Exam 3 Flashcards
(119 cards)
1
Q
Craniofacial Structures are composed of all 3 germ layers:
A
Ectoderm
Mesoderm
Endoderm
2
Q
Ectoderm:
A
Skin Cranial nerves (neural ectoderm)
3
Q
Mesoderm:
A
Muscles
Cartilage
Bone
Blood vessels
4
Q
Endoderm:
A
Lining of the mouth
Nasal cavity
Pharynx
5
Q
• Most structures in the head and neck can be traced back to the:
A
o Pharyngeal grooves (ectoderm)
o Pharyngeal arches (mesoderm)
o Pharyngeal pouches (endoderm)
• Neural crest cells also contribute to many tissues
6
Q
• Pharyngeal arches:
A
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
7
Q
As embryonic folding occurs, the pharyngeal arches…
A
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
8
Q
o Components:
—Each pharyngeal arch contains:
A
• 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)
9
Q
• Fate and Derivatives of the Pharyngeal arches:
o Cartilage …
A
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.
10
Q
Fate and Derivatives of the Pharyngeal arches:
o Muscles…
A
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
11
Q
Fate and Derivatives of the Pharyngeal arches:
o Nerves…
A
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
12
Q
• Fate and Derivatives of the Pharyngeal Pouches:
A
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
13
Q
• Fate and Derivatives of the Pharyngeal Pouches:
thyroid, parathyroid, and thymus glands
A
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.
14
Q
• Fate and Derivates of the Pharyngeal Grooves:
A
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.
15
Q
Explain why ectopic thyroid, parathyroid, and thymus tissue can sometimes be found in the neck. Describe where they are most likely to be found.
A
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.
16
Q
Give an example that demonstrates neural crest patterning is important for facial structure.
A
• 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.
17
Q
Summarize the development of the facial primordia.
A
• 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.
18
Q
the facial primordia. What happens to each of them?
A
• 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.
19
Q
Cleft lip
A
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.
20
Q
Disorder: Cervical sinus
A
• 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.
21
Q
Cervical cysts
A
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.
22
Q
Cervical vestiges
A
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.
23
Q
• 22.q11.2 Deletion Syndrome
A
(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
24
Q
Compare and contrast cleft lip and cleft palate.
A
??
25
Compare and contrast the flow of blood through a fetal and adult heart.
• 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
26
• Development of the heart:
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
27
• Development of the heart:
| o Cells of the primary heart field give rise to:
—Ventricles
—Left atrium
—Some of the right atrium
—Some of the outflow tract
28
• Development of the heart:
| o Cells of the 2nd heart field give rise to:
—Most of the outflow tract
| —Most of the right atrium
29
Describe how embryonic folding creates the primitive heart tube.
• 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
30
Explain how the heart's shape changes during cardiac looping.
• 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)
31
• 3 shunts in fetal circulation are needed to supply highly oxygenated blood to the body and developing brain:
1. Foramen ovale
2. Ductus arteriousus
3. Ductus venosus
32
1. Foramen ovale (present in the interatrial septum)
—Opening between right and left atria
—Shunts highly oxygenated blood from right atria to left atria
—Blood moves from LA to LV, aorta, body
33
o 2. Ductus arteriosus
—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
34
o 3. Ductus venosus
—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
35
Explain how blood flow in an infant changes at birth. What happens to the three shunts?
• 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.
36
Cyanosis
bluish skin. Caused by too much deoxygenated hemoglobin
| o Oxygen levels in circulatory system is very low, individual not receiving enough oxygen.
37
Stenosis
Narrowing of pathway
38
Atresia
tissue that doesn’t develop or is very underdeveloped and therefore, not functional
39
Hypoplasty
tissue/structure is smaller/underdeveloped from what it should be; smaller than normal
40
Hypertrophy
larger than normal; enlarged
41
Persistent
something that stays around longer than it should
42
Patent
A vessel that is open when it shouldn’t be
43
Secondary effect
Not the direct result of a disorder but...???
44
Palliative
relieving pain w/out dealing w/ the cause of the condition
45
Discuss the prevalence and diagnosis of congenital heart defects. How common are they, and how are they detected?
