RENAL HORMONES

RENAL HORMONES

1. DR NILESH KATE
MBBS,MD
PROFESSOR
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
RENAL
HORMONES.

2. OBJECTIVES.
INTRODUCTION
COMPONENTS OF RAS
PATHOPHYSIOLOGY OF RAS
COMPONENTS OF NATRIURETIC PEPTIDE SYSTEM
PATHOPHYSIOLOGY OF NATRIURETIC PEPTIDE
SYSTEM
KALLIKREIN-KININ SYSTEM
ADRENOMEDULLIN AND ENDOTHELINS
ERYTHROPOIETIN

3. INTRODUCTION
The kidney -- Essential role in the
maintenance of life in higher organisms,
Not only through regulating the blood
pressure and body fluid homeostasis
and clearing the wastes,
But also by acting as a major
Endocrine organ.
Friday, May 10, 2019

4. ENDOCRINE FUNCTIONS
Renin
kallikreins
 1,25- (OH)2 vitamin D3,
Erythropoietin
Friday, May 10, 2019

5. TARGET ORGAN
The kidney serves as an
important endocrine target
organ for a number of
hormones, thereby
controlling
the extracellular fluid volume,
electrolyte balance,
Acid-base balance,
and blood pressure.
Angiotensin
and
Aldosterone
Friday, May 10, 2019

6. “Local hormones,”
The kidney
is a major organ for
the production and
action of various
“local hormones,” or
autocrine/paracrine
regulators,
such as
Prostaglandins
(PGs),
Adrenomedullin
(AM),
and
Endothelins (ETs).
Friday, May 10, 2019

7. Renin Angiotensin System
(RAS)
Major componants
Juxta-glomerular
Apparatus.
Collection of
specialised cells
located near to
glomerulus.
Friday, May 10, 2019

8. JUXT-GLOMERULAR
APPARTUS.
TYPES OF CELLS
Juxta-glomerular
cells
Macula densa cells
Mesangial cells.
Friday, May 10, 2019

9. JUXTA-GLOMERULAR CELLS
Specialised
myoepithelial cells
Location – Media of
afferent arteriole
Friday, May 10, 2019

10. CHARACTERISTIC FEATURES
Well developed
Golgi appartus,
Endoplasmic reticulum &
abundunt mitochondria &
Ribosomes.
Renin is stored in the
secretory granules of JG
cells and, therefore, these
are also called Granular
cells
Friday, May 10, 2019

11. TYPE OF RECEPTOR
Baroreceptors
(tension receptors)
Respond to changes in
the transmural
pressure gradient
between the afferent
arterioles and the
interstitium.
Friday, May 10, 2019

12. RESPONSE – 2 TYPES
Densely innervated by the sympathetic
nerve
fibres and release their renin content in
response to the Sympathetic discharge.
Vascular volume receptors, they
monitor renal perfusion pressure and are
stimulated by hypovolaemia or decreased
renal perfusion pressure.
Friday, May 10, 2019

13. MACULA DENSA CELLS
Specialised renal
tubular epithelial cells
of a short segment of
the thick ascending limb
of loop of Henle which
passes
between the afferent
and efferent
arterioles.
Friday, May 10, 2019

14. Characteristic features
They are not well adapted for reabsorption.
They are not innervated.
These cells are in direct contact with the
mesangial cells
and in close contact with the JG cells.
They act as chemoreceptors and are stimulated
By decreased NaCl concentration and thereby
causing
Friday, May 10, 2019

15. Mesangial cells.
Interstitial cells of the JG apparatus.
They are in contact with both the macula densa cells (on
one side) and JG cells (on the other side).
Relay the signals from
macula densa to the granular cells after modulating the
signals.
In this way, a decreased intraluminal Na+ load, Cl– load, or
both in the region of macula densa stimulates the JG cells
to secrete renin

