Kidney Development PDF

Kidney Once upon a time, during the fourth week of development, a tiny embryo began to fold, forming a special ridge along its back called the urogenital ridge. This ridge was destined to shape two vital systems: the nephrogenic cord, which would form the urinary system, and the gonadal ridge, whic...

Kidney Once upon a time, during the fourth week of development, a tiny embryo began to fold, forming a special ridge along its back called the urogenital ridge. This ridge was destined to shape two vital systems: the nephrogenic cord, which would form the urinary system, and the gonadal ridge, which would give rise to the reproductive system. The Journey Through Kidney Stages The story of the kidneys unfolded as the nephrogenic cord gave rise to three sequential kidney forms: 1. Pronephros: This was the first and most primitive kidney, appearing like a small, non-functional blueprint. The pronephros, with its 3-15 tubules per segment, barely got a chance to work before being overshadowed by its successor. It served as a temporary guide for what was to come but didn’t contribute to the adult kidney in humans. 2. Mesonephros: Next came the mesonephros, a more advanced structure, forming from the middle nephrogenic cord. It was functional for a short time, producing urine and connecting to the cloaca through mesonephric ducts. By day 28, these ducts joined the cloaca, and by the 8th week, the mesonephros had fulfilled its purpose and began to regress. Despite its fleeting presence, the mesonephros contributed to the development of the aorta, gonads, and hematopoietic stem cells. 3. Metanephros: Finally, the metanephros emerged as the hero and permanent kidney. Its story began with the arrival of the ureteric bud, an outgrowth of the Wolffian duct, which invaded the metanephric blastema (a cluster of mesenchymal cells). Together, these two key players orchestrated a beautiful symphony of reciprocal induction: ○ The ureteric bud formed the collecting ducts, calyces, and renal pelvis.  ○ The metanephric blastema developed into the nephrons (the kidney’s functional units). By the 32nd week, all the kidney’s structural units were in place, though they would continue maturing postnatally. At full strength, these kidneys would house an impressive ~2 million nephrons in humans! The Bladder Joins the Story Meanwhile, in the embryo’s hindgut, the cloaca was busy transforming. By the 4th week, the uro-rectal septum divided the cloaca into two parts: 1. Urogenital sinus (anterior): This gave rise to:\n - The bladder from its upper part. ○ The urethra and parts of the reproductive tract. 2. Anal canal (posterior): This became the rectum. As the bladder developed, it absorbed parts of the mesonephric ducts, forming a triangular area at its base called the trigone. The ureters, which began as outgrowths of the mesonephric ducts, found their way into the bladder, while the ducts themselves moved inferiorly to contribute to the male reproductive tract. Key Features of the Kidneys Pronephros: The humble, primitive beginning, non-functional in humans but essential for early survival in lower vertebrates. Mesonephros: The temporary middle kidney, critical for early blood filtration and embryonic development. Metanephros: The ultimate, fully functional kidney that would sustain life after birth. Bladder: A masterpiece of cloacal division, it transformed into a vital storage organ for urine. Kidneys Embryonic folding during the fourth week of development marks the beginning of the urinary tract with the formation of a longitudinal mass known as the urogenital ridge. The ridge can divide into parts depending on the system it forms; the nephrogenic cord will form the urinary tract while the gonadal ridge will develop into the reproductive system. Beginning rostrally and progressing caudally, three kidneys will form over a few weeks within the nephrogenic cord: pronephros, mesonephros, and metanephros. The development of the kidney proceeds through a series of successive phases, each marked by the development of a more advanced kidney: the archinephros, pronephros, mesonephros, and metanephros. The pronephros is the most immature form of kidney, while the metanephros is most developed. The metanephros persists as the definitive adult kidney. The archinephric types of the kidney are the excretory system present in primitive vertebrates. It consists of a pair of archinephric ducts present dorsally inside the body cavity and extends the coelomic length. The archinephric kidney is found only in the living vertebrates which include the larvae of Myxine or Hagfish and some amphibians. Additional Information: - The archinephric kidneys have segmentally arranged tubules, a single pair per body segment. - Each tubule opens individually into a coelom by a peritoneal funnel and nephrotome. - Near