Term
| 5 impaired host defense Mechanisms that may cause pneomonia? |
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Definition
1) Aspiration of gastric contents (inadequatecough reflex).
2) Injury to the respiratory mucosalcilia (smoking).
3)Injury to the alveolar macrophages’
phagocytic/bacteriocidal activity (smoking, anoxia).
4) Pulmonary Edema.
5) Thick mucus secretions (cystic fibrosis or bronchial obstruction). |
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Term
| 4 Classical Stages of Lobar Pneumonia |
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Definition
1. Congestion-vascular engorgement, leaky capillaries with intra-alveolar fluid and bacteria.
2. Red Hepatization -massive exudate of red cells, neutrophils, and fibrin in the alveolar spaces (grossly like liver).
3. Grey Hepatization -red cells in the alveolar space lyse, but neutrophils and fibrin persist.
4. Resolution or Fibrosis-->alveolar macrophages ingest the fibrinpurulent material in the alveoli. In fibrosis, the alveolar spaces may become obliterated, or the alveolar walls may become excessively thickened w/ fibrous tissue |
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Term
| Histology of Bacterial Pneumonia and how it differs from Viral Pneumonia |
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Definition
Bacterial Pneumonia
-can be either lobar or lobular (lower lobe)
-bacterial pneumonia has fibrinous pleuritis
-bacterial pneuomnia is mostly composed of neutrophils
Viral Pneumonia
-patchy involvement
-little sputum
-inflammation is interstitial, mostly composed of lymphocytes, histiocytes, plasma cells
-there is always resolution to normal architecture |
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Term
| What is the difference between Antigenic Shift & Drift? |
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Definition
Antigenic drift :Mutations of the m aglutinin and neuramidase allow the virus to escape host antibodies.
• Antigenic shift: When RNA recombination of animal influenza virus segments occurs, making all humans susceptible. |
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Term
| Current situation on HINI |
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Definition
Swine Flue H1N1
- high risk groups for complications: pregnant, children < 5yrs, > 65 yrs, asthamatics, diabetics, immunocompromised, sickle cell pts., etc.
-significant pediatric & pregnant women morbidity and mortality
-Vaccine--brought the disease under control, By Aug. 2010, WHO declared the post pandemic period, will circulate seasonally for years. |
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Term
| Current Situation on H5N1? |
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Definition
Avian Influenza A (H5N1)
- most have occurred in ppl who have had direct contact w/ infected poultury, or ingestion, or contact w/ contaminated surfaces or water (direct intranalsa or conjunctival contact).
-most cases-->previously healthy children and young adults
3-5 days after exposure=fever, respiratory symptoms, lymphopenia, diarrhea, then severe respiratory disease (ARDS)
-Diarrhea, acute encephalitis, but no respiratory symptoms in some childre
-time course about two weeks,
-severity of disease though to be due to its tissue tropism-ubiquitous protease throughout the body to enter cell |
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Term
| What is aspiration pneumonia, and what is its most common complication? |
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Definition
Aspiration Pneumonia
- abnormal gag or swallowing reflexes- alcoholics or debilitated patients
-usually right sided, frequent cause of death
-common complication is lung abcesses |
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Term
| Which Organisms commonly cause nosocomial acquired pneumonia? |
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Definition
Nosocomial Pneumonia
• Severely ill:due to immunosuppression, prolonged antibiotic therapy, intravenous catheters, or mechanical ventilation.
• Serious due to multiple antibiotic resistances.
