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PP&T 4 test 1
Kidney, diuretics
156
Pathology
Professional
09/02/2011

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Term
where is a majority of reabsorption occurring for water and Na
Definition
proximal tubule
Term
what are two major causes of Chronic kidney disease
Definition
hypertension, diabetes
Term
what stage of CKD will you start to see symptoms with abnormal lab values
Definition
stage 3
Term
what is the number one marker of glomerular damage
Definition
albumin levels (protienurea)
Term
why is the proximal tubule so important
Definition
this is where reabsorption happens, also this is where drugs are secreted
Term
if you had high levels of Na, K or H2o in the urine what would this indicate
Definition
damage in the proximal tubule
Term
why is creatinine a crude index for kidney function
Definition
since it varies by muscle mass (esp in the elderly may not see the increase associated with kidney damage)
Term
what are some ways to estimate kidney function
Definition
creatinine clearance, glomerular filtration
Term
you would normally use the cockcroft-gault equation to calculate creatinine clearance when would you not
Definition
if the patient is obese (30% above ideal body weight)
Term
what is the normal range for creatinine clearance
Definition
90-160
Term
what is the normal range for glomerular filtration
Definition
90-140
Term
what does the MDRD equation tell us
Definition
  the glomerular filtration rate
Term
how do you calculate the GFR in pediatrics
Definition
schwartz equation
Term
what is the most accurate measure of GFR
Definition
marker clearance
Term
what is BUN dependent on
Definition
urea production, tubular reabsorption, glomerular filtration
Term
how does trauma and quick flow rate affect BUN
Definition
these will both increase BUN
Term
list some pre-renal causes to a increased BUN
Definition
dehydration, shock, blood loss, severe heart failure
Term
what are post renal causes of an increased BUN
Definition
obstruction of ureter, bladder neck , or urethra
Term
what are the three C's of a microscopic analysis of urine
Definition
Cells, casts, crystals
Term
what are some causes of crystal formation in urine
Definition
uric acid, alkaline urine, UTI
Term
proteinuria is a tell tale sign of what
Definition
problems in the glomerulus
Term
what is the problem with albumin not being filtered
Definition
leads to scarring, inflation, burning and ultimately nephron death
Term
what are two tests used to detect proteinuria
Definition
dipstick (multistix), sulfosalicylic acid test
Term
why is proteinuria an important biomarker
Definition
it is associated with cardiovascular disease, progressive renal disease
Term
what is oliguria
anuria
Definition
oliguria is urine output under 500 ml/day
anuria is < 100 ml/day
Term
what % of Na is leaves in the urine daily
Definition
1%
Term
what is the FeNa in a patient with acute renal failure due to tubular necrosis
Definition
>2%
Term
if you have aucte oliguria with high Na levels what does this indicate
Definition
acute tubular necrosis
Term
if you detect microalbuminuria what are the next three steps
Definition
estimate GFR and creatinine clearance
adjust meds
start on ARB or ACe
Term
what is the sole purpose of the parathyroid gland
Definition
to control serum calcium
Term
how does kidney failure affect the paraqthyroid and how
Definition
phosphate won't be cleared, this will cause binding to serum Ca this will then trigger the parathyroid to produce PTH hormone causing the increase of osteoclast activity
Term
how will kidney failure effect Ca levels in the body
Definition
it will cause phosphate to not be cleared and bind to Ca, also will not create the active form of vitamin D causing an issue in Ca absorption
