renal histology

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RENAL ANATOMY AND HISTOLOGYHistologyRenal FunctionRegulation of water and electrolyte balance and acid-base balance

Excretion of metabolic wastes, water and electrolytes in urine

Excretion of many bioactive substances, including many drugs

Regulation of arterial blood pressure by secretion of renin

Secretion of erythropoietin, a glycoprotein growth factor that stimulates erythrocyte production in red marrow when the blood O2 level is low

Conversion of the steroid prohormone vitamin D, initially produced in the epidermis, to the active form (1,25-dihydroxyvitamin D3 or calcitriol)

Gluconeogenesis during starvation or periods of prolonged fasting, making glucose from amino acids to supplement this process in the liverKidneyEach kidney has a thick outer cortex, surrounding a medulla that is divided into 8 to 12 renal pyramids; each pyramid and its associated cortical tissue comprises a renal lobe.

The apical papilla of each renal pyramid inserts into a minor calyx, a subdivision of two or three major calyces extending from the renal pelvis.

The ureter carries urine from the renal pelvis and exits the renal hilum, where the renal artery and vein are also located.

Striations extending from the medulla into the cortex are called medullary rays; these plus the attached cortical tissue are considered lobules.

NephronEach kidney contains around 1 million functional units called nephrons that consist of simple, single-layered epithelium along their entire lengths.

Cortical nephrons are located almost completely in the cortex while juxtamedullary nephrons (about one-seventh of the total) lie close to the medulla and have long loops of Henle.

Major Divisions:Renal corpuscle, an initial dilated part enclosing a tuft of capillary loops and the site of blood filtration, always located in the cortex;Proximal tubule, a long convoluted part, located entirely in the cortex, with a shorter straight part that enters the medulla;Loop of Henle (or nephron loop), in the medulla, with a thin descending and a thin ascending limb;Distal tubule, consisting of a thick straight part ascending from the loop of Henle back into the cortex and a convoluted part completely in the cortex; andConnecting tubule, a short final part linking the nephron to collecting ducts.

Cortical vs. Juxtamedullary NephronsThe cortical nephrons make up 85% of the kidney nephrons and are contained entirely in the cortex and almost dont reach the medulla. Their function is to filter the plasma, reabsorb critical ions and molecules, and send their filtrate to the collecting ducts.

The juxtamedullary nephrons make up 15% of the nephrons. They have long loops of Henle that extend deep into the medulla. They create the concentration gradient in the medulla necessary to either dilute or concentrate urine. (Countercurrent multiplication)Blood SupplyRenal artery divides into two or more segmental arteries at hilum

Renal artery Interlobar arteries Arcuate arteries Smaller interlobular arteries radiate from the arcuate arteries Afferent arterioles Plexus of capillary loops (glomerulus) Efferent arterioles Peritubular capillaries

From the juxtaglomerular corpuscles near the medulla, efferent arterioles do not form peritubular capillaries, but instead branch repeatedly to form parallel capillary loops called the vasa recta that penetrate deep into the medulla in association with the loops of Henle and collecting ducts. Cortex receives over 10X more blood supply than medulla

Renal CorpuscleContains a tuft of glomerular capillaries, surrounded by a double-walled epithelial capsule called Bowman capsule

The internal or visceral layer of this capsule closely envelops the fenestrated capillaries. The visceral layer consists of stellate epithelial cells called podocytes which together with the capillary endothelial cells compose the apparatus for renal filtration.

Podocytes extend large primary processes that curve around a capillary and extend short, interdigitating secondary processes or pedicels, between which are narrow spaces called slit pores.

The outer parietal layer has a simple squamous epithelium and forms the surface of the capsule.

Between the two capsular layers is the urinary space

Each renal corpuscle has a vascular pole, where the afferent arteriole enters and the efferent arteriole leaves, and a tubular pole, where the proximal convoluted tubule (PCT) begins

Mesangial CellsPhysical support of capillaries within the glomerulus;Adjusted contractions in response to blood pressure changesPhagocytosis of protein aggregates adhering to the glomerular filterSecretion of several cytokines, prostaglandins, and other factors important for immune defense and repair in the glomerulus.

