L3 Inherited Conditions Predisposing to Respiratory Infection Flashcards
(21 cards)
Dynin arms are extending from which subunit to which ?
From subunit A of one doublet to subunit B of next doublet
What is the difference between cilia and primary cilia ?
The cilia is 9+2
Whereas
The primary cilia is 9+0
What are the Types of cilia in humans ?
- Motile cilia —
What does the beat cycle of the cilia made of ?
Two phases :
- Effective stroke
- Recovery stroke
What is the features of PCD ?
- Monogenic
- Heterogeneous
- Autosomal recessive
- 50% of people have kartagener syndrome
What is kartagener syndrome ?
It is a triad of :
- bronchiectasis
- sinusitis
- situs inversus
What are The main clinical manifestations of PCD
- Chronic inflammation of URT and LRT (due to chronic infection)
- Insufficient mucociliary clearance —> bronchiectasis
- Chronic sinusitis
- Chronic otitis media
- Male infertility
- Female sub-fertility ( can overcome it by in vitro fertilization )
- Heterotaxy
- Ectopic pregnancy
How PCD can cause heart diseases ?
By laterality defects
What are the Laterality defects associated with PCD
- Situs inversus
- Situs ambigous ( heterotaxy )
Which has two types :
* left atrial isomerism
* right atrial isomerism
How you can differentiate between left and right atrial isomerism ?
By looking to the spleen :
- left atrial isomerism
- polysplenia
- levocardia ( heart is pointing to the left )
- right atrial isomerism
- asplenia
- dextrocardia ( heart is pointing to the right )
What are the defected genes in PCD ?
- Structural ( axonemal ) genes :
- dynein arm components ( DNA5 -DNA11 )
- radial spokes head ( RSPH9 )
- dynein - nexin regulatory complexes ( CCDC40 ) - Cytoplasmic genes
- LRRC50
What is DNAH5 gene defect ?
- The most common gene defect of PCD that will lead to the absence of outer dynien arms
- It will cause infertility and situs inversus
- ciliary movement will be disorganized and uncoordinated with neighboring cilia
What is cytoplasmic LRRC50 gene defect ?
- it will lead to a defect in the cytoplasmic protein LRRC50 which is responsible on fixing the outer and inner dynein arms … so both arms will be lost
- no motility or reduced beat amplitude with with few static cilia
( we do produce the arms but we don’t have the ability to fix them )
What is RSPH9 gene defects ?
- It is a defect in the heads of the radial spokes which are responsible on stabilizing the central pair
- the radial spokes are their but can’t stabilize the central pair
- movement is stiff with circular motion
What is CCDC40 gene defects ?
- Defect in this gene will produce a defected nexin-dynein regulatory complexes ( proteins ) so both inner dynein arms and nexin are absent leading to micro-tubular disorganization
- stiff movement with low beat amplitude
- very severe
What is the DNAH11 gene defect ?
It has complete normal structure but it is more stiff, less bending
Summarize ciliary movement changes in different gene defects
DNAH5 —> disorganized + uncoordinated with neighboring cilia
DNAH11 —> stiff and less bending
RSPH9 —> stiff and circular motion
CCDC40 —> stiff and reduced amplitude
LRRC50 —> complete immotility or low amplitude
How we can diagnose PCD ?
- Ultrastructural changes in PCD: TEM
- Nasal Nitric Oxide (NO) measurement: Low in PCD patients
- High-speed video microscopy
- Immunofluorescent staining (IF) analyses
- Genetic testing for PCD
What is the defected gene in CF ? Where it is expressed?
It cysts fibrosis transmembrane conductance regulator ( CFTR ) gene that is being expressed in :
- lungs
- gut
- pancreas
What is the Patho-physiology of CF ?
There is defected Cl- secretion and increases sodium absorption that will increase water absorption also leading to increase the viscosity of the mucus and impairing the mucociliary clearance
What are the common features between PCD and CF ?
- Nasal polyps
- Chronic sinusitis
- Digital clubbing
- Chronic otitis media ( 100% in CF and 90-100% in PCD )
- FEV1 is less in PCD than in CF
