Renal hormones Flashcards
Angiotensin II activation axon
Angiotensinogen (liver) + Renin –> Angiotensin I
Angiotensin I + ACE (lungs and kidney)–> angiotensin II
renin is secreted by
juxtaglomerular kidney cells
renin secretion is triggered by
- low Blood pressure (JG cells)
- low Na+ delivery (macula densa cells - distal convoluted tubule)
- increased sympathetic tone (β1-receptors)
increased sympathetic tumors increase Renin secretion via ….. receptors
β1
Angiotensin-converting enzyme - location
capillaries of the lungs but can also be found in endothelial and kidney epithelial cells
beside its action in angiotensin-aldosteron axons, ACE also
causes Bradykinin breakdown
Angiotensin II action
- acts at angiotensin II receptor (type 1-AT1) on vascular SMC –> vasoconstriction –> increases BP
- constricts EFFERENT arteriole of glomerus –> increases Filtration fraction to preserve GFR in low volumes states (eg. when low RBF)
- Aldosterone secretion (adrenal gland) –> a. increases Na channel and Na/K pump in principal cells b. enchance K+ and H+ exretion by way of prinicipal cell K channels and α-intercalated cells H+ ATPase –> creats favorable Na+ gradient for Na and H20 reabsorption
- ADH posterior pituitary –> increases aquaporin insertion in principal cells –> H2O reabsorption
- increases PCT Na/H+ exchanger activity –> Na+, HCO3- and H2O reabsorption –> permit contraction alkalosis
- Stimulates hypothalamus –> thirst
angiotensin action on vessels
- acts at angiotensin II receptor (type 1-AT1) on vascular SMC –> vasoconstriction –> increases BP
- constricts EFFERENT arteriole of glomerus –> increases Filtration fraction to preserve GFR in low volumes states (eg. when low RBF)
angiotensin action on CNS
- ADH posterior pituitary –> increases aquaporin insertion in principal cells –> H2O reabsorption
- Stimulates hypothalamus –> thirst
angiotensin action on PCT
Na/H+ exchanger activity –> Na+, HCO3- and H2O reabsorption –> permit contraction alkalosis
angiotensin action on adrenal gland
activates aldosterone syntase (zona glomerulosa) –> Aldosterone secretion
in addition to its pressor effect, ATII also
affects baroreceptor function –> limits reflex bradycardia which would normally accompany its pressor effects
ADH primary regulates ….. . also respond to …..
osmolarity
low blood volume states
ANP and BNP are released from ….. (and when)
from atria (ANP) and ventricle (BNP) in response to increased volume –> may act as a check of renin-angiotensin-aldosterone system
ANP and BNP - action
- relaxes vascular smooth muscle via cGMP –> increase GFR and decrease Renin
- Dilates afferent arteriole, constricts efferent arteriole and promote natriuresis
Juxtraglomerular apparatus consist of
- mesangial cells
- JG cells (modified SMCs of afferent arteriole)
- Macula densa (part of DCT)
Macula densa - function
NaCL sensor in DCT –> if low –> increase renin secretion –> efferent arteriole vasoconstriction –> Increases GFR
JGA maintain GFR via
renin-angiotensin-aldosterone system
β-blockers - BP
β-blockers can decrease BP by inhibiting β1 receptors of the Juxtraglomerular apparatus–>decrease renin release
hormones produce by kidney (which hormones are from where exactly)
- renin –> from Juxtraglomerular apparatus
- Erythropoietin –> from interstitial cells in peritubular capillary bed
- Prostagladins –> paracrine in afferent arterioles
- Calcitriol (1,25 OH2 vitamine D3 - active form) –> from PCT celsl
- Dopamine –> from PCT PCT cells
Erytrhopoietin is released by ….. in response to
interstitial cells in peritubular capillary bed in response to hypoxia
Erytrhopoietin - function
stimulates RBCs proliferation in bone marrow
Erytrhopoietin - clinica use as a drug
chronic kidney disease
kidney - Calcitriol
PCT cells convert 25-OH vitamin D3 to 1,25 (OH)2 vitamin D3 (calcitriol, active form) via PARATHORMONE ACTION (increases 1α-hydroxylase)
Kidney - prostagladins action and secretion
paracrine secretion vasodilates the afferent arterioles to increase RBF
effect of NSAID on renal function
NSAIDs inhibit prostagladins (that preferentially dilated afferent arteriole and increase RPF and GFR, not the FF)
- -> constriction of afferent arteriole –> decrease of RPF and GFR, not the FF –> IN LOW RENAL BLOOD SATES
- -> ACUTE RENAL FAILUE
Kidney - dopamine is secreted by
PCT cells
Kidney - dopamine action
- Promotes natriuresis
- at low doses –> dilates interlbular arteries, afferent arterioles and eferent arterioles –> increased RBF, little or no change in GFR
- at higher doses –> acts as vasoconstrictor
ANP - net effect
Na+ loss and volume loss (increases GFR and Na filtration with no compensatory Na reabsorption)
which hormone preserve renal function (GFR) in low-volume-states and how
Angiotensin II: 1. constricts efferent arteriole (Increases FF) 2. Na+ reabsorption in proximal and distal nephron)
aldosterone - secreted in response to
- low blood volume (via ATII)
2. high K+ concentration
aldosterone - effect on K+, Na+, H+
causes Na+ reabsorption, K+ secretion and H+ secretion
ADH is secreted in response to
- High plasma osmolarity
- low blood volume
- angiotensin II action
PTH is secreted in response to
- low plasma Ca2+
- high plasma PO4-
- low plasma 1,25-OH2 D3
PTH generally causes in KIDNEY (and area)
- increase Ca2+ reabsorption in DCT
- decrease PO4- reabsorption in PCT
- Increases 1,25 OH2 D3 production in PCT (increases Ca2+ and PO4- absorption from gut via vitamin D)
factors that shift K+ out of cells (causing hyperkalemia)
- digitalis (blocks Na+/K+ ATPase)
- Hyperosmolarity
- Cell lysis (crush injury, tumor lysis synsdrome, rhabdomyolysis)
- Acidosis
- β-blocker
- insulin deficiency
- exercise
β-blocker shift K+ causes hyperkalemia - mechanism
- Beta blockers suppress catecholamine-stimulated renin release, thereby decreasing aldosterone synthesis.
