Renal Flashcards
which portion of loop of Henle is impermeable to water?
ascending limb
electrolytes Na+/2K+/Cl- are absorbed via cotransport to maintain corticomedullary gradient.
describe water permeability in loop of henle
glomerular capillaries to descending loop (high and passive permeability)
thick and thin ascending loop (impermeable)
early distal convoluted tubule (low)
late distal convoluted to collecting ducts (regulated by vasopressin)
efferent constriction leads to what changes in GFR and FF? why?
some constriction
complete constriction
FF always increased (b/c RPF goes down
GFR increases at first (more time for filter) and then decreases with complete constriction (protein buildup-increased oncotic pressure)
FF=GFR/RPF
filtration fraction= GRF/renal plasma flow
nephron drug that increase urea reabsorption
vasopressin (ADH)- works in meddullary collecting tubules by increasing number of cell suface urea transporters. This contributes to formation of corticomedullary interstitial osmotic gradient
action at nephron of
inulin
paraaminohippuric acid (PAH)
amino acids
- free filtered and not absorbed or secreted. used to estimate GFR. similar to mannitol
- freely filtered and also secreted- used calculate renal plasma flow. similar to creatinine
deposits seen in which renal glomerulonephropathies:
- C3
- C1q
- IgE
- post-streptococcal glomerulonephritis
- MPGN type 1
- lupus nephritis
light microscopy features associated with Goodpastures Alport's syndrome/MPGN type 1 Minimal change disease Membranous glomerulonephropathy
- crescent formation
- lobular appearance with proliferating mesangial cells and increase mesangial matrix
- normal glomeruli
- uniform diffuse capillary wall thickening
renal toxicity associated with acyclovir, how to treat?
crystalline nephropathy-give aggressive intravenous hydration
VHL gene is found in which chromosome, mutation can lead to
3p, renal cell carcinoma
relationship between GFR and Cr, change in Cr when GFR is
- normal
- decreased
- good rule of thumb
- indirect but it’s not linear. more curved graph.
- if GFR is normal then small changes don’t change Cr
- if GFR is low then small changes change CR substantially
- good rule=every time GFR halves, Cr doubles
cells involved in organ rejection
- hyperacute-mins
- acute-week
- chronic-yrs
- preformed antibodies (i.e. ABO mismatch)
- host t-cells sensitization (histo shows dense infiltrate of mononuclear cells)
- host b-celle sensitization with t-cells sensitization
prevention/treatment of organ rejcetion
calcineurin inhibitors (cyclosporine or tacrolimus) or corticosteroids
renal plasma flow equation vs renal blood flow equation
-plasma volume that flow through kidney per unit time
=PAH clearance=(urine PAH * urine flow rate)/ plasma PAH
-the volume of blood that flows through kidney per unit time. the fraction of blood occupied by plasma is (1-hematocrit)
So, RBF=renal plasma flow divided by the fraction of blood occupied by plasma=(PAH clearance)/ (1-hematocrit)*
hypersensitivity of Goodpasture’s vs acute poststreptococcal glomerulonephritis
- type II: antibodies to basement membrane
- type III: immune complex formation
in horseshoe kidney under which artery does fused pole become trapped under
-inferior mesenteric artery
where is lowest concentration of PAH? why?
in boman’s space.
-b/c it is filtered and then actively secreted into nephron
what is important prognostic factor in poststreptococcal glomerulonephritis? why not corticosteroids?
- age, children tend to recovery more than adults
- not corticosteroids b/c they’re not used. this diseases recovers on it’s own
histological appearance:
- membraneous glomerulopathy
- membranoproliferative glomerulonephritis
- berger disease
- minmal change disease
- diffuse increased thickness of BM on LM without increased cellularity, “spike and dome”on silver stain, granular deposits on IF
- LM: large hypercellular glomeruli
- IF: IgA deposits in mesangium
- no abnormalities on LM or IF. only effacement of foot processes is seen in electron microscopy
effect of ureteral constriction or obstruction on GFR, FF, and RPF
- GFR decreases
- RPF remains the same
- FF decreases
without antidiuretic hormone the tubular fluid is most concentrated where? most dilute?
