Renal Flashcards
ureters and uterine arteries
water under the bridge
ureters pass under and behind the uterine arteries (and veins) and the vas deferens
gyn procedures may damage ureter
ureter starts anterior to the internal iliac (in the true pelvis) and then courses posterior to the uterine artery
note: gonadal arteries come off the aorta - below the level of the renal arteries
- first posterior to the gonadal artery
- then medial
JG apparatus
mesangial cells + JG cells (modified smooth muscle cells of afferent arteriole) + macula densa (at tip of thick ascending limb)
macula densa - senses NaCl concentration of filtrate
- decreased in NaCl concentration = not enough fluid was filtered –>
1) decreases resistance to blood flow in afferent arterioles –> returns GFR to normal
2) increases renin release
macula densa
senses decreased NaCl delivery to DCT –> adenosine release –> vasoconstriction
calcitriol
produced by the PCT cells
Cr and eGFR
Cr is freely filtered - also secreted to a small extent
afferent arteriole
juxtaglomerular cells
more a1 receptors on afferent arteriole
ang 2
renin - released in response to DEcreased volume (so decreased BP, decreased Na delivery to macula densa, increased SNS/b1 tone)
- b-blockers (and clonidine) decrease renin secretion
vasoconstricts - efferent and afferent arterioles, low levels increase GFR, high levels decrease GFR
-ang2 protects GFR during vasoconstriction - because efferent arteriole constricts more
stimulates Na/H exchange in PCT - contraction alkalosis
pressor effects - vasoconstricts by acting on AT1 receptors on vascular smooth muscle
-affects baroreceptor function so reflex bradycardia does not occur
aldosterone secretion
stimulates hypothalamus + ADH secretion
PGs
E2 and I2 are produced by kidneys
vasodilation of afferent and efferent
activated by stimuli that activate SNS and RAAS - modulate vasoconstriction, which would otherwise lead to renal failure
dopamine
acts like a rest and digest hormone at low levels
- dilates cerebral, cardiac, splanchnic, and renal arterioles
- constricts skeletal muscle and cutaneous arterioles
can be administered during hemorrhage
adenosine
vasoconstricts
ATP, thromboxane also vasoconstricts
other vasoconstrictors: endothelin
Hartnup disease
AR - inability to reabsorb tryptophan –> niacin deficiency
- pellagra-like symptoms = 4Ds - diarrhea, dementia (and hallucinations), dermatitis (C3/C4 broad collar rash), hyperpigmentation of sun-exposed limbs, death
urea handling
passive reabsorption (with water)
thin descending loop - urea secreted (into the lumen)
- UT1 transporter is activated by ADH - inserted into inner medullary cortical ducts
- corticocapillary osmotic gradient increases in the presence of ADH
thick ascending onwards - IMPERMEABLE to urea
morphine
organic base
organic acids and bases are excreted in proximal tubule
-treat aspirin OD by alkalinizing urine
resorptive functions of kidney
early PCT - NaHCO3- (glucose, aas, acids/etc.), lumen has negative charge (loss of Na+, glucose)
-phosphate, Ca2+
late PCT - NaCl, paracellular Cl- transport, lumen negative (Na+ follows into blood)
thin descending limb - permeable to water and urea (water moves out of tubule, solutes move into tubule)
thin ascending limb - permeable to NaCl, impermeable to water
thick ascending limb - impermeable to water, Na/K/2Cl transporter
- K+ and Cl- diffuse in blood, some K+ leaks back into lumen (lumen positive)
- lumen postive!! - drives Ca2+ and Mg2+ reabsorption
- loop diuretics bind at Cl- site
early DCT - impermeable to water, NaCl transporter
- thiazides act here
- there is also an Na/Ca antiporter on the BL membrane - activated by PTH
late DCT and collecting ducts
- principal cells (Na+ reabsorption and K+ secretion)
- a-intercalated cells (K+ reabsorption and H+ secretion)
- aldosterone and ADH (controls permeability of principal cells)
other things:
- SNS - vasoconstricts afferent arterioles, increased proximal tubule reabsorption
- ANP (acts via cGMP) - respond to increased volume
- vasodil and decreased Na+ reabsorption in late distal tubules and collecting ducts
- dilates afferent, constricts efferent, contributes to aldosterone escape mechanism - BNP - responds to increased tension, good negative predictive value for heart failure
- nesiritide is a BNP analog - used in acute decompensated heart failure
PTH
inhibits! Na-phosphate reabsorption
-binds to BL Gs-adenyl cyclase receptor
hallmarks of PTH action - urinary cAMP (travels through luminal channel) and phosphaturia
also decreases reabsorption of bicarbonate
K sparing diuretic
dont promote the excretion of K into urine
K- sparing diuretics block all functions of aldosterone
spironolactone - aldosterone antagonist, prevent aldosterone entry into nucleus
amiloride, triamterene - block eNaC
hypokalemia
K+ sets resting membrane potential
hypokalemia - insulin, b2 agonists, a antagonists, METABOLIC alkalosis
hyperkalemia - … hyperosmolarity
- plasma osm > cell osm
- -> water shifts out of cell and into plasma
- now, cell K+ concentration has increased significanlty
- -> K+ moves down its concentration gradient ==> hyperkalemia (of plasma)
thiazides and loop diuretics increase K+ secretion - why?
