Shared characteristics of the proximal and distal convoluted tubules

• Both are key sites of reabsorption and secretion, which is necessary for fine-tuning the ultrafiltrate to form urine
• Abundant mitochondria support high levels of cellular activity
• Both have plasma membrane infoldings that increase the surface area for optimal diffusion
• Though at opposite ends of the nephron, both reside within the renal cortex, near their renal corpuscles, due to the winding nature of nephrons

Anatomical Review

Kidney:

• Renal capsule covers the cortex
• Medulla comprises the renal pyramids.
• The cortico-medullary junction is where the cortex and medulla meet.
  Nephron:
• Arises from the renal corpuscle in the cortex as the proximal tubule
• Descends and ascends through the medulla as the nephron loop, becomes the distal tubule, then drains into a collecting duct.
  — As we learn elsewhere, collecting ducts drain urine through the renal pyramids to the renal calyxes, from which it exits the kidney.

Histological Features

Proximal convoluted tubule, aka, PCT.

• Bulging cuboidal/low columnar cells
• Basal membrane has infoldings with their own mitochondria.
• Microvilli that make up the brush border that fills the lumen; give the lumen a characteristic “fuzzy” appearance.
  — The basal membrane infoldings and brush border increase the surface area for diffusion; approximately 65% of reabsorption and secretion occurs within the PCT.
• Lateral processes are cytoplasmic extensions that form lateral intercellular space; held together by intercellular junctions.
• Large roundish euchromatic nucleus
  — It has several light-staining areas of euchromatin that reflect genome activity; know that the the dark-staining areas are heterochromatin, which comprises transcriptionally inactive portions of the genome.
• Abundant mitochondria, which produce visible basal striations; mitochondria support the energetic requirements of the sodium-potassium pump, which plays a key role in resorption of water and nutrients from the PCT.
• Abundance of dark-staining organelles, including the vesicles and mitochondria, give PCT cells a darker hue.

Distal convoluted tubule

• Cuboidal and uniform cells
• Lateral processes and intercellular junctions
• Basal membrane infoldings
• Luminal surface does not have a brush border, so the lumen appears wider and clearer than the PCT.
• Euchromatic nuclei that they tend to lie close to the lumen, even bulging into it.
• Numerous mitochondria and vesicles to support their high cellular activity, though not as much as the PCT; hence, these cells appear lighter in histological samples.
• Macula densa is a tightly packed region of the DCT that lies near the renal corpuscle and afferent arteriole of the nephron.

Identification tips:

• First, because we know that both the PCT and the DCT can be found nearby, identify the renal corpuscle.
• Then, identify a proximal convoluted tubule by its fuzzy lumen, which is created by the microvilli brush border. For clarity, we’ve outlined a portion of the brush border in yellow.
• Close by, identify a distal convoluted tubule by its wider, clearer lumen; we’ve used green lines to indicate the macula densa, which appears as a neat row of closely packed cuboidal cells near the mesangium of the renal corpuscle.

Key Points:

• The renal corpuscles lie within the renal cortex;
• They comprise the glomerular, aka, Bowman’s capsule and capillaries
  The capsule is a double-layer sac of epithelium:
  — The outer parietal layer folds upon itself to form the visceral layer.
  — The inner visceral layer envelops the glomerular capillaries.
• As blood passes through the glomerular capillaries, aka, glomerulus, specific components, including water and wastes, are filtered to create ultrafiltrate.
• The filtration barrier, which determines ultrafiltrate composition,
  comprises glomerular capillary endothelia, a basement membrane, and the visceral layer of the glomerular capsule.
• Nephron tubules modify the ultrafiltrate to form urine.

Overview Diagram:

• Tuft of glomerular capillaries; blood enters the capillaries via the afferent arteriole, and exits via efferent arteriole.
• The visceral layer of the glomerular capsule envelops the capillaries, then folds outwards to become the parietal layer.
• The capsular space lies between the parietal and visceral layers; this space fills with ultrafiltrate.
• Vascular pole = where the arterioles pass through the capsule
• Urinary pole = where the nephron tubule begins
• Distal tubule passes by the afferent arteriole.

Details of Capillary and Visceral Layer:

• Fenestrated glomerular capillary; fenestrations are small openings, aka, pores, in the endothelium that confer permeability.
• Thick basement membrane overlies capillaries
• Visceral layer comprises podocytes:
  — Cell bodies
  — Cytoplasmic extensions, called primary processes, give rise to secondary foot processes, aka, pedicles.
• The pedicles interdigitate to form filtration slits; molecules pass through these slits to form the ultrafiltrate in the capsular space.
• Subpodocyte space; healthy podocytes do not adhere to the basement membrane.

