Renal Flashcards
(81 cards)
1
Q
Kidney Embryology: Pronephros
A
week 4, then degenerates
2
Q
Kidney Embryology: Mesonephros
A
functions as interim kidney for 1st trimester, later contributes to male genital system
3
Q
Kidney Embryology: Metanephros
A
permanent, first appears in 5th week of gestation; nephrogenesis continues through 32-36 weeks of gestation
- Ureteric Bud: derived from caudal end of mesonephros; gives rise to ureter, pelvises, calyces, & collecting ducts; fully canlized by 10th week
- Metanephric Mesenchyme: ureteric bud interacts with this tissue; interaction induces differentiation & formation of glomerulus through to distal convoluted tubule
- Abberant interaction b/w these 2 tissues may result in several congential malformations of the kidney
4
Q
Kidney Embryology: Ureteropelvic Junction
A
last to canalize, most common site of obstruction (hydronephrosis) in fetus
5
Q
Potter’s Syndrome
A
- Oligohydramnios, compression of fetus, limb deformities, facial deformities, & pulmonary hypoplasia (cause of death)
- Babies who can’t Pee in utero (Potter)
- Causes: ARPKD, posterior urethral valves, bilateral renal agenesis
6
Q
Horseshoe Kidney
A
- inferior poles of both kidney’s fuse, as they ascend from pelvis during fetal development, horseshoe kidneys get trapped under inferior mesenteric artery & remain low in the abdomen
- kidney functions normally
- associated with Turner syndrome
7
Q
Multicystic Dysplastic Kidney
A
- due to abnormal interaction b/w ureteric bud & metanephric mesenchyme
- this leads to a nonfunctional kidney consisting of cysts & connective tissue
- if unilateral (most common), generally asymptomatic w/compensatory hypertrophy of contralateral kidney
- often diagnosed prenatally via ultrasound
8
Q
Ureters Course
A
- ureters pass under uterine artery and under ductus deferens (retroperitoneal)
- “water under the bridge” (uterine artery, vas deferens)
9
Q
Fluid Compartments
A
Body Weight 40% nonwater, 60% water
- 1/3 extracellular, 2/3 intracellular
- 1/4 plasma volume, 3/4 interstitial volume
- plasma volume measured by radiolabeled albumin
- extracellular volume measured by inulin
- Osmolarity=290 mOsm/L
10
Q
Glomerular Filtration Barrier
A
- responsible for filtration of plasma according to size & net charge
- composed of: fenestrated capillary endothelium (size barrier)
- fused basement membrane w/heparan sulfate (negative charge barrier)
- epithelial layer consisting of podocyte foot processes
- charge barrier is lost in nephrotic syndrome, resulting in albuminuria, hypoproteinemia, generalized edema & hyperlipidemia
11
Q
Renal Clearance
A
Cx = (Ux V)/Px = volume of plasma from which the substance is completely cleared per unit time
Cx< GFR; net tubular reabsorption of X
Cx> GFR; net tubular secretion of X
Cx = GFR; no net secretion of reabsorption
V=urine flow rate, Px=plasma concentration
Ux=urine conc. of X, Cx=clearance of X (mL/min)
12
Q
GFR
A
-Inulin clearance can be used to calculate GFR b/c it is freely filtered & is neither reabsorbed nor secreted
GFR = U(inulin) X V/Pinulin = C inulin
=Kf [(Pgc-Pbs)-(picg-pibs)]
(GC = glomerular capilary; BS = bowmans space)
pi bs normally equals 0
normal GFR = 100 mL/min
Creatinine clearance is approx. measure of GFR, slightly overestimates GFR because creatinine is moderately secreted by the renal tumules
-Incremental reductions in GFR define the stages of chronic kidney disease
13
Q
Effective Renal Plasma Flow
A
ERPF can be estimated using PAH clearance b/c it is both filtered & actively secreted in the proximal tubule
-all PAH entering the kidney is excreted
-ERPF = Upah X V/Ppah = Cpah
RBF = RPF/(1-Hct)
ERPF underestimates true RPF by ~10%
14
Q
Glucose Clearance
A
- glucose at normal plasma level is completely reabsorbed in proximal tubule by Na+/glucose cotransport
- at plasma glucose of ~160 mg/dL, glucosuria begins (threshold)
- at 350 mg/dL, all transporters are fully saturated Tm
- Glucosuria is an important clinical clue to diabetes mellitus
- normal pregnancy reduces reabsorption of glucose & aa in the proximal tubule, leadign to glucosuria & aminoaciduria
15
Q
Amino Acid Clearance
A
-Na+ dependent transporters in proximal tubule reabsorb amino acids
16
Q
Hartnup’s Disease
A
deficiency of neutral aa (tryptophan) transporter, results in pellagra
17
Q
AT II
A
affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor effects
-helps maintain blood volume & blood pressure
18
Q
ANP
A
-released from aria in response to inc. volume; may act as a “check” on renin-angiotensin-aldosterone system; relaxes vascular smooth muscle via cGMP, causing inc. GFR, dec. renin
19
Q
ADH
A
-primarily regulates osmolarity but also responds to low blood volume, which takes precedence over osmolarity
20
Q
Aldosterone
A
-primarily regulates blood volume, in low volume states, both ADA & aldosterone act to protect blood volume
21
Q
Juxtaglomerular Apparatus
A
- consistis of JG cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, part of the distal convoluted tubule)
- JG cells secrete renin in response to dec. renal blood pressure, dec. NaCl delivery to distal tubule, & sympathetic tone (beta1)
- JGA defends glomerular filtration rate via renin-angiotensin-aldosterone system
- beta-blockers can decrease BP by inhibiting Beta1-receptors of the JGA, causing dec. renin release
22
Q
Erythropoietin
A
Released by interstitial cells in peritubular capillary bed in response to hypoxia
23
Q
1-25 (OH)2 vitamin D
A
- proximal tubule cells convery 25-OH vit D to 1,25 (OH)2 vit D (active form)
- PTH converts it!
24
Q
Renin
A
-secreted by JG cells in response to dec. renal arterial pressure & inc. renal sympathetic discharge (beta1 effect)
25
Prostaglandins
- Paracrine secretion vasodilates the afferent arterioles to inc. GFR
- NSAIDs can cause acute renal failure by inhibiting the renal production of prostaglandins, which keep the afferent arterioles vasodilated to maintain GFR
26
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Renal Tubular Acidosis (RTA)
Type 1 ("distal")
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- defect in collecting tubule's ability to excrete H+
- untreated patients have urine pH>5.5
- associated with hypokalemia
- inc. risk for Ca phosphate kidney stones as a result of inc. urine pH and bone resorption
27
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Renal Tubular Acidosis (RTA)
Type 2 ("proximal")
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- defect in proximal tubule HCO3- reabsorption
- may be seen with Fanconi's syndrome
- untreated patients typically have urine pH <5.5
- associated with hypokalemia
- inc. risk for hypophosphatemic rickets
28
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Renal Tubular Acidosis (RTA)
Type 3 ("hyperkalemic")
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- hypoaldosteronism or lacking of collecting tubule response to aldosterone
- resulting hyperkalemia impairs ammoniagenesis in the proximal tubule, leading to dec. buffering capacity and dec. urine pH
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Casts in Urine: RBC
Glomerulonephritis, ischemia, or malignant HTN
| -bladder cancer, kidney stones, inc. hematuria, no casts
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Casts in Urine
presence of casts indicated that hematuira/pyuria is of renal (vs. bladder) origin
31
Casts in Urine: WBC
- tubulointersitial inflammation, acute pyelonephritis, transplant rejection
- acute cystitis (pyuria, no casts)
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Casts in Urine: Fatty Casts "oval fat bodies"
-nephrotic syndrome
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Casts in Urine: Granular
"muddy brown casts"
| -acute tubular necrosis
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Casts in Urine: Waxy casts
advanced renal disease/chronic renal failure
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Casts in Urine: Hyaline casts
Nonspecific, can be a normal findings
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Glomerular Disorders: Focal
<50% of glomeruli are involved
| Ex: focal segmental glomerulosclerosis
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Glomerular Disorders: Diffuse
>50% of glomeruli are involved
| Ex. diffuse proliferative glomerulonephritis
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Glomerular Disorders: Proliferative
hypercellular glomeruli
| Ex: Mesangial proliferative
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Glomerular Disorders: Membranous
thickening of glomerular basement membrane
| Ex: Membranous nephropathy
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Glomerular Disorders: Primary glomerular disease
