Pathoma Chapter 12 Flashcards
(77 cards)
1
Q
What is horseshoe kidney?
A
- Conjoined kidneys usually connected at the lower pole
- Most common congenital renal anomly
- Most commonly located in the lower abdomen
- Horseshoe kidney gets caught on the inferior mesenteric artery root during its ascent from the pelvis to the abdomen
2
Q
What is the difference between unilateral and bilateral renal agenesis?
A
- renal agnesis = absent kidney formation
- Unilateral agenesis leads to hypertrophy of the existing kidney
- One kidney now has to do the work of two kidneys
- Functions fine until later in life
- Hyperfiltration increases risk of renal failure later in life
- Bilateral Agenesis leads to oligohydramnios (not enough amnitic fluid is produced) with lung hypoplasia, flat face with low set ears and developmental defects of the extremities (Potter’s Sequence)
- Incompatabile with life
3
Q
What is Potter’s Sequence?
A
- Due to Oligohydramnios: not enough amniotic fluid is produced
- Lung Dysplasia (lungs don’t develop properly)
- When the lung develops, one way that it grows is by stretch
- Breathing in and out amniotic fluid streches the lung
- If not enough amniotic fluid, lung can’t develop
- Flat face with low set ears
- no amniotic fluid means face will get pressed up against the wall of the uterus causing flat face with low set ears
- Limb Deformaties
- limbs are also pressued up against mom so they develop abnormally
4
Q
What is dysplastic kidney disease?
A
- Noninherited
- Congenital malformation of the renal parenchyma characterized by cysts and abnormal tissue
- Usually unilateral
- When bilateral, must be distinguished from inherited polycystic kidney disease
5
Q
What is Polycystic Kidney Disease? What are the two different versions?
A
- Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla
- Autosomal recessive form presents in infants as worsening renal failure and hypertension
- Newborns may present with Potter sequence
- Kidneys are not working properly so not producing enough amniotic fluid
- Newborns may present with Potter sequence
- Autosomal dominant form presents in young adults as hypertension (due to increased renin), hematuria, and worsening kidney failure
- Due to mutation in the APKD1 or APKD2 gene
- Cysts develop over time
- Associated with berry aneurysms, hepatic cysts and mitral valve prolapse
- If have family history of renal disease and there is death occuring b/c of renal disease or brain hemorrhage, think autosomal dominant polycystic kidney disease
6
Q
What is Medullary Cystic Kidney Disease?
A
- Inherited: autosomal dominant
- Defect leading to cysts in the medullary collecting ducts
- Parenchymal fibrosis results in shrunken kidneys and worsening renal failure
7
Q
What is acute renal failure?
A
- acute, severe decrease in renal function (develops in days)
- Hallmark is azotemia (increase in waste products in the blood: increased BUN and creatinine)
- Often with Oliguria: low production of urine
- 3 types: prerenal, postrenal and intrarenal azotemia
8
Q
What is prerenal azotemia?
A
- Due to increased blood flow to the kidneys
- Ex. Cardiac Failure
- Decreased blood flow results in decreased GFR, azotemia and oliguria
- Reabsorption of fluid and BUN ensues (serum BUN:Cr ratio >15)
- Because there is low blood flow to the kidney, the renin/angiotensin system will be activated and aldosterone will cause reabsorption of sodium and water
- B.c of water reabsorption, more BUN will be reabsorbed
- Tubular function remains intact (fraction excretion of sodium [FANa] <1% and urinary osmalility is [osm] > 500
- tubules can absorb sodium and concentrate urine still
9
Q
What is postrenal azotemia?
A
- Due to obstruction of the urinary tract downstream of the kidney
- Have back pressure which will decrease glomerular pressure
- Decreased outflow results in decreased GFR, azotemia and oliguria
- During early stage of obstruction, increased tubular pressure forces BUN into the blood (serum BUN:Cr >15)
- Tubular Function remains intact (FENa <1% and urine osm >500)
- With longstanding obstruction, tubular damage ensues resulting in:
- decreased reabsorption of BUN (serum BUN:Cr <1)
- decreased reabsorption of sodium (FENa >2)
- inability to concentrate urine (urine osm <500)
10
Q
What is Acute Tubular Necrosis?
