CLIN PATH I: EXAM #2 (PULM - Restrictive Lung Dz)

FEV1 in restrictive lung disease

FEV1 and FVC are decreased (because it is restricting how the lungs work)

Most common feature of restrictive lung disease

infiltration of the lung by inflammatory cells/fluid, causing scarring, fibrosis, and capillary obliteration

Diffuse lung fibrosis causes:

increased lung elastic recoil (increased FEV1)

decreased compliance and lung volumes (decreased FVC)

V/Q mismatch (impaired gas exchange)

lung parenchyma

space bounded by basement membranes of endothelium and epitheliu

What does the lung parenchyma contain

fibroblasts (mesenchymal cells), collagen/elastin/proteoglycans (cellular matrix molecules), leukocytes

When does idiopathic pulmonary fibrosis often present?

5th decade

Clinical presentation of idiopathic pulmonary fibrosis

chronic inflammation of alveolar walls --> fibrosis/destruction of lung architecture

**impairs perfusion and gas exchange

**progressive dyspnea and cough, as well as digital cyanosis, clubbing, and pulmonary HTN

Major causes of idiopathic pulmonary fibrosis

environmental exposure and smoking

Epidemiology of idiopathic pulmonary fibrosis

uncommon

mostly male

unremitting progression

Which diseases are indistinguishable from IPF in later stages?

Scerloderma, sarcoidosis, hypersensitivity pneumonitis

Median survival of IPF

3 years from dx

Pathophysiology of IPF

1. vascular injury

2. epithelial injury

3: leukocyte influx

vascular injury causes an increase in permeability, so more plasma proteins will get into the extravascular space, causing thrombosis

epithelial injury causes loss of barrier integrity and the release of inflammatory mediators

leukocyte influx into the activate endothelium due to infection

**causes un-uniform remodeling and fibrosis

Stages of IPF

1. Injury of epithelial wall

2. Fibroblasts come in

3. Abnormal repair response (collagen over-production to repair the holes), and fibroblasts get inside alveoli

4. Thickening of alveolar walls (repeated injury)

5.Fibrosis due to chronic inflammation

6. Irreversible loss of basement membrane, disrupted gas exchange, etc. because of the inflammatory response

Clinical manifestations of IPF

progressive dyspnea

dry persistent hacking cough (chronic irritation)

inspiratory crackles (fibrotic airways)

digital cyanosis, clubbing, decreased cap refill

IPF can lead to:

R heart failure and peripheral edema

Imaging for IPF

reduced lung volumes

increased reticular opacities (periphery)

loss of structure definition

honeycombing

Pulmonary function test for IPF

reductions in TLC, FEV1, and FVC, but maintaining a preserved FEV1/FVC ration

What is a significant contributor to exercise-induced desaturation?

diffusion impairment

Arterial pCO2 is typically ________ with restrictive disease

low (due to increased ventilation from hypoxia and increased irritant stimuli)

Grave sign of restrictive lung disease

hypercapnia (inability to maintain adequate alveolar ventilation)

Epidemiology of TB

increase in those infected with HIV, those who travel and emigrate from areas w/ increased TB, homeless people, IVDA

increased bacterial resistance to medications

What causes TB?

infection w/ Mycobacterium tuberculosis (rod shaped acid-fast bacilli)

How does TB spread

droplets (airborne)

Transmission of TB is influenced by:

1. # of bacilli in droplets

2. virulence of bacilli

3. degree of ventilation (outdoors vs. inside w/ bad AC)

4. occasions for aerosolization

The majority of the TB bacilli are trapped in:

upper parts of the airways (where mucus-secreting goblet cells are)

**cilia on the surface of these cells beat the mucus and its entrapped particles upward for removal

Bacilli in droplets that bypass the mucociliary system and reach the alveoli are quickly:

surrounded and engulfed by alveolar macrophages

Phagocytosis by macrophages (innate immunity) results in either:

latent TB

OR

primary progressive TB (active)

What are recruited during TB exposure?

T cells to begin cell-mediated immunity

Patient is ___________ to TB once exposed

sensitized

How do they make a PPD test?

Antigens from killed TB

What do you look for on a CXR w/ TB?

Ghon complex

What is the next defensive step for TB for people with intact immune systems?

formation of granulomas (to limit the replication and spread of the bacteria)

What will the eventual destruction of macrophages in TB cause?

necrotic center

By 2 or 3 weeks, the necrotic environment resembles:

soft cheese (caseous necrosis)

What are Ghon complexes

Lesions undergo fibrosis and calcification, successfully controlling the infection so that the bacilli are contained in the dormant, healed lesions, called Ghon complexes

Ghon complex are more commonly in:

apex of lung

What happens to TB lesions in people with bad immune systems?

will progress into primary progressive TB (lesions will undergo liquefaction, so fibrous walls lose structural integrity)

In immunocompromised pts, the semiliquid necrotic material can then drain into:

bronchus or nearby vessels (causing cavitation)

**sign of active TB

What will cause extrapulmonary tuberculosis

if TB spreads to blood vessels

What will cause the formation of caseous granulomas

bacilli drain into lymphatic system and collect in the tracheobronchial lymph nodes of the lung

Pott's disease

when TB spreads to the bones/joints

Where can TB cause extrapulmonary infection?

bloodstream, lymphatics, pleural, bones/joints, meninges

Factors impacting TB disease progression

HIV, DM, sepsis, renal failure, smoking, malnutrition, chemotherapy, organ transplant, corticosteroid use, old age

