-----------------------------------------------------------------------------------------------Recap: What is…..?   BELLINI – collecting ducts (of Bellini) o Ductules inside the renal pyramids BERTIN – renal columns (of Bertin) o Parenchyma of the kidney from the cortex that extends into the medulla between two renal pyramids MALPHIGI/MALPHIGIAN – corpuscles o Renal pyramids themselves GEROTA’S – fascia o Outside the perirenal fat/fascia (ANTERIORLY) ZUCKERKANDL’S – fascia o Homologue of Gerota’s but POSTERIORLY TOLDT’S – fascia o Anterior perpendicular membrane of the kidney o Accdg to the web, it is continuous with the LIG. OF TREITZ o Treitz→Toldt’s→splenorenal lig. (different names but only one membrane) WAGR Syndrome o Wilm’s Tumor o Aniridia (congenital absence of, or incomplete formation of iris) o Genital anomalies  big clitoris  small penis  widely - spaced scrotum (like labia)  nonrugal formation of the scrotum (very shiny scrotum – sign of prematurity) diba boys? (normally the scrotum has rugal folds → DARTO’S FASCIA) o Renal failure (but could also be mental retardation[mild to moderate]) o Most of the time, WAGR patients are obese, hence WAGRO SYNDRYOME (wherein the O stands for OBESE).  That’s why you have to change your diagnosis - of an initially WAGR patient that becomes obese – to WAGRO VACTERL-H+H o Vertebral anomalies o Anal atresia o Cardiac anomalies o Tracheoesophageal fistula o Radial or Renal defect o Limb defect (either radius or o thumb) o Hydrocephaly/-us o Hypothyroidism DENYS – DRASH SYNDROME o Renal failure (problem with mesangium) o Wilm’s tumor Pseudohermaphrodism (FALSE)  Female pseudohermaphrodism  Presence of both external genitalia with ovaries  i.e. both penis and clitoris and upon ultrasonography, pair of ovaries!  TRUE HERMAPHRODITE – both pairs of the gonads are present (both testes and ovaries) and both external genitalia. (GUIDE is the INTERNAL GENITALIA)  TOWNES-BROCK SYNDROME o Branchio-oto-renal syndrome  Ear problem (oto/otic)  Renal - kidney problem  Branchio – facies (face) problem (branchial cleft) o Anal cap imperforation o i.e. polycystic kidney disease + anotia/microtia + imperforate anus + polydactyly o 2° to GDNF and SALL1 gene mutation (due to close proximity of these genes)  EAGLE-BARRET-FRÖLICH-OBRINSKY SYNDROME o Second longest named syndrome in the world. o Also termed as the PRUNE BELLY syndrome o Triad:  Absence of rectus abdominis  Dilatation of the urinary tract  Undescended testis -----------------------------------------------------------------------------------------------o UROGENITAL SYSTEM  Functionally, can be divided into: o Urinary System o Genital or Reproductive System  Anatomically and embryologically, these two are intimately interwoven. o Both develop from the same mesoderm, the INTERMEDIATE MESODERM.  Mesoderm between the somatic (will become the parietal peritoneum) and the somitic (is part of paraxial [somitomeric {backbone, ribs, all the muscles of the back} and the somatic])  Mesoderm between the future parietal peritoneum and the muscles of the back = kidney is positioned RETROPERITONEALLY o Both of their excretory ducts drain into the cloaca. URINARY SYSTEM o 21st and 25th day embryo, all colored white is extraembryonic cavity


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Intraembryonic cavity, remember that there is incorporation of the yolk sac inside to become the gut  This will be closed ventrally to form the abdominal cavity. So that somatic will become the parietal.

PRONEPHROS  Composed of 7-10 cell groups in segmental arrangement on the lateral sides of the neck (cervical).   It is very vestigial (rudimentary), sometimes most anatomists do not appreciate this as an organ. It will begin to appear during the first days of 4th week AOG and all indication of nephrotome will undergo degeneration at the end of 4th week. For one week, though it is equipped with two glomeruli and one nephric tubule, it is still not functional. Again, it is composed of two glomeruli that deeply indent the Bowman’s capsule. It is well-equipped with two glomeruli (coming from the dorsal aortae) and one nephric tubule but non-functional. * It is only functional among fishes.




