Clin Med Exam 2: Pulm

tuberculosis

infection of the lungs via mycobacterium tuberculosis

how is TB transmitted?

via aerosolized droplets (infected person coughs, spits or sneezes on another person who inhales the droplets)

after an infection of TB, what can occur?

latent or active TB

latent TB

immune system is able to successfully contain the infection, but not eliminate it. Macrophages and T cells wall off the areas of infection in granulomas, thereby preventing the infection from spreading within the host or to another host (not contagious)

active TB

immune system is not able to contain the infection within granulomas and it spreads throughout the body; can result from primary infection not successfully contained by the immune system or reactivation of latent TB

extrapulmonary TB

a form of active TB in which the infection occurs in other areas of the body outside the lungs

risk factors for TB

- immunocompromised (HIV, AIDS, immunomodulating medications, transplant patients)

- health care workers

- bronchoscopy

- aerosolized treatments

- autopsy

- oben abscess irrigation

- endotracheal intubation or suctioning

- sputum induction

sign and symptoms of latent TB

asymptomatic

signs and symptoms of active TB

- fever

- night sweats

- weight loss

- hemoptysis

signs and symptoms of extrapulmonary TB

give where it is and name

- Pott's disease (TB of the vertebrae)

- scrofula (TB of cervical lymph node)

- miliary (systemic TB)

diagnostics for latent TB

- tuberculin skin test/ PPD

- interferon gamma release assay (quantiferon and T spot)

how is a tuberculin skin test performed

0.1ml of tuberculin purified protein derivative (PPD) is injected into the forearm and the diameter of induration is measured 48-72 hrs later:

interpretation of a tuberculin skin test (PPD) ≥ 5mm

TB positive for HIV+, organ transplant or other immunosuppressed pts, and pts with a recent exposure

interpretation of a tuberculin skin test (PPD) ≥ 10mm

TB positive for:

- recent immigrants from areas with high TB incidence

- health care workers

- homeless pts

- pts with hematologic or head/ neck malignancies, renal failure or diabetes

- injection drug users

interpretation of a tuberculin skin test (PPD) ≥ 15mm

TB positive for people with no known risk factors

how is a interferon gamma release assay (quantiferon and T spot) performed?

the T cells in a pt's blood sample are stimulated with TB specific peptides and the activity of the T cells is approximated by measuring interferon gamma

3 components of the interferon gamma release assay (quantiferon and T spot)

- nil (negative control)

- mitogen (positive control)

- TB

list the normal and abnormal values for the nil of an interferon gamma release assay

normal: < 8.0 IU/ml

abnormal: > 8 (indicates an underlying inflammatory/ immune condition that is causing a false positive)

list the normal and abnormal values for the mitogen of an interferon gamma release assay

normal: ≥ 0.5 IU/ml

abnormal: < 0.5 IU/ml (indicates an underlying condition that inhibits activation of T cells: HIV, immunosuppressant meds, leading to a false negative)

list the values of the TB portion of an interferon gamma release assay that indicates TB infection

≥ 0.35 IU/ml

testing for active TB

• Initial Screening: Sputum Acid-Fast Bacilli (AFB) smear x3 (8h apart, ≥1 early morning sample) and CXR/CT

• Definitive / Gold Standard: Sputum culture for M. tuberculosis (2–6 weeks; gold standard for drug susceptibility) OR NAAT / PCR (results in hours to 2 days)

• CXR Findings: Primary = ill-defined consolidation, hilar lymphadenopathy, pleural effusion (30–40%); Reactivation = apical fibrocavitary lesions

____

sputum or bronchial lavage or biopsy

acid fast bacilli (AFB) stain: typically 3 smears are done 8 hrs apart

acid fast bacilli culture

nucleic acid amplification (PCR) for TB/ MTB DNA probe

imaging

imaging tests for TB

- chest x-ray

- CT

- bronchoscopy

what will a chest x-ray show for latent TB?

may be normal or show show non-specific changes (lesions, cavitations)

what will a chest x-ray show for active TB?

either ill-defined patchy consolidation or fibroproliferative disease with course reticulonodular densities

what will a chest x-ray show for healed/ treated TB?

