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Home , Renal column, Tubular fluid

Urinary Histology

N. Swailes, Ph.D. Department of Anatomy and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected]

Required reading

Mescher AL, Junqueira’s Basic Histology Text and Atlas, 12th Edition, Chapter 19: pp332-347 Ross MH and Pawlina W, Histology: A text and Atlas, 6th Edition, Chapter 20: pp698-723

Learning objectives

1) Describe the gross, visible organization of the and relate this to its microanatomy.

2) Describe and identify histologically the path taken by blood and during urine formation in the kidneys.

3) Demonstrate the organization and briefly overview function of the juxtaglomerular apparatus.

4) Identify and discuss the functional significance of urinary epithelium.

5) Trace the flow of urine from renal papilla to external urethral meatus and comment on the histological properties of each region passed.

6) Think about how changes in the histological structure and function of the can bring about the course of many common diseases.

Key terms

cortex medulla pyramid mesangial cells column ducts of Bellini interlobar artery uriniferous tubule arcuate artery papilla intralobular artery major/minor calyx interlobular artery pelvis renin corpuscle urinary epithelium (transitional) fenestrated capillaries Bowman’s capsule medullary ray proximal convoluted tubule juxtaglomerular cells aldosterone collectung tubule/duct erythropoietin

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A1: Introduction & General Organization of the Urinary System

During this lecture you will follow the entire length of the urinary system focusing in particular on the kidney and its tubular ultrastructure. You will discover some of the basic functions that the histological structure of the kidney is responsible for.

The main function of the urinary system is to filter the blood and transport the resulting waste products, dissolved in water, to be temporarily stored and then excreted from the body. It also conserves salts, glucose, proteins and water to regulate blood pressure and influence the acid-base balance in the body.

The regions of the involved in these functions are:

1. Kidney and Nephron - filter the blood to remove waste products/toxins - conserve salts, glucose, proteins and water - help regulate blood pressure, hemodynamics and the acid-base balance of the body.

2. - transport urine created by the kidneys to the . 1

3. Bladder - a temporary storage organ for 2 urine.

4. - conveys urine from the bladder 3 out of the body during 4 micturition.

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A2: The Kidneys: An Overview

The kidneys are glandular organs with both exocrine and endocrine properties. As a result they have two major functions:

1. Homeostasis: maintenance of a stable extracellular environment for normal cell function

The kidneys play an important role in homeostasis. The byproduct of this function is the production of urine. The formation of urine is determined by three main processes that are controlled within specialized units of the kidney called .

i. Filtration - blood plasma is selectively filtered at the glomerulus - the glomerular filtrate contains waste products of metabolism dissolved in water and enters the kidney tubules

ii. Secretion - kidney tubules modify glomerular filtrate by secreting substances into it from surrounding capillaries. This helps maintain: a. potassium balance in the body (by removing excess K+ from blood) + + b. acid-base balance (by removing H and NH4 from blood)

iii. Reabsorption - kidney tubules reabsorb solutes and water. This helps maintain: a. extracellular fluid volume and blood pressure b. water conservation c. sodium balance in the body (by reabsorbing Na+ into the blood)

2. Secretion of hormones: regulate a range of processes around the body.

i. Regulation of blood pressure - renin is produced in the kidneys - participates in regulation of blood pressure through renin-angiotensin- aldosterone system.

ii. Stimulation of erythropoiesis - erythropoietin is produced in the kidneys - stimulates production of erythrocytes in the bone marrow

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A3: Gross Structure of the Kidney

The kidneys are paired, Heinz baked bean-shaped organs located retroperitoneally on the posterior abdominal wall.

The following structures exit/enter each kidney at the hilus:

1. - branch of abdominal aorta - supply kidneys with ~22% of cardiac output 1 2. - returns blood to inferior vena cava

3. - funnel shaped region of 2

4. Ureter - muscular tube that drains urine from 3 renal pelvis to the bladder

Now examine the hemisected kidney and identify 4 the following internal structures:

5. - external CT layer of the kidney 5

6. 6 - outer part of the kidney

7. 7 - inner ‘segmented’ part of the kidney.

