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Kidney Lect 1

Renal Tissue and Cellular Structure

What are the (4) main functions of the kidney? 1) Maintain Salt and Water Balance, 2) Excretion (filtration, reabsorption, and secretion), 3) Endocrine, and 4) Metabolic
"A passive process, based on the size and charge of plasma components; removal of breakdown products of protein metabolism. Filtration occurs in the glomeruli." Filtration
"Retention of essential substances (water, glucose, amino acids, sodium, bicarbonate) from the filtrate back into the blood; this process occurs occurs in the tubules." Reabsorption
"Cellular transport into the tubular lumen of specific substances and drugs too large or too highly charged to enter the filtrate at the glomerulus." Secretion
What does the kidney do to Vitamin D? It metabolizes it to its active form, 1,25 dihydroxyvitamin D3
What does the kidney do during periods of hypoglycemia? Gluconeogenesis takes place in the kidney
How does the kidney contribute to the urea cycle? It converts citruline into arginine as part of the urea cycle's processing of NH4
What stain do you use to see the overall kidney morphology in light microscopy? H
What stain do you use to stain proteoglycans? What structures does it show under light microscopy? Periodic Acid Schiff's (PAS); used to appreciate thickness of basement membrane and extracellular matrix
What stain is used to asses the degree of collagen deposits in the interstitial matrix? (Mallory's) trichrome stain OR Silver stain (for collagen III in the matrix)
Ultrastructural examination is essential for correct diagnosis, especially of glomerular disorders--what microscopy technique is best suited for this? Electron microscopy
What technique would you use to assess the accumulation of C3, C4, or immunogloubulins in renal cells? Immunofluorescence microscopy: antibodies labeled with fluorescein that bind to the targets to see their accumulation int he renal tissue.
What (4) histological areas are always examined in a renal biopsy? Glomeruli, tubules, interstitium, blood vessles
Thick, strong, with capsular veins Capsule
Blood vessel entrance/exit; ureter exit Hilus
Main blood supply (and drainage) to kidney Renal artery & vein
Region with glomeruli & tubules; darker redish brown due to richer blood supply Cortex
Region with straight tubules; shaped zones due to thickness of tubules Medulla
Bundles of straight tubules in cortex which travel to a from the medulla (not part of the medulla) Medullary rays
Conical shped with their apex toward the renal hilus; lighter and striated in appearance Medullary pyramids
Apex of the renal pyramid Renal papilla
Medullary pyramid and cap of cortex (8-14 in humans); interlobar arteries Renal lobes
Medullary ray & associated nephrons; interlobular arteries Renal lobules
Area in middle of kidney continous with ureter Renal pelvis
Describe the branching pattern of the arteries supplying renal tissue Renal artery --> interlobar artery --> arcuate artery --> interlobular artery
What are the (6) main sections of a nephron (from proximal to distal)? Bowman's capsule, proximal tubule, thin limbs of the loop of Henle (descending and ascending), thick ascending limb of the loop of Henle, distal convoluted tubule, collecting duct
What sections of the nephron do you see in the CORTEX? Glomerulus, proximal convoluted tubule, distal convoluted tubule, collecting duct
What sections of the nephron do you see in the OUTER ZONE, OUTER STRIPE? Proximal straight tube, collecting duct
What sections of the nephron do you see in the OUTER ZONE, INNER STRIPE? Descending thin limb of the loop of Henle, ascending thick limbe of the loop of Henle, collecting duct
What sections of the nephron do you see in the MEDULLA? Descending thin limb of the loop of Henle, ascending thin limb of the loop of Henle, collecting duct
Bowman's capsule is associated with what blood vessel structure? Glomerulus (a tuft of capillaries)
What blood vessels are the proximal and distal tubules integrated with to achieve reabsorption and secretion? Peritubular capillaries
What blood vessels do the loops of Henle surround? What function do they fulfill? Vasa recta; produces hypertonic interstitium necessary to alter tonicity of the excreted urine
What blood vessels surround the collecting duct? What function do they fulfill? Vasa recta; allow for final assimilation of water and ions from the urine back to the blood
How are the nephrons classfied? By their relation to the glomerulus: superficial, midcortical, or juxtamedullary. Also by loop of Henle length (short or long looped)
What are the main components of the glomerulus? Associated blood vessles, epithelium of nephron tube (Bowman's capsule), intervening basement membrane, and stalk of support cells (mesangial cells)
Where do the entering afferent arteriole and the exiting efferent arteriole cluster? On the vascular pole of the glomerulus
Where does the nephron tubule exit? Urinary pole of the glomerulus
What percent of the blood exiting from the heart is filtered through the kidney? How much filtrate is produced in comparison? 20% (or 1 L/min of total cardiac output of 5 L/min)--> kidneys produce 180 liters of filtrate every 24 hours but only excrete 1-2 liters of volume
Describe the structure of the capillary endothelium in the glomerulus Fenestrated with almost no diaphragms spanning the pores; patent capillary loops. Glomerular capillaries merge to form the exiting efferent arteriole. Arterioles are surrounded by smooth muscle that determines filtration pressure.