- junction between descending and ascending limbs of the loop of Henle
- collecting ducts
bilateral blood vessels, smooth muscle and fat in kidney-def associated with what disease other findings?
- renal angiomyolipoma
- tuberous sclerosis-AD inheritance
- cortical tubers, subependymal hamartomas in bran (seizures and mental retardation) cardiac rhabdomyomas, facial angiofibromas and leaf-shaped patches of skin lacking pigment (ash-leaf patches)
bilateral renal cell carcinomas is associated with which AD condition. also look for what 3 findings
Von-Hippel-Lindau disease
also look for cerbellar hemangioblastomas, retinal hemangiomas, and liver cysts
modified smooth muscle cells of the afferent and efferent arteriole are aka
JG cells of JG apparatus.
apparatus also contains macula densa cells (tall narrow cells located in distal tubules)-
role of macula densa and JG cells of JG apparatus
-MD monitor osmolarity and volume of urine that pass into distal tubules and transmit information to JG cells where renin synthesis occurs
renal complication of pelvic surgery. not renal cell carcinoma b/c
- ligated ureters esp in hysterectomies
- can lead to hydronephrosis (flank pain that radiates to groin and causes distention (a palpable mass in kidney on deep palpation))
- RCC presents as a painless hematuria, flank pain and palpable mass
what factors increase risk of nephrolithiasis? which diuretic can prevent this? not acetazolamide or furosemide b/c?
stones are precipitated by high tubular concentration of Ca2+
- thiazide diuretics increase Ca2+ reabsorption from nephron by inhibiting Na+/Cl- transporter on apical side decrease Na+ concentrations and increasing Na+/Ca2+ antiport on basolateral membrane. it also causes hypovolemia which increases Na+ and water reabsorption in the proximal tubule along with passive paracellular Ca2+ reabsorption
- can also use potassium citrate to alkalinize the urine
- acetazolamide causes bicarb wasting at proximal convoluted tubule. this leads to metabolic acidosis and worsens hypercalciuria by causing release of calcium phosphate from bone
- loop diuretics blocks transcellular N+/K+/Cl- reabsorption which inhibits paracellular Ca2+ reabsorption
diuretic of choice in acute settings? why? name 3 common toxicities
loop diuretics b/c loop of Henle has significant resorptive capacity
-common side effects include hypokalemia, hypomagnesemia, and hypocalemia
serum IgG4 antibodies to phospholipase A2 receptor
membraneous nephropathy
winter’s formula- def, when is it used?, give example of when metabolic acidosis is not fully compensated for
- PaCO2= [1.5*HCO3-]+8+/-2
- used in metabolic acidosis to check for appropriate respiratory compensation
- sometimes DKA can lead to respiratory failure and lack of Kussmaul respirations
hyperacute rejection-def, hypersensitivity type, 2 examples, diagnosed when and how? organ appearance
medicated by preformed antibodies against antigens on host organ (type II hypersensitivity)
- ABO blood groups and anti-HLA antibodies
- immediately, diagnosed intra-operatively, mottling of organ
immediate hypersensitivity-hypersensitivity type, characterize immune response, give 4 examples
type I hypersensitivity
- IgE class switching on B-lymphocytes
- anaphylaxis, urticaria, asthma and seasonal allergies
mechanism of toxicity with ethylene glycol
- typical findings
- typical pt pop
- acute renal failure due to precipitation of calcium oxalate crystals in renal tubules
- anion gap metabolic acidosis, increased osmolar gap, calcium oxalate crystals in urine
- homeless alcoholic, oligouria, anorexia and flank pain (3 symptoms of acute renal failure)
muddy brown casts
acute tubular necrosis (ATN)
ischemic ATN-mc pt pop, tubule affect first,
- hospitalized pts with low CO (i.e recent MI)
- both PCT and thick ascending loop are susceptible. PCT more b/c it’s utilizes active ATP transport of ions
are ischemic changes in renal papillae seen in ATN?