Term
WHAT CAUSES 90% of all acute interstitial nephritis
Definition
drug induced nephropathy
Term
changes in cardiac output, toxic metabolites of P450, water reabsorption can all attribute to what
Definition
acute kidney injury
Term
what is the standard criteria for AKI
Definition
abrupt reduction of kidney function within 48 hrs showing an increase in serum creatinine by >.3mg/dl or 50% from base or decrease in urine output to < .5ml/kg/hr>6hr
Term
what are the three major types of AKI
Definition
prerenal
intrinsic
post-renal
Term
what are the 4 types of intrinsic AKI
Definition
glomerular, interstitial nephritis, tubular injury, vascular disease
Term
what are the two most common AKI
Definition
tubular injury, interstitial nephritis (caused by drugs)
Term
what is the cause of prerenal AKI
Definition
decreased blood flow
Term
what are the most prevalent drug causes of prerenal AKI
Definition
diuretics, radio contrast media, NSAID, ACE, ARB, cyclosporine
Term
what are the clinical features and urinalysis results of prerenal AKI
Definition
hypotension, tachycardia, dry mucous membrane
FENa<1%, urine Na<10, Osmolality>500
Term
how does ACE and ARB damage the glomerulus
Definition
they cause the efferent arteriole to open allowing more blood out causing the pressure in the glomerulus to drop
Term
when should you hold an ACE or an ARb
Definition
when SCr goes above 30%
Term
what is the reason behind NSAID's nephrotoxicity
Definition
they block PGE2 which causes the afferent artiole to constrict decreasing glomerulus pressure
Term
what is the third most common cause of ARF in hospitalized patients
Definition
contrast induced nephropathy
Term
what patients are at highest risk of contrast induced nephropathy
Definition
dietetics and CKD
Term
what are the steps of contrast indused nephrotoxcity
Definition
Contrast administration-->Renal vasodilation/osmotic diuresis->
Intense vasocontriction (in the medulla)->
Decreased medullary pO2->
Ischemic ATN
Term
what does a urinalysis of Acute tubular nephritis look like
Definition
muddy brown granular casts, FeNA>2%, urine Na>20, urine osmolality <300, proteinuria
Term
what is the most important factor for predicting aminoglycoside nephrotoxicity
Definition
the trough levels
Term
what dose of amphotericin B is generally nephro toxic in 80%
Definition
cumulative doses of 4 grams
Term
what AKI is most often caused by drugs
Definition
acute interstitial nephritis
Term
what is the presentation triad for acute interstitial nephritis
Definition
rash, increased eosinophils in urine and eosinophilla
Term
what class of drugs is most likely to cause acute interstitial nephritis
Definition
antibiotics (beta lactams)
Term
what are the main complications of AKI
Definition
electrolyte abnormalities (hyper- K, Mg an Phosphate, metabolic acidosis, volume overload, uremic syndrome
Term
who is the at risk population for AKI
Definition
elderly, diabetics, hypertension, vascular disease, heart failure, infections, poor nutrition
Term
what drug can alter FeNa
Definition
loop diuretics
Term
what are the goals of therapy with AKI
Definition
decrease further injury
correct or treat cause
supportive care
manage complications
properly dose all meds
Term
what are the indices of effect for AKI
Definition
resolution of Creatinine, BUN, K, P, Mg, H,restore urine output, clear edema
Term
what drug class do we use for symptomatic relief of AKI
Definition
diuretics
Term
how should we replace fluids in AKI
Definition
1/2 fluid in first 24 hours then 1/2 in second 24
Term
how can you prevent prerenal AKI in at risk patients
Definition
hydrate
use short acting low doses of captopril (ACE or ARB)
monitor Scr, K
Term
