BHS 116 – Physiology
Notetaker: Caitlyn McHugh
Date:10/09/2012, 2nd hour
Page1
Chronic Restrictive Lung Disease
Vascular Lung Disease
Pulmonary thromboembolism, hemorrhage and infarction
Pulmonary hypertension and vascular sclerosis
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Clicker Question: How does reducing the ventilation rate affect the pH of the blood?
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Blood pH increases
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Blood pH decreases
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Blood pH is not effected
Asthma- produces a lot of mucus, if not cleared it will solidify, can get pulled out of bronchi in its
entirety (ew)
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Can function with one lung, would be labored breathing
Chronic Restrictive Lung Disease
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Aka fibrotic lung disease
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Many types of diseases that fall under this category – all have very similar signs, symptoms
and pathophysiologic changes that occur in the lungs
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Many have no known cause
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Major things we see in common
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Reduced compliance—decreased stretch-ability of the lungs
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Primarily diseases effecting inspiration
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Lungs aren’t stretching as much as they should be so less air is able to get in
Spirogram
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Decreased total lung capacity – problem with inspiration, don’t bring as much air in
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Decreased vital capacity – all the extra room there is outside of residual volume
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Residual volume is the same
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Maximal amount of air taken into lungs after forceful expiration is reduced
(from 4.5L in a normal lung to 2.8 L in chronic restrictive disease lung )
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Look at FEV1/FVC ration
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Decrease in total lung capacity—proportionate decrease in forced expiratory
volume both decrease
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FEV1/FEC Ratio does not change = still 80% , what is seen in a normal lung, since
both are proportionally decreasing
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This measurement is for forced expiratory volume
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Can expire air fine and at a normal rate, but can’t inspire as well
Compare to chronic obstructive disease which is around 45-50%
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
o

Date:10/09/2012, 2nd hour
Page2
Variety of different causes
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Asbestos
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Chemotherapy agents
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Immunologic problems
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Occupational hazards
Types of Chronic Restrictive Lung diseases: Idiopathic Pulmonary Fibrosis, Hypersenstitivity
Pneumonitits, Diffuse Alveolar Hemmorrhage Syndromes
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Idiopathic pulmonary fibrosis (IPF)
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Idiopathic = unknown cause
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Characterized
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Diffuse interstitial fibrosis in the pulmonary interstitium
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Advances cases = hypoxia and cyanosis (decreased Oxygen delivery to tissues)
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Males more effected than females
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Tend to be seen in people over the age of 60
Initially
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Injury to alveolar wall—causes interstitial edema = alveolitis (inflammation of
alveoli)
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Mild injury = normal resolution to normal tissue
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Acute inflammatory reaction – everything resolves back to normal
Persistent injurious stimulus – proliferation of macrophages, lymphocytes,
neutrophils and alveolar epithelial cells  leading to progressive interstitial fibrosis
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Pathophysiologic mechanism
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Injurious stimulus is inhaledActivates macrophages (dust cells)
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Activated macrophages
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Stimulate cytokines to recruit neutrophils to the lungs and activate these
neutrophils
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Secrete own proteases and oxidants
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Secrete cytokines that activate fibroblasts and draw them into the area
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These neutrophils produce and secrete proteases and oxidants
Fibroblasts secrete extra-cellular matrix (ECM) proteins
All proteases and oxidants that are produced damage lung endothelium
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Type I pneumocytes are cells that are damaged—these line alveoli
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Stimulate hypetrophy and hyperplasia of type II pneumocytes—secrete
surfactant
BHS 116 – Physiology
Notetaker: Caitlyn McHugh

Date:10/09/2012, 2nd hour
Page3
Type II pneumocytes begin to start secreting cytokines and fibrogenic
compounds that also contribute to fibroblasts migrating to the site and
triggering proliferation of fibroblasts
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Fibroblasts secrete ECM proteins(like collagen)—find fibrotic proteins being
found in the interstitium
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Interstitial space between alveoli and pulmonary capillaries, if
fibrotic proteins disrupt this gap—increasing gap between the alveoli
and pulmonary capillary reduce diffusion of oxygen and CO2—
problems with O2 delivery to tissue and release of CO2 into alveoli
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Symptoms
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Non-productive cough—no mucous or blood
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Dyspnea-breathlessness
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Dry/velcro-like deep breath sounds
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Due to fibrotic tissue
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Cyanosis occurs as disease progresses decreased O2 delivery to peripheral tissues
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See peripheral edema –due to back up of system
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As fibrosis is occurring in lung interstitium—starts compressing blood
vessels in the lung
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Increase pulmonary blood pressure
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Pulmonary hypertension – right ventricle has to work a lot harder to
pump blood through the lungs due to firbosis
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Backup- right atrium has to pump blood into right ventricle, if RV can’t
pump blood out, leads to back up
