A 66 year old male with a history of smoking comes to see you complaining of difficulty breathing. You decide to do a pulmonary function test and analyze his results. What results would you expect to find if this patient has COPD?
COPD is a disease with decrease expiration.
A patient comes to see you with an FVC of 5L and and FEV1 of 4. 20 years later he comes back to see you with COPD that has caused 50% airway obstruction from the last time you saw him. What are his FVC and FEV1 values now?
Last time you saw him, he had an FVC:FEV1 ratio of 80%. If his airway obstruction has increased by 50%, his FVC:FEV1 ration should now be 40%. (FEV1 = 2 and FVC = 4.5ish).
A 30 year old patient comes to see you with a TLC of 7L. He smokes for 30 years and comes back to see you with a diagnosis of COPD. What happened to his TLC ratio during this time?
It increased to around 8L. As the disease progresses you get air trapping in the lungs that adds to the amount of air the lung can hold.
A 62 year old female comes to see you with a long history of smoking. She complains that she is coughing up cups of mucus. Tissue biopsy of her airways is shown below. What does this finding indicate?
This patient likely has chronic bronchitis. The Reid index is the ratio of mucus glands in the submucosa and the overall thickness of the bronchial wall. Smoking causes hyperplasia of these mucus glands, causing increased mucus production and increased Reid index. Diagnosis of chronic bronchitis is strengthened by a Reid index > 50%.
How does chronic bronchitis contribute to development of COPD?
Mucus that gets trapped in the airways also traps air and causes obstruction.
A 59 year old male comes to see you complaining of a productive cough and increased respiratory infections in the past year. He is also cyanotic. What is causing this patient to be cyanotic?
As airways are trapped, CO2 has a harder time getting out of the lungs and takes away some of the PAO2 in the alveoli. This results in a decreased PaO2 and cyanosis.
A 79 year old male comes to see you for his regular visit. He has a long history of COPD. You run some tests to see how he is doing and find a decreased FEV1:FVC ratio. His blood O2 saturation is 80%. How might this patient's chronic condition affect his heart?
Cor pulmonale. Hypoxia causes constriction of blood vessels around bronchioles that are not ventilating well. Mass constriction in diseases of COPD where ventilation is not great anywhere results in increased right ventricular pressure and eventual right heart failure.
How does emphysema result in obstructive pulmonary disease?
Destruction of the alveolar air sacs causes loss of elastic recoil in the alveoli. This makes it more difficult to expel air from the lungs. Additionally, when air is accelerated out of the bronchiole during expiration, the air pulls on the wall causing it to collapse due to absence of elastic recoil in the damaged alveoli. This causes obstruction and air trapping.
With all of the dust that gets into a normal person's lungs, why doesn't everyone have emphysema due to the alveoli's inability to produce mucus and get foreign particles out of the lung?
The lung produces proteases that get rid of foreign particles. These proteases are what cause inflammation and destruction of alveolar walls in people with emphysema. Healthy people don't get emphysema because they produce antiproteases (specifically alpha-1 anti-trypsin) that balance out the destructive activity of the proteases.
Why do smokers have a particularly high risk for emphysema?
They are bringing all sorts of garbage into the lungs that activate proteases. The proteases overrun the anti-proteases and destruction of alveoli occurs.
A patient comes to see you with difficulty breathing and jaundice. His liver biopsy is shown below and he is PAS positive. What is causing his condition?
Alpha-1 antitrypsin mutation (PiZ allele) that causes protein misfolding and accumulation in the ER of hepatocytes and causes liver cirrhosis. This also results in increased protease activity in the lungs due to decreased expression of the anti-protease, resulting in emphysema.
How do the two categories of emphysema differ? What do smokers most commonly get?
Centriacinar vs. Panacinar. The functional unit of the lung is the acinus (where the terminal bronchiole opens into the alveolar air sacs). The first place smoke hits is the central acinus and smoke rises…so smokers are at risk for centriacinar emphysema, more severe in the upper lobes. People with alpha-1 antitrypsin mutation (PiZZ) are more prone to panacinar emphysema in the lower lobes.
What people are at a genetically increased risk for developing emphysema if they smoke, but usually don't develop it if they don't smoke?
PiMZ allele heterozygotes. The PiM/PiM is the normal phenotype and the PiZ is the most common mutation causing alpha-1 anti-trypsin deficiency.
What is the physiological basis behind the pink puffers in emphysema? What other symptoms do patients with emphysema present with?
In order to prevent bronchiole collapse, they purse their lips, prolong expiration and increase the back pressure as they try to keep the airway open. They also present with dyspnea, nonproductive cough, exercise (from labored breathing) and increased AP diameter of the chest, or barrel chest.
A patient comes to see you with a nonproductive cough, weight loss and has labored breathing. His x-ray is shown below. What is causing the findings you see in his radiograph? How might his pulmonary function test be different from someone without this condition?
