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YEAR 1 - Organisation of the Body (Anton) > 15. Embryonic Development (TT) > Flashcards

15. Embryonic Development (TT) Flashcards

1
Q

What part of which germ layer do the urinary and genital systems originate from?

A

Intermediate mesoderm

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2
Q

Compare excretion in humans and aquatic vertebrates, and how this relates to the structure of the urinary system.

A

Aquatic vertebrates:

  • Ammonia is used mostly, since it is simple to produce
  • However, it is toxic, so lots of water is required to excrete it, and therefore it is only really used by aquatic animals

Humans:

  • Urea is used
  • The kidney is more important in terrestrial vertebrates because it allows excretion while conserving animals
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3
Q

Summarise the two important functions of the kidney.

A
  1. Removal of waste
  2. While conserving water
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4
Q

What are the three stages of kidney development in mammals?

[EXTRA]

A

There is a progression of 3 stages:

  1. Pronephros
  2. Mesonephros
  3. Metanephros

These form in the craniocaudal sequence.

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5
Q

What happens to each of pronephros, mesonephros and metanephros in humans?

A
  • Pronephros and mesonephros degenerate during embryogenesis
  • Metanephros forms the definitive kidney (IMPORTANT)
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6
Q

The definitive kidney forms from…

A

The metanephros of intermediate mesoderm.

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7
Q

What is the cloaca?

A
  • It is the point at the caudal end of the embryo through which the urinary, intestinal and genital systems exit.
  • Humans have a cloaca during development, but it later partitioned into a separate rectum and bladder.
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8
Q

What are the mesonephric ducts in kidney development?

A
  • Two epithelial tubes that run craniocaudally along the entire embryo
  • There are formed by mesenchymal to epithelial transitions in the intermediate mesoderm
  • They drain the mesonephros in the embryo into the cloaca, and they give rise to the ureteric buds in the formation of the metanephros
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9
Q

Describe the formation of the pronephros, mesonephros and mesonephric ducts. [EXTRA]

A

Pronephros and mesonephric ducts:

  • Near the start of the 4th week, mesenchymal to epithelial transitions in the intermediate mesoderm lead to the formation of two epithelial tubes, known as mesonephric ducts. They begin in cervical region, but inductive mechanisms cause them to extend in the caudal direction.
  • Simultaneous to this formation, the pronephros forms also form in the cervical region of the intermediate mesoderm, medial to the mesonephric ducts.
  • The pronephros takes the form of a series of hollow epithelial buds, but it is not functional and within two days of its formation, it begins to degenerate.

Mesonephros

  • As the mesonephric ducts develop caudally, they induce the intermediate mesoderm caudal to the pronephros to form into mesonephric buds, which begins around day 25.
  • Within each bud, mesonephric tubules form, forming a total of around 40 tubule pairs, although earlier tubules regress as more caudal ones develop, and by the end of the 5th week there are only 20 pairs (in the lumbar region).
  • Each of these tubules is similar in structure and function to the nephrons in the definitive adult kidney. The most cranial mesonephric tubules fuse on their lateral side to the mesonephric ducts, which have extended towards the cloaca and fused with its ventral side (around day 26), draining the tubules.
  • The tubules are functional and produce urine between approximately the 6th and 10th weeks, although in females they regress. In males, the mesonephric duct forms the genital duct in the adult.
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10
Q

When does the metanephros start to develop?

A

Around the end of week 4 (day 28).

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11
Q

What are the two portions of the definitive kidney? What part of the intermediate mesoderm is each derived from?

A
  • Excretory portion (nephron) -> Metanephric mesenchyme
  • Collecting portion -> Ureteric bud
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12
Q

Describe the formation of the metanephros.

A
  • The metanephros begins to develop around the very end of week 4 with the formation of the ureteric buds at the caudal section of each mesonephric duct. This occurs due to induction from the metanephric mesenchyme, which is intermediate mesoderm in the sacral region.
  • The ureteric buds each enter the metanephric mesenchyme occurs by day 32.
  • The epithelial-mesenchymal interaction between the ureteric bud (epithelial) and metanephric mesenchyme induces the ureteric bud to begin branching (branching morphogenesis). Bifurcation continues until around the 32nd week.
  • There is also a reciprocal induction, which is the way in which the ureteric buds induce the mesenchyme to form glomerular units.
  • The branching forms the ureter, pelvis, major and minor calyces, and collecting tubules (see other flashcard for this)
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13
Q

What two tissues does the metanephros form from?

A

Ureteric bud and surrounding mesenchyme

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14
Q

Describe how these structures are formed by the branching of the ureteric bud:

  • Pelvis
  • Major and minor calyces
  • Ureter
  • Collecting ducts
A
  • Ureter -> This is the part of the ureteric bud before any branching occurs
  • Pelvis -> Formed by the first bifurcation
  • Major calyces -> After 4 generations of branching by simple bifurcation, the branches formed coalesce to form the major calyces
  • Minor calyces -> Further branches coalesce to form the minor calyces
  • Collecting ducts -> Form at the tips of the minor calyces by further branching
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15
Q

Is the process of branching of the ureteric bud continuous?

A

No, there are periods of branching and periods of coalescing (which are required to form the calyces).

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16
Q

Describe how nephrons develop in the metanephros.

A
  • First appear around 10 weeks, in the distal region of the metanephros
  • The ampullae at the tip of each collecting duct interact with adjacent mesenchyme and induce nephron formation.
  • Nephric vesicles form ‘comma’ and then ‘S’ shaped tubules. These ultimately form a Bowman’s capsule, proximal convoluted tubules and loops of Henle.
  • Ampullae extend deeper into cortex and continue to branch, inducing the formation of more nephrons .
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17
Q

What is Wt1 and what is its importance?