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Leads to back up in vena cava and therefore the entire system, blood
starts leaking out of capillaries in tissues  edema
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Right sided heart failure—right ventricle works too hard and eventually fails
Histologically
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Increased fibrosis
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Areas of fibrosis alternating with normal tissue areas
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Blue stain = fibrous protein
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Pink staining = fibrotic tissue
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Normally can’t see a gap between alveolar air space and pulmonary capillary—here
there are thick regions of fibrotic tissue between alveoli giving a huge gap huge
diffusion distance and therefore poor exchange occurring
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
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Date:10/09/2012, 2nd hour
Page4
Gross sections of lung
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Honeycomb change- get dense fibrotic bands surrounding alveoli developing
throughout the lungs
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Huge thickening of interstitium seen with the naked eye
Treatment
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Corticosteroids to reduce inflammation
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Relentless progressive disease—by time it is diagnosed, survival is only about 2-4
years
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Requires a lung transplant
Hypersensitivity Pneumonitits aka Allergic Alveolitis
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Inflammation of alveoli due to immunological reaction
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Unlike bronchial asthma—damage here occurs at level of alveoli (asthma is a bronchiole
disease)
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Type III or type IV hypersensitivity reaction
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Causes
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Work-related antigens: fungal, bacterial antigens found in specific work related
scenarios
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Farmer’s lung = due to moldy hay
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Cheese-washers lung = moldy cheese
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Pigeon breeder lung = pigeons
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Anything out there that is an antigen can cause this
Symptoms
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Acute reaction
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Fever, cough, dyspnea within 4-8 hours
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Most resolve within a few days as long as specific antigen is removed—not
constantly exposed
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Chronic disease phase
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Persistent exposure
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Insidious onset of cough—fine for a long period of time after initial
symptoms but then have bad cough
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Dyspnea, malaise (fatigue), weight loss
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5% of these cases can result in respiratory failure and death if not treated
right away
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
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Date:10/09/2012, 2nd hour
Page5
Histological section of lung
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Mononuclear B and T cells are found all throughout the interstitium
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Interstitium is so thick – causes huge distances between alveoli and blood
vessels
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Acute = neutrophils present
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As progresses, get more lymphocytes and interstitial necrosis
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Immune cells start to wall off infectious agent
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Cellular activity occurring-increase the diffusion distance for O2 and CO2
Treatment
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Eliminating the antigen
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Form a granuloma – basically form a wall around the allergen
If done soon enough- won’t have permanent damage
Diffuse alveolar hemorrhage syndrome
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Cluster of immune mediated diseases
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3 major symptoms
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Hemoptysis – coughing up blood
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Anemia—low RBC count
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Diffuse pulmonary infiltrates—infiltration of cells diffusely throughout interstitium
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Classic disorder: Goodpasture syndrome
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Typically present with lesions in pulmonary basement membrane
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Immune attack of alveoli basement membrane causing an immune reaction that
triggers symptoms to happen
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Histologically
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Pink = interstitial space = very thick
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Red cells = RBC getting into alveoli
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Alveoli are being broken down by immune system and RBC start to fill
alveoli hence coughing up blood
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Become anemic because RBC are in alveoli and have lower numbers in
systemic circulation
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Blue staining in second image = stains for RBC
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Intra-alveolar hemorrhaging and fibrous hemorrhaging seen
Treatment
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Immune disorder—can do plasma exchange
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
Date:10/09/2012, 2nd hour
Page6
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Can exchange plasma from patient with bad antibodies with fresh plasma and
antibodies
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Body will keep producing bad antibodies so process has to keep being redone
Immunosuppressant drugs
Vascular lung disease : pulmonary thromboembolism, hemorrhage and infarction, pulmonary
hypertension
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Pulmonary Thromboembolism
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Most common preventable cause of death in hospitalized patients
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Most of the time, these emboli start in large vessels of lower leg
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8% of fatal cases are from patients just undergoing hip surgery
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Usually due to immobilization-bed ridden
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Venous blood in leg is stagnant- venous pump requires skeletal muscle
contraction
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Blood can pool—trigger for coagulation = stagnant blood flow, so blood
clots developmove through venous system, get to right atria and then right