- upstream inhibition of Na+ reabsorption + increased urine flow rate
- more Na delivery to DCT and collecting ducts - drives Na/K exchange
Ca balance
99% contained in bone
40% bound to plasma proteins
PCT - Ca2+ transport follows Na+ transport, more Ca2+ absorption during volume contraction
thick ascending limb - paracellular absorption due to lumen positive potential
-loop diuretics inhibit Ca2+ reabsorption
early distal tubule - luminal Ca2+ channel, PTH increases Ca2+/Na2+ exchange – > PTH increases Ca2+ reabsorption
- thiazides increase Ca2+ reabsorption
phosphate balance
85% of phosphate contained in bone
phosphate in ECF is a buffer for H+ (phosphate = PO4,3-)
reabsorption in PCT and proximal straight tubule
when plasma osm increases
osmoreceptors in the anterior hypothalamus are stimulated
ADH functions
1) increases water perm of principal cells (V2 receptors)
2) increases activity of Na/K/Cl transporter in thick ascending limb
3) adds UT1 transporters to collecting ducts of inner medulla
demeclocycline - inhibits V2-ADH receptors
nephrogenic DI
treat with thiazides! - how?
1) inhibit Na/Cl transport in early DT
2) decreased Na+ reabsorption –> decreased ECF volume –> decreased GFR
3) decreased GFR causes increased reabsorption in proximal tubule
= less water filtered, more water reabsorbed
reflex bradycardia
decrease in heart rate when baroreceptors sense an increased blood pressure
- PSNS - vagus nerve releases Ach - binds M2 receptors –> bradycardia
safety mechanism so abnormal increases in blood pressure dont occur
acetazolamide
= sulfonAMIDE
used in urinary alkalinization, metabolic alkalosis/altitude sickness, and increased ICP (pseudotumor cerebri caused by vitamin A tox, glaucoma)
tox - hyperchloremic metabolic acidosis, NH3 tox
mannitol
osmotic diuretic - used in DKA, drug OD
tox - pulmonary edema because - it initially increases plasma oncotic pressure and thus VOLUME –> pulm edema
thiazides
tox - hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, HLD, hyperuricemia, hypercalcemia, sulfa allergy
loop diuretics
furosemide, bumetanide, ethacyrnic acid
tox- OH DANG
- ototox, hypokalemia, dehydration, (sulfa) allergy, (interstitial nephritis), gout
- ethacrynic acid - can cause hyperuricemia
side note - loops also stimulate PG release
ACEI
uses - HTN (prevents unfavorable heart remodeling), HF, proteinuria, diabetic nephropathy (decreases intraglomerular pressure, slows GBM thickening)
inhibition of ACE prevents inactivation of bradykinin
contraindicated in C1 esterase inhibitor deficiency –> angioedema
teratogen
ARB
blocks binding of ang2 to AT1 receptor
also a teratogen
aliskiren
direct renin inhibitor
tox of ACEi, ARB, and alikiren = hyperkalemia, hypotension, decreased renal function
horseshoe kidney
associated with ureteropelvic junction obstruction + chromosomal aneuploidy syndromes
cystic kidney diseases
multicystic dysplastic kidney - NOT inherited, cysts + cartilage (other abnormal tissue)
PKD - cysts in cortex and medulla
ARPKD - associated with hepatic fibrosis + hepatic cysts, portal HTN
ADPKD
Medullary cystic kidney disease - AD, cysts in collecting ducts, parenchymal fibrosis (tubulointerstitial fibrosis –> inability to concentrate urine) + shrunken kidneys
Renal tubular defects
kidneys put out FaBulous Glittering LiquidS
Fanconi syndrome = PCT failure, occurs with hereditary defects (Wilson’s, tyrosinemia, glycogen storage disease), multiple myeloma, tetracyclines, tenofovir, lead poisoning
Barter syndrome, AR = thick ascending limb, Na/K/2Cl transporter affected
Gitelman, AR = DCT, Na/Cl transporter
Liddle syndrome, AD = collecting tubule, increased activity of ENaC
Syndrome of apparent mineralocorticoid excess - deficiency of 11b-hydroxysteroid dehydrogenase
-can be acquired by licorice consumption
