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.
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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
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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).
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7. Renin Angiotensin System
(RAS)
Major componants
Juxta-glomerular
Apparatus.
Collection of
specialised cells
located near to
glomerulus.
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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
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11. TYPE OF RECEPTOR
Baroreceptors
(tension receptors)
Respond to changes in
the transmural
pressure gradient
between the afferent
arterioles and the
interstitium.
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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.
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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.
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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
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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
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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.
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
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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.
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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.
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28. ERYTHROPOIETIN
Erythropoietin is a
peptide hormone
which regulates
Erythropoiesis.
Structure and function
Erythropoietin is
a Glycoprotein contai
ning 165 amino acids.
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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.
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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) .
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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.
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33. CLINICAL CORRELATIONS:
For most people in end-stage renal
failure, anemia with erythropoietin
deficiency occurs.
Doctors can administer recombinant
erythropoietin to these patients.
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34. DOPING DRUG
Erythropoietin is also
abused as doping
substance – especially
in endurance athletics
(cycling) .
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35. STIMULUS FOR
PRODUCTION.
Decrease in partial pressure of oxygen in
blood flowing through the organs.
Also supported by androgens &
catecholamines.
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