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Excretory System

Kidneys

Leona Melodia T. Matheus, MD, FPCS, FPSGS


Objectives
1. Discuss the organization of juxtaglomerular
apparatus.

2. Discuss filtration barrier.

3. Discuss the renal circulation.

4. Correlate common clinical conditions


affecting the urinary tract.
Excretory System
 Parts: Kidneys Urinary bladder
Ureters Urethra

 Functions of the kidney:


1. Regulation of water & electrolytes balance
as well as of the acid-base balance
2. Excretion of metabolic wastes along with
excess water and electrolytes in urine
3. Excretion of many bioactive substances
including many drugs
4. Regulation of arterial blood pressure by
secretion of renin
 Other renal functions:
1. Secretion of erythropoeitin (stimulates
erythrocyte production in red marrow
when blood O2 level is low)
2. Conversion of the steroid prohormone
vitamin D (produced in the epidermis),
to its active form, D3 or calcitriol
3. Gluconeogenesis during starvation or
periods of prolonged fasting (change
amino acids to glucose) to supplement
this process in the liver
Kidney: Gross Anatomy
 2 bean-shaped reddish-
brown organs

 Location: posterior
abdomen under cover
of the ribs
(retroperitoneal)

 Hilum of the kidney: on its concave medial border


– a vertical slit where renal artery, renal vein & ureter
enter / exit the kidney
 Renal Sinus: a space extending halfway through
the kidney
– Contains the: Cortex
1. Renal pelvis Medulla
2. Major calyces
Major
3. Minor calyces calyx

 Renal Parenchyma:
Renal
1. Cortex – outer pelvis

– Coarsely granular Minor


– Contain nephrons calyx

2. Medulla – inner
– Contain pyramids
Renal lobule
 Renal columns – cortical
extensions that separate
the renal pyramids
– A pyramid + cortical tissue
at its base and along its sides
= Renal lobe

 Medullary rays – medullary


striations extending into the
cortex
– Medullary ray + attached Renal lobe
cortical tissue = Renal lobule

 Renal papilla – tip of each pyramid projects into


a minor calyx
Kidney: Microscopic Anatomy
 Nephron: functional unit

 Parts of a Nephron:
1. Renal corpuscle
a. Bowman’s capsule
Connecting

b. Glomerulus tubule

2. Renal tubules
a. Prox. conv. tubule
b. Loop of Henle
c. Distal conv. tubule
d. Connecting tubule
 Cortical nephrons: located almost completely in
the cortex
Juxtamedullary nephrons: close to the medulla;
have long loops of Henle
Renal Circulation

Blood supply to the kidneys. A coronal view (L) shows the major blood vessels. An expanded
diagram (R) includes the microvascular components extending into the cortex and medulla from the
interlobular vessels. Pink boxes indicate vessels with arterial blood and light blue indicate venous
return. Intervening lavender boxes and vessels are intermediate sites where most reabsorbed material
reenters the blood.
 From interlobular arteries arise afferent arterioles, which
divide to form capillary loops called glomeruli, located
within a renal corpuscle where blood is filtered

 Blood leaves the glomerulus via efferent arterioles


– Efferent arterioles from cortical
glomeruli branch diffusely as
peritubular capillaries which are
associated with convoluted tubules

– Efferent arterioles from juxta-


medullary glomeruli branch as
long microvascular loops called
vasa recta that penetrate deep
into the medulla associated with
the loop of Henle

 Blood leaves the kidney in veins


that correspond to the arteries
Renal Function:
Filtration, Secretion, & Reabsorption
 Filtration: water and solutes in the blood leave
the vascular space and enter the lumen of the
nephron
 Tubular secretion: substances move from
epithelial cells of the tubules into the lumens,
usually after uptake from surrounding
interstitium and capillaries
 Tubular reabsorption: substances move from
the tubular lumen across the epithelium into the
interstitium and surrounding capillaries
Nephron: Renal Corpuscle
 About 200 μm in diam.; contains:
1. Glomerulus – loose knot of fenestrated capillaries
2. Bowman's/Glomerular capsule – double-walled
a. Visceral layer – closely envelops the capillaries
b. Parietal layer – outer surface of the capsule
c. Urinary/Capsular space – between the 2 layers;
receives the fluid filtered through the capillary wall
 Each renal corpuscle has 2 poles:
1. Vascular pole – where
afferent arteriole enters
and efferent arteriole
leaves
- After entering the
renal corpuscle,
afferent arteriole
divides into 2-5
capillaries of the
glomerulus

