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DR NILESH KATE
MBBS,MD
PROFESSOR
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
RENAL
HORMONES.
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
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, June 19, 2020
ENDOCRINE FUNCTIONS
 Renin
 kallikreins
 1,25- (OH)2 vitamin D3,
 Erythropoietin
Friday, June 19, 2020
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, June 19, 2020
“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, June 19, 2020
Renin Angiotensin System
(RAS)
 Major componants
 Juxta-glomerular
Apparatus.
 Collection of
specialised cells
located near to
glomerulus.
Friday, June 19, 2020
JUXT-GLOMERULAR
APPARTUS.
 TYPES OF CELLS
 Juxta-glomerular
cells
 Macula densa cells
 Mesangial cells.
Friday, June 19, 2020
JUXTA-GLOMERULAR CELLS
 Specialised
myoepithelial cells
 Location – Media of
afferent arteriole
Friday, June 19, 2020
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, June 19, 2020
TYPE OF RECEPTOR
 Baroreceptors
(tension receptors)
 Respond to changes in
the transmural
pressure gradient
between the afferent
arterioles and the
interstitium.
Friday, June 19, 2020
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, June 19, 2020
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, June 19, 2020
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, June 19, 2020
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, June 19, 2020
REGULATION OF GFR
 Auto regulation
 Hormonal regulation
 Nervous regulation
GFR DEPENDS ON DIAMETERS OF
AFFERENT AND EFFERENT ARTERIOLES
GFR GFR
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)
AUTO REGULATION
 Mechanism of Auto-regulation
1 Myogenic mechanism ( Respond to
change in arterial pressure).
2 Tubuloglomerular feedback
mechanism ( Respond to change in NaCl
concentration of tubular fluid.
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
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
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.
KALLIKREINS – KININ SYSTEM
 The kallikrein-kinin system consists of four
major components: kininogen,
 kallikreins,
 kinins,
 and kininases
Friday, June 19, 2020
Friday, June 19, 2020
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, June 19, 2020
Friday, June 19, 2020
1,25- (OH)2 vitamin D3,
 Calcitriol stimulates the small
intestine for protein synthesis allowing
absorption of Ca2+and phosphates.
 This ensures the availability of
Ca2+ and phosphate for bone growth.
Calcitriol simultaneously activates
osteoblasts to synthesize collagen.
Friday, June 19, 2020
Friday, June 19, 2020
ERYTHROPOIETIN
 Erythropoietin is a
peptide hormone
which regulates
Erythropoiesis.
 Structure and function
 Erythropoietin is
a Glycoprotein contai
ning 165 amino acids.
Friday, June 19, 2020
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, June 19, 2020
Friday, June 19, 2020
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, June 19, 2020
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, June 19, 2020
CLINICAL CORRELATIONS:
 For most people in end-stage renal
failure, anemia with erythropoietin
deficiency occurs.
 Doctors can administer recombinant
erythropoietin to these patients.
Friday, June 19, 2020
DOPING DRUG
 Erythropoietin is also
abused as doping
substance – especially
in endurance athletics
(cycling) .
Friday, June 19, 2020
STIMULUS FOR
PRODUCTION.
 Decrease in partial pressure of oxygen in
blood flowing through the organs.
 Also supported by androgens &
catecholamines.
Friday, June 19, 2020
Renal hormones

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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, June 19, 2020
  • 4. ENDOCRINE FUNCTIONS  Renin  kallikreins  1,25- (OH)2 vitamin D3,  Erythropoietin Friday, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 7. Renin Angiotensin System (RAS)  Major componants  Juxta-glomerular Apparatus.  Collection of specialised cells located near to glomerulus. Friday, June 19, 2020
  • 8. JUXT-GLOMERULAR APPARTUS.  TYPES OF CELLS  Juxta-glomerular cells  Macula densa cells  Mesangial cells. Friday, June 19, 2020
  • 9. JUXTA-GLOMERULAR CELLS  Specialised myoepithelial cells  Location – Media of afferent arteriole Friday, June 19, 2020
  • 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, June 19, 2020
  • 11. TYPE OF RECEPTOR  Baroreceptors (tension receptors)  Respond to changes in the transmural pressure gradient between the afferent arterioles and the interstitium. Friday, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 16. REGULATION OF GFR  Auto regulation  Hormonal regulation  Nervous regulation
  • 17. GFR DEPENDS ON DIAMETERS OF AFFERENT AND EFFERENT ARTERIOLES GFR GFR 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 1 Myogenic mechanism ( Respond to change in arterial pressure). 2 Tubuloglomerular 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, June 19, 2020
  • 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, June 19, 2020
  • 26. 1,25- (OH)2 vitamin D3,  Calcitriol stimulates the small intestine for protein synthesis allowing absorption of Ca2+and phosphates.  This ensures the availability of Ca2+ and phosphate for bone growth. Calcitriol simultaneously activates osteoblasts to synthesize collagen. Friday, June 19, 2020
  • 28. ERYTHROPOIETIN  Erythropoietin is a peptide hormone which regulates Erythropoiesis.  Structure and function  Erythropoietin is a Glycoprotein contai ning 165 amino acids. Friday, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 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, June 19, 2020
  • 34. DOPING DRUG  Erythropoietin is also abused as doping substance – especially in endurance athletics (cycling) . Friday, June 19, 2020
  • 35. STIMULUS FOR PRODUCTION.  Decrease in partial pressure of oxygen in blood flowing through the organs.  Also supported by androgens & catecholamines. Friday, June 19, 2020