- nonselective beta blockers decrease cellular uptake of potassium
acidosis causes hyperkalemia - mechanism
exchange of extracellular H+ for intracellular K+
hyperosmolarity causes hyperkalemia - mechanism
H20 flows out of the cell –> K+ diffuses out with H20
Cell lysis causes hyperkalemia - examples (3)
- crush injury
- tumor lysis synsdrome
- rhabdomyolysis
factors that shift K+ into cells (causing hypokalemia)
- hyposmolarity
- alkalosis
- β-adrenergic agonist (increase Na+/K+ ATPase)
- insulin (increase Na+/K+ ATPase)
alkalosis causs hypokalemia - mechanism
exchange of intracellular H+ for extracellular K+
insulin shifts K+ into cells - mechanism
increase Na+/K+ ATPase
β-adrenergic agonist shifts K+ into cells - mechanism
increase Na+/K+ ATPase
hypo-osmolarity shifts K+ into cell - mechanism
H2o flows into the cell, K+ diffuse with H20
concentration of sodium, potasium, chloride, biocarbonate, magnesium, calcium, phosphorus
- Na+ –> 136-145 mEg/L
- CL- –> 95-105 mEq/L
- K+ –> 3.5-5 mEq/L
- HCO3- –> 22-28 mEq/L
- Mg2+ –> 1.5-2.5 mEq/L
- Ca2+ –> 8.4-10.2 mg/dL
- Pi –> 3-4.5 mg/dL
high Na+ concentration - clinical manifestations
- irritability
- stupor
- coma
low Na+ concentration - clinical manifestation
- nausea
- malaise
- stupor
- coma
- seizures
high K+ concentration - clinical manifestations
- wide QRS and peaked T waves on ECG
- Arrhytmias
- muscle weakness
low K+ concentration - clinical manifestation
- U waves and flattened T waves on ECG
- Arrhytmias
- muscle cramps
- spasms
- weakness
high Ca2+ concentration - clinical manifestations
- renal stones
- Bone pain
- abdominal pain and constipation.
- urinary frequency
- anxiety, altered mental status
NOT NECESSARILY CALCIURIA
low Ca2+ concentration - clinical manifestation
- Tetatny
- seizures
- Proloned QT
- twitching (Chvostek sign)
- Spasm (Trousseau sign)
high Mg2+ concentration - clinical manifestations
- low deep tendon reflexes
- lethargy
- Bradycardia
- Hypotension
- Cardiac arrest
- Hypocalcemia
low Mg2+ concentration - clinical manifestation
- Tetany
- torsades de pointes
- hypokalemia
high Po4- concentration - clinical manifestations
- Renal stones
- mestatic calcificationss
- Hypocalcemia
low Po4- concentration - clinical manifestation
- Bone loss
- osteomalacia (adults)
- rickets (children)
stupor vs coma according to definition
stupor: unresponsiveness from which a person can be aroused only by vigorous, physical stimulation
Coma: unresponsiveness from which a person cannot be aroused
Electrolyte disturbances - ECG?
- U waves and flattened T waves in low K+
- wide QRS and peaked T waves in high K+
- torsades de pointes in low Mg2+
- QT prolongation in low Ca2+
- Bradycardia/cardiac arrest in high Mg2+
Renin-secreting tumor - BP, renin, Aldosterone levels
BP: increased
renin: increased
aldosterone: increased
Prmary hyperaldosteronism (Conn syndrome) - BP, renin, Aldosterone levels
BP: increased
renin: decreased
aldosterone: increased
SIADH - BP, renin, Aldosterone - levels
BP: increased
renin: decreased
aldosterone: decreased
Liddle syndrome - BP, renin, Aldosterone - levels
BP: increased
renin: decreased
aldosterone: decreased
Bartter syndrome - BP, renin, Aldosterone - levels
BP: not affected
renin: increased
aldosterone: increased
Gitelman syndrome - BP, renin, Aldosterone - levels
BP: not affected
renin: increased
aldosterone: increased
Bartter syndrome vs Gitelman syndrome according serum Mg 2+ levels
Barrter –> low (but more characteristic in Gitelman)
Gitelman –> decreased
Bartter syndrome vs Gitelman syndrome according urine Ca2+ levels
Barrter –> high
Gitelman –> low
angiotensin Effect on heart rate
in addition to its pressor effect, ATII also affects baroreceptor function –> limits reflex bradycardia which would normally accompany its pressor effects
Hypercalcemia causes frequent urination - mechanism
Excess calcium –> kidneys have to work harder to filter it out –> excessive thirst and frequent urination.
Electrolyte disturbances - ECG?
- waves and flattened T waves in low K+
- wide QRS and peaked T waves in high K+
- torsades de pointes in high Mg2+
- QT prolongation in high Ca2+
other electrical disturbances caused by Mg2+ level disturbances
low Mg –> hypokalemia
high Mg –> hypocalcemia
Causes of hypomagnesemia
- diarrhea
- aminoglycosides
- diuretics
- alcohol abuse
