Exam 3

Question 1

Craniofacial Structures are composed of all 3 germ layers:

Answer 1

Ectoderm
Mesoderm
Endoderm

Question 2

Ectoderm:

Answer 2

Skin
Cranial nerves (neural ectoderm)

Question 3

Mesoderm:

Answer 3

Muscles
Cartilage
Bone
Blood vessels

Question 4

Endoderm:

Answer 4

Lining of the mouth
Nasal cavity
Pharynx

Question 5

• Most structures in the head and neck can be traced back to the:

Answer 5

o Pharyngeal grooves (ectoderm)
o Pharyngeal arches (mesoderm)
o Pharyngeal pouches (endoderm)
• Neural crest cells also contribute to many tissues

Question 6

• Pharyngeal arches:

Answer 6

o Form as lumps of tissue on the VENTRAL side of the embryo during the 3rd week of development
o Total of 5 arches form in humans (1-6)
—5th arch is usually absent
• When present, it’s rudimentary

Question 7

As embryonic folding occurs, the pharyngeal arches…

Answer 7

become tucked inward, sitting OVER the heart prominence (cardiac bulge)
o Oropharyngeal membrane ruptures ~ day 26 leaving stomodeum open to amniotic fluid
o Arches are partially separated from each other by grooves and pouches
—Pharyngeal groove (ectoderm) – INvagination on the outside surface of the embryo
—Pharyngeal pouch (endoderm) – Evaginations on the inside surface of the pharynx
o Arch 1 is split into 2 parts:
—Maxillary & mandibular process

Question 8

o Components:

—Each pharyngeal arch contains:

Answer 8

• Cartilage
• Nerve (cranial nerve)
• Muscle
• Artery (aortic arches)
These components are each surrounded by mesenchyme.
When the arches form, the mesenchyme is mesoderm derived (head mesenchyme).
• Neural crest cells (ectoderm) migrate into the mesenchyme of each arch during week 4 and largely replace the mesoderm

• Arches, pouches, grooves are #ed 1-6 CRANIALLY to CAUDALLY (skip #5)

Question 9

• Fate and Derivatives of the Pharyngeal arches:

o Cartilage …

Answer 9

of each arch forms small bones of the middle ear and neck, cartilage of the larynx.

1st arch cartilage = Meckel cartilage.
• Forms bones of the middle ear
• Patterns the mandible, but DOES NOT form the mandible
2nd arch cartilage forms stapes of the middle ear, bones that anchor muscles of the tongue and larynx
3rd arch cartilage forms the hyoid bone, which anchors the tongue.
4th & 6th arch cartilage remain as cartilage associated with the larynx and thyroid.

Question 10

Fate and Derivatives of the Pharyngeal arches:

o Muscles…

Answer 10

1st arch muscle forms muscles used in chewing
2nd arch muscle forms muscles of facial expression
3rd arch muscle forms muscles that elevates pharynx, larynx (stylopharyngeus)
4th arch muscle – pharynx muscles
6th arch muscle – larynx intrinsic muscle
Muscles of the pharyngeal arches are presomitic (never form somites):
• They arise from unsegmented paraxial mesoderm

Question 11

Fate and Derivatives of the Pharyngeal arches:

o Nerves…

Answer 11

Each arch is supplied by its own cranial nerve (CN), which innervates the muscles associated w/ that arch.
1st arch = trigeminal nerve (CN V).
• It branches into both the maxillary and mandibular process.
• Only arch nerve that significantly innervates the facial skin.
2nd arch = facial nerve (CN VII).
• Facial expressions, taste sensation.
3rd arch = glossopharyngeal nerve (CN IX).
• Parasympathetic innervation of entire gut

Question 12

• Fate and Derivatives of the Pharyngeal Pouches:

Answer 12

o The endodermal lining of the pouches forms important organs in the head & neck. Shape of the pouches changes as the tissue differentiates.
o 1st pouch becomes eardrum, inner ear
o 2nd pouch becomes the tonsils
o 3rd pouch becomes thymus, inferior parathyroid
o 4th pouch becomes superior parathyroid
o 6th = rudimentary

Question 13

• Fate and Derivatives of the Pharyngeal Pouches:

thyroid, parathyroid, and thymus glands

Answer 13

o The thyroid, parathyroid, and thymus glands all migrate during their development.
—NOTE: the thyroid gland isn’t derived from the pharyngeal pouch!
• It forms from a separate thickening, then diverticulum, on the floor of the pharynx.
—The thyroid gland is the 1st endocrine organ to develop in the embryo. It is temporarily connected to the tongue via the thyroglossal duct.
—As the thyroid descends, the duct trails behind it. It eventually closes.
—The site of the thyroid diverticulum is marked by a small pit on the tongue surface – the foramen cecum.
o Defects in migration are common – remnants of the glands (or the entire gland) can become stuck anywhere along the migration route.

Question 14

• Fate and Derivates of the Pharyngeal Grooves:

Answer 14

o Pharyngeal grooves separate the pharyngeal arches on the outside surface on the embryo
o In week 4-5, pharyngeal arch 2 extends caudally, growing over arches 3 & 4. Grooves 2-4 become entrapped in a larger depression called the cervical sinus.
o Arch 2 & 4 meet and fuse, covering grooves 2-4. The cervical sinus is enclosed (cervical vesicle) and eventually generates.
o Only pharyngeal groove 1 survives and becomes the ear canal.

Question 15

Explain why ectopic thyroid, parathyroid, and thymus tissue can sometimes be found in the neck. Describe where they are most likely to be found.