What determines the filtration pressure in the glomerular capillaries? The contraction / relaxation of the muscles around the arterioles
What is Bowman's capsule? The blind beginning of the nephron tube; looks like a bulbous expansion.
Describe the epithelium of the Bowman's capsule Simple squamous epithelium that also forms the outer wall of the urinary space. @ vascular pole: continous with visceral epithelium of Bowman's capsule + reflects over glomerulus. @ urinary pole: parietal epithelium continous with proximal tube
What specialized cells form the visceral epithelium of Bowman's capsule and cover the glomerular capillaries? Podocytes
Podocyte processes or trabeculae interdigitate with processes from neighboring podocytes to forma series of _____ ____ or _____. Foot processes OR predicels
The spaces between foot processes are spanned by a ____ ___ ___, a specialized junctional complex. filtration slit diaphragm
What is Nephrin? Transmembrane protein of the immunoglobulin superfamily (like cadherins) that forms homodimers to link neighboring foot processes
What is podocalyxin? A glycoprotein rich in negatively charged sialic acid; coats the pedicels
Fusion of adjacent pedicels occurs only in ____ states. Pathological
Where is the basement membrane located? Between glomerular capillary endothelium and the podocyte foot processes
How many layes does the glomerular basement membrane have? Lamina rara externa (contacts glomerular podocytes), the lamina densa (central dense layer), and the lamina rara interna (contacts the capillary endothelium)
Describe the structure of the central lamina densa Enriched with collagen type IV (limits porosity of the glomerular basement membrane to substances < 40,000 Da [albumin is 68,000 Da])
Describe the structure of the lamina rara interna and externa Contain anchoring proteins laminin and firbonecting as well as heparan sulfate-rich anionic proteoglycans; + charged proteins pass while - charged proteins repelle
What pathological change do you see in patients with diabetes at the level of the basement membrane of the glomerulus? Decrease in membrane heparan sulfate-->proteinuria
What three hitological layers comrpise the glomerular filtration barrier? Fenestrated endothelium, glomerular basement membrane, foot processes with filtration-sit diaphragm
What two factors determine the glomerular filtration rate? 1) Blood pressure (hydrostatic pressure) and 2) oncotic pressure by plasma proteins. Blood pressure is controlled by smooth muscle in media of both afferent and efferent arterioles and contractile intraglomerular mesangial cells
What are the main functions of smooth-muscle like mesangial cells? 1) Contract to limit surface area for filtration, 2) synthesize extracellular matrix components, 3) secrete prostoglandins, 4) secrete and respond to horomonse, cytokines, growth factors, and paracrine agents
Smooth muscle-like mesangial cells express ___, which allows them to contract. They are sensitive to ____. Actin; angiotensin II
Smooth muscle-like mesangial cells synthesize what extracellular matrix components? Collagen (IV and V; more I and III when activated by cytokines), fibronectin, thrombospondin, laminin, vitronectin, and proteoglycans as well as metalloproteinases and serine-proteinases (for EM turnover)
What is the function of bone marrow-derived macrophages in the kidney? Phagocytose apoptotic cells and materials that have lodged in the basement membrane. These mechanisms utilize C3b or Fc receptors to bind opsonized particles; Express MHC-II antigens on their surface (antigen presenting cells)
What part of the proximal tubule acts as the "reabsorptive workhorse of the kidney"? The proximal tubule
The absorption of solutes is proportional to that of ____. Therefore absorption in the proximal tubule is _____. Water; isosmotic
How is the proximal tubule divided histologically? Three physiological distinct segments (S1, S2, S3) based on distribution of transporters; anatomically, 2 distinct segments (proximal convoluted and straight tubules); histologically, they look the same
What portion of the proximal tubule occupy much of the cortex around the glomeruli? The proximal convoluted portion
The proximal straight tubules tubules are part of the ____ ___, a cluster of straight tubules in the cortex, en route to the medulla medullary ray