A
  • Wilm’s tumour suppresor gene
  • Expressed in the early metanephric mesenchyme for induction of other tissues
  • It is required for the initial formation of the ureteric bud from the mesonephric duct
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18
Q

What is Wilm’s tumour?

A
  • A form of kidney cancer that is common in children
  • It is frequently caused by alterations to the Wt1 gene
  • Results in a palpable mass, pain in the abdomen, poor appetite and fever.
  • It is highly responsive to treatment.
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19
Q

Aside from Wt1, what are two factors that are important in inductive processes in kidney development? What does each do?

A
  • Ret (expressed in the ureteric bud) -> Important in branching morphogenesis + Transduces extracellular signals to inside the cell by phosphorylating tyrosine in downstream targets
  • Gdnf (expressed in the metanephric mesenchyme) -> Important in branching morphogenesis + It is the ligand for Ret receptor

They have strikingly complementary expression in the two tissues.

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20
Q

When in development do the kidneys ascend and how does this happen?

A
  • Between the 6th and 9th weeks, the metanephric kidney ascends to the lumbar region from its original caudal position
  • Caused primarily by differential growth -> The kidneys stay in place while the embryo lengthens
  • It remains retroperitoneal (behind the peritoneum)
  • It changes its blood supply to progressively higher segmental arteries (branches from the aorta) as it ascends
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21
Q

What happens when a kidney fails to ascend in development?

[EXTRA]

A

It can result in a pelvic kidney.

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22
Q

What is horseshoe kidney?

[EXTRA]

A

When the kidneys fuse before they ascend, so they are trapped under the inferior mesenteric artery.

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23
Q

What does the bladder form from?

A
  • Lower end of allantois
  • Caudal ends of mesonephri ducts
  • Urogenital sinus
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24
Q

What is the allantois?

A

It is an outgrowth from the hindgut.

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25
Q

How does the allantois relate to the cloaca?

A

The lower allantois is continuous with the cloaca because the allantois is an outgrowth of the hindgut.

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26
Q

What are the parts of the cloaca and how are they formed?

A
  • Urogenital sinus -> Goes on to form part of the bladder (UG sinus is continuous with the allantois)
  • Anorectal canal -> Connected to the GI tract

The urorectal septum separates these two.

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27
Q

Describe the formation of the bladder.

A
  • The urogenital sinus (more cranial part of the cloaca) grows larger, forming part of the bladder
  • The urorectal septum grows to separate the urogenital sinus from the anorectal canal (meaning that in the future there is a separate exits for the urogenital and digestive tracts)
  • The lower part of the allantois also goes on to form part of the bladder because it is continuous with the urogenital sinus
  • The ends of the mesonephric ducts merge into the developing bladder on the dorsal side, bringing the opening of the ureter into the bladder wall
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28
Q

Describe the formation of the trigone on the bladder.

A
  • Between weeks 4 to 6, the distal parts of the mesonephric duct and forming ureter are absorbed into the endoderm-lined bladder, forming the mesodermal trigone.
  • However, UB derived cells subsequently undergo apoptosis and are replaced by bladder derived cells -> This means that the lining of the bladder is ultimately mostly endodermal, despite having had mesodermal contribution at some point
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29
Q

Describe the formation of the urethra.

A
  • While the superior portion of the urogenital sinus forms the bladder, around day 53 the inferior portion forms the pelvic urethra
  • In males, the pelvic urethra forms the membranous urethra in females, and the membranous and prostatic urethra in males
  • The distal expansion of the urogenital sinus forms the vestibule of the vagina in females, and the penile urethra in males
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30
Q

When is the development of the metanephric kidney finished?

A

It is functional by 12 weeks.

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31
Q

What do the kidneys produce in the embryo?

A

The amniotic fluid -> Supports the foetus from mechanical shock

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32
Q

What is the foetal excretory organ?

A

Placenta -> Nitrogenous waste in the fetal blood is transferred across the placenta to the maternal blood

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33
Q

Describe a morphological change in the kidneys that occurs after birth.

A
  • Before birth, the kidneys produce a large amount of dilute urine
  • After birth, the loops of Henle lengthen so that the urine becomes more concentrated
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34
Q

For development of the genital system, see flashcards on section 13.

A

Do it!

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35
Q

What germ layer is the gut tube formed from predominantly?

A

Endoderm

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36
Q

The gut tube is formed from the endoderm. How is this germ layer formed?

A

During gastrulation, cells of the epiblast colonise the hypoblast to form the endodermal layer.

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37
Q

Describe the formation of the primitive gut tube and how this then differentiates.

A

During the 4th week, embryonic folding occurs:

  • The amnion folds down around the embryo, squeezing the neck of the yolk sac.
  • The anterior edges of the amnion fuse, forming the body cavity and the gut tube is the endoderm-lined space inside.
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38
Q

Draw how the yolk sac changes shape during development.

A
  • Initially, the yolk sac has a goldfish bowl shape
  • When the foregut and hindgut form due to embryonic folding, the tube narrows down leaving a vitelline duct
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39
Q

What does the vitelline duct connect in development?

A

Yolk sac and the mid-part of the gut tube.

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40
Q

The fusion of the amnion’s anterior sides during embryonic folding surrounds the embryo in what? Show this on a diagram.

A

It surrounds the embryo in amniotic fluid.

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41
Q

Label this.

A
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42
Q

Embryonic folding results in the formation of what cavity in the embryo?

A

Intraembryonic cavity a.k.a. coelom or coelomic cavity

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43
Q

What germ layer is the dorsal mesentry made of?

A

Mesoderm

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44
Q

Of what germ layer origin is the lining of the gut tube?