• Most common gram negative :Pseudomonas sp. and Enterobacteriaceae sp.,
• Most common gram positive: Staph aureus and Staph epidermidis |
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Term
| Difference btwn infection of Mycobacterium tuberculosis & having the disease? |
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Definition
-Infection means that a susceptible person acquires Mycobacterium Tuberculosis from someone w/ active disease and develops primary TB, recover and viable organism remains DORMANT
-Having the disease means the virus is active, and it is tested w/ PPD test
-False-neg PPD in HIV pos, sarcoidosis, malnutrition, fulminant TB
-False pos PPD when person is infected by atypical mycobacterial |
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Term
| What is the difference btwn Primary TB, Progressive TB, & Secondary TB? |
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Definition
1) Primary TB--> usually develoops in a previously unexposed person
2) Progressive Primary TB--> primary infection doesn't become latent; acute bacterial pneumonia w/ lower and middle lobe involvement; NO cavitation; hilar adenopathy, pleural effusion
3)Secondary TB--> in a previously sensitized host; occur shortly after a primary infec. or arise from reactivation of a dormant lesion; localized to the apex of the UPPER LOBES due to the high oxygen tension there; CAVITATION is bad; develop purlent sputum w/ life-threaning hemoptysis |
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Term
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Definition
| Ghon Focus--> area of caseous necrosis where the TB organism first implants in the lung, usually mid chest |
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Term
| What galloping consumption means? |
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Definition
| Galloping Consumption-->when there is dissemination of TB through the airways as apposed through lymphohematogenous (miliary) |
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Term
| Ways the Miliary Disease occur? |
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Definition
1) Miliary Pulmonary Dz--> organisms drain through lymphatics into lymphatic ducts which empty into the vena cava and into the pulmonary arterires which seed the lung
2)TB Empyema--> caseous cavity opens into a pleural space
3) Endotracheal/Endobrocnhial/ Endolaryngeal Lesions--> secondary to lymphatics or infective sputum
4) Systemic Milary TB--> infection seize the pulmonary venous return of the heart, disseminate through the arterial system all over body
5) Isolated organ TB--> when a disseminated seed only affects one organ
6) TB Lymphadenitis-->"scrofula"; cervial lymph nodes
7) Intestinal TB--> ilieum; granulomas ulcerate |
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Term
| What Mycobacteriaum avium-intraceullular is , and which pts become infected w/ these organisms? |
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Definition
MAC
--> found in soil, dust, water & domestic animals
-->in AIDS pts w/ CD4 < 50
--> In AIDS, widespread infectionin the mononuclear system: lymph nodes, liver, spleen, and also lungs and GI tracts
-->see numerous bacilli & macrophages w/ poorly formed or no granulomas |
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Term
| Types of tissue reactions that occur w/ histoplasmosis, Blastomycosis , & coccidiodomycosis |
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Definition
Histoplamosis
-->mimicker of TB; coin lesion on CXR; localized in lung apices w/ cough, fever & night sweats; NO CAVITY FORMATION; localized in extra pulmonary sites, or widely disseminated
-epitheloid cell granulomas w/ caseous necrosis
-3-5 mu, yeast which may be present intracelluarly or extracellulary
Blastomycosis
-dimorphic fungus
- suppurative granulomas
-forms round 5 to 15 mu (bigger than histo) w/ broad-based buds and double contoured wall
Coccidiodomycosis
-dimorphic fungus
- granulomatous, pyogenic
-20-60 mu, spherules filled w/ endo spores |
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Term
| Common causes of pneumonia in the immunocompromised host |
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Definition
1) Bacteria
1)Pseudomas aeruginosa, 2)mycobacteria, 3)legionella pneumophilia, & 4) Listeria monocytogenes
Viruses
-CMV
-Herpes
Fungi
1) Pneumocytis jiroveci, 2) Candida Species; 3) Aspegillus Species; 4) Mucor; 5) Cryptococcus Neoformans |
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Term
| 4 Major Molecular Genetic Changes for all histologic types of lung Carcinomas |
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Definition
1) p 53 Mutation
-most frequent mutation; secondary to direct DNA damage from smoking
2) Inactivation of the pathway controlling RB1 (retinoblastoma gene on 13q11)
--> common mechanism for inactivation is silencing of the CDKN2a (INK4) gene encoding p16 & overexpression of CCND1 encoding cycling D1
3) Loss of Heterozygoisty on 3p
-several tumor suppressor genes are active: FHIT, RASSF1A; Beta Catenin; SEMA3B
4) Loss of Heterozygosityon other chromosomes-8p, 5q, 13q, 17q, 18q, 22q & increased telomerase activity |
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Term
| Common Clinical Finding in lung carcinomas, including local manifestations of lung carcinomas |
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Definition
Common Clinical Findings in Lung Cancer
1) Persistent Cough 75%
2) Weight loss 40%
3) Chest pain 40%
4) Dyspnea 20%
Local Manifestations of Lung Cancer
-bacterial or lipid pneumonia, abscess, lobar collaspse
-pleural effusion
-Hoarseness-recurrent laryngeal nerve invaions
-Dysphasia-esophageal invaion
-Diaphragm paralysis-phrenic never invaion
-Rib destruction
-Superior Vena Cava Syndrome(due to compression by tumor)
-Horner's syndrome and Pancoast's Syndeome
-Pericarditis, pericardial tamponade |
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Term
| Which paraneoplastic syndromes occur in lung carcinioma |
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Definition
Paraneoplastic Syndromes
-Small Cell carincoma is associated w/ ADH and ACTH production
-Squamous Cell Carinoma-PTH related peptide, prostaglandins
-Carcinoid tumors are associated w/ serotonin and bradykinn causing the "carcinoid syndrome" |
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Term
| Epidemiology, location, gross and microscopic anatomy of squamous cell carcinoma |
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Definition
Squamous Cell Carcinoma
• Has the strongest relationship to smoking.