Clinical Correlation:

• Podocyte injury causes dramatic changes in shape, and, therefore, their ability to filter substances from the blood.

Cross Section of Renal Corpuscle:

• Center = fenestrated capillary walls
• Basement membrane comprises elements from both the endothelia of the capillaries and the epithelia of the visceral layer of the glomerular capsule.
• Podocytes and processes are external to the basement membrane
• Parietal layer comprises simple squamous epithelia resting on a basement membrane.

• Capsular space between the parietal and visceral layers of the capsule.
• Afferent and efferent arterioles pass through the vascular pole
• Mesangial matrix and cells fill the spaces between the capillaries and arterioles.
  — Mesangium supports the capillaries, secretes vasoactive factors, and contains phagocytes that eliminate immune complexes
• Juxtaglomerular apparatus, aka, JGA
• Located at the vascular pole
• Participates in systemic blood pressure regulation via the renin-angiotensin-aldosterone system (RAAS)
• Comprises:
  — Juxtaglomerular cells, which are specialized cells within the smooth muscle of the afferent arteriole, and the macula densa, which is a specialized area of the distal convoluted tubule that comprises taller, columnar-like cells packed tightly together.
  — Extraglomerular mesangial cells fill the space between the arterioles and the macula densa. These cells participate in tubuloglomerular feedback to regulate renal blood flow.

Filtration barrier:

• Fenestrated capillary endothelium
• Three layers of the basement membrane:
  — Lamina rara interna, which abuts the capillary endothelium
  — Lamina densa, which lies in the middle
  — Lamina rara externa, which is the outermost layer
• Podocytes and their processes
  — Filtration slit, and the diaphragm that covers it.
• Capsular space.

Key functions of each of these layers:

• The capillary endothelium blocks the passage of large molecules, including red blood cells, from entering the capsular space
• The basement membrane blocks intermediate-sized molecules and negatively charged molecules
• The podocytes of the visceral layer block smaller molecules
• Thus, only the smallest, positively charged molecules enter the capsular space to become ultrafiltrate.

Features in a histological sample:

• Identify the renal corpuscle as the collection of cells set off by the capsular space.
• Label the parietal and visceral layers that enclose the capsular space; we can see the parietal epithelial cell nuclei and a podocyte of the visceral layer.
• Indicate the tightly packed cells of the the macula densa, and the nearby afferent arteriole, which is characterized by its thick wall of smooth muscle. Notice the mesangial cells in the interstitial space.
• Within the glomerulus, identify a capillary lumen; we can see the brighter-staining red blood cells in this preparation.
• Overlying the capillaries, identify the glomerular basement membrane.

Urethra:

• Conducts urine from the urinary bladder to the external environment.
• Passes through the perineal membrane, which is a thick layer of connective tissue that supports the pelvic structures.
• Sphincters regulate the passage of urine through the urethra.
• Lies just posterior to pubic bones in anterior pelvis.

Female urethra

Key features:

• Lies anterior to the opening of the vagina.
• External urethral orifice opens to vestibule of the vagina.
• External urethral sphincter lies superior to/deep to perineal membrane;
  Existence of internal urethral sphincter is contested (if it exists, would be at neck of bladder and enclose internal urethral orifice)
• Enclosed by labia minora and labia majora, which are flaps of skin.
• 3-5 cm in length.

Male urethra

Key features:

• Comprises 3 continuous segments:
  — Prostatic, which passes through the prostate gland,
  — Membranous, aka intermediate, and,
  — Spongy, aka, penile, which passes through the corpus spongiosum of the penis.
• Conducts both urine and semen.
• Internal urethral orifice and sphincter at neck of bladder
• External urethral sphincter lies superior to/deep to perineal membrane
• External urethral orifice is located at tip of penis
• 18-20 cm long

Clinical correlations:

• Urinary incontinence (aka, urine leakage) is common, especially in women. The pathogenesis is often an inability to close the urethral orifices, which commonly occurs from weakened pelvic muscles or nerve damage.
• Benign prostatic hyperplasia (BPH) is common amongst older men. The pathogenesis is that the prostate gland enlarges, pinches off the urethra, which impairs urination, and urine retention in the bladder can result.