the funnel is an external glomerulus without Bowman’s capsule, suspended in the coelom. - The tubules together from each kidney open into a common longitudinal duct known as Wolffian or archinephric duct, which later gets attached to the cloaca. - The external glomerulus is a small knot or cluster of capillaries which is situated closely to the nephrotome. - The kidney structure in present-day vertebrates kidneys is of three types pronephros, mesonephros, and metanephros all of which have been derived from the archinephric type. - Pronephros: It is the most primitive and present in the embryonic stage of all vertebrates and is non-functional in adults. It develops from the anterior portion of the nephrotome. Only 3 to 15 uriniferous tubules are present, one pair in one segment. - Mesonephros develops from the middle portion of the nephrotome after the degeneration of the pronephros. - Metanephros kidney is the functional kidney in amniotes, developed from the posterior portion of the nephrotome behind the mesonephros. In Mammals, the pronephros is non-functional but in some lower vertebrates such as fish and amphibians, the pronephros acts as embryonic kidney and is essential for survival. In the pronephros, after filtration through the glomus, fluid enters the coelomic cavity, also known as the nephrocoele. From there the filtrate is collected via ciliated funnels (nephrostomes) connected to the pronephric tubules. Surrounding these tubules is a blood sinus into which reabsorbed fluid passes whilst unabsorbed fluid is excreted via the pronephric (Wolffian ducts). Mammalian mesonephros develops from a mesodermal region called the AGM zone (aorta-gonad-mesonephros) which contributes to the development of the aorta, gonads and hematopoietic stem cells. Organogenesis of the mesonephros initiated when the pronephric duct reaches the presumptive mesonephric mesenchyme and induces adjacent mesenchymal cells to condense. The condensate contributes to the formation of the mesonephric tubules that develop into nephrons. In the human embryo, at day 24-26, mesonephric ducts form on the lateral and ventral sides of the nephrogenic ridge and induce formation of the mesonephros. By day 28, these ducts join the cloaca and by 8 weeks post conception, the human mesonephros has reached its maximal size and starts to regress. In humans, all of the branches of the ureteric bud and the nephronic units have been formed by 32 to 36 weeks of gestation. However, these structures are not yet mature, and will continue to mature after birth. Once matured, humans have an estimated two million nephrons (approximately 1,000,000 per kidney) but this number is highly variable ranging widely from approximately 200,000 to over 2.5 million per kidney. In humans, metanephros grows as the result of the reciprocal inductive interactions between the two primordial mesodermal derivatives: ureteric bud, an epithelial outgrowth of the Wolffian duct and the metanephric blastema, a group of mesenchymal cells. The metanephric kidney begins to develop after the Wolffian duct has extended caudally along the body axis and has produced an outgrowth called the ureteric bud which is an epithelial tissue that invades the metanephric blastema. The ureteric bud causes the metanephric mesenchyme to differentiate and form nephrons whilst the metanephric mesenchyme causes the ureteric bud to grow and bifurcate to form collecting ducts. Around the fifth week of gestation in humans, the ureteric bud induces the mesenchyme to form tubular and glomerular epithelia. The nephron arises from the metanephric mesoderm while the collecting duct, calyces and renal pelvis arise from the ureteric bud. The bladder and urethra of the urinary system are ultimately derived from the cloaca – a hindgut structure that is a common chamber for gastrointestinal and urinary waste. The development of the bladder begins during week four when the urogenital septum divides the cloaca into two parts, the rectum posteriorly and the urogenital sinus anteriorly. The urogenital sinus will continue to grow to form the bladder, with the inferior end forming the urethra. As the mesonephric duct fuses with the cloaca, part of the duct gets incorporated into the posterior wall of the bladder. Although the ureteric bud is an outgrowth from the mesonephric duct, it has a separate opening into the urinary bladder. As the kidneys ascend, the ureters elongate and open into the bladder superiorly, while the roots of the mesonephric ducts are carried inferiorly, before fusing to form the trigone region. Endodermal cells from the urogenital sinus soon replace the mesodermal cells epithelium of the trigone region, thus completing development. In the 4th-7th weeks of development, the cloaca is divided into two parts by the uro-rectal septum: Urogenital sinus (anterior) – divided into three