Part 22: Renal Function & BP Modulation Flashcards
what is the normal blood pressure?
120/80 mmHg
what is the target BP in patients with CV risk, diabtes, or kidney disease?
<130/80 mmHg
what is considered a dangerous BP (hypertensive crisis)?
> 180/120 mmHg
what are 3 strategies to reduce BP?
- reduce blood volume
- reduce vascular resistance
- reduce force of heart contraction
why is high BP dangerous?
puts stress on BV and organs
what are the main functions of the kidneys? (4)
- production of regulatory enzymes & hormones including renin
- filtering out waste products, metbolites & chemicals from the blood
- regulate water and electrolyte
- regulate BP
_____ of the kidney are the individual filtering units of the kidneys
nephrons
what is the function of the nephrons?
filtering, used to remove substances from the blood and excrete them in urine
t/f there are multiple sites of ion & solute reabsorption along the nephron
t
the thick ascending limb of the nephron expresses ion transporters that allow the reabsorption of ____, ____, and ___ from the urinary compartment
Na; K; Cl
the flow of K can go back into the urinary compartment of the acsending loop and creates a _____ (positive/negative) potential that increases the reabsorption of _____ions such as ___ and ____ back into the blood
positive; Mg and Ca
where do loop diuretics like furosemide act?
in the ascending limb
what is the MOA of loop diuretics like furosemide?
blocks the NKCC2 to reduce the transport of Na, K, and CL in the thick ascending limb and Mg and Ca reabsorption are also decreased, meaning more will be excreted in urine (along with water)
can water move in/out of the thick ascending limb of the nephron?
no
t/f loop diuretics like furosemide are effective in promoting the excretion of large volumes of fluid
t
furosemide is typically indicated for the management of edema associaed with ____, but can also be used for ____ when patients requires a diuretic effect
congestive heart failure; hypertension
which ion transporters are found in teh distal convoluted tubule?
Na/Cl co-transporter (NCC)
in the distal convoluted tuble, NCC facilitate the reabsorption of ions into the ___
blood
which hormone acts on the distal convoluted tubule to increase reabsorption of Ca?
PTH
what type of diuretics block the NCC in the distal convoluted tubule?
thiazide-like diuretics, like hydrochlorothiazide
what is the MOA of thiazide-like diuretics?
block the NCC, reducing the reabsorption of Na in the distal convoluted tubule
why are other thiazide-like diuretics typically given over hydrochlorothiazide?
they typically have a longer half life than HCTZ
what is the regular dosing of HCTZ?
BID
t/f bc the reabsorption of multiple ions are linked together by co-transport mechanisms, impairing the reabsorption of Na can impact other ions
t
the actions of loop diuretics and thiazide diuretics are most likely to cause an overall loss of ____ ions, resulting in hypo-___
K , kalemia
what are some of the symptoms of hypokalemia?
- increased blood pH (alkylosis)
- muscle weakness
- cardiac arrhythmias
why might hypokalemia cause muscle weakness and cardiac arrhythmias?
due to the importance of K ions in action potential generation
t/f patients on loop and thiazide duiuretics should have regular blood monitoring for K levels
t
t/f it would be reasonable to recommned a patient taking a thiazide or loop diuretic to eat bananas
t
what is the benefit of K sparing diuretics?
they do not cause a net excretion of K in urine and promote reabsorption of K in the collecting tubule
K sparing diuretics act at what part of the nephron?
collecting tubule
____ is the final segment of the nephron where Na reabsorption can occur before excretion in urine
collecting tubule
in the collecting duct, Na follows its ____ and ____ gradient from the nephron lumen into the ___-cell through Na channels
concentration and electrical; principle
how is the transport of Na ions in the collecting tubule different than in other sections of the nephron?
only Na is going through the channels, there is no co-transport with Cl
how does reabsorption of Na in the collecting duct force more K to be excreted into the urine?
Na causes a build up of + charge in the principle cells that pushes out the K
aldoesterone stimulates _____ receptors in the prinicple cells, which causes increased gene transcription and upregulation of the _____ channel and the ____ pump
mineralocorticoid; ENAC Na channels; NA/K pump
aldosterone _____ (increases/decreases) the reabsorption of Na into the blood and also causes _____ (increased/decreased) excreted of K
increases; increased
how do K sparing diuretics work to lower the amount of K excreted in the urine?
they reduce the reabsorptio of Na in the collecting tubule principle cells, which will have the secondary effect of reducing excretion of K
what are the 2 classes of K sparing diuretics?
- aldosterone receptor antagonists
2. ENAC blockers
what class of diuretics does spironolactone belong to?
aldosterone receptor antagonist K sparing
what class of diuretics does amiloride belong to?
