Microanatomy of the Urinary System - Notes

Microanatomy of the Urinary System

Overview of Urinary System

• Excrete nitrogenous waste

• Conserve body fluids and electrolytes

• Reabsorb solutes and water

• Convey urine to bladder

• Store urine

• Expel urine

• Key Structures:

  • Urethra

  • Urinary bladder

  • Ureters

  • Kidney

    • Capsule

    • Cortex

    • Medulla

    • Pelvis

    • Interstitium

Functions

• Water and electrolyte homeostasis

  1. Filtration of cellular wastes from blood

  2. Selective reabsorption of water and solutes

  3. Regulation of fluid balance

  4. Maintain electrolyte homeostasis / acid base balance

• Excretion of metabolic waste products, bioactive substances (including drugs), and excess water

• Production of hormones: renin and erythropoietin

• Regulation of blood pressure via the Juxtaglomerular apparatus

• Activation of vitamin D

Clinical Signs of Renal and Non-Renal Diseases

• Relates to the microanatomy and function of the kidneys

• Abnormal urine

  • Content: glucose, blood, haemoglobin, myoglobin, bacteria, cells

  • Colour: haemoglobin, myoglobin, bilirubin

  • Volume: polyuria, oliguria and anuria

• Primary renal diseases according to site of injury

  • Glomeruli

  • Tubules

  • Blood vessels

  • Ascending infections

  • Renal neoplasia

  • Renal infarction

  • Renal failure

Structure of the Kidney

• Capsule

• Renal lobe/pyramid

• Outer Cortex

• Inner Medulla

• Papillae/Crest

• Calices

• Dilations of renal pelvis

• Pelvis

• Dilation of proximal ureter

• Renal hilus

Kidney Lobes

• Kidneys are composed of lobes that may be single, multiple or fused.

  • Unilobar kidney typical of carnivores.

  • Multilobar kidney typical of large ruminants.

    • Each lobe is distinctly outlined by deep grooves.

    • Lacks a renal pelvis.

  • Multilobar kidney of the pig; note the smooth surface.

• Bovine kidney: lobes are clearly demarcated.

• Porcine kidney: cortical portions of the lobes are fused.

• Carnivore, equine, and small ruminant kidneys: lobes fuse extensively to give the appearance of a single lobe 'unilobar'.

• Renal lobes and pyramids although not exact anatomical equivalents are used interchangeably

Important Tissues of the Kidney

• Capsule

  • Collagen fibres

  • Smooth muscle

  • Blood vessels

• Cortex

  • Renal corpuscles

  • Convoluted tubules

• Medulla

  • Loop of Henle

  • Collecting duct

• Pelvis

  • Urothelium

  • Submucosa

  • Smooth muscle

  • Adventitia

• NEPHRON

Nephron

• The functional unit of the kidney is the nephron

• Nephrons are the site of osmoregulation via:

  • Filtration of water and small molecules from blood plasma to form a filtrate

  • Selective reabsorption of most of the water and other molecules from the filtrate

  • The Corpuscle itself is not strictly part of the nephron

Important Structures in the Regions of the Kidney

• CORTEX

  • Renal corpuscles

  • Proximal tubules

  • Distal convoluted tubules

  • Collecting tubules

  • Peritubular capillary plexuses

• MEDULLA

  • Loops of Henle

  • Collecting ducts

  • Vasa recta

Renal Corpuscle

• Composed of the glomerulus and Bowman’s capsule

  • Glomerulus = loops (tuft) of capillaries with FENESTRATED ENDOTHELIUM within Bowman's capsule

  • Bowman’s capsule

    • Visceral epithelium=podocyte

    • Glomerular Basement Membrane

    • Urinary space

    • Parietal epithelium=squamous cells

  • Vascular pole

  • Urinary (tubular) pole

  • Mesangial cells lie between fenestrated capillaries

Renal Corpuscle

• Capillary loops (C) are enveloped by visceral epithelium consisting of podocytes (P).

• The parietal epithelium of Bowman’s capsule (arrows) is squamous epithelium and locates across the urinary space (US).

