renal histology

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RENAL ANATOMY AND HISTOLOGY

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Page 1: Renal Histology

RENAL ANATOMY AND

HISTOLOGY

Page 2: Renal Histology

HISTOLOGY

Page 3: Renal Histology

Renal Function

• Regulation 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 liver

Page 4: Renal Histology

Kidney

• Each 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.

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Nephron

• Each 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 Henleback into the cortex and a convoluted part completely in the cortex; and

• Connecting tubule, a short final part linking the nephron to collecting ducts.

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Cortical vs. Juxtamedullary Nephrons

• The cortical nephrons make up 85% of the kidney nephrons and are

contained entirely in the cortex and almost don’t 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)

Page 9: Renal Histology

Blood Supply

• Renal 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 Henleand collecting ducts.

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Cortex receives over 10X more blood

supply than medulla

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Renal Corpuscle• Contains 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 podocyteswhich 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

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Mesangial Cells

• Physical support of capillaries within the glomerulus;

• Adjusted contractions in response to blood pressure changes

• Phagocytosis of protein aggregates adhering to the glomerular filter

• Secretion of several cytokines, prostaglandins, and other factors

important for immune defense and repair in the glomerulus.

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Proximal Convoluted Tubule

• The 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.

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Loop of Henle

• From 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.

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The thin ascending and descending limbs

have simple squamous epithelium while

the thick ascending limb has simple

cuboidal epithelium

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Thin Segments

Loop!

Collecting ducts

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Distal Convoluted Tubule

• Beyond 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.

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Juxtaglomerular Apparatus

• Cells 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

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Macula Densa

• Higher 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.

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JG Cells

• Decreased 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.

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Collecting Tubule

• The 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-.

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Antidiuretic hormone (ADH) makes

collecting ducts more permeable to water

and increases the rate at which water

molecules are pulled osmotically from the

filtrate.

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Ureter

• The 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 umbrella

cells, have apical membranes consisting of hinged regions with dense

plaques of uroplakin proteins that protect the cytoplasm.

• Characteristic pattern of longitudinally folded mucosa, surrounded by

a thick muscularis that moves urine by regular waves of peristalsis.

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Inner longitudinal and outer circular muscles

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Bladder

• Urothelium is surrounded by a folded lamina propria and submucosa, followed by a dense sheath of interwoven smooth muscle layers and adventitia

• The bladder's lamina propria and dense irregular connective tissue of the submucosa are highly vascularized.

• As the urinary bladder fills its highly folded mucosa unfolds, the urothelium gets somewhat thinner by cell movements, and the hinged membrane plaques of umbrella cells partially unfold.

• The muscularis consists of three poorly delineated layers, collectively called the detrusor muscle

• All the urinary passages are covered externally by an adventitial layer, except for the upper part of the bladder that is covered by serous peritoneum.

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Urethra

• The urethra drains the bladder and is lined by unusual stratified

columnar and pseudostratified columnar epithelium.

• In males the urethra has three regions: the prostatic urethra in the

prostate gland; the short membranous urethra passing through the

urogenital diaphragm, and the long penile urethra.

• In women, the urethra is 4- to 5-cm-long, lined initially with transitional

epithelium, then by stratified squamous epithelium and some areas of

pseudostratified columnar epithelium

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ANATOMY

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Kidney Position

• The left kidney is related to ribs 11 and 12. Its upper pole is located at

vertebral level T11, and it is also located higher than the right kidney.

• The right kidney is only related to rib 12. Its upper pole is located at

T12. The presence of the liver is the reason the right kidney is lower

down.

• The kidneys are retroperitoneal organs, which lie on the ventral

surface of the quadratus lumborum muscle, lateral to the psoas

muscle and vertebral column, and superior to the iliacus.

Page 44: Renal Histology

Kidney Injury

• Fracture of the lower ribs,

• Fracture of the transverse processes of lumbar vertebrae,

• Gunshot or knife wound over the lower rib cage,

• And after a car accident when seat belt marks are present.

• Right kidney trauma is associated with liver trauma, whereas left

kidney trauma is associated with spleen trauma.

• Clinical findings include flank mass and/or tenderness, flank

ecchymosis, hypotension, and hematuria.

• One of the absolute indications for renal exploration is the presence

of a pulsatile or expanding retroperitoneal hematoma found at

laparotomy.

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Renal Capsule and Renal Fascia

• The kidneys are directly covered by a fibrous renal capsule (aka true capsule).• This can be readily stripped from the surface of the kidney except

in pathologic conditions where scarring makes it strongly adherent to the kidney.

