Flashcards in tc4 Deck (65):
what 3 substances can cause overestimation of GFR by serum creatinine levels?
these competitively inhibit tubular Cr secretion
what 4 meds can cause prerenal aki by decreasing renal blood flow
is urine Na and bun/cr ratio high or low in prerenal AKI? why?
Na is low (<20). ratio is high aka >20:1. both bc RAAS
is urine Na and bun/cr ratio high or low in ischemic ATN? why?
Urine Na is high >40. ratio is normal. both bc damaged tubules are unable to reabsorb properly.
3 general mechanisms that contrast induces AKI
1. constrict afferent arteriole and vasa recta -> lower GFR and blood flow to blood vessels
2. high osmolality so kidney has to work harder -> raise O2 demand of kidney
3. increase ROS, decrease antioxidants -> oxidative stress/damage
what do you give to patients before contrast to reduce risk of ATN AKI?
N-acetylcystine (antioxidant properties, promotes renal vasodilation) and isotonic saline (dehydration/low ECF is a risk factor)
in pigment nephropathy, filtered myoglobin precipitates with _____. causing tubular obstruction. what is the treatment for this?
precipitates with Tamm-Horsfall protein
treat by alkalinizing urine. it decreases precipitation
rhabdomyolysis is what causes pigment nephropathy (the myoglobin and hemoglobin come out into blood from muscles). but what are causes of rhabdomyolysis that aren't obvious? (2)
1. hmg coa reductase inhibitor aka statins
2. alcohol and drugs (like cocaine)
whats that thing that you have coke/tea colored urine and strip test is positive for blood. but if you do microscopy there's no red blood cells?
pigment nephropathy. it's bc of the myoglobin/hemoglobin.
Serum creatinine peaks within how many days of contrast induced AKI? returns to normal by when?
peaks in 5 days. normal in 7-10 days
what can cause AKI without oliguria
aminoglycosides nephrotoxicity. it's bc afferent arteriole constriction is not a major player in this pathophysiology so GFR isn't as decreased as in other AKIs. but AGs do constrict mesangial cells which causes mild decrease in GFR
2 main mechanisms of AG nephrotoxicity
1. constrict mesangial cells -> mildly lower GFR
2. principal cells take up AGs very concentrated. reduces ability to concentrate urine -> urine osmolalitly 300-350 (same as in glomerulus/plasma basically)
what casts do you see or not see in PRERENAL AKI?
ONLY see hyaline casts! which are NORMAL. made of Tamm Horsfall proteins (which precipitate with myoglobin in pigment nephropathy btw)
what casts in urine for ischemic ATN?
muddy brown granular casts and tubular cell casts
what things and casts in urine for glomerulonephritis?
proteinuria, RBCs, and RBC casts
serum phosphate is regulated by renal reabsorption or secretion?
serum K+ is regulated by renal reabsorption or secretion?
secretiooonnnn. can increase secretion if hyperkalemia.
kidney dz patient on ACEI or ARB or K+ sparing diuretic is bad news -> hyperkalemia
heart failure or liver failure pt on NSAID or ACEI or ARBs is bad news -> acute kidney injury
these are some important "pt has underlying condition and you put them on this drug and bad things happen" examples
synthesis of what amino acid by intact nephrons maintains elevated NH4+ urinary excretion in compensated CKD?
glutamine synthesis. idk why
which 2 mediators cause unregulated/fixed Na excretion in CKD? pg 432
NPs and PGE2
so if Na excretion > intake, pt will have orthostatic hypotension (hypovolemic state). if intake >excretion, pt will have edema and hypertension (hypervolemic state)
THIS IS NOT WHAT CAUSES HYPER OR HYPONATREMIA BC REMEMBER THAT'S A WATER BALANCE ISSUE, NOT NA+ even tho its all related what the heck
why does CKD continue to progress even if you remove initial insult/offender?
high SNGFR of intact nephrons = intraglomerular hypertension. this leads to hyperfiltration injury -> proteins deposited in mesangium and tubules (also NH4+, which activates alternative complement pathway, furthering inflammation and injury) -> glomerular sclerosis and tubular fibrosis = irreversible changes. GG.
bts this makes kidneys shrink so small shrunken kidneys are end stage CKD kidneys even tho in the beginning you have hypertrophic intact nephrons
in CKD you get LVH. which 2 things predisposes you to eccentric LVH? which one for concentric LVH?
eccentric: chronic anemia and volume overload (which you can both get from CKD)
concentric: CKD related Hypertension. obvis, from CKD.
its a never ending cycle gah
bad things hyper PTH does.
2. neuro calcium overload -> polyneuropathy and encephalopathy
3. bone bone disorders (osteitis fibrosa cystica)
guy has CKD, comes in with FEVER and PRECORDIAL CHEST PAIN that's worse with breathing and laying down. what is it??
uremic pericarditis. +- pericardial friction rub +- cardiac tamponade (will then have pulsus and electrical alternans where QRS goes up and down, inverted, right way up again, back and forth)
what does CKD do to blood lipids?
