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Embryology and Histology of Kidney Dr Gayatri Assistant professor Department of anatomy Kamineni Institute of Medical Sciences Narketpally KIDNEYS Early development and evolution of the kidney Intermediate Pronephros mesoderm Mesonephros Metanephros Ascent and abnormalities INTERMEDIATE MESODERM Mesoderm appears in the 3 week embryo Paraxial = somites Intermediate Lateral plate Two layers separated by the Coelome Intermediate mesoderm gives rise to ?Paired Glands? (Kidneys, Adrenals and Gonads) Intermediate mesoderm extends cranio caudally on each side of primitive dorsal aorta & project into dorsal wall of coloemic cavity. In cervical & upper thoraicsegmented-nephrotome Rest of IMM is unsegmented- nephrogenic cord. Three slightly overlapping kidney systems are formed in a cranial to caudal sequence during intrauterine life in humans: the pronephros, mesonephros, and metanephros. -Pronephros is rudimentary and nonfunctional; -Mesonephros may function for a short time during the early fetal period -Metanephros forms the permanent kidney Pronephros Pronephros Appear during 4th week ,in cervical &upper thoracic region as solid 7-10 segements,arranged horizontallypronephric tubule. Acquire lumen-nephrocele ,opens medially into coelom,dorsal wall evaginates & grows to join with successive tubules ? pronephric duct These groups form vestigial excretory units, that regress before more caudal ones are formed. By the end of the fourth week,all indications of the pronephric system have disappeared except pronephric duct. Mesonephros Appearence is associated with regression of pronephric system-4th week . About 70-80 mesonephric tubules develop in lower thoracic & lumbar region-horizontally, Lateral end opens-mesonephric duct/Wolffian duct,medial end forms dilated blind end indented to form internal glomerus. Proximal mesonephric tubules & duct disappear -5th week. At 8th week-26 tubules & single duct persist Mesonephric ridge Metanephros Appear last in lumbosacral region & persist as permanent kidney Consist : Collecting part- Ureteric bud Excretory part- Metanephric blastema Collecting part- Initially ureteric bud grows from dorsomedial aspect of caudal part of mesonephric duct. Later-bud grows dorsally & headwards, its distal end dilates & invade the caudal part mesonephric tissue, while doing this so bud shifts to dorsolateral. Dilated end of ureteric bud is surrouneded by mesonephric tissue [cap]-metanephric blastema. Bud divide cranial & caudal parts ? major calcyxsubdivides-13 generations. Dichotoms branching- chondroitin sulphate proteoglycan & glycosaminoglycan. 2,3,4th order generation ? minor calyx 5th onwards ? collecting tubules Dilated end ? pelvis of ureter. Stalk of bud ? ureter. Excretory part- develops from metanephric blastema, Initally 1st order branch of bud? capped by metanephric blastema[solid mass of bilaminar cells],further subdivisions- cells separate from main mass & from clusters of cells on each side of tubule? later form hollow renal vesicle[nephron]. One end of vesicle abuts collecting tubules & other end is dilated and invaginated by internal glomerular plexus. Each vesicle is S-shape curve b/w two fixed ends, middle segment extends towards future medulla as loop of Henle & associated part form PCT & DCT. Finally partition b/w blind end disappear ? metanephric kidney start functioning. Figure 14.6 Development of a metanephric excretory unit. Arrows, the place where the excretory unit (blue) establishes an open communication with the collecting system (yellow), allowing flow of urine from the glomerulus into the collecting ducts. MOLECULAR REGULATION OF KIDNEY DEVELOPMENT Epithelium of ureteric bud interacts with the mesenchyme of metanephric blastema. Mesenchyme of mesonephros-WT1-induction of ureteric bud WT1-regulate the production of GDNF &HGF- help in growth, proliferation & division of ureteric bud. FGF-2 & BMP-7 ? growth factors block the apoptosis & stimulate the proliferation in metanephric mesenchyme while maintaining the production of WT1. WNT4 & Pax2- produced by ureteric bud cause mesenchyme to epithelialize for excretory tubule differentation. Ascent of kidney In the 6th week the kidneys begin to ascend from the sacral region to their position in the upper abdomen. Initially kidney are present in :Pelvis /sacral? supplied by median sacral artery. Iliac fossa ? supplied by common & internal iliac artery. Finally undersurface of diaphragm where it ascent is arreseted by suprarenal gland & supplied by inferior suprarenal artery ? later becomes renal artery As the kidney ascends it receives new segmental arteries from the aorta and loses those vessels below (?climbing a ladder?). Thus sometimes there is more than one renal artery. Factors for ascent of kidney Diminutation of fetal curvatures. Continous lengthing of ureteric bud. Better nutrition. Decreased pelvic cavity for accommodation. Increased abdominal cavity. Sometimes one kidney fails to ascend => pelvic kidney Sometimes the left and right kidneys become attached in the pelvis then the horseshoe kidney can?t ascend above the inferior mesenteric artery(1:400) Anamolies of kidney According to number - Agenesis of one kidney. Multiple kidney. According to position ? pelvic kidney Fused kidney. According to sizeLobulated kidney. According to shape- Horseshoe kidney. Disc kidney. Polycystic kidney-failure of fusion of collecting & excretory