🐝 Ranke complex or Ghon focus (healed calcifications and calcified mediastinal lymph nodes)

testing for extrapulmonary TB

tissue biopsy from area of suspected infection

treatment of latent TB

• Prerequisite: Rule out active TB and test for HIV prior to initiating therapy

- Ioniazid (INH) x 9 months (+ supplemental B6)

(best treatment for healthy adults on minimal meds)

- Rifampin x 4 months

- Isoniazid and rifapentin x 3 months

(provider has to directly watch the patient take these meds)

(hint: R, I or R+I)

treatment for active TB and HIV-

Rifampin, Isoniazid, Pyrazinamide and Ethambutol (RIPE)

1. RIPE for 2 months

2. RIP (if pt has confirmed sensitivity to RIP drugs within the first 2 months)

3. RI for 4 months

• Infection Control: Negative-pressure isolation room until 3 consecutive negative AFB smears;

Directly Observed Therapy (DOT) recommended

treatment for active TB and HIV+

Highly Active Antiretroviral Therapy: HAART (but note that it may cause paradoxical worsening of TB due to immune reconstitution inflammatory syndrome/ IRIS. There are also a lot of drug interactions between TB meds and certain HIV meds so be aware)

treatment for active TB in pregnant patients

1. RIE therapy for 4-8 weeks

2. RI for 7 months (if pt has confirmed sensitivity to RI)

do not give pyrazinamide (especially during the 1st trimester)

hint: no P if Pregnant

how long do you treat multi-drug resistance TB

24 months

side effects of Rifampin

- turns bodily fluids reddish-orange

- polyarthralgias

- many drug interactions

- LFT abnormalities

hint: Rifampin turns bodily fluid Reddish-orange... ouch that must hurt (polyarthralgias)

side effects of Isoniazid

- peripheral neuropathy

- lupus like syndrome (flu symptoms, rash)

- LFT abnormalities

hint: Isoniazid = "I so numb" (peripheral neuropathy)

side effects of Pyrazinamide

- gout flares

- polyarthralgias

- LFT abnormalities

hint: the pyramids were built out of stones (uric acid crystals/stones can lead to gout) and the people who built them were probably very sore (polyarthralgias)

side effects of Ethambutol

- reversible optic neuritis (inflammation of the optic nerve leading to pain and vision changes, specifically color vision)

- LFT abnormalities

hint: Ethambutol causes Eye side effects

what monitoring needs to be done for a patient on TB meds? explain why

all TB meds are hepatotoxic and therefore liver function needs to be monitored throughout the course of treatment

monitor: ALT, AST, total bilirubin

stop TB treatment if:

- asymptomatic w/ a > 5x increase in AST

- symptomatic w/ a 3x increase in AST

- baseline normal LFTs w/ >3x increase in AST

cystic fibrosis pathology

Autosomal recessive disorder that causes a mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene leading to abnormalities in the chloride and water transport across the surface of epithelial cells. As a result, almost all the exocrine glands in the body produce an abnormally thick and viscous mucous secretion that clogs the lungs, pancreas, liver, intestines and reproductive tract

risk factors for cystic fibrosis

- caucasian

- family Hx

pulmonary symptoms of cystic fibrosis

- cough

- sputum production

- decreased exercise tolerance

- recurrent hemoptysis

- chronic rhinosinusitis

- digital clubbing

- increased AP chest diameter

- hyperresonance to percussion

- apical crackles

- sinus tenderness

- purulent nasal secretion

- nasal polyps

pancreatic symptoms of cystic fibrosis

steatorrhea

GI symptoms of cystic fibrosis

- diarrhea

- abdominal pain

- malnourished

- biliary cirrhosis

- gallstones

reproductive tract symptoms of cystic fibrosis

congenital bilateral absence of vas deferens with azoospermia (infertility) in men

requirements for a diagnosis of cystic fibrosis

positive IRT and sweat chloride

or

positive genetic testing

diagnostics for cystic fibrosis

- labs: immunoreactive trypsinogen (IRT)

- sweat chloride test

- genetic testing

- ancillary testing

ancillary testing for cystic fibrosis

- chest x-ray

- CT

- pulmonary function testing (PFT)

treatment for pulmonary cystic fibrosis

- prevent infection and obstructions: vaccines, chest physiotherapy (postural drainage, percussion, vibration, etc.) and regular aerobic exercise

- airway clearance: dornase alfa

- CFTR modulators targeted: (elexacaftor, tezacaftor, ivacaftor triple therapy)

-caftor think cftr

treatment for pulmonary exacerbations of cystic fibrosis

also which pahtogen presents when: (S. aureus ____, P. aeruginosa ____),

short course of antibiotics depending on the infection

chronic inhaled tobramycin/aztreonam or

azithromycin for P. aeruginosa

(S. aureus early, P. aeruginosa late),

treatment for a pulmonary exacerbation of cystic fibrosis caused by methicillin-sensitive staphylococcus:

- penicillinase-resistant penicillin (Cloxacillin, Dicloxacillin)

- cephalosporin (Cephalexin)

- trimethoprim/ sulfamethoxazole

- Erythromycin

- Amoxicillin/ clavulanate

- tetracyclines

- Linezolid

treatment for a pulmonary exacerbation of cystic fibrosis caused by MRSA

- oral trimethoprim/ sulfamethoxazole

- Clindamycin

- Linezolid

- tetracycline

treatment for a pulmonary exacerbation of cystic fibrosis caused by P. aeruginosa

- short course of inhaled Tobramycin or Aztreonam lysine

and/or

- oral fluoroquinolone

treatment for frequent/ recurrent pulmonary exacerbations of cystic fibrosis

long term suppressive antibiotic therapy (Azithromycin)

treatment for refractory cystic fibrosis

cardio-pulmonary transplant

treatment for GI cystic fibrosis

- pancreatic enzyme supplementation (pancrealipase)

- treat malabsorption issues

- treat constipation

palliative care for cystic fibrosis

- reassess code status

- hospice services

- sufficient sedation to ensure peaceful dying

common complications of cystic fibrosis

in infants?

in men?

- bronchiectasis

- meconium ileus (in infants)

- recurrent pulmonary infections

- malabsorption

- recurrent pancreatitis

- distal intestinal obstruction

- biliary cirrhosis

- infertility in men

define pulmonary hypertension

abnormally high blood pressure in the pulmonary vasculature (usually the arteries and arterioles)

normal pulmonary pressure values and values seen in pulmonary HTN

normal values: 9-18 mmHg

pulmonary HTN: > 25 mmHg at rest or 30 mmHg with exercise

mechanisms that can cause pulmonary HTN (including the most common cause)

- increased pulmonary vascular resistance (most common)

- increased pulmonary venous pressure

- increased pulmonary venous flow due to congenital heart disease

pulmonary hypertension pathology

Vasoconstriction of blood vessels connected to the lungs making it harder for the heart to pump blood through the lungs. Over time the affected blood vessels become fibrotic which increases the blood pressure in the lungs and further impairs blood flow. With an increased workload, the heart hypertrophies leading to right sided heart failure (cor pulmonale) and eventually hypoxia of the left ventricle (because blood flow to this side is restricted)

WHO group 1

pulmonary hypertension due to a group of diseases that directly affect the pulmonary arteries resulting in structural changes (fibrosis, constriction, etc), smooth muscle hypertrophy and endothelial dysfunction, all leading to increased pressure

list the diseases in WHO group 1

- idiopathic

- hereditary

- connective tissue disease (vasculitis, etc)

- portal hypertension

- drugs (either recreational or prescription)

- toxins

- HIV

- schistosomiasis (parasitic infection)

WHO group 2

pulmonary hypertension caused by left sided heart disease

list the diseases in WHO group 2

- left ventricular systolic or diastolic dysfunction

- valvular malfunction

WHO group 3

pulmonary hypertension caused by lung diseases and/or chronic hypoxia (hypoxia causes arteriolar vasoconstriction leading to increased pressure)

list the diseases in WHO group 3

- COPD

- interstitial lung disease (ILD)

- disordered sleeping (OSA and chronic alveolar hypoventilation syndrome)

- alveolar hyperventilation

- chronic high altitude exposure

- developmental lung abnormalities

WHO group 4

pulmonary hypertension due to chronic thrombotic or embolic disease

list the disease in WHO group 4

- chronic thromboembolic pulmonary hypertension

- obstruction of pulmonary circulation due to tumor or inflammation

subtype of WHO group 4

pulmonary veno-occlusive disease

WHO group 4: pulmonary veno-occlusive disease

pulmonary HTN caused by progressive occlusion of veins and venules with fibrosis, this eventually leads to backup into the arteries and arterioles, nodules, edema, hemorrhage, hemoptysis and death within 2 years

WHO group 5

pulmonary hypertension caused by an uncertain multifactorial mechanism (anything that doesn’t fit into the other categories)

list the diseases in WHO group 5

- haematological disease

- systemic disease

- metabolic disease

- others

which of the WHO groups is the most common cause of pulmonary HTN

WHO group 2

signs and symptoms of pulmonary HTN

(common and uncommon)

common:

- shortness of breath, especially during activity (exertional dyspnea)

- lethargy

- fatigue

uncommon:

- cough!!!!