ventricle to go into pulmonary circulation and is lodged in lung and blocks
blood flow
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Consequences
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Depends on size of embolus
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Larger the embolus – the greater the section of lung it can block off
2 consequences
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Increase in pulmonary arteriolar pressure—block section of lung,
causes back pressure, right ventricle has to pump harderright
ventricular hypertrophy which could lead to heart failure
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Ischemia of downstream lung tissue could lead to death of the lung
tissue
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Picture of infarcted lung tissue due to thromboembolus
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Treatments
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60-80% range are clinically silent and get broken down by fibrinolytic
system before blocking off major tissue
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5% can result in sudden death- large enough, block off significant portion of
lung
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Treatments for any in between
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tPA
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
Date:10/09/2012, 2nd hour
Page7
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anticoagulation drugs
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prevention
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patients that have major hip replacement are up and moving
very soon after surgery
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if aren’t able to, there are therapists that work with and move
legs so they aren’t stagnant for long periods of times
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elastic stockings that compress legs and serve as venous
pump
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Pulmonary hypertension
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Caused by decreased cross sectional area of pulmonary vasculature
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Decrease number of vessels open and to what extent they are open
Secondary result of other diseases
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Most causes are from other diseases = secondary pulmonary hypertension
(95%)
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Main one : COPD
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Emphysema –increased lung volume, as alveoli expand compress
blood vessels, smaller diameter for blood to go through, right
ventricle pumps harder
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Thromboemboli—blocks blood flow to lung
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Heart disease with left to right shunt
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Left side is high pressure side
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If septal defect, will move blood from left to right side, increases
blood volume moving through pulmonary system and therefore
increase pressure
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Mitral valve stenosis
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Separates left atria and left ventricle
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Back up in atria because of stenotic valve—backs up blood flow
from the lungs— leadsall the way back to right ventricle
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5% are caused by unknown factors: Primary pulmonary hypertension
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Directly affecting vasculature of the lungs
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Look at normal vasculature
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In mild, get thickening of intimal and medial layers – reversible (can
revert back to normal)
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Lumen is much smaller than a normal vessel
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
Date:10/09/2012, 2nd hour
Page8
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In advanced cases- severe thickening of arterial wall—very small
lumen
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Major disruption in arterial wall =Get plexiform lesion –
aneyruismal disruption of wall
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Get cellular matter growing and causing giant mass in vessel
wall itself of smooth muscle
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Almost total occlusion of the vessel wall
Pathogenesis- genetic link evidence with primary pulmonary
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Gene that is disruptive = Bone Morphogenetic protein Receptor Type
2 (BMPR2)
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First discovered in bone
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Have been linked to 50% of inherited form of primary
pulmonary HTN and 26% of sporadic forms
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BMPR2 signaling
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Normally is secreted and inhibits proliferation of vasculature smooth
muscle
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During development, smooth muscle is proliferating to a certain
thickness and BMPR2 stops it
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Triggers apoptosis of smooth muscle cells if starts to become thicker
so we don’t increase thickness of arterial wall
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In mutation, BMPR2 can no longer function sin this manner and
cannot inhibit smooth muscle proliferation
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Smooth muscle continues to proliferate uncontrolled,
thickens vessel wall, decreases lumen size
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Constriction of walls, leading to pulmonary hypertension
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50% of those with familial, but also environmental triggers can cause
mutations
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Initial symptoms
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Breathlessness, fatigue—body is working harder to pump blood out
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Vessel wall thickening – less blood to alveoli, less O2 and CO2 exchange,
less O2 delivered to rest of body
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If progressing
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Respiratory distress
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Cyanosis
BHS 116 – Physiology
Notetaker: Caitlyn McHugh
Date:10/09/2012, 2nd hour
Page9
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Death results because right side of heart is pumping hard, eventually
it will fail
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Treatments
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Can be alleviated with vasodilators that will open up vessel walls—only way
to really treat it is a lung transplant
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Clicker Question: Which of the following would you not see with Chronic Restrictive Lung Disease?
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Decrease in total lung capacity
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Normal residual volume
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Decreased FEV1/FEC ratio
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Reduced lung compliance