Friday, May 10, 2019

16. REGULATION OF GFR
Auto regulation
Hormonal regulation
Nervous regulation

17. GFR DEPENDS ON DIAMETERS OF
AFFERENT AND EFFERENT ARTERIOLES
GFR GF
R
Glomerulus
Afferent arteriole Efferent arteriole
Glomerular filtrate
Aff. Art. dilatation
Eff. Art. dilatationEff. Art.
constriction
Aff. Art.
constriction
Prostaglandins,
Kinins, Dopamine
(low dose), ANP,
NO
Angiotensin II
(low dose)
Angiotensin II
blockade
Ang II (high dose),
Noradrenaline (Symp
nerves), Endothelin, ADH,
Prost. Blockade)

18. AUTO REGULATION
Mechanism of Auto-regulation
1Myogenic mechanism ( Respond to
change in arterial pressure).
2Tubuloglomerular feedback
mechanism ( Respond to change in NaCl
concentration of tubular fluid.

19. TUBULOGLOMERULAR FEEDBACK
MECHANISM
 Renal arterial pressure
GFR
NaCl conc. in tubular fluid
Stimulate macula densa cells
Renin release
Afferent arteriole constriction /
dilation
Renal arterial pressure

20. HORMONAL REGULATION
HORMONES
Vasoconstrictors
1 NE
2 Angiotensin II
3 Endothelin
VASODIALATORS
1 PG
2 NO
3 ANP
4 Bradykinin
STIMULUS GFR
ECV
ECV
ECV
ECV, stretch NC
stretch, Ach, histamine
ECV
PG, ACE

21. NERVOUS REGULATION
Afferent & efferent – sympathetic from T4-L2
through splanchnic nerves.
Normally sympathetic tone minimum.
Mild to moderate stimulation – mild effect.
Strong acute stimulation – Fall in RBF due to
constriction of both afferent & efferent arterioles.

22. KALLIKREINS – KININ SYSTEM
The kallikrein-kinin system consists of four
major components: kininogen,
kallikreins,
kinins,
and kininases
Friday, May 10, 2019

23. Friday, May 10, 2019

24. 1,25- (OH)2 vitamin D3,
Final activation of vitamin D to the active
hormone calcitriol takes place in
the kidneys – 1-hydroxylation of
25- hydroxycholecalciferol
1,25- dihydroxycholecalciferol.
Friday, May 10, 2019

25. Friday, May 10, 2019

26. 1,25- (OH)2 vitamin D3,
Calcitriol stimulates the small
intestine for protein synthesis allowing
absorption of Ca
2+
and phosphates.
This ensures the availability of
Ca
2+
and phosphate for bone growth.
Calcitriol simultaneously activates
osteoblasts to synthesize collagen.
Friday, May 10, 2019

27. Friday, May 10, 2019

28. ERYTHROPOIETIN
Erythropoietin is a
peptide hormone
which regulates 
Erythropoiesis.
Structure and function
Erythropoietin is
a Glycoprotein contai
ning 165 amino acids.
Friday, May 10, 2019

29. Actions 
Receptors are present on the membranes
of red blood cell precursors.
Binding of the hormone reduces 
Apoptosis of these cells – multiple cells
survive and can therefore complete their
development into mature erythrocytes.
Friday, May 10, 2019

30. Friday, May 10, 2019

31. Synthesis and inactivation
In adults, approximately 90  %  of 
erythropoietin  is  synthesized  in  the 
kidneys (interstitial cells) , the remaining
amount in the  liver (perivenous
hepatocytes) .
Friday, May 10, 2019

32. Synthesis and inactivation
 The liver plays a key role in the production
of erythropoietin during the fetal period.
But in adulthood, the liver is no longer able
to compensate for a potential decrease in
production in the kidneys.
Friday, May 10, 2019

33. CLINICAL CORRELATIONS:
For most people in end-stage renal 
failure, anemia with erythropoietin
deficiency occurs.
Doctors can administer recombinant 
erythropoietin to these patients.
Friday, May 10, 2019

34. DOPING DRUG
Erythropoietin is also
abused as doping 
substance – especially
in endurance athletics
(cycling) .
Friday, May 10, 2019

35. STIMULUS FOR 
PRODUCTION.
Decrease in partial pressure of oxygen in
blood flowing through the organs.
Also supported by androgens &
catecholamines.
Friday, May 10, 2019