Renal Flashcards
Prosnephros
Week 4 then disintegrates
Mesonephros
functions as interim kidney for 1st trimester
later contributes to make genital system
Metanephros
permanent
appear in 5th week
nephrogenesis continues through weeks 32-36
Ureteric bud
derived from causal end of mesonephric duct
gives rise to ureter, pelvis, calyces, collecting duct, fully canalized by 10th week
Metanephric mesenchyme
ureteric bud interacts with this tissue
interaction induced differentiation and formation of glomerulus through to distal convoluted tubule
Aberrant interaction between these 2 tissues may result in several congenital malformations of the kidney
Ureteropelvic junction- last to canalize –> congenital obstruction
Cause of prenatal hydronephrosis
detected by US
Potter Sequence
Oligohydramnios –> compression of developing fetus –> limb deformities, facial anomalies, lack of amniotic fluid aspiration into fetal lungs –> pulmonary hypoplasia
Caused by ARPKD, obstructive uropathy, bilateral renal agenesis, chronic placental insufficiency
Horseshoe kidney
inferior poles of both kidneys fuse abnormally
get trapped in Inferior mesenteric artery and stay in low abdomen
Associated with hydronephrosis, renal stones, infection and increased risk of renal cancer
Higher incidence in chromosomal aneuploidy
Unilateral renal agenesis
ureteric bud fails to induce differentiation of metanephric mesenchyme –> complete absence of kidney and ureter
Multicycstic dysplastic kidney
ureteric bud fails to induce differentiation of metanephric mesenchye –> nonfunctional kidney with cysts and connective tissue
Nonhereditary and unilateral
Bilateral –> potter sequence
Duplex collecting system
Bifurcation of ureteric bud before it enters the metanephric blastema creates a Y shaped bifid ureter. Duplex collecting system can occur through 2 ureteric buds reaching and interacting with metanephric blastema
Associated with vesicoureteral reflux and ureteral obstruction
increase risk of UTI
Posterior Urethral valves
membrane remnant in the posterior urethra in males
persistence –> urethral obstruction
Dx prenatally by bilateral hydronephrosis and dilated or thick walled bladder on US
associated with oligohydramnios in severe obstruction
Renal blood flow
renal A –> segmental A –> interlobar A ==> arcuate A –> interlobular A –> afferent arteriole –> glomerulus –> efferent arteriole –> vasa recta –> venous outflow
Course of ureters
arise from renal pelvis –> under gonadal A –> over common iliac A –> under uterine A/vas deferens
Blood supply to ureter
proximal- renal A
Middle- gonadal A, aorta, common and internal iliac A
Distal- internal iliac and superior vesical A
3 common points of reteral obstruction
ureteropelvic junction, pelvic inlet, ureteropelvic junction
Fluid Compartments
60% total body water 40% ICF (K+, Mg2+, organic phosphates) 20% ECF (Na+, Cl-, HCO3-, albumin) Plasma volume measured via radiolabeling albumin ECF measured with inulin or mannitol Plasma volume= TBV x (1-Hct)
Glomerular filtration barrier
Fenestrated capillary endothelium (prevent >100 nm from entering)
BM iwth Type 4 collagen and heparan sulfate
Visceral epithelial layer with podocyte foot processes (prevent >50-60 nm from entering)
All three layers have - charged glycoproteins that prevent - charged molecules entry
Renal clearance equations
C= (UV)/P
If C < GFR –> net tubular resorption or not freely filtered
If C > GFR –> net tubular secretion of X
C = GFR –> no net secretion or reabsorption
GFR equations
Inulin clearance
C = GFR = U x V/P = K (PGC- PBS) - (piGC- piBS)
piBS = 0 usually
Normal GFR = 100
Creatinine is approximate (slightly overestimates because a little secreted)
Effective renal plasma flow