how would you minimize acute intestitial nephritis damage
Definition
stop the offending agent, use prednisone 1-2mg for 4-6 weeks
Term
if an AKI patient has hyperkalemia what should you do
Definition
get an EKG stop all K sources
use diuretics, sodium polystyrene
if moderate use insulin and glucose, NaHCO3, beta agonists (albuterol)
if severe all above as well as IV Ca and dialysis
Term
if patient has metabolic acidosis what should you do
Definition
give HCO3 (half the calculated dose)
Term
for renal replacement therapy what are the AEIOU
Definition
A- acid base imbalance (metabolic acidosis)
E electolytes (hyperkalemia)
I intoxication (salicylate, lithium)
O fluid overload
Uremia
Term
what are all the monitoring parameters for AKI
Definition
fluids, weight, vitals, blood chem, drug concentrations, urinalysis
Term
what are some susceptibility factors for CKD
Definition
>65, ethnic minority, smoker, reduced kidney mass, family history of kidney disease
Term
what are the most common initiating factors of CKD
Definition
diabetes, hypertension, drug toxicity, autoimmune disease, polycystic kidney disease
Term
what is intrinsic damage in CKD
Definition
damage to any part of the nephron
Term
what is adaption as it pertains to the intact nephron hypothesis
Definition
the remaining nephrons componsate for the decreased number of functional units
Term
what is a result of nephron adaption and what is the physiological result of nephron loss
Definition
nephron adaption will show an increase in creatinine and nitrogenous waste accumulation proportional to lost nephrons
the manifestation is a decrease in GFR
Term
what contributes to the progression of CKD
Definition
nephron injury, glomerular hypertension, hyperfiltration, angiotensin, proteinuria, scarring
Term
how does and ACE inhibitor work
Definition
it blocks the renin pathway not allowing angiotensin 1 changing into angiotensin 2
Term
how does an ARB work
Definition
this will essentially block angiotensin 2 from binding to the receptor negating it's activity
Term
what are the beneficial effects of blocking angiotensin 2
Definition
Decreases urinary protein excretion
Decreases glomerular and systemic pressure
Decreases fibrinogenesis
Decreases the risk of serum creatinine doubling
Decreases cardiovascular events
Term
where is erythropoietin produced
Definition
kidneys
Term
what is the main cause of anemia in CKD
Definition
decreased production of erthropoetin
Term
how does uremia contribute to anemia
Definition
inhibits the proliferation and differentiation of erythroid precursars
Term
when using an ESa to treat anemia what do you need to do first
Definition
make sure the patient has adequete levels of "building blocks" Fe, B12, folate
Term
when should you begin anemia screening in CKD
Definition
stage 1
Term
at what hemoglobin llevels should a patient be considered anemic (and require an anemia workup)
Definition
men hemoglobin<13.5 g/dl
females hemoglobin <12g/dl
Term
in CKD why is erthyropoietin levels not useful in diagnosing or classifying anemia
Definition
since uremia makes receptors less receptive
Term
when using ESA's what is the target HB level
Definition
10-12g/dl (should not be greater then 13)
Term
what are the most important iron measurements for an anemic patient with CKD
Definition
ferritin and transferrin saturation
Term
what are the goals of treating an anemic patient with CKB
Definition
maintain an adequete level of hemoglobin (not to normalize)
treat any underlying causes
prevent hypoxia complications
Term
when classifying someone with CKD as having metabolic bond disease what are the three manifestations used (can have 1 or combo of three)
Definition
Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism

Abnormalities in bone turnover, mineralization, volume, linear growth, or strength

Vascular or other soft-tissue calcification
Term
what is osteodystrophy
Definition
an alteration of born morphology
Term
what is osteitis fibrosa
Definition
enhanced osteoclast activity and bone absorption caused by excess PTH
Term
what is adynamic bone disorder
Definition
this is a suppression of PTH and decreases the amount of bone turnover
Term
what is osteomalaccia
Definition
this is defective minerlization typically due to aluminum overload or vit D deficiency
Term
how will you diagnose CKD-MBD
Definition
measure serum PTH and bone specefic alkaline phosphatase
Term
what are the diagnostic tests to diagnose renal osteodystrophy
Definition
serum biomarkers
bone biopsy (gold standard)
Term
what is TMV
Definition
turnover
mineralization
volume
used to classify renal osteodystrophy as a result of a bone biopsy
Term
which type of vascular classification results in the lowest survival rate
Definition
arterial intima calcification
Term
describe the steps in vascular calcification
Definition
during uremia you will have increased phosphorus levels, this will allow Cbfa-1 to bring osteoblasts into the smooth muscle where they will then develop matrix with collagen and non-collagen, this will allow the risk factors that will start to deposit (increased CA, P)
Term
how will we manage nonskeletal calcifications complications
Definition
maintain Ca, phosphorus, vit D, PTH within normal ranges
manage cardiovascular risk factors
strict management and monitoring of drug therapy
Term
describe the progression of chronic renal failure / uremic syndrome
Definition
glomerular breakdown-> increased capillary permeability-> proteinuria, inflammation, fibrosis-> biochemical abnormalities, bone disorders
Term
list uremic syndrome complications
Definition
anemia, malnutrition, fluid electorlyte disorder, cardiac disease, bone metabolism disorders, hypertension, hyperlipidemia
Term
kidney dysfunction and uremic syndrome result in biochemical abnormalities leading to bone and vascular issues, what are they
Definition
decreased vit D synthesis and activity
impaired Ca and P homeostasis
overactive parathyroid gland
Term
describe how you activate vitamin D
Definition
sunlight transforms 7-hydrocholesterol to cholecalciferol (vit D3)
in the liver a hydroxy is added to form calcidiol
finally in the kidney 1 alpha hydroxylase adds a second hydroxy to form active 1,25 dihydroxyvitamin d3 (calcitriol)
Term
ergocalciferol and cholecalciferol are what
Definition
vitamin D prohormones
Term
what is the normal activity of vitamin D
Definition
to act on parathyroid gland causing a release of PTH
Term
what are the results of stage 1-3 CKD on vitamin D
Definition
decreased production of calcidiol
decreased 1 alpha hydroxylase activity
Term
what is the affect of stages 3-5 CKD on vitamin D
Definition
little to no 1-alpha hydroxylase activity
and parathyroid gland resistance to calcitriol
Term
describe what is happening with fibroblast growth factor 23 in uremia
Definition
phosphate is not responive to FGF23 leading to a progressive increase in FGF23
Term
what contributes to hypocalcemia in CRF/uremia
Definition
phosphate retention (binds Ca)
decreased vit D
parathyroid becomes resistant to Ca
increased levels of PTH
Term
when measuring vitamin D which analog is clinically relevant measure of vit D statud
Definition
calcidiol
Term
what is the normal range for Ca
Definition
8.5-10.2
Term
how do we measure parathyroid hormone
Definition
using IPTH
or the more accurate alkaline phosphatases
Term
where is the majority of Na and HCO3 absorbed
Definition
proximal tubule
Term
what is the main driving source for conserving electrolytes
Definition
Na/K transporter using ATP to exachange Na for K+
.

++
Term
aside from exchanging Na for K what does the Na/K ATPase do
Definition
sets up conditions to help reabsorb water based on solute concentrations
Term
in the thick ascending limb of the loop of henle what reabosrbs NaCl
Definition
NA/K/2Cl cotransporter
Term
what establishes the counter current multiplier
Definition
Na/K atpase transporter, Na/K/2Cl co transporter
Term
what is a driving force for reabsorbing water
Definition
since the water becomes hypotonic once it passes through the medular regions pores will open exposing high concentration of solutes and creating reabsorption of water
Term
where does a loop diuretic work
Definition
Na/K/2Cl in the ascending loop of henle (also disrupts the CCM)
Term
how much cardiac output goes through the kidneys every minute
Definition
1/5 of cardiac output (1 liter/min)
Term
electrolytes in the ultrafiltrate are excreted from where to where in the proximal tubule
Definition
from the lumen to the interstitial fluid
Term
in the distal tubule what measures the Na concentration and where do they communicate this info
Definition
the macula densa cells can detect Na levels and communicate it to the juxtaglomerular apparatus
Term
where is renin released (angiotensin precursor)
Definition
juxtaglomerular apparatus
Term
how does vasopressin (ADH) conserve water
Definition
it opens up the aqua pores allowing the hypotonic ultrafiltrate to force water out via concentration gradients
Term
what 6 things do you need for the counter current multiplier mechanism
Definition
  1. meager blood supply
  2.  nephrons arranged in a way to interact with one another
  3.  active transport for Na in the ascending loop of henle
  4.  differnetial permeability in the loop of henle (descending is freely permeable while ascending is not permeable to water)
  5. Differential permeability to water in the distal tubule, collecting tubule, and collecting duct  depending on the presence or absence of antidiuretic hormone (ADH, Vasopressin).