Answer 15

o The thyroid, parathyroid, and thymus glands all migrate during their development.
—NOTE: the thyroid gland isn’t derived from the pharyngeal pouch!
• It forms from a separate thickening, then diverticulum, on the floor of the pharynx.
—The thyroid gland is the 1st endocrine organ to develop in the embryo. It is temporarily connected to the tongue via the thyroglossal duct.
—As the thyroid descends, the duct trails behind it. It eventually closes.
—The site of the thyroid diverticulum is marked by a small pit on the tongue surface – the foramen cecum.
o Defects in migration are common – remnants of the glands (or the entire gland) can become stuck anywhere along the migration route.

Question 16

Give an example that demonstrates neural crest patterning is important for facial structure.

Answer 16

• EX.: Duck-quail chimera – the population of neural crest cells that forms the mandibular prominence was transplanted from a quail to a duck embryo. The share of the mandible is determined by neural crest cells.

Question 17

Summarize the development of the facial primordia.

Answer 17

• The face if formed from 5 facial primordia/prominences – regions/clumps of cells undergoing rapid growth – that appear in week 4:
o Frontonasal prominence
o 2 paired maxillary prominences
o 2 paired mandibular prominences

o The prominences are mostly composed of neural crest cells. Their proliferation is the driving force that shapes the prominences into distinctive facial shapes.

Question 18

the facial primordia. What happens to each of them?

Answer 18

• Facial development occurs mainly between weeks 4-8
o The frontonasal prominence grows VENTRALLY and LATERALLY.
—The frontal portion forms the forehead
—The caudal most portion forms the medial and lateral nasal prominences, which form the nose.
• The nose forms 1st as a placode, then the placode is pulled into a depression (nasal pits).
• Median nasal prominences on the left and right sides merge at the midline.
• Lateral nasal prominences form the sides of the nose (external nares).
o The maxillary and mandibular prominences are clustered around the stomodeum (future opening of the mouth).
—The maxillary prominences also fuse at the midline, caudal to the nasal prominences, forming the philtrum, upper lip, and cheeks.
—The mandibular processes fuse early, forming the chin, lower lip, and jaw.

Question 19

Cleft lip

Answer 19

o Mild defects affect facial appearance and speech
o Severe defects interfere w/ feeding and breathing (nasal cavity is open to mouth cavity).
o Surgical repair is highly successful
• Clefts are classified based on location:
o Anterior cleft defects involve the lip and primary palate
o Posterior cleft defects involve the secondary (hard or soft) palate

• Abnormal closure or persistence of pharyngeal structures can lead to birth defects. Abnormalities of the 2nd groove are relatively common.

Question 20

Disorder: Cervical sinus

Answer 20

• The Cervical Sinus is a depression formed by the 2nd, 3rd, & 4th pharyngeal grooves. Normally the sinus closes and disappears during development.
o EXTERNAL cervical sinus – blind opening from outside the body. Caused by persistent GROOVES.
o INTERNAL cervical sinus – blind extension from tonsils. Caused by persistent 2nd POUCH.
o If the entire cervical sinus persists, a fistula can remain connecting the tonsils to the outside of the body.

Question 21

Cervical cysts

Answer 21

o Remnants of the cervical sinus can be trapped inside the neck (no opening to outside or pharynx), forming a circular or oblong cyst. Usually apparent in childhood or early adulthood when cyst slowly fills w/ fluid and sloughed epithelial cells.

Question 22

Cervical vestiges

Answer 22

o Pharyngeal arch cartilage that aren’t incorporated to ligaments/bones usually disappear. Remnants of cartilage may persist as cartilage rods or small bony remnants under the skin in the side of the neck.

Question 23

• 22.q11.2 Deletion Syndrome

Answer 23

(AKA DiGeorge syndrome [severe end of spectrum] and the acronym CATCH-22):
o Most common chromosomal deletion
o Infants are born w/ little to no thymus & parathyroid gland tissue, nasal clefts, thyroid hypoplasia, cardiac abnormalities.
o Due to micro deletion in the q11.2 region of chromosome 22. Up to 35 genes are involved (depending on size of deletion).
o Loss of TBX1 causes defects in formation of the 3rd & 4th pharyngeal pouches, and therefore the thymus & parathyroid glands are very small.
o Endoderm usually signals to & directs neural crest during migration. Individuals w/ 22.q11.2 have impaired neural crest migration – causes nasal clefts, cardiac defects

Question 24

Compare and contrast cleft lip and cleft palate.

Answer 24

??

Question 25

Compare and contrast the flow of blood through a fetal and adult heart.

Answer 25

• Intraembryonic circulatory arc:
o Flow of blood away from heart:
—Heart —> aortic sac —> aortic arches —> dorsal aorta
o A system of cardinal veins brings the blood back to the heart
—Cranial cardinal vein & caudal cardinal vein – common cardinal vein – heart
• Fetal circulation summary
o Oxygenated blood from the placenta is carried by the umbilical vein past the liver via the ductus venosus. It empties into the sinus venosus, which in turn empties into the right atrium.
o The right atrium would normally send the blood to the lungs, but instead the foramen ovale allows blood to be shunted directly to the left atrium
o Blood then travels thru the left atrium to the left ventricle and out to the body of the embryo
o Enough blood passes into the pulmonary artery to supply the lungs w/ the oxygen they need
o Only 12% of the right ventricle output goes to the lungs, rest travels to ductus arteriosus

Question 26

• Development of the heart:

Answer 26

o After leaving the primitive streak, precardiac cells move cranially and form the primary heart field (cardiac crescent) which is made from cardiogenic mesoderm (splanchnic mesoderm) at the cranial-most end of the trilaminar disc
o A 2nd hard field is located medial to the primary heart field
o The heart fields are distinct populations of progenitor cells that will become different parts of the heart

Question 27

• Development of the heart:

o Cells of the primary heart field give rise to:

Answer 27

—Ventricles
—Left atrium
—Some of the right atrium
—Some of the outflow tract

Question 28

• Development of the heart:

o Cells of the 2nd heart field give rise to:

Answer 28

—Most of the outflow tract

—Most of the right atrium

Question 29

Describe how embryonic folding creates the primitive heart tube.