involves only glomeruli, thus a primary disease of the kidney
Ex: minimal change disease
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Glomerular Disorders: Secondary glomerular disease
involves glomeruli & other organs, thus a disease of another organ system, or a systemic disease that has impact on the kidneys
Ex: SLE, diabetic nephropathy
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Glomerular Diseases: Nephritic Syndrome
- Acute poststreptococcal glomerulonephritis
- Rapidly Progressive Glomerulonephritis
- Berger's IgA glomerulonephropathy
- Alport syndrome
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Glomerular Disorders: Nephrotic Syndrome
- Focal Segmental Glomerulosclerosis
- Membranous Nephropathy
- Minimal Change Disease
- Amyloidosis
- Diabetic Glomerulonephropathy
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Glomerular Disorders: Mixed Nephritis/Nephrotic
- Diffuse proliferative glomerulonephritis
| - Membranoproliferative glomerulonephritis
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Nephrotic Syndrome
- presents with massive proteinuira (>3.5g/day, frothy urine), hyperlipidemia, fatty casts, edema
- associated with thromboembolism (hypercoagulable state due to AT III loss in urine) and inc. risk of infection (loss of Ig)
46
Focal Segmental Glomerulosclerosis
Nephrotic Syndrome
- LM-segmental sclerosis & hyalinosis
- EM-effacement of foot processes similar to minimal change disease
- most common cause of nephrotic syndrome (adults)
- associated with HIV infection, heroin abuse, massive obesity, interferon treatment, & chronic kidney disease due to congenital absence or surgical removal
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Membranous Nephropathy
Nephrotic Syndrome
- LM-diffuse capillary & GBM thickening
- EM-"spike & dome" appearance w/subepithelial deposits
- IF-granular. SLE's nephrotic presentation
- second most common primary nephrotic in adults, can be idiopathic or drugs, infections, SLE, tumor
48
Minimal Change Disease (Lipoid Nephrosis)
Nephrotic Syndrome
- LM-normal glomeruli
- EM-foot process effacement
- selective loss of albumin, not globulins, caused by GBM polyanion loss
- may be triggered by recent infection or immune stimulus, most common in children
- responds to corticosteroids
49
Amyloidosis
Nephrotic Syndrome
- LM- congo red stain shows apple-green birefringence under polarized light
- associated with chronic conditions (multiple myeloma, TB, RA)
50
Membranoproliferative Glomerulonephritis (MPGN)
Nephrotic Syndrome
Type 1: subendothelial IC deposits with granular IF "tram-track" appearance due to GBM splitting caused by mesangial ingrowth, associated with HBV, HCV
Type 2: intramembranous IC deposits "dense deposits", associated w/ C3 nephritic factor
-also present as nephritic
51
Diabetic Glomerulonephropathy
Nephrotic Syndrome
-nonenzymatic glycosylation (NEG) of GBM, inc. permeability, thickening
-NEG of efferent arterioles, inc. GBM, cause mesangial expansion
LM-mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesion)
52
Nephritic Syndrome
- inflammatory process
- when involves glomeruli, it leads to hematuria & RBC casts in urine
- associated with azotemia, oliguria, HTN (salt retention), & proteinuria (<3.5g/day)
53
Acute Poststreptococcal Glomerulonephritis
Nephritic Syndrome
- LM-glomeruli enlarged & hypercellular, neutrophils, "lumpy-bumpy" appearance
- EM-sunepithelial immune complex (IC) humps
- IF-granular appearance due to IgG, IgM, and C3 deposition along GBM & mesangium
- most frequent in children
- peripheral & periorbital edema, dark urine, HTN
- resolves spontaneously
54
Rapidly Progressive (crescentic) Glomerulonephritis (RPGN)
Nephritic Syndrome
-LM & IF- crescent-moon shape. crescents consist of fibrin & plasma proteins (C3b) with glomerular parietal cells, monocytes, & macs
-Several disease:
~Goodpasture's syndrome: type II hypersensitivity; abs to GBM & alveolar basement membrane, linear IF (hematuria/hemoptysis)
~Granulomatosis w/Polyangiitis (Wegener's) (cANCA)
~Microscopic polyangiitis (pANCA)
poor prognosis, rapidly deteriorating renal function (days to weeks)
55
Diffuse Proliferative Glomerulonephritis (DPGN)
Nephritic Syndrome
- due to SLE or MPGN
- LM- "wire looping" of capillaries
- EM-"subendothelial & sometimes intramembranous IgG-based ICs often with C3 deposition
