DR. POOJA PRIYADARSINI
SENIOR RESIDENT
DEPARTMENT OF BIOCHEMISTRY
AIIMS, BHUBANESWAR
RENAL
HORMONES.
OBJECTIVES.
❖ INTRODUCTION
❖ COMPONENTS OF RAS
❖ PATHOPHYSIOLOGY OF RAS
❖ KALLIKREIN-KININ SYSTEM
❖ VITAMIN D
❖ ERYTHROPOIETIN
INTRODUCTION
■ The kidney -- Essential role in the
maintenance of life in higher organisms
■ Regulation of the blood pressure and
body fluid homeostasis
■ Removal of wastes
■ As a major Endocrine organ.
ENDOCRINE FUNCTIONS
■ Renin
■ kallikreins
■ 1,25- (OH)2 vitamin D3,
■ Erythropoietin
TARGET ORGAN
■ The kidney serves as an
important endocrine target
organ for a number of
hormones
■ Controls the
 extracellular fluid volume,
 electrolyte balance
 Acid-base balance
 blood pressure.
■Angiotensin
■Aldosterone
■PTH
■ADH
“Local hormones,”
■ The kidney
is also a major organ
for the production
and action of various
“local hormones,” or
autocrine/paracrine
regulators
■ such as
 Prostaglandins
(PGs),
 Adrenomedullin
(AM)
 Endothelins (ETs).
Renin Angiotensin System
(RAS)
■ Major component
of RAS is:
“Juxta-glomerular
Apparatus"
■ Collection of
specialised cells
located near to
glomerulus.
JUXT-GLOMERULAR
APPARTUS.
■ TYPES OF CELLS in
JG Apparatus
 Juxta-
glomerular cells
 Macula densa
cells
 Mesangial
cells/Lacis cells
JUXTA-GLOMERULAR CELLS
■ Specialised
myoepithelial cells
■ Location – Tunica
Media of afferent
arteriole
CHARACTERISTIC FEATURES
• They have 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
TYPE OF RECEPTOR
■ Baroreceptors
(tension receptors)
■ Respond to changes in
the transmural
pressure gradient
between the afferent
arterioles and the
interstitium.
RESPONSE
■ Densely innervated by the sympathetic
nerve fibers and release their renin
content in response to the
Sympathetic discharge.
■ Vascular volume receptors(monitor renal
perfusion pressure)are stimulated by
hypovolaemia or decreased renal
perfusion pressure.
MACULA DENSA CELLS
■ Specialised renal
tubular epithelial cells
of a short segment of
the distal convoluted
tubule which passes
between the afferent
and efferent
arterioles.
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
■ Stimulated by decreased NaCl concentration
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
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. dilatation
Eff. 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.
HORMONAL REGULATION
■HORMONES
VASOCONSTRIC
TORS
1 NE
2 Angiotensin II
3Endothelin
VASODIALATORS
1 PG
4 NO
5 ANP
6 Bradykinin
■ STIMULUS GFR
ECV
ECV
ECV
ECV, stretch NC
stretch, Ach, histamine
ECV
PG, ACE
NERVOUS REGULATION
■ Afferent & efferent arterioles– innervated by
sympathetic nerves 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,
■ bradykinin
■ kininases
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.
Active vitamin D
■ Stimulates the small intestine for
protein synthesis allowing absorption
of Ca2+and phosphates.
■ Promotes renal reabsorption of Calcium
and Phosphorous.
■ This ensures the availability of
Ca2+and phosphate for bone growth.
Calcitriol simultaneously activates
osteoblasts to synthesize collagen.
ERYTHROPOIETIN
■ Erythropoietin is a peptide hormone
which regulates Erythropoiesis.
■ Erythropoietin is
a Glycoprotein contai ning 165 amino
acids.
Actions
■ Receptors are present on the membranes
of red blood cell precursors.
■ Binding of the EPO reduces Apoptosis
of these cells – multiple cells survive
and can therefore complete their
development into mature erythrocytes.
Synthesis and inactivation
■ In adults, approximately 90
erythropoietin synthesized
% of
in the
kidneys (interstitial cells)
Remaining amount in the liver (perivenous
hepatocytes) .
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.
CLINICAL CORRELATIONS:
■ For most people in end-stage renal
failure, anemia with erythropoietin
deficiency occurs.
■ Doctors can administer recombinant
erythropoietin to these patients.
DOPING DRUG
■ Erythropoietin is also
abused as doping
substance – especially
in endurance athletics
(cycling) .
STIMULUS FOR
PRODUCTION.
■ Decrease in partial pressure of oxygen in
blood flowing through the organs.
■ Also supported by androgens &
catecholamines.
RENAL HORMONES.pptx

RENAL HORMONES.pptx

  • 1.
    DR. POOJA PRIYADARSINI SENIORRESIDENT DEPARTMENT OF BIOCHEMISTRY AIIMS, BHUBANESWAR RENAL HORMONES.
  • 2.
    OBJECTIVES. ❖ INTRODUCTION ❖ COMPONENTSOF RAS ❖ PATHOPHYSIOLOGY OF RAS ❖ KALLIKREIN-KININ SYSTEM ❖ VITAMIN D ❖ ERYTHROPOIETIN
  • 3.