no. instead papillary necrosis is assocaited with DM, analgesic nephropathy and sickle cell anemia
which allows for diabetic nephropathy to be diagnosed at the earliest stage?
microalbuminuria-(30-300mg/day in a 24-h collection or 30 to 300 micrograms of protein per milligram of creatinine in a spot collection)
define calcineurin- name two drugs that block it’s activation
- essential protein in activation of IL-2 which promotes growth and differentiation of T cells
- cyclosporine and tacrolimus work by inhibiting calcineurin activation
which organ plays role is digitoxin clearance? not liver b/c
- which pt pop should have decreased dosage?
- what are creatinine levels
- name other symp of dig toxicity
- kidney. liver enzymes have no role in dig clearance
- elderly have age-related renal insuffienciency and thus dose should be lowered
- creatinine levels are normal b/c it’s related to muscle mass and elderly have decreased muscle mass leading to lower levels of creatinine, in renal failure creatinine increases but the levels look normal b/c it was previously reduced
- visual changes and GI disturbances
equation for FF
-normal value in a healthy individual
=GFR/1-Hct
=GFP/RPF
20%
- where is most of K+ filtered by glomeruli resorbed
- name primary site of regulation of K+ urine concentration
- name 4 things that can cause increased K+ excretion
- proximal tubule (2/3rds of filtered amt) and loop of Henle (2/3rds of remaining filtered amt) regardless of K+ serum levels
- late distal and cortical collecting tubules via alpha intercalated cells (reabsorb) and principal cells (secrete)
- high serum K+, increased aldosterone, alkalosis (principal and alpha intercalated cells promote K+ entry for H+ exit and increased intracellular K+ levels promotes K+ secretion), increased fluid flow (diuretics or volume overload)
NSAIDs-assocaited chronic renal injury manifests how? glomerular and vascular abnormalities? pt pop
- papillary necrosis (NSAIDs concentrate in renal medulla and decreased PG synthesis leads to constriction of medullar vasa recta promoting ischemia)
- chronic interstitial nephritis (uncouple oxidative phosphorylation in renal mito causing direct cell damage)
- there is usually mild glomerular and vascular abnormalities seen in advanced stages
- suffering from chronic pain
which class of diuretics can cause pulmonary edema if used in excess? why?
- mannitol or any other osmotic diuretic
- works by increasing plasma or tubular osmolality, normally this leads to increased diuresis, however if too much is given then increase plasma osmolarity can lead to pulmonary edema
which trail results support that addition of low dose diuretic leads to increased overall survival in pts with CHF? which drug is this? what is proposed mech of benefit? is it certain?
RALES trial
- spironolactone for class III and IV CHF pts
- more likely secondary to inhibition of neurohormonal effects of aldosterone (which can cause ventricular remodeling and cardiac fibrosis)
electrolyte disturbances seen in amphotericin B. mech of these metabolic changes?
