renal system Flashcards
Describe renal hormones
The kidney as an endocrine organ – Renin (RAS) – Erythropoietin – Calcitriol • The kidney as a target organ for hormones – Antidiuretic hormone (AVP, pituitary) – Aldosterone (RAAS, adrenal gland) – Cardiac hormones
renin, where is it produced, what is stumuli for release
• Produced in the cells juxtaglomerular
apparatus (JGA)
• Stimuli for release:
– Low blood pressure (detected by baroreceptors)
– Decrease in Na (detected at the macular densa)
– Stimulation of the renal sympathetic nerves
Erythropoietin
• Kidney is the major site of production –
interstitial cells
• Also produced in the liver - perisinusoidal cells
• Glycoprotein hormone
• Half life ~5 hours
• Binds to EpoR (located in bone marrow, CNS)
and activates JAK2 signalling cascade
Roles of epo?
Classical -> stimulate production of red cells
Wound healing Cardioprotection Angionesesis Neuroprotectnat in premmie baboes Renal and retinal protecion
Simulation and actions of EPo and erthropoiesis
Hypoxia detected (decreased O2 bc low RBC)-> epo prodction -> stimulates erythroppoiesis in bone marrow->erythroppoiesis increase RBC -> blood o2 return to normal
what stimulates epo?
How much oxygen can be delivered to tissue, -> tissue will detect -> will induce HIF and stim epo:
Low tissue oxygenation can be bc not enough hemoglobin -> iron defficient , or hemorrhage
Or if not enough o2 attached to hemo e.g high altitude
epo production baby and adult
In liver as baby and in kidney as adult
how you get rbc from red blood cell?
In bone marrow, stem cells turn into BFU-E then CFU-E then erythroblasts then reticulocytes then red cell mass
EPO acts on BFU-E AND CFU-E
What are the Actions of Epo on the bone marrow
cts on red blood cell progenitors and precursors
(in the bone marrow)
• Protects these cells from apoptosis.
• Targets
– Burst forming units (BFU-E)
– colony forming units (CFU-E)
• cooperates with various other growth factors
(e.g., glucocortioicds, IL-6).
• Precursors of red cells, the proerythroblasts and
basophilic erythroblasts also express Epo-R.
describe Erythropoietin receptor
- Located on erythroid progenitors - Cytokine receptor - Signals through JAK2-STAT pathway - Increased Epo production in people with mutations in the Epo-R –increased hematocrit.
CAN ACTIVATE MULTIPLE SECONDARY MESSENGER SYSTEMS TO HAVE DIFFERENT TARGET
What is gold medal mutation?
- Point mutation in the Epo-R causes Primary familial polycythaemia - Increased hematocrit esp good for endurance sports
Altered Epo production
?
Low Epo production in kidney failure
• Anemia (multiple causes)
• Early sign of renal failure is tiredness due to
lack of Epo production
epo can be therapteutic for aneamia
what are some Non-haemopoietic effects of EPO
Actions of Epo in wound healing:
1) improves mobility of cells and increases migration
rate, particularly in keratinocytes and fibroblasts,
resulting in an overall quicker wound closure.
2)(2) reduces inflammatory reaction.
(3) Increased angiogenic response, accelerated
microvascular network formation, and improved
maturation are associated with improved nutrition and
metabolism of the wound
Epo as a performance enhancing drug
Widely used by endurance athletes, particularly cyclists • Increased hematocrit to >55% • Increased blood viscosity • Strokes! Cardiac events! • Death!!!
summary of Calcitriol
Steroid hormone
• Produced in the cells of the proximal tubule
• 1,25-dihydroxyvitamin D3
• Hormonally active metabolite of vitamin D
• Calcitriol increases the level of calcium (Ca2+)
in the blood by increasing the uptake of
calcium from the gut and stop loss from urine
Calcitriol receptor?
Is in nucleus
Transcriptually regulates does whole range of things
Calcitriol receptor?
Is in nucleus
Transcriptually regulates does whole range of things
classical and novel actions of D3
May act on breast colon and prostate -> inhibial clonal proliferation
In vascular cells reduces inflammation
Increases insulin secretion in pancreas
DRAW AND READ UP ON SMOE MORE
Clinical uses:
Hypocalcemia
• Rickets (infants, children),
• Chronic kidney disease
• Osteoporosis
Hormones
acting on the
kidney:
theres big ass graph draw it out, understand it
Arginine vasopressin ADH
• Antidiuretic hormone
• Peptide hormone
• Produced in hypothalamus and stored in the
posterior pituitary
• Inhibited by alcohol
• Stimuli for release:
– Low blood pressure (detected by baroreceptors)
– Low blood volume (eg hemorrhage or dehydration)
Vasopressin controls?
active water reabsorption
Vasopressin secretion is stimulated by water deficit. This is detected by osmoreceptors in the hypothalamus (major mechanism) and volume receptors in the left atria. Vasopressin secretion is thus triggered by an increase in ECF osmolarity or a large loss in ECF volume Low ECF osmolarity and elevated ECF volume suppress vasopressin secretion. Stimuli for vasopressin secretion also cause thirst
Vasopressin controls?
active water reabsorption
Vasopressin secretion is stimulated by water deficit. This is detected by osmoreceptors in the hypothalamus (major mechanism) and volume receptors in the left atria. Vasopressin secretion is thus triggered by an increase in ECF osmolarity or a large loss in ECF volume Low ECF osmolarity and elevated ECF volume suppress vasopressin secretion. Stimuli for vasopressin secretion also cause thirst
How does it work?
