Development of Urinary Tract & Common Abnormalities

Evolution of Kidney Development (3 stages)

Note the image: pronephric system are at the superior (cervical region) portion, mesonephric system at the middle portion and the metanephric system at the inferior (sacral region) portion of the embryo)

Mesonephric duct opens into the urogenital sinus.

Yellow: endodermal (gut)
Blue: intermediate mesoderm (kidney & genital)

Each vertebrate’s excretory system develop:

  • filtration units
  • nephric duct (connected to filtration unit)

1) Pronephros (1 pair of kidneys)

  • lowest verterbrates have 1 pair of kidneys
  • a few nephrons (filtration unit) connected to an unbranched pronephric duct
  • totally disappear at birth (human)

2) Mesonephros

  • More advanced classes (fish, amphibian)
  • A second pair of kidneys
  • linear array of nephrons (filtration unit) connected to an unbranced mesonephric duct
  • May remain at birth (part of male reproductive tract)

3)Metanephros

  • Amniote classes (reptiles, birds, mammals, humans)
  • Adult life human kidney

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As mentioned above, the urinary & genital system both develop from: intermediate mesoderm (along the posterior abdominal wall)

The pronephros
During 4th week, pronephros appear at the cervical region.
By the end of 4th week, pronephros disappears.

Note the intermediate column:
intermediate mesoderm where the urinary & genital system are derived from

Note the:

  • Pronephric tubule
  • Primary Nephric duct
  • Glomus (primitive glomerulus)

The mesonephros
At the end of 4th week, during the regression of the pronephros, the 1st tubules of mesonephros starts to appear.
By middle of 2nd month, a large mesonephros is visible.Then, the cranial tubules gradually starts degenerating.
By the end of 2nd month, most of the mesonephros disappears, but the mesonephric duct remains (only in males)

Note the intermediate mesoderm

Note the:

  • Bowman’s capsule
  • Mesonephric tubule
  • Mesonephric duct
  • Glomerulus

The pronephric components disappear.

The metanephrous
During the 5th week, the metanephros/permanent kidney appears in the sacral region of the intermediate mesoderm.

Note:

  • Mesonehpric duct
  • Urogenital sinus
  • Ureteric bud

The mesonephric duct opens into the urogenital sinus.
The ureteric bud is an outgrowth from the mesonephric duct. The ureteric bud joins the metanephric blastema (also known as metanephros).

Note:

  • Urogenital septum
  • Cloaca
  • Allantois

Portion of the hindgut (yellow) incorporated into the umbilical cord is known as the: Allantois.

Postallantoic part of the hindgut is called the: Cloaca.

The urorectal septum divides the hindgut (cloaca) into:

  • Dorsal : anorectal canal (the ASS)
  • Ventral: urogenital sinus (where the mesonephric duct opens into)

This is a pig embryo, note the location of the mesonephros & metanephros relative to one another.

URETERIC BUD
 

This image depicts the development of the metanephros to the adult kidney.
Note the ureteric bud: Dark pink

The ureteric bud elongates and become separate from the mesonephric duct (green), and is now opening into the vesico-urethral canal (pink) -> future urinary bladder.

The ureteric bud goes on penetrating the metanephric tissue (orange). The bud then dilates and forms the renal pelvis -> splits into branches (major calyces) -> each calyx forms 2 buds -> each bud forms 12/more generation of branching (2nd, 3rd, 4th orders forming the minor calyces) (1st, 5-12th orders forming the 1-3 millions of collecting tubules).

Therefore, the ureteric bud will develop the:

  • Minor & major calyx
  • Collecting Tubule
  • Collecting duct
  • Ureter

METANEPHROS


Note the:

  • Metanephric tissue caps
  • Renal vesicle

 

The metanephric mesoderm/metanephros/metanephric blastema at the end of collecting tubule are shaped in a way forming the metanephric tissue cap/metanephric mass, which will be induced by the collecting tubule to form nephrons. This metanephric tissue cap will form cell clusters, and lumen will then be formed within the cell clusters forming renal vesicle (metanephric vesicle). The renal vesicle will form a S-shaped tubule which will then develop into the bowman’s capsule. Capillaries will grow at the other end, forming glomerulus, whereby the Bowman’s capsule will fit around it. The tubules + glomerulus forms a nephron. Then the tubules of the nephron lengthen and forms the PCT, Loop of Henle & DCT.
Therefore, the metanephros will develop the:
  • Bowman’s capsule
  • PCT
  • Loop of Henle
  • DCT
 SUMMARY:

 

*IMPORTANT FOR EXAM: The permanent kidney:

Note the regions of the functional kidney derived from the metanephric mesoderm & ureteric bud.

1) Mesonephros/metanephric blastema/metanephric mesoderm:

  • Bowman’s Capsule
  • Proximal Convoluted kidney
  • Loop of Henle
  • Distal Convoluted Kidney

2) Ureteric Bud:

  • Minor & major calyx
  • Collecting Tubule
  • Collecting duct
  • Ureter

20 nephrons open into 1 collecting tubule.