• Usually arises around the hilus of the lung (segmental or subsegmental bronchus).
•But peripheral tumors may be seen.
•Begins as an area of in situ carcinoma.
Gross Morphology
-gray, white, firm w/ necrosis often in the center, star like at the edge; penetrating type (occlude the lumen); Creeping type (grow laterally along the bronchi)
Histology:
-keratinized cells w/ intercellular bridges and keratin pearls |
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Term
| Morphologic Sequence in the Development of SCC? |
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Definition
Early
1) Hyperplasia
2) Squamous Metaplasia
Intermediate
1)Dysplasia
Late
1) Carinoma in Situ
2) Invasive Carcinoma |
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Term
|
Definition
EGFR
-frequently mutated in nonsmall cell lung carcinomas
-determination of muation status determines significant response to tyrosine kinase inhibitors (females do better b/c they typically get nonsmall cell carcinomas)
-Tyrosine kinase inhibitors-gefitnib (Iressa) and erlotinib-useful in tx, especially adenocarcinomas |
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Term
| Epidemiology, location, gross & microscopic anatomy of adenocarcinoma |
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Definition
Adenocarcinioma Epidemiology
-most common worldwide, 75% linked to smokers
- most comon in females who have never smoked
Gross Morphology
-Peripheral Tumor-->gray, white, w/ central fibrosis and pleural puckering, most common
-Diffuse pneumonia-like lobar consolidation (mucinous brochoalveolar carcinoma)
Histology
-malignant epithelial tumor showing glandular differentiation or mucin production
-Branchiolaveloar Carcinomas (BAC):-grow along pre-existing alveoli (lepedic or butterfly growth)
-->a) Non-mucinous-clara cell and/or Type II pneumocyte differentiation; easier to resect
-->B) Mucinous-differentiation of mucous cells, low-grade; difficult to resect
mucinous; low-grade; difficult to resetc |
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Term
| Molecular Changes in Adenocarcinomas |
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Definition
1)K-ras point mutations in 30%
2) Overexpression of Her2 Neu & Cox-2 genes
3)Overexpression of EGFR,
-->Iressa, anti-EGFR drug works well in small % of BAC in mostly Japanese females |
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Term
| Definition of Large Cell Carcinoma |
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Definition
Large Cell Carcinoma
-defined as a tumor that lacks squamous, adeno, or small cell differentiation
-usually peripherally located
-Type II pneumocyte or Clara cell differentiation
-Acts like an adenocarcinoma
-an undifferentiated epithelial tumor which clacks the cytologic & architectural features of SCC, Adenoca. or SCC |
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Term
| Epidemiology & Location of SCC? |
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Definition
Small Cell Carcinoma
␣ Highly associated with smoking
␣ Most aggressive of all lung carcinomas
␣ Usually occur in the major bronchi (95%) or in the lung periphery as a coin lesion (5%).
␣ Thought to arise from a pleuripotent bronchial precursor cell.
Tends to be widespread at presentation -“limited”
versus “extensive” disease is used.
␣ Usually not resected, but treated with chemotherapy and radiation. |
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Term
| Gross Morphology & Histology of SCC? |
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Definition
SCC Gross Morphology:
␣ White, tan, soft, friable with necrosis
␣ Spreads along bronchi submucosally, circumferentially, and often invades lymphatics.
␣ Frequent hilar and mediastinal lymph node involvement.
Histology:
␣ Small cells (< 30 mu.) with scant cytoplasm and ill-defined cell borders.
␣ Finely granular nuclear (salt and pepper) chromatin
␣ Nuclear molding and necrosis, high mitotic rate, spindling.
␣ Crush artifact. |
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Term
| Molecular Changes in SCC? |
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Definition
SS Molecular Genetics
␣The 4 common changes plus:
␣Up regulation of pro-apoptotic
molecule BCL 2.
␣c-kit mutations 40-70%
␣Myc 20-30% |
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Term
| Morphologic Definition of Carcinoid Tumor, Typical vs. Atypical? |
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Definition
Carcinoid Tumor
␣ A neuroendocrine tumor composed of small to intermediate sized cells.
␣ The most common symptoms are cough and hemoptysis due to bronchial obstruction.
Two Types:
Typical carcinoid: < 2 mitotic figures per 10 high power fields and no necrosis.
␣ a low-grade tumor. ␣ 10 to 15% metastasizing to regional lymph nodes, and
five to 10% with widespread metastases.