A
- Injury and necrosis of tubular epithelial cells
- Most common cause of acute renal failure
- Intrarenal azotemia
- Necrotic cells plug tubules and the obstruction causes a decrease in the GFR
- It causes backpressure and backpressure counteracts glomerular pressure
- Brown, granular casts are seen in the urine
- Dysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN/Cr <15), decreased reabsorption of sodium (FENa >2%) and inability to concentrate urine (urine osm <500)
11
Q
What are the two causes of Acute Tubular Necrosis? What can prevent chemotherapy induced Acute Tubular Necrosis?
A
- Ischemia
- decreased blood supply resulting in necrosis of tubules
- often preceded by prerenal azotemia
- If bloodflow remains low for an extended period of time, can become ischemic
- proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to ischemic damage
- Nephrotoxic
- Toxic agents result in necrosis of tubules
- Proximal tubule is particularly susceptible
- Causes include aminoglycosides (most common), heavy metals (lead), myoglobinuria (crush injury to muscle), ethylene glycol (associated with oxalate crystals in urine), radiocontrast dye, and urate (ex. tumor lysis syndrome)
- Hydration and allopurinol are used prior to initiation of chemotherapy to decrease risk of urate-induced Acute Tubular Necrosis
- Toxic agents result in necrosis of tubules
12
Q
What are the clinical features of Acute Tubular Necrosis? How do you treat it?
A
- Oliguria with brown, granular casts
- Elevated BUN and creatinine
- low GFR means you can’t filter out BUN and Cr
- Hyperkalemia (due to decreased renal excretion) with metabolic acidosis
- Metabolic acidosis is due to the fact that you have a decrease in excretion of organic acids
- will have increased anion gap
- Reversible but often requires supportive dialysis since electrolyte imablances can be fatal
- Oliguria can persist for 2-3 weeks before recovery
- tubular cells (stable cells) take time to reenter the cell cycle and regenerate
13
Q
What are the brown, granular casts found in Acute Tubular Necrosis?
A
- Epithelial cells die, sloth off and obstruct the the tubule
- Dead epithelial cells then get casted in the shape of the tubule
- See dead endothelial cells making up the cast in the urine
- Looks brown and granular because cells are dead
14
Q
What is Acute Interstitial Nephritis?
A
- Drug-induced hypersentivity involving the interstitum and tubules results in acute renal failure (intrarenal azotemia)
- Causes include NSAIDS, penicillin, and diuretics
- Presents as oliguria, fever, and rash days to weeks after strating a drug
- Eosinophils may be seen in urine
- Resolves with cessation of drug
- May progress to renal papillary necrosis
15
Q
What is Renal Papillary Necrosis?
A
- Necrosis of renal papillae
- Presents with gross hematuria and flank pain
- Causes include:
- Chronic analgesic abuse (long term phenacetin or aspirin use)
- Diabetes Mellitus
- Sickle Cell trait or disease
- Severe Acute Pyelonephritis
16
Q
What is nephrotic syndrome?
A
- Glomerular disorders characterized by proteinuria (>3.5 g/day) resulting in:
- Hypoalbuminemia: pitting edema
- Hypogammaglobulinemia: increased risk of infection
- Hypercoagualable state: due to loss of antithrombin III
- Antithrombin III breaks up thrombin and other coagulation factors so you can’t produce thrombin
- Hyperlipidemia and hypercholesterolemia: may result in fatty casts in urine
- loss of protein causes blood to be tthin so liver reacts by putting excess fat in the blood to beef it up
17
Q
What is Minimal Change Disease (MCD)?
A
- Most common cause of nephrotic syndrome in children
- Usually idiopathic but may be associated with Hodgkins lymphoma
- Normal glomeruli on H&E stain
- lipid may be seen in the proximal tubule
- Effacement of foot process on eletron microscopy
- in MCD, you lose the foot processes on the glomerular filtration barrier
- No immune complex deposits; negative immunofluorescence
- Selective proteinuria
- change is so minimal that only protein lost is albumin
- Excellent response to steroids (damage is mediated by cytokines from T cells)
18
Q
What is the relationship between Minimal Change Disease and Hodgkins Lymphoma?
