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Anatomy of the Individual > Laterality > Flashcards

Laterality Flashcards

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1
Q

What percentage of the population have minor anatomical anomalies?

A

7-41%

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2
Q

What percentage of the population have major anatomical anomalies?

A

2-3%

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3
Q

What is the chance of an infant having a major anomaly if they have no minor anomalies?

A

1%

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4
Q

What is the chance of an infant having a major anomaly if they have 3 or more minor anomalies?

A

20%

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5
Q

What is the name for standard anatomy?

A

Situs solitus

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6
Q

How does asymmetry of unpaired organs arise in situs solitus?

A

Embryonic primordia form in midline then undergo complex movements
May involve initial bilateral pairs

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7
Q

How does asymmetry of paired organs arise in situs solitus?

A

Right and left forms depend on morphology and NOT position

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8
Q

Give examples of asymmetric paired organs in situs solitus

A

Lungs

Cardiac appendages

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9
Q

Asymmetry of paired and unpaired organs in situs solitus is directional. What does this mean?

A

Consistent with reference to cranial/caudal and dorsal/ventral axis

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10
Q

What is situs?

A

Directional asymmetry

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11
Q

What is heterotaxia?

A

Laterality disorders

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12
Q

What is situs inversus?

A

A global situs defect
Mirror image of organs:
- Relative positional relationships maintained
- Therefore everything works and functions normally

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13
Q

What is the incidence of situs inversus according to Fulcher and Turner, (2002)?

A

1 in 6000-8000 live births

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14
Q

What is situs ambiguus?

A

Asymmetry of unpaired organs
At least one organ with reversed orientation along L/R axis
Everything else situated normally

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15
Q

What is the incidence of situs ambiguus?

A

1 in 10,000 live births

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16
Q

What is isomerism?

A

Asymmetry of a pair organ defect either:

  • In isolation OR
  • With situs ambiguus
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17
Q

What can left isomerism also be called?

A

Situs ambiguus with polysplenia

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18
Q

What are the features of left isomerism?

A

Heart has 2 long, narrow atrial appendages
Both lungs bi-lobed
Long hyparterial bronchi (ie. inferior to pulmonary arteries)
Polysplenia

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19
Q

What is right isomerism also called?

A

Situs ambiguus with asplenia

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20
Q

What are the features of right isomerism?

A

Heart has 2 pyramidal atrial appendages
Both lungs are tri-lobed
Short eparterial bronchi (ie. superior to pulmonary arteries)
Asplenia

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21
Q

What is the structure of the liver in both left and right isomerism?

A

Midline (usually)

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22
Q

If situs inversus totalis ‘works’ just as well as situs solitus, how much of the population would you expect it to be seen in?

A

50%

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23
Q

What might establish the cranial/caudal axis of solitus initially?

A

Gravity

Sperm entry site

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24
Q

What defects does cadmium induce in rats and mice? (Reference?)

A

Left limb defects in rats
Right limb defects in mice
(Layton and Layton, 1979)

