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Anatomy of the Individual > Laterality > Flashcards

Laterality Flashcards

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
Q

What is Hensen’s node?

A

Transient, local thickening of blastoderm

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26
Q

What is step 1 in establishing the L/R axis?

A

Break the global embryological symmetry and create a centre of information

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27
Q

How does step 1 in establishing the L/R axis arise?

A

Cilia on the dorsal surface of the node push molecules in the yolk sac cavity preferentially to the left in the developing embryo

28
Q

What mutated proteins/genes in mice results in impaired nodal flow and hence result in laterality disorders?

A

Polaris
iv
inv
Kif3B-/-

29
Q

Genes for what motor proteins can affect ciliogenesis or cilia motility and hence may result in laterality disorders?

A

Kinesins

Dyneins

30
Q

What happens in right flow is artificially induced in the node of wild type mice?

A

Situs inversus results

31
Q

In mice with no intrinsic nodal flow, what happens?

A

Flow can be induced artificially

32
Q

What is primary ciliary dyskinesia and what can it result in?

A

Absence or dysmotility of respiratory cilia:

- Results in recurrent respiratory infections

33
Q

What percentage of patients with primary ciliary dyskinesia have situs inversus? What is this disorder called?

A

50%

Kartagener syndrome

34
Q

What are the 3 mutant genes associated with primary ciliary dyskinesia and what do they code for?

A

DNAI1 - Dynein intermediate chain

DNAH5 and DNAH11/LRD - Dynein heavy chain

35
Q

What do mice with lrd (left/right dynein) have?

A

Only situs inversus

No primary ciliary dyskinesia

36
Q

What is step 2 in the determination of left/right axis?

A

L/R info propagated and spread to outlying tissues

Nodal moves to left lateral plate mesoderm by diffusion or facilitated transport

37
Q

What does nodal do in the left lateral plate mesoderm during step 2?

A

Triggers genes asymmetrically expressed in left LPM
Activates Activin receptors:
- AtRIB
- ActRIIB

38
Q

What activates transcription during step 2 in establishing the L/R axis?

A

Nodal (auto-regulation)
Lefty-genes
pitx2

39
Q

What restricts step 2?

A

Time

Space

40
Q

What regulates step 2? How?

A

Lefty genes:

- Competitive binding feedback inhibitors

41
Q

What does maintenance of asymmetry during step 2 depend on and what structures provide this?

A 
Depends on:
- Intact midline for mediation
- Chemical/Physical barrier
Provided by:
- Notochord
- Floorplate
42
Q

Why might dicephalus thoracophagus conjoined twins display laterality disorders?

A

Primitive streaks are parallel:

- No barrier between right LPM of left embryo and left LPM of right embryo

43
Q

Why do craniophagi conjoined twins rarely have laterality disorders?

A

No LPM fusion

44
Q

What human nodal gene mutations are seen in <3% of patients with heterotaxia?

A

ACVR2B
LEFTYA
CFC1

45
Q

When is nodal crucial?

A

During gastrulation prior to LPM

46
Q

What happens in specimens with homozygous spatiotemporal differences in Nodal levels?

A

They lack mesoderm and die

47
Q

What happens in specimens with heterozygous spatiotemporal differences in Nodal levels?

A

They complete gastrulation and develop heterotaxia

48
Q

What is step 3 in the development of the L/R axis?

A

Signals passing to and being recognised by organ primordia

Asymmetric morphogenesis

49
Q

What happens to unpaired organs during step 3? Give examples

A

Displace from midline (eg. liver)

Unilaterally regress from a bilateral pair (eg. aorta)

50
Q

What happens to paired organs during step 3? Give an example

A

Direct translation of L/R signal (eg. lungs)

51
Q

What protein/gene may be responsible for recognition of the signals during step 3?

A

Pitx2

52
Q

What results in loss of function of the Pitx2 protein in mice?

A

Right pulmonary isomerism

Asymmetric morphogenesis of multiple organs

53
Q

Is heterotaxia genetically heterozygous or homozygous?

A

Heterozygous

54
Q

What environmental factor is linked to left isomerism?

A

Maternal diabetes

55
Q

What happens when mice are exposed to retinoic acid in utero?

A

Laterality disorders result as morphogen is transported across node

56
Q

What does retinoic acid signalling act in response to?

A

Asymmetric organs

57
Q

What does retinoic acid signalling do?

A

Allows for:

  • Symmetric somite development
  • The formation of bilateral symmetry in ribs and vertebrae
58
Q

How can laterality disorders affect clinical situations?

A

Can complicate diagnosis and treatment:

May alter surgical interventions

59
Q

What investigations are important in laterality disorders?

A

Imaging for:

  • Diagnosis
  • Treatment
60
Q

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

A) Undiagnosed = 24-41%
B) Misdiagnosed = Up to 30%
C) Seen again by surgeon = Up to 12%

61
Q

What issues did Fulcher and Turner, (2002) discuss can arise with situs inversus and lymphoma?

A

Multiple enlarged nodes around aorta
IVC on left
Large node to right of aorta mistaken for IVC:
- Biopsy issues especially if isolated polysplenia

62
Q

Describe the case study by Fang et al., (2009). (Pacemaker)

A

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
Q

How could situs inversus be compensated for in pacemaker insertion?

A

Invert fluoroscopic image to simulate situs solitus

64
Q

When was the first situs inversus heart-lung transplant?

A

1989

65
Q

How did Deuse and Rietz, (2009) compensate for transplanting a levocardic heart into a patient with situs inversus and dextrocardia?

A

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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