Download BY2202 The Kidney and Urinary Tract Origin, Form and Function 1

BY2202
The Kidney and Urinary Tract
Origin, Form and Function 1
Dr. Neil Docherty
Relevant Learning Outcomes From BY2202 •  Interpret cell-cell communication in the nervous and
endocrine systems
•  Outline the evolution and development of the renal and
digestive systems
•  Describe the fundamental structure and function of
the human cardiovascular, respiratory, renal and
digestive systems
N.B.
•  We will be focusing on development of the human kidney
and its role as a key element of integrative physiology
•  Drawing attention to its role in a couple of homeostatic
mechanisms
-volume regulation
-Red blood cell production (erythropoesis)
Todays Objec=ves •  To summarise the sequen/al development of the mature kidney •  To highlight the role of reciprocal induc=ve events (epithelial-­‐mesenchymal interac/ons) in nephrogenesis •  To detail the organisa/on of the nephron as the func/onal unit of the kidney •  To link func/onal phenomena in the nephron (filtra=on, reabsorp=on, secre=on) to func/onal endpoints (excre=on, volume and pH regula=on) Prologue
What the Urinary System
Contributes to The Body
Through the production of urine and hormones
1)  WASTE EXCRETION
2) EXTRACELLULAR FLUID SALT/WATER BALANCE
3) REGULATION OF pH in EXTRACELLULAR FLUID
4)REGULATION OF RED BLOOD CELL PRODUCTION
(ERYTHROPOESIS)
Perspective Check
The job of the kidney should not be listed
as “making urine”, rather the production of
urine is a mechanism through which the kidney
delivers on major homeostatic functions (1-3 above).
Func=onal Anatomy of The Mature Kidney Functional unit
is The Nephron
•  Cortex •  Medulla –  Pyramids •  Sinus –  Minor calices –  Major calices –  Renal pelvis “coronal”
view of kidney
•  Ureter Kidney Development (Nephrogenesis)
ECTODERM
Week 3 of human
development
MESODERM
ENDODERM
• Muscle
• Cartilage
• Bone
• Dermis
• Vascular system
• Urogenital system
• Adrenal Cortex
*See notes from lectures 3,4 and 5 of BY1101 with Professor Paula Murphy
Key Concepts; Cleavage. Gastrulation, Organogenesis, Induction)
Nephrogenesis Originates in the
Intermediate Mesoderm
17d
20d
19d
21d
Looking in at a cross section of the embryo we see
PARAAXIAL-INTERMEDIATE AND LATERAL PLATE FORMED
Nephrogenesis (Chronology along Longitudinal Axis) •  Three systems develop –  Pronephros (week 4) •  Degenerates •  Leaves no remnant –  Mesonephros (weeks 4-­‐8) •  Degenerates •  Leaves its duct –  Metanephros (week 5) •  Persists •  Becomes the mature kidney Emergence of The Collec=ng System (Branching of The Ureteric Bud) •  Ureteric bud forms the collec/ng system •  Ureter •  Renal pelvis •  Major calices •  Minor calices •  Collec/ng tubules (1 -­‐ 3,000,000) Forma=on of the Filtra=on and Renal Tubular Components Establishment of excretory units (nephron)
•  Sieve from blood (glomerulus)-vascular derived
•  Excretory epithelial tube (tubule)-derived from connective tissue around
branches of ureteric buds
•  Linkage to collecting system (ureteric bud derived component)
Molecular Control
From Last slide Excretory epithelial tube (tubule)-derived from connective tissue
around terrminal buds
•  The ureteric bud enters the metanephros •  It induces the metanephros to form tubules •  The metanephros reciprocally induces the ureteric bud to con/nue to proliferate and form the collec/ng system Reciprocal epithelial-­‐mesenchymal interac2on Driven by growth factors and transcrip2on factors Molecular Control-1
Step 1 •  The metanephros expresses WT1 –  Required for competence to respond to induc/on –  Leads to produc/on of •  GDNF •  HGF Molecular Control-2
Meanwhile •  The ureteric bud forms (tyrosine kinase) receptors –  RET •  for GDNF –  MET •  for HGF Molecular Control-3
Consequently •  A signaling pathway is now established •  GDNF and HGF •  Promote growth and branching of the ureteric bud Molecular Control-4
Reciprocally •  The ureteric bud produces –  FGF2 –  BMP7 •  Metanephric growth •  Maintain WT1 produc/on Molecular Control-5
Furthermore •  The ureteric bud produces •  WNT9B •  WNT6 •  The metanephros responds by producing •  PAX2 •  WNT4 –  PAX2 •  Condensa/on of the mesenchyme –  WNT4 •  Epithelialisa/on of the condensed mesenchyme Outcome •  Collec/ng system develops from ureteric bud •  Nephrons (excretory units) develop from metanephros •  Metanephric cells have largely changed from a mesenchymal to an epithelial configura/on Renal agenesis •  Unilateral (~1 / 750) –  Increased risk of hypertension? •  Bilateral (~1 / 10,000) –  Including agenesis of the ureters –  Muta/ons affec/ng GDNF –  Fatal within hours of birth •  Oligohydramnios and Pocer Sequence •  Lung hypoplasia •  Other severe problems in 85% Summary
Origin, Regions and Maturation
DEVELOPMENT WEEK 5
“sagittal” view of embryo
THE METANEPHRIC AND MATURE KIDNEY
“coronal” view of kidney
• 
• 
• 
• 
Cortex Medulla –  Pyramids Sinus –  Minor calices –  Major calices –  Renal pelvis Ureter 1x106 nephrons
Establishment of excretory units (nephron)
•  Sieve from blood (glomerulus)
•  Excretory epithelial tube (tubule)
The Nephron-Functional Unit of Kidney
(A Closer Look at Microanatomy and Cell
Types)
Review the detail below
after second lecture
Cells of the Vascular Component
(Endothelium, vascular smooth muscle cells
stretch sensory afferents neurones,
sympathetic fibres pericytes)
Cell of the Tubular Component
(Epithelium, Osmosensory Cells)
Cells of Stromal Component
Mesangial cells
Functionality Associated With Nephron
(8 KEYWORDS)
The phenomena of FILTRATION,
REABSORPTION and SECRETION
As tuned by INTRINSIC and EXTRINSIC
control mechanisms
Leads to delivery on the key functions of
•  EXCRETION
•  VOLUME REGULATION
•  pH REGULATION
N.B. Two types of nephrons
Cortical (more excretory)
Juxtamedullary (more involved in volume regulation)
Today’s Learning Outcomes From today’s lecture, you should be able to; 1) Summarise the steps involved in the sequen/al development of the mature kidney 2) Highlight the role of reciprocal induc/ve events (epithelial-­‐mesenchymal interac/ons) in nephrogenesis 3) Detail the organisa/on of the nephron as the func/onal unit of the kidney 4) Explain the significance of the terms filtra/on, reabsorp/on, and secre/on in terms of nephron func/on