How to treat TB:

RIPES

Rifampin

INH

Pyramidine

Ethambuterol

Streptomycin

Clinical manifestations of TB - latent

virtually asymptomatic

Clinical manifestations of TB - active

low grade fever, cough, night sweats, fatigue, weight loss, purulent sputum

Clinical manifestations of pulmonary HTN (cor pulmonale)

dyspnea, chest pain, syncope, edema, fatigue, cyanosis

Pulmonary HTN is often seen with:

underlying disease (IPF, COPD, sleep apnea)

Epidemiology of pulmonary HTN

rare

high mortality rate if left untreated

more common in women ages 21-40

Most common cause of death with pulmonary HTN

decompensated RHF

What is pulmonary HTN defined as

>25mmHg at rest or >30mmHg with exercise

**pulmonary artery pressure

Pulmonary HTN is an issue with __________

afterload (right sided)

What happens when there is vascular injury with Pulmonary HTN

decrease NO

decrease prostacyclin

increase thromboxane

increase endothelin 1

Hallmark of PAH

plexiform lesions (vascular formations originating from remodeled pulmonary arteries)

Process of Pulmonary HTN

pulmonary vascular fibrosis and thrombosis

remodeling/decreased compliance (stiff)

increase RV afterload

increase pulmonary vascular resistance and pulmonary artery pressure (not enough blood to LA)

tachycardia to compensate for decreased CO (heart does not fill as well - decrease preload)

Best drug for pulmonary HTN

Revatio

What will cause hypoxia with pulmonary HTN

heart cannot pump hard enough as the lung pressure increases (RV and RA hypertrophy)

Impact of pulmonary HTN on the kidneys

CO is decreased, so there is less kidney perfusion (will activate RAAS and cause Na/water retention)

Cor pulmonale

Right ventricular enlargement secondary to a lung disorder that causes pulmonary artery hypertension.

**usually chronic (but can be acute/reversible)

Which valve issue can cause right sided HF

MS

Acute Cor Pulmonale is associated with?

massive pulmonary embolism

injury due to mechanical ventilation (ARDS)

Chronic Cor Pulmonale is associated with?

extensive loss of lung tissue (surgery/trauma)

unresolved pulmonary emboli

pulmonary HTN

pulmonary veno-occlusive disorders

pulmonary interstitial fibrosis

Clinical Manifestations of cor pulmonale

dyspnea on exertion

fatigue

chest pain

parasternal lift

syncope w/ exertion

pitting peripheral edema

passive hepatic congestion (anorexia or RUQ discomfort)

pulmonary emoblism

material enters the venous system and eventually gets stuck in a small vessel and forms a plug (lumen and perfusion obstruction)

Normally, the pulmonary circulation can:

remove venous emboli (but if there is a large one or many small ones it cannot)

Tx of pulmonary embolism

Anticoagulant because this is a clotting problem

**If you cannot take anticoagulants due to GI bleed - do an IVC filter (put an umbrella of mesh in the artery and makes a net for the clot)

More than 95% of PE arise from thrombi in:

deep veins of lower extremities

Most prevalent risk factor of PE in hospitalized patients:

venous stasis (prophylactic therapy)

The two most common causes of increased activation of the coagulation system:

malignancy and tissue damage

Venous thrombi are composed of:

fibrin, erythrocytes, some leukocytes, & platelets

PE w/o pre-existing cardiopulmonary disease

pulmonary artery pressure increases in proportion to occlusion (causes RV strain and EKG changes to T wave)

PE w/ pre-existing cardiopulmonary disease

pulmonary artery pressure does not correlate w/ extent of embolism

**increase in fatalities (too unstable for angiography)

V/Q in Pulmonary Embolism

reduced pulmonary perfusion distal to occlusion site increases lung segments w/ high V/Q ratio

With complete occlusion - V/Q ratio reaches:

infinity (represents alveolar dead space)

What will PE do to ventilation

causes hyperventilation

Most common finding with acute PE

low pCO2 (due to tachypnea)

**can still have a O2 sat over 90

Thromboembolus

venous thrombi that migrates from lower extremities (most common)

Air emboli

from cardiac or neurosurgery (central venous catheters - occur on right side of heart)

Amniotic fluid emboli

during pregnancy

Fat emboli

from a long bone fracture or liposuction

Septic emboli

from endocarditis (causes splinter hemorrhages) or thrombophlebitis

Tumor emboli

renal cell carcinoma w/ invasion

Risk factors of PE - Virchow's Triad

1. venous stasis

2. injury to vascular wall

3. hypercoagulability

what causes venous stasis

bed rest, immobility, arrhythmias (blood sits in LA appendage), air travel, obesity

what causes hypercoagulability

OCs, birth control, polycythemia, cigarette smoking

what causes vessel wall damage

trauma, penetrating wounds, fx of long bones, surgical procedures, manipulations during labor, burns

PE is associated with sudden onset of:

dyspnea, pleuritic chest pain, hemoptysis

Homan's sign

DVT (can cause PE - swollen, red, tender, warm)

What can be heard w/ PE

inspiratory crackles and friction rub

What occurs in severe PE

cardiopulmonary arrest

Many perfusion defects are corrected within ________

9-14 days

In some pts, the emboli can become organized, which means they are:

incorporated into the pulmonary arterial wall (epithelialized fibrous mass)

Chronic pulmonary thromboembolism

when emboli are incorporated into the pulmonary arterial wall