PAH clearance (100% excretion) eRPF = U x V/P = C RBF = RPF/ (1-Hct) = usually 20-25% cardiac output underestimates true renal flow slightly
Filtration
FF= GFR/RPF (Normal = 20%)
filtered load= GFR x plasma conc
Prostaglandins dilate afferent arteriole
Ang II constricts efferent arteriole
Afferent arteriole constriction
decrease GFR and RPF
No change FF
Efferent arteriole constriction
increase GFR
decrease RPF
FF increases
increase plasma conc
decrease GFR
No change RPF
decrease FF
Constriction of ureter
decrease GFR
no change RPF
decrease FF
Dehydration
decrease GFR
DECREASE RPF
Increase FF
Calculation of reabsorption and secretion rate
Filtered load = GFR x P Excretion rate = V x U Reabsorption = filtered- excreted Secretion rate = excreted - filtered (V x UNa) / (GFR/ PNa)
Early PCT
contains brush border
Reabsorb glucose and AA, HCO3, Na, Cl, PO4, K, H2O, uric acid
PTH –> inhibit Na+/ PO4 cotransport –> increase PO4 excretion
ATII –> stimulate Na+/H+ exchanger –> increase Na+, H2O and HCO3 reabsorption
Thin descending loop of Henle
passively reabsorbs H2O via medullary hypertonicity
Concentrating segment
Make urine hypertonic
Thick ascending loop of Henle
reabsorbs Na, K and Cl
indirectly induces paracellular reabsorption of Mg and Ca via + lumen potential
impermeable to H2O
Make urine less concentrated as it ascends
Early DCT
reabsorbs Na, Cl
impermeable to H2O
Makes urine hypotonic
PTH –> increase Ca/Na exchange –> increase Ca reabsorption
Collecting tubule
reabsorbs Na in exchange for secreting Na and K (aldosterone)
Aldosterone
mRNA –> protein synthesis
principal cells increase apical K+ conductance, increase Na/K pump, increase ENaC –> lumen negative –> K secretion
a intercalated cells lumen negative –> increase H ATPase –> increase H secretion –> increase HCO3/Cl exchanger
ADH
V2 receptor –> insert aquaporin H2O channels on apical side
Fanconi syndrome
generalized reabsorption defect in PCT –> increase excretion of AA, glucose, HCO3, PO4
Lead to metabolic acidosis, hypophosphatemia, osteopenia
Causes: Hereditary defects, ischemia, multiple myeloma, nephrotoxins, lead poisoning
Bartter Syndrome
reabsorption defect in TAL (Na/K/Cl transport)
Metabolic alkalosis, hypokalemia, hypercalciuria
AR
Like loop diuretics
Gitelman Syndrome
Reabsorption defect of NaCl in DCT
Metabolic alkalosis, hypoMg, hypoK, hypocalciuria
AR
Like thiazide diuretic
Liddle Syndrome
Gain of function mutation –> decrease Na channel degradation –> increase Na reabsorption in collecting duct
Metabolic alkalosis, hypoK, HTN, low aldosterone
AD
Syndrome of Apparent Mineralcorticoid Excess
cortisol activate mineralcorticoid receptors
Hereditary 11B HSD deficiency –> increase cortisol –> increase mineralcorticoid receptor activity
metabolic alkalosis, hypoK, HTN, low serum aldosterone
AR
Treat with K sparing diuretics
Renin
secreted by JG cells in response to low renal perfusion pressure, increase renal sympathetic discharge and decrease NaCl delivery to macula densa
AT II
maintain blood volume and blood pressure
affects baroreceptor function, limits reflex brady
ANP and BNP
released from atria and ventricles in response to high volume, inhibit RAAS, relax vascular smooth muscle via cGMP –> increase GFR, decrease renin
Dilates afferent arteriole
ADH
regulate serum osmolarity and respond to low blood volume states. Simulates reabsorption of water in collecting ducts and reabsorption of urea in collecting ducts to maximize osmotic gradient
Aldosterone
regulate ECF volume and Na content
increase release in low blood volume states
Responds to hyperK by increase K excretion
JG apparatus
JG (afferent arteriole) and macula densa (distal loop of henle)
JG cells secrete renin in response to low renal blood pressure and increase sympathetic tone
Macula densa sense low NaCl delivery to DCT –> increase renin release –> efferent arteriole vasoconstriction –> increase GFR