Atypical carcinoid: 2 to 10 mitotic figures per 10 high power fields, and/or small areas of necrosis.
␣ a more aggressive tumor
␣ 40 to 50% metastasizing to regional lymph nodes and beyond. |
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Term
| Cell of derivation, most common molecular genetic changes, & prognostic factors of Carcinoid Tumor? |
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Definition
Carcinoid Tumors
Molecular Genetics:
␣ Distinctive: Mutations of the MEN1 gene and absence of its protein product menin.
␣ In atypical carcinoids: the 4 common changes and P14 ARF protein loss(43%).
Prognostic Factors:
␣ Stage is the most important prognostic factor. ␣ However, typical carcinoids with lymph node
metastases still have an excellent prognosis.
␣ Aerogenous spread in atypical carcinoids is a poor prognostic factor.
␣ Five-year survival of typical carcinoids is 90 to 98%.
␣ Five-year survival of atypical carcinoids is 61 to 73%.
Cell of Derivation:
-derived from Kulchitsky cell-a neuroendocrine cell present in the airways |
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Term
| Epidemiology & Prognostic Factors in Mesothelioma |
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Definition
Mesothelioma
␣ > 90% of malignant mesotheliomas occur in men and are related to asbestos.
␣ >60 years age, M:F=9:1
␣ The latency period - 30 to 40 years.
␣ Relative Risk: crocodolite>amosite>chrysolite
␣ Other causes: therapeutic radiation, pleural scarring, and exposure to the nonasbestos fiber, erionite, found only in Cappadocia, Turkey.
␣ Mortality almost 100%. |
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Term
| Histological Types of Mesothelioma |
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Definition
Histological Types
␣ Epithelioid mesothelioma -composed of large cells which may mimic other tumors such as large cell carcinoma or large cell lymphoma.
␣ Sarcomatoid mesothelioma -spindled cells which may be mistaken for a sarcoma, or sarcomatoid carcinoma
␣ Desmoplastic mesothelioma -very dense collagen with atypical tumor cells in at least 50% of the tumor.
␣ Biphasic mesothelioma -a combination of epithelioid and sarcomatoid patterns. |
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Term
| Molecular Changes in Mesothelioma? |
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Definition
Molecular Changes
Disruption of the RB gene pathway: tumor suppressors P16 INK4 and p14 ARF are inactivated.
␣ Mutations of the tumor suppressor NF2 gene is common.
␣ GPC3, another tumor suppressor, is downregulated. |
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Term
| Diagnostic Immunohistochemical profile of Small Cell Carcnioma, Squamous Cell Carcinoma, & Adenocarcinoma |
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Definition
Small Cell Carcinioma:
--up regulation of pro apoptotic molecule BCL-2
Squamous Cell Carcinoma
overexpression of EGFR
Adenocarcinoma
-K-ras point mutations
-Overexpression of Her 2 Neu and Cox-2 genes
-Oveerexpression of EGFR & Met |
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Term
| Definition of Chronic Obstructive Pulmonary Diseases & its relationship to cigarette smoking. |
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Definition
COPD
␣ COPD (defined by the American Thoracic Society and the European Respiratory Society) : “A preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking.”
␣ 90% are heavy smokers.
␣ Related to injury by smoke irritants.
␣ Males : Females = 1.8:1, W:AA = 2.8:1 |
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Term
|
Definition
4 Major Obstructive Diseases
1) Emphysema
2) Obstructive Chronic Bronchitis & Bronchiolitis
3)Asthma
4)Bronchiectasis |
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Term
| 4 Anatomic Types of Emphysema in relation to the area of Acinar Damage & their location in the lung |
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Definition
Emphysema
1)Centriacinar or centrolobular (94% of cases)
-->affects the central acinus
-->more severe in upper lobes
-->seen w/ chornic bronchitis/ bronchiolitis
2) Panacinar or panlobular (second most common)
-->associated w/ alpha-1 antitrypsin deficiency
-->most severe at the bases, and anterior margins of the lung
3) Paraseptal (distal acinar)
-->next the the pleura
-->occurs next to areas os scarring
-->more severe in the upper lobes; BULLAE
4) Irregular |
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Term
| Antitprotease Theory in relationship to emphysema, alpha-1 antitrypsin deficiency, and cigarette smoking |
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Definition
Emphysema & Alpha-1 AT Deficiency
--> neurtophils make protease in lower lobes, no alpha-1 AT to get rid of protease
-->damage occurs mostly in the lower lobes
Emphysema & Smoking
-->Functional alpha-1 anti-trypsin deficiency
-->around respiratory bronchioles, neturohils and macrophages gather to release proteases
-->free oxygen radicals from the cigarette smoke inactive antiproteases, and cause direct tissue destruc.