casts
*bladder cancer and kidney stones present with hematuria and NO casts
RBC casts - Gnephritis, malignant HTN WBC - inflammation, acute pyelo, transplant rejection fatty casts - nephrotic syndrome granular casts - acute tubular necrosis waxy casts - ESRD, CRF
uric acid stones
-cysteine stones
radiolucent - visible on CT or US, but NOT on XR
occur in acidic pH urine
side note - cysteine stones are similar - radiolucent, Na Cn nitroprusside test is positive, may form staghorn calculi
-remember - Ammonium Mg phosphate stones (aka struvite) also form staghorn calculi
Am Mg phos stones - form in alkaline environments in the setting of infection with urease-positive orgs
interesting - high dietary calcium reduces the risk for renal stone formation
- dietary calcium is ingested with oxalate in food –> forms insoluble salts that cant be absorbed –> excreted in feces
- low dietary calcium –> hyperoxaluria
Wilms tumor
C11
malignant, blastema –> see primitive glomeruli, tubules, stromal cells
WAGR - Wilms, aniridia (no iris), genital abnormalities, retardation
Beckwith-Wiedemann syndrome - Wilms, neonatal hypoglycemia, muscular hemihypertrophy, organomegaly (tongue!)
angiomyolipoma
TS
renal oncocytoma
benign
large eosinophilic cells
painless hematuria
RCC
men 50-70s - presents as a met
associated with paraneoplastic syndromes
will involve renal vein…
RCC can be sporadic or inherited (AD - RCC + hemangioblastoma of cerebellum)
retroperitoneal LNs
uremia
azotemia, encephalopathy with asterixis nausea, anorexia pericarditis platelet dysfunction (uremia inhibits platelet adhesions and aggregation) deposition of urea crystals in skin
CRF
constellation of features:
low GFR - salt and water retention
hyperkalemia with metabolic acidosis
poor phosphate excretion + decreased calcitriol
-hyperparathyroidism –> secondary hyperparathyroidism –> renal osteodystrophy
urothelial carcinoma
risk factors: smoking (polycyclics, naphthylamine), azo/aniline dyes (hair coloring), cyclophosphamide (cancer, nephrotic syndrome in kids), phenacetin (contained in vicks cold tablets)
flat pathway - associated with early p53 mutations
papillary pathway
squamous cell carcinoma
lower urinary tract does NOT have squamous cells
risk factors - chronic cystitis, Shistosoma hematobium (young middle eastern male), long standing nephrolithiasis
adenocarcinoma of bladder
urachal remnant - connects bladder to yolk sac, occurs at dome of bladder
exstrophy - bladder exposed to outside world
cystitis glandularis - columnar metaplasia due to chronic irritation
nephrotic syndrome
proteinuria - hypoalbuminemia, decreased AT3 (hypercaogulable state), hypogammaglobulinemia
-due to loss of negative charge of glomerular filtration barrier
increased fat - HLD, increased TGs, fatty casts
pathognomic = maltese cross-nephrotic syndrome - free cholesterol in urine
can get spontaneous peritonitis - S pneumo in kids and E coli in adults
fusion of podocytes alway seen in nephrotic syndrome
MCD - kids
- effacement of foot processes due to cytokines (Hodgkins)
- treat with steroids, 2nd line is cyclophosphamide
FSGS - Hispanic, AA pts, AIDS, IVDA, pts with pre-existing illness
- collagen deposition in glomerulus + hyalinosis
- effacement of foot processes
- next worst glomerular disease, after RPGN
membranoproliferative glomerulonephritis
- membrano- IC deposits –> thickened membrane
- granular IF
- also associated with hep
mesangial cell proliferation –> tram tracks through deposits
1) subendothelial deposits - classic tram track, associated with HBV/HCV
- cryoglobulinemia
- polyarteritis nodosa
2) within basement membrane - associated with C3 nephritic factor
- lowest complement levels
*can produce nephritic or nephrotic syndrome
systemic nephropathies
DM