As we already know, the ureteric bud is connected with the metanephric blastema/metanephros. (which the resulting collecting duct formed from the ureteric bud will induce the metanephros to form the renal vesicles). IF the ureteric bud for some reason fails to contact/connect or induce the metanephric blastema -> then the fetus will suffer from Congenital Polycystic Kidney (numerous collecting ducts surrounded by cysts/undifferentiated cells of the metanephros). There are 2 types:

1) Autosomal dominant 

  • Cysts from ALL parts of nephron
  • More common
  • Renal failure during adulthood

2) Autosomal recessive

  • Multiple cysts from collecting tubule
  • Progressive disorder
  • Renal failure in infancy 

 

It’s our genes that controls the formation of growth factors and determines whether the kidney develops normally or not.
It requires the epithelial-mesenchyme interaction. The signaling between these two different tissues is required to form the functional unit of the systems in which it is used.
The differentiation of the kidney involves the:
  • WT1 Transcription gene (expressed by the metanephrous mesoderm) via the GDNF & HGF Growth factors

It makes the tissue component differentiate & form the nephrons (in response to the ureteric bud induction via FGF-2, BMP-7 Growth Factors).

Mutation in WT1 gene produces abnormal differention, causing -> Wilm’s Tumour.

Branchial arches

  • Forms the anatomical bases for head & neck development
  • Related to gill (brachial system) & located near the developing pharynx (pharyngeal) of the embryo.

The branchial apparatus consists of:

  • Branchial (pharyngeal) arches
    • mesoderm
  • Branchial (pharyngeal) clefts
    • ectoderm
  • Pharyngeal pouches
    • endoderm
    • Simultaneous with the development of the arches & clefts
      • a number of outpocketings arise in the lateral wall of the pharyngeal gut
    • these pouches penetrate the surrounding mesoderm
      • but do not make open communication with the external clefts
  • Branchial membranes
    • ectoderm
    • endoderm

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Branchial (Pharnygeal) arches

  • Develop during the 4th week as rounded ridges on each side of the future head & neck region
  • 4 arches appear by the end of 4th week
    • separated from each other externally by grooves – branchial clefts
  • Function
    • support the lateral walls of the primitive pharynx
    • play an important role in formation of the face & neck
  • The mouth initially appears as a slight depression in the surface ectoderm
    • stomodaeum
    • at 1st separated from the primitive pharynx by the buccopharyngeal membrane

Branchial arches – Components

Each arch has a mesodermal core covered externally by ectoderm & internally by endoderm.

Neural crest cells migrate into the arches & give rise to skeletal components. The mesoderm of each arch gives rise to muscles.

A typical arch contains the following

  • A cartilaginous bar
  • A muscle element
  • An artery
  • A nerve

* REFER PRINTED NOTES ON THE ARCHES, CLEFTS, POUCHES, TONGUE & THYROID GLAND FORMATION

1) 1st branchial arch (Mandibular arch)

Clinical anatomy

  • Malformations result from deficiencies in components of the arch (primarily neural crest migration)
    • Treacher-Collins Syndrome (mandibulofacial dyostosis)
      • no ossification
        • abnormal external, middle and inner ear
      • no development of mandible
        • mandibular & malar hypoplasia
      • lower eyelid defects
    • Pierre Robin Syndrome
      • Mandibular hypoplasia
      • Cleft palate *
      • Eyes & ear defect
    • DiGeorge Syndrome
      • Absense of the thymus
      • Malformations of the mouth
      • Nasal clefts
      • Glossoptosis*
        • tongue displaced downwards
      • Cardiac abnormalities

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– The rest read from printed notes.

Formation of tongue
http://embryology.med.unsw.edu.au/Notes/head6.htm

Development of Nervous System

Prenatal Development of Central Nervous System

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At the beginning of the 3rd week, developing notochord induces overlying ectoderm to become neuroectoderm. Thus forming an elongated, slipper-shaped plate of thickened ectoderm – the neural plate.

  • Neural plate invaginates and forms neural tube
    • Pre-requirement for folding
      • Notochord
  • Anterior part
    • Forms
      • Forebrain
      • Midbrain
      • Hindbrain

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This neural plate invaginates, and the lateral edges of the plate becomes elevated to form the neural folds. This depressed region is the neural groove.

With further development, the neural folds become more elevated and each end fuses at the dorsal midline to form the neural tube.

Neural crest

After the fusion, the non neural ectoderm forms the epidermis. At the neural plate border where the neural plate converges, are the neural crest cells. The neural crest cells undergoes a epithelial to messenchymal transition, delaminating from the neuroepithelium and migrating through the periphery where they differentiate into many cell types.

