PNEUMONIA

Lung infection

Fever + Productive Cough + Consolidation on CXR

Pneumonia (PNA) is an infection in the lungs. The telltale signs of pneumonia are a fever, productive cough and a chest x-ray consolidation. In addition to fever/cough/consolidation, PNA can cause an elevated white count, pleuritic chest pain (the wet lung expands stretching the pleura), and dyspnea (loss of alveoli). The phlegm can be yellowish (pus) or rusty (blood from the alveoli). Here are the risk factors: impaired cough reflex (Drugs, etoh, coma, neuromuscular disease, old age), impaired mucociliary escalator (smoking, after a viral infection, Kartagener’s), tube obstruction (tumor, foreign body) or immunodeficiency (AIDS, old age, CVID).

Pneumonia is treated empirically with Ceftriaxone and Azithromycin. If they’ve been hospitalized within the last 3 months (Healthcare Associated PNA), then you have to bust out the big gun antibiotics (consider coverage for MRSA and Pseudomonas). Ventilator Associated PNA is especially likely to involve these dangerous bugs.

When a patient presents with a fever and cough, you should order a chest x-ray and get their pulse ox. See the CXR page for details. But let’s just say it shows PNA. What next? Blood cultures are standard practice, but they only help 10% of the time. Sputum cultures are even less sensitive and specific. If they’re really sick or old, then they need to be admitted to the hospital for IV antibiotics. If they’re young and hardy, then they can be treated with a few days of oral antibiotics.

Here are some different patterns of pneumonia that can be elucidated based on the chest x-ray findings.

Lobar PNA - the infection begins in an alveolus. Fluid enters the infected alveolus. That fluid can overflow into nearby alveoli. Given enough time, it can flood an entire lobe

Bronchial PNA - the infection begins in the bronchi. Fluid enters the bronchus near the infected tissue. Gravity immediately pulls that fluid down, eventually filling lots of different clumps of alveoli, separated in space. There will be lots of separate pockets of consolidation. This process reminds me of Pachinko games.

Empyema is an infection of the pleural cavity. Quite dangerous.

Lung Abscesses occur when anaerobic bacteria take root. The thick abscess walls block entry of antibiotics, so suspect a lung abscess when a case of pneumonia fails to get better after a course of antibiotics. The anaerobes produce a foul smelling sputum (similar to the colonic anaerobes that make your poop stinky). Also note that Staph aureus can cause abscesses as well, although only the anaerobic abscesses produce foul smelling sputum.

Aspiration pneumonia is caused by “swallowing down the wrong pipe.” If you accidentally inhale your saliva (which is full of bacterial mouth flora), it can seed an infection in your lungs. Because the right bronchus is angled more vertically, while the left is angled more horizontally, aspirated saliva typically falls down the right bronchus and infects the right lower lobe. Aspirated pneumonia is often anaerobic, and benefits from an anaerobic antibiotic like Clindamycin. Those with dementia, alcoholism, strokes, seizures or vomiting are more likely to aspirate.

Interstitial Pneumonia (Atypical Pneumonia) is pneumonia that occurs when there are intracellular pathogens -- viruses, Chlamydia and Mycoplasma. These guys enter the alveolus and immediately invade the nearest cells (pneumocytes in the alveolar wall). The body recognizes this! But instead of sending PMNs and flooding the alveoli, it sends lymphocytes! The lack of neutrophils explains why the symptoms are so mild. They usually self-resolve, but treatment consists of Azithromycin. On chest x-ray, look for bilateral hazy splotches. The chest x-ray will often look worse than you expect.

4 STAGES OF PNEUMONIA

Stage 1

Congestion (Day 1)

Here is the alveoli. It’s filled with air and a single macrophage (Mɸ)

Bacteria travel down the airway, and enter the alveolus. The Macrophage needs help, so it releases cytokines (fever)

The cytokines immediately flood the alveolus (productive cough). Since the bug traveled down the airway, it’s probably an aerobe. So the flooding should drown it! Fun fact: the fluid is what radiologists call “consolidation.”

