Pathoma Kidney and Urinary Tract Pathology Flashcards
1
Q
What is the inheritance pattern of multicystic dysplastic kidney and what will be seen on histology?
A
It is sporadic and non-hereditary, usually unilateral
May be bilateral for the purposes of confusing you on examinations
Multiple cysts with CARTILAGE is typical
2
Q
Where do the cysts arise from in ADPKD vs ARPKD? What genes are awry in both conditions?
A
ADPKD - can arise from any duct (cuboidal epithelium)
-> polycystin 1 / 2 (PKD1/2) can be mutated
ARPKD - arise from collecting duct**
-> polyDUCTin is wrong -> cilia syndrome
3
Q
What are the clinical manifestations of ARPKD and what is the function of the missing protein? When does it present?
A
Missing protein = polyDUCTin - another nonmotile cilia syndrome
Presents in infancy, often prenatally
-> associated congenital hepatic fibrosis leading to portal hypertension
-> renal failure and hypertension.
Think “Cysts in the liver, cysts in the kidney”
4
Q
What are the clinical manifestions of ADPKD? One of these is a cardiac condition.
A
Cysts in the liver, brain, and kidney:
Liver - benign hepatic cysts
Brain - berry aneurysms of Circle of Willis
Kidney - Cysts destroying renal parenchyma, hypertension due to renin secretion -> progressive renal fialure
Heart - mitral valve prolapse
5
Q
What is medullary cystic kidney disease and how can you distinguish it from the polycystic kidney diseases? How is it inherited?
A
Autosomal dominant disease which predominantly features tubulointerstitial parenchymal fibrosis resulting in SHRUNKEN kidneys and progressively worsening renal function.
Cysts would be present in the medulla (collecting ducts), but are generally small and insignificant. Medullary cystic is a bit of a misnomer.
6
Q
What happens to the serum BUN/Cr ratio in intrarenal vs extrarenal causes of ATN and why?
A
serum BUN/Cr ratios -> increases above 15 in extrarenal causes, as tubules try to preserve volume and are functioning properly, and BUN can be reabsorbed while Cr cannot. Think BUN is resorbed to preserve medullary gradient.
Ratio falls below 15 in intrarenal AKI (i.e. ATN) because tubules are not functioning properly in reabsorption of BUN.
7
Q
What happens to the FENa in intrarenal vs extrarenal causes of ATN and why?
A
FENa = fractional excretion of sodium
Extrarenal - will be below 1% -> proper reabsorption of Na (until damage causes tubular failure)
Intrarenal - tubules failing - will be above 1%
8
Q
What happens to urinary sodium in pre-renal vs intrinsic renal? Urinary osmolality?
A
Urinary sodium: <20 mEq/L in pre-renal, >40 in intrinsic renal
Urinary osmolality: >500 mOsm/kg in pre-renal, <350 in intrarenal
-> loss of urine concentrating ability
9
Q
What physiologically causes post-renal azotemia and how do the values of post-renal change overtime from early to late?
A
Post-renal azotemia causes a backpressure which decreases GFR:
Early on:
Looks like pre-renal azotemia with decreased GFR:
Urine osmolality is normal (>500), FENa normal (<1%), and BUN/CR >15.
Late - excessive tubular damage causes intrarenal picture
Urine osmolality drops (<350), FENa abnormal (>2%), and BUN/CR <15
10
Q
What accounts for 90% of intrarenal azotemia and what will appear in the urine? What are the two subtypes?
A
Acute tubular necrosis - Muddy brown granular casts
- Ischemic - usually preceded by pre-renal azotemia
- Nephrotoxic
11
Q
What are the endogenous, toxic causes of ATN?
A
Hemoglobinuria (intravascular hemolysis)
Myoglobinuria - very common, due to severe muscle trauma / rhabdomyolysis
Endotoxemia - cytokine overproduction
Urate crystals - tumor lysis syndrome
12
Q
What are the exogenous toxic causes of ATN?
A
Aminoglycosides, radiocontrast dye, lead, cisplatin (gyno malignancies), ethylene glycol (oxalate crystals), amphotericin B
13
Q
How does the damage appear in ATN and where is it worst?
A
Appears patchy in ischemic causes and more continuous in nephrotoxic causes
Worst in proximal tubule and outer medullary segment of TALH
14
Q
What are the three distinct phases of ATN?