  • Therefore, neural crest forms the PNS.
  • Structures derived from neural crest:
    • Dorsal root ganglia
    • Schwann Cells
    • Melanocytes
    • Pia-arachnoid (Leptomeninges)
    • Autonomic neurons
    • Adrenal medulla
  • During this time, susceptible to Fetal alcohol syndrome.
    • neural crest cells affected by ethanol
    • many mental/physical disability can arise from this

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  • The fusion of neural plate begins from the 4th somite (cervical region)
  • There are 2 parts where the neural tube is still open (no fusion yet):
    • Cranial neuropore
    • Caudal neuropore
  • These opened parts will close only at
    • 25th – 27th day of life (1st month after birth)

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Layers of neural tube

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  • Neural tube is composed of 3 layers
    • Neuroepithelial layer (neuroblasts)
      • innermost
      • It is a thick layer of pseudo-stratified epithelium lining the lumen of the neural tube.
      • Its component cells undergo rapid cell division to form new cells – neuroblasts
        • divide into – apolar –> bipolar –> multipolar
        • which migrates to the adjacent mantle zone
        • Forms:
          • Gliablasts
            • astrocytes
            • oligodendrocytes
          • Mesenchymal cells
            • Microglial cells
    • Mantle layer (gray mater)
      • middle
      • The neuroblasts migrated from the neuroepithelium forms a zone around the neuroepithelial layer
      • The neuroblasts are characterized by
        • large round nuclues
        • pale nucleoplasm
        • dark staining nucleolus
      • Mantle zone later forms the gray mater of spinal cord
    • Marginal layer (white mater)
      • outermost
      • predominantly composed of nerve fibers (processes of cells in the mantle zone)
      • Marginal zone later forms the white mater of the spinal cord.

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6 stages of neural cell development
Prenatal Cellular development in brain

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  • Stage 1
    • Mitosis/ Neurogenesis
      • neuroepithelial cell –> form neuroblasts
      • in the ventricular zone
  • Stage 2
    • Migration
      • from ventricular zone to their destination
      • migration aided by glial cells
        • acts like ladder
      • Filopodia assist in finding location after leaving radial glial cells
      • Abnormal migration will lead to
        • learning disabilities
        • schizophrenia
        • autism
  • Stage 3
    • Differentiation
      • gives rise to specific neurons & glial cells
  • Stage 4
    • Synaptogenesis
      • forming synapse with other neurons
      • dictates intelligence of fetus
      • Involved:
        • Neuronal maturation
        • Elongation of axons
        • Established terminals
        • Elongation of dendrites – form new spines
        • Expression of neurotrophins (from dendrites)
          • Neurotrophic factors
            • stimulate cell growth
            • helps neurons to mature
  • Stage 5
    • Cell death
      • Apoptosis – active cell death during development
      • Necrosis – passive cell death due to injury
  • Stage 6
    • Synapse rearrangement
      • depends on cognitive input & apoptosis

 

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Primary & Secondary brain vesicles

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Post-natal brain development

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  • At birth, brain weights 25% of full adult brain
    • Growth spurt of brain up til 4th year
  • At age 6, increases to 95%.
    • Due to myelination
      • Schwann cells
      • Oligodendrocytes
    • Proliferation of glial cells
    • Last wave of neurogenesis
    • Maturation of neurons
    • Increase in synaptic creativity
  • Cells of cerebullum forms many synaptic connections

Psychological Stages of Development

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Brain development (From birth – 21 years old)

Regions of the brain:

  • Temporal
    • Hearing
  • Parietal
    • Sensory
  • Limbic
    • Emotional component
      • more emo, less short term memoy
  • Frontal
    • Motor

Development of Pre-frontal cortex

  • Basis of age-related changes in cognitive function
    • view of life
  • Plays a role in
    • working memory
    • planning and carrying out sequences of actions
    • inhibiting inappropriate responses

Neuroplasticity in Adults

  • Neurons & synapses that are not activated by experience usually do not survive
    • use it or lose it!
  • Mature brain changes and adapts
    • Skill training leads to reorganization of motor cortex
    • Adult musicians who play instruments have an enlarged representation of the hand
      • in somatosensory cortex
    • no new neurons, but new synaptic rearrangement
  • Neurogenesis (new neurons formation) only present in
    • olfactory bulb
    • hippocampus

Autism

  • 3 core symptoms
    • reduced ability to communicate
    • reduced capacity for social interaction
    • preoccupation with a single subject/activity
      • repetitive behaviour
  • Signs begin before 3 years old
  • Brain damage tends to be widespread
  • Heterogenous
    • level of brain damage and dysfunction varies
      • Autism spectrum disorder
    • probably no single cause
  • Genetic basis
    • Mutigene disorder/mutation
    • Siblings – 5% chance
    • Monozygotic twins – 60% concordance rate
  • Mutation due to
    • Environmental hazards
      • pesticides
      • heavy metals
      • solvents
    • Autoantibody

Postnatal cerebral development in Adolescence

  • Prefrontal love is the last to fully develop

 

OLIS

Development of Musculoskeletal System

Read up Foundation 1 Embryology & 1st aid basic sciences.