Answer 29

• The splanchnic and somatic mesoderm split
o The space between is called the pericardial coelom – precursor to the pericardial cavity
• The splanchnic mesoderm of the precardiac region thickens to form the myocardial primordium
• The endocardial primordia forms as a tube between the myocardial primordium and the endoderm of the yolk sac/primitive gut
• Lateral/ventral folding events of the early embryo bring the primordia together where they fuse at the midline (ventral to the gut) to form the primitive heart tube
• 2 separate lumen become the single lumen of the heart
• The primitive single tubular heart consists of:
o Endocardial lining
o Cardiac jelly
o Myocardium
• The tubular heart is located in the pericardial coelom
• Formation of the tubular heart has occurred by the end of the 3rd week

Question 30

Explain how the heart’s shape changes during cardiac looping.

Answer 30

• Cardiac looping:
o Around day 23, the primitive heart folds and loops to establish the future heart chambers in the correct spatial locations
o The heart is the 1st asymmetrical structure to develop in the embryo
o The initially straight heart tube begins to take on an S shape
—The inflow tract (atrium) becomes positioned dorsal to the outflow tract (conotruncus)
o As the heart continues to grow, the atrium can be seen bulging out on either side of the heart

• Atrioventricular partitioning begins when endocardial cushions begin to form
o Endocardial cushions – thickening on the dorsal and ventral sides of the heart at the junction of the atrium and ventricle
o The cushions will eventually grow into the atrioventricular canal and meet, separating into the left and right channels
—The right atrioventricular canal will develop into the tricuspid valve
—The left atrioventricular canal will develop into the mitral (bicuspid valve)

Question 31

• 3 shunts in fetal circulation are needed to supply highly oxygenated blood to the body and developing brain:

Answer 31

1. Foramen ovale
2. Ductus arteriousus
3. Ductus venosus

Question 32

1. Foramen ovale (present in the interatrial septum)

Answer 32

—Opening between right and left atria
—Shunts highly oxygenated blood from right atria to left atria
—Blood moves from LA to LV, aorta, body

Question 33

o 2. Ductus arteriosus

Answer 33

—Temporary blood vessel connecting pulmonary artery and aorta, directing blood away from the lungs
—Derived from left 6th aortic arch
—Allows blood leaving right ventricle to bypass lungs
—Fetal lungs aren’t fully developed and cant handle the full amt of blood entering the pulmonary artery

Question 34

o 3. Ductus venosus

Answer 34

—Connects umbilical vein to sinus venosus
—Allows oxygen-rich blood returning from placenta to bypass liver
—Liver is a dense capillary bed that would deoxygenate blood as it slowly passed thru
—Not involved in right-left shunting in the heart

Question 35

Explain how blood flow in an infant changes at birth. What happens to the three shunts?

Answer 35

• Circulation after birth: closing the shunts
o The embryo must prepare for the moment when oxygenating the blood must be done using lungs instead of the placenta
o When the umbilical cord is but, all blood flow via the umbilical vein stops
o The baby takes a breath, fluid is expelled form the lungs, and the lungs expand enough to hold a larger amt of blood
o More blood starts being directed to the lungs, and this combined w/ the lack of blood flow from the umbilical vein causes the blood pressure of the left atrium to increase w/ respect to the right atrium
—This increase in blood pressure causes the foramen ovale collapse on itself, and all blood from the right atrium will begin to enter the right ventricle
o Ductus venosus begins closing when umbilical veins are occluded due to loss of blood flow. Fully closed by 1 week.
o Ductus arteriosus closes quickly after birth. Wall of the vessel constricts in response to oxygen, prostaglandin levels.
o For each shunt, functional closure is rapid. Anatomical closure takes longer.

Question 36

Cyanosis

Answer 36

bluish skin. Caused by too much deoxygenated hemoglobin

o Oxygen levels in circulatory system is very low, individual not receiving enough oxygen.

Question 37

Stenosis

Answer 37

Narrowing of pathway

Question 38

Atresia

Answer 38

tissue that doesn’t develop or is very underdeveloped and therefore, not functional

Question 39

Hypoplasty

Answer 39

tissue/structure is smaller/underdeveloped from what it should be; smaller than normal

Question 40

Hypertrophy

Answer 40

larger than normal; enlarged

Question 41

Persistent

Answer 41

something that stays around longer than it should

Question 42

Patent

Answer 42

A vessel that is open when it shouldn’t be

Question 43

Secondary effect

Answer 43

Not the direct result of a disorder but…???

Question 44

Palliative

Answer 44

relieving pain w/out dealing w/ the cause of the condition

Question 45

Discuss the prevalence and diagnosis of congenital heart defects. How common are they, and how are they detected?

Answer 45

• Congenital heart malformations are the most common birth defect
• Heart defects are classified as either cyanotic or acyanotic
• Causes of congenital heart defects is unknown in most cases
o 15% of cases can be attributed to genetic factors
• Known risk factors:
o Maternal diabetes, obesity, phenylketonuria
o Maternal smoking
o Rubella infection
• Diagnosis of some severe defects can be made by prenatal ultrasound
• Infant diagnosis is usually by presence of “murmur” upon stethoscope examination, presentation of cyanosis or abnormal pulse oximetry result
o Pulse oximetry – non-invasive measurement of oxygen saturation levels. Used to screen for heart defects at 24-48 hrs after birth. Does not rule out all defects.
• At 1-week checkup, physician will check for cyanosis, trachypnea, poor perfusion, weak pulse to screen for late latent defects

Question 46

Patent ductus arteriosus (PDA):

Answer 46

o Ductus arteriosus normally closes immediately after birth
—When lungs begin functioning, bradykinin is released that causes wall of the DA to constrict
o Common in premature infants
o Small PDA is asymptomatic. Risk of endocarditis (inflammation of heart valves)
o Large PDA is life-threatening and requires closure
o High pressure blood from aorta will flow backwards into lungs and cause pulmonary hypertension. Untreated PDA will eventually cause congestive heart failure.
o Treatment: indomethacin therapy or surgical closure. Some catheter devices used
o (Retrograde flow)