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25
What is Hensen's node?
Transient, local thickening of blastoderm
26
What is step 1 in establishing the L/R axis?
Break the global embryological symmetry and create a centre of information
27
How does step 1 in establishing the L/R axis arise?
Cilia on the dorsal surface of the node push molecules in the yolk sac cavity preferentially to the left in the developing embryo
28
What mutated proteins/genes in mice results in impaired nodal flow and hence result in laterality disorders?
Polaris iv inv Kif3B-/-
29
Genes for what motor proteins can affect ciliogenesis or cilia motility and hence may result in laterality disorders?
Kinesins | Dyneins
30
What happens in right flow is artificially induced in the node of wild type mice?
Situs inversus results
31
In mice with no intrinsic nodal flow, what happens?
Flow can be induced artificially
32
What is primary ciliary dyskinesia and what can it result in?
Absence or dysmotility of respiratory cilia: | - Results in recurrent respiratory infections
33
What percentage of patients with primary ciliary dyskinesia have situs inversus? What is this disorder called?
50% | Kartagener syndrome
34
What are the 3 mutant genes associated with primary ciliary dyskinesia and what do they code for?
DNAI1 - Dynein intermediate chain | DNAH5 and DNAH11/LRD - Dynein heavy chain
35
What do mice with lrd (left/right dynein) have?
Only situs inversus | No primary ciliary dyskinesia
36
What is step 2 in the determination of left/right axis?
L/R info propagated and spread to outlying tissues | Nodal moves to left lateral plate mesoderm by diffusion or facilitated transport
37
What does nodal do in the left lateral plate mesoderm during step 2?
Triggers genes asymmetrically expressed in left LPM Activates Activin receptors: - AtRIB - ActRIIB
38
What activates transcription during step 2 in establishing the L/R axis?
Nodal (auto-regulation) Lefty-genes pitx2
39
What restricts step 2?
Time | Space
40
What regulates step 2? How?
Lefty genes: | - Competitive binding feedback inhibitors
41
What does maintenance of asymmetry during step 2 depend on and what structures provide this?
``` Depends on: - Intact midline for mediation - Chemical/Physical barrier Provided by: - Notochord - Floorplate ```
42
Why might dicephalus thoracophagus conjoined twins display laterality disorders?
Primitive streaks are parallel: | - No barrier between right LPM of left embryo and left LPM of right embryo
43
Why do craniophagi conjoined twins rarely have laterality disorders?
No LPM fusion
44
What human nodal gene mutations are seen in <3% of patients with heterotaxia?
ACVR2B LEFTYA CFC1
45
When is nodal crucial?
During gastrulation prior to LPM
46
What happens in specimens with homozygous spatiotemporal differences in Nodal levels?
They lack mesoderm and die
47
What happens in specimens with heterozygous spatiotemporal differences in Nodal levels?
They complete gastrulation and develop heterotaxia
48
What is step 3 in the development of the L/R axis?
Signals passing to and being recognised by organ primordia | Asymmetric morphogenesis
49
What happens to unpaired organs during step 3? Give examples
Displace from midline (eg. liver) | Unilaterally regress from a bilateral pair (eg. aorta)
50
What happens to paired organs during step 3? Give an example
Direct translation of L/R signal (eg. lungs)
51
What protein/gene may be responsible for recognition of the signals during step 3?
Pitx2
52
What results in loss of function of the Pitx2 protein in mice?
Right pulmonary isomerism | Asymmetric morphogenesis of multiple organs
53
Is heterotaxia genetically heterozygous or homozygous?
Heterozygous
54
What environmental factor is linked to left isomerism?
Maternal diabetes
55
What happens when mice are exposed to retinoic acid in utero?
Laterality disorders result as morphogen is transported across node
56
What does retinoic acid signalling act in response to?
Asymmetric organs
57
What does retinoic acid signalling do?
Allows for: - Symmetric somite development - The formation of bilateral symmetry in ribs and vertebrae
58
How can laterality disorders affect clinical situations?
Can complicate diagnosis and treatment: | May alter surgical interventions
59
What investigations are important in laterality disorders?
Imaging for: - Diagnosis - Treatment
60
Regarding left lower quadrant pain in individuals with situs inversus, what percentage of patients in a study by Nelson et al., (2001): A) Went undiagnosed B) Were misdiagnosed C) Were seen again by surgeon
A) Undiagnosed = 24-41% B) Misdiagnosed = Up to 30% C) Seen again by surgeon = Up to 12%
61
What issues did Fulcher and Turner, (2002) discuss can arise with situs inversus and lymphoma?
Multiple enlarged nodes around aorta IVC on left Large node to right of aorta mistaken for IVC: - Biopsy issues especially if isolated polysplenia
62
Describe the case study by Fang et al., (2009). (Pacemaker)
46 year old female with situs inversus and dextrocardia Atrial and ventricular leads into right atrium and ventricle via right subclavian vein: - Extra angle on leads due to abnormal SVC course and reversed heart - Longer procedure
63
How could situs inversus be compensated for in pacemaker insertion?
Invert fluoroscopic image to simulate situs solitus
64
When was the first situs inversus heart-lung transplant?
1989
65
How did Deuse and Rietz, (2009) compensate for transplanting a levocardic heart into a patient with situs inversus and dextrocardia?
Took extra SVC from donor Left in recipient: - Generous atria - IVC - Full SVCs Innominate donor vein connected recipient's left SVC with right atrium Recipient's right SVC connecting directly to right atrium Extra aorta to allow bending under innominate vein Pericardium left open to allow levocardia position

Anatomy of the Individual (10 decks)

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