A

Endodermal

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45
Q

After embryonic folding, what are the two types of mesoderm in the coelomic cavity?

A
  • Visceral (splanchnic) mesoderm lines the outside of the gut tube
  • Parietal mesoderm lines the body wall
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46
Q

After embryonic folding, what is the inner and outer lining of the gut tube?

A
  • Inner lining -> Endoderm
  • Outer lining -> Visceral mesoderm
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47
Q

What structure partions the coelomic cavity and what does it go on to form? [IMPORTANT]

A
  • Septum transversum
  • It forms the diaphragm
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48
Q

Which side of the body wall is the gut tube attached to and what by?

A
  • Dorsal body wall, by the dorsal mesentry
  • It is also attached to the ventral body wall at the level of the stomach and liver by the ventral mesentery, within which the liver develops
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49
Q

Across which cavity does the septum transversum form?

A

Coelomic cavity

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50
Q

Draw the formation of the septum transversum.

A

Note that the gaps at the posterior side are filled by pleuroperitoneal membranes that complete the septum, which forms the future diaphragm.

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51
Q

What are the three main sections of the gut tube? What does each comprise?

A
  • Foregut
    • Stomach
    • Liver
    • Pancreas
    • Part of the duodenum
  • Midgut
    • Small bowel
    • Up to halfway along the descending colon
  • Hindgut
    • Last part of the descending colon
    • Rectum
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52
Q

Draw a diagram to show the different structures in each segment of the gut in the developing embryo.

A
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53
Q

Describe the important structures of the gut tube that are found at the each end of the gut tube.

A

At the rostral end:

  • Gut tube opens at the mouth (stomodeum)
  • Buccopharyngeal membrane -> This is a segment where the endoderm is in direct contact with the ectoderm

At the caudal end:

  • Gut tube opens at the anus (cloaca)
  • Cloacal (anal) membrane -> This is a segment where the endoderm is in direct contact with the ectoderm.
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54
Q

What does the cloacal (anal) membrane end up as in after development?

A

Hilton’s white line in the anal canal.

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55
Q

What are the two important sites of direct contact between the endoderm and ectoderm in the gut tube that you need to know about?

A
  • Buccopharyngeal membrane (at cranial end)
  • Anal (cloacal) membrane (at caudal end)
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56
Q

How does patterning of the gut tube occur?

A
  • Differential expression of hox genes in the early developing gut mesoderm -> Causes differentiation of the mesoderm.
  • Differences in gut epithelial structure are thought to arise by interactions between the mesoderm and endoderm -> i.e. the mesenchymal structures induce the formation of corresponding epithelial structures
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57
Q

How many hox genes are involved in patterning of the gut tube?

A

In mammals there are four sets (hox a-d) and they are expressed in a rostral-to-caudal pattern along the developing gut tube.

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58
Q

What is some experimental evidence for the importance of hox genes in patterning the gut tube?

A

In situ hydridisation can be used to show the different levels of hox gene expression at different points along the gut tube.

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59
Q

In what part of the gut tube are hox genes expressed? What is the result of this?

A
  • In the mesoderm that surrounds the endodermal lining of the gut tube
  • This means that the mesoderm induces the endoderm to form different structures
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60
Q

In gut tube development, is it the surrounding mesoderm that patterns the endodermal lining of the gut tube, or is it vice versa? What is the evidence for this?

A
  • This means that the mesoderm that surrounds the endodermal lining of the gut tube induces the endoderm to form different structures
  • The evidence from this comes from placing a section of mesoderm from a different part of the body near a section of endoderm from a different part of the gut tube -> The mesoderm induces formation of the endoderm from the corresponding organ
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61
Q

Describe the development of the very cranial end of the gut tube (i.e. the pharynx).

A
  • The mouth forms at the rostral end of the gut tube at the stomodeum
  • The pharyngeal specialisations (e.g. tongue) develop from the pharyngeal arches and pouches
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62
Q

Remember to revise the structures that are derived from the pharyngeal pouches that relate to the gut tube differentiation.

A
  • The pharyngeal pouches are endodermal structures, so they are involved in the formation of many of the upper gut tube structures.
  • See the flashcards on this.
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63
Q

What are the buccopharyngeal and cloacal membranes?

A
  • Points of direct contact between the endoderm and the ectoderm
  • They go on to rupture and form the two ends of the alimentary tract.
  • At the rostral end, the gut tube opens at the stomodeum (the site of the future mouth), while at the caudal end it opens at the cloaca (the future anus).
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64
Q

Describe the formation of the lungs. [IMPORTANT]

A
  • Just caudal to the pharyngeal pouches, there is a single midline bud from the gut tube that goes on to form the lungs.
  • Just like in patterning of other gut tube structures, the surrounding mesoderm is involved in patterning the endodermal lining of the gut tube:
    • Wnt signals from the surrounding mesoderm cause local up-regulation of Nkx2.1 in the endoderm
    • This Nkx2.1 is the first signal of bud formation
    • Bud growth is stimulated by FGF10 (and BMP4 helps)
    • Shh confines action of the FGF10 to the tip of the bud, so that there is outgrowth rather than growth in all directions
    • When the bud is of a certain size, ECM deposition (of fibronectin and HSPG) along the midline causes branching morphogenesis
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65
Q

What is the name of the process that occurs during lung bud outgrowth? What signalling molecules allow this process to occur?

A
  • Branching morphogenesis
  • FGF10, BMP4, Shh
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66
Q

What sort of developmental abnormalities of the lungs can occur?

A

Since the lungs bud from the gut tube in development, the two may remain connected in an abnormal way. For example, the oesophagus may remain connected to the trachea at birth.

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67
Q

What defines what is foregut, midgut and hindgut in development?

A

Each section has its own blood supply.