- hypokalemia and hypomagnesemia
- can lead to EKG changes
- increase in distal tubular membrane permeability due to renal tubular dysfunction caused by amp b
mech of salicylate metabolic disturbance-early, late, vomiting causes
- 1st causes acute respiratory alkalosis due to stimulation of respiratory center and hyperventilation
- later on build of organic acids (ketoacids, lactat, and pyruvate) causes and anion gap metabolic acidosis
- can also be sight metabolic alkalosis due to volume contraction from vomits
expected values of solute filtered vs substance excreted for
- glucose
- PAH
- inulin
- sodium
- urea
- full resorbed up to 200 (at which glucosuria begins) and then after 375 all transports are fully saturated (Tm)
- completely secreted, estimate for RPF. substance excreted is higher than substance filtered every time
- neither absorbed or secreted. amt filtered=amt excreted
- fractional excretion is abt 1% so amt excreted is 1% of amt filtered
- 40-50% is reabsorbed (or 50-60% excreted) so amt excreted is 55% amt filtered
complication of nephrotic syndrome characterized by sudden onset flank pain, hematuria, and left sides varicocele
-thrombus in renal vein due to loss of antithrombin II causing hypercoagulable state
organs effect by Henoch-Schonlein purpura
GI-abdominal pain
Kidneys-IgA nephropathy (similar to Berger disease) (episodic hematuria)
Skin-palapable purpura on buttocks and lower extremities
Joints arthralgias and arthritis in large joint of lower extremities (ankle and knee joints)
cresent formation on light microscopy
RPGN
name three type of RPGN- antibodies and diseases associated with them
type 1=anti glomerular basement membrane anitbodies (liner GBM deposits of IgG and C3) (Goodpastures)
type 2=immune complex mediated “lumpy bumpy” (PSGN, SLE, IGA nephropathy, or henoch-schonlein purpura)
type 3=pauci immune, just c-ANCA in serum (granulomatosis with polyangiitis-wegener’s)
types of proteinuria
- selective
- tubular
- overload
- functional
- orthostatic
- isolated
- minimal change disease or another problem with glomerulus. albumin in urine
- presence of low molecular weight proteins due to proximal tubular destruction
- protein in urine due to over production, multiple myleoma
- increased protein excretion in tall,thin aldolescents
- incidental finding in asymptomatic person with normal renal function and urinary sediment
tumor lysis syndrome-def, metabolic disturbances, renal disturbances where? prevent how?
- high cell turnover treated with chemo cause lysis of intracellular contents
- potassium, phosphorus, and uric acid increase in serum
- uric acid precipitates in acidic environment of distal tubules and collecting ducts
- prevent with alkalization and hydration
uric acid is a metabolite from what in tumors?
tumor nucleic acid
role of NH4+ and H2PO4- in kidney’s attempt to correct metabolic acidosis
-these are examples of titratable acids or buffers these help to increase amt of H in urine without excessing pH limit of 45.
diseases assocaited with spacitiy
- Lesch-Nyhan
- Niemann-Pick disease
Fabry disease- def, early mainfestations, late complication
- inherited deficiency in alpha-galacosidase A that causes accumulation of globoside ceramide trihexoside in tissues
- angiokeratomas, hypohidrosis (low sweating), and acroparesthesia
define angiokeratomas
punctate, dark red, non blanching macules and panules that classically occur between umbilicus and knees
define acroparesthesia
episodic burning neuropathic pain in extremeties
CT appearance of AKPD? when do symptoms present? where else can cysts be found?
- homogenous with regular outline and nonenhancing with contrast CT vs mets
- 4-5 decade of life
- can also have hepatic cysts
which is more reproductive side effects spironolactone or eplerenone? name 3
spironolactone
-gynecomastia, decreased libido, and impotence
diffusion across glomerular membrane is directly related to and indirectly related to
- direct: concentration difference, total membrane surface area, and solubility of substance
- inverse: total membrane thickness and molecular weight of molecule (square root of it)
name two mechanisms by which furosemide increases GFR. one of mechanisms inhibited by?
- inhibiting Na-K-2Cl sympoter in loop of Henle
- stimulating PGs release, leading to efferent dilation (increased GFR and RBF)
- NSAIDs can limit PGs stimulation effect
imaging useful in minimal change disease
- electron microscopy shows foot processes effacement
- normal IF and LM
calculate Relative risk. how is 2x2 table arranged. calculate odds ratio
- [a/(a+b)]/[c/(c+d)]
- exposure in rows and outcome in columns
- ad/bc
clearance calculation used to calculate FF
- (urine concentration*urine flow rate)/ plasma concentration
- FF=GFR/RPF
- clearance of creatinine or inulin approximate GFR
- clearance of PAH approximates RPF
left kidney lies immediately deep to which rib
- spleen?