8. Renal papilla 8 - region of the renal medulla that projects into a minor calyx.

9. Minor calyx - numerous narrow tributaries that drain 9 urine away from each renal papilla to a major calyx. 10

10. Major calyx - formed when two or more minor calyces unite, they drain into the renal pelvis.

11. Vasculature (see later) 11 - a network of vessels branching from the renal artery and draining to the renal vein.

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A4. Renal Lobes The cortex and medulla of each kidney can be divided into 8-15 renal lobes composed of:

1. Renal cortex - forms the base of the renal lobe

2. - extensions of renal cortex into the 1 renal medulla - note that only half a column flanks a pyramid on each side

3. Renal pyramid - pyramidal shaped region of the 2 medulla deep to the renal cortex

3 4. Renal papilla - the apex of the renal lobe - contains numerous tiny holes known as area cribrosa

The uriniferous tubule - is the functional unit of the kidney 4 - produces and modifies urine - is an epithelial lined tube 6 5 - originates in the renal cortex 4 - terminates at the renal papilla. - has two embryologically distinct components:

i. The nephron 1 - derived from the metanephros 2 1. Bowman’s capsule 2. Proximal convoluted tubule (PCT) 3a 3. a. Thick descending limb (TDL) 3b b. Thin descending limb (tDL) c. Thin ascending limb (tAL) 3c d. Thick ascending (TAL) 3d 4. Distal convoluted tubule (DCT) 5. Connecting tubule

ii. The collecting duct - derived from the ureteric bud

6. Collecting duct

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A5. Renal Blood Supply The vessels within the kidney are often named according to their location within the kidney.

Efferent arteriole

Glomerulu Interlobular Arcuate Peritubular s a. a. capillaries (around convoluted Afferent arteriole Interlobar tubules) a.

Segmental a. (around loop of Henle) Renal a.

Interlobular v.

Arcuate v.

Interlobar v. Renal v.

Clinical Correlation: Erythropoietin (EPO) Interstitial cells associated with the release the hormone EPO into the bloodstream. EPO targets red blood cell precursors in the bone marrow and is essential for their successful development into healthy erythrocytes. Recombinant EPO is a common blood-doping agent used by athletics cheats to increase efficiency of the oxygen delivery system by increasing circulating erythrocyte levels. 6 | Page: Urinary Histology Swailes

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A6. Renal Lobules 1 The kidney can be further differentiated into lobules. A renal lobule is centered about a medullary ray and is flanked on each side by .

1. Medullary ray - a series of collecting ducts that extend from the cortex into the medulla and 2 drain a collection of local nephrons. 2

2. Interlobular artery - branches of the arcuate arteries that supply the renal cortex.

3. Renal lobule - region of a renal lobe located between two interlobular arteries - contains nephrons that drain into the collecting ducts within a medullary ray.

Follow the flow of blood through the kidney to the glomerulus: what happens next?

A7. Renal Corpuscles (glomerulus + Bowman’s capsule) This arrangement creates the barrier for filtration of blood:

1. Vascular pole Efferent Vascular pole Blood reaches the vascular pole of the renal arteriole corpuscle and then travels into the:

i. Afferent arteriole - supplies the glomerulus - is wider than the

ii. Efferent arteriole - after passing through the glomerulus blood leaves via the efferent arteriole - goes on to supply the peritubular and/or vasa recta capillaries that run in close proximity to the kidney tubules.

iii. Mesangial cells Afferent - specialized extra- and intra-glomerular cells Extraglomerular arteriole - phagocytic to keep the glomerulus clean mesangial cells - contractile to control blood flow through the glomerulus

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Podocyte

2. Glomerulus The glomerulus forms the surface across which filtration occurs. It is composed of:

i. Fenestrated endothelial cells - contain pores 70-90nm wide. - form a barrier to blood cells and macromolecules whose diameter exceeds this. Primary

ii. Basal lamina Pedicel process - lamina rara interna (closest to endothelial cells) - lamina densa (middle and thickest layer) - lamina rara externa (closest to )

iii. Visceral layer of the Bowman’s capsule - aka “podocytes” - highly modified epithelial cells - primary processes run along the long axis of Slit the capillary diaphragm

iv. Pedicels - foot-like processes branching from the primary processes of podocytes - interdigitate with neighboring pedicels - spaces between are called filtration slits (20- Pedicel 40nm wide) Fenestrated endothelial v. Slit diaphragm cell - thin membrane that spans adjacent pedicles - contains pores created by transmembrane Basal proteins called nephrins lamina - it is the principal molecular filter of the glomerulus

Parietal layer Urinary pole 3. Bowman’s capsule and Urinary pole The filtrate is now in this most proximal region of the nephron

i. Visceral layer (podocytes) – see previous

ii. Bowman’s space - the space into which the filtrate drains - continuous with the PCT PCT iii. Parietal layer - outer wall of the capsule Bowman’s space - composed of a simple squamous epithelium 8 | Page: Urinary Histology Swailes

A8. Renal Tubules

1. Proximal convoluted tubule (PCT) 1 Efficient at reducing filtrate volume by ~75% by: - actively resorbing Na+ - reabsorbing water

Look for: - simple cuboidal epithelium with microvilli - basal striations (mitochondria for ATP) - large cells (sections may ‘miss’ the nucleus) - long (therefore most prevalent in cortex)