Stage 2

Red Hepatization (Days 1 - 3)

Next, the cytokines make the nearby blood vessels more leaky. RBCs, WBCs and fibrin enter (fibrinous exudate). The fluid starts to saturate the lung, making it dense (like the liver). The RBCs give the lung a red color, hence “red hepatization”

The neutrophils fight the bacteria

They win!

Stage 3

Gray Hepatization (Days 4 - 10)

The macrophage starts cleaning up the debris, starting with the RBCs.

Without the red cells, the lung turns gray!

Stage 4

Resolution or Organization

Now the macrophage eats the rest of the debris

Now one of 2 things can happen. If the macrophages are intact, they drink the fluid, and air returns. The Type 2 Pneumocytes (stem cells) regenerate new pneumocytes. This is Resolution

But if the macrophages are overwhelmed, then Fibroblasts step in. They don’t drink the fluid, they replace it with collagen. A permanent scar forms! This is Organization.

PNEUMONIA (BACTERIA)

Pneumonia Facts

- - Strep pneumoniae is the most common cause of pneumonia
  - Staph aureus pneumonia is common after the flu.
  - H. influenzae and Moraxella catarrhalis are other common causes of CAP.
  - Klebsiella causes pneumonia with currant jelly sputum
  - Legionella causes interstitial pneumonia. It’s common on cruise ships and at hotels (air conditioning colonization) that can be quite severe in older smokers. They experience high fevers, headache, confusion, diarrhea and hyponatremia. Diagnose with urine antigen test or cultures with a silver stain on charcoal yeast media. Treat with fluoroquinolones.
  - Coxiella burnetii (Q fever) is associated with barnyard animals.
  - Daptomycin is a strong MRSA-covering antibiotic. But don’t use it for pneumonia -- it’s inactivated by surfactant.
  - Mycoplasma pneumonia is the most common pathogen in young healthy adults

Lobar pneumonia of the right lower lobe

PERTUSSIS

Whooping cough

Pertussis is a bacterial respiratory infection, associated with a powerful cough, that is thankfully rare in the modern era thanks to vaccination. Pertussis is caused by Bordetella pertussis, a gram negative coccobacillus. It’s really easy to recognize Pertussis. The child will have a flu-like illness for a few days (Catarrhal phase), but then their cough will get really severe (Paroxysmal phase). They cough so hard that they gasp, vomit (posttussive emesis) or even pass out. In unvaccinated adults, pertussis can cause a 100-day cough.

B. pertussis uses its Pertussis Toxin to ramp up adenylate cyclase and cAMP in infected human cells (it does so by inactivating the inhibitory Gi subunit). This somehow prevents phagocytosis, enabling pertussis to live within epithelium and macrophages. The ↑AC can also ↑insulin and lead to hypoglycemia. Somehow, this also attracts a lymphocyte-heavy immune response. The white blood cell count can be dramatically elevated!

The diagnosis is usually made clinically; their chest XR is normal. Culturing Bordetella pertussis requires a special Bordet-Genou agar (made of potato) or Regan-Lowe medium (made of charcoal, blood and abx).

Treat with Azithromycin (TMP-SMX works too). The infection is prevented with the Tdap or DTaP vaccine.

Posttussive emesis

BRONCHIOLITIS

Coughing 1 year old

Bronchiolitis is an infection of the bronchioles. It only affects kids less than 2 years old. It causes a fever, cough, dyspnea and wheezing. Notably, asthma doesn’t occur before 2 years of age, so there’s little overlap. The diagnosis is clinical. RSV (Respiratory Syncytial Virus) is the major cause of Bronchiolitis. RSV begins replicating in the nose (runny nose). 2 - 3 days later, it spreads into the lungs (wheezing, cough).