Question 47

Transposition of the great arteries

Answer 47

o Compound disorder involving 4 malformations:
—Pulmonary stenosis – primary defect: severity determines overall severity
—Overriding aorta – aorta straddles both ventricles
—Ventricular septal defect – below overriding aorta
—Right ventricular hypertrophy – secondary effect of pulmonary stenosis
o Most common cyanotic heart defect
o Affected individuals have “tet spells” – transient, rapid-onset period of hypoxia during extortion due to spasm of pulmonary valve
o Treatment = surgical widening of pulmonary stenosis, repair VSD

Question 48

Tetralogy of Fallot

Answer 48

o Compound disorder involving 4 malformations:
—Pulmonary stenosis – primary defect: severity determines overall severity
—Overriding aorta – aorta straddles both ventricles
—Ventricular septal defect – below overriding aorta
—Right ventricular hypertrophy – secondary effect of pulmonary stenosis
o Most common cyanotic heart defect
o Affected individuals have “tet spells” – transient, rapid-onset period of hypoxia during extortion due to spasm of pulmonary valve
o Treatment = surgical widening of pulmonary stenosis, repair VSD

Question 49

Septal defects

• Atrial septal defects (ASD)

Answer 49

o Results in a common atrium (not able to separate deoxygenated and oxygenated blood = mixed blood)
o Due to higher pressure in the left atrium, blood flows form the left to the right atrium
o Greater than normal amts of blood are diverted to the lungs, resulting in pulmonary hypertension (high blood pressure)
o Additional blood flow causes hypertrophy and increased blood pressure of the right atrium
o Eventually, the increase in right atrium blood pressure results in blood moving back toward the left atrium and cyanosis
o Treatment = surgical closure of the septum – may result in right ventricular failure

Question 50

Septal defects

• Ventricular septal defects (VSD)

Answer 50

o Majority are in membranous septum, some muscular
o Due to higher pressure of the left ventricle, blood flows form the left to the right ventricle
o Excessive blood diverted to the lungs, resulting in pulmonary hypertension
o Results in hypertrophy and increased blood pressure of the right ventricle
o Increase in right ventricle blood pressure eventually results in blood moving back toward the left ventricle
o Most heal on their own in the 1st few yrs of life, but surgery can be used

Question 51

Obstruction

• Tricuspid atresia

Answer 51

o Tricuspid valve does not develop and stops the flow of blood from the right atrium to right ventricle
—Stenosis (narrowing) may also occur
o Causes hypoplastic right ventricle and pulmonary artery
o An ASD and VSD are needed to keep baby alive
o Mitral valve atresia can occur, but is less prevalent
o Treatment = surgery

Question 52

Obstruction

• Aortic/pulmonary stenosis

Answer 52

o Occurs when the outflow tract is partitioned asymmetrically
o Atresia occurs when the stenosis is so extreme that blood glow is completely blocked
—Usually leads to death in the early fetal period
o The ventricle pumping blood thru the affected artery becomes hypertrophic
o Treatment = surgery to replace heart valve

Question 53

Hypoplasia

• Persistent truncus arteriosus

Answer 53

o Outflow tract (conotruncus) fails to divide into pulmonary aortic channels
o A VSD (ventricular septal defect) is usually present
o Treatment = surgery
—VSD is closed, and the pulmonary arteries are connect to the right ventricle
o Still a high rate of survival even w/out surgery
o (Mixing of oxygenated and deoxygenated blood to lungs)

Question 54

Hypoplasia

• Hypoplastic left heart syndrome (HLHS)

Answer 54

o Left side of the heart (left atrium and ventricle, mitral valve, aortic semilunar valve) doesn’t develop completely
o Hypoplastic left ventricle can’t pump the necessary amt of blood to the body
o The only way for babies to survive HLHS is failure of the 2 fetal shunts to close
o Blood from the right ventricle travels thru the ductus arteriosus to the body
o Blood returning from the lungs access the right side of the heart thru the foramen ovale
o HLHS detection:
—May initially go undetected go undetected due to the open shunts
• If it goes undetected, the ductus arteriosus closes completely 1-2 days after birth
• Usually results in death
—HLHS can be detected about 18 weeks into pregnancy w/ an ultrasound
—If detected, a prostaglandin is given to keep the ductus arteriosus open
• This is a temporary measure

Question 55

1. Norwood operation

Answer 55

—done in the 1st week of life
• GOAL – to connect the aorta to the right ventricle
• The ductus arteriosus connecting the aortic and pulmonary arteries is closed
• The main pulmonary artery is separated form the left and right pulmonary arteries
• The aortic artery is separated form the left ventricle
• The aortic artery is connected to the pulmonary artery, allowing blood from the heart to enter the body via the right ventricle
• A BT (Blalock-Taussig) shunt is introduced, which connects the aorta and pulmonary artery, allowing some blood to be directed to the lungs
• If an ASD isn’t present, 1 will be artificially created
• The heart pumps mixture of oxygenated and deoxygenated blood to the body

Question 56

2. Hemi-Fontan/Glenn operation

Answer 56

– done between 4-6 months of age
• GOAL – reduce the workload o the right ventricle
• The superior vena cava (SVC) is connected to the pulmonary artery
o The SVC loses connection w/ the right atrium
• The BT shunt is removed
• Deoxygenated blood from the SVC moves to the lungs, becomes oxygenated, empties into the left atrium, moves to the right atrium, then to the right ventricle, mixed w/ deoxygenated blood from the inferior vena cava (IVC), and is sent to the body

Question 57

3. Fontan operation

Answer 57

done between 18-36 months of age
• GOAL – send all deoxygenated blood to the lungs
• The IVC is connected to the pulmonary artery
• A wall called a baffle is built in the right atrium, separating the right atrium from the vena cava
• Deoxygenated blood from the SVC and IVC moves to the lungs, becomes oxygenated, empties into the left atrium, moves to the right atrium, then to the right ventricle and is seen to the body

Question 58

Identify the 4 parts of the urinary system and their purpose.

