Pathology-Respiratory System Flashcards
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?
Status asthmaticus
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.
A 9 year old male presents with high fever, drooling, dysphagia, a muffled voice and inspiratory stridor. Physical examination of his mouth is shown below. What is the most likely pathogen causing this patient’s condition? Is this a medical emergency?
H. influenza type b is the most common cause of acute epiglottitis in non-immunized AND immunized children. This is a medical emergency because the patient is at risk of airway obstruction of inflammation of the epiglottis continues.
A 38 year old female presents to your clinic with a hoarse “barking” cough and inspiratory stridor. What pathogen often causes the patient to present with these symptoms?
Laryngotracheobronchitis (croup) causes inflammation of the upper airway and is most often a result of parainfluenza virus infection.
A 58 year old female comes to see you complaining of hoarseness. She works as a waitress and says that it kind of goes away on the weekends but comes back when she goes to work. Tissue biopsy is shown below. What is your diagnosis of this patient?
Vocal cord nodules are overuse injuries that usually occur bilaterally (as seen below). Note that the biopsy is composed of myxoid connective tissue, characteristic of vocal cord nodules.
Two patient came to see you today. One was 6 years old and the other 36. Both patients had elevated WBC counts and were complaining of hoarseness in their voice. How might the same disease present differently in these two patients?
This sounds like laryngeal papilloma caused by HPV 6 and HPV 11 infection (hence the elevated WBC). Although both patients present with hoarseness, you usually have multiple lesions in children and a single lesion in adults.
A 57 year old male presents with chronic cough and stridor. He has a long history of tobacco and alcohol use. He has been previously diagnosed with HPV 6 and 11. What is your diagnosis in this patient?
Laryngeal carcinoma. This is a squamous cell carcinoma arising from the epithelial lining of the vocal cord. Alcohol, tobacco and laryngeal papillomas (from HPV 6 & 11 infection) all increase your risk for this cancer.
What factors put someone at risk for pneumonia?
Loss of cough reflex, loss of the muco-ciliary escalator or blockade of an airway (by mucous or diseased tissue).
What are the typical presentations of pneumonia?
Fever/chills (from organisms leaking into blood), cough, yellow-green (pus) or rusty (blood) sputum, tachypnea, pleuritic chest pain (bradykinin & PGE2 presence from infection), decreased breath sounds (exudate), dullness to percussion (exudate) and an elevated WBC count.
What diagnostic tools do we use with pneumonia?
CXR, Sputum gram-stain & culture, blood cultures.
A 21 year old male comes to your clinic complaining of chills, rusty sputum, pleuritic chest pain and malaise. Physical exam reveals tachypnea, a fever, decreased breath sounds over the right lung and dullness to percussion in the middle left lung. The patient’s chest radiograph is seen below. What pathogen is the most common cause of pneumonia seen in this radiograph? What would you expect tissue biopsy of the lung to look like?
The most common causes of lobar pneumonia (note consolidation of an entire lobe) is bacterial infection. The most common types are S. pneumoniae (95%) and Klebsiella pneumoniae. Note neutrophils and exudate filling up the entirety of the alveolar air sacs.
What pathogen is responsible for most community-acquired pneumonia cases? What demographic is most commonly affected?
S. pneumoniae. Middle-aged adults and elderly.
What pathogen is responsible for most pneumonia cases in alcoholics, diabetics and malnourished patient? What is this type of pneumonia often complicated by?
Kelbsiella pneumoniae. This bacteria is a part of our normal flora and patients who get it are those at increased risk for aspiration (alcoholics and elderly in nursing homes). The thick mucoid capsule of this bacteria results in thick jelly sputum that has a tendency to form abscesses.
What are the four classic phases of lobar pneumonia?
1) Congestion: inflammation induced by the immune response. 2) Red hepatization: neutrophils and RBCs fill the alveolar air sacs. 3) Grey hepatization: RBCs are broken down 4) Resolution: exudate is removed and alveolar air sac lining is regenerated
A 21 year old male comes to your clinic complaining of chills, rusty sputum, pleuritic chest pain and malaise. Physical exam reveals tachypnea and a fever. The patient’s chest radiograph is seen below. What pathogens are the most common causes of pneumonia seen in this radiograph? What would you expect the gross tissue of the lung to look like?