- IF-granular
- most common cause of death in SLE. SLE & MPGN can present as nephrotic syndrome and nephritis syndrome concurrently
56
Berger's Disease (IgA nephropathy)
Nephritic Syndrome
- related to Henoch-Schonlein purpura
- LM-mesangial proliferation
- EM-mesangial IC deposits
- IF-IgA-based IC deposits in mesangium
- often present/flares with a URI or acute gastroenteritis
57
Alport Syndrome
Nephritic Syndrome
- mutation in type IV collagen, split basement membrane
- X-linked
- glomerulonephritis, deafness, & less commonly, eye problems
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Types of Kidney Stones
1. Ca
2. Ammonium Magnesium Phosphate "struvite"
3. Uric Acid
4. Cystine
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Kidney Stones: Ca
80%
inc. pH (calcium phosphate), dec. pH (calcium oxalate) percipitates
- radiopaque on x-ray
- conditions that cause hypercalcemia (cancer, inc. PTH) can cause hypercalciuria & stones
- oxalate crystals can result from ethylene glycol (antifreeze) or vit. C abuse
- Treatment: thiazides, citrate
- most common presentation: calcium oxalate stone in patient w/hypercalciuria & normocalcemia
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Kidney Stones: Ammonium Magnesium Phosphate "struvite"
15%
precipitates at inc. pH
radiopaque on x-ray
-caused by infection w/urease-postitve bugs (proteus mirabilis, staphlococcus, klebsiella) that hydrolyze urea to ammonia, urine alkalinization
-can form staghorn calculi that can be nidus for UTIs
61
Kidney Stones: Uric Acid
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5%, precipitates with dec. pH
-radiolucent with x-ray
-visible on CT & ultrasound
-strong association with hyperuricemia (gout), often seen in diseases with inc. cell turnover like leukemia
Treat: alkalization of urine
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62
Kidney Stones: Cystine
1%, precipitates with dec. pH
- radiopaque on x-ray
- most often secondary to cystinuria
- hexagonal crystals
- treat with alkalinization of urine
63
Hydronephrosis
- back-up of urine into the kidney, can be caused by urinary tract obstruction or vesicoureteral reflex.
- causes dilation of renal pelvis & calyces proximal to obstruction
- may result in parenchymal thinning in chronic, severe cases
64
Renal Cell Carcinoma
-Originates from proximal tubule cells, polygonal clear cells filled with accumulated lipids & carbohydrates
-most common in men 50-70, inc. incidence with smoking/obesity
-manifests clinically with hematuria, palpable mass, secondary polycythemia, flank pain, fever, & weight loss
-invades renal vein then IVC & spreads hematogenously
-metastasizes to lung & bone
-most common renal malignancy
-associated with gene deletion on chromosome 3 (deletion may be sporadic or inherited as von Hippel-Lindau syndrome)
-Associated with paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP)
-"silent" cancer b/c in retroperitoneum, commonly presents as a metastatic neoplasm
Treatment: resection if local disease, resistant to convential chemo and radiation
65
Wilms' Tumor (Nephroblastoma)
- most common renal mallignancy of early childhood (2-4)
- contains embryonic glomerular structures
- presents with huge, palpable flank mass and/or hematuria
- deletion of tumor suppressor gene WTI on chromosome 11
- may be part of Beckwith-Wiedemann syndrome or WARG complex: Wilm's tumor, Aniridia, Genitourinary malformation, & mental retardation
66
Transitional Cell Carcinoma
-most common tumor of renal tract system (can occur in renal calyces, renal pelvis, ureters, bladder)
-painless hematuria (no casts) suggests bladder cancer
-associated with problems in your Pee SAC:
Phenacetin, Smoking, Aniline Dyes, and Cyclophosphamide
67
Acute Pyelonephritis
- affects cortex with relative sparing of glomeruli/vessels
- presents w/fever, costovertebral angle tenderness, nausea, & vomiting
- white cell casts in urine
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Chronic Pyelonephritis
- result of recurrent episodes of acute pyelonephritis
- typically requires predisposition to infection such as vesicoureteral reflux or chronically obstructing kidney stones
- course, asymmetric corticomedullary scarring, blunted calyx
- tubules can contain eosinophilic casts (thyroidization of kidney)
69
Drug-Induced Interstitial Nephritis (tubulointerstitial nephritis)