On the lateral sides of the notochord will become the muscles and bones of the back (somites), hence called SOMITIC. Between the somitic and somatic is the intermediate mesoderm, hence, back of the parietal Lateral view of the 21st and 25th day embryo  There is the presence of the three kidney systems:  On the cervical region is the PRONEPHROS.  On the upper thoracic to the lower thoracic is the MESONEPHROS.  Adult type located on the pelvic region is the METANEPHROS.

MESONEPHROS   Extends from the upper thoracic to the lower lumbar (accdg. to Mosby, T3 – L3). The largest ovoid mass (or organ) on the posterior abdominal wall during 6th to 8th week (still retroperitoneal). It has an excretory tubule which is a S – shaped loop. Renal corpuscle is composed of the S-shaped nephric tubule + ONLY ONE glomerulus.

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-----------------------------------------------------------------------------------------------PHYSIOLOGIC HERNIATION Aside from the hematopoietic function of the liver, the elongation of the jejunum and ileum, and the fact that the abdominal cavity per se cannot contain all the enlarging organs, presence and enlargement of the mesonephros is one of the factors that lead to the physiologic herniation during the 6th – 8th week. ----------------------------------------------------------------------------------------------- At first it is a solid organ, but eventually, during 7th -8th week it undergoes segmentation. These Sshaped looped nephric (excretory) tubules is composed of Bowman’s capsule (which will be indented with glomerulus) and an S-shaped loop.

They are slightly overlapping in appearance, meaning before the mesonephros starts to appear, all the cranial ones will undergo degeneration. So they are not present at the same time. Kidney System PRONEPHROS Basic Functional Unit Nephrotome Description Nonfunctional Functional, but for a very short time Adult type  On the lateral side of the segmented mesonephros is the MESONEPHRIC DUCT. All the newly produced urine of the mesonephros will be collected by these ducts.


Renal corpuscle Nephron

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 

WOLFFIAN DUCT – other term for mesonephric duct. This is an oblique lateral view of the abdominal part of the embryo. The gut tube is suspended by the dorsal mesentery. On the lateral side of the dorsal mesentery is the GONAD). If female: OVARY :: male: TESTIS The mesonephros will begin to appear during the 3rd day of the 4th week and will start to degenerate during the 8th week along with the degeneration of the mesonephric duct. But, among males, the mesonephric duct will become the ductuli efferentes (epigenital ductule), epididymis, paradidymis, vas deferens, seminal vesicle and ejaculatory duct [these are termed as the derivatives of the said duct]. But because of the absecnce of the Y chromosome in genotypically female embryos, it undergoes degeneration. On the lateral-most part of this genitourinary ridge is the PARAMESONEPHROS. The paramesonephric duct (MÜLLERIAN DUCT) is non-functional among males because it will become the fallopian tubes, uterus and upper 1/3 of the vagina. On the caudal-most part of the mesonephric duct, near the cloaca, is the outgrowth of the URETERIC BUD (from mesonephric mesoderm) that penetrates the metanephros. The ureteric bud, as its name implies, will become the ureter. During the mid-2nd month or the 6th week, the mesonephros achieves its largest size. And by the end of the 2nd month or 8th week, it will undergo degeneration. All signs of mesonephros will undergo apoptosis.

That ureteric bud penetrates the blastema and some blastemal tissue will mold over the distal part of this kidney because that metanephric cap will give induction for branching. The first part is to dilate this distal part. This dilatation will become the RENAL PELVIS. Further induction will split this dilated portion into a cranial and a caudal one, the MAJOR CALYCES. Further induction will split these major calyces into another set of collecting ducts, the MINOR CALYCES (3rd generation). Will continue up to 12 generations until it forms the Bellini (the smallest ductules of the collecting system). The collection of Bellini’s will form the renal pyramid of Malphigi. Those parts without Bellini are called Bertin. Between two pyramids of Malphigi are the columns of Bertin. The endpoint of Bellini’s formation is the renal cortex. Once the distal-most Bellini reaches the cortex, it will stop branching (Mosby). But accdg. to Langman’s, definitely at the start of 5th month AOG, no more Bellini will be formed.