A
- Initiation phase - potentially reversible period if insult is corrected
- Maintenance period - irreversible loss of renal function lasting 1-3 weeks, as tubular cells take time to re-enter cell cycle / regenerate
- Recovery phase - renal function returning to normal, marked by polyuria
15
Q
What are the metabolic risks in the maintenance phase of acute renal failure?
A
Oliguria -> hyperkalemia, anion gap metabolic acidosis (unable to excrete daily produced acids), increased BUN (uremia) and creatinine
16
Q
What happens to urine production, electrolytes, and nitrogenous substances during the recovery period of ARF?
A
Polyuria -> BUN and serum creatinine fall as GFR recovers
Risk of hypokalemia from overexcretion
17
Q
What is the drug-induced hypersensitivity cause of intrarenal azotemia called? What are the symptoms?
A
Acute interstitial nephritis (AIN / ATIN)
-> involvement of interstitium with WBCs and eosinophils causes an acute renal failure
Symptoms are oliguria, fever, and rash starting days after administering a drug.
18
Q
What is the general progression of AIN?
A
Generally resolves with cessation of the drug, but may progress to renal papillary necrosis
19
Q
What drugs commonly cause acute interstitial nephritis?
A
Remember the P's Pee - diuretics -> since many are sulfa drugs Pain-free - NSAIDs Penicillins and cephalosporins Proton pump inhibitors RifamPin
Sulfa antibiotics can also cause it (i.e. TMP/SMX)
20
Q
What are causes of renal papillary necrosis other than progression from AIN?
A
SAAD papa with papillary necrosis
Sickle cell disease / trait - damages vasa recta
Analgesic nephropathy - think of the kletes in sketchy
Acute Pyelonephritis - damages tubules
Diabetes mellitus - damages vasa recta
-> conditions reduce renal blood flow and induce coagulative necrosis
21
Q
How does renal papillary necrosis present?
A
Gross hematuria and flank pain
-> will hurt alot because there is necrosis and sloughing off of papillae
22
Q
What is the #1 defining characteristic of nephrotic syndrome which causes the majority of the other symptoms?
A
Heavy proteinuria (>3.5 g/day), leading to hypoalbuminemia.
Most of the other symptoms will be as a result of this protein loss.
23
Q
What are the other general symptoms of nephrotic syndrome other than proteinuria (some will be related). What will be seen in the tubules?
A
- Generalized edema - dependent areas and periorbital, secondary to hypoalbuminemia
- Hyperlipidemia - liver increases lipoprotein synthesis to compensate for how thin blood has become due to protein loss
- Lipiduria - leakage of plasma lipoproteins into urine
- > creates fatty casts / “oval fat bodies” in the tubules - Increased risk of bacterial INFECTIONS and thromboembolic complications - due to loss of immunoglobulins and antithrombin III, respectively.
24
Q
What is the pathogenesis of Minimal Change Disease (MCD)?
A
Usually a primary disease, but may begin secondary to another immune disease, commonly Hodgkin’s lymphoma (cytokine-mediated cellular recruitment).
Insult is due to cytokine production -> damage podocytes -> massive proteinuria, mostly albumin.
25
What proteins are lost in MCD and what is the treatment? Why does this make sense?
Selective albuminuria due to loss of negative charge in GBM
Responds well to corticosteroids
- > corticosteroids should be the empiric treatment in children with nephrotic syndrome, without renal biopsy
- > makes sense b/c the damage is cytokine mediated, which would be able to be tuned down by steroids
26
What disorders and comorbidities are associated with causing secondary FSGS?
Most common cause of nephrotic syndrome in Blacks and Hispanics
1. Sickle cell disease - blacks
2. Heroin abuse - think of Mexican druglords
3. HIV infection - think of dz association with African American men
4. Glomerular hyperfiltration - obesity. Think of low income minorities.
27
What is primary FSGS caused by, and what will happen to the glomeruli / ECM?
Idiopathic
- > it is like really bad MCD -> nonselective proteinuria
- > damage to podocytes -> leakage of plasma proteins = hyalinosis
- > hyalinosis -> increased ECM production = sclerosis
Patchy hyalinosis and sclerosis can be seen.
28
What does focal vs segmental mean?
Focal - affects only certain foci of the kidney -> not all glomeruli affected (opposite of diffuse)
SeGMental - Sections of the glomerulus are affected, not the whole glomerulus. Just remember than SGM is in the word segmental. GM = glomerulus, S = sectioning. Sectioning of glomerulus
29
Why do we say FSGS is like a really bad minimal change disease?