- liver?
tip of rib 12
- left 9th, 10th and 11th rib
- right side upper quadrant (8-11th rib)
name examples of causes of HTN and hypokalemia due to increased levels of renin and aldosterone
- secondary hyperaldosteronism
- renovascular dz
- malignant HTN
- renin secreting tumor
- diurectic use
name examples of causes of HTN and hypokalemia due to decreased renin and increased aldosteronone
primary hyperaldo
- aldosterone secreting tumor
- bilateral adrenal hyperplasia
-name examples of causes of HTN and hypokalemia due to decreased renin or aldo
non-aldo causes
- congenital adrenal hyperplasia
- deoxycorticosterone-producing adrenal tumor
- Cushing syndrome
- exogenous mineralcorticoids
major side effects of commonly used diuretics -loops diuretics -thiazide -potassium carbonic anhydrase inhibitors -osmotic diurectics
- hypokalemia, hypomagneseia, hypocalcemia, and ototoxicity
- hypokalemia, hyponatriemia, hyperuricemia, and hypercalcemia
- hyperkalemia (spironolactone can also cause gynecomastia and antiandrogen effects)
- metabolic acidosis
- hypernaturemia, pulmonary edema
uses for
- loops
- thiazide diuretics
- carbonic anhydrase inhibitors
- sodium channel blockers
- mineralocorticoid receptor antagonists
- volume-overloaded states (CHF)
- HTN, calcium nephrolitiasis prophylaxis
- refractory metabolic alkalosis and intracranial HTN
- last two are used in synergy with loop and thiazide diuretics to limit potassium loss
multicystic kidney dysplasia-def, absence of? atresia where? effect on kidney?
- multiple cysts of varying size in kidney and absence of normal pelvocaliceal system
- uretheral or uretropelvic atresia
- affected kidney is nonfunctional
action of ADH hormone in urea and water absorption. mech of urea
increase their absorption allowing for maximally concentrated urine
-increased passive urea transporter in inner medullary collecting duct allows for substantial fraction of high concentrated urea to diffuse down it’s gradient to medullary interstitium where is contributes to medulla osmolarity pulling more water from tubules
mc end result of ATN? other result
- tubular re-epithelizaiton and regain renal function
- if associaited with multi organ failure, renal func may be permanently impaired (foci of interstitial scarring)
histology of PSGN. lab findings
- hypercellular glomerulus on LM
- lumpy bumpy granular deposits of IgG and C3 on IF
- electron dense on epithelial side of basal membrane on EM
- anti-streptolysin O (ASO) titers, anti-DNase B titers, decreased C3 and total complement levels, cryoglobulins, C4 is normal
consider MM in which pt, presenting with which symptoms?
- easy fatiguability (anemia)
- constipation (hypercalcemia)
- bone pain (osteoclast activating factor from myeloma cells and bone lysis)
- renal failure (bence jones protein and gammglobulin amyloidosis)
mutltiple myeloma vs hypersensitivity interstitial nephritis
- mm has eosinophilic casts composed of bence jones protein (blue color)
- HIN has eosinophil CELL casts (inflammatory cells)
how to PAH secreted in tubules?
- carrier protein mediated process
- can be saturated at high blood concentrations
can filtration of PAH be saturated
no, at an give blood concentration a constant portion of PAH will be filtered
crescents in RPGN are made up of?
- parietal cells
- macs
- monocytes
- fibrin
toxicity of Amp B
-renal toxicity can lead to severe hypokalemia and hypomagnesemia
pyruvate to acetyl Coa
pyruvate to oxaloacetate
pyruvate to lactic acid
- pyruvate dehydrogenase (aerobic)
- pyruvate carboxylase (gluconeogenesis)
- lactate dehydrogenase (anaerobic)
loop diuretic with highest risk of otoxicity? risk increased with what 2 factors? what other drugs can cause this? reversible?
- furosemide or ethacrynic acid
- can occur with higher dosages, rapid IV administration or
- when used in combination with other ototoxic agents (aminoglycosides, salicylates, and cisplatin)
- usually reversible
smoking is a risk factor for which type of GU cancer? what about rubber exposure
- smoking is risk for both RCC and transitional cell cancer
- only transitional cell