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Skeletal system develops from:

  • Paraxial mesoderm
    • forms somites
      • a segmented series of blocks on each side of neural tube
      • somites form:
        • vertebral column
        • muscles of axial skeleton
        • body wall
        • head
  • Lateral plate mesoderm (somatic layer)
    • forms:
      • pelvic
      • pectoral girdle
      • long bones (of limbs)

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  • 1st pair of somites appear on the 20th day
    • at cervical region
  • formation of the somites
    • cranial-caudally
    • 3 somites per day
    • By the 5th week, have 44 pairs
      • Occipital – 4
        • 1st pair disappear at 4th week
      • Cervical – 8
      • Thoracic – 12
      • Lumbar – 5
      • Sacral – 7
      • Coccygeal – 8 to 10
        • Last 7 pairs disappear at 4th week
  • Ventromedial: sclerotome
    • mesoderm of sclerotome
      • surrounds neural tube & notochord
        • forms vertebral column
  • Dorsolateral: dermo-myotome
    • dermatome
      • forms skin
    • myotome
      • forms muscle

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  • Sclerotomic blocks
    • separated by intersegmental arteries
    • caudal part of each segment proliferate
      • caudal half of one sclerotome binds to cranial half of next one (see image below)
      • therefore body of vertebrae is of intersegmental origin (segmented)

 

 

 

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  • Messenchymal cells between cranial and caudal half of sclerotome
    • form intervertebral disc
      • annulus fibrosus (purple)
  • The remains of notochord
    • forms nucleuss pulposus

Developmental abnormalities

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Neural tube defect

  • diagnostic:
    • maternal alpha-fetoprotein
  • prevention
    • folic acid supplementation

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  • Neural crest cells
    • forms mesoderm of head
      • which forms bones of face & skull
  • Occipital somites
    • forms cranial vault & base of skull

Types of ossification (skull)

Membranous (messenchyme –> bone)

  • Neurocranium (inner part of skull)
    • forms cranial cavity
      • houses the brain
    • membranous part of neurocranium
      • fontanelles
        • flat ones of cranial vault sutures
        • enables baby’s skull to enlarge to accommodate growing brain
        • failure of formation
          • brain exposed to amnion causing degeneration
            • anencephaly
          • with herniation of brain
            • cranial meningocele
  • Viscerocranium (outer part of skull)
    • facial skeleton
      • from 1st & 2nd pharyngeal arches
  • Chondrocranium
    • base of skull

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Cells of somites migrate to form precursors of:

  • limb bud
  • body wall musculature

but retains nerves from segment of origin (?).

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By the end of 4th week,

  • limb buds out pocket
    • from ventral body wall
    • start from a mesoderm core
      • derived from somatic layer of lateral plate mesoderm
    • upper limb buds appear 1st
    • lower limb buds appear 2 days later
    • mesenchyme in bud condenses
      • 6th week – 1st cartilage model
      • 7th week – 1st limb muscles at base of limb bud
        • pattern of muscle depends on connective tissue into which myoblasts migrate
          • head region
            • C/T from neural crest cells
          • axial, body wall, limbs
            • C/T from somatic mesoderm
  • thickened ectoderm at distal border of limb bud (at the tip)
    • Apical ectodermal ridge (AER)
      • induces the pattern of the limb
        • differentiation of
          • limb bone
          • cartilage
          • muscle
      • if defected
        • fingers/toes may not form properly

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At the 7th week,

  • limbs rotate in the opposite direction
    • upper limb: 90% lateral
      • extensor muscles
        • lateral & posterior surface
      • thumb
        • lateral side (anatomical position)
    • lower limb: 90% medial
      • extensor muscles
        • anterior surface
      • great toe
        • medial side (anatomical position)

Bone growth with age

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Muscle development

 

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Prospective muscle cells

  • Epimere
    • extensors of vertebral column
    • innervated by: dorsal rami of spinal nerve
  • Hypomere
    • limb and body muscle wall
    • innervated by: ventral rami of spinal nerve
    • thoracic hypomere
      • splits into 3 layers
        • external intercostal
        • internal intercostal
        • innermost intercostal
    • abdominal hypomere
      • splits into 3 layers
        • external oblique
        • internal oblique
        • transversus abdominis

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Anomalies

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Dwarfism

  • 9 members of fibroblast growth factors & fibroblast growth factor receptors (FGFR)
    • regulate cellular events in proliferation and differentiation
  • FGFR-3
    • expressed in cartilage growth plates in long bones
    • mutation in p-arm of chromosome 4
      • autosomal dominant – hereditary
      • amino acid substitution
      • proliferation on chondrocytes in epiphyseal plate is disturbed
        • achondroplasia
          • most common causes of dwarfism
          • large head, small face, limbs shorted than trunk, bowed

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  • Amelia
    • complete absense of limbs
  • Meromelia
    • partial absense of limbs
  • Phocomelia
    • long bones absense
    • rudimentary hands & feet

Causes:

  • hereditary
  • drug induced
  • mothers on thalidomide
    • teratogen damage
      • mostly 3rd – 8th week

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  • Polydactyly
    • extra digits
  • Ectrodactyly
    • absence of digits
  • Syndactyly
    • abnormal fusion
      • caused by: anti-convulsant phenytoin
  • Lobster claw deformity
    • cleft hand & foot
  • Congenital hip dislocation
    • due to underdevelopment of acetabulum & head of femur
    • mostly female

Embryogenesis & Development of the genital system

Read Dr. JPJ’s lecture & foundation 1 Dr. Daw Khin Win. Also will be good to read from First Aid.