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68
Q

Describe the blood supply to the foregut, midgut and hindgut in development.

A
  • Foregut -> Celiac artery
  • Midgut -> Superior mesenteric artery
  • Hindgut -> Inferior mesenteric artery

On the diagram, the brown is the dorsal mesentery, while the yellow is the gut tube!

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69
Q

Describe the venous drainage of the different sections of the gut.

A

It is all via the hepatic portal vein.

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70
Q

At what level is there also a ventral mesentry that connects to the gut tube? What are the different parts?

A
  • It is at the level of the stomach and liver
  • The two parts are:
    • The part between the stomach and liver -> Lesser omentum
    • The part between the liver and the anterior abdominal wall -> Falciform ligament
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71
Q

Label this.

A
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72
Q

It is worth noting that in the embryo the liver is closely apposed to…

A

The diaphragm.

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73
Q

Which part of the gut tube does the stomach form from and what is its blood supply?

A

Foregut -> Supplied by the celiac artery.

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74
Q

Describe the rotation of the stomach.

A

Forms from the foregut. It involves two rotations:

  • Clockwise rotation (90*) around the craniocaudal axis, with the left side of the stomach becoming anterior.
  • Anticlockwise rotation around the dorsoventral axis due to the lengthening of the left side of the stomach.
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75
Q

What structures form as a result of the rotation and expansion of the stomach?

A
  • Lesser sac
  • Greater omentum -> Fuses to the mesentery that surrounds the transverse colon.
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76
Q

What is the effect of the first stomach rotation on nerve position?

A

Moves the left and right vagus nerves to anterior and posterior position respectively.

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77
Q

Describe and draw the formation of the lesser sac, greater sac and greater omentum. [EXTRA]

A
  • The rotation of the stomach 90* clockwise causes the dorsal mesentry to start folding
  • Eventually this forms a pocket (called the lesser sac) with just a small hole (epiploic foramen) keeping it continuous with the remainder of the abdomen
  • The dorsal mesentery is also affected by this rotation and bulges out into the abdomen.
  • The two sides of the dorsal mesentery later fuse to form a sheet of mesentery attached to the greater curvature of the stomach and to the transverse colon, called the greater omentum.

Just watch this video:

https://www.youtube.com/watch?v=nTWjL69IwT0

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78
Q

Which mesenteries are the greater and lesser omenta derived from?

A
  • Greater omentum -> From the dorsal mesentery
  • Lesser omentum -> From the ventral mesentery
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79
Q

What is the greater omentum and what heppens to it?

A
  • It is sheet that forms when the dorsal mesentry is stretched by the stomach rotatation, begins to droop down and becomes double folded.
  • It then fuses with the mesentry surrounding the transverse colon.
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80
Q

When does differentiation of the gastric mucosa occur and how?

A
  • Around week 8 -> Hydrochloric acid production begins prior to birth.
  • Differentiation requires epithelial-mesenchymal interactions
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81
Q

What signalling factors are important in the differentiation of the gastric mucosa?

A
  • Hox B6 is expressed in the underlying stomach mesoderm
  • Sox9 is expressed in the differentiating epithelial layer
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82
Q

What is pyloric stenosis? What are the symptoms? [IMPORTANT]

A
  • Hypertrophy of the muscle that surrounds the pyloric sphincter
  • It can result in projectile vomiting
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83
Q

Which organs form from gut diverticula that undergo branching morphogenesis?

A
  • Liver
  • Pancreas
  • Lungs
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84
Q

What drives the formation of the liver?

A

FGF signals from the adjacent cardiac region.

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85
Q

Describe the formation of the liver.

A
  • The liver forms due to FGF signalling from the cardiac region inducing a hepatic field in the endoderm at around the level of the foregut-midgut junction
  • In the 4th week, a hepatic diverticulum develops, which gives rise to:
    • Hepatic bud
      • Forms the liver by branching morphogenesis
      • More cranial
    • Cystic bud
      • Forms the gall bladder
      • More caudal
  • Bile production starts around week 12 and the liver also has a major role in haematopoiesis in the developing embryo.
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86
Q

When does the hepatic diverticulum arise?

A

In week 4.

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87
Q

What does the expansion of the liver lead to?

A
  • As it grows into the septum transversum, the mesoderm of the septum transversum becomes the ventral mesentery.
  • The ventral mesentery will form the lesser omentum and the falciform ligament.
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88
Q

What is a major role of the liver in the embryo?

A

Haematopoiesis

89
Q

On which side of the lesser omentum do the liver bud and vasculature pass through?

A

The free caudal side.

90
Q

Describe the formation of the pancreas.

A
  • The pancrease forms from two buds:
    • Dorsal bud (due to FGF)
    • Ventral bud (due to VEGF)
  • Development involves branching morphogenesis, during which the endocrine islets begin to separate from the exocrine mass.
  • The ventral pancreatic bud rotates to fuse with the dorsal bud, producing the definitive pancreas.
91
Q

What does each of the two pancreatic buds produce?

A
  • Dorsal bud -> Head, body and tail
  • Ventral bud -> Uncinate process of the head
92
Q

Which signalling molecule induces the formation of each of the two pancreatic buds?

A
  • Dorsal bud -> FGF from the notochord
  • Ventral bud -> VEGF (indues Pdx1)
93
Q

Describe how the pancreatic buds fuse and why.

A
  • The ventral bud moves around the duodenum and fuses with the ventral bud
  • This occurs due to differential growth of the pancreas
94
Q

What is an annular pancreas? [IMPORTANT]

A

Where there is an abnormality in the fusion of the two pancreatic buds, resulting in a pancreas that constricts the duodenum.

95
Q

Is the pancreas intraperitoneal?

