DEVELOPMENT OF UROGENITAL

SYSTEM

By

Dr Samina Anjum

PHYLOGENETIC STAGES

• Pronephros, a structure similar to that found in primitive vertebrates.

• Mesonephros, a more advanced system found in fish & amphibia.

• Metanephros which elaborates into the final human form.

DEVELOPMENT OF 3 SETS OF OVERLAPPING KIDNEY SYSTEMS IN CRANIOCAUDAL SEQUENCE

PRONEPHROS (EARLY 4th WEEK)

Rudimentary, transitory and non functional

Represented by 7 to 10 solid cell groups in cervical region

These groups form vestigial excretory units, nephrotomes

Pronephric duct runs caudally and opens into cloaca

PRONEPHROSCranial segments regress before more caudal ones are formed

End of 4 wks - Disappears

MESONEPHROS/ INTERIM KIDNEYS FUNCTION FOR 4 WKS

The Mesonephros and ducts are derived from intermediate mesoderm of upper thoracic to upper Lumber L3 segments. Functional for a short time during early fetal period

Early in 4th week the first excretory tubules of mesonephros appear, during regression of pronephric system Formation of S- shaped excretory tubules & glomerulusFormation of Bowman's capsuleRenal corpuscleLaterally the tubules enter into mesonephric/ Wolffian duct, a continuation of the pronephric duct

IN THE MIDDLE OF SECOND MONTH

Mesonephros forms large ovoid organ on each side of midline.

Gonad develops on the medial side of urogenital ridge

BY THE END OF SECOND MONTH:While caudal tubules are still differentiating, cranial tubules & glomeruli show degenerative changes

Mesonephric duct opens into cloaca

In males a few caudal tubules and the mesonephric duct persist and participate in formation of genital system, but disappear in female

METANEPHROS/DEFINITIVE/PERMANENT KIDNEYAppears in 5th wk

Permanent kidney develops from two sources:

Metanephric diverticulum / Ureteric bud give rise to collecting system

Metanephric mesoderm/ blastema give rise to excretory units

COLLECTING SYSTEM• Collecting ducts develops from ureteric bud as an out

growth of mesonephric duct• The ureteric bud penetrates the metanephric tissue

which is moulded over its distal end as a cap.

• The ureteric bud penetrates the metanephric tissue

which is moulded over its distal end as a cap. • The ureteric bud will grow into, and branch several times

within, the metanephric mesenchyme, like a plant root penetrating and growing within ground soil.

Cont…

• The distal end of bud dilates forming the renal pelvis and splits into cranial and caudal portions, major calyces

• Each calyx will form two new buds while penetrating into the metanephric mesoderm. These buds continue to subdivide until 12 or more generations of tubules formed

Cont…• The tubules of 2nd order enlarge and absorb those of 3rd

and 4th generations, forming the minor calyces of renal pelvis.

• During further development collecting tubules of 5th and successive generations elongate considerably and converge on the minor calyx, forming the renal pyramid.

EXCRETORY SYSTEM

DERIVATIVES OF METANEPHROS

Metanephric diverticulum / Ureteric bud:• Ureters• Renal pelvis• Calyces• Collecting tubules (1-3 million)

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

• Nephrons are formed until birth, at which time there are 1 million nephrons in each kidney.

• Urine formation by 10th week• At birth, kidneys have a lobulated appearance, but the

lobulation disappears during infancy as a result of further growth of nephrons, although no increase in their number

REGULATION OF KIDNEY DEVELOPMENT

• The ureteric bud is essential for induction of differentiation in the metanephric mesoderm.

• The metanephric cap is essential for bifurcation of the ureteric bud.

• The collecting ducts are essential for differentiation of the nephrons.

POSITION OF KIDNEYInitially in the pelvic region, later shifts to a more cranial region in the abdomen. Attain adult position by the 9 weeks

This ascent of kidney is caused by:• Diminution of body curvature• Growth of body in lumber and sacral regions (abdomen

and pelvis)

HILUM OF KIDNEY• Faces ventrally initially; but as the kidney ascends, it

rotates medially almost 90 degrees. By the 9th week the hilum is directed anteromedially. Eventually the kidneys become retroperitoneal on the posterior abdominal wall.

CHANGES IN BLOOD SUPPLY OF KIDNEYS

In the pelvis metanephros receives its arterial supply from pelvic branch of aorta.

During its ascent to the abdominal level, it is vascularized by the arteries that originate from aorta at continuously higher levels.