This is just a very short summary of the derivatives of the germ layers. Will update later on the embryogenesis process (3rd-8th week of development)

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Ectoderm

Tall columnar cells, it gives rise to external layer & organs that communicates with the external environment

  • skin
    • only epidermis
  • nervous system (neural crest cells)
    • CNS, PNS
  • Sensory epithelia
    • ear
    • nose
    • eye
      • corneal epithelium
      • conjunctiva
      • lens
      • retina
      • muscles of iris
  • Glands
    • invagination of epidermis
  • Ear
    • external auditory meatus
    • tympanic membrane (outer part)
    • membranous labyrinth
  • Lower part of anal canal
  • Terminal urethra
  • Teeth
    • enamel

Mesoderm

It gives rise to most muscles except the skin muscle (erector) & iris muscle. Derived from the invagination of ectoderm. It forms blood, connective tissue, bone, muscle, urogenital system (except bladder, prostate & urethra), gonads, cortex of adrenal gland (medulla is ectodermal), teeth (except enamel) and spleen.

Composed of 3 parts:

1) Paraxial mesoderm

  • At 3rd week segmented into somites
    • ventromedial part: sclerotome
      • forms vertebral column
    • dorsolateral part: dermomyotome
      • myotome: muscles
      • dermatome: skin

2) Intermediate mesoderm

  • In cervical & upper thoracic segments, it becomes segmental clusters: Nephrotomes
    • Caudally: forms unsegmented Nephrogenic cord
      • Kidney systems & gonads
    • Laterally: forms the ductal zone
      • Gives origin of the ducts of the kidney

3) Lateral plate mesoderm

  • Splits into 2 layers
    • Parietal
      • pain sensitive
      • lines the amnion
      • forms ventral & lateral body walls (together with ectoderm)
    • Visceral
      • pain insensitive
      • forms wall of gut
      • cells in the coelomic cavity form the mesothelial cells & serous membrane which lines the
        • pleural
        • peritoneal
        • pericardial cavities
  • Septum transversum
    • horseshoe shaped mesodermal plate at cranial end of embryo
    • adjoining the pericardial sac
    • forms
      • diaphragm
      • liver parenchyma
  • Somatopleura
    • parietal layer of peritoneal, pleura & pericardial sacs
    • dermis & subcutaneous tissue
    • skeletal & muscle elements of limb buds
  • Splanchnopleura
    • visceral layer of serous sac
    • muscles of heart & gut

Other than that: heart, blood cells (angioblasts)

Endoderm

It covers the ventral surface of the embryo and forms the roof of the yolk sac. Rapid growth of CNS causes lengthening of embryo causing cephalocaudal folding. Rapid development of somites causes broadening of embryo and lateral folding. Flat endoderm of the slipper shaped embryo is now tubular (primitive gut). Cavities incorporated by head & tail fold are the foregut & hindgut. Allantois is also derived from the endoderm.

Midgut is in communication with the yolk sac cavity (vitelline duct) which gets narrowed and constricted during the foldings.

There are 2 places where there is no intervening mesoderm

  • Buccopharyngeal membrane
  • Cloacal membrane

Derivatives

  • Epithelium
    • of the GIT
    • respiratory tract
    • urinary bladder & urethra
    • tympanic cavity & auditory tube (inner ear)
  • Duct system of liver
  • parenchyma of thyroid gland
  • pancreas

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Abnormal embryogenesis (3rd to 8th week)

  • Nutritional factors
    • Iodine deficiency
    • Hypervitaminosis
      • mental retardation
    • Mercuric fungicides
      • multiple neurological symptoms
  • Hormonal factors
    • Diabetes
      • skeletal defects
    • Progesterone
      • masculinising effects on female
    • Cortisone
      • cleft palate
  • Infections
    • German measles
      • cataract
      • deafness
      • PDA,ASD,VSD
    • Syphilis
      • deafness
      • mental retardation
    • Toxoplasmosis
      • hydrocephalis (big head)
      • microphthalmia
  • Drugs
    • Thalidomide (for leprosy)
    • Aminopterin
    • Diazepam
    • Thiouracil
    • Streptomycin
    • Alcohol
  • Xray
    • skull defect
    • spina bifida
    • cleft palate
    • microcephaly
    • mental retardation
    • blindness

