confusion and falls.

Unique Feature of Pneumonia Caused by Streptococcus pneumoniae

• Rust-colored sputum

Usual Outcome of Pneumonia

• Resolution without alveolar damage.
• Complications can occur with virulent strains or organisms
• Possible complications include:
  • Abscess
  • Empyema
  • Endocarditis and meningitis (from bacterial dissemination)
    • Staph aureus causes endocarditis
    • Strep pneumo causes meningitis

Abscess from Pneumonia

• Cavitation in lung parenchyma due to pus collection.
• Complication of bronchopneumonia and lobar pneumonia.

Empyema

• Accumulation of pus in the pleural cavity.
• Complication of lobar pneumonia only.

Treatment for Pneumonia

• Amoxicillin 500mg three times a day.
• Clarithromycin for penicillin-allergic patients.
• Amoxicillin is a broad-spectrum penicillin

Antimicrobial Classification

• Action (effect).
• Mechanism of action.
• Classified as Bacteriostatic (stops growth) or Bactericidal (kills).

Antimicrobial Classification by Mechanism

• Cell wall synthesis inhibitors
• Protein synthesis inhibitors
• Nucleic acid synthesis inhibitors
• Bacterial metabolism inhibitors

Cell Wall Synthesis Inhibitors

• Penicillins
• Cephalosporins
• Vancomycin (MRSA infections)

Protein Synthesis Inhibitors

• Aminoglycosides
• Tetracyclines
• Chloramphenicol
• Erythromycin, Clarithromycin, Azithromycin (ACE)
• Clindamycin

Nucleic Acid Synthesis Inhibitors

• Rifampin
• Fluoroquinolones
• Metronidazole

Bacterial Metabolism Inhibitors

• Sulfonamides
• Penicillins contain a β-lactam ring.

Mechanism of Penicillin Action

• Bind and inactivate penicillin-binding proteins (PBPs) which are used in bacterial cell wall synthesis.

Mechanisms of Bacterial Resistance to Penicillins

• Producing β-lactamases (penicillinases).
• Downregulation of porins.
• Mutations of PBP.
• Upregulation of efflux channels.

Penicillins: Bactericidal or Bacteriostatic?

• Penicillins are bactericidal.

Penicillin Classification

• Narrow spectrum penicillins
• Broad spectrum penicillins
• β-lactamase resistant penicillins
• Antipseudomonal penicillins

Narrow Spectrum Penicillins

• Penicillin G (benzylpenicillin).
• Penicillin V.

Broad Spectrum Penicillins

• Amoxicillin.
• Ampicillin.

Beta Lactamase Resistant Penicillins

• Methicillin
• Oxacillin
• Nafcillin
• Dicloxacillin
• Effective against Staph aureus infections (except MRSA).

Antipseudomonal Penicillins

• Piperacillin
• Ticarcillin

Use of Penicillin G

• Treats Syphilis

Use of Penicillin V

• Treats Group A Streptococcus infections like pharyngitis, preventing Rheumatic fever.

Broad Spectrum Antibiotics and Penicillinase

• Broad spectrum antibiotics aren't penicillinase resistant.
• They have broad gram-negative coverage.

Difference Between Ampicillin and Amoxicillin

• Amoxicillin has excellent oral absorption,preferred over ampicillin.

Clinical Use of Amoxicillin

• Community-acquired pneumonia
• Endocarditis prophylaxis
• Otitis media
• Sinusitis

Beta Lactamase Resistant Penicillins Use

• Methicillin, Oxacillin, Nafcillin, and Dicloxacillin are for Staph aureus infections (except MRSA).

Oxacillin, Nafcillin, and Dicloxacillin

• Undergo biliary excretion.

Dicloxacillin

• Treats mastitis (Staph aureus).

Antipseudomonal Penicillins

• Treat pseudomonas aeruginosa and Klebsiella pneumonia (hospital-acquired pneumonia).

Drugs Co-Administered with Penicillins

• Beta-lactamase inhibitors
• Probenecid
• These enhance penicillin activity by preventing resistance and slowing down excretion, respectively.