Erythropoietin
released by interstitial cells in peritubular capillary bed in response to hypoxia. Stimulate RBC proliferation in bone marrow
Calciferol
PCT cells convert 25OH vit D3 –> 1,25OH vit D (1a hydroxylase)
prostaglandins
paracrine secretion vasodilates the aferent arteriolesto increase RBF
Dopamine
secreted by PCT cells, promotes natriuresis
low doses –> dilate interlobular arteries, afferent arterioles and efferent arterioles –> increase RBF
At high doses –> vasoconstrictor
ANP
secreted in response to high atrial pressure
increases GFR and Na filtration with no Na reabsorption in distal nephron
NET EFFECT: Na loss and volume loss
Ang II
in response to low BP
Efferent arteriole constriction –> high GFR and FF with Na reabsorption in proximal and distal nephron
NET EFFECT: preserve FF in low volume state and Na reabsorption to maintain volume
PTH
low plasma Ca, high plasma PO4 or low plasma 1,25OH vit D
increases reabsorption of Ca (DCT), decrease PO4 reabsorption (PCT) and increase 1,25OH vit D production
Aldosterone
low blood volume and hyperK
NET: increase Na reabsorption, increase K secretion, increase H secretion
ADH
high plasma osmolarity and low blood volume
Bind to principal cells –> increase aquaporins and water reabsorption
increase reabsorption of urea in collecting ducts to maximize corticopapillary osmotic gradient
Shift K into cell –> hypoK
hypo osmolarity
alkalosis
B adrenergic agonist
Insulin
Shift K out of cell –> Hyper K
Digitalis hyperosmolarity lysis of cells acidosis B blocker Insulin deficiency succinylcholine
Sodium electrolyte imbalance
Low: nausea, malaise, stupor, coma, seizures
High: irritability, stupor, coma
Potassium electrolyte imbalance
Low: U wave and flattened T wave on ECG, arrhythmia, muscle cramps, spasm, weak
High: Wide QRS and peaked T, arrhythmias, muscle weakness
Calcium electrolyte imbalance
Low: tetany, seizures, QT prolong, twitching, spasm
High: stones, cones, groans, thrones, psychiatric overtones
Mg electrolyte imbalance
Low: tetany, torsades de pointes, hypokalemia, hypocalcemia
High: low DTRs, lethargy, brady, hypotension, cardiac arrest, hypocalcemia
Phosphate electrolyte imbalance
Low: bone loss, osteomalacia, rickets
High: renal stones, metastatic calcifications, hypocalcemia
Respiratory acidosis
Hypoventilation High bicarb, high PCO2 airway obstruction acute/chronic lung disease opioids weak respiratory muscles
High anion gap Metabolic acidosis
low PCO2, low bicarb, anion gap >12 Methanol uremia DKA propylene glycol Iron Lactic acidosis Salicylates
Normal anion gap Metabolic acidosis
Low PCO2, low bicarb, anion gap = 8-12 HyperCl Addison RTA Diarrhea Acetazolamide Spironolactone Saline infusion
Respiratory Alkalosis
Hyperventilation: low bicarb, low PCO2 anxiety Hypoxemia Salicylates (early) Tumor PE
Metabolic Alkalosis
High PCO2 and high bicarb loop diuretics vomiting antacid use hyperaldosteronism
RTA 1
Distal
a intercalated cells unable to secrete H –> no new HCO3 –> metabolic acidosis
urine pH= basic
Serum K low
caused by amphotericin B, congenital anomalies, SLE
Associated with increase stones and increase bone turnover
RTA 2
Defect in PCT HCO3 reabsorption –> excrete in urine –> metabolic acidosis
urine pH= basic when resorptive threshold exceeded, acidic when depleted
Serum K low
Causes: fanconi, multiple myeloma, carbonic anhydrase inhibitors
Associated with risk of rickets
RTA 4
hypoaldosteronism –> decrease ammonium secretion
acidic urine pH
high serum K
RBC casts
glomerulonephritis, HTN emergency
WBC casts
tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
Granular casts
Acute tubular necrosis
Fatty casts
Nephrotic syndrome
Waxy casts
end stage renal disease
Hyaline casts