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The urerter, renal pelvis, major and minor calyces + one million to three million collecting tubules of Bellini’s anlage is the ureteric bud.


3rd or permanent or definitive type of kidney begins to appear at 5th week AOG until adulthood. It just so happened that the metanephros appeared in the pelvic region. Metanephric tissue is also termed as BLASTEMA The metanephric system is composed of two systems:  The collecting duct develops from the ureteric bud that outgrows from the distalmost part of the Wolffian, near the cloaca.

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o This is the system that forms the functional unit of the metanephros, the nephron (glomerulus + bowman’s capsule + thick and thin ascending and descending parts). o Metanephric cap handles the induction of the ureteric bud. This cap (mesenchyme) must undergo epithelialization. So from a mesenchyme, it forms a RENAL VESICLE.


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o Once this vesicle has been formed, it will form tubes, first of which is the distal convoluted tubule. There will be no communication whatsoever between the distal part of the Bellini and the distal convoluted tubule until:   There is presence of low caspase The plasma from the glomerulus reaches the nephron (meaning the urine has formed). The capillaries are deeply indented into the bowman’s capsule.   The blastema will upregulate the WT1 (Wilm’s tumor 1) in a very low amount. Mutation in the gene or overexpression would lead to WILM’S TUMOR (proliferation of any blastemal caps, which leads to tumor) WT1 – regulates the expression of these two proteins: o o Glial-derived neurotrophic factor (GDNF) Hepatocyte growth factor (HGF, or scatter factor)

o That channel connecting the collecting system and the excretory system is only achieved once the nephron is fully developed. o Because of the elongation (further development of the nephron) the next to develop is, from the distal convoluted tubule, the thick ascending, the loop of Henle (only part of the nephron that extends to the renal pyramid), thin descending and proximal convoluted tubule (lateral to which is the bowman’s capsule). o Once the glomerulus is deeply indented into the bowman’s capsule, with the help of the foot processes of the glomerulus (podocytes) -----------------------------------------------------------------------------------------------Where does urine come from? The ultrafiltration of the plasma. -----------------------------------------------------------------------------------------------o All the plasma located in the glomerulus must diffuse and be absorbed by the bowman’s capsule o The reason why the mesenchyme must undergo epithelialization is because the basal lamina of the mesenchyme is different with that of the nephric tubule. Cell Type Mesenchyme Composition Type I & III Collagen, Fibronectin Type IV Collagen, Laminin, Syndecan & Ecadherin

-----------------------------------------------------------------------------------------------In terms of gross anatomy, the common denominator between the liver and the kidney is the presence CAPSULE the toughness of the Glisson’s capsule and that of the renal capsule. -----------------------------------------------------------------------------------------------o It is due to the HGF that leads to formation of a near liver organ. It just so happened that the liver has a bare area.

This blastemal induction must be received by the ureteric bud through Tyrosine Kinase Receptors (TKR): o o o RET will receive all the signals from the blastema carried by the GDNF. MET will receive all the signals and induction given by the scatter factor.


o The composition of the mesenchyme’s basal lamina is not amenable to any diffusion, but that of epithelium’s basal lamina is very amenable to any diffusion and absorption of plasma. o Cell adhesion molecules (Syndecan & E-cadherin) are responsible for: (1) condensation of mesenchyme; and (2) prevention of more plasma diffusing from glomerulus to bowman’s capsule (because not all plasma should be aborbed by a certain glomerulus). MOLECULAR REGULATION  Differentiation of organs (kidneys) is facilitated by the epithelium - mesenchyme interaction. Epithelium is represented by the ureteric bud, whereas the mesenchyme is represented by the blastema.