Answer 58

• Urogential (urinary and reproductive) system arises from intermediate mesoderm of the early embryo
o Formation of urinary system begins before formation of the reproductive system
—Urinary system has 4 major components:
• 1. Kidneys – filter blood and remove wastes
• 2. Ureters – transport urine out of the kidneys to the bladder
• 3. Bladder – stores urine
• 4. Urethra – transports urine outside the body

Question 59

Describe the parts of the adult kidney, including the structure of a nephron.

Answer 59

• Kidney is composed of the following parts:
o Renal capsule – tough outer covering
o Renal cortex – contains nephrons (except loop of Henle)
o Renal medulla – contains loop of Henle
o Calyxes – collect urine, funnel to ureter

• Kidneys receive blood from renal arteries, which branch off the abdominal aorta

• Kidneys are organized into renal lobes, which are made up of nephrons (the functional unit of the kidney)
o Lobe = renal pyramid (wedge of medulla) + renal cortex outside it
o A kidney can have up to 18 lobes and 1.5 mil nephrons
o All nephrons are made before birth

o	Nephron composition:
—Glomerulus – network of capillaries
—Bowman’s capsule – sac that surrounds the glomerulus
—A system of tubules
•	Proximal convoluted tube
•	Loop of Henle
•	Distal convoluted tube
•	Collecting tube

Question 60

• A total of 3 kidneys are formed throughout human development:

Answer 60

o 1. Pronephros – homologue of a kidney; rudimentary in humans; final form in primitive fishes
o 2. Mesonephros – similar to kidneys seen in fish and aquatic amphibians
o 3. Metanephros - The functioning adult human kidney

Question 61

Pronephros

Answer 61

• The pronephric duct induces formation of pronephric tubules which make up the pronephros (1st kidney)
• The pronephric duct begins to extend caudally, giving rise to the mesonephric duct (nephric duct/wolffian duct)
o This induces formation of additional tubules from the intermediate mesoderm
o Mesonephric tubules make up the mesonephros (2nd kidney)

Question 62

Mesonephros

Answer 62

• As mesonephric tubules are induces caudally, the cranial pronephric tubules degenerate
• At about day 35, the ureteric bud forms at the caudal nephric duct dear the cloaca and enters the metanephrogenic mesenchyme (part of the intermediate mesoderm)
• Together, the metanephrogenic mesenchyme and the ureteric bud differentiate into the metanephros (kidney #3, the definitive adult kidney)
• The mesonephros degenerates when the metanephros becomes functional
• Certain mesonephric tubules and ducts won’t degenerate, and will form part of the genital system

Question 63

Explain how the ureteric bud and metanephrogenic mesenchyme work together to create the kidney.

Answer 63

• The metanephrogenic mesenchyme and the ureteric bud induce each other to form the kidney
• The metanephrogenic mesenchyme induces the ureteric bud to elongate and branch
• Tips of the growing branches induce the surrounding tissue to form cellular aggregates which differentiate into renal nephrons
• The mesenchyme derived tubules form the capsule, proximal and distal convoluted tubules, and the loop of Henle
• The ureteric bud forms the collecting duct and ureter

Question 64

Explain the role of mesenchymal-to-epithelial transformations in kidney development.

Answer 64

• Mesenchymal cells condense around the tip of the branching ureteric bud. As the nephrogenic vesicles elongate and form the renal tubules, a slit shaped structure will form at the distal end.
• The shape of the slit is caused by the mesenchymal-to-epithelial transformation of the nearby cells. These new epithelial cells will become podocytes of Bowman’s capsule.
• Vascular endothelial cells grow from the aorta into the slit-shaped structure and will eventually from the mature glomerulus.
• As the tubule continues to develop, all the tubular cells undergo a mesenchymal-to-epithelial transformation
• The proximal and distal convoluted tubes form, as well as the Loop of Henle
• The tubule develops in a distal to proximal fashion w/ regard to the ureteric bud
• The mature nephron is made from 3 different types of mesoderm:
o Mesoderm from vascular endothelial cells, the ureteric bud, and metanephrogenic mesenchyme
• Mesenchymal-to-epithelial transformations (MET) allow cells lining the tubule to form tight sheets of epithelium cells
o Podocytes – special epithelial cell type formed
—Surround the glomerular capillaries and have long foot processes.
• These foot processes interdigitate and form a diaphragm salts can pass thru

Question 65

Describe the placement of the kidneys within the embryo, and how this changes during development.

Answer 65

• Late in embryogenesis, the kidneys migrate from the pelvic region to the abdominal region
o Combination of caudocranial and lateral displacement
o This brings the kidney in contact w/ the adrenal gland
o As the kidney ascends, it receives arteries from more cranial parts of the aorta; most caudal arterial connections degrade
o Kidneys rotate 90 degrees as they move, changing position of renal pelvis.
o Migration of the metanephric kidney causes most of the mesonephric kidney to degenerate

Question 66

Explain the formation of the bladder, ureter, and urethra. What tissues are they derived from?