Patients with mild-to-moderate Bronchiolitis can display dyspnea, wheezing, cough and fever. On physical exam, they can show some increased effort with breathing, which manifests as tachypnea, nasal flaring, intercostal retractions and abdominal breathing

Severe Bronchiolitis is a big deal. The child will display all the symptoms of mild-to-moderate Bronchiolitis, in addition to markedly abnormal vital signs, apnic spells, grunting and even cyanosis. They won’t be able to feed adequately, because they can’t stop breathing long enough to suck on a bottle. Severe infections are more likely to occur in preemies, underweight babies and those under 6 weeks old.

The treatment is pretty minimal. Give them O2 if their O2 sat drops below 94%. There’s also a big emphasis on maintaining good hydration! And you can give tylenol as needed. But you DON’T treat them with steroids, antibiotics or bronchodilators. Pretty frustrating, but you just have to let the disease run its course. Preemies are sometimes given Prophylactic Palivizumab. It’s a monoclonal antibody against RSV (Paramyxovirus).

BRONCHITIS

Coughing smoker

Bronchitis is an infection of the bronchi, usually viral. It often occurs in older smokers. Bronchitis is often similar to pneumonia (although the symptoms tend to be milder and longer lasting), but you can differentiate them by a more normal chest x-ray and less of a fever. The cough sputum tends to be less colorful.

PNEUMOCYSTIS PNEUMONIA

AIDS pneumonia

Pneumocystis jirovecii pneumonia (PCP) is the most common AIDS defining illness. PCP can begin once the CD4+ T cell count drops below 200. Pneumocystis jirovecii is an “atypical” extracellular yeast (yeast just means single celled fungus). For a long time, researchers thought it was a protozoan, but ribosomal RNA analysis revealed that it was actually a fungus.

PCP can cause life-threatening interstitial pneumonia, characterized by a fever, hypoxia and respiratory distress. Sometimes it’s asymptomatic though. The chest x-ray shows diffuse bilateral interstitial opacities. On chest CT, there are Ground-glass opacities, sometimes with numerous pneumatoceles (bubbles). The LDH is usually moderately elevated on your labwork. The diagnosis is definitively made with a bronchoalveolar lavage. The alveoli are typically filled with frothy exudate. Disc-shaped yeast seen on Methenamine silver staining. Looks like a “crushed tennis ball.”

Once an AIDS patient’s CD4+ count drops below 200, they should start using prophylactic TMP-SMX (Bactrim) to prevent PCP. Steroids are used in severe infections. If the patient has a sulfa allergy, use Pentamidine or Atovaquone instead of TMP-SMX.

Crushed tennis ball shape

ENDEMIC LUNG FUNGI

In North America there are four fungi that can cause lung disease in a healthy human. Their spores are wafting about in the air, just waiting for you to inhale them. All of them are treated with -azoles (mild infections) or Amphotericin B (severe). They cause a mild, drawn-out, nagging pneumonia plus B-symptoms. In immunocompromised hosts, these fungi will disseminate, and fuck you up real good.

All but Coccidioidomycosis are dimorphic. Dimorphic means they are sometimes unicellular (yeast) and sometimes multicellular (molds). The yeasts look like little circles. The molds can form complex branches (hyphae). They switch depending on the temperature. They are “molds in the colds” and “yeasts inside beasts.” Animals (including humans) have a warm body temperature, so the Dimorphic fungi will look like yeasts whenever they’re inside the body.

Aspergillus is a ubiquitous fungus that causes illness in the developing world. It can cause four different diseases.

1. 1. Invasive Aspergillosis is the disseminated infection form. It will look like septic pneumonia. Aspergillus is catalase-positive, which explains why this is common in neutrophil deficiencies (Chronic Granulomatous Disease, Leukocyte Adhesion Deficiency, Hyper IgE Syndrome) as well as AIDS.
  2. An aspergilloma is a fungus ball that has colonized an old cavitary lung lesion (prior TB infection).
  3. Allergic Bronchopulmonary Aspergillosis is discussed in the bronchiectasis section. Colonization of crummy lungs seen in CF causes recurrent asthma attacks.

The Aflatoxins produced by Aspergillus are capable of causing Hepatocellular Carcinoma.