These two are proto-oncogenes, and if mutated, will undergo cancer formation especially the RET gene. -----------------------------------------------------------------------------------------------Mutation of the RET gene will lead to three very important diseases: o Hirschsprung’s Disease o Endocrine System Carcinomas (MEM1 & MEM2 – collections or constellations of endocrine tumors)

o Medullary Thyroid Carcinoma ----------------------------------------------------------------------------------------------- The ureteric buds also express these two genes:   Importance: 1. Blocks apoptosis (with normal expression)  (Mosby) FGF2 blocks caspases until the Bellini reaches the renal cortex – RECANALIZATION between the collecting and excretory is induced by the lowering or underexpression of these two. Once the final Bellini has formed, as it reaches the renal cortex, it will lower the expression of FGF2, there FGF2 (Fibroblast growth factor) BMP7 (bone morphogenetic protein)

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will be increased recanalization.




-----------------------------------------------------------------------------------------------As long as major calyces are being produced, caspastic activity must be blocked, OR ELSE, you will have a distal convoluted tubule connected to the renal pelvis directly. -----------------------------------------------------------------------------------------------2. Proliferation of the metanephric cap 3. Maintiaing the production of WT1 4. Keeping the metanephric duct on the distal most part of the Bellini.    PAX2 will condense the mesenchyme and will add the cell adhesion molecules. WNT4 is responsible for this newly condensed mesenchyme to undergo tubule formation.

COMPLETE (A) and PARTIAL (B) TYPES Both are still viable to life. Since there is splitting of the ureteric bud, there will be congestion of its own major and minor calyces. There is no need for kidney transplantation. Problem would be on its distal drainage: either the ectopic (abnormal) ureter will drain its content via the: o o (1) vagina (called VAGINURIA), (2) urethra per se (or directly) which could lead to incontinence (could not be collected by the urinary bladder) (3) directly to the VESTIBULE (skin or mucosa between the vaginal opening and the urethral opening)


WNT6 & WNT9B (from the ureteric bud) must be expressed first before PAX2 & WNT4 can do its function. -----------------------------------------------------------------------------------------------What if.... You have failure of recanalization, meaning there is domination of FGF2 and BMP7? What will happen to the renal cortex? Continuing urine formation but there will be excessive amount (the basal lamina will accept the plasma from the deeply indented glomerulus, but once absorbed it cannot undergo backflowing). Since there will be neither apoptosis nor recanalization, the urine will stagnate the inside of the nephron = POLYCYSTIC KIDNEY DISEASE on the renal cortex. What happens is that the nephrons over dilate because of accumulation of urine. Since there is no caspases, the urine that is formed will be transferred to the major and minor calyces. Two types:  AUTOSOMAL RECESSIVE – half is carried by the mother, half by the father. It is more progressive. It will derange the collecting system (either the minor calyces are not formed or the renal pelvis did not dilate). It is in need of kidney transplantation or early dialysis because of the renal failure (early).  AUTOSOMAL DOMINANT – the gene is carried by either the father or the mother. It is not progressive (no renal failure even until adulthood) It affects the nephron (either loop of henle is blocked or under development of a certain part of the nephron)

Another complication would be if the patient will undergo emergency surgery (i.e. The ovarian artery would need to be surgically tied, sometimes, if the surgeon was weak in anatomy, he might tie up the URETER instead.). Hence, it is an anatomical problem, unless diagnosed early.

This early splitting is secondary to domination of caspases on the posterior abdominal wall. Remember that all the peritoneum that lies on the back will undergo degeneration, which is the eitology of almost all duplication of ureters. -----------------------------------------------------------------------------------------------POSITION OF THE KIDNEYS During the 5th week, the metanephros is positioned in the pelvic region. But with time, it will undergo an ASCENT to a more cranial position. Reasons: o Growth of lumbar and sacral vertebrae o Sacrospinal curvature (diminution of the vertebral column) o Elongation of the ureters o (Mosby) Descent of gonads leads to ascent of kidneys. (There is the descent of the gonads [especially in males, the testes] because the temperature of the testes should be 2° lower than that of the body’s.) o Regression of the mesonephros (which was the largest growing organ then) – whose space would be filled by the metanephros. -----------------------------------------------------------------------------------------------Adult surface anatomy of the kidney: T12 – L3  It just so happened that the right kidney is much lower due to the formation of the liver, unless you have situs inversus et totalis. *For situs solitus: higher left lower right. The arteries on the lateral sides of the urinary bladder which are remnants of the umbilical arteries are the SUPRAVESICULAR. (Latin for urinary bladder is vesico.)