The ___ ____ ____ folds as tall, regular microvilli called a ___ ___, increasing the surface area of the proximal tubules by 36x. Apical plasma membrane; brush border
Where/how are amine acids, glucose, citrate, and bicarbonate ions absorbed? In the proximal tubule via secondary active transport in the apical plasma membrane; they are coupled with Na+ ions in positively charged carrier complexes
In the proximal tubule, apical ___ ___ (zonula occludens) are less frequent and thinner than in other tissues; desmosomes are (infrequent/frequent) Apical tight junctions; infrequent
Specific claudins in the tight junction create a "___" epithelium in the proximal tubule leaky; permits paracellular movement of water and Ca++ from the lumen to the interstitial space below the epithelium
How does water move through the apical membrane of the proximal tubule? Via aquaporins and via the claudins in the tight junctions
What is the endocytic apparatus? Vesicular invaginations between bases of microvilli, clathrin coated vesicles, large vacuoles, lysosomes and condensing vacuoles on apical membrane; peptides from filtrate endocytosed and degraded before release outside of basolateral aspect of cells
What is megalin? How is it regulated? Specific endocytosis receptor receptor for albumin and small proteins recovered int he proximal tubule; TGF-beta downregulates megalin during inflammation-->proteinuria; statins also inhibit endocytosis-->proteinuria
Why is the basolateral plasma membrane of the proximal tubule so folded? To provide surface area for Na+K+ATPase transporters; this actively pumps Na+ OUT of the cell and into basolateral extracellular space; Na+ electrochemical gradient powers secondary active transport at apical border
What organelle is occupies the folds between basolateral invaginations? Why? Mitochondria; provide ATP for active transport
What are the four major portions of the loop of Henle? Thin descending limb, thin ascending limb, medullary thick ascending limb (mTAL), cortical thick ascending limb (cTAL)
How does the length of the loop of Henle vary? With the location of the glomerulus of origin: superficial glomeruli have very short loops, while juxtamedullary glomerulli have very long ones
How do long loops of Henle concentrate urine? Develop hypertonic interstitium in the medulla, which is maintained by a countercurrent exchange between tubules and vasa recta (which surround loops of Henle)
Approximately what portion of nephrons contain long loops of Henle? 13%
The ___ portions of the loop of Henle have simple squamous epithelium, but only display slight variations of the number of interdigitations and mitochondria thin
What things is the thin descending limb permeable to? Impermeable? Permeable to water and urea (passively move into hypertonic interstitium of medulla); impermeable to Na+ and Cl-; throughout descent, tubular fluid is in equilibrium with interstitium
What things is the thin ascending limb permeable to? Impermeable? Impermeable to water and highly permeable to Na+ and Cl- (as well as Mg++ and Ca++): salt passively exits tubule as flow ascends into relatively less hypertonic regions of medulla; more claudins and less aquaporins prevent H2O movement
Where does the transition to the thick ascending limb of the loop of Henle (TAL) occur? Near the hairpin turn in short looped nephrons and at the transition from the outer to inner medullary zones in the long-looped nephrons
The ___ is often called the diluting segment because... TAL; lumenal contents are hypotonic when they exit
What type of epithelium is found in the thick ascending limb of the loop of Henle (TAL)? How is the cytoplasm organized? Simple cuboidal epithelium with numerous invaginations of the basolateral plasma membrane; site of Na+/K+ ATPase active transport pumps. Cytoplasmic folds have (rounder) mitochondria. Apical membrane slightly irregular and has Na+K+2Cl- symporter
What does the Na+K+2Cl- symporter do? What class of drugs inhibit it? What's the result? Movement of Na+ and Cl- from the lumen into the interstitium; loop diuretics (e.g. furosemide) inhibits, resulting more Na+ and Cl- reamining in lume. Ion pumping in TAL creates hypertonic interstitium