A

No, it becomes secondary retroperitoneal since the apposition of the pancreas and the posterior abdominal wall, results in fusion of mesenteries.

96
Q

How does the spleen form?

A
  • The spleen develops next to the pancreas within the dorsal mesentery.
  • It is not strictly associated with the gut -> It forms from MESODERM ONLY [IMPORTANT]
97
Q

Which germ layer does the spleen form from? [IMPORTANT]

A

Mesoderm only

98
Q

What are the derivatives of the midgut?

A
  • Inferior duodenum
  • Jejunum and ileum
  • Caecum and vermiform appendix
  • Ascending and proximal 2/3 of transverse colon
99
Q

What are the names for the normal position of organs in the abdomen, their total inversion and partial inversion?

A
  • Normal = Situs solitus
  • Total inversion = Situs inversus
  • Partial inversion = Heterotaxia
100
Q

Describe how assymteric development of the abdomen occurs.

A
  • Cilia in the primitive node generate left-right asymmetry.
  • This is amplified by a genetic cascade where the gene Nodal is expressed on the left side of the embryo in the lateral plate mesoderm.
101
Q

What causes the folding of the gut tube?

A

The gut tube folds due to differences in gut gene expression in the mesentry:

  • Asymmetric expression of BMP2 & Pitx2 in the gut and mesentery drives N-cadherin expression and rotation
102
Q

Describe the rotation and fixation of the midgut.

A

At first, the midgut grows out into the umbilicus (week 6):

  • It rotates around the superior mesenteric artery (which is in essence the dorsoventral axis) by 90* clockwise.

Then the midgut retracts back into the coelomic cavity (week 10):

  • As the embryo grows, the intestines become more folded
  • As they retract, they rotate a further 180* as this happens.
  • This forms the adult intestinal arrangement.
103
Q

In total, how much does the midgut rotate?

A

270* clockwise

(90* at first and then another 180*)

104
Q

What causes the folds in the jejunum and ileum to form?

A

When the midgut is herniating out into the umbilicus, rapid growth causes folding.

105
Q

What is volvulus?

A

Abnormal rotation of the midgut can cause twisted strangulation can occur, which is often fatal.

106
Q

What is omphalocele?

A
  • Failure of the midgut to return into the coelomic cavity after rotating.
  • This needs to be fixed surgically after birth,
107
Q

What are the derivatives of the hindgut?

A
  • Distal 1/3 of transverse colon
  • Descending colon
  • Rectum
  • Superior part of anal canal
108
Q

How does rotation of the hindgut occur?

A

It is largely secondary to the rotation of the midgut.

109
Q

What are the regions of the gut tube that are intraperitoneal, retroperitoneal and secondary retroperitoneal?

A

Intraperitoneal:

  • Stomach
  • Small intestine (except the duodenum)
  • Liver
  • Gall bladder
  • Spleen
  • Transverse colon
  • Sigmoid colon

Retroperitoneal:

  • Thoracic oesophagus
  • Rectum

Secondary retroperitoneal:

  • Pancreas
  • Duodenum
  • Ascending colon
  • Descending colon
110
Q

Is the thoracic oesophagus intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Retroperitoneal

111
Q

Is the stomach intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Intraperitoneal

112
Q

Is the duodenum intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Secondary retroperitoneal

113
Q

Is the pancreas intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Secondary retroperitoneal

114
Q

Is the gall bladder intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Intraperitoneal

115
Q

Is the small intestine intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Intraperitoneal (except the duodenum)

116
Q

Is the ascending and descending colon intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Secondary retroperitoneal

117
Q

Is the transverse colon intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Intraperitoneal

118
Q

Is the rectum intraperitoneal, retroperitoneal or secondary retroperitoneal?

A

Retroperitoneal

119
Q

Why is the duodenum secondary retroperitoneum?

A

Because of the pancreas (that it is attached to) becoming secondary retroperitoneal.

120
Q

Why are the ascending and descending colon secondary retroperitoneal?

A

They are pushed against the psoterior abdominal wall and fuse with it.

121
Q

What happens to the cloaca in development?

A
  • It is partitioned by the urorectal septum
  • This separates the anorectal canal from the urinary system (allantois)
122
Q

What happens to the cloacal membrane?

A

It ruptures at the end of 8th week, exposing the anorectal canal.

123
Q

What is the name for the intrinsic nervous system of the gut?

A

Enteric nervous system

124
Q

Describe the development of the enteric nervous system of the gut. What is the origin of the neurons? [IMPORTANT]

A
  • Neural crest cells migrate into the gut tube
  • They spread from foregut to hindgut, while proliferating
125
Q

What is Hirschsprung’s disease?

A
  • Condition where neural crest cells fail to migrate and form the enteric nervous system of the gut
  • This is due to mutations in the c-ret receptor or GDNF ligand
  • The result is a non-functional colon
126
Q

What is teratogenesis?

A

The development of a congenital abnormality.

127
Q

What is the sensitive period?

A

The stage of development when an organ or system is most susceptible to genetic or environmental factors that can alter the development -> i.e. When it is mostly susceptible to teratogenesis

128
Q

What are the general causes of developmental disorders?

A
  • Genetic
  • Environmental
  • Both (multifactorial)
129
Q

What are the different categories of developmental disorders?

A
  • Structural malformations
  • Brain defects that are not structurally detectable but present as behavioral effects
  • Deficiencies of fetal growth, birth weight and tissue maturation
  • Effects leading to premature birth, stillbirth or neonatal death
130
Q

What is the name for the database that covers developmental disorders in Europe?

A

EUROCAT

131
Q

How common are abortions of abnormal foetuses?

A

3/4 are aborted.

132
Q

What is the cause of cyclopia?