ENAC blocker K sparing diuretic
spironilactone is a ____ molecule with affinity for ____ receptors and ____ receptors
steroid; androgen and aldosterone
what off target effect is important to consider when thinking about giving spironolactone as a diuretic?
its anti-androgen effects, like the supression of testosterone production
spironolactone is also indicated for patients with elevated ____ production, to counter the Na and water retention
aldosterone
what is the MOA of amiloride?
blocks the Na channels in the principle cell membrane, reducing the amount of Na reabsorbed in the collecting tubule
why do the K sparing diuretics only have a mild diuretic effect?
only a small portion of total body Na is reabsorbed in the collecting tubule where these agents act
when might K sparing diuretics be a good therapeutic option?
- pt has low K
2. if patient is already on a diuretic and requires another
what is renin?
an enzyme released by the kidneys, stimulated by a drop in renal arterial BP
why is renin released by the kidneys when renal arterial BP is low?
filtration of the blood in the kidneys is highly dependent on BP to achieve adequate glomerular filtration
what is angiotensin?
a peptide made by the liver
renin cleaves angiotensin into ___
angiotensin 1 (AT1)
angiotensin converting enzyme (ACE) converts angiotensin 1 into _____
angiotensin 2 (ATII)
_____ is the active compound that stimulates angiotensin 2 type 1 receptors in the adrenal cortex, causing the release of ____
angiotensin 2; aldosterone
aldosterone causes a _____(increase/decrease) in BP
increase
stimulation of ATII receptors in BV causes increased _____ions in the vascular smooth muscle
intracellular Ca
increases intracellular Ca in vascular smooth muscle caused by the stimulation of AT2 receptors in BV, leads to ___
vasoconstriction and increased BP
AT2 receptor is a _____ coupled receptor
Gq
renin is also released in response to activation by teh ____ nervous system
sympathetic
ACE inhibitors reduce the conversion of ____ to ____
AT1 to AT2
how do angiotensin receptor blockers (ARBs) work?
competitive antagonists of the AT2 receptor, which reduced the actions of angiotensin 2 in target tissues
what is the MOA of renin inhibitors?
prevent the formation of AT1 near the begining of teh RAS
to what class of drugs does ramipril belong?
ACE inhibitor
what agents are commonly one of the first agents chosen for patients with hypertension?
ACE inhibitors
how do ACE inhibitors like ramipril lower BP?
help stop the conversion of AT1 to AT2 which would act on BV to constrict and to release aldosterone to retain water, both which would raise BP
ACE metabolizes _____ into inactive products
braykinin (BK)
what is bradykinin?
a peptide that causes vasodilation
what is the benefit of ACE inhibitors reducing the ability of ACE to metabolize bradykinin?
more active bradykinin, which causes vasodiltion and decreaseed bP
what is an ADR of ACE inhibitors preventign the breakdown of bradykinin?
more bradykinin in the blood can lead to a dry persistent cough in some patient (not infectious, but can be bothersome)
activation of the Gq pathway of the angiotensin receptor causes increased ____ activation, which increases intracellular levels of ____ and ____, which results in increased intrcaellular ____ion levels, which results in ____ (vasoconstriction or vasodilation)
phospholipse C; DAg & IP3; Ca; vasocnstriction
in the adrenal cortex, activation of the Gq pathway of teh angiotensin receptor causes the secretion of ____
aldosterone
what class of antihypertensives does Lorsartan belong to?
competitive antagonists of AT2 receptor
how does losartan work?
blocks the AT2 receptor, so the Gq pathway that causes the adrenal cortex to release aldosterone and Ca that would both increase BP
losartan prevents physiologic effects of AT2 in the ____ and ___
heart and kidney
to what class of antihypertensives does aliskiren belong to?
direct renin inhibitor
why are direct renin inhibitors not prescribed as much as other antihypertensives when they are belived to be just as effective?
they are new and the older drugs have more data and evidence
aliskiren was approved for use in Canada in the year ____
2007
t/f renin inhibitors like aliskiren prevent the activation of teh whole RAS
t
all drugs affecting the RAS are contraindicated in which group? why?
pregnancy; RAS is importnat to fetal development
what are the 4 steps of dosage adjustments for renal impairment?
- estimate the patient’s renal function by calculating their creatinine clearance
- determine the % renal excretion of drug
- determine normal dosing interval
- determine empiric dosage adjustments
what is creatinine?
a metabolic byproduct that is almost completely removed frpm the body by the kidneys
the serum level of creatinine is relatively ___ (high/low) for a person with good renal function
low
the creatinine clearanec estimates the rate of ____
glomerular filtration
what is the normal ClCr for men?
100-120 mL/min
what is the normal ClCr for women?
90-100 mL/min
what ClCr indicates renal impairment that may require dose adjustments?
<60 mL/min