On EM, we see effacement of the foot processes
Like minimal change disease, no immune complexes will be seen on IF
However, it responds poorly to steroids and progresses to chronic renal failure
30
Who is membranous nephropathy (also called membranous glomerulonephritis since it is the sister of membranoPROLIFERATIVE glomerulonephritis) common in and what causes the primary form? Is it immune-mediated?
Most common cause of nephrotic syndrome in Caucasian adults
Primary form is due to antibodies to the phospholipase A2 receptor
Caused by antibodies in all cases, so YES it is immune-mediated. However, we don't get a lot of complement deposition so it is nephrotic rather than nephritic.
31
What are the causes of secondary membranous nephropathy?
1. Medications - NSAIDs, penicillamine (also causes of AIHA, antibody production)
2. Infections - HBV, HCV, syphilis -> all things causing massive antibody production
3. Malignancies - solid tumors put new Ags in circulation
4. SLE - this is the nephrotic presentation of SLE (ANA-mediated antibody disease)
32
What is the pathogenesis of membranous nephropathy, other than the initial generation of antibodies?
Immune complexes form / deposit in subepithelial area
- > activation of complement, especially MAC (although C5a doesn't seem to recruit more cells)
- > podocyte and mesangial cell activation and production of injurious substances
- > capillary wall damage + proteinuria WITHOUT hypercellularity
33
What does LM and DIF show in membranous nephropathy?
LM - diffuse capillary wall THICKENING (membranous) with NORMOcellular glomeruli
DIF - Lumpy bump, granular appearance with immune complex deposition (IgG and complement)
EM - "spike and dome" appearance as spikes of GBM encircle the immune complexes (membrane is proliferating, forming a DOME), with spikes separating the immune complex domes.
-> subEPIthelial immune complex deposition (vs MPGN1/2)
34
What disease is associated with a mixed nephrotic / nephritic presentation? What disease is it related to?
Membranoproliferative Glomerulonephritis (MPGN)
Membrano - nephrotic
Proliferative - nephritic (inflammatory cells), as well as proliferation of mesangial cell processes
Related to membranous glomerulonephropathy -> immune deposits are just actually subendothelial or intra-membranous instead of subepithelial
35
What is MPGN, Type I caused by if it is primary or seconday? Where do things deposit?
Primary - idiopathic (all nephrotic syndromes can be idiopathic)
Secondary - related to SLE, or associated with HBV or HCV, other autoimmune conditions -> pretty much the same causes as membranous nephropathy
Subendothelial immune complex deposits
36
What is MPGN type II also called, and what causes it? What will happen to serum complement levels?
Type 2 = 2 letters = DD
Dense-Deposit disease -> development of an auto-antibody called C3 nephritic factor
-> IgG antibody stabilizes C3 convertase of alternative pathway (C3bBb) for persistent complement activation and decreased C3 levels
37
What does LM show for MPGN, both Types I and II?
Both show a "tram-track" or "split" appearance with PAS stain (stains only the glycoproteins in the basement membrane) -> GBM is split through the middle by mesangial cell processes
Glomerulus is hypercellular and proliferative, also appears somewhat lobulated (semidiscretely divided)
38
What do DIF show for MPGN Type I vs Type II?
Type I - granular deposition of IgG, C3, C1q, and C4 in the glomerulus diffusely (all complement components, not just alternative)
Type II - C3 deposition would be prominent in GBM adjacent to dense deposits, and in mesangium. C3 nephritic factor is IgG but will not stain because the C3 is formed peripherally. Also C1q and C4 would not be present (classical pathway components)
39
What would TEM show for MPGN Type I vs Type II?
Type I - Predominantly subendothelial electron-dense deposits, with duplication of GBM associated with mesangial cell processes coming (proliferating) through (tram-tracking is actually more prominent in this condition)
Type II - Extremely electron dense material in the lamina densa (dense-deposit disease) which splits GBM into two layers. No idea whats even accumulating cuz its not even C3.
40
What light microscopic changes of the glomeruli accompanies diabetic nephropathy?
Diffuse and nodular glomerulosclerosis
-> GBM thickening
-> Exaggerated mesangial expansion
-> Frank, hypocellular nodules with eosinophilic material
called Kimmelstiel-Wilson nodules (pathognomonic)
41
What is the pathogenesis of diabetic nephropathy? What will happen to GFR?
Nonenzymatic glycosylation of the glomerular basement membrane as well as arterioles, predominantly the efferent arteriole. Leads to hyaline arteriolosclerosis of vessels and sclerosis of mesangium
-> increases GFR initially, followed by decrease in GFR later in the disease
42
Where does amyloid tend to deposit in the kidney? How does this cause dysfunction?