A

Errors in sonic hedgehog signalling

133
Q

Describe how somite segmentation can be involved in developmental disorders

A
  • Pairs of somites bud off periodically at the anterior tip of the presomitic mesoderm (PSM) every 6 hours
  • This involves 3 major signalling pathways: Delta-Notch, Wnt and FGF
  • When this goes wrong, there are vertebral defects
134
Q

What are the 3 major signalling pathways involved in somite segmentation? How are these related to developmental defects?

A
  • Delta-Notch, Wnt and FGF
  • Errors with these pathways can lead to vertebral defects
135
Q

Describe how aortic arch remodelling is related to developmental defects. Which signalling molecules are involved?

A

Tbx1 errors can lead to abnormalities.

136
Q

What are some examples of outflow tract defects?

A
  • Persistent truncus arteriosus
  • Double outlet right ventricle
  • Transposition of the great arteries
  • Overriding aorta
137
Q

Are congenital heart defects mostly genetic or environmental?

A

Only ∼20% of congenital heart disease cases can be attributed to a specific genetic cause:

  • Non-genetic factors are likely to be important for heart development
  • Supported by the large phenotypic variability seen between individuals with the same genetic mutation
138
Q

Give some examples of environmental factors that can cause congenital heart defects.

A

Hypoxia, which can result from:

  • Smoking
  • Living at high altitude
  • Maternal diabetes
  • High body mass index
  • Hypertension
  • Prescription medications
139
Q

Describe how vertebral defects are multifactorial.

A

Vertebral defects result from somite segmentation defects:

  • These result largely from errors in 3 major signalling pathways: Delta-Notch, Wnt and FGF
  • They can also be contributed to by hypoxia, which can induce the vertebral defect when the embryo is heteroxygous for a defective gene
140
Q

What are some environmental factors that result in developmental disorders?

A
  • Ionising radiation
  • Pollution
  • Drugs, including alcohol
  • Maternal infection
  • Maternal nutritional deficiency
  • Maternal metabolic disorders
  • Maternal obesity
  • Smoking
  • Trauma and pressure effects
141
Q

What is a teratogen?

A

An agent or factor which causes malformation of an embryo.

142
Q

What is another name for the sensitive period?

A

Critical period

143
Q

Is the sensitive period the same for each teratogen?

A

No, it depends on which specific structures or organs are vulnerable to that teratogen, each of which has a specific sensitive period.

144
Q

During which part of the sensitive period are the effects of teratogens most serious?

A

During the earlier stages of the critical period.

145
Q

What developmental disorders does ionising radiation lead to and how?

A

X-rays cause mutations and chromosome breakage and reduce the rate of cell division:

  • Leukaemia -> Mutations in haematopoietic tissue
  • Mental retardation/microcephaly -> Reduction of cell division in the rapidly growing brain
146
Q

How does pollution lead to developmental disorders?

A

Chromosomal breakage

147
Q

What are some drugs that have been found to be teratogenic?

A
  • Thalidomide
  • 13-cis-retinoic acid (Roaccutane)
  • Diethylstilbestrol (DES)
  • Alcohol
148
Q

What was thalidomide used for, what did it cause and what was the mechanism?

A
  • Was used to treat morning sickness in pregnant women between 1957 and 1962
  • Caused miscarriage, stillbirth, craniofacial and limb defects
  • Probable mechanism: inhibits angiogenesis in embryonic limb buds
149
Q

What is the sensitive period for thalidomide in pregnancy?

A

21-40 days after fertilisation

150
Q

What was 13-cis-retinoic acid used for and what did it cause?

A
  • Effective treatment for severe cystic acne.
  • Effects: Spontaneous abortion, defects of face, ears, cardiovascular system, and cerebellum, hydrocephalus
151
Q

What is 13-cis-retinoic acid, chemically?

A

A synthetic form of vitamin A.

152
Q

What is the sensitive period for 13-cis-retinoic acid?

A
  • Up to 25 days -> Craniofacial & CVS
  • Up to 120 days -> Brain
153
Q

What was diethylstilbestrol, what was it used for and what did it cause?

A
  • Progesterone-like substance
  • Given to prevent abortion (in the 1940s)
  • Caused glandular changes in the vagina (adenosis, with some cases of adenocarcinoma), and reproductive tract anomalies, including reduced testicular size, in males
154
Q

What are the effects of alcohol on development?

A

Mothers may show full or partial syndrome:

  • Microcephaly
  • Mental retardation
  • Low bridge of nose
  • Hypertelorism
  • Indistinct philtrum
  • Increased incidence of heart defects
155
Q

What are some other drugs and hormones that cause developmental defects?

A
  • Anticonvulsants (anti-epileptic drugs)
  • Cancer chemotherapy -> Intrauterine growth retardation
  • Lithium -> Tenfold increase in congenital heart defects
  • Recreational drugs -> Cocaine/omphalocoele
  • Androgenic hormones -> Masculinisation of the female genitalia
156
Q

What is the most common maternal infection that leads to developmental defects?

A

Rubella

157
Q

What are the effects of maternal infection of rubella on developmental defects?

A
  • Deafness
  • Cataracts
  • Heart defects
  • Mental retardation
  • Glaucoma
  • Damage to the CNS
  • Stillbirth
  • Miscarriage
  • Intrauterine growth retardation common
158
Q

What is the sensitive period for maternal infection of rubella?

A
  • Early exposure for cataracts and heart defects
  • Later for deafness
159
Q

What are the effects of maternal infection of syphilis on developmental defects?

A
  • Most common outcome: Stillbirth or neonatal death
  • If the baby is viable, it is likely to have multiple problems including:
    • Deafness
    • Blindness
    • Saddle-shaped nose
    • Mis-shapen teeth.
160
Q

When is the critical period for maternal infection of syphilis?