VESICOSTOMY– putting an opening (i.e. patient with obstructed urethra – micturates through the pubic area – there is a need for this procedure.) CYSTECTOMY – surgical partial or complete removal of urinary bladder. LATERAL/MEDIAL UMBILICAL LIG - Distal remnants of the umbilical areteries MEDIAN UMBILICAL LIG – (urachus) connetion between the urinary bladder and the umbilicus

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PELVIC KIDNEY Sometimes, a kidney fails to ascend because of the hindrance given by the ARTERIAL FORK (provided by the common iliac, external iliac [once it passes through the poupart’s lig], internal iliac [one of the branches is the umbilical artery] which is the first hindrance that must be surpassed by the ascent of the kidney. Kidney transplant – we connect it to the common iliac vein. Be careful in diagnosing pelvic kidney because it just might be post-transplant kidney. *Pacemaker clavicle – 1 inch below the left The widest and uppermost part of the urogenital sinus is called the URINARY BLADDER, which is connected to the umbilicus through the allantois. Next to that is the narrowest part of the urogenital sinus, the PELVIC PART. It will develop into two urethrae : (1) prostatic, and (2) membranous. Endoderm of the prostatic urethra will proliferate and become the PROSTATE GLAND. -----------------------------------------------------------------------------------------------In males, if the catheter stops, you have already reached the membranous part of the urethra (the narrowest part of the male’s urethra). The homologue of male’s prostate in females is the SKENE’S GLAND (Paraurethral gland or the gland on the lateral side of the urethra). -----------------------------------------------------------------------------------------------The third and the longest part of the urogenital sinus is called the PHALLIC or PENILE part. Among boys, the length of the phallic part of the urogenital sinus is dependent on the length of the genital tubercle, hence it is dependent on the genes coming from the father. Only 8/10 of that part is endodermal in origin. Meaning the distalmost part of the phallic part is ectodermal in origin - the urethra inside the glans penis is ectodermal in origin. -----------------------------------------------------------------------------------------------The stomodeum, proctodeum, and extrernal urethral meatus are all ectodermal in origin. ----------------------------------------------------------------------------------------------The insertion of the mesonephric duct is on the posterior part of the urinary bladder. Since the mesonephric duct will be responsible for the outgrowth of these ureteric buds, they are present posteriorly. During the differentiation of the cloaca, the mesonephric duct with its ureteric bud is being absorbed on the posterior part of the urinary bladder. Since these two pairs of ducts are mesodermal in origin, that certain part (of incorporation) on the posterior part of the urinary bladder will become mesodermal. Eventually after birth, since there will be domination of the endoderm on the posterior side of the urinary bladder, this part (trigone) will be replaced by endoderm.

HORSESHOE KIDNEY Sometimes, although very rare, that the arterial fork will be very hard to pass, to a point that the lower poles of the two kidneys will fuse on the midline and produce a horseshoe shape. This is common in patients with TURNER’S SYNDROME. This is usually located on the L5 vertebral level because of the prevention given by the root of the INFERIOR MESENTERIC artery. It is very viable to life not unless there is presence of obstruction. The nephrons and collecting systems are well-developed; it just so happened that the shape is extraordinary (horsehhoe). -----------------------------------------------------------------------------------------------FUNCTION OF THE KIDNEY Dependent on the function of the glomerulus; these tuft of capillaries are able to extravasate plasma into the bowman’s capsule during the 10th week AOG. This is very important because also during that time is the first day of the fetus to swallow amniotic fluid irregularly. The implication of this swallowing reflex is the recanalization of the collecting system with the excretory. It is the newly formed urine that will break off that diaphragm between the ureteric bud and the nephron. The metanephros will start to produce urine during the 12th week AOG (end of 1st trimester) and the fetus would also start to micturate (but regularly at 5th month AOG). There will be recycling of amniotic fluid (that will be swallowed by the fetus). The kidney is not yet responsible for the excretion of waste but it is the job of the placenta. Flow of amniotic fluid: Absorbed by Chorionic frontosum (placenta) → decidua basalis → helecine capillaries (uterus). BLADDER AND URETHRA During 4th – 7th week AOG, a certain septum will divide the cloaca into two divisions. The URORECTAL SEPTUM comes from the mesoderm from the yolk sac’s distal-most part and that of the allantois. The two divisions: anteriorly is the UROGENITAL SINUS and posteriorly is the ANAL CANAL. This urorectal septum, once it reaches the skin of the distalmost part of the embryo (perineum [skin between the vulva and the anal opening]). The perineum’s perineal body is secondary to the attachment of the urorectal septum to the skin.