What structure distinguishes the apical plasma membrane from the basolateral folds in the loop of Henle? What is the function of this structure? In electron micrographs, you can see that the apical plasma membrane have extensive tight junctions; blocks paracellular movement of water
What structures are responsible for the TAL's filtration properties? Extensive tight junctions and no aquaporins --> water impermeable; claudins on tight junctions: Mg++, Ca++, and Na+ permeable. TAL thus makes hypertonic medullary interstitium and delivers hypotonic dilute tubular fluid to distal convoluted tubule
What is the macula densa? Last segment of the cortical thick ascending limb; each macula densa returns to its glomerulus of origin. Component of the juxtaglomerular apparatus responsible for the secretion of renin
Tese tubules are located in the cortex intermingled with the proximal convoluted tubules Distal convoluted tubules
Histologically, how do the proximal and distal convoluted tubules differ? Distal: shorter (fewer cross-sections per area on slide) and a lower cuboidal epithelium; apical surface has no microvilli (smooth lumne); tight junctions broader and have sealing claudins (no paracellular movement)
What is the distal convoluted tubule impermeable/permeable to? Impermeable to water; basolateral surface is highly folded with Na+K+ATPase pumps and accompanying mitochondria. Basolateral active transport pumps serve as driving force for reabsorption of Na+ and Cl- by a mechanism not fully understood
How does aldosterona and parathyroid hormone (PTH) affect the distal convoluted tubule? The distal convoluted tubule responds to aldosterone to reabsorb Na+ and to parathyroid hormone (PTH) to reabsorb Ca++
What are the three segments of the collecting duct? The connecting segment, the cortical collecting duct, and the medullary collecting duct
What is the main function of the collecting duct? What hormones control this? Responsible for adjustments to the volume and tonicity of the excreted urine. Vasopressin (antidiuretic, ADH) and aldosterone.
How does the collecting duct epithelium change as one progresses to the medullary papilla? Initially, collecting duct lined by simple cuboidal epithelium; becomes tall columnar, and eventually becomes pseudostratified at the exiting papillary ducts; full length has distinct lateral cell borders; no basolateral interdigitations obscure this line
In the collecting duct, what are the two cell types seen under EM? Principal (light) cells and intercalated (dark) cells.
Describe the structure of the principal (light) cells Light cells: pale cytoplasm, small random mitochondria, few basal infoldings, few microvilli, single cilium. Cilium senses flow and mechanically linked to Ca++ channel.
How do principal (light) cells respond to aldosterone? To antidiuretic hormone? Principal cells respond to aldosterone by reabsorbing Na+ and secreting K+. They respond to antidiuretic by increasing the luminal permeability to water (inserts new water channels)
Why are intercalated cells called "dark" cells? What do they do? More electron dense when visualized under electron microscope; secrete H+ and therefore play a large role in acid/base balance and the acidification of urine
What are the functions of the juxtaglomerular apparatus? Control GFR so as not to flood out capacity of distal nephron; prevent excessive salt and water loss; adjust renal hemodynamics during periods of increased or decreased perfusion; activate renin, angiotensin II, aldosterone cascade
What are the components of the juxtaglomerular apparatus? It's sensors? Afferent arteriole and its juxtaglomerular cells, efferent arteriole, the macula densa, and the extraglomerual mesangial cells. Sensors are the afferent arteriole stretch receptors and macula densa Cl-/osmolality receptors
The specialized smooth muscle of the afferent arteriole is composed of specialized cells called ___ ____. Juxtaglomerular cells (JG)
What intracellular components are found in JG cells? intracellular actin, myosin, and dense bodies (like all smooth muscle cells); also contain more RER, Golgi, and a store of secretory vesicles (filled with RENIN)
How do JG cells control the release of renin? With decrease in arteriolar stretch due to decrease blood pressure-->renin granule secretion. With elevated blood pressure, JG cells produce myogenic response to vasoconstrict the afferent arteriole.