A
- in MCD, you lose the foot processes on the glomerular filtration barrier
- cytokines damage the foot processes
- In Hodkins lymphoma, get massive production of cytokines by Reed-Sternberg cells
- Cytokines can attack the kidney and knock out podocytes
19
Q
What is Focal Segmental Glomerulosclerosis?
A
- Most common cause of nephrotic syndrome in Hispanics and African Americans
- Usually idiopathic but can be associated with HIV, heroin use, and sickle cell disease
- Focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis is seen on H&E staining
- not all glomeruli are affected
- glomeruli that are affected have only part of it not working
- Effacement of foot processes on EM (flattened podocytes)
- No immune deposits; negative IF
- Poor response to steroids
- Progresses to chronic renal failure
- Patient with Minimal Change Disease that do not respond to steroids progress to Focal Segmental Glomerulosclerosis
20
Q
What does mebranous mean in terms of renal pathology?
A
- thickening of the membrane due to immune complex desposition
21
Q
What is Mebranous Nephropathy?
A
- Most common cause of nephrotic syndrome in Caucausian adults
- May be associated with Hep B or C, solid tumors, SLE or drugs (NSAIDS and penicillamine)
- immune complex deposition forms under podocyte or subepithelial
- Due to immune complex deposition
- Get granular immunoflorescence
- subepithelial deposits with spike dome appearance on EM
- Poor response to steroids
- Progresses to chronic renal failure
22
Q
Why does Membranous Nephropathy have a spike and dome appearance on EM?
A
- immune complex deposition forms under podocyte or on subepithelial cell
- podocyte responds by trying to lay down additional basement membrane
- generate a dome over the deposit
- in between the deposits, end up creating spikes
23
Q
What causes Membranoproliferative Glomerulonephritis?
A
- get immune complex deposition under the endothelium or under the basement membrane
- the mesangial cell that is holding the capillary together will notice the immune complex deposit and will proliferate its cytoplasm to cut through the deposit
- creates a tram track appearance b/c splits deposit in half
24
Q
What is Membranoproliferative Glomerulonephritis and what are the two subtypes?
A
- thick glomerular basement membrane formation with tram track appeance due to immune complex deposition
- Granular immunoflorence
- Divied into two suptypes based on location of the deposits
- Type I: subendothelial
- Associated with Hep B and Hep C
- more associated with Tram Tracks
- Type II: dense deposit disease
- intramembranous
- Associated with C3 nephritic factor
- Autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation and low levels of circulating C3)
- Type I: subendothelial
- Poor response to steroids
- Progresses to chronic renal failure
25
What is the effect of Diabetes Mellitus on the kidneys? How can progression to kidney failure be slowed down?
* High serum glucose leads to nonenzymatic glycoslylation of the vascular membrane resulting in hyaline arteriolosclerosis
* when you stick sugar on the basement membrane without the use of enzyme, thats nonenzymatic glycosylation: basement membrane becomes leaky and protein leaks into wall of blood vessel causing hyaline arteriosclerosis
* hyaline arteriolosclerosis causes thickening of the blood vessel wall which causes a decrease in the size of the lumen
* Glomerular effererent arteriole is more affected than the afferent arteriole, leading to high glomerular pressure
* Hyperfiltration injury leads to microalbuminuria
* Eventually progresses to nephrotic syndorme
* characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules
* ACE inhibitors slow progression of hyperfiltration-induced damage
* Angiotension II squeezes on efferent arteriole
* If you stop that from happening, have less squeezing down on efferent arteriole thus slowing down progression
26
How does systemic amyloidoisis affect the kidneys?
* Kidney is te most commonly involved organ in systemic amyloidosis
* Amyloid deposits in the mesangium, resulting in nephrotic syndrome
* Characterized by apple-green birefringence under polarized light after staining with Congo red
27
What is nephritic syndrome?
* Glomerular disorders characterized by glomerular inflammation and bleeding
* Limiting proteinuria (\<3.5 g/day)
* Oliguria and azotemia
* Salt retention with periorbital edema and hypertension
* RBC casts and dysmorphic RBCs in urine
* Biopsy reveals hyperceulluar, inflammed glomeruli
* immune complexes cause the inflammation
* immune complex deposition activates complement
* C5a attracts neutrophils which mediate damage
28
What type of casts are found with nephritic syndromes and why?
