PathWiki: Respiratory: Slides 4-5

Slide Description (from manual): This lung is from a patient who had α-1- antitrypsin deficiency, showing severe panlobular (aka. panacinar) emphysema.

Slide Description (from manual): This is a histologic section of lung showing severe emphysema.

Modified Soup

What are we looking at? Slide 4 is a slide using contrast medium injected in the pulmonary vessels to better demonstrate the enlarged alveoli. The enlarged alveoli are the darker black spots in the slide. (notice how they are distributed throughout the slide vs at a single focus.) Slide 5 is a histology H&E slide showing enlarged alveoli with septal destruction. A diagnosis of emphysema is made based on the morphology of the lung. Compare this to chronic bronchitis which is diagnosed on the basis of clinical symptoms.

What is the morphology (gross, structural, histological)? Dependent on the type of emphysema. Remeber these changes are irreversible!

Panacinar emphysema --> Pale, volumous lungs, that can obscure the heart. The acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli. Tends to affect the lower lobes.

Centriacinar emphysema --> Less volumous and pinker than panacinar emphysema. Generally affects the upper two thirds of the lungs more severely than lower third. Central parts of the acini, respiratory bronchioles, are affected with normal and emphysematous airspaces within the same lobule. Tends to affect the upper lobes, especially the apical regions.

What is the cause (etiology)? Genetic and environment. There is a clear association between heavy cigarette smoking and emphysema.

What is the mechanism of disease (pathogenesis)? The current thinking is that there are two critical imbalances which can cause emphysema - protease/antiprotease and oxidant/antioxidant imbalance.

Protease/antiproteased imbalance --> Genetic α-1- antitrypsin deficiency. α-1- antitrypsin is normally present in serum, tissue fluids, and macrophages. It is a major inhibitor of proteases, especially elastase which is secreted by neutrophils during inflammatory reactions. Those with the genetic mutation for this protein have a marked decrease in α-1- antitrypsin in their serum. This tends to lead to emphysema in the lower lobes of the lung.

1. Neutrophils normally remain within the perpheral capillaries.

2. Stimulus increases number of leukocytes in the lung or release of their granules containing protease.

3. Low levels of α-1- antitrypsin --> destruction of elastin goes unchecked --> emphysema

Oxidant/antioxidant imbalance --> Normal lung contains healthy complement of antioxidants to minimize oxidant damage. Tobacco smoke contains reaxctive oxygen species which deplete these antioxidants resulting in tissue damage. Activated neutrophils also add to the pool of reactive oxygen species. A secondary consequence of oxidative injury is inactivation of native antiproteases which results in a functional α-1- antitrypsin deficiency even if the patient doesn't have the genetic mutation for it. This tends to form emphysema in the upper lobes of the lung.

What are the signs and symptoms? Dyspnea and tachypnea are usually the first symptom which begins insidiously but is steadily progressive. Weight loss is usually apparent which can be confused with the same weight loss caused by cancer. Wheezing and coughing may be initial complaints for those with underlying bronchitis. Decreased FEV1 to FVC ratio. In cases of "pure" emphysema without bronchitis the patient will be barrel chested, dyspneic, prolonged expiration, and sitting forward in a hunched over position --> pink puffers. Blue bloaters --> Those with extreme emphysema with chronic bronchitis usually have less prominent dyspnea and respiratory drive. They tend to retain more carbon dioxide and for an unknown reason are obese. Tend to seek help after the onset of CHF and associated edema.

Additional Information:

Related to emphysema

Compensatory emphysema- Compensatory dilation of alveoli in response to loss of lung substance. eg lung resection

Senile emphysema- Overdistented lungs of elders due to age-related changes in lung geometry. No tissue destruction. Senile hyperinflation is a better term to use.

Obstructive overinflation- Lung expands because air is trapped within it. Commonly by a tumor or foreign object. Can be life threatening.

Mediastinal (interstitial) emphysema - Entrance of air into the connective tissue strona of the lung. May occur spontaneously with sudden increase in intra-alveolar pressure that causes a tear in the interstitium. At risk are those on respirators with partial obstructions or those who suffer a perforation injury. The trapped air may literally cause the patient to blow up like a ballon - head and neck swelling, with crepitation all over the chest. Air is spontaneously reabsorbed when the site of entry is sealed.

Basic Information

Relevant Robbins

Robbins 459-463

Three Main Points

1. Emphysema is defined as as having both enlargement of the alveolar space and destruction of tissue.

2. Two important theories to the cause of emphysema: protease/antiprotease & oxidant/antioxidant imbalance

3. Centrilobular emphysema --> upper lobes, Panlobular emphysema --> lower lobes

Lab Questions:

1. What is the role of α-1 antitrypsin in relation to emphysema?

α-1- antitrypsin is normally present in serum, tissue fluids, and macrophages. It is a major inhibitor of proteases, especially elastase which is secreted by neutrophils during inflammatory reactions. Those with the genetic mutation for this protein have a marked decrease in α-1- antitrypsin in their serum. The result is the unchecked desctruction of elastin within the alveoli. Deficiency in this protein tends to cause emphysema in the lower lobes of the lung as compared to centrilobular emphysema which happens in the apical region of the lung.

2. What organs are affected by alpha-1 antitrypsin deficiency?

Lungs - emphysema in adults

Liver - liver disease. Mostly hepatitis which in rare cases can lead to cirrhosis. Most common genetic cause of liver disease in children.

3. What is a bulla? What complication can it give rise to?

Essentially a bulla is a bubble. Emphysematous bullae are a sequeale of distal acinar emphysema. They are usually seem in the upper two thirds of the lung as grossly appearing cystoid lesions. They can lead to compmression of lung tissue resulting in impaired pulmonary functioning and respiratory distress. They also are the underlying reason for spontaneous pneumothorax in healthy young adults.

Vignette

Your patient is a 61 year old man with a 50 pack year history of smoking. He's barrel-chested, hunched over the chair in the examination room and is tachypneic. Lung function tests show that he has a decreased FEV1 to FVC ratio. Blood gases show normal levels of oxygen and he has normal hemoglobin. Serum levels of α-1 antitrypsin are normal. What is the most likely explaination for this patient's clinical symptoms? Where do you suspect to see any morphological changes?

*Emphysema due to an oxidant/antioxidant imbalance leading to epithelial damage and functional antitrypsin deficiency. The common site for emphysematous change in smokers without an antitrypsin deficiency is within the apical regions of the lungs.