In the mesangium, but can deposit anywhere
Causes dysfunction by compressing and decreasing luminal area of surrounding capillaries
-> causes a nephrotic syndrome
43
How do you tell amyloid nephropathy from diabetic nephropathy?
1. Congo red stain
2. General clinical picture should make it obvious
- > they can look very similar via LM.
44
Why do azotemia, oliguria, HTN, proteinuria, and edema happen in nephritic syndrome?
Reduction in GFR due to hypercellular inflammation blocking filtration
-> azotemia, oliguria, hypertension (sodium retention)
Glomerular membrane damage but not high enough GFR for massive proteinuria
-> RBCs lost, proteins not as much. Proteinuria -> edema from loss of oncotic pressure.
45
What urinary finding is a hallmark of glomerulonephritis?
RBC casts -> due to glomerular bleeding
46
What is the general shared characteristic of glomeruli in nephritic syndrome? What is the pathogenesis behind that?
Hypercellular, inflamed glomeruli
Immune-complex deposition activates complement; C5a attracts neutrophils, which mediate damage
47
What is the pathogenesis of acute post-strept glomerulonephritis (PSGN)? What type of hypersensitivity is it? This is all obvious, but what type of Strept must cause the infection to cause this syndrome?
Infection with nephritogenic strain of GAS -> production of antibodies to microbial antigens, especially strept exotoxins -> formation and deposition of immune complexes within glomeruli -> activation of complement with leukocyte infiltration and proliferation of mesangial cells
- Type III hypersensitivity reaction
Nephritogenic strain = Strain which possesses M protein to cause antibody production. Occurs following impetigo or strept pharyngitis.
48
What is seen on EM for PSGN and how does this differ from nephrotic syndrome in appearance?
Large, subepithelial deposits (below podocytes, like membranous glomerulonephropathy), which are LARGER and more interspersed, like humps (vs MGN where they are closer together and smaller).
Humps > domes in terms of size
49
What is seen on LM and DIF for PSGN?
LM - diffuse, enlarged, globally hypercellular glomeruli with neutrophils / macs and proliferation of mesangial cells
IF - "lumpy bumpy" appearance due to IgM / IgG / C3 deposition along GBM and mesangium
50
What is the prognosis for PSGN and the worst case scenario?
Vast majority recover with conservative management (gotta deal with that cola-colored urine), but generally the immune complexes will pass thru
Worst case - rapidly progressive glomerulonephritis (RPGN), or slow progression to chronic GN
51
What causes rapidly progressive glomerulonephritis (RPGN) and what are the crescents made of?
Usually follows a nephritic presentation, but can follow any severe glomerular injury which involves severe glomerular capillary wall damage -> leakage of fibrin into Bowman space, and formation of crescents (crescentic glomerulonephritis)
Crescents are made of fibrin, prolferating parietal cells (outer epithelial covering of Bowman's space), and macrophages
52
What type of RPGN will show a linear, diffuse immunofluoresence pattern and who does it classically affect?
Anti-GBM antibody, against noncollagenous domain in Type IV collagen
-> IgG staining of basement membrane of glomerulus and tubules
Classically presents in young adult males as part of Goodpasture syndrome
Goodpasture syndrome - Type II hypersensitivity
Noninherited auto immune disease, when you have anti-GBM antibodies against your lungs as well
-> associated with pulmonary hemorrhage
53
What is Type II RPGN and what does it follow? What will IF show?
Immune-complex RPGN
-> follows another glomerulonephritis which causes immune complex damage, allowing fibrin leak
i.e. Post-streptococcal GN, **diffuse proliferative glomerulonephritis due to SLE**, IgA nephropathy
DIF - granular, lumpy bumpy staining
54
What is Type III RPGN also called and what are the causes?
Pauci-immune = immune-negative, usually due to a type of small vessel vasculitis, but can be idiopathic.
All are associated with development of an ANCA, either c-ANCA or p-ANCA
55
What small vessel vasculidities are associated with Type III RPGN and what antibodies cause them?
Granulomatosis with polyangiitis - WeCener - c-ANCA - proteinase-3 antibody (P doesn't go with P)
Microscopic Polyangiitis - p-ANCA- anti-MPO
Churg-Strauss - p-ANCA
56
What does IF show for Type III RPGN?
No staining for IgG or C3 -> immune negative = pauciimmune
57
What is the most common glomerular disorder worldwide? Common clinical presentation? What will be seen in the urine?