Lower vessels usually degenerate Accessory renal arteries

FUNCTION OF KIDNEY

• The definitive kidney becomes functional by 12th week

• Urine is passed into amniotic cavity and mixes with amniotic fluid

• Fluid is swallowed by the fetus and recycles through the kidneys

• During fetal life kidneys are not responsible for excretion of waste products

The kidneys and suprarenal glands of 28 weeks fetus. The external evidence of the lobes usually disappears by the end of first year.

ABNORMAL LOCATION OF THE KIDNEY

Pelvic kidney--- if fails to pass through arterial fork formed by umbilical arteries. Remains in the pelvis close to common iliac artery

Horse shoe kidney in a 13 wk female fetus

In 1/600 people kidneys are pushed so close together during their passage through the arterial fork that the lower poles fuse. The large U-shaped kidney usually lies in the hypogastrium, anterior to the inferior lumbar vertebrae. Normal ascent of these fused kidneys is prevented because they are caught by the root of the inferior mesenteric artery. A horseshoe kidney usually produces no symptoms because its collecting system develops normally and the ureters that arise from anterior surface of kidney enter the bladder normally.

WILM’S TUMOR• Is a cancer of kidney that

usually affects children by 5 years of age.

• Many are now known to be associated with genetic defects (WT1 genes on chromosome 11).

• May be associated with other abnormalities and syndromes e.g. WAGR syndrome, Denys – Drash syndrome.

• Nowadays, treatment gives a better than 90% --- 5 year survival.

Small kidney from a 4 year old child contains a lobulated tan-white mass (Wilms tumor of the kidney).

RENAL DYSPLASIAS AND AGENESIS

Spectrum of severe malformations that represent the primary diseases requiring dialysis and transplantation in the 1st years of life

In unilateral agenesis the other kidney usually undergoes compensatory hypertrophy and performs the function of missing kidney

RENAL AGENESIS May arise if the interaction

between the metanephric mesoderm and the ureteric bud fails to occur. Reason: Genes Mutations

Bilateral renal agenesis is usually associated with oligohydroamnios because little or no urine is excreted into the amniotic cavity

3. CONGENITAL POLYCYSTIC KIDNEY DISEASE

AUTOSOMAL RECESSIVE POLYCYSTIC

KIDNEY DISEASEOccurs in 1/5,000 births

A progressive disorder in which cysts form from collecting ducts.

The kidneys become very large and contain many hundreds of small cysts. Renal failure occurs in infancy or childhood

Survival depends upon postnatal dialysis and kidney transplantation

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Cysts form from all segments of the nephron and usually do not cause renal failure until adulthood.

More common (1/500 or 1/1,000 births) but less progressive than the autosomal recessive disease

4. DUPLICATION OF THE URETERResults from early splitting of ureteric bud

Complete or Partial

Ectopic ureter

A kidney with two ureters & renal pelvis

DEVELOPMENT OF URINARY BLADDER

During 4th to 7th week of development, the cloaca divides into UROGENITAL SINUS anteriorly & the anal canal posteriorlyUrorectal septum: the tip will form the perineal body

Three portions of urogenital sinus are: Upper & largest part Pelvic part Phallic part: as genital tubercles grow this part is pulled ventrally

A thick fibrous cord

18 wk fetus

Median umbilical ligament

During differentiation of cloaca, the caudal portions of mesonephric ducts are absorbed into the wall of urinary bladder to form the Trigone

Mesonephric ducts move close together to enter the prostatic urethra and in the male become the ejaculatory ducts

With time the mesodermal epithelium of trigone changes & is replaced by endodermal epithelium

DEVELOPMENT OF URETHRAOrigin of epithelium in both sexes --- endoderm

Surrounding C.T. and smooth muscle --- splanchnic mesoderm

At the end of 3rd month, epithelium of prostatic urethra begins to proliferate and forms a number of outgrowths that penetrate the surrounding mesenchyme.

In the male, these buds form the PROSTATE GLAND

In the female, the cranial part of urethra gives rise to the URETHRAL AND PARAURETHRAL GLANDS

BLADDER DEFECTS

URACHAL FISTULA

URACHAL CYST

URACHAL SINUS

EXSTPROPHY OF BLADDERVentral body wall defect Epispadias is a constant feature and open urinary tract extends up to umbilicus Is due to the failure of lateral body wall folds to close in the midline in the pelvic regionThis anomaly is rare, occurring in 2/100,000 live births

EXSTROPHY OF CLOACAMore severe ventral body wall defectProgression and closure of lateral body folds are disrupted to a greater degreeThe defect involves both the anterior abdominal wall and the anterior wall of urinary bladderNormal development of urorectal septum is altered resulting in other defects like:Imperforate anus Other anal canal malformationsDefects in external genitaliaOccurrence is rare i.e. 1/30,000 births