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Flashcards in Quiz #2 Deck (27):
1

chronic bronchitis

hypertrophy of mucus secreting glands
Reid index- ratio of thickness of glands/total wall (>0.5)

mucus plugging - infections,
blocks ventilation
hypoxic vasoconstriction - low O2 and high CO2
can get pulmonary hypertension ad eventually right heart failure

shunting!

2

Symptoms of Chronic Bronchitis

Blue Bloater
clinical defnitiion
productive cough
3 months over 2 years
associated with smoking

3

Emphysema

Pink Puffer - hyperventilate - maintains their O2 level so not hypoxic (unlike blue bloaters) - barrel chest
imbalance of proteases and antiproteases - alpha 1 antitrypsin is key, downregualted by smoking
destrcution of - too many proteases -destruction of upper lobe - centriacinar

people with alha anti tryp deficiency get lower lobe damage - panacinar

alveoli get damaged from excess protease, lose eleastic recoil, collapse and obstruction

4

hypersensitivity pneumonitits

Type 3/4 hypersensitivity reactions - exposure to organic antigen

It is suggested that HP is an immunologically mediated disease:
Most patients have specific antibodies in their serum suggesting type III hypersensitivity
Complement and immunoglobulins have been demonstrated in vessel walls by immunofluorescence also suggesting type III HS 
Presence of noncaseating granulomas suggests T cell-mediated (type IV) delayed type hypersensitivity against the antigen.

5

obstructive lung disease

reduced FEV1, FVC, and FEV1/FVC ratio - air trapped inside, lung volumes increase

chronic bronchitits and emphysema - COPD
asthma

6

restrictive lung disease

lung volumes go down (cant get air in)

7

bronchiectasis

Bronchial obstruction: (tumors, foreign bodies, and mucus impaction).

Congenital or hereditary conditions: (cystic fibrosis, intralobar sequestration, immunodeficiency states, and primary ciliary dyskinesia and Kartagener syndromes)

Postinfectious conditions: (necrotizing pneumonia caused by bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas), viruses (adenovirus, influenza virus, HIV), and fungi (Aspergillus species)

8

histologic findings in asthma

Thickened basement membrane
Inflammatory infiltrate consisting predominantly of eosinophils.
Charcot-Leyden crystals (arrow): These needle-shaped crystals are formed from eosinophil proteins. Note the bilobed eosinophils nuclei in the background.

Curschmann spiral (arrow): dense mucus with entrapped epithelial cells take the form of a small airway
Creola body (arrow): Consists of an epithelial sheet which has formed into a three-dimensional figure.

9

sarcoidosis

THE MORPHOLOGIC DIAGNOSIS OF SARCOIDOSIS RELIES ON THREE FINDINGS:
1) Tight, well formed granulomas
2) Lymphangitic distribution of granulomas
3) and exclusion of an alternative cause by history, stains and cuture.

bilateral symmetric hilar lymphadenopathy and bilateral nodular infiltrates in her upper lobes.
-- on chest x ray

Sarcoidosis is an immune-mediated multisystem disease. The most widely accepted explanation is that it is a Type IV delayed-type hypersensitivity reaction to an unidentified antigen in a genetically susceptible host. Epithelioid cell granulomas are a result of stimulation of the cell-mediated immunity. The process may resolve spontaneously or it may progress to form extensive noncaseous granulomas and fibrosis.
Both genders and all races and age groups, but has a predilection for young adults < 40 years of age. In the US african americans are 10 times more commonly affected than whites. Higher prevalence in nonsmokers.

Sarcoidal granulomas can involve any organ, but in more than 90% of patients, there is intrathoracic lymph-node enlargement, pulmonary involvement, skin or ocular (anterior uveitis is the most common) signs and symptoms. Sarcoidosis also involves salivary glands, spleen, liver, bone marrow, brain and heart.

10

idiopathic usual interstitial pneumonia (UIP)

Hallmark is that it is patchy with temporal heterogeneity. Which means that there is early and late lesions present as evidence of ongoing injury.

Causative agent is unknown. Believed that IPF is caused by repeated cycles of epithelial injury by some unidentified agent. Abnormal repair at these sites gives rise to the fibroblastic foci. It is believed that TGF-b1 released from injured type 1 alveolar cells is the driver for the fibrogenic process.

Poor prognosis with a mean survival of 3 years. Lung transplantation is the only definitive therapy availalble.
 

11

asbestosis

The left side shows asbestos bodies (arrows). An asbestos body is a fusiform or beaded rod with knobbed ends and a translucent center coated with iron-containing proteinaceous material (right image is an iron stain; stains iron blue).

Asbestos bodies are formed when macrophages attempt to phagocytose asbestos fibers; the iron is deposited from the ferritin in the macrophage.

Asbestosis is a fibrosing process due to interaction of asbestos fibers with lung macrophages.