• Protein conservation = main function

Ultrafiltration at the Glomerulus

• Vascular pole

  • Blood enters (arrives at) the glomerular capillaries via the afferent arteriole (main)

  • Blood exits at the efferent arteriole

• Ultrafiltration at the glomerulus

  • Blood pushed through FILTRATION BARRIER

    • fenestrated endothelium

    • glomerular basement membrane

    • podocyte foot processes

  • ULTRAFILTRATE enters URINARY SPACE

• Urinary pole

  • Ultrafiltrate enters PROXIMAL CONVOLUTED TUBULE

Podocytes and Glomerular Capillary Loops

• Scanning electron micrograph of podocyte (rat).

• Cell body (C) of one podocyte is in the center of the field.

• Numerous pedicels of varying size extend from the cell body, wrap around the glomerular capillaries, and interdigitate with other podocytes

• Podocytes do not lie between the capillaries of the glomerulus in the sense of being positioned directly between them.

• Rather, they are part of the glomerulus structure and surround the capillaries within the glomerulus.

Filtration Barrier

• Formed from 3 components

  1. Endothelium of glomerular capillary loops (CL) with fenestrations.

  2. Glomerular Basement Membrane (GBM)= fused basal laminae of capillaries and podocytes

  3. Podocytes with pedicels (foot processes)

• Outcome = Albumin and larger molecules are retained; all smaller molecules cross freely with ultrafiltrate

• Which of the 3 structures retains albumin?

  • lamina densa of the basement membrane = exclusion barrier for molecules the size of $(IgG)$ and albumin.

Filtration Barrier (TEM of GBM)

• 3 layers of the GBM

  1. lamina rara interna $[LRI]$,

  2. lamina densa $[LD]$, and

  3. lamina rara externa $[LRE]$

• Filtration slits $(FS)$

• FILTRATION SLITS ARE $25-60nm$

Barrier System

• Barrier system that strictly controls the transfer of molecules across the cell

• allows controlled transfer of small molecules and limited amounts of protein across the fenestrae (filtration mechanism)

• gaps allow “free” transfer of plasma proteins, red and white blood cells, water, and most molecules across endothelial cells

Formation of Urine

1. Primary/glomerular filtrate is produced by ultrafiltration of blood in renal corpuscle.

2. The composition of ultrafiltrate is similar to blood plasma; does not contain most proteins.

3. Reabsorption of most of substances: 98% of filtrate is reabsorbed

   • most of water and $Na^+$, all glucose and all amino acids from ultrafiltrate are reabsorbed.

4. Tubular secretion: $K^+$, $H^+$, $NH_4^+$, bile salts, drug metabolites.

5. Waste molecules + some water remain in the tubular system and eventually will empty into the ureter; urine is stored in the bladder pending voiding/micturition

Mesangial Cells

• Phagocytic

• Contractile

• Support

• Mesangial cells and matrix = mesangium

Renal Tubules

• Teleost don't have a glomerulus

• Renal tubule (Rt) without a glomerulus is surrounded by the well-developed renal portal system (Rps) and forms primitive urine by tubular secretion.

• i. Proximal tubule

• ii. Thin descending and thick ascending limb of nephron (Henle’s) loop

• iii. Distal convoluted tubule

Proximal Convoluted Tubule

• Begin at urinary pole of renal corpuscle

• Only in cortex

• Single layer of cuboidal epithelial cells with microvilli ('brush border')

• Basement membrane

• Highly metabolically active cells with many mitochondria

  • $Na^+/K^+$ pumps

  • Aquaporins

  • Peroxisomes

  • Endosomes

  • Lysosomes

• Resorb glucose, $Na^+/H_2O$, amino acids, peptides and low molecular weight proteins.

• Lateral borders have inter-digitations of lateral cells processes, thus cell limits are indistinct.

• The basal surface has a folded membrane = basal striations.

Proximal Tubules

• Proximal convoluted tubules (PCT) are present in cortex only.

• PCT cells are highly active and absorptive – 85% of $Na^+$ and water from the glomerular filtrate are absorbed in the PCT, as well as 100% of glucose and amino acids.