* glomerulus is bleeding so have RBCs going into the tubules
* the RBCs get casted in the shape of the tubule and are urinated out as a square cast of RBCs
29
What is Poststreptococcal Glomerulonephritis (PSGN)? How does it present and how is it treated?
* Nephritic syndrome that arises after group A beta hemolytic streptococcal infection of the skin or pharynx
* occurs with nephritogenic strains: strain carrying M protein virulence factor
* May occur after infection with nonstreptococcal organisms as well
* Presents 2-3 weeks after infection as hematuria (cola-colored urine), oliguria, hypertension and periorbital edema
* Usually seen in children but may occur in adults
* Mediated by immune complex deposition: immune complexes start subendothelial and work their way up and pile up in subepithelial
* Deposits will eventually pass their way through
* Treatment is supportive
* Children rarely progress to renal failure
* Some adults develop rapidly progressive glomerulonephritis (RPGN)
30
What are the histological findings associated with Poststreptococcal Glomerulonephritis (PSGN)?
* Hypercellular, inflammed glomeruli on H&E
* Mediated by immune complex deposition (granular immunoflorescence)
* Subepithelial humps on EM
31
What is Diffuse Proliferative Glomerulonephritis?
* Due to diffuse antigen-antibody complex deposition usually sub-endothelial
* Most common type of renal disease in SLE
* Caused by mebranous nephropathy in lupus patients
32
What is Rapidly Progressive Glomerulonephritis?
* Nephritic syndrome that progresses to renal failure in weeks to months
* Characterized by crescents in Bowman's space (of glomeruli) on H&E
* Cresecents are comprised of fibrin and macrophages
* Various forms of Rapidly Progressive Glomerulonephritis which can be classified via immunofluorescence findings
33
Different Immunofluorescence findings in Rapidly Progressive Glomerulonephritis: Linear Immunofluorescence Pattern
* Goodpasture syndrome
* have an antibody against collagen in glomerular and alveolar basement membranes
* Presents as hematuria and hemoptysis
* Clasically in young adults
34
Different Immunofluorescence findings in Rapidly Progressive Glomerulonephritis: Granular Immunofluorescence Pattern
* Poststreptococcal Glomerulonephritis (PSGN) or diffuse proliferative glomerulonephritis
* Diffuse proliferative glomerulonephritis is due to diffuse antigen-antibody complex deposition in the sup-endothelial
* Most common type of disease in SLE
35
Different Immunofluorescence findings in Rapidly Progressive Glomerulonephritis: Negative Immunofluorescence Pattern
* limited immune so need to perform C-ANCA (Anti-proteinase 3 which binds in cytoplasm) and P-ANCA (Anti-myeloperoxidase which binds around nucleus)
* Positive C-ANCA (Anti-proteinase 3): Granulomatosis with polyangitis
* get involvement of lung = hemoptysis
* get involvement of kidney = rapidly progressive glomerulonephritis
* also involves nasopharynx: ex. sinus infections
* nasopharynx symptoms not seen in Goodpasture syndrome
* Positive P-ANCA (Anti-myeloperoxidase)
* Microscopic polyangitis or Churg-Strauss
* granulomatous inflammation, eosinophilia and asthma are only seen in Churg-Strauss
36
What is IgA nephropathy (Berger Disease)?
* IgA immune complex deposition in mesangium of glomeruli
* most common nephropathy worldwide
* Presents during childhood as episodic gross or micrscopic hematuria with RBC casts, usually following mucosal infections
* IgA is increased during infections
* IgA immune complex deposition in the mesangium is seen on immunoflorescence
* May slowly progress to renal failure
37
What is Alport Syndrome?
* Inherited defect in Type IV collagen
* Mostly X-linked
* Results in thinning and splitting of the glomerular basement membrane
* Presents as isolated hematuria, sensory hearing loss and ocular disturbances
38
What is a urinary tract infection?