IgA nephropathy - Berger disease (NOT Buerger)
Usually in older children or young adults - persistent microhematuria with episodes of macrohematuria following a mucosal infection (usually respiratory)
->RBC casts can be seen in the urine
58
What is the pathogenesis of Berger disease? Include the type of cell which is most damaged.
Susceptible individuals increase IgA synthesis following infection (or with celiac disease or decreased IgA clearance in hepatobiliary diseases)
- > increased polymeric IgA
- > deposition in mesangium of glomeruli
- > activation of alternative complement pathway with primary mesangial injury
59
What is seen on LM, IF, and TEM for Berger disease?
LM - variable focal / segmental mesangial proliferation + increased matrix
IF - granular deposition of IgA and C3, predominant in the mesangium.
TEM - Mesangial immune complex deposits of IgA
60
What is the inheritance of Alport syndrome, and what is the major defect?
X-linked, defect in Type IV collagen alpha chains
- > defective assembly and dysfunction of the GBM
- > thinning and splitting of BM
61
What are the clinical manifestations of Alport syndrome?
Can't see, can't pee, can't hear a bee
1. Renal disease - hematuria with RBC casts (nephritic syndrome), which progressively worsens to chronic kidney disease.
2. Sensorineural hearing loss (involves BM of ear)
3. Ocular involvement - retinal flecks, anterior lenticonus (weird lens shape) (due to involvement of BM of the eyes)
62
What does TEM show for Alport syndrome?
Irregular basement membranes of glomeruli and tubules, with alternating areas of thickening and thinning.
Along with interspersed breaking apart of lamina dense giving a "Basket-weave" appearance
63
How does LM look for classes III and IV lupus glomerulonephritis?
Class III - focal proliferative lupus glomerulonephritis
-> scattered glomeruli with increased cellularity, inflammatory cell infiltrates, and fibrinoid necrosis / thrombosis
Class IV - diffuse proliferative glomerulonephritis
-> Majority of glomeruli with the features of Class III
Wire looping of capillaries is common in both types.
64
What special LM finding is seen most often with Types III and IV lupus glomerulonephritis and why?
Types III & IV are both commonly seen to have "wire looping" of capillaries
-> rigid thickening of glomerular capillary walls, especially due to subENDOthelial immune complex deposition.
Think "wire lupus".
Can happen in other types as well, but less common.
-> remember that this can progress to a Type II RPGN.
65
Are immune complex deposits of lupus in the kidney limited to the glomerulus?
No -> immune complexes commonly deposit within tubular basement membranes as well
66
How do you tell Wegener's and Goodpasture's syndrome apart clinically?
Wegener's - much more likely to present with sinusitis
Goodpasture's should not present with sinusitis, just the pulmonary symptoms
These will both present with RPGN. Differentiate the two often on the basis of the IF. Biopsy is linear for Goodpasture, and pauci-immune for Wegener's (Granulomatosis with Polyangiitis).
67
What do urinalysis, dipstick, and culture show for bacterial cystitis?
urinalysis - >10 WBC/hpf, with urine often cloudy
dipstick - leukocyte esterase and nitrite positive (bacterial)
Culture - >100,000 CFU / mL
68
What should you be thinking if there is sterile pyuria? What does this term mean in terms of lab tests?
Makes you suspect urethritis, probably Chlamydia or Neisseria gonorrhea
Labs with urine with >10 WBC/hpf
Culture will be negative (far less than 100,000)
69
What are some conditions which increase the risk of UTI becoming acute pyelonephritis?
1. Obstruction of urine flow at any level - BPH, neurogenic bladder in diabetes, urethral stricture
2. Vesicoureteral reflux
3. Instrumentation of GU tract / indwelling catheter
4. Pregnancy - gravid uterus obstructs one or both ureters
5. Immune dysfunction states - AIDS, diabetes, steroids
6. Age / sex
70
What is the pattern of susceptibility to UTIs with respect to age and sex?
Before age 1: Boys - since posterior urethral valves is such a common congenital anomaly, also VUR
After age 1 to age 55: Women - short urethral, lack of prostate antibacterials, honeymoon cystitis
After age 55: Men, due to BPH
71
What does acute pyelonephritis look like microscopically / what is spared? Common causative organisms?
Intense neutrophilic interstitial / tubular infiltrate, with marked tubular destruction -> causes WBC casts which are pathognomonic, as well as systemic symptoms.
-> glomeruli and vessels are relatively spared
Organisms: E. coli, Klebsiella, Enterococcus
72
What are the possible structural underlying causes of vesicoureteral reflux?
