Pathology Flashcards
Hypoxia
common cause of secondary erythrocytosis SaO2 < 92% (PaO2 < 65mmHg) is the threshold for devleopment of erythrocytosis
Polycythemia
Erythrocytosis
hematocrit > 52% in men and > 48% in women
Can reuslt from true increase in RBC mass (absolute erythrocytosis) or decrease in plasma (relative erythrocytosis)
red blood cell mass is necessary to distinguish absolute from relative
Normal rbc mass indicates plasma volume contraction as the cause of polycythemia
silicosis and tuberculosis link
Silicosis impairs the macrophage effector arm of cell mediated immunity (CMI.) Mø are the main effectors of CMi against intracellualr mycobacteria.
In silicosis there may be disruption of macrophage phagolysosomes by internalized silica particles. Macrophage killing of intracellular mycobacteria may be imparied as a result, causing increased susceptibility of patients with silicosis to pulmonary tuberculosis.
The extracellular releas of llysosomal enzymes resulting from release of silica particles in lyossomes throught to contribute to alveolar and interstitial lung injury in silicosis.
cystic fibrosis mechanism for massive fluid loss
Patients with CF produce eccrine sweat that contains high concentrations of Na and Cl compared to normal people.
CFTR - cystic fibrosis transmembrane conductance regulator protein is mutated.
Normally, the CFTR protein serves as a chloride channel that regulates the flow of sodium, chloride and water across the epithelial membranes of the airways, biliary tree, intestine, vas deferens, sweat ducts, and pancreatic ducts.
Eccrine sweat is isotonic with ECF when it’s first produced. As sweat travels through the eccrine duct to skin surface, chloride is resorbed via the CFTR and Na follows. CFTR facilitates production of hypotonic sweat in normal people. CF patients are unable to reabsorb chloride and sodium in eccrine ducts and therefore secrete high sodium and high-chloride containning sweat. This is the basis of sweat chloride test - diagnostic for CF.
COPD spirometry findings
Residual volume increased in COPD: asthma, chronic bronchitis, emphysems and bronchiectasis cause air trapping and hyperinflaation of lungs. In normal individuals, airway resistance is smallest when the lungs are inflated, due to radial traction of the pulmonary tissue on the conducting airways. based on same principle, COPD patients act to minimize airway resistance by maintaining a hyperinflaated state. Lung volume measurements demonstrate increase in TLC, RV, and elevation of RV/TLC ratio (i.e. more residual volume increase than TLC increase.) Findings indicate air trapping in the lungs.
Anaphylaxis symptoms and mechanism
results from widespread mast cell degranulation. Histamine is the major effector of anaphylaxis, tryptase is also released in excess and can be used as marker for mast cell activation.
Anaphylaxis is a type 1 hypersensitivity reaction characterized by:
urticaria with or without cutaneous angioedema
laryngeal edema (results in dyspnea)
visceral edema
hypotension
all take seconds to minutes of inciting factor.
when the antigen is bound to high affinity IgE receptors on the surface of mast cells, the IgE receptors crosslink and aggregate, clustering Fc receptors. This produces various intracellular cascades that ultimately cuase mast cell degranulation.
Anemia findings (PO2, % sat, O2 content)
PO2 (dissolved oxygen) is normal
% saturation (O2 per gram of Hb) is normal
Decreased O2 content (both dissolved and O2 attached to Hb)
In anemia, from chronic blood loss, blood hemoglobin concentration is decreased. Thus, the PaO2 (dissolved Oxygen - independent of hemoglobin concentration) and the SaO2 (% hemoglobin saturation with oxygen) can be normal but he total oxygen content of the blood is decreased.