Beta Lactamase Inhibitors Examples

• Clavulanic acid
• Sulbactam

Use of Beta Lactamase Inhibitors

• Enhance narrow and broad-spectrum penicillin activity by preventing resistance
• Amoxicillin + Clavulanic acid is found in Augmentin

Probenecid with Penicillins

• Probenecid slows excretion of penicillins.
• It is a gout drug that increases uric acid excretion

Adverse Effects of Penicillins

• Hypersensitivity (10% of patients, rash to anaphylaxis)
• Methicillin can cause interstitial nephritis

General Characteristics of Streptococcus

• Gram-positive cocci (grape-like clusters).
• Facultative anaerobes.
• Catalase negative.

General Characteristics of Staphylococcus

• Gram-positive cocci (chains/pairs).
• Facultative anaerobes.
• Catalase positive.

Classification of Streptococcus

• Based on cell wall's carbohydrate (C) antigen into four groups.
  • Group A Streptococcus (GAS)
  • Group B Streptococcus (GBS)
  • Group D streptococcus (GDS)
  • Non-groupable Streptococci

Group A Strep (GAS)

• Streptococcus pyogenes

Group B Strep (GBS)

• Streptococcus agalactiae

Group D Strep

• Enterococci

Non-Groupable Strep

• Streptococcus pneumoniae
• Viridians streptococci

Types of Hemolysis

• Alpha hemolytic - partial hemolysis
• Beta hemolytic - complete hemolysis
• Gamma hemolytic (non-hemolytic) - no hemolysis.

Alpha Hemolytic Streptococcus Species

• Streptococcus pneumoniae
• Viridians Streptococci

Beta Hemolytic Streptococcus Species

• Streptococcus pyogenes (GAS)
• Streptococcus agalactiae (GBS)

Gamma-Hemolytic Streptococcus

• Enterococci (Group D strep)

Differentiating Alpha Hemolytic Strep

• Streptococcus pneumoniae = Optochin sensitive, lysed by bile acid
• Viridans streptococcus = Optochin resistant, bile acid resistant
• Use optochin and bile tests: Pneumo is sensitive to optochin/bile, Viridians is resistant.

Differentiating Beta Hemolytic Strep

• GAS (Streptococcus pyogenes= bacitracin sensitive
• GBS (Streptococcus agalactiae) = bacitracin resistant
• GAS is sensitive to bacitracin, GBS is resistant.

Diseases Caused by Streptococcus pneumoniae

• Pneumonia
• Meningitis

Virulence Factors of Streptococcus pneumoniae

• Protein adhesins
• IgA protease
• Polysaccharide capsule
• Pneumolysin

Role of Protein Adhesins

• Bacteria colonization.

Role of IgA Protease

• Lyses IgA on mucosal surfaces.

Role of Polysaccharide Capsule

• Inhibits phagocytosis.

Role of Pneumolysin

• Hemolyzes cells
• Partially reduces hemoglobin into green pigment (alpha hemolysis).

Diagnosis of Streptococcus

• Gram stain
• Catalase test
• Hemolysis test
• Glucose fermentation test
• Optochin and bile test

Expected Results on Streptococcus Pneumoniae Lab tests

• Gram-positive, lancet-shaped diplococci.
• Catalase positive.
• Alpha hemolysis.
• Ferments glucose to lactic acid.
• Optochin and bile sensitivity.

Quellung Reaction

• Capsular swelling when mixed with antibody.
• Specific for S. pneumoniae, along with optochin and bile sensitivity.

Vaccines for Streptococcus pneumoniae

• PCV (Polysaccharide Conjugate Vaccine) - for infants (7 valent).
• PPV (Polyvalent Polysaccharide Vaccine) - for adults (> 65), immunocompromised (23 valent).

Arteries Supplying the Lung

• Pulmonary artery.
• Bronchial artery.
• The bronchial arteries come from the descending aorta

Lung Structures Supplied by Bronchial Arteries

• Bronchi
• Connective tissue
• Visceral pleura

Origin of Pulmonary Artery

• The Pulmonary artery arises from the heart.

