BHS 116 – Physiology
Notetaker: Vivien Yip
Date: 10/12/2012, 1st hour
Page1
Clicker Q
Which of these will cause primary pulmonary hypertension?
- BMPR2 mutation
Lecture 32 Pulmonary Infections – Tuberculosis, Pneumonia and Fungal Infections
Constricted lung disease
- Granulomatous disease
o TB tuberculosis
- Fibrotic disease
o Pneumonia
- Diseases which constrict the chest cavity
Describe the pathophysiology, pathogenesis, and differences between primary and secondary TB
Bacterial exposure
Symptoms
Contagious
Pathophysiology
Primary Pulmonary TB
1st time exposure
Asymptomatic
No
Formation of Ghon complex
(subpleural lesion in lung and
enlarged lymph nodes)
Fibrosis (walling off) and
calcification
Secondary Pulmonary TB
2nd time exposure
Malaise, low grade fever, night sweats
Yes
Attraction of immune cells to Ghon
complex causing destruction of lung tissue
creating large cavities
More damage than primary TB
Mycobacteria
- Aerobic
- Gram +ve
- Non motile
o Mycobacteria tuberculosis hominis
 Transmitted by inhalation
o Mycobacteria tuberculosis bovis
 Transmitted by milk from diseased cows
 Used in TB vaccines
 Leads to systemic TB, not localized in lungs, can have granulomas in other parts
of the body
Describe the gross morphological and histological changes in the lung during TB
Primary Pulmonary TB – Ghon Complex
- Subpleural lung tissue lesion
- Enlarged infected lymph nodes
- Tissue undergoes caseous necrosis and can also occur in regional lymph nodes
- Segregated to small areas of the lung
Tubercle Granuloma
- Necrotic center surrounding by epitheloid cells
- On periphery: fibroblasts, lymphocytes, giant cells (multinucleated)
BHS 116 – Physiology
Notetaker: Vivien Yip
Date: 10/12/2012, 1st hour
Page2
Primary TB Mechanism
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Microbacterium tuberculosis is inhaled
Macrophages takes up bacterium
Bacterium is endocytosed but does not get destroyed and digested by macrophage
Instead, it propagates inside macrophage, and more bacteria is formed
Eventually the infected macrophage will lyse which leads to spread of bacteria in region, now
called a bacteremia
During this time, some of the macrophages are going to present TB antigens to helper T cells
Helper T cells are activated and activate more macrophages (mostly in lungs) and B cells
Macrophages release compounds
o NOS, Nitric oxide synthase, will kill bacteria
o Additionally, release TNF, tumor necrosis factor, which recruits more monocytes and
other types of cells that form these hybrid cells, epitheliohistiocytes, form wall around
infected area
Any infected macrophages or tissues going through necrosis gets walled off and contained 
producing a granuloma  prevents further infection of bacteria
Bacteria can stay alive in granuloma for decades
At this stage where we are hypersensitized and responsive
Hyper T cells are active, on alert, if another infection or second exposure occurs, becomes
secondary TB
If never exposed TB bacteria again, granulomas can stay for decades, never become activated
Asymptomatic at this stage, noncontagious
Hypersensitized state makes us reactive during TB test
o Inject a bit of antigen in skin, T cells will react to it causing inflammation
BHS 116 – Physiology
Notetaker: Vivien Yip
Date: 10/12/2012, 1st hour
Page3
Pathogenesis of TB – Primary to Secondary TB
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Progression into secondary TB
Start w/ primary infection, Ghon complex occurring
o In people that have a weakened immune system, might go directly to progressive primary
TB (only 5% of the time, rare occurrence)
o Weakened immune system, not good at walling off bacterial infection, will spread to
more regions of the lung
o Will have infection in more regions of the lung, symptoms similar to pneumonia and
congested lungs
o Bacteria are propagating, get inflammatory response
Most of the time we get latent lesions, walled off infected regions and infected cells, bacteria can
still be surviving in the granulomas
o There are times where bacteria are destroyed in the granulomas, get calcification, scar
formation
o Scar in both lymph node and the region of the lung that was infected
o Can last for decades, can stop here if never reexposed
If reexposed to TB bacteria again, get into secondary TB, much more destructive
o Symptomatic and contagious
o Most of the damage occurs in the upper lobe of the lung that was affected originally,
o Bacteria is aerobic, needs oxygen to propagate
o Lung physio: upper lung gets more ventilation, higher O2 concentration at apex, bacteria
more attracted to this area
o Immune cells start to attack the bacteria, massive immune response
Chronic inflammatory state, a lot of collateral damage, huge portion of lung tissue are destroyed