• Selectively resorb anions, cations, urea

• Activate vitamin D

• Target for nephrotoxins (FYI ex.: gentamycin; ethylene glycol)

Proximal & Distal Convoluted Tubules

• Microvilli – present in PCT only

• Basal striations – folds of plasma membrane with ATP driven $Na^+$ pump both in PCT and in DCT

• Mitochondria provide ATP for $Na^+$ pump

Loop of Henle (Nephron Loop)

• Continues from proximal convoluted tubule

• U-shaped with segments/portions/limbs

  • Thick descending = cuboidal epithelium

  • Thin segment = squamous epithelium

  • Thick ascending = cuboidal epithelium

• In medulla only

Loop of Henle Segments

• $T$ = Thin segment

• $A$ = Ascending thick segment

• $CT$= collecting tubules

• $CD$ = collecting ducts

• $V$ = vasa recta= capillary loop that parallels the course of Nephron loops, facilitating ion and water exchange

Distal Convoluted Tubule

• Continues from thick ascending segment of loop of Henle

• Single layer of cuboidal epithelial cells with basal striations

• No microvilli (brush border)

• Only in cortex

• Site of action of ALDOSTERONE

• Contain specialized chemoreceptor cells of MACULA DENSA

Collecting Ducts

• Connect distal convoluted tubule to renal papillae/crest

• Lumen contains primitive urine

• Cuboidal to low columnar epithelium

• Site of action of ANTIDIURETIC HORMONE (ADH) via aquaporin receptors

• Not part of nephron

• ADH (vasopressin) is secreted by neurons in the hypothalamus - reabsorbs solute-free water and returns it to the circulation

Collecting Ducts - Cell Types

• Collecting ducts are lined by simple low columnar to cuboidal epithelium composed of principal and intercalated cells

• Principal cells reabsorb $Na$ and $H_2O$

• Intercalated cells participate in acid-base balance

Renal Papilla (Canine) - Papillary Ducts

• Terminal portion of collecting ducts are papillary ducts which empty at the area cribrosa (AC) of the renal crest or renal papilla (species specific).

• Vasa recta, (thin arrows) take away water passing through collecting and papillary ducts.

• The papilla, or renal crest, is the terminal portion of the inner medulla, which extends into the renal pelvis or calices.

Vasculature

• High blood supply (25% cardiac output)

• Terminal (end) artery system

  • Renal artery

  • Interlobar artery

  • Arcuate artery

  • Interlobular artery

  • Intralobular (arcuate) artery

  • Afferent arteriole

  • Glomerulus (capillaries)

  • Efferent arteriole

  • Peritubular capillaries (surround tubules)

  • Vasa recta (surrounds loop of Henle)

  • Intralobular vein

  • Interlobular vein

  • Arcuate vein

Interstitium

• Sparse (especially in the cortex)

• More interstitium is present in the (inner) medulla

• Interstitial cells: fibroblasts, bone marrow–derived cells, and a unique lipid-laden interstitial cell (stellate-shaped) that is especially prominent in the inner medulla - produce prostaglandin E2.

• Lymphatics are found in the interstitium surrounding intrarenal arteries.

• The kidney has efferent innervation to the smooth muscle of arteries, afferent and efferent arterioles, and descending vasa recta.

Juxtaglomerular Apparatus

• The DCT is intimately associated with the renal vasculature: juxtaglomerular apparatus

Functions of the Kidney

• Water and electrolyte homeostasis

  1. Filtration of cellular wastes from blood

  2. Selective reabsorption of water and solutes

  3. Regulation of fluid balance

  4. Maintain electrolyte’s homeostasis/ acid base balance

• Excretion of toxic metabolite waste products, and excess water

• Production of hormones: renin and erythropoietin (stimulates the production of red blood cells

• Regulation of blood pressure= Juxtaglomerular apparatus

• Activation of endogenous vitamin D (calcitriol, active form)

• *Skin – liver – kidney

• renal erythropoietin-producing (REP) cells are fibroblast-like cells (kidney stromal cells) that produce erythropoietin (EPO)

Juxtaglomerular Apparatus Components

• TWO components:

  • Macula densa cells (part of DCT wall) are chemoreceptors that sense $Na^+$ concentrations in filtrate.