nonspecific
Nephritic syndrome
glomerular inflammation –> GBM damage –> loss of RBCs into urine (hematuria)
low GFR –> oliguria, azotemia, increase renin release, HTN
Protein <3.5
Nephrotic Syndrome
podocyte damage –> impaired charge barrier –> proteinuria (>3.5)
hypoalbuminemia edema
frothy urine with fatty casts
Nephritic- Nephrotic syndrome
severe GBM damage –> loss of RBC and impaired charge barrier
>3.5 proteinura
Can occur with any form of nephritic syndrome
Acute poststrep GN
Nephritic
Children 2-4 weeks after group A strep
resolve spontaneously
TYPE III hypersensitivity
peripheral periorbital edema, tea colored urine, HTN, decrease levels of C3
glomeruli enlarged and hypercellular, starry sky granular appearance, subepithelial IC humps
PRGN
Nephritic
poor prognosis
Crescent shaped (fibrin and plasma protein with glomerular parietal cells, monocytes and macrophages)
Linear IF –> good pasture (anti GBM) Type 2 hypersensitivity
Negative IF, Pauci immune- granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis or microscopic polyangiitis
Granular IF- PSGN or DPGN
Diffuse proliferative GN
Nephritic
SLE (wire lupus)
IF granular
subendothelial IgG with C3 deposition
IgA nephropathy
Nephritic
episodic hematuria that occurs with respiratory or GI infection. Henoch Schnlein
Mesangial proliferation
IgA deposits
Alport Syndrome
Nephritic
Mutation in COL4 –> thin/ split glomerular BM
X linked Dominant
eye problems, GN, sensorineural deafness
basket weave appearance due to irregular thickening of GBM
MPGN
Nephritic + Nephrotic
Type 1- secondary to Hep B/C infection = sunendothelial deposits with granular IF
Type 2- C3 nephritic factor –> decrease C3 factors = intramembranous deposits
Minimal change disease
Nephrotic
children
triggered by recent infection, immunization, immune stimulus
Normal glomeruli, neg IF, effacement of podocyte foot processes
FSGS
Nephrotic
Secondary to HIV, SCD, heroin, obese, interferon tx, congenital malformations
segmental sclerosis, hyalinosis, neg IF, effacement of foot processes
Membranous nephropathy
Nephrotic
secondary to drugs, infections, SLE, solid tumors
diffuse capillary and GBM thickening, IF granular, spike and dome appearance (subepithelial deposits)
Amyloidosis
Nephrotic
Congo red stain with polarized light
Associated with chronic conditions that predispose to amyloid deposition
Diabetic GN
Nephrotic
mesangial expansion, GBM thickening and increased permeability
glomerulosclerosis eosinophilic
Calcium oxalate hypocitraturia
dumbbell shaped
most common
via ethylene glycol, vit C abuse, hypocitraturia, malabsorption
Calcium phosphate stoes
high pH
wedge shaped prism
Struvite
high pH
coffin lid
Proteus, Staph saprophyticus, klebsiella
Staghorn caliculi
Uric acid
low pH
rhomboid/ rosettes
Risk: low urine volume, arid climate, acidic pH
associated with hyperuricemia, leukemia
Cystine
low pH
hexagon
Cystine reabsorbing PCT transporter lose function
Nitroprusside +
Hydronephrosis
distention/ dilation of renal pelvis and calyces
caused by urinary tract obstruction
Dilation occurs proximal to site of pathology
Cr elevated
Stress incontinence
outlet incompetence –> leak with high intra abdominal pressure
+ bladder stress test
Obese, vaginal delivery, prostate surgery
pelvic floor muscle strengthening, weight loss
Urgency incontinence
Detrusor overactivity
UTI
Kegel, bladder training, antimuscarinics
Overflow incontinence
incomplete emptying
polyuria, bladder outlet obstruction, neurogenic bladder
catheterize, relieve obstruction
Acute cystitis
inflammation of bladder
Sx: suprepubic pain, dysuria, urinary frequency, urgency
Risk: female, sex, catheter, DM, impaired bladder emptying
Bacteria: E coli, staph sap. Klebsiella, proteus mirabilis
Neg urine culture, + leukocyte esterase and nitrites