• The kidneys are further surrounded by the perirenal fascia (of Gerota, aka false capsule).• The fascia defines the perirenal space (aka perinephric space),

which contains:Kidney, adrenal gland, ureter, gonadal artery and vein, and perirenal fat.

• Note that the fascia is important in the staging of renal cell carcinoma.

• Also any fat located outside the perirenal space is called pararenalfat, and is best seen posterolaterally.

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Nutcracker Syndrome

• Nutcracker syndrome (NCS) refers to the wide spectrum of clinical

presentations caused by compression of the left renal vein between

the abdominal aorta and the superior mesenteric artery.

• Can lead to hematuria and left flank pain.

• Because the left gonadal vein drains to the left renal vein, the condition can

also result in left testicular pain or left lower quadrant pain in women.

• The right gonadal vein drains directly to the inferior vena cava

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Horseshoe Kidney

• Normally, between the 6th and 9th weeks of development, the

kidneys ascend to a lumbar site immediately inferior to the suprarenal

glands, following a path just on either side of the dorsal aorta.

• Horseshoe kidney occurs when the inferior poles of both kidneys fuse

during fetal development. The horseshoe kidney gets trapped behind

the inferior mesenteric artery as the kidney attempts to ascend toward

the normal adult location.

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Accessory renal arteries

• During its ascent, the kidneys are progressively revascularized by a

series of arterial sprouts from the dorsal aorta. As new, more

superiorly located blood vessels are produced, the older, inferiorly

located vessels degenerate.

• Accessory renal arteries develop as sometimes one or more of the

transient inferior renal arteries fail to regress.

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Oligohydramnios

• Oligohydramnios - A deficiency (lack of) in amniotic fluid due to a

congenital abnormality of fetus.

• One of the causes is a lack of kidney formation (renal agenesis) or

malformations (renal dysplasias like multicystic dysplastic kidney) and

therefore lack of urine production that would contribute to amniotic

fluid.

• Therapy: dialysis and transplantation in first years of life

Page 51: Renal Histology

Ureteral Constriction and Urolithiasis

• Ureter constriction locations

• Ureteropelvic junction

• Ureteral crossing of iliac vessels

• Ureterovesical junction

• Proximal ureter - Upper limit of T12-L2/L3 regions of spinal cord

• Middle ureter - Lower limit of T12-L2/L3 regions of spinal cord

• Distal ureter - PS neurons from S2-S4 regions of spinal cord

• In general a renal calculus will refer ureter pain from flank, down the

abdomen and into the perineum, thigh and genitalia

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Male vs. Female Ureter

• Male ureters -- pass posterior to ductus deferens to reach bladder

• Female ureters -- pass posterior and inferior to uterine artery to reach

bladder

• Ureter injury is rarely due to external trauma because they are well

protected. The more common causes of injury are iatrogenic. Most

commonly, the abdominal hysterectomy in females.

• The uterine arteries run across the anterior side of the ureters. These

arteries are ligated during hysterectomies, putting the ureters at risk.

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Duplicated Ureters and Renal Pelvis

• If ureteric bud splits prematurely duplication of ureters can result.

• The splitting can occur partially or completely and metanephric tissue

can be divided into two parts, each with its own renal pelvis and

ureter.

• In normal development, during the fifth week ureteric buds sprout

from distal portion of mesonephric region.

• The intermediate mesoderm and ureteric buds interact with one

another and cause the following formations:

• Ureteric bud collecting duct system and ureters

• Intermediate mesoderm nephrons

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Pelvic Spaces

• Rectovesical pouch - most inferior aspect of peritoneal cavities in males; posterior surface of the bladder in males

• Rectouterine pouch - most inferior aspect of peritoneal cavities in females; superior to the bladder in females

• Excess peritoneal fluid flows to these locations when one is in a standing or sitting position.

• When supine, excess fluid flows to the hepatorenal recess (in either sex) instead.

• Retropubic space (of Retzius) - fat-filled space posterior to pubis that is continuous with deep perineal space; defines the anterior surface of the bladder• Rupture of the bladder or urethra results in an extraperitoneal extravasation of

urine within this space

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Male and Female Pelvis

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Micturition

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Congenital Malformations

• Urachal cyst/Urachal sinus

• Remnant of the allantois persists in the urachus

• Urachal fistula

• Persistence of the entire lumen of the intraembryonic portion of the allantois.