Note the barrel chest indicative of emphysema. Normally, the collapsing tendency of the lung is in equilibrium with the expanding tendency of the chest wall (marked by the functional residual capacity (FRC)). In emphysema, the lung loses its recoil and the chest wall has greater pull…causing barrel chest and an increased FRC.
What are late complications of emphysema?
Hypoxemia (paO2 < 60 due to loss of capillaries around destroyed alveoli). Cor pulmonale (right heart hypertrophy and failure due to pulmonary blood vessel constriction and pulmonary hypertension).
What type of hypersensitivity reactions usually cause asthma in what type of people?
Type I (allergen) hypersensitivity reaction in people who are genetically susceptible.
A 12 year old girl comes to the ED after having an asthma attack during gym class. This was her first ever attack. Histological analysis of her airways would show prominence of what type of inflammatory cells? How do these cells cause asthma?
CD4+ T cells that become TH2 helper cells. The TH2 helper cells secrete IL-4 (allow plasma cell release of IgE), IL-5 (eosinophil recruiter) and IL-10 (promotes further TH2 cell differentiation).
A 17 year old boy comes to the ED with his third asthma attack this year. How does exposure of the allergen cause immediate symptoms in this child?
PHASE I: Cross linking of IgE on mast cells causes degranulation and histamine release. Mass histamine release causes vasodilation (in arterioles) and vascular permeability (in post-capillary venules). PHASE II: mast cells produce leukotrienes C4, D4 and E4 (causing vasoconstriction, BRONCHOCONSTRICTION and increased vascular permeability). PHASE III: major basic protein released by eosinophils perpetuates bronchoconstriction.
A 13 year old female presents to the ED with dyspnea and wheezing after playing in her PE class this morning. She has a productive cough. What would you expect to find in the sputum produced by her cough?
Curschmann spirals and Charcot-Leyden crystals (crystaline aggregates of major basic protein).
What is it called when asthma get so bad that the bronchoconstriction does not relent and causes death?
What are some of the nonallergic causes of asthma?
Exercise, viral infection, aspirin (aspirin-induced bronchospasms and NASAL POLYPS) and occupational exposures.
What causes the condition seen the lung biopsy of the patient below?
Note dilates airways where they should not be dilated. Necrotizing inflammation with damage to the airway wall causes airway dilation in bronchiectasis. This happens in cystic fibrosis (mucus plug -> infection -> inflammation and damage to the airway), Kartagener syndrome (defective dynein arm of cilia), tumors/foreign bodies (obstruction -> infection), necrotizing infections and allergic bronchopulmonary aspergillosis (hypersensitivity reaction to entry of aspergillis).
A 22 year old male patient presents with sinusitis, infertility, sinus inversus, and recurrent pulmonary infection. What is your diagnosis?
Kartagener syndrome. The patient has a defective dynein arm of the cilia and you see defects where ever the body normally utilizes cilia.
A patient comes to see you complaining of cough, dyspnea and foul-smelling sputum. She has a history of recurrent pulmonary infections. Labs show a decreased paO2 and pulmonary hypertension. If you took a biopsy of the lung, deposition of what material would may be present?
In bronchiectasis, patients have long-standing inflammatory reactions that dilate the airways. Long-standing inflammation causes production of amyloid (SAA) which is converted to AA and deposited in the tissue.
A 17 year old male comes to see you with sneezing, congestion and runny nose. What is the most common cause of these symptoms?
Adenovirus is the most common pathogen that causes inflammation of the nasal mucosa and the common cold.
A 6 year old female comes to your clinic during the springtime complaining of seasonal allergies. She also has a previous history of asthma and eczema. If you looked at the tissue in her nose what type of cells would you see in the inflamed tissue?
She has allergic rhinitis, a type I hypersensitivity reaction likely to pollen. This is commonly associated with asthma and eczema, and you would see eosinophilic infiltrate.
You saw two patients today. One, a 7 year old boy with nasal polyps. Another, a 32 year old female with nasal polyps. If you rule out polyps due to allergic rhinitis, what would you suspect in each patient?
Child = cystic fibrosis. Adult = Aspirin intolerant asthma (aspirin-induced bronchospasms, nasal polyps and asthma).
A 14 year old male presents with profuse epistaxis (nose bleeds). What type of tumor may be causing this condition?
Angiofibroma. It is almost exclusively seen in adolescent boys and is a benign tumor of the nasal mucosa composed of blood vessels and fibrous tissue.
A 33 year old Chinese male presents with cervical lymphadenopathy. Biopsy of the lymph nodes reveals pleomorphic keratin-positive epithelial cells scattered in a background of lymphocytes. What is your diagnosis and what other disease is commonly associated with this? What other demographic commonly has this condition?
Nasopharyngeal carcinoma is a malignant tumor of the nasopharyngeal epithelium. The biopsy showed keratin positive cells, indicating that the tumor was epithelial in origin. This cancer is often associated with EBV and can also be found commonly in young African children.