Acute pyelonephritis
Neutrophils infiltrate renal interstitium
affect cortex spare glomeruli
fever, flank pain, nausea/ vomiting, chills
via ascending UTI
Risk: catheter, UTI, vesicouteral reflux, DM, pregnancy
Chronic pyelonephritis
recurrent acute pyelonephritis
Coarse asymmetric corticomedullary scarring, blunted calyx
Tubules contain eosinophilic casts
Xanthogranulomatous pyelonephritis
orange nodules that mimic tumor
widespread kidney disease
via Proteus infection
Prerenal azotemia
hypovolemia, low CO, low effective circulating volume
low RBF –> low GFR –> increased reabsorption of Na+/H2O and urea
urine osm >500
urine Na < 20
Fe(Na) <1%
BUN:Cr >20
Intrinsic Renal Failure
acute tubular necrosis, acute GN, vasculitis, Malignant HTN, TTP-HUS ATN --> low GFR, granular casts urine osm <350 Urine Na >40 FE (Na) >2% BUN:Cr <15
Postrenal azotemia
stones, BPH, Neoplasm, Congenital anomalies
outflow obstruction
urine osm <350
Acute interstitial Nephritis
acute interstitial renal inflammation
Pyuria and azotemia after administration of drugs that act as haptens, inducing hypersensitivity
Fever, rash, hematuria, pyruria, CVA tenderness
Acute tubular necrosis
increase FE (Na)
1. inciting event
2. Maintenance - oliguria 1-3 weeks
3. Recovery- polyuria, BUN and Cr fall
Ischemic- secondary to low renal blood flow –> death of tubular cells (PCT and TAL susceptible)
Nephrotoxic- secondary to injury with toxins, crush injury, hemoglobinemia (Proximal tube susceptible)
Diffuse cortical necrosis
acute generalized cortical infarction of bowth kidneys
Vasospasm + DIC
Associated with obstetric catastrophes, septic shock
Renal papillary necrosis
Sloughing of necrotic renal papillae –> gross hematuria and proteinuria
triggered by recent infection or immune stimulus
Associated with SCD, Acute pyelonephritis, Analgesics, DM
Consequences of renal failure
decline in renal filtration –> excess nitrogenous waste products and electrolyte disturbances
Metabolic acidosis, dyslipidemia, high potassium, uremia, Na+ / H2O retention, growth retardation, EPO deficiency, renal osteodystrophy.
Renal osteodystrophy
Hypocalcemia, hyperphosphatemia and failure of vit D hydroxylation associated with CKD –> hyper PTH
PO4 bind with Ca and deposit –> low Ca, 1,25 vit D –> low intestinal Ca absorption
subperiosteal thinning of bones
ADPCKD
Cysts in cortex and medulla –> bilateral enlarged kidneys
flank pain, hematuria, HTN, urinary infection, progressive renal failure
PKD1 mut (chr 16) or PKD2 mut (chr4)
complications: CKD, HTN
Associated with berry aneurysms, MVP, benign hepatic cysts, diverticulosis
ARPCKD
cystic dilation of collecting ducts
infants
Associated with congenital hepatic fibrosis
lead to potter sequence
systemic HTN, progressive renal insufficiency, portal HTN
AD tubulointerstitial kidney disease
causes tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine
Medullary cysts
SMALLER kidneys of US
simple cysts
filled with ultrafiltrate
asymptomatic
Complex cysts
require follow up or remove due to RCC risk
Renavascular disease
renal impairment due to ischemia from renal A stenosis or microvascular disease
low renal perfusion –> high renin –> high Ang –> HTN
caused by atherosclerotic plaques or fibromuscular dysplasia
asymmetric renal size, epigastric/ flank bruits
RCC
polygonal clear cells (chr 3) filled with accumulated lipids and carbohydrates
originate in PCT –> invade renal V –> IVC –> hematogenous spread –> metz to lung and bone
hematuria, palpable masses, polycythemia, glank pain, fever, weight loss
men 50-70
risk: obese, smokers
Paraneoplastic: PTHrP, EPO, ACTH, Renin
Renal oncocytoma
Benign epithelial cell tumor from collecting ducts
Large eosinophilic cells with abundant mitochondria without perinuclear clearing.