- NEG –> BM becomes leaky –> protein leaks INTO BV wall –> hyaline arteriolosclerosis
- efferent arteriole is more affected… (–> increased eGFR and increased CrCl aka hyperfiltration injury)
- urine microalbuminuria
- Kimmelstiel Wilson nodules - large eosinophilic nodules, consist of type 4 collagen
- ACEIs will slow this (remember ang2 constricts efferent arteriole)
systemic amyloidosis - MM, TB, RA
- Congo red staining and apple-green birefringence under polarized light
- “biting into apple, youre bitting into amyloid”
lupus + kidney disease
membranous nephropathy (idiopathic, phospholipase A2 receptor antibodies, SLE, hepatitis, drugs, NSAIDs)
- thick basement membrane
- subepithelial deposits
- silver stain or EM - supepithelial deposits with spike and dome lesions
**diffuse proliferative glomerular nephritis - wire loop lesions
glomerulonephritis
glomerular inflammation and bleeding, glomerular destruction –> salt retention (not filtering as much sodium) –> periorbital edema, HTN
- oligouria
- by wouldnt have pitting edema and ascites (arent spilling that much protein)
immune complex deposition –> complement, C5a attracts neutrophils –> hypercellular glomeruli
-treat with emergent plasmapheresis
PSGN - hypercellular glomeruli
- lumpy bumpy (migrating subendo–> supepi –> out complexes)
- increased anti-DNAse B titers, decreased complement (C3)
- resolves spontaneously
- remember group A strep causes pharyngitis +impetigo, SCARLET fever, toxic-shock-like syndrome, nec fasciitis*
RPGN = crescents (fibrin + macrophages + Bowman’s capsule parietal epithelial cells)
- linear IF - Goodpastures
- granular - diffuse proliferative GN = wire looping of capillaries, IC deposits
- presents as nephrotic syndrome too - negative - Wegners (cANCA, pR3-ANCA), microscopic polyangiits &Churg-Strauss syndrome (p-ANCA/MPO-ANCA)
- Wegners aka granulomatosis with polyangiitis
- Churg-Strauss - associated with eosinophilia, granulomatous inflammation of small/med vessels, and asthma
IgA nephropathy (Berger syndrome) - deposits in mesangium, granular
- MOST common
- occurs in Henoch-Schonlein purpura
- presents after a mucosal infection, presents with renal insufficiency or acute gastroenteritis
- episodic gross hematuria in kids
- episodic microscopic hematuria in adults
- will do damage in 10-20 years
Alport - type 4 collagen defect
- basket-wave appearance of EM - thinning and splitting of GBM (looks like thick BM with “holes”)
- presents as isolated hematuria, sensory hearing loss, and ocular disturbances
nephritic syndromes
PSGN
RPGN (3 subtypes)
IgA nephropathy
Alport
isosmotic volume contraction
diarrhea - volume of fluid lost is similar to ECF
hyperosmotic volume contraction
water deprivation - ex sweating
remember - plasma has RBCs, RBCs will experience water shifts so keep that in mind when thinking about increases/decreases in HCT
-in this case - HCT unchanged - ECF volume decreases and RBC volume decreases
isosmotic volume expansion
infusion of isotonic NaCl
hyposmotic volume contraction
aldosterone insufficiency
hyperosmotic volume expansion
high NaCl intake
hyposmotic volume expansion
SIADH
hyperkalemia
digitalis (digoxin blocks Na/K ATPase), b-blocker, insulin defiency
Winters formula
predicts respiratory compensation for MET acidosis
PCO2 = 1.5*HCO3 + 8 (+/- 2)
-otherwise there is a mixed acid-based disorder
Non-AG acidosis
HARD-ASS hyperalimentation - IV supply of nutrients addison's disease = acute adrenal failure (no aldosterone) renal tubular acidosis diarrhea acetazolamide spironolactone saline infusion
renal clearance equation
Cx = UxV/Px
glomerular filtration barrier
podocytes make the glomerular basement membrane - so if you damage to podocyte, you damage the basement membrane
heparAN sulfate - strong negative charge
linear IF
goodpastures