This patient has bronchopneumonia. Note the patchy consolidation centered around the bronchioles multi focally and bilaterally. There are many bacteria that cause this to include: staph a., H. influenzae, Pseudomonas a., Moraxella catarrhalis and Legionella p.
What cell in the lung is responsible for making this tissue normal again?
This lung exhibits red hepatization after a lobar pneumonia. Type II pneumocytes are the stem cells of the lung and are responsible for making this normal again.
A 28 year old female presents with a non-productive cough, low-grade fever and generalize malaise. Her chest x-ray is shown below. What type of pneumonia does this patient have? What would you expect to see on tissue biopsy of this patient’s alveoli?
Note the diffuse interstitial infiltrates made evident by prominent lung markings in the chest x-ray. This is interstitial (atypical) pneumonia. This type of pneumonia leaves the alveoli wide open and clear, but causes inflammation in the alveolar walls as seen below.
A 25 year old male is thinking about joining the military. When doing all of his paperwork, he decides to get his immunizations done. He cannot join because he had a positive PPD. He has a history of travel to Africa for a humanitarian project. The next day he dies in a car accident and his lung biopsy is shown below. What is your diagnosis of this patient?
Note formation of a subpleural Ghon complex. This is indicative of primary Tb infection. With primary, Tb patients often go asymptomatic as focal caseating necrosis takes place in the lower lobe of the lung and in the hilar lymph nodes. Calcification and fibrosis of the foci forms the Ghon complex seen in this patient.
A 47 year old male comes to see you with complaints of fever, night sweats, hemoptysis and weight loss. He has a past medical history of HIV. Tissue biopsy is shown below. What is in your differential with this patient? How do you narrow that down?
Note the central caseating necrosis surrounded by histiocytes. A patient presenting with these symptoms either has secondary Tb or a fungal infection. You can do an AFB stain and look for red acid-fast bacilli, that would indicate Tb (seen below).
What is the main problem in restrictive lung diseases? What pulmonary function test values are common in patients with this type of lung disease?
Filling the lung. In obstructive disease, the problem is emptying the lung.
You had a patient with restrictive lung disease characterized by progressive shortness of breath and cough. You ruled out drugs and radiation therapy as a cause, what would your diagnosis of this patient be? How do you treat this patient?
Idiopathic pulmonary fibrosis. Note the extremely thickened alveolar walls. This results from cyclical lung injury, cyclical lung healing, TGF-beta released by injured pneumocytes and continued fibrosis. This patient will ultimately need a lung transplant.
A 63 year old construction worker comes to see you complaining of increased dyspnea and chronic cough. You determine that the patient needs a lung biopsy and it is shown below. What is your diagnosis and what is the most common serious complication associated with this condition?
Note the long rod-shaped particle with little brown beads from iron deposition. This confirms asbestos exposure. Patients with asbestos exposure are prone to fibrosis of the lung, fibrosis of the pleura, cancer of the lung and cancer of the pleura. Specifically, patients are more likely to get lung cancer than mesothelioma (pleural cancer).
A 32 year old African American female presents with dyspnea and cough. On physical examination you note uveitis, cutaneous nodules, decreased salivation and dry eyes. What is your diagnosis and where is this condition most commonly found in the body.
Note noncaseating granuloma in the lung with giant cells internally and epitheliod histiocytes surrounding it. Note the image below forming the typical asteroid body of giant cells, typical of sarcoidosis. Though granulomas are found systemically, the lung and hilar lymph nodes are most commonly affected.
A patient is having trouble breathing when working out and he comes to see you. On auscultation of his lungs you hear bilateral rales. Tissue biopsy of his lung is shown below. What is your diagnosis and what other histological findings would you expect to see in this patient?