* Infection of urethra, bladder or kidney
* Most commonly arises due to ascending infection
* starts in urethra and works its way up
* Increased incidence in females
* Risk factors include sexual intercourse, urinary stasis, and catheters
39
What is Cystitis and what are the symptoms?
* Infection of the bladder
* Presents as dysuria (painful urination), urgency and suprapubic pain
* systemic signs (fever) are usually absent
40
Lab Findings of Cystitis
* Urinalysis:
* cloudy urine with \>10 WBCs/high power field
* Dipstick:
* positive leukocyte esterase (due to pyuria or pus in the urine)
* positive for nitrites (bacteria convers nitrates to nitrites)
* Culture: greater than 100,000 colony forming units
41
What are the causes of Cystitis?
* E.Coli: most common
* Staphylococcus saprophyticus
* increased incidence in young, sexually active females (E. coli is still more common in that population)
* Klebsiella
* Proteus mirabilis
* alkaline urine with ammonia scent
* Enterococcus faecalis
42
What is sterile pyuria and what does it suggest?
* Sterile pyuria is the presence of pyuria (pus) with a negative urine culture
* Suggests urethritis due to Chlamydia or Neisseria gonorrhoeae (dominant presenting sign of urethritis is dysuria)
43
What is pyelonephritis and what causes it?
* Infection of the kidney
* Usually due to ascending infection
* Increased risk with vesicoureteral reflux
* Presents with fever, flank pain, WBC casts, and leukocytosis in addition to symptoms of cystitis (infection ascends from bladder to kidney)
* Most common pathogens are:
* E coli: 90%
* Enterococcus
* Klebsiella
44
What is a white blood cell cast?
* when infection ascends up from the ureter to the kidney, WBCs follow by traveling up the kidney tubules
* WBCs end up taking the shape of the tubules
45
What is Vesicoureteral reflux?
* ureters plug into the bladder at a particular angle to prevent reflux of urine back into the ureters
* if there is a malformation of this angle, there is an increased risk of reflux up into the kidney
* reflux into the kidney can lead to chronic scarring or fibrosis with atrophy of the tubules
46
What is Chronic Pyelonephritis?
* Intersitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
* Due to vesicoureteral reflux (children) or obstruction (BPH or cervical carcinoma)
* Leads to cortical scarring with blunted calyces
* scarring at upper and lower poles is chracteristic of vesicoureteral reflux
* Atrophic tubules containing eosinophilic, proteinaceous material resemble thyroid follicles (thyroidization of the kidney)
* Waxy casts may be seen in urine
47
What is nephrolithiasis?
* precipiation of a urinary solute as a stone
* Risk factors include high concentration of solute in the urinary filtrate and low urine volume
* low urine volume leads to increased concentration of solute
* Presents as colicky pain with hematuria and unilateral flank tenderness
48
Frequency/Causes/Treatment for Calcium Oxalate or calcium phosphate kidney stones
* Frequency
* most common type
* Usually seen in adults
* Causes
* Most common cause is idiopathic hypercalciuria
* patient puts excess calcium into the urine and calcium level in the blood is normal
* Hypercalcemia and its related causes must be exluded
* Also seen with Crohn's Disease
* small bowel damage in Crohn's disease results in increased reabsorpiton of oxilate which can then bind calcium causing formation of calcium oxilate stone
* Treatment
* Hydrochlorothiazide (calcium sparing diuretic)
* decreases calcium in the urine
49
Frequency/Causes/Treatment for Ammonium magnesium phosphate kidney stones
* Frequency:
* Second most common type
* Cause:
* Most common cause is infection with urease-positive organsims (Proteus vulgaris or Klebsiella)
* Alkaline urine leads to stone formation
* Treatment:
* Classically results in staghorn calculi in renal calyces which act as nidus for urinary tract infections
* treatment involves surgical removement of stone and eradication of pathogen
50
Frequency/Causes/Treatment for Uric Acid Kidney Stones
* Not visible on X-Ray
* Frequency:
* Third most common stone
* Radiolucent as opposed to the other types which are radiopaque
* Causes:
* Risk factors include hot, arid climates, low urine volume, and acidic pH
* Most common stone seen in patients with gout
* Hyperuricemia (in leukemia or myeloproliferative disorders) increases risk
* in leukemia or myeloproliferative dirsorders, generating lots of cells so making lots of uric acid when breaking down nuclei
* Treatment:
* Treatment involves hydration and alkalinization of urine (potassium bicarbonate)
* Allopurinol is also adminstered in patients with gout
51
Frequency/Causes/Treatment for Cystine Stones
* Frequency:
* rare cause of nephrolitiasis
* most commonly seen in children
* Causes:
* Associated with cystinuria
* a genetic defect of tubules that results in decreased reabsorption of cysteine
* cysteine piles up in the filtrate
* Treatment
* May form staghorn calculi
* Treatment involves hydration and alkalinization of the urine
52
What is Chronic Kidney Failure and what causes it?