parts: The upper part of the urogenital sinus forms the bladder. The pelvic part forms the entire urethra and some of the reproductive tract in females, and the prostatic and membranous urethra in males. The phallic/caudal part forms part of the female reproductive tract, and the spongy urethra in males. Anal canal (posterior) The urinary bladder is initially drained by the allantois. However, this is obliterated during fetal development and becomes a fibrous cord – the urachus. A remnant of the urachus can be found in adults; the median umbilical ligament, which connects the apex of the bladder to the umbilicus. As the bladder develops from the urogenital sinus, it absorbs the caudal parts of the mesonephric ducts (also known as the Wolffian ducts), becoming the trigone of the bladder. The ureters, which have formed as outgrowths of the mesonephric ducts, enter the bladder at the base of the trigone. The final structure varies between sexes: High-Yield Reviewer: Development of the Kidneys ________________________________________ 1. Functions of the Kidney Primary role: Excretory and homeostatic organ. Evolved to maintain internal high osmolarity as protovertebrates migrated to freshwater. Functions: o Removes final metabolic waste products (e.g., salt, uric acid). o Manages excretion and reabsorption of salts and fluids. o Regulates internal fluid concentration. ________________________________________ 2. Kidney Organogenesis A complex and stepwise process involving three sequential structures: 1. Pronephros (nonfunctional in humans). 2. Mesonephros (temporary excretory organ). 3. Metanephros (definitive kidney). Processes involved: o Cell proliferation, adhesion, apoptosis, differentiation, shape changes, and migration. o Requires signaling molecules from diverse families. ________________________________________ 3. Stages of Kidney Development a. Pronephros Primitive kidney; first stage of kidney development. Appears around day 22 of human gestation. Develops in the cervical region of the embryo. Nephrotomes: Tubular structures connected to the pronephric duct. Nonfunctional in humans: Pronephric duct cannot excrete waste outside the embryo. ________________________________________ b. Mesonephros Develops as the pronephric duct elongates caudally into the thoracolumbar region.  Mesonephric duct (Wolffian duct): Continues caudally and connects to the cloaca. Mesonephric tubules: o Derived from intermediate mesoderm; form capsules around capillary tufts (analogous to glomeruli). o Perform temporary filtration of blood and drain filtrate into the Wolffian duct. Function resembles fish and amphibian kidneys. ________________________________________ c. Metanephros (Definitive Kidney) Begins development in the fifth week of gestation. Develops from two structures: 1. Ureteric Bud (branch of the mesonephric duct): Forms the ureter, renal pelvis, major/minor calyces, and collecting ducts. 2. Metanephrogenic Blastema: Undifferentiated intermediate mesoderm adjacent to the ureteric bud. Forms the renal tubules and induces differentiation of the glomeruli. Key process: o Signals from the ureteric bud induce blastema differentiation. o Renal tubules join with collecting ducts to form a continuous passage for urine flow. ________________________________________ 4. Primitive and Evolutionary Kidneys Archinephros: Hypothetical ancestral kidney of primitive vertebrates and larvae of hagfishes and caecilians. Provides a basis for understanding vertebrate kidney evolution. ________________________________________ 5. Ureter, Renal Pelvis, and Bladder Development Ureteric Bud: Outpouching of the mesonephric duct that forms major structures of the kidney’s collecting system. Bladder: Originates from the cloaca (shared outlet of the gastrointestinal and urinary tracts during early development). ________________________________________ Key Timelines Day 22: Pronephros appears. Week 4-5: Pronephros degenerates, mesonephros forms. Week 5: Metanephros begins development, ureteric bud forms. Later Gestation: Metanephros becomes fully functional definitive kidney. ________________________________________ Essential Structures and Functions Structure Function Pronephros Nonfunctional in humans; early signaling role in kidney development. Mesonephros Temporary blood filtration; resembles amphibian kidneys. Metanephros Definitive kidney; functions in filtration, reabsorption, and excretion. Ureteric Bud Forms collecting ducts, ureter, calyces, and renal pelvis. Metanephrogenic Blastema Differentiates into nephrons (renal tubules and glomeruli). ________________________________________ Important Processes Filtration: Blood is filtered by glomeruli in the mesonephros and metanephros. Branching Morphogenesis: Formation of collecting ducts and calyces by the ureteric bud. Apoptosis and Differentiation: Degeneration of pronephros and mesonephros; formation of functional metanephric structures. ________________________________________ High-Yield Facts 1. The mesonephric duct connects to the cloaca and is later involved in male reproductive system development. 