Case 7: Luke Tomczak - Pneumonia

Lung Protective Mechanisms

Physical barriers

Reflex barriers

Chemical barriers

Cellular barriers

Lung Physical Barriers

Epithelial cells

Cilia

Cell junctions

Mucus

Pattern recognition receptors

Physical Barrier: Epithelial Cells

Type 1 and 2 pneumocytes (alveolar cells)

Type 1:

• Squamous cells

• Gas exchange

• Maintain ion/fluid balance

Type 2:

• Produce and secrete pulmonary surfactant (decrease surface tension)

• Express immunomodulatory proteins

• Transepithelial water movement

• Regenerate pneumocytes

Physical Barrier: Cilia

In resp tract (not alveoli)

Push mucus to pharynx (mucociliary clearance)

Physical Barrier: Cell Junctions

Apical junctional complex

Tight and adherens junction proteins between epithelial cells

Prevent foreign particle entry into tissues

Physical Barrier: Mucus

Secreted by mucous glands and goblet cells in epithelium

Trap foreign particles for mucociliary clearance

Physical Barrier: Pattern Recognition Receptors (PRRs)

In airway and alveoli

Detect pathogens and initiate innate immune response

Lung Reflex Barriers

In Edwin McKenzie

Cough

Sneeze

Gag

Lung Chemical Barriers

Antimicrobial peptides (AMPs)

Chemical Barrier: AMPs

In mucus

Neutralize/kill pathogens

Ex: Defensins, lysozymes, lactoferrin, IgA, collectins

AMPs: Collectins

In alveoli

Secreted by type 2 pneumocytes

Surfactant Protein A (SP-A) and Surfactant Protein D (SP-D)

• Bind sugar patterns on pathogens for phagocytosis

Lung Cellular Barriers

Immune cells

Immune Cells

Epithelial cells

Neutrophils

Monocytes

Macrophages

Dendritic cells

Innate lymphoid cells

NK cells

Immune Cells: Epithelial Cells

Ciliated in airways for mucociliary clearance

Produce mucus, AMPs, and cytokines (inflammation and immune cell recruiting)

Immune Cells: Neutrophils

Phagocytes

Recruited by chemotaxis from inflammation

• Enter alveolar spaces

Immune Cells: Monocytes

From bone marrow

Immature phagocytes in blood

• Cannot fight infection

Recruited by chemotaxis from inflammation

• Become macrophages in tissues

Immune Cells: Macrophages

Phagocytes

• Etherocytosis: Resolution = Macrophages phagocytose neutrophils + self

Alveolar and interstitial macrophages

Alveolar Macrophages

In alveoli (no cilia) = Rely on macrophages to phagocytose pathogens

• Migrate to bronchioles and deposit

• Cilia carry to pharynx

Toll-like receptors (TLRs) bind PRR recognizing pathogen-associated molecular patterns (PAMPs)

• Cause phagocytosis and secrete pro-inflammatory cytokines + chemokines

Interstitial Macrophages

In lung interstitium

Express MHC 2 proteins = Bind and present antigens to CD4+ T-cells

Produce immunosuppressive cytokines and chemokines

• Regulate immune cell activity and tissue-damaging inflammation

Immune Cells: Dendritic Cells

APC

Surface MHC 1 and 2 proteins

• Bind and present antigens to T-cells in lymph nodes

• Initiate adaptive immune response

Produce cytokines for viral infection

Immune Cells: Innate Lymphoid Cells

Respond to distress cytokines from epithelial cells

Regulate inflammation and tissue repair

Main: ILC2

Immune Cells: NK Cells

Target abnormal host cells (virus-infected, transformed)

Produce cytokines

Failure of Respiratory System Pathways

1. Poor physical clearance

2. Disrupted mucociliary function

3. Impaired phagocytic and inflammatory cells

Resp System Failure: Poor Physical Clearance

No cough

Weak diaphragm and expiratory muscles

Poor epiglottis function

Resp System Function: Disrupted Mucociliary Function

Viral infections causing structural damage

Primary ciliary dyskinesia (poor cilia function)

Smoking

Resp System Failure: Impaired Phagocytic and Inflammatory Cells

Alveolar macrophage deficiencies

Viral infections, smoking, alcohol

Lung Infection Effects on Ventilation

Edema

In Airway: Increase resistance = Decrease airflow

In Pleura: Decrease compliance and lung distension = Decrease VC

• Insufficient pressure to draw air in

Lung Infection Effects on Gas Exchange

Low V/Q: Decrease gas exchange (particularly CO2)

Alveolar Edema: Increase alveolar-capillary barrier space = Prevent O2 diffusion

Hypoxia

Low O2 reaching tissues

From pO2

Hypoxemia

Low O2 in blood

From SPO2

PaO2/FiO2: Indicate when patient needs O2

• Low ratio = Severe shunting

Oxyhemoglobin Curve

Hemoglobin affinity for O2

Plateau at 60-70 mmHg

Oxyhemoglobin Curve: Right Shift

Decreased hemoglobin affinity for O2

• More O2 unloading into tissues

Increase P50

• 50% sat at higher-than-normal PO2

Oxyhemoglobin Curve: Left Shift

Increase hemoglobin affinity for O2

• Less O2 unloading into tissues (hemoglobin bind tighter)

Decrease P50

• 50% sat at lower-than-normal PO2

Chest Pain Indications

Changing during Resp: Lung pathology

Unchanged during Resp: Suspect MI

Pneumonia: Description

Acute LRT infection

Acquisition:

• Community: Infection outside hospital

• Nosocomial: Infection in hospital setting

Location:

• Lobar: In pulmonary lobes (single or multi)

• Interstitial: Inflammation and fibrosis in interstitium and parenchyma

Pneumonia: Epidemiology

Very common

Risk Factors:

• Younger and older age

• Comorbidities (aspiration, COPD, chronic lung/heart diseases)

• Viral resp infection

• Smoking and alcohol

Pneumonia: Etiology

Viruses (more common) and bacteria

Viruses:

• Influenza A and B

• Coronavirus

• Rhinovirus

• Parainfluenza virus

• Adenovirus

Bacteria:

• Typical:

  • Streptococcus pneumoniae (most common)

  • Group A streptococci

• Atypical: Resist beta-lactams, cannot identify with traditional techniques

  • Legionella

  • Mycoplasma pneumoniae

Pneumonia: Pathogenesis

Alveolar infection

1. Pathogen enter LRT (droplets, aerosol)

• Compete against lung microbiome

• Colonize nasopharynx and alveoli

2. Immune system cannot clear pathogen = Inflammation

• Pus in parenchyma = Decrease compliance + shunt

3. Immune cells increase inflammation and neutrophil chemotaxis

Pneumonia: Investigation

X-ray

• Pulmonary infiltrate (opacity) → Air bronchogram (darker air-filled bronchioles on top)

• Typical: Opacity in 1 lobe

• Atypical: Reticular (radiating) opacity

Severe: Identify pathogen + evaluate treatment

• CBC

• Sputum gram stain + culture

• Urinary antigen test

Pneumonia: Clinical Presentation

Fever

Resp symptoms:

• Cough

• Dyspnea/SOB

• Chest pain

Pneumonia: Treatment/Management

Antibiotics: Target S. pneumoniae

• Amoxicillin + macrolide

Abscesses: Drain + longer treatment