    INTRODUCTION ■ The kidney-- Essential role in the maintenance of life in higher organisms ■ Regulation of the blood pressure and body fluid homeostasis ■ Removal of wastes ■ As a major Endocrine organ.
  • 4.
    ENDOCRINE FUNCTIONS ■ Renin ■kallikreins ■ 1,25- (OH)2 vitamin D3, ■ Erythropoietin
  • 5.
    TARGET ORGAN ■ Thekidney serves as an important endocrine target organ for a number of hormones ■ Controls the  extracellular fluid volume,  electrolyte balance  Acid-base balance  blood pressure. ■Angiotensin ■Aldosterone ■PTH ■ADH
  • 6.
    “Local hormones,” ■ Thekidney is also a major organ for the production and action of various “local hormones,” or autocrine/paracrine regulators ■ such as  Prostaglandins (PGs),  Adrenomedullin (AM)  Endothelins (ETs).
  • 7.
    Renin Angiotensin System (RAS) ■Major component of RAS is: “Juxta-glomerular Apparatus" ■ Collection of specialised cells located near to glomerulus.
  • 8.
    JUXT-GLOMERULAR APPARTUS. ■ TYPES OFCELLS in JG Apparatus  Juxta- glomerular cells  Macula densa cells  Mesangial cells/Lacis cells
  • 9.
    JUXTA-GLOMERULAR CELLS ■ Specialised myoepithelialcells ■ Location – Tunica Media of afferent arteriole
  • 10.
    CHARACTERISTIC FEATURES • Theyhave 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
  • 11.
    TYPE OF RECEPTOR ■Baroreceptors (tension receptors) ■ Respond to changes in the transmural pressure gradient between the afferent arterioles and the interstitium.
  • 12.
    RESPONSE ■ Densely innervatedby the sympathetic nerve fibers and release their renin content in response to the Sympathetic discharge. ■ Vascular volume receptors(monitor renal perfusion pressure)are stimulated by hypovolaemia or decreased renal perfusion pressure.
  • 13.
    MACULA DENSA CELLS ■Specialised renal tubular epithelial cells of a short segment of the distal convoluted tubule which passes between the afferent and efferent arterioles.
  • 15.
    Characteristic features ■ Theyare 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 ■ Stimulated by decreased NaCl concentration
  • 16.
    Mesangial cells. ■ ■ ■ ■ Interstitial cellsof 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
  • 17.
    REGULATION OF GFR ■Autoregulation ■Hormonal regulation ■Nervous regulation
  • 18.
    GFR DEPENDS ONDIAMETERS OF AFFERENT AND EFFERENT ARTERIOLES ↑GFR ↓GFR Glomerulus Afferent arteriole Efferent arteriole Glomerular filtrate Aff. Art. dilatation Eff. Art. dilatation Eff. 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)
  • 19.
    AUTO REGULATION ■ Mechanismof Auto-regulation 1 Myogenic mechanism ( Respond to change in arterial pressure). 2 Tubuloglomerular feedback mechanism ( Respond to change in NaCl concentration of tubular fluid.
  • 20.
    HORMONAL REGULATION ■HORMONES VASOCONSTRIC TORS 1 NE 2Angiotensin II 3Endothelin VASODIALATORS 1 PG 4 NO 5 ANP 6 Bradykinin ■ STIMULUS GFR ECV ECV ECV ECV, stretch NC stretch, Ach, histamine ECV PG, ACE
  • 21.
    NERVOUS REGULATION ■ Afferent& efferent arterioles– innervated by sympathetic nerves 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 – KININSYSTEM ■ The kallikrein-kinin system consists of four major components: kininogen, ■ kallikreins, ■ bradykinin ■ kininases
  • 24.
    1,25- (OH)2 vitaminD3, ■ Final activation of vitamin D to the active hormone calcitriol takes place in the kidneys – 1-hydroxylation of 25- hydroxycholecalciferol 1,25- dihydroxycholecalciferol.
  • 26.
    Active vitamin D ■Stimulates the small intestine for protein synthesis allowing absorption of Ca2+and phosphates. ■ Promotes renal reabsorption of Calcium and Phosphorous. ■ This ensures the availability of Ca2+and phosphate for bone growth. Calcitriol simultaneously activates osteoblasts to synthesize collagen.
  • 28.
    ERYTHROPOIETIN ■ Erythropoietin isa peptide hormone which regulates Erythropoiesis. ■ Erythropoietin is a Glycoprotein contai ning 165 amino acids.
  • 29.
    Actions ■ Receptors arepresent on the membranes of red blood cell precursors. ■ Binding of the EPO reduces Apoptosis of these cells – multiple cells survive and can therefore complete their development into mature erythrocytes.
  • 31.
    Synthesis and inactivation ■In adults, approximately 90 erythropoietin synthesized % of in the kidneys (interstitial cells) Remaining amount in the liver (perivenous hepatocytes) .
  • 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.
  • 33.
    CLINICAL CORRELATIONS: ■ Formost people in end-stage renal failure, anemia with erythropoietin deficiency occurs. ■ Doctors can administer recombinant erythropoietin to these patients.
  • 34.
    DOPING DRUG ■ Erythropoietinis also abused as doping substance – especially in endurance athletics (cycling) .
  • 35.
    STIMULUS FOR PRODUCTION. ■ Decreasein partial pressure of oxygen in blood flowing through the organs. ■ Also supported by androgens & catecholamines.