Answer 66

• The caudal end of the hindgut is called the cloaca, and it initially forms as a single large chamber
o In the early embryo, it serves as the termination point for the digestive, urinary, and reproductive systems.
o It also induces formation of the allantois
• The mesodermally derived urorectal septum is initially located between the hindgut and base of the allantois

• At about 6 weeks of development, the urorectal septum grows toward the cloacal membrane, dividing the cloaca into the urogenital sinus and the rectum
o This also divides the cloacal membrane into the anal membrane and the urogenital membrane
• The urogenital sinus gives rise to the urinary bladder and the urethra
• By 3 months, the fetal kidneys begin to excrete urine into the amniotic cavity, making up most of the volume of the amniotic fluid

• Initially, urine empties into the bladder via the mesonephric duct
• The urogenital sinus cells then wrap themselves around the ureter and the ducts
o Urine now passes from the collecting tube of the nephron to the ureter and into the urinary bladder
• The ducts migrate ventrally and open to the urethra (outlet of the bladder), leaving only the ureter to empty into the bladder

Question 67

Anomaly

Answer 67

something that’s abnormal; deviated from normal; usually asymptomatic

Question 68

Unilateral

Answer 68

Only on 1 side of the body

Question 69

Bilateral

Answer 69

On both sides of the body

Question 70

Benign

Answer 70

No symptoms or mild symptoms that don’t interfere w/ life

Question 71

Extopia

Answer 71

Tissue someplace where it shouldn’t be; may be due to error in migration

Question 72

Cyst

Answer 72

Fluid filled sac

Question 73

Describe the role of the kidneys in producing amniotic fluid. What is the effect of renal insufficiency on the amniotic fluid and infant?

Answer 73

• Kidneys take over the production of amniotic fluid w/in the amniotic sac at 4 months
o Before this time it is produced by the placenta
o Amniotic fluid is 98% waster, 2% salts, waste, fetal cells (amniotic stem cells)
o Cushions to protect fetus; lubricates fetus to allow movement; “breathed” into lungs; swallowed thru digestive tract

• Too much or too little amniotic fluid is dangerous for the baby
o Causes compression of developing oranges, underdevelopment
o Can be detected by ultrasound during prenatal exams

Question 74

Discuss the prevalence and diagnosis of congenital urinary system defects. How common are they, and how are they detected?

Answer 74

• Anomalies of the urinary system are common: 3-4% of all live births
o 2nd most common site of birth defects (heart is #1)
o Represent 20-30% of all diagnosed congenital defects
o Many are asymptomatic or only manifest later in life

• Functioning kidneys are required for life

Question 75

Minor kidney defects…

Answer 75

such as abnormal position of kidney or ureters are often completely asymptomatic throughout the lifespan
o Individual may be prone to UTIs or kidney stones

Question 76

Moderate kidney defects

Answer 76

that compromise kidney function can also be asymptomatic
o Other kidney will grow (hypertrophy) and take over for its function
o Increased workload may eventually damage the kidney

Question 77

Severe kidney defects

Answer 77

impair kidney function and lead to progressive damage
o Kidney can’t process fluid. Fluid build up in tissues, lungs
o Toxic waste products (salts, heavy metals, amino acids) build up in blood
o Untreated will lead to End Stage Renal Disease, death

Question 78

Renal agenesis

Answer 78

-absence of kidney tissue
—Usually due to poor interaction of the ureteric bud and metanephrogenic mesenchyme
—Unilateral – the existing kidney undergoes hypertrophy and works to make up for the lack of the a second
—Bilateral – child usually dies a few hours after birth
• Usually detected in utero due to the lack of amniotic fluid
• Causes Potter’s sequence
o Potter’s sequence is a consequence of reduced levels of amniotic fluid
—Pulmonary hypoplasia
—Oligohydramnios
—Twisted skin (wrinkled)
—Twisted face (Potter facies)
—Extremities defects
—Renal agenesis (bilateral)

Question 79

Renal Duplication

Answer 79

—May be due to widely branching ureteric buds or the formation of too many buds
—Also usually asymptomatic but sometimes associated w/ UTIs and vesicoureteric reflux (urine moves from the bladder into the ureter)

Question 80

Renal Hypoplasia

Answer 80

-underdeveloped kidney
—Kidney is smaller, w/ fewer nephrons than usual, but otherwise normal
—Causes are unknown, but may be due to deficiencies in necessary growth factors
—The normal kidney usually makes up for the hypoplastic kidney
—Usually asymptomatic

Question 81

Pelvis kidney

Answer 81

—Type of ectopic kidney
—Kidney doesn’t migrate properly to the abdomen and remains in the pelvis (defect in migration)
—Usually asymptomatic but may induce abdominal pain and trouble urinating

Question 82

Crossed kidney

Answer 82

—Another type of ectopic kidney
—Both kidneys are found on the same side of the body
• During migration, 1 crosses over to the other side of the body
—Often results in a fused kidney (super kidney)
—Cause is unknown
—Usually asymptomatic, but symptoms may include reflux and/or kidney stones

Question 83

Horseshoe kidney (super kidney)

Answer 83

—Kidneys fuse at their inferior poles and are physically blocked from leaving the pelvis
—Usually asymptomatic, but symptoms may include abdominal pain, kidney stones, and UTIs

Question 84

Polycystic kidney disease

Answer 84

—1000s of cysts form on the nephrons of the kidney (may also be present on the liver and pancreas)
—Genetic trait
—Symptoms often don’t appear until middle-age and include abdominal pain and high blood pressure
—The cysts interfere w/ renal function and eventually lead to complete loss of kidney function
—Unclear why this occurs: may be due to mutations in the the PKD1 and/or PKD2 genes

Question 85

Multicystic dysplastic kidney

Answer 85

—Multiple irregular cysts form in the kidney, rendering it nonfunctional
—Occurs during fetal development
—May be bi- or unilateral
• In bilateral cases, infant exhibits Potter’s sequence and doesn’t survive

Question 86

Medullary sponge kidney

Answer 86

—Small cysts and dilated collecting tubules in 1 or both kidneys
—Fairly benign disorder of the kidneys
—Symptoms: UTIs, kidney stones
—Causes in unknown. May be genetic.