part. Histology of kidney Types of nephron Cortex- renal corpuscle proximal convolated tubule distal convoluted tubule collecting tubule &papillary duct. Medulla- loop of Henle with ascending & desending loop. Renal corpuscles - Glomerulus,Bowmans capsule Proximal convoluted tubule & Distal convoluted tubule-active transport of ion. PCT- 75% of glomerular filtrate. DCT- ADH ? absorption of water & salt. Collecting duct Collecting duct ? cuboidal/tall coloumnar cells,microvilli,cell outline clear,large lumen. Medulla-loop of Henle ? passive transport of ion. Descending limb; thick- cont.. PCT thin-low cuboidal cell. Loop of Henle- simple squamous epithelium. Ascending limb;thin-simple squamous epithelium thick-cont..DCT. Loop Of Henle - absorb 15% of water, create hypotonic environment & concentration of urine. Maintain counter current mechanism. Urine ? PCT-Hypotonic Loop of Henle- Isotonic DCT- Hypertonic Juxtra glomerular apparatus ? vascular pole,4 cells,maintain blood pressure by secreting Renin Juxtra glomerular cells-large & round. Macula densa cells-coloumnar & crowed. Mesangial cells ? correspond pericyte. Intersitial cells Histology of kidney Renal medulla Renal medulla Collecting ducts Renal tubule Glomerulus Urinary pole Vascular pole Renal corpuscle Renal corpuscle Kidney (panoramic view) Nephron Introduction Ascent of the Kidneys In the 6th week the kidneys begin to ascend from the sacral region to their position in the upper abdomen. The metanephric ducts elongate and become the ureters. As the kidney ascends it receives new segmental arteries from the aorta and loses those vessels below (?climbing a ladder?). Thus sometimes there is more than one renal artery. Sometimes one kidney fails to ascend => pelvic kidney Sometimes the left and right kidneys become attached in the pelvis then the horseshoe kidney can?t ascend above the inferior mesenteric artery(1:400) Ontogeny Recapitulates Phylogeny Ernst Haeckel 1860? Ontogeny is the development of the individual Phylogeny is the evolution of the species So this is the idea that during development an organism (or an organ) goes through the same stages as during their evolution. Consider the Frog It development retraces the evolution of vertebrates from fish to reptiles This idea should be From the tadpole stage Water breathing with tail and no limbs (like a fish) Rudimentary limbs Reduction of tail Development of lungs ? breathes air Fully developed limbs, loss of tail moves onto land To the fully developed frog considered as a ?Parable? It is not necessarily true but it is a useful idea. Pronephros the first kidney A cavity, like the coelom develops inside the intermediate mesoderm Balls of bloods vessels from the aorta bulge into the space ? The Glomerulus. The glomerulus allows excess water to leave the blood while salts and macromolecules are retained. This kind of kidney is found in primitive fish (eg Lampreys) and in the embryos of most vertebrates Initially the water filters into the coelom Later, part of the cavity inside the intermediate mesoderm links up with similar parts in adjacent segments to form a duct. Pronephros ? in humans Appears at Day 21 In segmented intermediate mesoderm in the cervical region It degenerates by day 24 It is never functional in humans Mesonephros ? middle kidney When some primitive fish returned to the sea they had the reverse osmotic problem, water tended to diffuse out of their blood. They developed the mesonephric kidney located in the thoracic region. The mesonephros had a smaller glomerulus but a larger system of tubules so that the filtration part Many bony fish and some amphibians was reduced and the reabsorbing have a mesonephric kidney. part was increased. This was an important preadaption The tubules all connect with the to life on the land where drying out mesonephric (Wolfian) duct. is a constant problem. Mesonephros - in humans The Mesonephros first appears early in week 4 In thoracic and lumbar segments of intermediate mesoderm. Urine is produced and drains along the mesonephric (Wolfian) duct to the cloaca/bladder In week 5 the thoracic segments regress but the mesonephric kidney continues functioning until week 10 Fate of the Mesonephric (Wolfian) ducts The development of the metanephric kidney accompanied the changes in the reproductive system. The gonads of primitive vertebrates release their eggs and sperm into the coelom, from there they pass via small pores into the cloaca. In higher vertebrates the eggs are still released into the coelom, but the cloacal pores have become specialised tubes which open adjacent to the ovary. In the embryo, this egg collecting tube (paramesonephric duct) lies parallel to the mesonephric duct. Male and Female genital ducts Initially both sexes have both mesonephric and paramesonephric ducts In females Eggs are still released into the coelom (peritoneal cavity) but are gathered up in the uterine tubes. The two paramesonephric ducts become the uterine tubes. Distally the paramesonephric ducts fuse together to form the uterus and vagina. The mesonephric duct degenerates completely. In higher vertebrates sperm is never released into the coelom but reaches the outside by passing through some derivative of the urinary system. In birds, reptiles and mammals the testis develops a connection with the mesonephric duct (at the time that the mesonephros is degenerating). In males The mesonephric duct becomes the ductus deferens, seminal