End up with large gaping cavities in upper portion of lung (major sign of secondary)
Bacteria gains access to blood stream, bacteria can now affect other tissues
o Spleen, immunologic clearing house for blood
o Liver, general toxic cleaner, purifies blood
o Gets in blood now called military TB and is systemic
BHS 116 – Physiology
Notetaker: Vivien Yip
Date: 10/12/2012, 1st hour
Page4
Pathophysiology of Tuberculosis
- Total lung capacity is reduced
- Residual volume is reduced
- Maximal expiratory flow rate is reduced
o Because lungs cannot expand to the normal volume, destroyed parts of lung
- Act as a constricted lung even though there is no physical constriction (fibrosis)
Describe primary and secondary ocular TB
Primary
- Ocular TB in absence of systemic TB or TB that has gained entry through the eye
Secondary
- Ocular involvement as a result of TB invasion from a distant site
- Results from systemic/military TB
Ocular TB
- Most common manifestation of ocular TB is uveitis
o Chronic anterior uveitis, panuveitis (entire uveal region), or choroidits
- Histologically, same granulomas as seen in lungs, only now is localized to choroid
o Retina, iris, ciliary body can also be involved, but rare
Describe the diagnostic tests and treatments for TB
Diagnostic tests
- Mantoux PPD
o Purified protein derivative, inject inactive TB to skin, look for inflammatory response
- Chest X ray
o Positive Mantoux test, see if granulomas are in lung or calcification
- Ocular
o Fine needle aspiration, acid fast stain, PCR
Treatments
- Vaccine
o BCG, bacillus calmetter Guerin (made from M. Bovis antigens)
- Long term antibiotics (2-6 months/longer)
o Isoniazid, rifampin, pyrazinamide, streptomycin, ethambutol
o Creating new antibiotics all the time, many resistant strains of TB
Describe the pathophysiology & stages of pneumonia
Pneumonia
- Broadly defined as infection in the lung
- Commonly acquired acute pneumonias are caused by infection w/ streptococcus pneumonia or
pneumococcus
- This bacterial infection occurs in the lung and onset is usually fast
- Symptoms: high fever, chills, chest pain, muscopurulent cough
- Alveoli fill w/ fluid and leukocytes (neutrophils)
- Results in decrease in respiratory membrane area resulting in decrease in ventilation of alveolar
space
- Get thicker interstitium due to extra fluid, cellular material and bacteria, a lot less space for air
and ventilation
- Can be 2 distinct anatomic and radiographic patterns
o Bronchopneumonia
 Small regions of the lung are affected
BHS 116 – Physiology
Notetaker: Vivien Yip
Date: 10/12/2012, 1st hour
Page5
o
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Lobar pneumonia
 90% are caused by streptococcus pneumonia infections
 Entire lobe is affected
Pneumonia is dangerous for those that are immunocompromised, in health individuals, it usually
clears up after the 4 stages:
Stages of pneumonia
1. Earliest stage, congestion
a. Alveoli filled w/ neutrophils, fluid (edema) and bacteria
2. Red hepatisation
a. RBCs enter alveoli and there is fibrin deposition (almost clot formation)
3. Gray hepatisation
a. RBCs are lysed and fibrous exudate increases
4. Resolution
a. Exudates are enzymatically digested and resorbed or expectorated (coughed up)
Acute pneumonia
- Red hepatization
o Alveoli are filled w/ neutrophils, proteinaceous fluid, RBCs and the infectious bacteria
o Forms pus like mucous that is coughed up
- Gray hepatisation
o Fibromyloid masses (Loose cellular content, more proteinaceous/fibrin deposit, clot
inside alveoli)
o Composed of macrophages and fibroblasts
o Get intraalveolar fibrosis
Pathophysiology
- Pneumonia of the R lung
- Decreased ventilation in R lung
- Decreased ventilation/perfusion ratio
- Results in decreased oxygenation of blood
o Get mixed blood
o L lung gets full saturation ~97%
o R lung can’t fully saturate ~60%
o Mean total systemic saturation is at 78%
Diagnostic Tests
- Microscopic Examinationo f the gram stained sputum
- Testing of blood ofr pneumococci (severe cases)
Treatment
- Penicillin, other antibiotics
Describe the fungal infections of the lung
- Fungi are classified into:
o Yeasts
o Mold
- Most of these infections occur in individuals that are immune-compromised (HIV)
- Health individuals can usually fight off these types of infection, uncommon
- Cryptococcis is a yeast infection that occur in the lungs
o get from inhalation of soil
o localized to lungs but can spread to brain
BHS 116 – Physiology
Notetaker: Vivien Yip
-
invasive aspergillosis is a mold infection that localizes to the lungs
o can spread to brain via blood
Clicker Q
Which cell type is responsible for the hypersensitivity reaction in TB
- helper T cells
Date: 10/12/2012, 1st hour
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