Describe the appearance of the macula densa cells Base of macula densa cells interdigitate with underlying extraglomerular mesangial cells and with JG cells; nuclei forced apically toward the lumen
What is the function of the macula densa? If Cl- flow rates high in TAL, macula densa blocks release of renin by JG cells; acts on JG cells of afferent arteriole (directly) via adenosine and NO, (indirectly) via angiotensin II and thromboxaine
Where are the extaglomerular mesengial cells located? Between the afferent arteriole, the efferent arteriole, the macula densa and the glomerulus.
What do the extraglomerular mesengial cells do? Interact with both the macula densa cells and the JG cells; assist in regulating renin secretion and vasoconstriction
What does the efferent arteriole control? How does it do so? Contracts to increase hydrostatic pressure within glomerulus; if blood flow low, angiotensin II preferentially causes efferent arteriole constriction to preserve GFR; response modulated by prostaglandins (vasodilation)
What are the two main types of tissue of the renal interstitium? Cortex and medulla
What are the (2) types of cells found in the cortex interstitium? 1. Fibroblast-like cells elaborate a small amount of extracellular matrix, and also contain contractile filaments. May be the cells that secrete erythropoietin. 2. Phagocytic, derived from the monocyte cell line.
What are the (3) types of cells found in the medulla interstitium? Type I - Fibroblast-like; Type II - Rounded cells w/ many free ribosomes and lysosomes; Type III - Similar to pericytes
Describe the fibroblast type cells of the medulla Type I - Fibroblast-like, with many lipid droplets, SER, and mitochondria with vesicular cristae. Site of prostaglandin synthesis.
Describe the rounded cells of the medulla Type II - Rounded cells w/ many free ribosomes and lysosomes; no lipid droplets. Function unknown.
Describe the pericyte-like cells of the medulla found in basement membrane of vasa recta. May act as source of regenerative cells.
What areas of the kidney get the most blood flow? 80% goes to outer cortex (~85% of glomeruli there), 10-15% goes to inner cortex (15% of glomeruli), while 5-10% goes to medulla
How does blood flow change during ischemia? During periods of hypovolemia? Periods of ischemia pose greater risk to low flow areas; during hypovolemic states, blood flow from outer cortex diverted to inner cortex
Describe the branching of the renal arteries The renal arteries branch into interlobar arteries at the base of the medullary pyramids, and penetrate the medulla between renal lobes.
Describe the branching of the interlobar arteries Interlobar arteries divide into arcuate arteries which turn a right angle to lie at the junction of the cortex and medulla. Arcuate arteries do not anastomose; each responsible for supplying a specific portion of the cortex.
Describe the branching of the arcuate arteries Interlobular arteries arise from the arcuate, and penetrate the cortex between medullary rays.
Describe the branching of the interlobular arteries Interlobular arteries can give rise to afferent arterioles directly, or the afferent arterioles may arise from short intralobular arteries.
Describe the branching of the afferent arterioles Afferent arterioles branch to form the glomerular capillary tuft, which then reforms into the exiting efferent arteriole.
Describe the different in blood vessel structure that varies with glomerulus position in the cortex. In superficial glomeruli a peritubular capillary plexus is formed to assimilate reabsorbed materials. In juxtamedullary glomeruli, vasa recta descend into the medulla and accompany the loops of Henle to the papillary tips.
Describe the vein flow in the kidney Both capillary networks reform into arcuate veins. The remaining venous flow is the reverse of the arterial flow.
Created by: karkis77