    ØIn the presence of ADH the DT, CT and CD are permeable to water.
    ØIn the absence of ADH the DT, CT and CD are impermeable to water.
    6.  recirculation and concentration of urea
Term
how does vasopressin creat aquaporin
Definition

coupling to V2 receptors activating GS-adenylyl cyclase-cAMP-PKA pathway

 

Term
what is amiloride
Definition
a channel blocker
Term
why would you use an osmotic diuretic
Definition
for acute situations like poisoning
Term
explain how loop diuretics work (furosemide)
Definition

they cause 15-20% od filtered Na to be excreted, as well as lots of water, K, Ca

they block the NA/K/2cl co transporter in the thick ascending limb to be inhibited

Term
what blocks the aldosterone dependent channels
Definition
spironolactone
Term
how long will carbonic anhydrase inhibitors be active for
Definition
a few days since it will deplete bicarb
Term
how will carbonic anhydrase get sodium bicarb from the lumen to the urine
Definition
NaHCO3 loses Na picks up a hydrogen then carbonic anhydrase will break it up to H2O and CO2 which can easily pass the membrane onse through carbonic anhydrase will reform H2CO3 then eventually NAHCO3
Term
diuretics can cause hypokalemia how
Definition
it decreases Na in the loop of henle causing further down the line a frantic attempt to restore Na by pushing out K
Term
when would you use a loop diuretic
Definition
acute pulmonary edema, hypercalcemia, congestive heart failure, hypertension, renal failure, chemical intoxication
Term
what would you use a thiazide for
Definition
heart failurre, renal failure, hypercalciuria, diabetes, hypertension
Term
what are the unwanted side affects of a loop diuretic
Definition
hypokalaemia, metabolic alkalosis, hypovolameia,0 temporary deafness, retention of lithium, displacement of plasma bound drugs, cross sensitivity with sulfa drugs
Term
how does a thiazide work
Definition
they inhibit the Na/Cl cotransporter in distal convoluted tubule 
Term
what is the side effects of a thiazide
Definition
hypokalaemia (can lead to hyperglycemia), metabolic alkalosis, retention of lithium, elevated uric acid and lipids, cross sensitivity to sulfa drugs
Term
what are examples of K sparing diuretic
Definition
triamterene, amiloride, spironolactone
Term
how can a thiazide cause a gouty attack
Definition
they are are organic acids and compete with uric acid in renal handling causing plasma concentration of uric acid to increase
Term
what is the mechanism of action for the loop diuretics
Definition
block the Na/K/2Cl transporter this will also create an isotonic solution in the interstitium which will force out more water
Term
what are the two mechanism of action for K sparing diuretics
Definition

1.) sodium channel blocker

2.) aldosterone receptor blockers

Term
what are some side effects of K sparing diuretics
Definition
impotence, decreased libido, gynecomastia, menstrual irregularities, hyperkalemia
Term
what is a good diuretic combo and why would you do this
Definition

loop diuretic with a thiazide

this is done to overcome tolerance

Term
how does hypokalemia effect loop diuretic action
Definition
you will develop tolerance since you really need K to bind to expose the second Cl site where the action of the drug is
Term
what is the concept of using an osmotic diuretic
Definition
put a high concentration of anontoxic, not metabolized, freely filtered by glomerulus and not reabsorbed from renal tubule
Term
how does an osmotic diuretic work
Definition
the high osmotic gradient developed in the vascular system will draw in water and brings the water through the kidneys with it
Term
what are some issues with using osmotic diuretics
Definition
cardiovascular overload, hypersensitivity, inablity to clear the agent
Term
what is the target of the vasopressin receptor antagonist
Definition
V2 receptor in the collecting duct
Term
what are the effects of the carbonic anhdrase inhibitors on  acid base balance and K
Definition

depletes base and retains hydrogen cause metabolic acidosis

 

acidosis causes a shift in intracellular H/K and increased Na/K exchange causing hypokalemia

Term
wht would you use a carbonic anhydase inhibitor
Definition
glaucoma, epilepsy, alkalinize urine
Term
the Na/K co-transporter is driven by ATP under the influence of
Definition
aldosterone
Term
the Na/K/2CL transporter is principle mech for conservation of water in concert with
Definition
ADH
Term
when dealing with net filtration what will you use
Definition
glomerular hydrostatic force-( COP+ bowmans capsular preassure)
Term
the clearance of inulin will show you what
Definition
GFR
Term
what is the measure of renal plasma flow
Definition
CPAH
Term
how can you calculate renal blood flow
Definition
CPAH/hematocrit
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