- hemoptysis

- Ortner’s syndrome (hoarseness)!!!

class I pulmonary HTN

symptoms do not limit physical activity (asymptomatic)

class II pulmonary HTN

slight limitation to physical activity

patient is comfortable at rest but experiences symptoms with moderate physical activity (walking the dog)

class III pulmonary HTN

marked limitation to physical activity

patient is comfortable at rest but experiences symptoms with mild exercise (walking to the mailbox)

class IV pulmonary HTN

inability to carry out any physical activity

patient experiences symptoms even at rest and may have signs of right sided heart failure

Ortner's syndrome

compression of the left recurrent laryngeal nerve due to a dilated pulmonary artery leading to hoarseness

diagnostics for pulmonary HTN

Baseline assessment before initiation of therapy

Fxnl significance: exercising capacity

Echocardiogram

RH catheterization

• Initial: Echocardiogram (estimates RV systolic pressure, RV enlargement);

EKG (RVH, right atrial enlargement); elevated BNP/pro-BNP.

• Definitive: Right Heart Catheterization (RHC) confirming mean pulmonary artery pressure (mPAP) >20 mmHg at rest.

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- PE

- chest x-ray

- EKG

- echocardiogram

what will a PE show for pulmonary HTN

abnormal heart sounds

what will a chest x-ray show for pulmonary HTN

- visible/ enlarged pulmonary arteries

- right ventricular enlargement

- right atrial dilation

- underlying cause of pulmonary HTN may be apparent

what will an EKG show for pulmonary HTN

- tall R waves in V1 and inverted T waves in V1-V3

- right ventricular hypertrophy

- chronic right ventricular overload

treatment of WHO group 1 pulmonary HTN

- treat underlying cause

- calcium channel blockers (nifedipine, diltiazem)

treatment of WHO group 1 pulmonary HTN for functional class II

oral endothelin receptor antagonists (ambrisentan, bosentan)

phosphodiesterase inhibitors (sildenafil, tadalafil)

soluble guanylate cyclase stimulators (riociguat)

treatment of WHO group 1 pulmonary HTN for functional class III or IV

prostanoid agents (IV Epoprostenol, sub Q and IV Teprostenol and inhaled Iloprost)

why is iloprost not often used for pulmonary HTN

because it's inhaled and the patient already has impaired lung function

treatment of WHO group 2 pulmonary HTN

treat underlying disease

treatment of WHO group 3 pulmonary HTN

- treat underlying disease

- supplemental O2 for 15+ hrs a day

treatment of WHO group 4 pulmonary HTN

anticoagulation

surgical treatment for pulmonary HTN

atrial septostomy: small hole created between the two atrial chambers leading to increased exercise capacity but also causes decreased PaO2

lung transplant (or lung + heart if the HTN is related to chronic heart disease)

asthma pathology

condition characterized by reversible bronchoconstriction, airway edema and inflammation, airway hyperreactivity and airway remodeling (goblet cell hyperplasia that causes increased mucous production and clogging of airways)

explain why asthma is considered reversible

with treatment, the airway remodeling that occurs during asthma can be corrected and the patient will retain their normal lung function

cardiac asthma

wheezing precipitated by decompensated heart failure

cough variant asthma

predominant symptom is cough instead of wheezing

exercise induced asthma

bronchoconstriction begins during exercise or within 3 minutes after its end, peaks within 10-15 minutes and then resolves after 60 minutes

caused by the airways attempting to humidify an increased volume of expired air during exercise

how often do daytime symptoms of intermittent, mild, moderate and severe asthma occur?

intermittent: ≤ 2 days/week

mild: > 2 days/week but not daily

moderate: daily

severe: throughout the day

how often do nighttime awakenings occur with intermittent, mild, moderate and severe asthma?

intermittent: ≤ 2x/month

mild: 3-4x/month

moderate: > 1x/week but not nightly

severe: often 7x/week

dosage of SABAs for intermittent, mild, moderate and severe asthma

intermittent: ≤ 2 days/week

mild: > 2 days/week but not > 1x/day

moderate: daily

severe: several times per day

level of interference with normal activity in intermittent, mild, moderate and severe asthma

intermittent: none

mild: minor limitation

moderate: some limitation

severe: extreme limitation

lung function (FEV1) in intermittent, mild, moderate and severe asthma

intermittent: FEV1 > 80% predicted

(normal FEV1 between exacerbations)

mild: FEV1 ≥ 80% predicted

moderate: FEV1 > 60% predicted

severe: FEV1 < 60% predicted