2. Tubular/Urinary pole –
where PCT begins
 Parietal layer of glomerular
capsule: simple squamous
– At the tubular pole, epith.
changes to simple cuboidal,
characteristic of PCT

 Visceral layer: made of


stellate epithelial cells
called Podocytes
– Cell body of podocytes give
rise to 1o processes, and in
turn to 2o foot processes or
Pedicels
– Pedicels interdigitate forming
elongated spaces, the filtration slit pores which are bridged
by a semipermeable diaphragm called slit diaphragm
– Glomerular filtration barrier
consists of 3 components:
1. Fenestrated capillary
endothelium (block blood
cells & platelets)

2. Glomerular basement
membrane (combined
basal laminae of capillary
& podocyte (restricts
large proteins & some
organic anions)

3. Filtration slit diaphragms


between pedicels (restricts
small proteins & organic
anions)
 Mesangial cells: another cell of the renal corpuscle
found in spaces between capillaries that lack
podocytes
– Not usually seen in routine sections
– Functions:
a. Physical support of capillaries within the glomerulus
b. Adjusted contractions in response to BP changes
c. Phagocytosis of protein aggregates adhering to the
glomerular filter (e.g. Ag-Ab complexes)
c. Secretes factors for
immune defense &
& repair in the
glomerulus
(e.g. cytokines &
prostaglandins)
Nephron: Proximal Convoluted Tubule
 Longer than DCT; mainly cortical

 Lined by simple cuboidal cells


with long microvilli (brush
borders) in the lumen and
abundant mitochondria
– Cells are large with very acidophilic
cytoplasm and central nuclei
– Brush border (for reabsorption) give
the lumen a fuzz-filled appearance
– PCT cells are specialized for both
reabsorption and secretion
 PCT cells reabsorb more than 50% of the H2O
& electrolytes, all glucose and other organic
nutrients from the filtrate
– These molecules are transferred
to the peritubular capillaries

 Organic anions and cations (e.g.


creatinine, & antibiotics) not
filtered in the renal corpuscle
may be released in the peri-
tubular capillaries, are taken up
by the cells of PCT and undergo
secretion into the filtrate
 PCT cells also perform
hydroxylation of Vit. D
to an active form D3 or
Calcitriol and release to
the capillaries
– Vitamin D is produced
by skin keratinocytes;
D3 or Calcitriol is involved
in regulating calcium balance

 Fibroblastic interstitial cells in cortical areas near


the PCT produce erythropoeitin, the growth
factor secreted in response to a prolonged decrease
in local O2 concentration
Nephron: Loop of Henle
 PCT extends down as a short
straight tubule into the medulla
(thick descending limb) and
continues as the loop of Henle
 Loop of Henle is a U-shaped
structure with thin descending
& ascending limbs made of
simple squamous epith.
 Thin ascending limb becomes
the thick ascending limb (TAL)
lined by simple cuboidal epith.,
Cross section of renal medulla
extending back into the cortex A: Ascending thick loops of Henle
T: Thin loops of Henle
CD: Collecting ducts
 Nephron loop and surrounding tissue are involved
in further adjusting the salt content of the filtrate
by the counter-current multiplier mechanism
– Parts of the loop of Henle with a cuboidal epith. actively
transport Na+ and Cl– out of the tubule against a
concentration gradient
into the interstitium,
making that compartment
hyperosmotic

– Thin limbs lined by


squamous epith. have
little capacity for active
transport
– Thin descending limb allows
free diffusion of H2O but is
fairly impermeable to NaCl

– Thin ascending limb is


permeable to NaCl but not
to H2O

– Vasa recta take up H2O from


the medullary interstitium
and return it to the general
circulation

– As urine flows into the thick


ascending limb, active
transport of NaCl occurs
again; it is also impermeable
to H2O
Juxtaglomerular Apparatus
 In the cortex, TAL (also known as distal straight
tubule) comes in contact with the arterioles at the
vascular pole of the renal
corpuscle & thickens focally
as the macula densa
– Its cells become columnar
and closely packed
– This is part of a sensory
structure, the Juxtaglomerular
apparatus that uses feedback
mechanisms to regulate
glomerular blood flow
(keeps glomerular filtration
rate relatively constant)
 Juxtaglomerular granular
(JG) cells: smooth muscle cells
in the adjacent afferent arteriole
becomes modified, with a more
rounded nuclei that developed
a secretory phenotype