-->upper lobe distribution |
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Term
| What is Chronic Bronchitis, and Morphologic Changes? |
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Definition
Chronic Bronchitis
-persisten cough w/ sputum production for at least 3 MONTHS in 2 CONSECUTIVE years, which is not caused by a specific underlying disease (TB or Ca)
-->chronic irritation of the bonchi by inhaled tobacco smoke, dust
-->neutrophils & macrophages stimulate mucous secretion
Morphology
-->hypertrophy of submucosal glands
-->inc. numbers of goblet cells
-->squamous metaplasia
-->mucous plugs |
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Term
| What is Chronic Bronchiolitis and Morphologic Changes? |
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Definition
Chronic Bronchiolitis
--->small airways
-->ventilation/perfusion mismatch w/ arterial oxygen desaturation
-->results in pulmonary arterial vasospasm, pulmonary hypertensin, cor pulmonale
Morphology:
-->globlet cell metaplasia w/ inc. amounts of mucous and mucous plugs
-->there is fibrosis of the bronchiolar wall
-->Chronic bronchiolitis is usually found associated w/ chronic bronchitis and/or centrilobular emphysema |
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Term
| What is the definition of Asthma> |
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Definition
Asthma
␣ Episodic wheezing, shortness of breath, and cough especially at night or early morning.
␣ Due to reversible bronchoconstriction.
␣ Increased in incidence in the past 30 years.
␣ Two major types: extrinsic (atopic) and intrinsic (non atopic), but overlaps are quite common. |
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Term
| What is Extrinsic (Atopic) Asthma? |
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Definition
Extrinsic (Atopic) Asthma
␣ Most common type of asthma.
␣ Most common type in children.
␣ Initiated by a Type I hypersensitivity reaction, inhaled antigens (for example, dust mites, mold spores, animal dander). |
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Term
|
Definition
Intrinsic Asthma
␣ Viral respiratory infections, most common trigger.
␣ Exercise, cold air, drugs (aspirin, tartrazine dye, bronchodilators), inhaled irritants or air pollution.
␣ Usually no allergic or asthma family history.
␣ Initiated by non-immune mechanisms. |
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Term
| Morphologic Changes in Asthma? |
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Definition
Bronchial Morphologic Changes in Asthma
␣ Mucous plugs.
␣ Bronchial epithelium- increased goblet cells,
thickened basement membrane.
␣ Bronchial smooth muscle- hypertrophy.
␣ Bronchial submucosal glands- hypertrophy.
␣ Edema with accompanying inflammatory cells (eosinophils, mast cells, lymphocytes, macrophages, and neutrophils). |
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Term
| Definition of Status Asthmaticus? |
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Definition
Status Asthmaticus
--> an attack that last for days or weeks, if not ended, may result in death
-->give adrenegic agnoists (epinephrine & albuterol) & methylxanthines (Theophylline) |
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Term
|
Definition
Bronchiectasis
␣ Permanent dilation (fusiform/saccular) of bronchi due to destruction of muscle and elastic tissue.
␣ Infection alone.
␣ Obstruction then infection.
␣ Prefers lower lobes, especially vertical airways.
␣ Also seen with congenital disorders: cystic fibrosis, primary ciliary dyskinesia. |
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Term
| Morphologic Changes in Bronchiectasis |
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Definition
Morphology of Bronchiectasis
--> lower lobes bilaterally are affected, especially the distal vertical airway passages
-->dilated airways w/ mucopurulent material
--> microscopic examination, there is necrotizing ulceration, squamous metaplasia of the respiratory epithelium
-->acute & chronic inflammation and abscess formation & fibrosis
-->mixed bacterial and fungi may be seen |
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Term
| Role of Cystic Fibrosis, Primary Ciliary Dyskinesia, & Allergic Bronchopulmonary Asperillosis in Bonchiectasis |
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Definition
Cystic Fibrosis
-->bronchial mucus obstruction causes infection, bronchiectasis, and bronchiolitis obliterans
Primary Ciliary Dyskinesia
-->cause poorly functioning cilia--leads to infection/bronchiectasis
Post-infectious Bronchiectasis
-->TB, Staph aureus, H.flu, Pseudomonas, adenovirus, flu virus
-->Allergic Bronchopulmonary asperillosis-Complicates astham and cystic fibrosis. A hypersensitivity rxn to Aspergillus fumigatus causes mucous plugs and bronchiectasis |
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