- acute interstitial renal inflammation
- pyuria (classically eosinophils) & azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity
- nephritis typically occurs 1-2 weeks after certain drugs (diuretics, penicillin derivatives, sulfonamides, rifampin), but can occur months after starting NSAIDS
- associated with fever, rash, hematuria, & costovertebral angle tenderness, but can be asymptomatic
70
Diffuse Cortical Necrosis
- acute generalized cortical infarction of both kidneys
- likely due to a combination of vasospasm & DIC
- associated with obstetric catastrophes (abrupto placentae) & septic shock
71
Acute Tubular Necrosis
-most common cause of intrinsic renal failure
-self-reversible is some cases, but can be fatal if left untreated
-death most often occurs during initial oliguric phase
3 Stages:
1) Inciting Event
2) Maintencance Phase - oliguric; lasts 1-3 weeks, risk of hyperkalemia
3) recovery phase-polyuric; BUN & serum creatinine fall; risk of hypokalemia
-associated with renal ischemia (shock, sepsis), crush injury (myoglobinuria), drugs, toxins
-key findings: granular "muddy brown" casts
72
Renal Papillary Necrosis
- sloughing of renal papillae, gross hematuria & proteinuria, may be triggered by a recent infection or immune stimulus, associated with:
- diabetes mellitus
- acute pyelonephritis
- chronic phenacetin use (acetaminophen is phenacetin derivative)
- sickle cell anemia & trait
73
Acute Renal Failure (acute kidney injury)
- in normal nephron, BUN is reabsorbed (for countercurrent multiplication), but creatinine is not
- acute renal failure is defined as an abrupt decline in renal failure with inc. creatinine & inc. BUN over a period of several days
74
Prerenal Azotemia
Acute Renal Failure (acute kidney injury)
- as a reslut of dec. RBF (hypotension), dec. GFR
- Na+/H2O & urea retained by kidney in an attempt to conserve volume, so BUN/creatinine ration inc.
75
Intrinsic Renal Failure
Acute Renal Failure (acute kidney injury)
- generally due to acute tubular necrosis or ischemia/toxins; less commonly due to acute glomerulonephritis (RPGN)
- patchy necrosis leads to debris obstructing tubule & fluid backflow across necrotic tubule, dec. GFR
- urine has epithelial/granular casts
- BUN reabsorption is impaired, dec. BUN/creatinine ration
76
Postrenal Azotemia
Acute Renal Failure (acute kidney injury)
- due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies)
- develops only with bilateral obstruction
77
Consequences of Renal Failure
- inability to make urine & excrete nitrogenous wastes
- Acute (ATN) & Chronic (HTN, diabetes)
- Na+/H2O retention (CHF, pulmonary edema, HTN)
- hyperkalemia
- metabolic acidosis
- uremia-clinical syndrome marked by inc. BUN & inc. creatinine (nausea, anorexia, pericarditis, asterixis, encephalopathy, platelet dysfunction)
- anemia (failure of erythropoietin production)
- renal osteodystrophy
- dyslipidemia (especially inc. triglycerides)
- growth retardation & developmental delay (in kids)
78
Renal Osteodystrophy
- failure of vit D hydroxylation, hypocalcemia, & hyperphosphatemia, secondary hyperparathyroidism
- hyperphosphatemia also independently dec. serum Ca2+ by causing tissue calcifications, whereas dec. 1,25 (OH) vit D, dec. intestinal Ca2+ absorption
- causes subperiosteal thinning of bones
79
Renal Cysts: ADPKD
- formerly adult polycystic kidney disease
- multiple large, bilateral cysts that ultimately destroy the kidney parenchyma
- present with flank pain, hematuria, HTN, urinary infection, progressive renal failure
- Autosomal Dominant mutation in PKD1 or PKD2, death from complications of chronic kidney disease or HTN (caused by inc. renin production)
- associated with berry aneurysms, mitral valve prolapse, benin hepatic cysts
80
Renal Cysts: ARPKD
- formerly infantile polycysitc kidney disease
- infantile presentation in parenchymal
- autosomal recessive
- associated with congential hepatic fibrosis
- sig. renal failure in utero can lead to Potter's syndrome
- concerns beyond neonatal period include HTN, portal HTN, & progressive renal insufficiency
81
Medullary Cystic Disease
- inherited disease causing tubulointerstitial fibrosis & progressive renal insufficiency with inability to concentrate urine
- medullary cysts usually not visualized; shrunken kidneys on ultrasound
- poor prognosis