A

Can cross the placental barrier from the 5th month of pregnancy.

161
Q

What are the symtpoms of zika virus infection?

A

Zika virus infection is usually mild or asymptomatic. Symptoms last around two to seven days and include:

  • Rash
  • Itching all over the body
  • Fever
  • Headache
  • Joint pain (with possible swelling, mainly in the smaller joints of the hands and feet)
  • Muscle pain
  • Conjunctivitis (red eyes)
  • Lower back pain
  • Pain behind the eyes
162
Q

What are the effects of maternal zika infection on developmental defects?

A
  • Microcephaly and craniofacial disproportion
  • Spasticity
  • Seizuresdysfunction including feeding difficulties, ocular abnormalities.
  • Some data suggest that also the genitourinary, cardiac and digestive systems can be affected
163
Q

How is zika viurus transmitted?

A
  • Mosquitos
  • Intercourse
164
Q

Which cells doe zika virus after in development and when is the sensitive period?

A

Neuronal cells in all stages of development, including neural progenitor cells.

165
Q

What are 3 examples of maternal vitamin deficiencies that can lead to developmental defects?

A
  • Vitamin A deficiency
  • Vitamin D deficiency
  • Folic acid deficiency
166
Q

Describe the effects of maternal vitamin A deficiency on developmental defects.

A
  • Congenital cataracts
  • Immunodeficiency
  • General failure to thrive
167
Q

Describe the effects of maternal vitamin D deficiency on developmental defects.

A

Bone growth defects (e.g. rickets)

168
Q

Is vitamin D deficiency becoming more or less common in the UK?

A

More, due to poor diet and lack of exposure to sunlight.

169
Q

Describe the effects of maternal folic acid deficiency on developmental defects.

A
  • Folic acid plays a role in cell production and division
  • Correlated with neural tube defects
170
Q

What condition can vitamin D deficiency lead to?

A

Rickets

171
Q

Describe the effects of maternal diabetes (mild and severe) adn obesity on the development of the child.

A
  • Advanced diabetes
    • 10x increase of neural tube defects
    • Palate and facial defects
    • Sacral agenesis/lower limb defects
  • Mild diabetes
    • Not associated with congenital abnormalities
    • High birth weight (>90th percentile)
    • Increased risk of birth injury, e.g. shoulder dystocia
  • Obesity (BMI > 33) without diabetes mellitus
    • Higher birth weight
172
Q

What is the importance of high and low birth weight?

A

Both are associated with increased risk of perinatal mortality (death from mid-foetal stage to the 7th day).

173
Q

What are some maternal risk factors for low birth weight?

A
  • High blood pressure
  • Heart problems
  • Smoking
  • Alcohol and narcotic consumption
  • Poor nutrition
  • Low socioeconomic status
  • Exposure to environmental pollutants
174
Q

Explain the association between maternal smoking and birth weight.

A

Babies born to smoking mothers are more likely to be low birth weight (below 2.5 kg):

  • Smoking causes intrauterine growth retardation, increased risk of prematurity, increased perinatal mortality, and possible postnatal behavioural effects
  • No consistent evidence that smoking causes structural defects
175
Q

What is oligohydramnios and what are the effects?

A
  • Insufficient amniotic fluid
  • Can lead to pressure defects, e.g. squashing of the face, club foot
176
Q

What is aminiotic band syndrome and what are the effects?

A

Twists of the amniotic membrane can cause partial limb amputation by compromising blood supply.

177
Q

What are some tactics for prevention of developmental disorders?

A
  • Good diet, including vitamin supplementation before and during pregnancy
  • Pre-pregnancy advice about smoking, drugs and alcohol consumption
  • Pre-pregnancy care for diabetes and help with obesity
  • Monitoring during pregnancy
  • Improvement of living conditions associated with low socioeconomic status
  • Pollution reduction
  • Monitoring the introduction of new drugs
178
Q

What are branchial/pharyngeal arches?

A

A series of externally visible anterior tissue bands lying under the early brain that give rise to the structures of the head and neck.

179
Q

When does pharyngeal arch development start?

A

Day 21

180
Q

Give a summary of the different structures that derive from the pharyngeal arches.

A
  • Skull
  • Brain
  • Special sense organs
  • Skeletal elements:
    • Face
    • Jaw and its support
    • Pharyngeal and laryngeal cartilage
  • Muscles
    • Of mastication
    • Of facial expression
    • Of pharynx and larynx
  • Teeth
  • Tongue
  • Endocrine glands
  • Thymus
181
Q

How many pairs of pharyngeal arches are there and what are their numbers?

A

5 bilateral pairs:

  • Pairs 1-4
  • Pair 6

(There is no 5th arch in humans, just as with aortic arches)

182
Q

How do the pharyngeal arches form?

A
  • Endoderm pouches out from foregut
  • Comes into close contact with ectoderm
  • Neural crest cells migrate in from neural tube
183
Q

What are the different parts of the pharyngeal arch section?

A
  • Pharyngeal arches -> Buldges
  • Pharyngeal pouches -> Endoderm between arches
  • Pharyngeal clefts -> Ectoderm between arches
184
Q

Draw the different tissue types in the pharyngeal arches.

A
185
Q

What are the derivatives of the ectoderm, endoderm, mesoderm and neural crest of the pharyngeal arches?

A
186
Q

How do pharyngeal arches contribute to segmental structure?

A

Each branchial arch will give rise to:

  • A rod of cartilage (neural crest)
  • Muscles (mesoderm)
  • A nerve
  • An artery
187
Q

What determines the exact identity of what each pharyngeal arch will form?