painless hematuria, flank pain, ab mass
Wilms tumor
childhood
embryonic glomerular structures
large, palpable, unilateral flak mass, hematuria HTN
WAGR
wilms, aniridea, genitourinary malformations, retardation (WT1 deletion)
Denys Drash
wilms, diffuse mesangial sclerosis, dysgenesis of gonads
WT1 mut
Beckwith Wiedemann
Wilms, macroglossia, organomegaly, hemihyperplasia, omphalocele
WT2 mut
Urothelial carcinoma of the bladder
painless hematuria
associated with phenacetin, smoking, amiline dyes and cyclophosphamide
SCC of bladder
chronic irritation of bladder –> squamous metaplasia –> dysplasia and SCC
Risk factors: schistosoma, chronic cystitis, smoking, chronic kidney stones
painless hematuria
Mannitol
osmotic diuretic, increase tubular fluid osmolarity –> increase urine flow
used in drug overload, elevated intracranial or intraocular pressure
Adverse: PE, Na imbalance, contra in anuria and HF
Acetazolamide
carbonic anhydrase inhibitor, alkalinizes urine
used in glaucoma, met alk, altitude sickness, intracranial HTN
Adverse: proximal renal tubular Acidosis, paresthesias, NH3 tox, sulfa allergy, hypoK, calcium phosphate stone
Loop diuretics
Furosemide, bumetanide, torsemide
sulfa- inhibit Na/K/Cl of TAL, abolish hypertonicity of medulla –> prevent concentrated urine
use in edema, HTN, hyperCa
Adverse: ototox, hypoK, hypoMg, Dehydration, allergy, met alk, nephritis, gout
Ethacrynic acid
nonsulfa Na/K/Cl inhibitor
used in diuresis in patients allergic to sulfa
Adverse: more ototox
Thiazaide diuretics
hydrochlorothiazide, chlothalidone, metolazone
inhibit NaCl reabsorption in DCT
used for HTN, HF, hyperCalciuria, neph DI, osteporosis
Adverse: hypoK, met alk, hypoNa, hypoglycemia, HypoCa, sulfa
K sparing diuretics
Spironolactone- aldosterone antag
Amiloride- Na block
used for hyperaldosteronism, K= depletion, HF, neph DI, antiandrogen
Adverse: hyperK
Diuretics Urine NaCl
increase with diuretics
serum NaCl decrease
Diuretics urine K
increase in loop and thiazide diuretics
Diuretics blood pH
acidemia- carbonic anhydrase inhibitor, spironolactone and hyperkalemia
Alkalemia- loop diuretics and thiazides
Diuretics urine Ca
increase with loop diuretics
decrease with thiazides
ACEi
-opril
inhibit ACE –> low Ang II –> low GFR
used in HTN, HF, proteinuria, diabetic nephropathy
Adverse: cough, angioedema, teratogen, creatinine increase, hyperK, hypotension
ARBs
-sartan
block AngII to AT1 receptor- DO NOT DECREASE BRADYKININ
used in HTN, HF, proteinuria, CKD, with ACEi intolerance
Adverse: hyperK, low GFR, hypotension, teratogen
Alliskiren
renin inhibitor (block Ang I –> Ang II)
used in HTN
Adverse: hyperK, low GFR, hypotension, angioedema, contra in patients taking ACEi or ARBS or pregnant.