Question 87

Ectopic ureter

Answer 87

—Ureter terminates at a site other than the urinary bladder
• Usually terminates at the urethra. Can also connect to vagina and vestibule in women; van deferens, seminal vesicle, ejaculatory duct
—Symptoms include incontinence and potentially reflux of waste back towards the kidneys

Question 88

Duplicated ureter

Answer 88

—2 ureters drain from a single kidney
—May result from duplication of a ureteric bud or abnormal branching of the ureteric bud
—May be partial (extra ureter connects to ureter) or complete (extra ureter connects to bladder)
—Symptoms include UTIs and incontinence

Question 89

Compare the prognosis for the following renal cystic disorders: polycystic kidney disease, multicystic dysplastic kidney, and medullary sponge kidney.

Answer 89

• Polycystic kidney disease:
o Symptoms usually doesn’t appear until adulthood
o Treatment = change in diet surgery to remove nonfunctional kidney or kidney transplant
o (Middle – in nephrons, affects filtering; larger cysts than medullary sponge kidney)
• Multicystic dysplastic kidney:
o In unilateral unhealthy/nonfunctional kidney removed
o If bilateral infant exhibits Potter’s sequence and doesn’t survive
o (Worst b/c large irregular cyst that obliterate function of kidneys, bilateral worse than unilateral)
• Medullary sponge kidney:
o Fairly benign disorder
o Treatment = prevention of kidney stones and pain management
o (Least worst bc smaller cyst and they’re not in nephron but in collecting tube causing minor blockages, dot not interfere w/ kidney to filter blood)

Question 90

Explain how we know that SRY is the testis-determining factor.

Answer 90

• Major candidates for the “testis-determining factor” – all located on the Y chromosome
o H-Y antigen (antigen only on the cells of males) – XX males exist w/out it
o ZFY gene – XX males exist w/out it
o SRY gene – ZFY deficient XX males have Sry, and the gene is absent in XY females
—Believed to be the testes determining factor

Question 91

Genetic sex

Answer 91

determined at fertilization

o (what sex chromosomes one has: XX, XY)

Question 92

Phenotypic sex

Answer 92

seen at ~7 weeks of development

o Primary sex determination – development of the gonads
o Secondary sex determination – development and formation of duct system, external genitalia, body har, muscle tone, breasts, etc.
—Usually determined by hormones secreted from from the gonad
• No gonad = female phenotype

• Sometimes, genotype and phenotype don’t correspond

Question 93

Describe the origin, migration, and fate of primordial germ cells. How do the PGCs initiate formation of the reproductive system? What structures do the PGCs become in an adult male or female?

Answer 93

• Primordial germ cells (PGC) – seen in the human yolk sac by the 4th week of development
o Migrate from the yolk sac to the mesoderm of the posterior body wall where they induce formation of the genital ridge (future gonad)

• Arrival of the PGCs in the genital ridge induces some cells of the adjacent mesonephric tissue (the 2nd embryonic kidney) to enter the genital ridge also

• The germ cells and the gonad depend on each other for proper development
o Germ cells reach the genital ridge at about 6 weeks

• The gonads determine the sex of the gametes
o Ex.: XX PGCs will develop into spermatogonia if implanted into a male gonad
• (Yolk sac —> yolk stalk —> embryo —> gut —> genital ridge (intermediate mesoderm)

Question 94

The genital ridge

Answer 94

o Can be seen at ~4 weeks
o Develops from the intermediate mesoderm adjacent to the kidneys
o Will give rise to the gonad
o Is bipotential until about week 8
o Contains primitive sex cords which will give rise to mature sex cords

Question 95

Dev. Of the male gonad

Answer 95

o Presence of Sry causes the bipotential genital ridge to differentiate into the testes
—Sry can be detected for a very short time around week 8
o Sex cords become separated from the outer connective tissue by the tunica albuginea
—Outer sex cords form the seminiferous tubules
—Inner sex cords form the rete testes which connect to the the efferent ductules

Question 96

Dev. Of female gonad

Answer 96

o If testes don’t form
—Ovaries develop later than testes, and the presence of PGCs is necessary for ovary development
o Sex cords are present, but are less well developed than in the testes
—Likely give rise to ovarian follicle cells
o Once in the developing ovary, the PGCs (oogonia) where they become stalled
o Each oocyte becomes associated w/ follicular cells to form a primordial follicle

Question 97

• Bipotential duct system

Answer 97

o 2 types of ducts are present:
—Mesonephric (Wolffian) duct
—Paramesonephric (Mullerian) duct – form lateral to the Wolffian ducts and connect to the urogenital sinus

Question 98

Male duct system

Answer 98

o Testes are required for formation of the male duct system
o Sertoli cells secrete Mullerian INHIBITING substance, which causes the Müllerian duct to degenerate
—Also stimulate the formation of Leydig cells which produce testosterone, allowing the mesonephric (Wolffian) ducts to continue growing
• The mesonephros will give rise to the efferent ductules, epididymis, vas deferens, and seminal vesicle

Question 99

Female duct system

Answer 99

o The absence of testes is required for formation of the female duct system
—Female duct system will form in the presence of an ovary or w/ no gonads
o No Mullerian inhibiting substance is produces (bc no Leydig cells), so the mesonephric duct degenerates
o The Müllerian duct will give rise to the oviducts, uterus, cervical, and upper vagina

Question 100

Compare the origin of the male and female genitalia. Which structures are derived from the genital tubercle, urethral groove, genital folds, and genital swellings?