• 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
46
Patent ductus arteriosus (PDA):
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)
47
Transposition of the great arteries
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
48
Tetralogy of Fallot
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
49
Septal defects
| • Atrial septal defects (ASD)
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
50
Septal defects
| • Ventricular septal defects (VSD)
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
51
Obstruction
| • Tricuspid atresia
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
52
Obstruction
| • Aortic/pulmonary stenosis
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
53
Hypoplasia
| • Persistent truncus arteriosus
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)
54
Hypoplasia
| • Hypoplastic left heart syndrome (HLHS)
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
55
1. Norwood operation
—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
56
2. Hemi-Fontan/Glenn operation
– 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
57
3. Fontan operation
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
58
Identify the 4 parts of the urinary system and their purpose.
• 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
59
Describe the parts of the adult kidney, including the structure of a nephron.
• 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
```
60
• A total of 3 kidneys are formed throughout human development:
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
61
Pronephros
• 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)
62
Mesonephros
* 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
63
Explain how the ureteric bud and metanephrogenic mesenchyme work together to create the kidney.
* 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
64
Explain the role of mesenchymal-to-epithelial transformations in kidney development.
• 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
65
Describe the placement of the kidneys within the embryo, and how this changes during development.
• 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
66
Explain the formation of the bladder, ureter, and urethra. What tissues are they derived from?
• 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
67
Anomaly
something that’s abnormal; deviated from normal; usually asymptomatic
68
Unilateral
Only on 1 side of the body
69
Bilateral
On both sides of the body
70
Benign
No symptoms or mild symptoms that don’t interfere w/ life
71
Extopia
Tissue someplace where it shouldn’t be; may be due to error in migration
72
Cyst
Fluid filled sac
73
Describe the role of the kidneys in producing amniotic fluid. What is the effect of renal insufficiency on the amniotic fluid and infant?
• 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
74
Discuss the prevalence and diagnosis of congenital urinary system defects. How common are they, and how are they detected?
• 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
75
Minor kidney defects...
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
76
Moderate kidney defects
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
77
Severe kidney defects
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
78
Renal agenesis
-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)
79
Renal Duplication
—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)
80
Renal Hypoplasia
-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
81
Pelvis kidney
—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
82
Crossed kidney
—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
83
Horseshoe kidney (super kidney)
—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
84
Polycystic kidney disease
—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
85
Multicystic dysplastic kidney
—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
86
Medullary sponge kidney
—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.
87
Ectopic ureter
—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
88
Duplicated ureter
—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
89
Compare the prognosis for the following renal cystic disorders: polycystic kidney disease, multicystic dysplastic kidney, and medullary sponge kidney.
• 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)
90
Explain how we know that SRY is the testis-determining factor.
• 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
91
Genetic sex
determined at fertilization
| o (what sex chromosomes one has: XX, XY)
92
Phenotypic sex
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
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?
• 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)
94
The genital ridge
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
95
Dev. Of the male gonad
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
96
Dev. Of female gonad
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
97
• Bipotential duct system
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
98
Male duct system
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
99
Female duct system
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
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?
• 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
101
• In the absence of DHT:
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
102
Explain the 5 factors that determine an individual's sex.
• 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
103
• Chimera
– 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)
104
• Genetic mosaic
– 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”
105
Reproductive system abnormalities
• 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
106
Turner syndrome
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.
107
• Klinefelter syndrome
– 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
108
• True gonadal intersex (hermaphroditism)
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)
109
• Pseudohermaphroditism
o Only 1 type of gonad is present, but the external genitalia differs from the gonadal sex
110
o Female pseudohermaphroditism
(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)
111
o Male pseudohermaphroditism
(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
112
• Androgen insensitivity syndrome (testicular feminization)
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
113
• 5-alpha reductase deficiency
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
114
• Malformations of the female duct system
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
115
• Cryptochidism
(undescended testicles)
o Spermatogenesis can’t occur due to temp in the body cavity
—Results in sterility
116
• Ectopic testes
o Can migrate to the thigh, ventral abdominal wall, etc.
117
• Hypospadias
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
118
• Clitoromegaly
o Often due to congenital adrenal hyperplasia
o Can arise from testosterone treatments
o (Overgrowth of clitoris)
119
• Labia scrotalization
(Fusion of labia)
o May stay fused until puberty when estrogen production increases
o Urination is still possible