VLDL and TAGs increase
LDL IS UNCHANGED. unless nephrotic proteinuria present
what happens to sex hormones CKD? clinical presentation?
estrogen and progesterone and testosterone are low
thus, LH and FSH are high (but in women no LH spike so no ovulation)
both genders have hypogonadism and are infertile
which serum biomarkers are elevated in 2ndry hyperPTH osteitis fibrosa cystica?
osteoblasts -> alkaline phosphatase and osteocalcin
osteoclasts -> tartrate resistant acid phophatase (TRAP)
what is the threshold of (serum Ca2+) X (serum phophate) when tissue calcification starts happening?
> 55 mg2/dL2
the 4 mechanisms causing pruritus in CKD
1. inflammatory cytokines
2. excess beta endorphins
3. increased mast cells, they release histamine
4. dermal calcifications from excess PTH irritate sensory nerve endings
the 3 pulmonary manifestations of CKD and their mechanisms
1. restrictive lung dz from pulmonary calcification and fibrosis
2. uremic penumonitis = cytokine mediated permeability lung edema. PAWP IS NORMAL TO LOW
3. serosanguinous pleural effusions in stage 4 and 5
which variables in starling forces equation does inflammation alter?
Kf (fluid permeability)
S - surface area of capillary
sigma (protein permeability)
OPis - interstitial osmotic pressure (bc its affected by permeability)
in nephrotic syndrome, the pathogensis for edema differs if serum albumin is above or below 2.0 g/dL. if it's >2, what is stimulating increase in Na reabsorption and where in the nephron is it happening? what about for <2?
>2: proteolytic enzymes like plasminogen/plasmin stimulate ENaC in cortical collecting duct -> Na reabsorption increases -> increased HPc
<2: decreased capillary oncotic pressure. then, hypovolemia -> RAAS -> aldosterone -> stimulate ENaC in CCD
hemodynamic findings (increased, decreased, or normal) during acute exacerbation of COPD (which will cause edema): ECV, CO, JVP, SVR/BP, PaCO2
ECV decreased (bc edema and its acute so body doesn't have time to adjust)
CO high (to compensate)
JVP normal to low
SVR/BP: decreased (b/c CO2 is increased which is a vasodilator). btw this is vasodilation theory/mechanism that initiates edema in this case
just think of it ias paCO2 is the primary increase and everything is following or compensating for that.
so far i 've only come across one thing that causes edema that doesn't involve increased RAAS. what is it.
nephrotic syndrome where serum albumin >2 g/dL
3 theories/mechanisms by which hepatic cirrhosis causes decreased Na excretion. remember theyre named by the INITIATING EVENT that caused the decrease in Na excretion
1. vascular underfill: hepatic venous obstruction -> edema -> hypovolemia -> RAAS
2. vasodilation theory: lots of vasodilators in cirrhosis for some reason -> decrease ECV -> activate RAAS
3. hepatic venous outflow obstruction -> activate intra sinusoidal baroreceptors -> activate SNS -> activate RAAS ->
drug of choice for edema caused by hepatic cirrhosis and why
spironolactone. bc its an aldosterone inhibitor. bc RAAS is the major factor. btw this is what you need in idiopathic edema. other diuretics will only increase aldosterone and thats bad
4 mechanisms of hypothyroidism caused edema (myxedema)
1. decreased albumin synthesis. lowers plasma oncotic pressure. OPc and OPis difference increases
2. decreased sigma (increased protein permeability)
3. lymphatic flow is sluggish
4. mucopolysaccharides bind water, prevent removal by lymphatics and makes it nonpitting
mechanism of idiopathic edema
1. dilation of precapillary sphincters
2. decrease in sigma (increased protein permeability) -> edema -> VASCULAR UNDERFILLING -> RAAS
is vascular overfilling or underfilling responsible for NSAID induced edema?
which nuclei are responsible for regulating plasma osmolality and volume?
osmolality: supraoptic nucleus
volume: periventricular nucleus
what senses change in ECF tonicity? what senses change ECF volume?
tonicity: hypothalamic osmoreceptors
volume: arterial baroreceptors, JG baroreceptors, atrial volume receptors
what drugs can cause SIADH
what category of hyponatremia does it fall under
cancer drugs (vincristine, cyclophophamide), psychoactive drugs (SSRIs, amitriptyline, phenothiazines), other drugs (NSAIDs, opioids, carbamazepine)
hypotonic isovolemic hyponatremia.
acute and refractory treatments for SIADH.
acute: h20 restriction, furosemide + NaCl
refractory: tolvaptan (v2 antagonist, aquaretic), and Demeclocycline (causes ADH resistance aka diabetes insipidus in a normal person)
dominant clinical presentation in hyponatremia
the main problem is brain cells are swelling so you get neuro and neuromuscular symptoms like asterixis, confusion, seizures, muscle fasciculations, dilated pupils, Babiski signs. cns swelling also causes anorexia, nausea, vomiting, and tentorial cerebral herniation! can also have cheyne-stokes respirations if severe/very acute
no ECG findings,
chronic hyponatremia causes increased risk of hip fractures, especially in elderly. why?