Answer 100

• Like the development of the gonads, the genitalia also go thru a bipotential stage that lasts until about week 8
• The external indifferent genitalia consists of the:
o Genital tubercle – a midline swelling
o Urethral groove – opening of the urogenital sinus caused by the breakdown of the cloacal membrane
o Genital folds – surround the urethral groove
o Genital swellings – lateral to the genital folds
• Masculinizing influences are needed to develop male genitalia. Female genitalia develop by default

• Testosterone produced by the testes is converted to dihydrotestosterone (DHT)
o DHT causes:
—The genital tubercle to elongate to form the penis
• As the penis elongates, the urethra takes shape
o Forms in the proximodistal direction by ventral folding and midline fusion of the genital folds
—The genital swellings to form the scrotum

Question 101

• In the absence of DHT:

Answer 101

o The genital tubercle becomes the clitoris
o The genital folds become the labia minora
o The genital swellings become the labia majora
o The urethral groove will form the vestibule, which contains the external vagina and urethra

Question 102

Explain the 5 factors that determine an individual’s sex.

Answer 102

• An individual’s sex is determined by a combination of genetic and phenotypic factors:
o The # and type of sex chromosomes
o Types of gonads (ovaries of testes)
o Internal reproductive anatomy (tissues derived from ducts like uterus or seminal vesicle)
o External genitalia (labia/vagina or penis)
o Sex hormones during embryonic development and life

• Intersex individuals have an atypical combo of these male and female features
o Example:
— Female anatomy on outside, male on inside
—Genitals are in-between the normal male and female genitalia appearance
—Genetic mosaics and chimeras
o Assigned one gender at birth, may not be correct

Question 103

• Chimera

Answer 103

– composed of 2 or more genetically distinct cells (ie. 2 different zygotes)
o Usually results from 2 zygotes fusing early in development
—(Twins = 1 dies and is absorbed by the other so certain parts of living twin’s body are composed of dead twin)
• (Welfare mom)

Question 104

• Genetic mosaic

Answer 104

– an individual has 2 or more cell populations that are of different genotypes
o Due to NONDISJUNCTION of chromosomes during MITOSIS early in the life of the individual
o Is often seen in individuals w/ chromosomal abnormalities

• “A chimera is always a mosaic but a mosaic is not always a chimera”

Question 105

Reproductive system abnormalities

Answer 105

• A variety of sex chromosome abnormalities exist
• Causes reproductive system anomalies. The # and type of sex chromosomes control development of gonads, ducts, and genitalia
o X-inactivation lowers impact of extra X’s, but not completely (escaping X-inactivation)
• Usually due to NONDISJUNCTION of chromosomes during gametogenesis
o Or during mitosis early in development, generating a mosaic

Question 106

Turner syndrome

Answer 106

XO genotype
o Missing X chromosome
o Primary defect – primordial germ cells don’t reach the gonad during migration causing infertility
—Secondary defect – ovaries don’t develop correctly but uterine tubes, uterus, vagina are intact.

Question 107

• Klinefelter syndrome

Answer 107

– XXY genotype
o (Extra X = extra estrogen which causes hypogonadism (smaller testes)
—Usually causes infertility
—May result in health problems that typically affect women
—May cause delayed motor development

Question 108

• True gonadal intersex (hermaphroditism)

Answer 108

o Individual possesses both ovarian and testicular tissue
o May be the result of:
—Genetic mosaic (46XX/46XY) – ovary develops from XX cells, while testes develops from XY cells
—46 XX individuals usually have an X that carries a trans located Sry gene
—46 XY individuals usually have a mutation in Y
o All types usually have at least 1 ovotesis (contains seminiferous tubules and follicles) and may have the other gonad as a ovotestis, testis, or ovary
o (Depending on severity, can lead to fertility issues and formation of ducts)

Question 109

• Pseudohermaphroditism

Answer 109

o Only 1 type of gonad is present, but the external genitalia differs from the gonadal sex

Question 110

o Female pseudohermaphroditism

Answer 110

(XX intersex) – gonadal sex is female, secondary sex characteristics are male
—Caused by over-production of androgens (hormones necessary for masculine characteristics – testosterone)
• 1. Congenital adrenal hyperplasia (CAH) – causes the body to produce more androgens
o (genetic)
• 2. Elevated exposure to androgens during pregnancy
o (external source)

Question 111

o Male pseudohermaphroditism

Answer 111

(XY intersex) – gonadal sex is male, secondary sex characteristics are female
—Usually caused by problems w/ production of or receptors for testosterone
—Includes androgen insensitivity syndrome and 5-alpha-reductase deficiency

Question 112

• Androgen insensitivity syndrome (testicular feminization)

Answer 112

o Genetically XY, internal reproductive organs are male
o Testes produce testosterone, but cells cant’ respond to it due to a mutation in a testosterone receptor
o The body is still able to respond to estrogen, resulting in female external genitalia
o PGCs arrest in the testes and don’t develop further, resulting in sterility
o MIS is produces, so the paramesonephric duct degenerates

Question 113

• 5-alpha reductase deficiency

Answer 113

o Genetically XY, internal reproductive organs are male
o In people with this deficiency, DHT can’t be produced resulting in female secondary sex characteristics
—5-alpha-reductase converts testosterone to DHT

Question 114

• Malformations of the female duct system

Answer 114

o Usually due to a defect in the fusion of the paramesonephric ducts
o Successful pregnancies can occur in almost all cases

o Bicornuate uterus
—Uterine tube unfused

o Septate uterus
—Wall down middle of uterus

Question 115

• Cryptochidism

Answer 115

(undescended testicles)
o Spermatogenesis can’t occur due to temp in the body cavity
—Results in sterility

Question 116

• Ectopic testes

Answer 116

o Can migrate to the thigh, ventral abdominal wall, etc.

Question 117

• Hypospadias

Answer 117

urethra open on the ventral side of the penis
o (Caused by genital folds not completely fusing)
o Absence of the penis – failure of genital tubercle formation

Question 118

• Clitoromegaly

Answer 118

o Often due to congenital adrenal hyperplasia
o Can arise from testosterone treatments
o (Overgrowth of clitoris)

Question 119

• Labia scrotalization

Answer 119

(Fusion of labia)
o May stay fused until puberty when estrogen production increases
o Urination is still possible