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Gonadal sex

Indifferent gonads are composed of 3 cell types

  • Primitive germ cells (migrate to genital ridge)
    • lodge in the medulla
      • testes
      • cortex regresses
    • lodge in the cortex
      • ovary
      • medulla regreses
    • gonadal dysgenesis
      • non-migration of primitive germ cells
  • Cells of the coelomic epithelium
    • Sertoli cells of testes
    • Granulosa cells of the ovary
  • Mesenchyme of the gonadal ridge
    • interstitial cell
    • stroma

Phenotypic sex

Foetal testes secretes

  • Mullerian Regression Factor
    • by Sertoli cells
  • Androgenic steroids
    • by interstitial cells
    • testosterone (induce retension of Wolffian system)
    • DHT (induce formation of external genitalia)

Gonads

Male

  • Suspensory ligament degenerates
  • Gubernaculum attached
    • shortening of gubernaculum forms Processus vaginalis of peritoneum
    • brings testis and mesonephric duct from loin to goin
      • descent of testis
  • Mesonephric duct
    • forms duct of epididymis, vas deferens, seminal vesicle & ejaculatory duct
  • Paramesonephric duct regresses
  • Urethral folds fuse to form urethral groove

Female

  • Medullary sex cords (Rete ovarii)
    • degerates & form vascular stroma
  • Cortical sex cords
    • broken down into fragments by mesenchyme
      • form primary ovarian follicles
      • follicular cells derived from surface epithelium
  • Cranial part of genital ridge
    • suspensory ligament
  • Caudal part of genital ridge
    • Gubernaculum
      • Cranial: Ovarian ligament
      • Caudal: Round ligament of uterus
  • Broad ligament
    • arrests descent of artery
  • Mesonephric duct regresses
  • Paramesonephric duct
    • Cranial : fimbriae
    • Middle: fallopian tube
    • Caudal: body of uterus
      • caudal tip: Mullerian tubercle –> vagina
  • Origin of vagina
    • Upper part: Paramesonephric duct
    • Lower part: Urogenital sinus (sinovaginal bulbs)
  • Urethral folds do not fuse, but form labia minora

Development of urinary tract & common abnormalities

Evolution of Kidney Development (3 stages)

Note the image: pronephric system are at the superior (cervical region) portion, mesonephric system at the middle portion and the metanephric system at the inferior (sacral region) portion of the embryo)

Mesonephric duct opens into the urogenital sinus.

Yellow: endodermal (gut)

Blue: intermediate mesoderm (kidney & genital)

Each vertebrate’s excretory system develop:

  • filtration units
  • nephric duct (connected to filtration unit)

1) Pronephros (1 pair of kidneys)

  • lowest verterbrates have 1 pair of kidneys
  • a few nephrons (filtration unit) connected to an unbranched pronephric duct
  • totally disappear at birth (human)

2) Mesonephros

  • More advanced classes (fish, amphibian)
  • A second pair of kidneys
  • linear array of nephrons (filtration unit) connected to an unbranced mesonephric duct
  • May remain at birth (part of male reproductive tract)

3)Metanephros

  • Amniote classes (reptiles, birds, mammals, humans)
  • Adult life human kidney

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As mentioned above, the urinary & genital system both develop from: intermediate mesoderm (along the posterior abdominal wall)

The pronephros

During 4th week, pronephros appear at the cervical region.

By the end of 4th week, pronephros disappears.

Note the intermediate column:

intermediate mesoderm where the urinary & genital system are derived from.

Note the:

  • Pronephric tubule
  • Primary Nephric duct
  • Glomus (primitive glomerulus)

The mesonephros

At the end of 4th week, during the regression of the pronephros, the 1st tubules of mesonephros starts to appear.

By middle of 2nd month, a large mesonephros is visible.Then, the cranial tubules gradually starts degenerating.

By the end of 2nd month, most of the mesonephros disappears, but the mesonephric duct remains (only in males)

Note the intermediate mesoderm

Note the:

  • Bowman’s capsule
  • Mesonephric tubule
  • Mesonephric duct
  • Glomerulus

The pronephric components disappear.

The metanephrous

During the 5th week, the metanephros/permanent kidney appears in the sacral region of the intermediate mesoderm.

Note:

  • Mesonehpric duct
  • Urogenital sinus
  • Ureteric bud

The mesonephric duct opens into the urogenital sinus.

The ureteric bud is an outgrowth from the mesonephric duct. The ureteric bud joins the metanephric blastema (also known as metanephros).

Note:

  • Urogenital septum
  • Cloaca
  • Allantois

Portion of the hindgut (yellow) incorporated into the umbilical cord is known as the: Allantois.

Postallantoic part of the hindgut is called the: Cloaca.

The urorectal septum divides the hindgut (cloaca) into:

  • Dorsal : anorectal canal (the ASS)
  • Ventral: urogenital sinus (where the mesonephric duct opens into)

This is a pig embryo, note the location of the mesonephros & metanephros relative to one another.