2. Loop of Henle - thick limbs (simple cuboidal epithelium) - thin limbs (simple squamous epithelium) - plays an important role in concentrating and 2 making urine hypertonic in association with the vasa recta

3. Distal convoluted tubule (DCT) - sodium pumps absorb Na+ and secrete of K+ - process is regulated by aldosterone - maintains body’s water-salt balance + + - also secretes H and NH4 into urine to help maintain acid-base balance. 3 Look for: - simple cuboidal epithelium few microvilli - basal striations (mitochondria for ATP) - small cells (sections cut all nuclei) - short (therefore least prevalent in cortex)

4. Collecting duct - ADH makes epithelium permeable to water which is extracted from the urine. 4 - no ADH means epithelium is impermeable to water and it is lost in the urine.

Look for: - simple cuboidal epithelium - cells bulging into a large lumen - large central nucleus - prominent intercellular limits

5. Ducts of Bellini - formed when collecting ducts converge - simple columnar epithelium 5 - prominent intercellular limits

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A9. Juxtaglomerular apparatus

The juxtaglomerular apparatus includes the following structures:

1. Macula densa - a row of Na+ monitoring cells in the DCT - located immediately adjacent to the . - low DCT Na+ levels suggest filtrate is flowing too slowly through the nephron because of low arterial blood pressure. - in response, macula densa cells signal to surrounding JG cells which release renin to increase blood pressure and glomerular flow rates to normal (see below).

2. Mesangial cells - modified smooth muscle cells around the arterioles and glomerular vessels. - phagocytic to keep glomerular basal lamina clean - contractile to modulate filtration rate when blood pressure is high

3. Juxtaglomerular granular cells (JG-cells) - modified smooth muscle cells of the afferent (and occasionally efferent) arterioles - contain granules (enzyme renin) - low Na+ levels or decreased arterial blood pressure detected by macula densa triggers release of renin granules

Renin: cleaves the plasma protein angiotensinogen to form angiotensin I.

Angiotensin I: is converted to angiotensin II in other regions of the body.

Angiotensin II: triggers systemic vasoconstriction to raise blood pressure and; stimulates aldosterone release from the adrenal glands

Aldosterone: promotes Na+ and water uptake from DCT into peritubular capillaries raising blood volume and therefore increasing blood pressure.

Macula densa

DCT

JG-cells Mesangial cells

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A10: Storage and Excretion of Urine

Upon leaving the ducts of Bellini at the area cribrosa of the renal papilla, the urine enters a series of structures specialized for the transportation and storage of urine – they do not modify its composition.

General structure of excretory passageways All of the excretory passageways share the same general structure – except the urethra.

1. Mucosa i. Transitional epithelium - stratified epithelium specialized for life in the urinary passageways. - surface cells are large dome ‘umbrella’ cells. - tight junctions create an osmotic barrier that prevents water movement. - plasma membrane of cells is specialized to allow distension

ii. Lamina propria - loose irregular connective tissue - contains elastin fibers to permit stretch

2. Muscularis externa - thick zone of smooth muscle - contracts to transport urine through the lumen of the passageway

3. /serosa - dense irregular connective tissue coat. - superior surface of the bladder has a serosa (because it has an additional layer of mesothelial (peritoneum) cells

Transitional epi. Mucosa Lamina propria

Adventitia/serosa Muscularis externa

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Minor/Major calyces and Renal Pelvis - urine flows along the minor calyces - multiple minor calyces converge to form major calyces - major calyces unite to drain into the renal pelvis - renal pelvis drains urine into the ureter.

Ureters - deliver urine to the bladder using powerful peristaltic waves of contraction. - mucosa appears folded in histological section. - muscularis is thick to create strong peristaltic action

Urinary bladder - temporarily stores urine until it can be conveniently evacuated. - ureters enter the bladder obliquely through its wall which prevents backflow of urine along the ureter as the bladder fills. - mucosa is folded except for a smooth area known as the trigone (a triangular space between the openings of the ureters and urethra). - muscularis is thick and composed of three layers of muscle that are interlaced to squeeze urine from its lumen.

Urethra The urethra in females is short (4-5cm). In males the urethra is long (15-20cm) and has three named regions:

i. - lined by transitional epithelium - contains the openings of the prostatic ducts and ejaculatory ducts.

ii. - so-called because it passes through the urogenital diaphragm/membrane. - lined by a stratified columnar/patchy pseudostratified columnar epithelium - marks a transition point of the urethral epithelium.

iii. - so-called because it traverses the length of the corpus spongiosum of the penis - it has a stratified squamous non-keratinized epithelium

The lamina propria of all three regions is composed of a loose fibroelastic connective tissue that may contain numerous glands of Littre whose mucus secretions lubricate the epithelium of the urethra.

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