NET: THREE VARIABLES AFFECT TOTAL OXYGEN CONTENT OF BLOOD:
1. HEMOGLOBIN CONCENTRATION 2. OXYGEN SATURATINO OF HEMOGLOBIN (SaO2) 3. PARTIAL PRESSURE OF OXYGEN DISSOLVED IN THE BLOOD (PaO2)
cyanide intoxication
inhibits cytochrome C oxidase, resulting in failure of ETC and erobic metabolism. The SaO2 of venous blood increases in cyanide intoxication due to failure of oxygen unloading in tissues
Morbid Obesity and PaO2
associated with obesity hypoventilation syndrome and hypoxia (low PaO2)
High altitudes PAO2 and PaO2 findings
both decreased since the (fraction of inspired O2) FiO2 is decreasd which causes hypoxemia in normal individuals.
Mild Asthma and PaO2
Decreased PaO2 due to airway constriction during exacerbations leading to poor alveolar ventilation and obstructive pattern of lung disease.
CO poisoning findings: PO2, %sat, O2 content
Normal PO2
decreased % sat (CO competes with O2)
decreased total O2 content
Polycythemia (high Hb) findings PaO2, %sat, total O2
PaO2 normal, % sat normal, total O2 increased
small amount of O2 is dissolved in blood plasma, that’s PaO2 and limited by solubility of O2.
% saturation is O2/gram of Hb
Extrinsic allergic asthma: classic sputum findings
paroxysmal breathlessness and wheezing in young patient unrelated to aspirin ingestion, pulmonary infection, inhallation of irritants, stress, and/or exercise shoudl raise strong suspicion of extrinsic allergic asthma.
Classic sputum findings:
eosinophils and charcot-leyden crystals
eosinophils are recruited and activated by IL-5 secreted by Th2 type helper T cells.
found in chronic eosinophic bronchitis in asthmatics.
Uncontrolled severe asthma treatment
Omalizumab - effective and acceptable add-on therapy for patients with severe allergic asthma. shown to be effecitve in reducing dependency on both oral and inhaled steroids.
these are anti-IgE humanized IgG1 monoclonal antibody approved by FDA for moderate to severe psersistent astthma, sensitivity to a perennial alergen and incomplete response to steroids.
Ried Index
used to measure severity and duration of chronic bronchitis. normal = 0.4.
ratio of mucous gland thickness to total bronchial wall between the respiratory epithelium and the bronchial cartilage.
sensitive meausre of mucous gland enlargment.
since progressive mucous gland enlargment is the major contribuotr to gradual bronchial wall thickening in chronic bronchitis and since incresaing wall thickness cuases worsening airflow obstruction, elevations of reid index above normal 40% corelate well with duration and severeity of chronic bronchitis.
Adult Respiratory Distress Syndrome
major risk factor is sepsis.
one of the major diagnostic criteria for ARDS is absence of cardiogenic pulmonary edema - means the pulmonary capillary wedge pressure is usually normal.
elevated wedge pressure would be more suggestive of cardiogenic (hemodynamic) cause of pulmonary edema, such as pulmonary venous hypertension.
ARDS: diffuse injury to pulmonary microvascular endothelium and/or alveolar epithelium resulting in increased pulmonary capillary permeability and leaky alveocapillary membrane.
interstitial and intra-alveolar edema inflammation and hyaline membrane formation cause lung compliance ot decrease, the work of breathing to increase, and the oxygen diffusion capacity of the lung to decrease. More severe involvement and/or atelectasis of regional alveoi can cause V/Q mismatch (decreased ventilation with maintained perfusion).
ARDS results in large part from increased pulmonary capillary permeability.
result is decerase in lung compliance, increase in work of breathing and worsened V/Q mismatching. Pulmonary capillary wedge pressure is typically normal. Elevated PCWP suggests cardiogenic cause in patientw ith pulmonary edema.
most common mutation in CF
∆F508 CFTR found in 70% of cases is a 3 base pair deletion that removes a phenylalanine at position 508. deletion cauess abnormal posttranslational processing (failure to fold and glycosylate) of CFTR protein which leads to degradation of abonral protine before it gets to cell membrane.
Sweat chloride concentrations of > 60mEq/L found in CF. loss of CFTR protein from apical membrane of exocrine duct epithelial cell.
CF commonly characteriezed by pancreatic insufficiency, sinopulmonary infections, malabsorption.
CFTR activated by cAMP-mediated phosphorylation and gated by ATP.