– Secrete Renin: a protease that


cleaves angiotensinogen into
angiotensin I, which in turn is
converted into angiotensin II
in the lungs, a potent
vasoconstrictor = raises BP
and stimulates adrenals to
secrete aldosterone
 Lacis / Polkissen cells:
extraglomerular mesangial
cells located at the angle
between the afferent and
efferent arterioles at the
vascular pole
– Have many of the same
supportive, contractile, and
defensive functions as the
cells inside the glomerulus
Nephron: Distal Convoluted Tubule
 Lined by simple cuboidal
epithelium without brush
border and more empty
lumens

 Cells are smaller and


flatter than PCT cells with
more nuclei seen on
sections

 DCT cells are also less


acidophilic due to fewer
mitochondria
 Rate of Na+ and H2O
absorption is regulated
by aldosterone
– Important for the body’s
water-salt balance

 DCT also secretes K+


and H+ into the urine
– Important for the acid-
base balance in the
blood
Nephron: Connecting Tubules
and Collecting Ducts
 The last part of each nephron, the
connecting tubule pass the
filtrate into a collecting system
that transports it to a minor calyx
where more H2O is reabsorbed if
the body needs it
 A connecting tubule from each
nephron join together in the
medullary rays to form collecting
ducts lined by simple cuboidal
epith. (Ave. diam. = 40 μm)
 In the outer medulla,
collecting ducts merge
further as larger straight
collecting ducts (of Bellini),
up to the pyramid tips with
increasingly columnar cells
(Overall diam. = 200 μm)

 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
of pale-staining principal cells
– Principal cells are rich in
Aquaporins, membrane proteins
that function as specific channels
for water molecules
– Medullary CDs are the final site of
H2O reabsorption from the filtrate

 Scattered among the principal cells are darker


intercalated cells (IC cells)
– A few of these cells also occur in DCTs
– Help maintain acid-base balance by secreting either H+
or HCO3–
Histologic Features and Major Functions of Regions within Renal tubules
Region of Tubule Histological Features Location Major Functions

PCT Simple cuboidal epith; cells Cortex Reabsorption of all


well-stained, w/ numerous organic nutrients, all
mitochondria, prominent proteins, most H2O &
basal folds & lat. inter- electrolytes
digitations; long microvilli,
lumens often occluded
Loop of Henle
Thin limbs Simple squamous epith; few Medulla Passive reabsorption of
mitochondria Na+ & Cl–
TAL Simple cuboidal epith; no Medulla & Active reabsorption of
microvilli medullary various electrolytes
rays
DCT Simple cuboidal epith; cells Cortex Reabsorption of
smaller than in PCT, short electrolytes
microvilli & basolateral
folds, more empty lumens
Collecting
System Most abundant, cuboidal to Medullary rays Regulated absortion of
Principal cells columnar; pale-staining, & medulla H2O & electrolytes;
distinct cell membranes regulated secretion of K+
Few & scattered; slightly Medullary rays Reabsorption of K+ (low
Intercalated cells darker staining K+ diet); help maintain
Clinical Correlation
 Inflammation within the glomeruli, or glomerulo-
nephritis, can range from acute or chronic

 It usually stems from humoral immune reactions


which can involve:
– Deposition of circulating Ag-Ab complexes within
glomeruli
– Circulating Abs binding to either glomerular Ags or
extraneous Ags deposited in the glomeruli

 The accumulating immune complexes can then


elicit a local inflammatory response
 In diseases such as Diabetes mellitus and
Glomerulonephritis, glomerular filter is altered
and becomes more permeable to proteins.
– Proteins are subsequently released in the urine
(Proteinuria)
– Proteinuria indicates potential kidney disorders

 Diabetic glomerulosclerosis, the thickening and


loss of function in the GBM, is the leading cause
of (irreversible) end-stage kidney disease in the
United States
– Treatment requires either a kidney transplant or
regular artificial hemodialysis
Kidneys and Hemorrhage

 Significant bleeding decreases blood volume


promotes decreased BP & increased renin secretion

 Angiotensin II & aldosterone act together to


increase BP and help restore blood volume

 Other factors that lower BP by decreasing blood


volume (e.g. sodium depletion and dehydration)
also activate the renin–angiotensin II– aldosterone
mechanism that helps maintain normal BP
Have a nice day!!!
Excretory Passages
 convey urine from kidney
to environment

 Histologic features:
1. 3 layers
a) Mucosa (inner coat)
b) Tunica muscularis
(muscular coat)
c) Tunica adventitia
(fibrous coat)
2. L.E.: Transitional epithelium

3. No submucosa

4. Arrangement of Tunica muscularis:


(opposite that of the GIT)
a) Inner longitudinal muscle layer
b) Outer circular muscle layer