* AKA end-stage kidney failure
* May result from glomerular, tubular, inflammatory or vascular insults
* Most common causes are diabetes mellitus, hypertension, and glomerular diseases
53
What are the clincial features of chronic kidney failure?
* Uremia
* Increased nitrogenous waste products in blood (azotemia) causes nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis and deposition of urea crystals in skin
* Salt and water retention with resultant hypertension
* Hyperkalemia with metabolic acidosis
* can't get rid of potassium and acid
* have anion gap metabolic acidosis
* Anemia due to decreased erythropoietin production by renal peritubular intersitital cells
* Hypocalemia due to decreased 1-alpha hydroxylation of vitamin D by proximal renal tubule cells and hyperphosphatemia
* phosphate binds with calcium so free calicum will be low
* Renal osteodystrophy (damage to the bone b/c of renal failure) due to secondary hyperparathyroidism, osteomalacia and osteoporosis
54
What is renal osteodystrophy? What are the three components?
* damage to the bone that occurs b/c of renal failure
1. osteitis fibrosis cystica
* patients have hypocalcemia and thus PTH levels rise
* causes a reabsorption of calcium which causes burnout of the bone
* leads to fibrosis and cyst formation
2. Osteomalacia
* can't mineralize the new bone that forms
3. Osteoporosis
* patients have metabolic acidosis
* one of the buffering systems against metabolic acidosis is to buffer it against the bone
* calcium is leached from the bones
55
What is the treatment for Chronic Renal Failure?
* Treatment involves diaylsis or renal transplant
* Cysts often develop within shrunken end-stage kidneys during dialysis, increasing risk for renal cell carcinoma
56
What is an angiomyolipoma?
* Hamartoma comprised of blood vessels, smooth muscle and adipose tissue
* Increased frequency in tuberous sclerosis
57
What is Renal Cell Carcinoma and what are the clinical findings for it?
* Malignant epithelial tumor arising from kidney tubules
* Presents with classic triad of hematuria, palpable mass and flank pain
* all three symptoms rarely occur together
* Hematuria is the most common symptom
* Fever, weight loss or multiple paraneoplastic syndrome may also be present
* Rarely may present with left-sided varicocele
* left spermatic vein drains into renal vein on left side
* blockage of the left renal vein will cause the left spermatic vein to varicocele
* Right spermatic vein drains directly into the IVC thus right sided varicocele is not seen
58
What are the lab findings for Renal Carcinoma?
* gross exam reveals a yellow mass
* microscopically, the most common variant exhibits clear cytoplasm
59
What causes Renal Carcinoma and what are the two forms of it?
* Pathogenesis involves loss of VHL (3p) tumor suppressor gene, which leads to increased IGF-1 (promotes growth) and increased HIF trasncription factor (increases VEGF and PDGF)
* Tumors may be hereditary or sporadic
* Sporadic tumors classically arise in adult males (60 years) as a single tumor in the upper pole of the kidney
* Major risk factor for sporadic tumors is cigarette smoke
* Hereditary tumors arise in younger adults and are often bilateral
* Von Hippel-Lindau disease is an autosomal dominant disorder associated with inactivation of VHL gene leading to increased risk for hemangioblastoma of the cerebellum and renal cell carcinoma
60
What is Wilm's Tumor?
* Malignant kidney tumor comprised of blastema (immature kidney mesenchyme), primitive glomeruli and tubules and stromal cells
* Most common malignant renal tumor in children
* Average age is 3 yrs
* Presents as large, unilateral flank mass with hematuria and hypertension due to renin secretion
* Most cases are sporadic
61
Syndromic Wilm's Tumors are found in what disorders?