A
  • Pharyngeal arch identity defined by differential gene expression
  • Particularly Hox genes
  • Neural crest cells migrating into arches have a Hox code
188
Q

What are the processes of the first pharyngeal arch?

A
189
Q

Which parts of the skull do the pharyngeal arches form?

A

Facial skeleton

190
Q

What are the embryological origins of the different bones of the skull?

A
191
Q

What cranial bones does the neural crest of the first pharyngeal arch contribute to? What are the cartilage models that preceed the bones?

A
  • Maxilla -> Palatopterygoquadrate bar
  • Mandibular -> Meckel’s cartilage
192
Q

What cartilage models do the malleus and incus form from?

A
  • Malleus -> From Merkel’s cartilage
  • Incus -> From palatopterygoquadrate bar
193
Q

Describe how facial bone development occurs. Which pharyngeal arch is responsible?

A

1st pharyngeal arch is responsible:

  • Neural crest forms the maxilla and mandibule (via the the maxillary and mandibular processes)
  • The 2 processes, together with the frontonasal prominence, surround the primitive mouth (stomodeum) of the 4-5 week old embryo
  • Medial and lateral nasal prominences form in the frontonasal prominence
  • Medial nasal processes fuse to form the intermaxillary segment
  • Maxillary processes form the cheeks
  • The intermaxillary segment forms:
    • Medial part of the nose
    • Philtrum (of upper lip)
    • Primary palate
194
Q

What causes cleft lip and face?

A

Failure of fusion of the different facial processes.

195
Q

Describe the development of the palate. [IMPORTANT]

A
196
Q

What are the processes from which the primary and secondary palates originate?

A
197
Q

What causes cleft palate?

A

Failure of fusion of the primary palate (intermaxillary segment) and the paired secondary palatal shelves (maxillary primordia).

198
Q

For the 1st pharyngeal arch, state the derived:

  • Nerves
  • Muscles
  • Skeletal elements
A
  • Nerves -> Trigeminal nerve
  • Muscles -> Muscles of mastication
  • Skeletal elements -> Maxilla and mandible, Malleus and incus
199
Q

For the 2nd pharyngeal arch, state the derived:

  • Nerves
  • Muscles
  • Skeletal elements
A
  • Nerves -> Facial
  • Muscles -> Muscles of facial expression
  • Skeletal elements -> Styloid process + Stapes
200
Q

For the 3rd pharyngeal arch, state the derived:

  • Nerves
  • Muscles
  • Skeletal element
A
  • Nerves -> Glossopharyngeal nerve
  • Muscles -> Stylopharyngeal muscle
  • Skeletal element -> Hyoid bone
201
Q

For the 4th (and some of 6th) pharyngeal arch, state the derived:

  • Nerves
  • Muscles
  • Skeletal elements
A
  • Nerves -> Vagus
  • Muscles -> Pharyngeal and laryngeal muscles
  • Skeletal elements -> Laryngeal cartilages
202
Q

Draw a diagram to summarise the neural crest derivatives of the pharyngeal arches.

A
203
Q

What is the stylopharyngeus muscle used for and what is it derived from?

A
  • Used for vocalisation and swallowing
  • Derived from 3rd pharyngeal arch
204
Q

What are the pharyngeal and laryngeal muscles used for and what are they derived from?

A
  • Used for vocalisation and swallowing
  • Derived from the 4th and 6th pharyngeal arch
205
Q

How mny pharyngeal clefts are there?

A

4

206
Q

What are the derivatives of each of the pharyngeal clefts?

A
  • 1st cleft -> External ear
  • The other 3 clefts are overgrown by the second arch and disappear
207
Q

How many pharyngeal pouches are there?

A

4

208
Q

What are the derivatives of each of the different pharyngeal pouches?

A
  • 1st pouch -> Middle ear
  • 2nd pouch -> Tonsils
  • 3rd pouch -> Thymus + Inferior parathyroid
  • 4th pouch -> Superior parathyroid + ultimobranchial body
209
Q

From where does the thymus develop and what happens after it forms?

A
  • Forms from the 3rd pharyngeal pouch
  • After it forms, it migrates to the lower neck

(The thymus is purple here)

210
Q

From where do the parathyroid glands develop and what happens after they forms?

A
  • Form from the 3rd and 4th pharyngeal pouches
  • They migrate caudally along with the thyroid

(They are the colourful dots on the black thyroid)

211
Q

Describe the development of the tongue. [EXTRA?]

A
212
Q

What is the nerve of the 1st pharyngeal arch and what does it innervate?

A

Trigeminal nerve:

  • Motor -> Muscle of mastication
  • Sensory -> Skin of face, Oral and nasal mucosa, Anterior 2/3rd of tongue
213
Q

What is the nerve of the 2nd pharyngeal arch and what does it innervate?

A

Facial nerve:

  • Motor -> Muscles of facial expression
  • Sensory -> Anterior 2/3rd of tongue (taste)
214
Q

What are the nerves of the 3rd, 4th and 6th pharyngeal arch and what do they innervate?

A
215
Q

Describe the blood supply to the different pharyngeal arches.

A

Each pharyngeal arch is supplied by a different aortic arch.

216
Q

What is DiGeorge syndrome? [IMPORTANT]

A
  • 22q11 deletion
  • Involves a range of symptoms, including including cleft lip or palate
217
Q

What are some components contained within the umbilical cord?

A
  • Two umbilical arteries
  • One umbilical vein
  • Obliterated allantois duct

All surrounded by Wharton’s jelly and contained within an outer layer of amnion.

218
Q

What is hiatus hernia?

A

Where part of the stomach pushes up into the lower chest through a weakness in the diaphragm.

219
Q
A

YEAR 1 - Organisation of the Body (Anton) (15 decks)

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