1. Deficiency in longitudinal muscle of the ureter which causes ureter to enter bladder without sufficient tunneling -> does not close during detrussor contraction
2. Congenital para-ureteral diverticulum -> dilatation disallows bladder contraction
3. Inflammation of bladder wall, making it stiff.
73
What is the cause of chronic pyelonephritis and how does it appear grossly?
Repeated bouts of acute pyelonephritis
Appears as severe scarring of renal parenchyma, calyces, and pelvis. This leads to **blunted calyces**. Cortex will be thinned by numerous broad scars
74
What are the underlying conditions which predispose to chronic pyelonephritis? What pattern of scarring will vesicoureteral reflux cause?
Vesicoureteral reflux and chronic obstructing kidney stones.
Very bad vesicoureteral reflux will cause scarring at upper and lower poles of the kidney (think of the jets shooting into the kidney)
75
How will chronic pyelonephritis appear microscopically?
Tubules contain eosinophilic casts resembling thyroid tissue -> **thyroidization of tubules.**
Everything else will be scarred and fibrosed -> glomerulosclerosis and interstitial fibrosis, with tubular atrophy (obviously)
76
What are the most common causes of calcium stones?
1. Conditions of high calcium:
- Idiopathic hypercalcemia
- Hypercalciuria with hypercalcemia (bone disease, sarcoidosis, hyper-PTH)
2. Conditions associated with high oxalate:
- Crohn's disease -> small bowel damage increases oxalate resorption (unabsorbed fats become saponified with calcium, increasing free oxalate for resorption)
- vegetarians -> diet rich in oxalates
77
Are calcium stones, AMP stones, uric acid stones, and cystine stones radiotranslucent or radioopaque? Which ones can form staghorn caliculi?
Calcium stones - radio-opaque
Ammonium-magnesium-phosphate - radio-opaque (mineral) -> commonly cause staghorn caliculi
Uric acid stones - radiotranslUcent
Cystine stones - radiolucent (no minerals in amino acids)
-> rarer cause of staghorn calciuli
78
Who tends to get uric acid stones?
1. Patients with gout
2. Patients with tumor lysis syndrome / rapid cell turnover (i.e. leukemia treatment)
3. Patients with very acidic urine
79
Which types of stones are particularly prone to precipitate in acidic urine?
Uric acid stones, cystine stones
-> both types are radiotranslucent and can be treated with acetazolamide for alkalinization
Calcium OXALATE stones are also associated with acidic urine, but not precipitated by it
-> since acidic urine proximally is associated with increased citrate resorption -> increased calcium oxalate stone risk.
80
What causes cystinuria? When should you suspect this?
Autosomal recessive PCT cystine-reabsorbing transporter
```
Poor absorption of four amino acids:
COLA
Cystine
Ornithine
Lysine
Arginine
```
-> Suspect when a child presents with Staghorn caliculi
81
What are the three most common causes of CKD?
Diabetes, hypertension, and glomerular disease
-> lead to hyperfiltration. Increased GFR progressively damages and scars tubules
82
What are the consequences of uremia in chronic renal failure?
Nausea, anorexia
Pericarditis - uremic pericarditis is serous or fibrinous
Platelet dysfunction - bleeding
Encephalopathy with asterixis
Pruritis - Deposition of urea crystals in skin
83
What are two factors which cause anemia in CKD? What normally produces this factor?
1. Decreased synthesis of erythropoietin by interstitial fibroblasts of the peritubular capillary bed
2. Decreased RBC survival -> due to RBC microvascular trauma and oxidative stress
84
What happens to acid-base balance in early vs late CKD?
Early - non-anion gap metabolic acidosis -> ammonia production is not adequate due to too low # of nephrons
Late - anion gap metabolic acidosis -> GFR becomes so low that sulfate, urate, hippurate, and phosphate are retained
85
Is hyperkalemia generally a problem in CKD? Why or why not? When is it a problem?
No -> as GFR declines, aldosterone-mediated K+ secretion increases, and also colon begins secreting more K+
Hyperkalemia doesn't become a problem til GFR drops <20 mL/min
86
How does CKD affect sodium balance?
Inability to adapt to acute changes in sodium loss or increase sodium loading
- > Generally Na+/H20 retention
- > worsening of HF, pulmonary edema, hypertension
87
What does CKD do to growth in children?
Increased resistance to growth hormone -> growth retardation in children
88
What factors drive low calcium and high PTH in CKD?