Number of Lung Lobes:

• Right = Three. Superior, Middle, and Inferior.
• Left = Two. Superior and Inferior

Landmarks on the Lungs

• Cardiac notch: lateral deviation of the left lung's anterior border caused by the heart.
• Lingula: anterior projection of the left lung's superior lobe below the cardiac notch.

Surface Anatomy of Lungs and Pleura

• Apex: above 1st rib inside the neck.
• Inferior border: down to 6th rib anteriorly and 10th rib posteriorly.
• Relations along the midclavicular line.

Types of Pleura

• Parietal Pleura.
• Visceral Pleura (directly in contact with the lung), insensitive to pain.

Parts of Parietal Pleura

• Cervical pleura
• Costal pleura
• Mediastinal pleura
• Diaphragmatic pleura

Pleural Recesses

• Costodiaphragmatic recess. Between 6th and 8th ribs. A place between the lungs where fluid collects due to gravity.
• Costomediastinal recess.

Thoracentesis Location;

• Aspiration of fluid
• 9th intercostal space along the MID-AXILLARY LINE
• 7th intercostal space but along the SCAPULAR LINE
• The needle should be inserted superior to the rib. Approach inferior to the rib to avoid injury

Relation of Airways to Vasculature

• Bronchus - Most posterior on both lungs
• Pulmonary Veins - Always inferior on both lungs
• Right Pulmonary Artery- Most Anterior for right lungs
• Left Pulmonary Artery is most superior for the lefts lungs

Hilum

• Figure one with left pulmonary is most superior
• Figure one with right pulmonary is most anterior

Foreign Body Aspiration

• The right lung, specifically the inferior lung, is most common for foreign entry.
• The right bronchus is wider, shorter and runs more vertically.

Bronchopulmonary Segment

• Is the anatomic, functional, and surgical unit of the lung. Surgical removal is safe due to other segments.

Bronchopulmonary Segment Contains;

• Bronchus and alveoli
• Artery
• Lymph Vessel
• Autonomic Nerve
• No vein, vein is found in the connective tissue

Characteristics of a Bronchopulmonary Segment

• Subdivision of a lung lobe.
• Pyramid-shaped apex toward lung root.
• Connective tissue to support structure
• Segmental bronchus
• Blood vessels
• Autonomic Nerves

Muscles for Breathing

• Diaphragm contracts during breathing.
• Other muscles are also utilized for breathing
• the diaphragm keeps the diaphragm alive through the spinal roots: C3, C4, C5

Structures that perforate the diaphragm

• Inferior vena cava @ T8
• Esophagus and vagus nerve @ T10
• Abdominal aorta, thoracic duct, azygos vein @ T12

Bifurcation Location

• The trachea bifurcates at T4.
• The common carotid bifurcates at C4.
• The abdominal aorta bifurcates at L4.

Air Volumes

• IRV - Inspiratory reserve is 3100 ml
• TV- Tidal volume is 500 ml
• ERV - Expiratory reserve is 1200 ml
• RV - Reserve volume is 1200 ml

Lung Capacity Definitions

• IC- Inspiratory Capacity is IRV + TV (2600ml)
• FRC - Functional Reserve Capacity is ERV+ RV (2400ml) VC - Vital Capacity is TV + IRV+ ERV (4800 ml) TLC - Total lung capacity is IRV + TV + ERV + RV

LITER

The above volumes can be remembered using this acronym

Epithelium of the Airways

• Pseudostratified, ciliated columnar starting with the trachea

Goblet Cells

• Mucous producing glands in airways
• Cilia clears out particles and mucus in respiratory system
• Smoth muscles are found in the bronchi

Trache and Aveoli

• No muscles found in the trachea and no smooth muscles in the aveoli

Types of Alveolar Cells

• Squamous is Type 1
• Cubiodila is Type 2

Type I Pneumocytes

• Suited for optimal diffusion; lines alveoli
• The function of pneumocytes is to prevent alveolar collapse by secreting pulmonary surfactant to reduce surface tension.
• Type 2 pneumocytes are type 1 precursurs

Embryologic Structure

• Derived from the fore endoderm, same as the liver and pancreas.