vesicle and parts of the prostate gland. The paramesonephric duct degenerates completely. Metanephros ? definitive kidney The metanephros or definitive kidney of higher vertebrates, begins when the metanephric ducts (ureteric buds) sprout from the distal end of the mesonephric duct at about 5 weeks. The ureteric buds induce intermediate mesoderm in the sacral region to form a metanephric blastema which forms the glomeruli and tubules of the nephrons. Evolution of the Kidneys: Metanephros The ureteric buds bifurcate again and again to form the calyces and collecting duct system of the definitive kidney. The kidneys begin producing urine by week 12, and it adds to the volume of the amniotic fluid. The fetus drinks this fluid in utero. The fetal kidneys are not responsible for excretion as the placenta serves this function Metanephros: The third urinary organ, the metanephros, or permanent kidney, appears in the fifth week. Its excretory units develop from metanephric mesoderm(Fig. 14.4) in the same manner as in the mesonephric system. The development of the duct system differs from that of the other kidney systems. Collecting System. Collecting ducts of the permanent kidney develop from the ureteric bud, an outgrowth of the mesonephric duct close to its entrance to the cloaca (Fig. 14.4). The bud penetrates the metanephric tissue, which is molded over its distal end as a cap (Fig. 14.4). Subsequently the bud dilates, forming the primitive renal pelvis, and splits into cranial and caudal portions, the future major calyces (Fig. 14.5, A and B). . Excretory System. Each newly formed collecting tubule is covered at its distal end by a metanephric tissue cap (Fig. 14.6A). Under the inductive influence of the tubule, cells of the tissue cap form small vesicles, the renal vesicles, which in turn give rise to small S-shaped tubules (Fig. 14.6, B and C ). Capillaries grow into the pocket at one end of the S and differentiate into glomeruli. These tubules, together with their glomeruli, form nephrons, or excretory units. The proximal end of each nephron forms Bowman?s capsule, which is deeply indented by a glomerulus (Fig. 14.6, C and D). The distal end forms an open connection with one of the collecting tubules, establishing a passageway from Bowman?s capsule to the collecting unit. Continuous lengthening of the excretory tubule results in formation of the proximal convoluted tubule, loop of Henle, and distal convoluted tubule (Fig. 14.6, E and F ). Hence, the kidney develops from two sources: (a) metanephric mesoderm, which provides excretory units; and (b) the ureteric bud, which gives rise to the collecting system. Nephrons are formed until birth, at which time there are approximately 1 million in each kidney. Urine production begins early in gestation, soon after differentiation of the glomerular capillaries, which start to form by the10th week. At birth the kidneys have a lobulated appearance, but the lobulation disappears during infancy as a result of further growth of the nephrons,although there is no increase in their number. Position of kidneys Kidneys lie on the psoas muscle beside the vertebral bodies. The diaphragm and 11th and 12th ribs lie behind the upper half of each kidney. Therefore they move with breathing Left is higher than right (liver) Upper poles T12 Hilum is at L1/2 Lower poles at L3 Upper poles are more medial (psoas). In the hilum: Renal vein is the most anterior. Followed by renal artery & pelvis/ureter Note that the left renal vein is longer . It crosses the aorta Is crossed by the SMA Receives left gonadal vein Anterior relations Right Adrenal Liver bare area Hepatorenal pouch Duodenum Pancreas Right colic flexure Jenunum Left Adrenal Stomach Spleen Pancreas Descending Colon Jenunum Lecture summary Early development and evolution Pronephros Mesonephros Metanephros Ascent and abnormalities Position and relations Lobes and segments Orientation and surroundings The medial border of each kidney is anterior to the lateral border (psoas). Thus the coronal plane of the kidney is at 30 degrees to the coronal plane of the body. Layers surrounding the kidney Outside the renal capsule is perirenal fat Then is the renal fascia which also surrounds the adrenals This is embedded in extraperitoneal fat (pararenal fat) Renal Lobes and their papillae/calyces There are 14 lobes originally Each lobe corresponds with a renal pyramid (plus its cap of cortex), and empties via its papilla, into a minor calyx Lobes fuse so that there are between 14 and 6, usually 8 (26%) Most fusion happens at the upper and lower poles so that those papillae are compound. Simple papillae have valve-like slits where the ducts open ? Non-refluxing Compound papillae allow reflux Vescicouretal reflux occurs in children and if the urine can enter the parenchyma of the kidney it causes infection and damage 5 Segments of the Kidney Each segment is the area supplied one branch of the renal artery. (end arteries) The front of the kidneys has four segments: apical, upper anterior, middle anterior, lower The back of the kidney has the posterior segment and the posterior aspects of the apical and lower. Easy way to remember: like your hand holding a glass four fingers in front and the thumb behind. The posterior branch of the artery branches off first and passes over the renal pelvis to reach the posterior aspect. The four anterior branches continue in the plane between the vein and renal pelvis.