It also functions as a tumor initiator and a promoter.

There are two distinct geometric forms of asbestos: serpentine (curly and flexible fibers) and amphibole (straight, stiff, and brittle fibers). Both amphiboles and serpentine are fibrogenic, but only the amphibole is associated with mesothelioma.

Development of asbestosis, like the other pneumoconioses, depends on the interaction of inhaled fibers with lung macrophages and other parenchymal cells. Asbestos fibers penetrate small airways and ducts. Macrophages attempt to ingest and clear the fibers and are activated to release chemotactic factors and fibrogenic mediators. Chronic deposition of fibers and release of mediators leads to inflammation and interstitial fibrosis.

12

Pulmonary Edema

can result from:
hemodynamic disturbances (increased pulmonary venous pressure and decreased oncotic pressure) or
from direct increases in capillary permeability as a result of microvascular injury.

The most common cause of hemodynamic edema is left-sided failure as in this patient.
In pulmonary edema resulting from direct microvascular injury the pulmonary capillary hydrostatic pressure is usually not elevated.

13

Pulmonary Hypertension

classified into five groups.
PAH where only small pulmonary arteries are affected (Like in this case 4).
PH due to left heart failure (Case 1)
PH from lung parenchymal diseases or hypoxemia (such as in UIP)
Chronic thromboembolic pulmonary hypertension (recurrent thromboemboli)
PH of multifactorial basis.

Heritable PAH has autosomal dominant with incomplete penetrance (10-20% family members develop overt disease). Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) is the most common gene identified. BMPR2 is a cell surface protein belonging to the TGF-b receptor superfamily.
In normal vessels, BMPR2 signaling causes apoptosis and inhibition of proliferation of smooth muscle cells.
Mutation of BMPR2 promotes smooth muscle proliferation and survival.
Over 300 mutations have been identified in BMPR2 and it is found in >70% pts with heritable PAH.
The fact that only 10 to 20% individuals with BMPR2 have phenotypic disease points to the presence of modifier genes and/or environmental triggers

A two-hit model has been proposed in which a genetically susceptible individual with BMPR2 mutation requires additional genetic or environmental insults to develop the disease.

14

goodpasture syndrome

an autoimmune disease in which kidney and lung injury are caused by circulating autoantibodies against the α3 chain of collagen IV. When only RENAL DISEASE IS CAUSED BY THIS ANTIBODY IT IS CALLED ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE. The antibodies initiate inflammatory destruction of the basement membrane in renal glomeruli and pulmonary alveoli. Most patients are teenagers or in 20s and it is more common in males.

Pathogenesis: The trigger that initiates the anti-basement membrane antibodies is unknown. It is believed that some environmental insult such as viral infection or smoking is required to unmask the cryptic epitopes. As with other autoimmune disorders, a genetic predisposition is indicated by association with certain HLA subtypes.

Clinical Features Most cases begin clinically with respiratory symptoms, principally hemoptysis, and radiographic evidence of pulmonary infiltrates. Soon, manifestations of glomerulonephritis appear, leading to rapidly progressive renal failure. The most common cause of death is uremia.

15

most common cause of community-acquired acute bacterial pneumonia

Streptococcus pneumoniae.

16

community acquired pneunomia

Haemophilus influenzae  Life-threatening pneumonia and meningitis in children, acute exacerbation of COPD

Staphylococcus aureus  Secondary bacterial & nosocomial pneumonia, IV drug abusers

Klebsiella pneumoniae  Chronic alcoholics

Pseudomonas aeruginosa  Nosocomial & cystic fibrosis; neutropenia, BV invasion

Legionella pneumophila  Artificial aquatic environments; immuno-compromised

17

HIV/AIDS risk for infection

CD4+ T cell count Organisms

>200 cells/mm3 Bacterial and mycobacterial infections


<200 cells/mm3 Pneumocystis


<50 cells/mm3 Cytomegalovirus & Mycobacterium avium-intracellulare

18

clinical/pathologic progression of TB

Infection by M tuberculosis proceeds in steps from initial infection of macrophages to a subsequent T1 response that both contains the bacteria and causes tissue damage. Early in infection the mycobacteria replicate unchecked within macrophages, while later the T helper response stimulates macrophages to contain the proliferation of the bacteria which usually happens after 3 weeks.

The antigen presenting cells that have encountered bacteria secrete IL-12 that lead to differentiation of TH1 response. The TH1 cells produce IFN-gamma that enables macrophages to contain the M. tuberculosis infection. Activated macrophages also secrete TNF that promote recruitment of more macrophages.

