The Microscopic Structure of the Kidney

Transcription

1 The Microscopic Structure of the Kidney Dr. Mahmud Abuauba MBChB, DCH, MD, PhD Consultant Pediatrician & pediatric Nephrologist Assistant Professor of Pediatrician Zawia Kidney Center 5 th May 2018

2 برعاية مركز عالج أمراض الكلى-الزاوية

3 THE URINARY SYSTEM SIX ORGANS Paired kidneys (2) Paired ureters (2) Unpaired urinary bladder (1) Unpaired urethra (1)

4 THE URINARY SYSTEM

5 THE KIDNEYS

6 CORTEX & MEDULLA Coronal or long. section: two regions: Outer, darker, granular region Renal cortex Cortical labyrinth Cortical Medullary rays arch Inner lighter, striated region Renal medulla ~10-18 medullary pyramids

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12 RENAL CORTEX Renal lobule= medullary ray + neighbuoring cortical labyrinth, with medullary ray in the center of lobule bounded by interlobular As Renal lobe= renal pyramid + renal column + cortical arch Renal lobe is a segment drains through the renal papilla

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14 RENAL MEDULLA Composed of conical-shaped medullary tissue; renal or medullary pyramids Base toward the CM border Apex points toward the hilum, renal papillae, project into minor calyx Renal papillae perforated by opening of ducts of Bellini forming area cribosa Renal pyramids separated by corticallike tissue (renal column of Bertin)

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16 RENAL MEDULLA Contains Straight portion of PT & DT Henle s loop, ALH & DLH Vasa recta MCT Papillary or ducts of Bellini

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18 RENAL CORTEX Cortical arch is portion of cortex overlying renal pyramid Formed of cortical labyrinth & medullary rays Cortical labyrinth consists of renal corpuscle & convoluted tubules Medullary ray, straight tubules of several nephrons with single or more collecting tubules

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20 RENAL CORTEX Contains Glomeruli PCT, DCT Connecting tubules CCT

21 URINIFEROUS TUBULE Uriniferous tubule is the basic functional unit of the kidney Uriniferous tubule formed of nephron & collecting tubule UT entirely is epithelial in nature UT are densely packed so the CT of kidney (stroma) is scant

22 Uriniferous tubule

23 NEPHRON I Nephron = renal corpuscle + renal tubules Each kidney has approx. a million ( million) nephrons

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25 NEPHRON II Several nephrons (10) are drained by a single CCT Several CCT join to form larger tubule, MCT Several MCT join to form ducts of Bellini, perforate & open at papilla There are 250 collecting ducts Each collects urine from nephrons

26 NEPHRON III Cclassifications All nephrons are in the cortex Cortical nephrons (85%); have short Henle s loop, to outer medulla with short thin des HL & no thin Asc HL Superficial nephrons Mid-cortical nephrons

27 NEPHRON III Juxtamedullary nephrons (15%=1/7); have very long Henle s loop, sometimes descend to the tip of papilla Have short thick des HL, long thin Dec HL & thin Asc HL & thick Asc HL To establish medullary hypertonicity for concentrating urine

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29 S1 Cortical nephron JM nephron S2 S3

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31 NEPHRON IV Each nephron consists of: Renal corpuscle Renal tubule

32 RENAL CORPUSCLE Each renal corpuscle cconsists of: Glomerulus, a tuft of capillaries Bowman s capsule, a doublewalled epithelial capsule Has two poles: vascular & urinary pole

33 Renal Corpusle

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37 GLOMERULUS I About m A tuft of capillaries Invaginated into Bowman s capsule Formed from AGA AGAs are short, stright, enter renal corpuscle at vascular pole Filtrating surface area is 0.8 m2

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40 GLOMERULUS II Each AGA divides into 3-5 branches; into a tuft of capillaries (20-40 loops) glomerulus Fenestrated endothelial cells (70-90 nm); no diaphragm, act as a physical barrier Capillaries coalesce again to form efferent glomerular arteriole EGA is longer & narrower

41 Neck of the PT at urinary pole Bowman s capsule Consists of two layers: Visceral layer; internal; modified epithelial cells called podocytes Parietal layer; external, single layer of squamous epith supported by basal lamina & reticular fibers In between, Bowman s or urinary space, receives ultrafiltrate