Ascent of the kidneys (which are connected with the ureters) also leads to ascent of the ureteric bud laterally and cranially. On the other hand, the mesonephros moves left and descending because of the descent of the gonads (which also leads to the descent of the orifices of these two mesonephrics). It will form a triangular part on the posterior part of the urinary bladder called the TRIGONE. Since this part, the mesonephric duct will reach the prostatic urethra, and this mesonephric duct’s part is

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incorporated to the newly formed prostate gland, this newly formed duct is named as the EJACULATORY DUCT.

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All the gonads or internal genitalia are exposed + the bladder The external genitalia are widely spaced, like labia.’ ♀ Labia majora Labia minora Clitoris ♂ Scrotal sac Penile urethra Penis


Since in females, the müllerian will undergo degeneration, the Skene’s gland does not have any ducts. ----------------------------------------------------------------------------------------------ALLANTOIS – lumen that connects the urinary bladder to the umbilicus.

WILM’S TUMOR – space-occupying cancer of the kidney WAGR – i.e. clitoral hypertrophy + wilm’s tumor + underdeveloped iris + renal failure *Boundaries:  EJACULATORY DUCT – end of internal genitalia (males)  MEMBRANOUS PART – start of external genitalia (males)  VAGINA – upper 1/3 is internal, lower 2/3 is external genitalia (females) COLOBOMA – clefting of the iris  2° to PAX2 gene mutation  During the formation of the eye/optic placode or epidermal thickening, it will undergo capping and must close ventrally. Failure of closure will lead to failure of closure of the iris.  Madeline (missing in Paris, but from England) – unilateral coloboma ----------------------------------------------------------------------------------------------END OF TRANSCRIPTION Note: The texts within the --------------------------------------‘s are either clinical correlates, reviews, or trivial knowledge. We hope that this slightly long transcription will help you in achieving a high mark in ANATOMY. Never think that YOU CAN’T DO IT because what you put your mind to is what you’ll eventually end up doing. So just keep your head up, study hard, and never lose sight of that goal. GOOD LUCK AND GOD BLESS BATCH 2014!

URACHAL FISTULA – allantois persists even after birth.  Primary manifestation: OMPHALURIA (micturation through umbilicus)  *OMPHALOCHEIZA (defacating through umbilicus) persistence of vitelline duct (Meckel’s duct). URACHAL CYST - local area of the urachus persists due to the continuing secretory activity of the allantois’ lining (purely mucus). Differentiate through palpation: Patient with URACHAL CYST VITELLINE CYST Highly indentable Non-movable (it can move, but will stick on its area) Pittable INFRAumbilical and midline Directly BEHIND the (linea alba) umbilicus URACHAL SINUS – distal part of the urachus persists  Primary manifestation: odor, secretion/oozing of mucus + pus (bacterial product) through the umbilicus  Pus due to domination/presence of staphylococcus aureus epidermidis EXTROPHY OF BLADDER – infraumbilical failure of the abdomen to close with exposure of the urinary bladder.  Constant with patients with this abnormality is EPISPADIA (the micturation on the penile shaft’s dorsal aspect)  *HYPOSPADIA – micturation on the penile shaft’s ventral aspect. EXTROPHY OF THE CLOACA - More grotesque type of extrophy, even the perineum is widely spaced.  Defect in which there is failure of lateral ventral body wall folds to fuse at the midline.

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