Sarcoidosis findings and ddx
hilar adenopathy, pulmonary disease and constitutional symptoms. Histologically, non-caseating granulomas are seen, which distinguish sarcoidosis from tuberculosis infection.
Pancoast Tumors symptoms
Horner syndrome Ptosis, Anhydrosis, Miosis
SVC syndrome - compression by tumor
arm weakness - compression of lower trunk of brachial plexus
arm paresthesias
hoarseness - recurrent laryngeal nerve involvement
Alpha1-Antitrypsin deficiency
panacinar emphysema - smoking dramatically increases risk
Neutrophil elastiase is major protease of extracellular elastin degradation. released by neutrophils and macrophages. major inhibitor is alpha1-AT.
complete deficiency - liver cirrhosis.
panacinar emphysema results fropm unapposed action of neutrophil elastase on alveolar walls. May result from oxidant produncts of smoke (free radicals) can inactivate endogenous alpha1-AT, producing functional alpha1-AT deficiency. smoking enhances elastase activity in macrophages and macrophage elastase unlike neutrophil derived elastase is not inhibited by alpha1-AT.
pCO2 and cerebral perfusion
pCO2 is the most potent cerebral vasodilator. It decreases cerebral vascular resistance leading to increased cerebral perfusion and increased intracranial pressure. Patients with COPD usually have low pO2 (hypoxia) and high pCO2 (hypercapnea). Thus their cerebral circulation is most likely to be increased.
Supplementary O2 must be used judiciously in patients with COPD because hypoxia drives their respiratory function (whereas nin normal individuals, the pCO2 mediates the respiratory drive.) in patients with longstanding COPD, O2 supplementation can lead to respiratory suppresion and coma.
Delayed Type Hypersensitivity Reactions
Contact dermatitis, granulomatous inflammation, the tuberculin skin test and candida extract skin reaction. Mediated by Th1 lympjhocytes that release interferon-g to cause recruitment and stimulatoin of Macrophages. DTH rxns take days to reach peak activity. in contrast to other hypersensitivity reactions which have clinical effects in minutes.
T lymphocyte mediated reactions. no involvement of antibody or complement. delayed because unlike reactions mediated by Ab that occur minutes after antigen exposure (ABO blood group, hyperacute rejection, erythroblastosis fetalis) delayed reactions occur one to two days folowing antigen exposure. this is why you need to wait 48-72 hours for annual PPD test. In DTH, antigen is taken up by dendritis cells and presented to CD4+ Th lymphocytes on MHC2 molecules. Th-lymphocytes (Th1) release IF-gamma which acts to stimulate and recruit Mø leading to monocytic infiltratio of the area where the antigen was introduced. produces walling-off of M. tuberculosis infection in lung and other forms of granulomatious infalmmation with monocytic and giant cell infioltrates.
Other types of hypersensitivity reactions: Type 1 - IgE mediated (anaphylaxis, asthma) Type 2 - antibody mediated (ABO incompat) Type III - immune complex, post-strep glomerulonephritis.
neutrophils not involved in any hypersensitivity reactions. increased numbers - left shift with predominance of band forms. can be falsely elevated in corticosteroid use due to demargination (release from vascular walls)
examples: contact dermatitis, granulomatous inflammation, tuberculin skin test, candida extract skin reaction
Pulmonary Embolism
hospitalized and post-operative patients are at risk for PE.
presents wiht:
tachypnea, tachycardia, cough, pleuritic chest pain
hypoxemia reults from ventilation perfusion mismatch. occlusion of pulmonary capillary.
risk factors: immobilization (venous stasis) recent surgery (hypercoagulable state)
thrombi most commonly from deep veins in pelvis and lower extremities.
thrombotic occlusion of pulm circulation raises pulmonary resistance and increases RV afterload, which may cause right heart faiulre. can cause sudden drop in perfusion of the corresponding areas of lung parenchuma. Causes Ventilation perfusion mismatch because appropriate amounto f air enters the alevoli, the amount of blood that passes through the affected areas is not sufficienty for normal gas exchange.