1. Phosphate retention due to declining GFR
2. FGF23 - another hormone which increases urinary phosphate excretion, secreted by osteocytes, inhibits calcitriol formation -> hypocalcemia -> increases PTH.
3. Metastatic calcification - Ca+2 and phosphorous combining due to high phosphorous -> hypocalcemia
4. Decreased 1alpha hydroxylase activity in the kidney (less access to proximal renal tubule cells) -> hypocalcemia.
Drives PTH levels up -> secondary hyperparathyroidism.
89
What bone disease happens secondary to secondary hyperparathyroidism?
Osteitis fibrosa cystica
-> increased osteoclasts, abnormal bone turnover and fibrosis, with formation of bone cysts and hemorrhagic elements which make them appear brown in color
- > this is the disease caused by renal osteodystrophy, the primary problem caused by CKD
- > leads to subperiosteal bone thinning
90
What are the three components of renal osteodystrophy?
1. Osteitis fibrosa cystica - due to high PTH, as previously explained
2. Osteomalacia - due to inability to mineralize osteoid
3. Osteoporosis - due to metabolic acidosis (slow leeching of calcium to buffer the acid) + PTH
91
What two risks are associated with dialysis in CKD?
1. Prediposes for the development of cysts within the shrunken kidneys (due to obstruction and compensatory hyperplasia, not well understood) -> Acquired Cystic Kidney Disease
2. Renal Cell Carcinoma - increased risk of cancer in the setting of the hyperplasia of Acquired Cystic Kidney disease
92
How does the presentation of angiomyolipoma differ between sporadic and genetic/hereditary-predisposed individuals?
Tumor of blood vessel, smooth muscle, and fat
Sporadic - usually solitary lesion -> usually presents with hemorrhage
Hereditary - happens in Tuberous sclerosis (disease of hamartomas) -> usually multiple and bilateral, which is why it causes renal failure
93
What is the most common primary malignancy of the kidney? What is the cell of origin? How old / what sex are patients who generally present with it?
Renal cell carcinoma (RCC)
Cell of origin is proximal tubular (PCT) renal epithelial cells
Patients are generally older males (i.e. 60)
94
What paraneoplastic syndromes are most commonly associated with RCC?
1. Polycythemia - due to production of EPO
2. Cushing syndrome - due to ACTH secretion
3. Hypercalcemia - PTHrP
4. Hypertension - increased renin production
95
What is the function of VHL / how do things go awry in RCC?
Tumor suppressor gene on chromosome 3 (impaired in VHL diseaes) which inhibits hypoxia inducible factor
-> defect leads to increased transcription of HIF -> increased transcription of VEGF and PDGF
-> promotes tumor angiogenesis (explains the hematuria)
96
What are the most common benign / malignant tumors associated with von Hippel Lindau?
Hemangioblastomas - especially cerebellum
Pheochromocytomas
Bilateral renal cell carcinomas, happening at younger ages
97
What are the major risk factors for sporadic RCCs?
Cigarette smoking and obesity
Long-term dialysis with acquired cystic kidney disease
Occupational Exposures - cadmium, organic solvents (trichloroethylene in plastics), drugs like cyclophosphamide and phenacetin
98
Where does RCC commonly metastasize to? What can a left-sided RCC cause which a right-sided cannot?
Moves through IVC -> commonly goes to lung and bone
Left-sided = varicocele, due to compression of renal vein, which drains the testicular vein on the left but not the right
99
What is the most common pediatric renal neoplasm, how does it present? What cells is it comprised of? Is it normally sporadic or genetic?
Wilms tumor (Nephroblastoma) - presents as hematuria and hypertension (renin secretion)
Triphasic - Comprised of blastemal (primitive mesenchyme), epithelial (primitive tubules and glomeruli), and developed mesenchymal (stromal cells)
Normally sporadic, but may be genetic in 10% of cases.
100
What are the three syndromes associated with Wilms tumor? What gene is awry in each?
1. WAGR syndrome - WT1 DELETION
2. Denys-Drash syndrome - WT1 mutation
3. Beckwith-Wiedemann syndrome - WT2 (only one that is due to imprinting problem)
WT is a tumor suppressor gene on chromosome 11
101
What are the features of WAGR syndrome?
Wilms tumor
Aniridia
Genitourinary tract abnormalities - cryptorchism in males and streak gonads in females
R - Retardation (mental)
102
What are the features of Denys-Drash syndrome?