The image indicates plexiform lesions (tuft of capillaries), which are seen in long-standing pulmonary hypertension. With pulmonary hypertension you would also expect to see smooth muscle hypertrophy of the pulmonary arteries and intimal fibrosis.
A 46 year old male comes to see you complaining of dyspnea. Physical exam reveals cyanosis in the extremities. Tissue biopsy of his lung is shown below. What is causing this patient’s condition?
Note the formation of hyaline membranes throughout the alveoli. This is typical of ARDS because damage to the alveolar-capillary interface allows leakage of plasma proteins into the air space. These proteins are then reorganized into hyaline as they are seen on this biopsy. This ultimately results in a thicker wall for air to pass through and hypoxia. Additionally, the thicker wall has increased surface tension, causing it to close more readily and cause cyanosis.
A 31 year old female comes to your clinic complaining of dyspnea. Physical exam reveals cyanosis in the extremities. Her chest x-ray is seen below. What cells are being damaged in this patient’s condition and how do you treat her?
Note the diffuse white out of the lung. This is a classic finding of ARDS. Any disease that activates neutrophils and induces protease-mediated and/or free radical damage to type I and type II pneumocytes can cause ARDS. Treatment involves treating the underlying cause of pneumocyte damage and PEEP (positive end-expiratory pressure to prevent alveolar collapse).
A mother gives birth to a 27 week old baby. After a few hours the baby becomes tachypnic and is using accessory muscles for respiration. Shortly thereafter the baby becomes hypoxemic and cyanotic. Chest x-ray is shown below. What is causing this baby’s condition and how would you treat it?
Note the diffuse granularity of the lung on the x-ray. This combined with the history is classic acute neonatal respiratory distress due to decreases lung surfactant and thus increased surface tension in the lung, making it harder for the baby to breath. In most neonates, lung surfactant production is not sufficient until 34 weeks.
A 55 year old male smoker presents to your clinic with suspected lung cancer. You analyze the biopsy of his tumor seen below. What is your diagnosis and what associated symptoms may present in this patient?
Small cell carcinoma. Note the poorly differentiated small cells that look like lymphocytes and that they are mitotically active. The tumor will be located centrally in the lung. This is common in male smokers and is associated with paraneoplastic syndromes (Eaton-Lambert muscle weakness, ADH, ACTH).
A 55 year old male smoker presents to your clinic with suspected lung cancer. You analyze the biopsy of his tumor seen below. What is your diagnosis and what associated symptoms may present in this patient?
Squamous cell carcinoma is the most common tumor in male smokers. It will be located centrally in the lung. Note the keratin pearls and intercellular bridges (desomosomes). It is associated with production of PTHrP production, which causes hypercalcemia.
A 55 year old female smoker presents to your clinic with suspected lung cancer. You analyze the biopsy of her tumor seen below. What is your diagnosis and what associated symptoms may present in this patient?
Adenocarcinoma. This is the most common lung tumor in female smokers and in non-smokers. Note the gland-forming, mucin producing cells in the biopsy. These tumors usually manifest in the periphery of the lung.
A 49 year old female comes to see you in clinic due to suspected lung cancer. She has no history of smoking and it appears that the lesion is on the periphery of her lungs. CXR reveals pneumonia-like consolidation. Her biopsy is shown below. What is your diagnosis?
Bronchioloalveolar carcinoma. This is when columnar cells from Clara cells grow along the bronchioles and alveoli. This condition has a very good prognosis.
How does carcinoid tumor (seen below) differ from small cell carcinoma of the lung?
Carcinoid tumors are well-differentiated neuroendocrine tumors where small cell is poorly differentiated. They would both stain positive for chromogranin (shown below) because they are both neuroendocrine cells. Carcinoid is not related to smoking where small cell is. Small cell is located centrally where carcinoid tumors form a poly-like mass in the bronchus (seen below). Carcinoid tumors are also a low-grade malignancy.
Which way does the trachea shift in a patient who had a spontaneous pneumothorax from a congenital bleb?
Toward the side of the pneumothorax.
How would a mesothelioma look on a gross section?
It encases the entire lung.
