CVR 21 biochem of lung Flashcards
What happens to elastase when you smoke?
ZAAT mutation activates it causing proteolysis leading to tissue damage and emphysema
How do we treat patients with alpha 1 antitrypsin deficiency
Purified AAT before damage which restores anti neutrophil elastast activity and slow loss of function but has no effect on pulmonary gain.
What does smoking do wot alpha 1 antitrypsin?
methionone 358 oxidises which effects the binding ability of elastase leading to emphysema
How does gain of function mutations come about in alpha 1 anti
accumulation of ZAAT polymers in lumen
What does a Z mutation do on alpha 1 anti?
Deficiency of AAT in lung polymerasation reaction between chains preventing it from being released from hepatocyte
What does a S mutation do?
reduced Serpin activity
What is a pIttsburg mutation?
Impairs AAT acting on serpin leading to clotting disorder
What does alpha 1 antitrypsin disorders do?
Reduce AAT, increasing activity of elastase damaging alveoli causing hard breathing emphysema COPD and is progressive with liver cirrhosis.
What does AAT do?
met 358 site reacts with elastase in suicide raction inhibitiion protease
Interpleural pressure on inhalation
decreases.
What is elastic recoil?
inversely related to lung compliance and is the rebound of lungs.
What happens if elastase inreases
elastin decreases and elasticity decreases causing emphysema
What is neonatal respiratory distress syndrome?
rapid breathing in newborn with sternal retraction. 1-2% newbornds with 20% contribution to neonate death. Correlates with suractant.
What tests are used to assess suractant in amniotic fluid?
Lecithin sphingmyelin
phosphatidyglycerol
Surfactant/albumin ratio
How do we treat NRDS
mother gets corticosteroids to increase enxymeatic activity of phosphatase and phosphatidic acidfor suracacnt synthesis.
Neonate gets exogenous surfactant immediately at birth
Oxygen
CPAP IV salts and sugar
What is surfactant
Comes from type 2 alveolar cell. Develope into tubular myelin. Either degraded or recylced. Proteins that are linked to surface tension phosphilipid packaging and invovled in defence. Prevents collapse and increases compliance
What are the four suractants assosiated proteins
SP-A SP -B SP-C SP-D
How is a pulmonary surfactant formed
phoshatidycholine gains palmitate forming DPPC which joins apolipoproteins orming unique lipoprotein found only in lung
Whats the strongest component of the surfactant
DPPC due to its apolar tail being less bent
What does alveolar interdependence mean
each alveoli is surrounded by others and when one collapses the others stretch and distend to exert an expanding force on the collapsing one.
What is compliance
ability of lungs and thorax to expand
What is the hysteresis
air water surface tension occuring at the beginning of inflation
What cell is responsible for gas exchange
Type 1 pneumocytes and is unable to replicate
What do pulmonary endothelial cells produce
vasoactive peptides like TPA of ACE 1 and 2 inactivation of bradykinin which is a vasodilator.
Controls blood flow and pressure and viscisoty
What do goblet cells do?
Secrete mucus. Present from bronchioles up in the epithelium. Increased in CF
What do mast cells do?
Speed immune response. Rich in heparin and histamine. Asthma importance causing bronchoconstriction and mucus.
What do lung macrophages do?
immune defence. phagocytosis cell turnover. Antimicrobiall. Antiviral.
What do smooth muscle cells do?
control diameter and tension of bronchi. Produce cytokine IL5 and IL13
What are large alveoloar and flat alveolar type
Large = Type 2 Flat = Tyype 1
Which is their more of cell types in alveloar
Type 1.
Type 2 is 5%
