Formation of Urine: Formation of Urine – Columbia

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The Urinary outflow tract:
The Urinary outflow tract:

••

monitors and regulates extra-cellular fluids
•• monitors and regulates extra-cellular fluids
excretes harmful substances in urine, including
excretes harmful substances in urine, including
nitrogenous wastes (urea)
nitrogenous wastes (urea)
returns useful substances to bloodstream
returns useful substances to bloodstream
••
maintain balance of water, electrolytes (salts), acids, and
•• maintain balance of water, electrolytes (salts), acids, and
pH in the body fluids
pH in the body fluids

nephrons in the kidney generate urine that is propelled
to the ureters and then to the bladder for storage and excretion

Formation of Urine:
Formation of Urine:

blood filtered to
blood filtered to
the glomerulus
the glomerulus
capillary walls thin
capillary walls thin
blood pressure higher
blood pressure higher

inside capillaries than
inside capillaries than
s capsule
in Bowman’’s capsule
in Bowman

Formation of Urine
Formation of Urine

nitrogen-containing waste products of protein
nitrogen-containing waste products of protein

metabolism, urea and creatinine
metabolism, urea and
through tubules to be excreted in urine
through tubules to be excreted in urine
urine from all collecting ducts empties into
urine from all collecting ducts empties into

, pass on
creatinine, pass on

renal pelvis
renal pelvis

urine moves down ureters to bladder
urine moves down ureters to bladder
empties via urethra
empties via urethra

1

The urogenital system derives predominantly from
intermediate mesoderm

Formation of Urine
Formation of Urine

in healthy nephron, neither protein nor
in healthy

RBCs
nephron, neither protein nor RBCs

filter into capsule
filter into capsule

in proximal tubule, most of nutrients and large
in proximal tubule, most of nutrients and large

amount of water reabsorbed back to
amount of water reabsorbed back to
capillaries
capillaries

salts selectively reabsorbed according to
salts selectively reabsorbed according to

s needs
body’’s needs
body

water reabsorbed with salts
water reabsorbed with salts

During development, 3 successive kidneys form:

pronephros in an early embryo

2

Mesonephros in intermediate embryo

A metanephros is always drained exclusively by one duct, the
ureter.
In birds in reptiles the ureter separates from the nephric duct
and enters the cloaca. In mammals, the ureter separates from
the nephric duct and enters the bladder

As the embryo grows, the ureters lengthen, and the
kidneys rotate and ascend along the dorsal body wall

urogenital sinus

ureter

bladder

Wolffian duct

common
nephric duct

kidney

trigone

urethra

renal development begins when the ureteric bud invades
kidney mesenchyme (the metanephric blastema)

3

the different compartments of the urinary outflow tract are lined with

distinct cell types that perform diverse functions

making a kidney

the ureters

the kidney

the bladder

How are the diverse cell types in the kidney, ureter and bladder formed?

the kidney is radially patterned

4

The kidney forms via interactions between 3 main cell
types

Ureteric bud

nephron
progenitors

EMBRYONIC
KIDNEY

collecting
ducts

nephrons

local proliferation at ureteric bud tips forms an ampulla

insterstitium

Stroma

The ampulla splits to form two new tips

4thG

ub

Wolffian duct

2ndG

3rdG

The collecting duct system grows by dichotomous
branching

5

NEPHRONS FORM EXCLUSIVELY AT URETERIC BUD TIPS IN RESPONSE TO LOCAL
SIGNALS

Nephron
progenitors condense at ub tips, aggregate

and trans-differentiate into epithelial cells
that make up Comma and S-shaped bodies

nephrons differentiate from mesenchymal progenitors

Diverse cell types lining the nephron perform distinct functions

6

Reciprocal signaling between epithelial and
mesenchymal cell types is crucial for organ formation

Reciprocal Signaling is required for branching morphogenesis and
for nephron differentiation during renal development

co-culture experiments demonstrate reciprocal

signaling between ureteric bud epithelial and nephron progenitors

branching morphogenesis

•no ureteric bud, nephron progenitors undergo apoptosis

nephron induction

X

7

•no nephron progenitors, no branching morphogenesis

ub

Ret/Gdnf signaling exemplifies a reciprocal loop

signals from the ureteric bud control nephron
induction

signals from nephron progenitors control branching
morphogenesis

The Ret gene is expressed in ureteric bud tips where it controls
branching morphogenesis

Gdnf secreted by nephron progenitors binds to Ret via
the Ret receptor (Gfra1) inducing branching
morphogenesis

nephron
progenitors

ureteric bud

Ret/Gfra1

Gdnf

8