- Increases water
permeability in the distal
tubule and collecting duct
(AVP ACTS TO CHANGE HOW MUCH H20 IS ABSORBED) - Results in concentrated
urine
AVP (receptor binding and signalling)
• Vasopressin binds to V2
receptors on the basolateral
membrane of epithelial cells in the distal
tubule/collecting duct.
• V2
is a GPCR that couples to Gs
, thus elevating cAMP.
• Increased cAMP induces trafficking of aquaporin 2
(AQP-2) water channels to the luminal membrane.
• Increased insertion of AQP-2 into the luminal
membrane increases free water reabsorption
Abnormalities in AVP secretion
Abnormalities in AVP secretion
- AVP secretion may decrease with aging
-Diurnal secretion may be altered
-Decreased renal sensitivity to AVP
Diabetes insipidus - Excrete large amounts of urine
- excessive thirst
- Central or nephrogenic
how can test for diabetes insipisdues with vaeopresson
administer it exogenously and see how they respond
IS it nephrogenic
Aquaroprin issues
kidney in origin hard to trear
Other actions of AVP
clasically -> last 10% fluid balance
but has evidence avp can be involved in emotional and social behaviour
Cognition
Circadian ryhthym
Aldosterone produced?
Produced in adrenal gland, =zona glomerulosa
Aldosterone summary
- Aldosterone is a steroid hormone (mineralocorticoid)
- Produced in the adrenal cortex (Zona glomerulosa)
- It binds to the mineralocorticoid receptor (MR)
- Increases the transcription of ENaC and Na-K pumps
in the collecting tubule epithelia. - This increases Na+
reabsorption and K+
secretion -> into urine
Actions of Aldosterone
binds to MR in kidney duct epithelial cell -? goes to nuclues -? changes structure of channels
Stimulation of aldosterone
Theres a graph, draw it!
what are Actions of Aldosterone on K+
Aldosterone is the major hormonal regulator of K+
secretion.
• Increased plasma K+ directly stimulates aldosterone
release from the adrenal cortex, whilst decreases in
plasma K+
suppress aldosterone secretion.
• Tight control of body K+
levels is vital as even small
changes in plasma K+ can have detrimental effects,
particularly on the heart
Tubular secretion of K+
draw this
K \+ secretion is coupled to Na+ reabsorption in the distal region of the nephron. The basolateral Na+ /K+ -ATPase that actively reabsorbs Na+ also pumps K+ into epithelial cells. K \+ can then diffuse into the lumen via ‘leak’ channels on the luminal membrane
what conditions do you have Altered Aldosterone production
Conns -> inc aldosterone, results in hypertension and hypokalemia
secondary Hypersaldosteronism -> inc aldo and renin -> results in hypertension and hypokalemia
Cushings -? musce wasting, hypertension
Addisons -? dec cortisol and aldosterone -> results in hypoglycaenia, fatigue, hypotension, dehydration,
Primary aldosteronism (Conn’s syndrome)
Renin-independent increase in the secretion of aldosterone.
~ 99% of cases due either to anadenoma or due to idiopathic
hyperaldosteronism (IHA), which accounts for around 60% of cases
(almost all of which are bilateral).
CAUSE : ANADENOMA
Secondary hyperaldosteronism
A diverse group of disorders - activation of the RAAS – high renin
Secondary hyperaldosteronism can be divided into 2 categories,
– hypertension - includes renovascular hypertension, which results from
renal ischemia and hypoperfusion leading to activation of the R-A-A
axis.
– absence of hypertension - occurs as a result of homeostatic attempts
to maintain the sodium concentration or circulatory volume or to
reduce the potassium concentration.
describe Low Aldosterone production
bc whole adreno functioning bad
• Addison’s disease (Both low Aldo and Cort)
• Fatigue, weight loss, hypotension
• Treatment – hormone replacement
what are the Cardiac hormones on the kidney
Atrial Natruietic peptic (ANP)
natriuseis -> NA excretion
Stimulated by INCREASED BLOOD VOLUME
Receptors in heart detect change in BV
can act in brain-> hypo, medulla oblongata, and adrneal cortex -> inhibit avp and aldosterone
kidney to increase GFR to result in fluid and electroltye excretion
distinguish what works on kidney or made BY kidney
summarise!