URETERIC BUD

 

This image depicts the development of the metanephros to the adult kidney.

Note the ureteric bud: Dark pink

The ureteric bud elongates and become separate from the mesonephric duct (green), and is now opening into the vesico-urethral canal (pink) -> future urinary bladder.

The ureteric bud goes on penetrating the metanephric tissue (orange). The bud then dilates and forms the renal pelvis -> splits into branches (major calyces) -> each calyx forms 2 buds -> each bud forms 12/more generation of branching (2nd, 3rd, 4th orders forming the minor calyces) (1st, 5-12th orders forming the 1-3 millions of collecting tubules).

Therefore, the ureteric bud will develop the:

  • Minor & major calyx
  • Collecting Tubule
  • Collecting duct
  • Ureter

METANEPHROS

Note the:

  • Metanephric tissue caps
  • Renal vesicle

The metanephric mesoderm/metanephros/metanephric blastema at the end of collecting tubule are shaped in a way forming the metanephric tissue cap/metanephric mass, which will be induced by the collecting tubule to form nephrons. This metanephric tissue cap will form cell clusters, and lumen will then be formed within the cell clusters forming renal vesicle (metanephric vesicle). The renal vesicle will form a S-shaped tubule which will then develop into the bowman’s capsule. Capillaries will grow at the other end, forming glomerulus, whereby the Bowman’s capsule will fit around it. The tubules + glomerulus forms a nephron. Then the tubules of the nephron lengthen and forms the PCT, Loop of Henle & DCT.

Therefore, the metanephros will develop the:

  • Bowman’s capsule
  • PCT
  • Loop of Henle
  • DCT

SUMMARY:

*IMPORTANT FOR EXAM: The permanent kidney:

Note the regions of the functional kidney derived from the metanephric mesoderm & ureteric bud.

1) Mesonephros/metanephric blastema/metanephric mesoderm:

  • Bowman’s Capsule
  • Proximal Convoluted kidney
  • Loop of Henle
  • Distal Convoluted Kidney

2) Ureteric Bud:

  • Minor & major calyx
  • Collecting Tubule
  • Collecting duct
  • Ureter

20 nephrons open into 1 collecting tubule.

As we already know, the ureteric bud is connected with the metanephric blastema/metanephros. (which the resulting collecting duct formed from the ureteric bud will induce the metanephros to form the renal vesicles). IF the ureteric bud for some reason fails to contact/connect or induce the metanephric blastema,then the fetus will suffer from Congenital Polycystic Kidney (numerous collecting ducts surrounded by cysts/undifferentiated cells of the metanephros). There are 2 types:

1) Autosomal dominant

  • Cysts from ALL parts of nephron
  • More common
  • Renal failure during adulthood

2) Autosomal recessive

  • Multiple cysts from collecting tubule
  • Progressive disorder
  • Renal failure in infancy

image

It’s our genes that controls the formation of growth factors and determines whether the kidney develops normally or not.

It requires the epithelial-mesenchyme interaction. The signaling between these two different tissues is required to form the functional unit of the systems in which it is used.

The differentiation of the kidney involves the:

  • WT1 Transcription gene (expressed by the metanephrous mesoderm) via the GDNF & HGF Growth factors

It makes the tissue component differentiate & form the nephrons (in response to the ureteric bud induction via FGF-2, BMP-7 Growth Factors).

Mutation in WT1 gene produces abnormal differention, causing Wilm’s Tumour.

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Renal Agenesis

Renal agenesis occurs when 1 or both kidney fails to develop in fetus.

It can be caused by genetic/environmental factors:

  • Untreated diabetes of the mother

The metanephric blastema/metanephros fails to mature and the ureteric bud also fails to branch/elongate. Hence they whole kidney is not formed.

There are 2 types of renal agenesis:

1) Unilateral renal agenesis

  • 1 kidney missing
  • remaining kidney handles the workload
  • compatible with life

2) Bilateral renal agenesis

  • 1:10000 live births
  • both kidneys missing
  • results in renal failure

It is absolutely important that the fetus develops the kidneys by the 10th week, because that will be when the fetus starts urinating and provide it’s own amniotic fluid. In normal conditions, the fetus excretes urine and form the amniotic fluid, and then engulfs it. The engulfment of the amniotic fluid creates pressure on the oesophagus and will hence develop lumen (otherwise oesophagus will remain patent/solid).

So, if there is renal agenesis, there will be less amniotic fluid formed (oligohydramnios) and hence many other organs cannot be formed normally:

  • oesophageal atresia
  • anorectal atresia
  • hypoplastic lung
  • absent sex organs

If there is polyhydramnios (too much amniotic fluid), there will be abnormal facial appearance due to the pressure on the fetus’s face.