2. The glomerulus of the definitive kidney forms from precursors of vascular endothelial cells. 3. The ureteric bud is essential for signaling metanephrogenic blastema differentiation. 4. Pronephros is rudimentary and nonfunctional in humans but plays a signaling role in kidney organogenesis. Story: The Development of the Head and Neck Once upon a time, around the 4th and 5th weeks of development, the head and neck began their journey. Mesenchymal tissues in the cranial region of the embryo grew, creating pharyngeal arches, separated externally by pharyngeal clefts (ectodermal) and internally by pharyngeal pouches (endodermal). These arches were like small construction teams, each contributing specific parts to the developing head and neck. Pharyngeal Clefts There were four clefts, but only the first cleft left a permanent mark, forming the external auditory meatus. The other clefts briefly created cervical sinuses, which were obliterated by the rapid growth of the second arch. Pharyngeal Arches The embryo built six pharyngeal arches, but the 5th arch disappeared soon after forming. Each arch was a package with its own cranial nerve, muscles, cartilage, and blood vessels. Here's how they contributed: First Arch (Mandibular Arch): Structures: ○ Maxillary prominence → Maxilla, zygomatic bone, part of the temporal bone. ○ Mandibular prominence → Mandible. ○ Cartilage: Meckel’s cartilage → Malleus, sphenomandibular ligament.  Maxillary cartilage → Incus. ○ Artery: Terminal portion of the maxillary artery. Muscles: Mastication, mylohyoid, tensor tympani, anterior belly of digastric. Nerve: Trigeminal nerve (CN V), which also supplied general sensation to the anterior 2/3 of the tongue and facial skin. Second Arch (Hyoid Arch): Structures: ○ Cartilage: Reichart’s cartilage → Stapes, styloid process, stylohyoid ligament, upper body, and lesser horn of the hyoid. ○ Arteries: Stapedial artery (regresses) and hyoid artery (forms corticotympanic artery). Muscles: Facial expression, stapedius, stylohyoid, platysma, posterior belly of digastric. Nerve: Facial nerve (CN VII), providing taste to the anterior 2/3 of the tongue via chorda tympani. Third Arch: Structures: ○ Cartilage: Lower body and greater horn of the hyoid. ○ Artery: Common carotid and proximal internal carotid. Muscle: Stylopharyngeus. Nerve: Glossopharyngeal nerve (CN IX), which gave taste and sensation to the posterior 1/3 of the tongue. Fourth Arch: Structures: ○ Cartilages: Thyroid, corniculate, and cuneiform cartilages. ○ Arteries: Right → Proximal subclavian artery. Left → Aortic arch. Muscles: Pharyngeal constrictors, levator veli palatini, cricothyroid.  Nerve: Superior laryngeal branch of vagus (CN X), innervating the root of the tongue. Sixth Arch: Structures: ○ Cartilages: Laryngeal cartilages. ○ Arteries: Right → Proximal pulmonary arteries. Left → Ductus arteriosus. Muscles: Intrinsic laryngeal muscles (except cricothyroid). Nerve: Recurrent laryngeal branch of vagus (CN X), providing sensation and parasympathetic innervation to the pharynx, larynx, and viscera. Pharyngeal Pouches On the internal surface, five pairs of pouches appeared, but only four contributed to adult structures: 1. First Pouch → Eustachian tube, middle ear cavity. 2. Second Pouch → Lining of the palatine tonsils. 3. Third Pouch → ○ Dorsal → Inferior parathyroid glands. ○ Ventral → Thymus. 4. Fourth Pouch → ○ Dorsal → Superior parathyroid glands. ○ Ventral → Ultimobranchial body (C cells). Featur Arch/Cleft/Pou Derivatives Associated Key Notes e ch Nerve 1st Mandibular Maxilla, mandible, Trigeminal (CN General Arch malleus, incus, V) sensation to muscles of anterior 2/3 mastication of tongue. 2nd Hyoid Stapes, styloid Facial (CN VII) Taste to Arch process, lesser anterior 2/3 horn of hyoid, of tongue muscles of facial (chorda expression tympani). 3rd Greater horn of Glossopharynge Taste and Arch hyoid, al (CN IX) sensation to stylopharyngeus posterior 1/3 of tongue. 4th Thyroid cartilage, Vagus (CN X, Root of the Arch pharyngeal Superior branch) tongue. constrictors, cricothyroid 6th Laryngeal Vagus (CN X, Sensation to Arch cartilages, intrinsic Recurrent pharynx, laryngeal muscles branch) larynx, and (except part of cricothyroid) external ear. 1st External auditory Only cleft to Cleft meatus form a permanent structure. 2nd-4t Temporary Rapid growth h Clefts cervical sinuses of 2nd arch (obliterated)  closes these clefts. 1st Eustachian tube, Pouch middle ear cavity 2nd Palatine tonsil Pouch lining 3rd Inferior Pouch parathyroid glands, thymus 4th Superior Pouch parathyroid glands, ultimobranchial body