  • Modified smooth muscle cells = Juxtaglomerular cells of mainly afferent and to a lesser degree efferent arteriole.

    • These cells detect variations in blood pressure (baroreceptors) and secrete renin into vessel lumen.

J.G. Apparatus

• Macula densa (orange) of DCT (yellow): $Na^+$ chemoreceptor

• J.G. cells of afferent/efferent arteriole: baroreceptor

• J.G. cells secrete hormone RENIN in response to low $Na^+$ in filtrate and low blood pressure

Juxtaglomerular Apparatus and Blood Pressure

• Decreased blood pressure at afferent arteriole

  • Juxtaglomerular cells release RENIN

• Decreased $Na^+$ in distal convoluted tube

  • Stimulates MACULA DENSA

  • Juxtaglomerular cells release RENIN

• $ANGIOTENSINOGEN → ANG I$ Liver

• $ANGIOTENSIN I →ANG II$ Lungs and kidneys (Angiotensin Converting Enzyme)

• $ANG II→ALDOSTERONE$ Zona Glomerulosa of adrenal gland

• $Na^+/H_2O$ RETENTION AT DISTAL CONVOLUTED TUBULES

• Increased blood pressure

• Increased sympathetic tone

  • Juxtaglomerular cells release RENIN

Layers of Tubular Organs

• 4 layers (tunics or tela)

  • T. MUCOSA, 3 layers

    • Lamina mucosa/epithelium

    • Lamina propria

    • Lamina muscularis

  • T. SUBMUCOSA

  • T. MUSCULARIS

  • T. SEROSA /ADVENTITIA

• True submucosa because lamina muscularis (muscularis mucosae) separates submucosa from mucosae

Ureters

• Convey urine from renal pelvis to bladder

• Tunica mucosa = Transitional epithelium (syn. urothelium) composed of epithelial cells which flatten when stretched (U)

• Tunica submucosa – lamina propria (LP) (no lamina muscularis)

• Tunica muscularis (M)

  • 3 layers of smooth muscle

    • Outer and inner longitudinal

    • Middle circular layer

  • Autonomic innervation--> peristalsis

• Tunica adventitia

Urinary Bladder

• Stores urine

• Tunica mucosa = UROTHELIUM (Transitional epithelium)

  • Lamina propria present

  • Lamina muscularis (thin incomplete bands of smooth muscle, except CAT)

• Tunica submucosa

• Tunica muscularis

  • 3 layers

    • Outer and inner longitudinal

    • Middle circular layer

  • Smooth muscle (detrusor muscle)

  • Skeletal muscle sphincter near urethra

• Tunica serosa/adventitia

• Bulging cells of urothelium become flattened when the bladder is distended with urine

• Glands (g) in the horse

• The basic pattern is an outer longitudinal and inner circular layer of smooth muscle, except on the dorsal surface where the circular layer is external. This arrangement permits, according to the principles of mechanics, preferential bulging of the dorsal surface.

Urethra

• Similar to ureters and urinary bladder

• Transitional cells proximally

• Stratified squamous epithelium distally

• Accessory sex glands

  • Mucous glands

  • Diffuse prostate in ruminants, boar and cats

• Male

  • Vascular stratum (corpus spongiosum)

  • Tunica muscularis / Urethral sphincter

    • Smooth muscle proximally (close to bladder)

    • Skeletal muscle distally

• Female

  • Shorter

  • Lined initially with transitional epithelium, then stratified squamous (near the external urethral orifice )

Renal Development

• The kidney develops from intermediate mesoderm

• Pronephros – regresses in mammals

• Mesonephros

  1. Forms nephrons that secrete fluid into amnion early in development; regresses later

  2. Mesonephric duct (Wolffian duct) – retained in males forming epididymis, vas deferens, seminal vesicles

• Metanephros persists to form adult kidney

  1. Ureteric bud - outgrowth of mesonephric duct

  2. Collecting tubules form, bifurcate (leading to lobular architecture), and nephrons begin to develop

  3. Metanephros duct becomes ureter

• Urinary bladder and urethra are derived from endoderm