The kidney filters the blood and produces urine.

Key features:

Fibrous capsule (aka, renal capsule)

• A layer of connective tissue that protects the kidney.

Hilum

• Cleft on concave, medial surface where the renal arteries and veins, nerves, and ureters enter and exit the kidney.
• Continuous with the renal sinus.

Renal sinus

• A space where fat, blood vessels, and structures that drain urine reside.

Renal pyramids

• Contain urine-collecting tubules and ducts, which is what gives them their striated appearance.
• Collectively, the renal pyramids constitute the renal medulla (which is why some authors refer to the renal pyramids as the medullary pyramids).

Renal medulla

• Inner area of the kidney that comprises the renal pyramids.

Renal cortex

• Outer area of the kidney that extends between the pyramids of the medulla as renal columns.

Renal papilla

• Is at the apex of the renal pyramid

Corticomedullary junction

• Is the wide base of the renal pyramid, where it meets the cortex

Renal lobe

• Comprises a single renal pyramid and the renal column and cortex that surround it.

Renal calyces

• Minor and major
• Drain urine from the collecting ducts of the pyramids.

Renal pelvis

• Wide, flattened end of the ureter that receives the urine from the major calyces, and funnels it out of the kidney.

Arterial Supply:

Renal artery

• Enters the kidney at the hilum; recall that the renal artery arises from the descending abdominal aorta.
• Gives rise to segmental arteries.

Segmental arteries

• Branch to form interlobar arteries, which travel between the renal lobes, within the renal columns.

Interlobar arteries

• Give rise to arcuate arteries; notice that these arteries “arc” over the bases of the renal pyramids.

Arcuate arteries

• Give rise to multiple interlobular arteries, which radiate through the cortex (hence, their alternative name, cortical radiate arteries).

Interlobular arteries

• Give rise to afferent arterioles

Afferent arterioles

• Carry blood to glomerulus

Efferent arterioles

• Carry filtered blood away from glomerulus

Peritubular capillary beds

• Where gas exchange occurs
• Vasa recta weaves around nephron loop of juxtamedullary nephron.

Nephron Anatomy:

• Nephrons are the functional units of the kidney; they filter the blood to produce urine.
• Two nephron types:
  — Cortical (aka, superficial), which reside primarily in the renal cortex
  — Juxtamedullary, which travel through the renal pyramids

Features of the Juxtamedullary nephron:

• Renal corpuscle comprises:
  — Outer glomerular capsule (aka, Bowman’s capsule)
  — Inner glomerulus, which is a dense collection of capillaries
• Proximal convoluted tubule
• Nephron loop
• Distal convoluted tubule
• Collecting duct, which drains to the renal papilla

Key points:

• The ureters and urinary bladder are retroperitoneal organs, which means that they lie behind the peritoneum (the peritoneum is discussed in depth, elsewhere).
• The tunics (aka, layers) of their walls are specialized to accommodate changes in urine volume and to actively move urine through the urinary tract.
• The paired ureters conduct urine from the kidneys to the urinary bladder;
• The urinary bladder stores and expels urine.

Ureter Tunics:

• Adventitia, which is its outermost layer
• Muscularis, which comprises an outer circular and inner longitudinal layer
• Mucosa, which comprises the lamina propria and transitional epithelium
• Notice that the ureter does not have a submucosa.
• Transitional epithelium comprises cells that change shape to accommodate changes in urine volume; thus, we’ll see it also in the urinary bladder.

Urinary Bladder Tunics:

• Adventitia, its outermost layer
• Muscularis, which comprises the detrusor muscle, a collection of three layers of smooth muscle; the detrusor muscle contracts to expel urine and relaxes during urine storage
• Submucosa, which comprises connective tissues that support the urinary bladder walls
• The mucosa, which, like the mucosa of the ureter, comprises lamina propria and transitional epithelia

Features of Urinary Bladder:

• Mucosal rugae on the internal surface of the urinary bladder; as in the ureter, these folds facilitate expansion to accommodate urine.
• Ureters empty into the posterior/inferior bladder wall.
• Internal urethral orifice is opening at neck of the bladder; this is where urine exits the urinary bladder.
• Trigone, is a smooth, triangularly shaped portion of the bladder wall; its shape and smooth surface act as a sort of funnel to direct urine from the openings of the ureters to the urethra.

Clinical Correlation:

Detrusor overactivity is characterized by involuntary detrusor muscle contractions, which can cause urinary incontinence.