CNS impairment causes confusion and unsteady gait so they fall more
chronic hyponatremia also causes osteoporosis. so bones break more easily when they do fall
meds that cause nephrogenic diabetes insipidus
demeclocyline (treats SIADH remember)
how do cells adapt to hypernatremia, given a couple of days
they make idiogenic osmoles: glutamine and nyoinositol. they increase intracell tonicity and minimize cell shrinkage
if you correct hyponatremia or hypernatremi too fast what are the consequences.
correct hyponatremia too fast: osmotic demyelination syndrome (seen in acute severe hypernatremia)
correct hypernatremia too fast: cerebral edema (seen in hyponatremia)
where in nephron is 90% of filtered K+ load reabsorbed?
proximal tubules and TAL. this part is not really regulatable. the part you can change is amt of K+ excretion in principal cells (basolateral Na/K ATPase) of cortical connecting tubules and CCD
what are the 2 feed forward mechanisms to protect against hyperkalemia when you eat. these work in 3-5 minutes BEFORE serum K+ increases
1. portal hepatic GI sensors -> increase K+ secretion
2. proteins stimulate pancreas to release glucagon -> stimulates liver to make cAMP -> cAMP increases GFR -> increase K+ secretion
how does high tubular flow rate (caused by diuretics and osmotic diuresis) stimulate K+ secretion?
high flow rate -> primary cilium bends -> raises intracellular calcium -> activate BK channels -> increased K+ secretion
which 4 meds cause hypER kalemia and how?
1. digoxin -> inhibits Na/K ATPase
2. aldosterone antagonists (Spironolactone, ACEI's)
3. beta antagonists - inhibit SNS stimulation of RAAS, and remember beta stimulation causes K uptake into cells
4. NSAIDs - decrease RAAS. especially if used with ACEIs or ARBs
what is the triad that SAME and Liddle syndrome present with?
2. metabolic alkalosis
what is the mutation in Liddle syndrome causing?
gain in function of ENaC in principal cells -> increase Na reabsorption and thus increase K+ and H+ secretion
Gitelman syndrome. I was born with a ______ diuretic .
Bartter syndrome. I was born with a _______ diuretic.
how do they present?
Gitelman = thiazide diuretic. LOF of NaCl cotransport in DCT
Bartter syndrome = loop diuretic. LOF of Na/K/Cl in TAL
both present with hypokalemia, metabolic alkalsosis, and hypOtension (unlike Liddles which has htn but same other 2 signs)
(remember K+ is a vasodilator, naturally comes out of cells during exercise to increase blood flow to muscles). so during hypokalemia, K+ vasodilating effect is not there -> rhabdomyolysis -> pigment nephropathy AKI
hypokalemia decreases phase __a___ current. __b__(inc/dec) Na conductance in Purkinje cells. both cause __c___
a. phase 4 repolarizing current (reduced Na/K atpase activity)
b. increase Na conductance
c. enhanced automaticity/excitability -> tachyarrhythmias
hypokalemia reduces Na/K atpase activity, but it also destroys protein for which other channel? what's the result of this?
for Kir channel. slows repol -> prolong QT interval -> EAD triggered torsades de pointes. SEE ACTION POTENTIAL GRAPH PICTURE
ECG findings in hypokalemia
ST depression (meh can't rlly see it though)
low T wave amplitude (bc slower repol)
increased U wave amplitude
long QT interval (bc slower repol)
later on T wave will invert so don't get U wave confused as T wave, which will still be upright
don't forget about that Atrial tachycardia w/ 2:1 AV block, caused by digoxin toxicity, which youre more prone to when you have hypokalemia bc it increases affinity of cardiac for digoxin.
the atrial tachy w/ av block is due to DAD TRIGGERED ACTIVITY
a. causes depol or hyperpol?
b. leads to increased or decreased membrane excitability?
b. constant depol -> inactivates fast Na channels -> decreased excitability -> muscle weakness
but it can also just depol and increase excitability -> enhanced automaticity in cardiac cells -> tachyarrhythmias
ALSO acute severe hyperkalemia messes up cardiac conduction of fast action potentials -> ventricles can't be excitated -> asystole -> SCD
what does hyperkalemia do to ECG
rapid repol -> tall T waves
decreased cardiac conduction and slower phase 0 depol -> prolong QRS complex, P wave, and PR interval
reduced Ikr current -> shorten QT interval
but..ecg is not a sensitive indicator of hyperkalemia so...normal ECG doesn't exclude hyperkalemia
treatment of acute hyperkalemia. 3 steps
1. calcium gluconate - limit cardiac toxicity
2. nebulized B2 agonist + insulin and glucose -> shift K+ into cells
3. loop diuretic and resin (patiromer or sodium polystyrene sulfate) to increase renal and fecal k+ excretion
treatment of CHRONIC hyperkalemia. 2 steps
1. dietary K+ restriction, discontinue K+ retaining meds
2. loop and thiazide diuretics, and resin to increase renal and fecal K+ excretion