• May cause urine to drain from the umbilicus

• Rectovesical fistula

• Various congenital defects are associated with improper partitioning of the

cloaca. A rectovesical fistula is an improper communication between the

rectum and the urinary bladder

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Divisions of the Urethra

• Preprostatic urethra

• Prostatic Urethra

• Membranous Urethra

• Bulbous Urethra

• Spongy Urethra

• Distal Penile Urethra

Page 62: Renal Histology

Urine Leakage• Type II

• Posterior urethra is torn above the urogenital diaphragm

• Can be caused by a fractured pelvis, or improperly inserted catheter

• Urine leaks within the retropubic space

• Type III: Most Common• Anterior urethra is torn below the urogenital diaphragm. The membranous urethra is also torn due to

disruption of the urogenital diaphragm

• Caused by a saddle injury

• Urine leaks extraperitoneally into the superficial perineal space

• Type IV• Neck of bladder and proximal prostatic urethra are injured

• This injury is especially serious if the internal urethral sphincter is injured

• Extraperitoneal leakage into the retropubic space

• Type V• Penile urethra is torn

• Caused by a crushing injury to the penis

• Extraperitoneal leakage beneath the deep fascia. Will be confined to the penis if the fascia is intact.

• If fascia is damaged, leakage can occur in the superficial perineal space

Page 63: Renal Histology

Visceral Pain of the Pelvic Region

• Kidneys

• T12-L2 dermatomes

• Proximal ureter

• Renal plexus + abdominal aortic plexus

• Middle ureter

• L1-L2

• Distal ureter

• L3-L4

• Bladder

• S2-S4, T11-L2

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IMAGING

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Imaging Densities

• Air

• Fat

• Tissue/Water

• Bone

• Metal

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Contrast

• CT contrast media: Iodine (very nephrotoxic)

• MRI contrast media: Gadolinium

• The use of contrast for CT scans is contraindicated if the patient is

allergic or in the event of contrast induced nephropathy, or if the

patient has kidney disease.

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Use US in pregnant women.

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T1 vs. T2• Dark on T1-weighted image:

• Increased water, as in edema, tumor, infarction, inflammation, infection, hemorrhage (acute/chronic)

• Low proton density, calcification

• Flow void

• Bright on T1-weighted image:• Fat

• Subacute hemorrhage

• Melanin

• Protein-rich fluid

• Slowly flowing blood

• Paramagnetic substances: gadolinium, manganese, copper

• Bright on T2-weighted image:• Increased water, as in edema, tumor, infarction, inflammation, infection, subdural collection

• Subacute hemorrhage

• Dark on T2-weighted image:• Low proton density, calcification, fibrous tissue

• Paramagnetic substances: deoxyhemoglobin, methemoglobin (intracellular), iron, ferritin, hemosiderin, melanin

• Protein-rich fluid

• Flow void

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Look to the water: Bright on T2

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Renal Size and Location

• The normal longitudinal dimension of the right kidney is 11 cm ± 1 cm, and that of the left kidney is 11.5 cm ± 1 cm

• The contours of the kidneys are usually smooth; occasionally, some slight nodularity is present as a result of fetal lobulation.

• The kidneys are located in the retroperitoneum surrounded by a layer of renal fascia and perinephric fat.

• The upper pole of the left kidney occurs at the level of the T11 vertebra, whereas the upper pole of the right kidney occurs at the level of the T12 vertebra.

• The left kidney is related to rib 11 and rib 12. The right kidney is related only to rib 12.

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Ureters

• The ureters pass posterior to the gonadal vessels and anterior to the

psoas major muscle.

• They cross anterior to the common iliac (or external iliac) arteries and

veins and the pelvic brim to enter the lesser pelvis.

• In the lesser pelvis the ureters run posteroinferiorly on its lateral walls.

Opposite the ischial spine they curve anteromedially to enter the

urinary bladder.

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Cortex and Medulla on US

Terms used in US

• Hyperechoic• Hypoechoic• Isoechoic

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Xray

Normal Kidney

Ureter

Bladder

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CT

Terms used in CT

• Hyperdense• Hypodense• Isodense

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MRI

Terms used in CT

• Hyperintense• Hypointense• Isointense

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Contrast Enhanced CT

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T2 weighted Magnetic Resonance

Urogram – Normal Ureter

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Normal Bladder - US

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Normal Bladder - CT

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Normal Bladder - MRI

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Renal Vessels on US

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Renal Arteries (L) and Renal Veins (R)

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Common indications

US:

• Hydronephrosis

• Renal Size

CT

• Stone

• Mass

MRI

• Mass

• Low renal function

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Advantages and disadvantages

US:

• No radiation

• Bed side

• Obesity/Bowel/Operator dependent

CT:

• Good anatomic overview

• Good for stone evaluation

• Radiation

MRI:

• No radiation

• Not good for stones

• Expensive

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ABNORMAL IMAGING