42 PODOCYTES Modified epithelial cells of visceral layer Have cell body & primary processes (arise from body) both not in contact with the capillary Secondary processes or pedicels arise from the primary processes Pedicels in intimate contact with LRE

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47 FILTRATION SLIT Pedicels interdigitate forming filtration slit 25 nm (20-40) & covered by slit diaphragm 6 nm thick SD has circular pores of 3-5 nm Acts as a physical barrier Pedicels covered by glycocalyx Glycocalyx contains sialoprotein (podocalyxin)

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50 Filtration Slit

51 Proteinuria

52 GLOMERULAR BASEMENT MEMBRANE Is produced by fusion of basal lamina of endothelial cells & podocytes As a physical & charge barrier Consists of three layers: Lamina rara interna Lamina densa; collagen IV Lamina rara externa Laminin, fibrenectin, heparan sulphate

53 FILTRATION BARRIER Is a barrier between blood in capillaries & Bowman s space Consists of three layers: Fenestrated endothelial cells GBM Filtration slits of podocytes Glycocalyx

54 FILTRATION BARRIER Lamina densa is a meshwork of type IV collagen & laminin in a matrix containing vely charged proteoglycan (heparan sulfate) acts as a charge & physical barriers Laminae rarae contain fibronectin that binds them to cells

55 FILTRATION BARRIER Particles >10 nm in diameter don t cross GBM While vely charged proteins with MWt > 69 kda pass sparingly The largest protein succeeded to cross GBM has MWt 70kDa, therefore small amounts of albumin appear in urine

56 MESANGIUM Located between glomerular capillaries & consists of: Mesangial matrix & mesangial cells Mesangial cells: Intraglomerular mesangial cells Extraglomerular mesangial cells Supporting, phagocytosis, contraction, resorption

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59 Mesangial cells They are contractile & have Ang II receptors that when activated the glomerular blood flow is reduced Also contain ANF receptors that relax mesangial cells & RBF Therefore, they regulate the RBF & glomerular filtration

60 RENAL TUBULE The second part of the nephron

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62 RENAL TUBULE Is the part of uriniferous tubule orginates at the urinary pole of the renal corpuscle Divided into 12 segments

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64 Proximal tubule S1, 1 st 2/3 of para convoluta S2, last 1/3 of para convoluta & much of para recta S3, remainder of para recta Loop of Henle Thin descending limb Thin ascending limb Distal tubule Medullary thick ascending limb Cortical thick ascending limb Distal convoluted tubule Connecting tubule Collecting tubule or duct Cortical collecting tubule Outer medullary collecting tubule Inner medullary collecting tubule

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66 S1 S3 S2 S1 Cortical nephron JM nephron S2 S3

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69 PROXIMAL TUBULE I First part of renal tubule Drains the urinary space Pars convoluta = PCT Pars recta = straight PT = DTkLH Divides into three segments: S1;1 st 2/3 of pars convoluta S2; last 1/3 of PC & much of PR S3; remainder of pars recta

70 PROXIMAL TUBULE II Confined to renal cortex Is longer than DCT therefore more numerous on histological cross section It is surrounded by peritubular capillaries Composed of single layer of cuboidal epithelial cells

71 PROXIMAL TUBULE III Have brush border of microvilli & apical canaliculi in between These canaliculi help in formation of pinocytosis to absorb macromolecules as proteins

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73 PROXIMAL TUBULE IV Rich in mitochondria and it is highly metabolically active,mainly S1 Because basolateral membranes have abundant Na-K pump which responsible for active reabsorption of Na ions back into peritubular capillaries

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75 HENLE S LOOP A U-shaped structure starts as continuation of PR & ends as ATkLHL Consists of three (or 5) parts: Descending thick LHL Descending thin LHL Loop or turn of Henle Ascending thin LHL Ascending thick LHL composed of single squamous

76 HENLE S LOOP

77 HENLE S LOOP 1/7 are JM nephrons Consists of four types of cells: l Type I only in midcortical & superficial nephrons l Type II,III,IV in JM nephrons JM nephrons have long LHL Cortical nephrons have short LHL

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81 DISTAL TUBULE Starts as continuation of ATnLHL Subdivided into three parts: Pars recta = ATkLHL (part of HL) Macula densa Pars convoluta = DCT DT has single cuboidal epithelial cells, no brush border, no canaliculi ATkLHL is highly metabolic