IgG antibodies against type for collagen (in BM) - type 2 HSR
granular IF
lupus - diffuse proliferative glomerulonephritis
- pts with lupus will have serum ANA antibodies, rim pattern staining
- IC = DNA-anti-DNA antibody
- IC are bigger, charged - will not deposit uniformly, ex can get under endothelial cell (fenestrated) but cant get through BM
post-streptococcal glomerulonephritis
-IC are very small and soluble - will deposit under the epithelial membrane (subepithelial deposit)
IgA nephropathy (Berger disease) - only IgA glomerulonephritis can be ddx by IF, BECAUSE you have you a tag against IgA
- otherwise IF uses tag against IgG - so you know that ICs exist but you dont know where they are located
- need EM to determine where complexes are located
membrano-syndromes
EPO
made in interstitium (?) of peritubular capillary cells
EPO for CKD-anemia
- side effects include increased risk for thromboembolic events and HTN (EPO receptors on vascular endothelium and SMCs)
causes of azotemia
azotemia is an increase in BUN
BUN nl = 10
Cr nl = 1 mg/dL (sometimes Cr is secreted in the gut)
pre-renal azotemia - low RBF –> decreased GFR –> proximal tubule will have more time to reabsorb urea
- decreased GFR - CR filtration is decreased
- BUN increases more than Cr, BUN/CR > 15:1
acute renal failure (oligouria) - filtration of BUN and Cr decreased equally
- BUN cant be reabsorbed
- ratio unchanged, absolute values are increased
- most common cause is ischemic, acute tubular necrosis (will see brown casts and increased serum Cr)
- most common cause is not treating pre-renal azotemia
ischemic tubular necrosis - issue is that the BM gets damaged
- when pt recovers from acute tubular necrosis - cant regenerate cell where there is no basement membrane
- PST and thick ascending segment (in inner medulla) are most susceptible
nephrotox drugs
nephrotoxic acute tubular necrosis - involves proximal tubule, it is the first part hit by the drug
gentamycin (AG) - proximal tubule, BM remains intact
IV pyelogram (dye for urinary system)
renal arteries and veins
L1 level
UTIs
bladder has protections
- mucosa normally does not allow bacterial attachment - cystitis (fimbriae attach)
- normal urine is bactericidal (urea, osmolarity) - capsules
- urine flow
pyelo: risk of hematogenous spread (and risk is greater in hospitalized, elderly)
multiple myeloma
excess excretion of free light chains (Bence Jones proteins) –> precipitate with Tamm-Horsfall protein –> obstructing CASTS
MM - can cause poor bicarb absorption
edema
pitting edema:
transudates
non-pitting:
exudates (pus)
lymphedema (mastectomy, Peau de orange inflammatory carcinoma, lymphogranuloma venereum chlamydia, Wuchereria bancrofti)
how many liters of isotonic saline do you have to inject into plasma to increase it by 1 L
3 L
- 2 L distribute into interstitial space, 1 L into plasma
CCBs
used for HTN
amlodipine, nifedipine - dihydropyridine CCBs
- peripheral edema - due to dilation of precapillary vessels –> increased Pc
- dizziness or lightheadedness, flushing
familial hypocalciuric hypercalcemia
benign, AD
defective Ca2+ sensing by PTH and renal tubule cells
- PTH is not suppressed when Ca2+ is high
- constellation - high PTH, high Ca2+ and lower urinary Ca2+
cyclophosphamide and mesna
cyclophosphamide = chemo
–> converted to acrolein by kidneys –> toxic to urothelium
mesna - sulfyhydryl compound that binds and inactivates toxic metabolites
acid-base disorders
metabolic acidosis - Winters
metabolic alkalosis - PaCO2 increases 0.7/1 meQ/L rise in bicarb
acute respiratory acidosis - 1 mEq/L rise in HCO3 for every 10 mmHg CO2
acute respiratory acidosis
2 mEq/L drop in HCO3 for every 10 mm Hg decrease in CO2
CKD and drug effects
long-acting insulin is cleared by the kidney –> hypoglycemia