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Ascent of the developed kidney

 

image

After developing in the pelvic region, it shifts to the lumbar region due to straightening of the body curvature of the fetus

In the pelvic region,

Blood supply of the kidney is from: Pelvic branch of aorta

In the lumbar region,

Blood supply of the kidney is from: Renal artery.

The lower arteries degenerates.

Inability of kidney to ascend:

image

This condition is known as pelvic kidney, where the kidney remains in the pelvic region. It can be caused by:

1) the inferior mesenteric artery blocking the ascent

2) both kidney fused at the lower lumbar level and produce HORSESHOE KIDNEY

3) If it’s fully fused at the upper and lower part, then it is known as LUMP KIDNEY

Other abnormalities with ascent of kidney:

image

1) Ectopic kidney
image

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2) Abnormal duplication of the ureter (complete & incomplete)

Complete duplication of the ureter: opens into the prostate/vaginal causing hydroureter. Urine cannot be excreted/ drained therefore there will be dilatation of the ureter (hydroureter) or dilatation of the kidney (hydronephrosis).

 

image

3) Abnormal renal rotation (ventral & lateral position)

image

4) Supernumeric kidney (more than 2 kidneys)

SUMMARY OF DEVELOPMENTAL ANOMALIES OF THE KIDNEY

 

 

 

 

 

 

 

 

 

1) Formation of kidney (lack of interaction between ureteric bud & metanephros)

  • Polycystic kidney
  • Renal agenesis (unilateral/bilateral)
  • Wilm’s Tumour

2) Ascend of kidney

  • Horseshoe/Lump kidney
  • Ectopic kidney
  • Abnormal duplication of the ureter (complete/incomplete)
  • Abnormal rotation of the kidney
  • Supranumeric kidney

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Development of the Urinary Bladder

image

As discussed, during the 4th – 7th week,

The cloaca divides into the urogenital sinus & anorectal canal by urorectal septum. The tip of the urorectal septum is known as the perineal body.

With the opening of the mesonephric duct into the urogenital sinus, the urogenital sinus is divided into 3 parts:

1) Vesico-urethral canal

  • forming the urinary bladder

2) Pelvic part

  • forming the prostatic & membranous part of the male urethra

3) Phallic part

  • forming the penile part of the urethra

Notice that the cloaca is developed from the primitive gut (yellow), which is endodermal. Therefore, it can be concluded that:

  • Urinary bladder : Endodermal
  • Kidney: Mesodermal

The allantois which is embryologically connected to the umbilicus (urine is able to reach the umbilicus), will be obliterated into urachus (median umbilical ligament). However, if the allantois is unobliterated (patent allantois) at birth, then the baby’s umbilicus will smell of urine.

Mesonephric & paramesonephric duct

(revise reproductive system)

image image

IN MALE,

Y chromosone has the Testis-Determining Factor, which suppresses the paramesonephric duct and facilitates the development of the mesonephric duct.

The mesonephric duct elongates and highly coiled to form the:

  • epididymis
  • vas deferens
  • seminal vesicle
  • ejaculatory duct

The cranial part of the mesonephric duct forms the:

  • appendix of the epididymis

The mesonephric tubules forms the efferent ductule of testis.

The paramesonephric duct is obliterated in males.

Summary,

  • Mesonephric duct: Male
  • Paramesonephric duct: Female

The mesonephric duct incorporates with the urinary bladder forming the internal trigone, therefore the internal trigone is the only part of the urinary bladder which is mesodermal (the others endoderm).

*What is the importance of the internal trigone?

Anatomically: No submucosa

Physiologically: Most stretch receptors are located in the internal trigone, therefore at 150ml of urine collected in the urinary bladder, the stretch receptors are alerted and hence this is the starting point of the micturition reflex.

Anomalies of the urinary bladder/tract

1) Penile abnormalities

Abrnomal fusion of the urethral plates (folds) during the development of penile urethra is the causative factor

  • Epispadius

image

The abnormality of the urethral development where the urethra generally opens on the dorsum (top/side) of the penis rather than the tip.

  •  Hypospadius

imageimage

Relatively common abnormality in which the opening of the urethra is on the underside of the penis

2) Ectopia vesicae/Bladder exstrophy

image

It is a rare development abnormality that is present at birth.

The bladder & related structures are turned inside out, the posterior vesical wall turns outward (exstrophy) through an opening in the abdominal wall and urine is excreted through this opening. There is deficiency of the anterior abdominal wall.

3) Patent allantois

4) Micropenis

image image

 

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Question:

A 2 year old child is brought to the hospital with complaints of difficulty in urination. On examination, the external urethral meatus is found on the under aspect of the penis in the middle (hypospadius). Which of the following developmental error is true for this patient?

  • Abnormality of the ureteric bud (kidney)
  • Abnormality of the metanephros (kidney)
  • Abnormality of the vesico-urethral canal (urinary bladder)
  • Abnormality of the urethral plate (CORRECT)
  • Abnormality of the mesonephric duct (up til ejaculatory duct only)