Wilms tumor, early onset-nephrotic syndrome, male pseudohermaphroditism (gonads are testes, but secondary sex characteristics are female, i.e. 5-alpha hydroxylase deficiency)
103
What are the features of Beckwith-Wiedemann?
Wilms tumor, macroglossia, organomegaly, hemihyperplasia (one side very large)
11q15 paternal UPD.
-> IGF2 is also on this chromosome -> increases IGF2.
104
What are the important risk factors for transitional cell bladder cancer?
Pee SAC
Phenacetin - discontinued NSAID
Smoking - aromatic hydrocarbons like naphthylamine
Aniline dyes - used by hairdressers, rubber industry
Cyclophosphamide
105
What is the classic presentation of transitional cell carcinoma? Does it recur?
Usually seen in older adults, presents with PAINLESS hematuria (renal cell carcinoma typically presents with flank pain)
Since the risk factors have field effect, these tumors are often multifocal and frequently recur.
Flat -> early p53 mutations, early invasion, poor prognosis
Papillary -> low grade, slower to invade, better prognosis
106
What cells are an oncocytoma comprised of? What must they be differentiated from? Is it benign or malignant?
Comprised of oncocytes - renal collecting duct intercalated epithelial cells (distal collecting duct, for H+/K+ exchange) which stain very eosinophilically due to abundant mitochondria and lack of perinuclear clearing (vs chromophobe RCC part of Birt-Hogg-Dube)
It is a benign tumor
107
How does oncocytoma appear grossly? What will be the patient's presenting symptoms?
Usually asympatomatic, but may have hematuria / flank pain
Appear as a sometimes-large, well circumscribed brown mass with a central white scar
108
When do patients get squamous cell carcinoma of the bladder? What's the prognosis? What species of Schistosoma predisposes?
Environments of chronic irritation and inflammation
- Longstanding nephrolithiasis
- Chronic cystitis (older women)
- Typically older adults
-Schistosomiasis is endemic to Egypt (can happen in young adults) -> remember this is S. hematobium
Poor prognosis
109
What is the most common cause of primary bladder adenocarcinoma? Where do they appear?
Arise from urachal remnant and are mucinous tumors which arise in dome or posterior wall of bladder
-> detected via mucinuria
Urachus is duct which attaches fetal bladder to umbilicus
110
What is cystitis glandularis? Why is it relevant?
Columnar metaplasia of cells of the bladder (in response to chronic irritation, but cause unknown)
It is a risk factor for adenocarcinoma of the bladder
111
What is the most common bladder tumor in kids?
Rhabdomyosarcoma - embryonic small blue cell tumor. Grow as gelatinous polyploid masses called "sarcoma botryoides" -> botryoides means grape-like
112
What causes exstrophy and what does it increase your risk of?
Congenital failure to form the caudal portion of the anterior abdominal and bladder walls
Increases your risk of adenocarcinoma of the bladder, like cystitis glandularis and urachal remnant.
113
What type of incontinence are diabetics most likely to have?
Overflow incontinence - afferent and efferent autonomic denervation prevents sensation of bladder being full, and prevents activity of bladder reflex
-> urine dribbles out of full bladder
114
What type of incontinence is BPH most likely to cause?
Usually overflow incontinence (due to obstruction and improper bladder emptying), but can also cause bladder irritation due to enlargement of prostate -> urge incontience
115
What type of incontinence is MS associated with?
Urge incontinence (overactive bladder / detrusor instability)
116
What is the cause of stress incontinence and what conditions does it exist in?
Outlet incompetence (i.e. intrinsic sphincteric deficiency due to trauma or pudendal nerve injury in childbirth, or urethral hypermobility)
- > often happens in pregnancy, obesity, or post-vaginal deliver
- > coughing or Valsalva manuever (increased intraabdominal pressure / stress) -> leakage of urine.
117
How should you think about the electrolyte state which occurs in cystic fibrosis (CF)? What should be done to reverse this?
Na+/Cl- wasting in sweat -> hyponatremic state, loss of ECF
-> contraction alkalosis ensues, with activation of RAA system to preserve volume -> alkalosis + hypokalemia
Entire state in general is very similar to ECF depletion with loop diuretic use (inhibition of NKCC -> loss of Na+/Cl- in urine).
118
What type of incontinence is associated with dripping due to coughing, lifting, or sneezing? Risk factors?
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Stress incontinence - due to urethral hypermobility or intrinsic sphincter deficiency
-> risk factors = obesity, vaginal delivery, prostate surgery, and postmenopausal women (estrogen maintains pelvic floor integrity)
#10962
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