Proximal Convoluted TubuleThe first tubular part, the proximal convoluted tubule (PCT), is mainly cortical, has simple cuboidal cells with long microvilli in the lumen, abundant mitochondria, and large, interdigitating basolateral folds.

The cells of the proximal tubules have central nuclei and very acidophilic cytoplasm because of the abundant mitochondria.

Cells show prominent vacuoles.

The long brush border may be disorganized and give the lumens a fuzz-filled appearance

In the PCT, all glucose and other organic nutrients, all small proteins and peptides, and much water and electrolytes are reabsorbed from the filtrate and transferred to the peritubular capillaries.

Loop of HenleFrom the PCT filtrate flows into the loop of Henle, located in the medulla, which has squamous thin descending and ascending limbs; the latter extends as a thick ascending limb (TAL) back into the cortex.

In the cortex the TAL contacts the arterioles at the vascular pole of its parent renal corpuscle and there thickens focally as the macula densa.

Tall epithelial cells of the macula densa and specialized smooth muscle cells in the adjacent afferent arteriole called juxtaglomerular cells, which secrete renin, comprise a juxtaglomerular apparatus (JGA) that is an important regulator of blood pressure.

The thin ascending and descending limbs have simple squamous epithelium while the thick ascending limb has simple cuboidal epithelium

Thin SegmentsLoop!Collecting ducts

Distal Convoluted TubuleBeyond the macula densa, the tubule continues as the distal convoluted tubule (DCT), where electrolyte levels of the filtrate are adjusted further and which lead to short connecting tubules.

The simple cuboidal cells of the distal tubules differ from those of the proximal tubules in being smaller and having no brush border and more empty lumens.

Common to see luminal nuclei.

Juxtaglomerular ApparatusCells of the macula densa typically have apical nuclei, basal Golgi complexes, and a more elaborate and varied system of ion channels and transporters.

Adjacent to the macula densa, the tunica media of the afferent arteriole is also modified. The smooth muscle cells are modified as juxtaglomerular granular (JG) cells, with a secretory phenotype including more rounded nuclei, rough ER, Golgi complexes, and zymogen granules with

Also at the vascular pole are lacis cells which are extraglomerular mesangial cells that have many of the same supportive, contractile and defensive functions as these cells inside the glomerulus

Macula DensaHigher GFR leads to higher luminal concentrations of Na+ and Cl- in the TAL of the nephron, which are monitored by cells of the macula densa. Increased ion levels in the lumen cause these cells to release ATP, adenosine, and other vasoactive compounds that trigger contraction of the afferent arteriole, which lowers glomerular pressure and decreases the GFR. This lowers tubular ion concentrations, which turns off the release of vasoconstrictors from the macula densa.

JG CellsDecreased arterial pressure leads to increased autonomic stimulation to the JGA as a result of baroreceptor function. This causes the JG cells to release renin into the blood. Renin angiotensinogen into angiotensin I. Angiotensin-converting enzyme (ACE) on lung capillaries clips this further to angiotensin II, a potent vasoconstrictor that directly raises systemic blood pressure and stimulates the adrenals to secrete aldosterone. Aldosterone promotes Na+ and water reabsorption in the distal convoluted and connecting tubules, which raises blood volume to help increase blood pressure. The return of normal blood pressure turns off secretion of renin by JG cells.Collecting TubuleThe last part of each nephron, the connecting tubule, carries the filtrate into a collecting system that transports it to a minor calyx

A connecting tubule extends from each nephron and several join together in the cortical medullary rays to form collecting ducts of simple cuboidal epithelium

In the apex of the pyramid, several collecting ducts merge further as a papillary duct which delivers urine to the minor calyx

Collecting ducts are composed mainly of pale-staining principal cells with few organelles, sparse microvilli, rich with aquaporins and distinct cell boundaries

Scattered among the principal cells are variably darker intercalated cellswith more abundant mitochondria and projecting apical folds. Intercalated cellshelp maintain acid-base balance by secreting either H+ or HCO3-.

Antidiuretic hormone (ADH) makes collecting ducts more permeable to water and increases the rate at which water molecules are pulled osmotically from the filtrate. UreterThe ureters are lined by urothelium, or transitional epithelium, which protects underlying cells from hypertonic or toxic effects of urine.

Large, bulbous superficial cells of the urothelium, called u