5. Tunica adventitia: loose collagenous tiss.


Transitional Epithelium:
Urothelium

 Found only in conducting


passages of urinary system

 Cells are organized as 3 layers:


a. Single layer of basal cells:
rest on a very thin
basement membrane

b. Intermediate region:
one to several layers of
columnar cells
c. Superficial layer of very
large, bulbous cells:
Umbrella cells

- occ. bi- or
multinucleated

- protect underlying cells


against toxic effects of
hypertonic urine

- well developed in UB
where contact with urine
is greatest
Renal Pelvis and Calyces
 Renal pelvis: funnel-
shaped end of the ureter;
branches into major and
minor calyces

 Same histological
characteristics
– Mucosa: thin, lined by 2-3
cell layers of transitional
epithelium
– Lamina propria: LCT w/
small BV and few
lymphocytes; no glands
Ureter
 Stellate-shaped lumen

 Mucosa:
– LE: transitional epith.
– LP: Superf. part = DCT
Deep part = LCT
• (+) diffuse lymphatic tiss.; No glands

 Tunica muscularis: ILOC


except near UB = 3 layers (IL
MC OL)

 Tunica adventitia: LCT


Urinary Bladder
 Capacity (adult): 400-600 ml; urge to empty
occur at 150-200ml.

 Mucosa:
- LE: Transitional epith.
*Empty = irregular folds
*Distended = thin epith.,
cells flattened & stretched
- LP: superf. = DCT
deep = LCT
*(+) occ. mucous glands at
internal urethral orifice
 T. muscularis: 3 poorly
delineated layers called
Detrusor muscle
– distinct at UB neck near
the urethra

 T. adventitia: outer
layer except for upper
part (covered by serous
peritoneum)
Male Urethra
 Long: 18 - 20 cms.
 3 Divisions:
– Prostatic urethra = 3-4 cm long; traverses
prostate gland from base to apex
– Membranous urethra = 1-1.5 cm long (shortest
segment); from lower pole of prostate to bulb
of the penis
– Penile urethra = 15 cm long (longest segment);
from bulb of the penis to tip of the glans penis
• Enlarged terminal portion: Fossa navicularis
 Mucosa:
– LE: Prostatic = Transitional epithelium
Membranous = Pseudostrat. Columnar epithelium
Penile = Strat./Pseudostrat. Columnar epith.
Fossa navicularis = Strat. Sq. Nonkeratinized epith.
– LP: LCT w/ abundant elastic fibers and smooth muscles
(+) Littre’s glands: mucus-secreting; made of
pale-staining columnar cells
(+) Lacunae of Morgagni: recesses or deep irregular
outpocketings of the mucosa into the lamina propria

 Tunica muscularis: IL / OC muscle layers

 Tunica adventitia: LCT


Urethra. Human.
Paraffin section. Note
the spongy urethra (U)
lined by pseudostratified
columnar epithelium (Ep) U
surrounded by a loose
connective tissue sheath
(CT) housing a rich ET
vascular supply (BV).
Entire urethra is enveloped Ep
by erectile tissue (ET) of
the corpus spongiosum. GL
Additionally, mucous
glands of Littre (GL)
deliver their secretory
product into the lumen of
the urethra, lubricating its
epithelial lining.
Female Urethra
 In females, urethra is exclusively a urinary organ
– 4-5 cm long

 L.E.: 1st part: Transitional epithelium


Middle part: Strat. Columnar epithelium
Terminal part: SSNKE
L.P.: LCT w/ elastic fibers & lymphocytes
(+) Lacunae of Morgagni; (+) Littre’s glands
 Tunica Muscularis: IL OC smooth muscle layers
– At middle part, reinforced by skeletal muscle fibers
forming the urethral sphincter (voluntary)

 Tunica Adventitia: LCT w/ BV & LV


Have a nice day!!!
Kidney: Secretions
 Renin: a protease that participates in the
regulation of blood pressure

 Erythropoeitin: a glycoprotein that stimulates


the production of erythrocytes

 Vitamin D: produced by skin keratinocytes;


hydroxylated in the kidneys to an active form,
D3 or Calcitriol, involved in regulating
calcium balance
Renal artery
Renal Segmental a. (Hilum)

Circulation Lobar a. (Sinus)

Interlobar art. Interlobar a. (bet. pyramids)

Arcuate a. (base of pyramid)


Segmental art.
Interlobular a.
Lobar art.
Afferent arteriole

Renal art. Glomerulus (Renal corpuscle)

Efferent arteriole

Peritubular capillaries Vasa recta


(PCT/DCT) (Medulla)

Interlobular v.

Arcuate v.

Interlobular Arcuate
art. art. Renal vein

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