19

small cell lung cancer

In small cell carcinoma, the cells are arranged in sheets (no features of squamous cell or adenocarcinoma that will be discussed in the later cases). There are numerous mitoses (arrows). The cell of origin of small cell carcinoma is believed to be the neuroendocrine progenitor cells that are present in the bronchial mucosa. These progenitor cells as well as carcinoma arising from these have dense core granules by electron microscopy and stain positive for neuroendocrine markers such as chromogranin and synaptophysin (shown in the right side panel) Positive staining is brown. Positive cytokeratin on the right top panel proves that this carcinoma is epithelial in origin.

Small cell carcinoma. This is a highly malignant tumor of the lung with neuroendocrine features ( dense-core secretory granules by electron microscopy and expression of neuroendocrine markers) . It accounts for 20% of all lung carcinomas. There is a strong association with cigarette smoking and the male-to-female ratio is 2:1. The carcinoma grows rapidly and 70% patients are first seen in an advanced stage.
 
Small cell carcinoma is particularly sensitive to radiation and chemotherapy. Most small cell carcinomas have metastasized prior to diagnosis making surgical resection ineffective. The survival time of untreated small cell carcinoma is about 6 to 17 weeks.

20

carcinoid tumor

Carcinoid is a low grade endocrine tumor. These also arise from the neuroendocrine progenitor cells like small cell carcinoma, however, they are low grade histologically and have a much better prognosis. Dense core granules by electron microscopy and positive neuroendocrine markers will be seen in these tumors.
Note the difference: These cells have more eosinophilic (pink) cytoplasm compared to small cell carcinoma.

Bronchial carcinoids are the most common tumor of childhood.
There is no association with cigarette smoking.
Histologically, these cells have a lot more cytoplasm, uniform nuclei.
Patients with typical carcinoids have excellent prognosis 90% 5-year survival after surgery.
Atypical features such as necrosis and mitoses lowers the 5-year survival

21

Zones of lungs and pressure

Zone 1:
PA> Pa > Pv

Zone 2:
Pa> PA > Pv

Zone 3:
Pa> Pv > PA

22

Stages of Pulmonary Edema

First institial edema - fluid leaks into intertitial space because of increased pressures, usually doesn't impair lung functioning

Next, alveolar edema, fluid moves from interstital space into alveolar space - this can cause dysnea and coughing up pink frothy sputum

23

Causes of pulmonary edema

increased capillary hydrostatic pressure --> due to MI or fluid overload

increased capillary permeability --> due to toxins or sepsis

reduced lymph drainage --> increased central venous pressure

decreased intersitital pressure --> due to rapid removal of pleural effusion or pntx

decreased osmotic - due to high altitude

24

pulmonary edema

Pulmonary  Edema  causes  stiffening  of  th  normally   easily distensible  lung,  thus impairing
 ventilation,  in   addition  to  hypoxemia

Tachypnea caused bu J receptor activation and hypoexia oversomes the ventialteoy impairment

shunt is mechanism of hypoxemia ***
 

25

pulmonary embolism

Triad:
1) hypercoabulatible state: oral contraceptives, underlying issue
2) statis - hspital bed, long travel
3) trauama to lower extremities

V/Q  mismatching and shunt -- mechamism of hypoxemia (perfusion w/o vetialtion)

diagnosis: wells score
d-dimer is senstive not specific - only used with low ot intermediate score and clinical suspicion
 

26

Pulomonary Hypertension

1. pulmonary arterial hypertension: genetic or assocaited with another comobid like HIV or drugs
(increased TPG and high PVR)
2. left heart disease (low TPG)
3. lung disease or hypoxemia: COPD, sleep ap, high alt
4. chronic PEs
5. misc: sarcoid, etc.

Transpulmonary Pressure Gradient (TPG)= mPAP-­‐mPCWP

All types can cause right heart failure

27

drugs to treat obstructive lung disease

Anti-­‐Inflammatory Agents:
Mast  Cell  Stabilizers (cromolyn) - usually inhaled (topical) Inhibit pulmonary mast cell  degranulationin  response  to a  variety  of stimuli (e.g., antigens, exercise, occupational  etc.) - preventative
inhibits histamine and PGD2 release from mast cells by releasing annexin A1

Corticosteroids: act on inflammatory cells (macrphages and mast cells --> decrease cytokine release) and structural cells (smooth muscle) - mostly inhalation, but some systemic use if severe
Leukotriene  Modifiers - blocks converdation of AA
PDE4 Inhibitors: increases  cAMP  in  inflammatory cells: 1. Decreases  the  release  of  inflamm.  mediators  in  neutrophils 2.  Decreases  the  release  of  cytokines 3.  Decreases  apoptosis

Immunomodulators  (A-­IgE  &  A-­IL5  Absor)

Bronchodilators
Methylxanthines: thophylline -- histoen deacetylase, small therapeutic window - tox = nausea, vomit, seizure
β2-­Agonists - sympathetic activator but without cardiac toxicity --> albuterol, also upregualte cAMP
problem is tolerance
Anti-­muscarinic  drugs - act on acetylcholine (block) - bonrchodilation