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83 Shorter than PCT, ratio 1:7 DISTAL TUBULE Macula densa At junction of ATkLHL & DCT It is part of juxtaglomerular apparatus DCT From MD to connecting tubule Cudoidal cells, No brush border

84 Macula densa Is a part of DT at junction of ATkLHL & DCT Also part of juxtaglomerular apparatus Consists of modified columnar cells with closely packed nuclei Sensitive to ionic content & water of tubular fluid

85 Juxtaglomerular apparatus

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87 CONNECTING TUBULE It is a short segment of renal tubules that connects DCT to cortical collecting tubules DCT of several nephrons join to form short connecting tubule Several connecting tubules join to form collecting tubule

88 S1 S3 S2 S1 Cortical nephron JM nephron S2 S3

89 COLLECTING TUBULE Consists of three parts: CCT IMCT OMCT (papillary duct, Bellini ducts) It is not part of the nephron embryologicaly different The epithelium of CT is sensitive to vasopressin or ADH to water reabsorption

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92 Development of the renal pelvis, calyces, collecting tubules A: at 6 weeks, B: at the end of the 6 th wk, C: 7 weeks & D: newborn

93 COLLECTING TUBULE CCT consists of two types of cells: Principal cells (P cells), Na reabsorption & water reabsorption 2ndary to ADH Intercalated cells (I cells); AB balance MCT formed by union of several CCT; has same cells as CCT Papillary CT or ducts of Bellini formed by union of several MCT & open at area cribosa; has only principal cells

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97 Prof. Dr. Peter AGRE Nobel Laureate Nobel Prize in Chemistry 2003

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100 RENAL INTERSTITIUM It is the space between uriniferous tubules & blood & lymphatic vessels Composed of: scanty loose CT; collagen & elastic fibers in both cortex & medulla Three types of cells; fibroblast; macrophages & interstitial cells

101 RENAL INTERSTITIUM Interstitial cells have numerous lipid droplets & synthesize & secrete medullipin I Medullipin I is converted (liver) to medullipin II; a potent vasodialtor which lowers BP Also secrete PGs (E2), prostcyclin

102 JUXTAGLOMERULAR APPARATUS Is a combination of specialized tubular & vascular cells located at vascular pole of glomerulus Consists of: Juxtaglomerular cells of the AGA Macula densa of the distal tubule Extraglomerular mesangial or Lacis cells

103 Juxtaglomerular apparatus

104 Juxtaglomerular apparatus

105 Juxtaglomerular apparatus

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107 JUXTAGLOMERULAR CELLS Specialized, modified (VSMC) myoepithelaial cells; mainly tunica media of AGA as it enters glomeruls, occasionally EGA Contain secretory granules; renin Renin is a proteolytic enzyme that converts angoitensinogen into angiotensin I to regulate BP

108 JUXTAGLOMERULAR CELLS JGCs receive sympathetic nerve via 1 adrenergic receptors Acts as a baroreceptor (BP) Sensitive to change of BP So regulate arterial blood pressure

109 MACULA DENSA Is a speciliazed short segment of DT, as ATkLHL passes near its own corpuscle Located at vascular pole between AGA & EGA Composed of modified epithelial cells that are tall, narrow & have dense closely packed nuclei Appears as dark spot by LM

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111 MACULA DENSA They are not innervated Act as chemoreceptors (Na&Cl) Sensitive to Na & Cl load in DT The JG cells & MD cells are in intimate contact, because no basal lamina between them

112 LACIS CELLS Extraglomerular mesangial cells Polkissen or polar cushions Are one type of mesangial cells forming interstitium of JGA Located between AGA, EGA & MD Are in intimate contact with intramesangial cells Function is unknown (renin)

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114 Bladder & Urinary passages Conduct & store urine till excreted to exterior Mucosa of calyces, renal pelvis, ureters, UB consists of transitional epit with basal lamina Muscle fibers of UB run in every direction until reach bladder neck then arranged into 3 layers Adventia covers them externally

115 Bladder & Urinary passages Internal long layer becomes circular around prostatic urethra, true involuntary urethral sphincter It extends to external meatus in Middle layer ends at bladder neck Outer layer ends at prostate in & at external meatus

116 THANKS FOR ATTENTION