1. WAGR syndrome
* **W**ilms tumor
* **A**niridia
* **G**enital abnormalities
* mental and motor **R**etardation
* associated with deletion of WT1 tumor supressor gene
2. Denys-Drash Syndrome
* Wilms tumor, progressive renal (glomerular) disease and male pseudohermaphroditism
* Associated with mutations of WT1
3. Beckwith-Wiedemann Syndrome
* Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy (muscles are different sizes on each side), and organomegaly
* Associated with mutations in WT2 gene cluster especially IGF-2
62
What is Urothelial (Transitional Cell) Carcinoma? What are the risk factors for it and how does it present?
* Malignant tumor arising from urothelial lining of the renal pelvis, ureter, bladder or urethra
* Most common type of lower urinary tract cancer
* Usually arises in the bladder
* Major risk factor is cigarette smoke
* Other risk factors are napthylamine (also in cig smoke), azo dyes and long term cyclophosphamide or phenacetin use
* Generally seen in older adults
* Classically presents with painless hematuria
* Tumors are often multifocal and recur
* often have multiple tumors that recur
* Have field deficit: all of endothelial surface is mutated and its only a matter of time before multiple tumors develop
63
What are the two pathaways that Urothelial (Transitional Cell) Carcinoma arises from?
1. Flat
* develops as high-grade flat tumor and then invades
* associated with early p53 mutations
2. Papillary
* develops as long grade papillary tumor that progresses to a high grade papillary tumor and then invades
* not associated with early p53 mutation
64
What is squamous cell carcinoma?
* Malignant proliferation of squamous cells, usually involves the bladder
* arises in a background of squamous metaplasia (normal bladder surface is not lined by squamous epithelium)
* Risk factors include chronic cystitis (causes chronic infection), Schistosoma haematobium infection (Egyptian male), and long standing nephrolithiasis
* Chronic inflammation is a risk factor
* Schistosoma embeds itself in bladder wall and causes chronic inflammation
65
Adenocarcinoma
* Malignant proliferation of glands, usually involving bladder
* Causes:
* Urachal remnant: tumor develops at the dome of the bladder
* urachus connects fetus to bladder with yoke sac
* allows bladder to drain waste into the yoke sac
* goes from the dome of the bladder through the umbilical cord
* lined by glandular cells
* supposed to go away but if it doesn't can cause cancer
* Cystitis glandularis
* chronic inflammation of the bladder resulting in columnar metaplasia in the bladder
* Exstrophy
* congenital failure to form the caudal portion of the anterior abdominal wall and bladder walls
* exposes part of the bladder to the outside world
66
Bartter Syndrome (AR)
* Reabsorptive defect in NaCl in the thick ascending loop
* Acts like loop diuretic
* losing sodium, potassium and chloride
* causes you to have a metabolic alkalosis b/c losing chloride
67
Gitelman syndrome
* reabsportive defect in NaCl in distal convoluted tubule
* Acts like thiazide diuretic
* less severe than Bartter syndrome
* only losing sodium and chloride
68
Liddle Syndrome
* Gain of function mutation of Na+ channel
* Increased Na+ reabsorption in collecting duct
* mimics having too much aldosterone
* Losing K+
* Results in hypertension
* Treat with Amiloride (K+ sparing)
69
Common Causes of Metabolic Alkalosis
* Vomitting
* Loop Diuretics
* Hyperaldosteronism
* Antacid use
70
Common Causes of Anion gap Metabolic Acidosis
* Addition of an acid that isn't Hydrochloric acid
* MUDPILES
* **M**ethanol
* **U**remia
* **D**iabetic Ketoacidosis
* **P**ropylene glycol
* **I**ron tablets
* **L**actic acidosis
* **E**thylene glycol
* **S**alicylates
71
Common Causes of Normal Gap Metabolic Acidosis
* Addition of Hydrochloric acid
* HARDASS
* **H**yperalimentation
* **A**ddison disease
* **R**enal tubular acidosis
* **D**iarrhea
* **A**cetazolamide
* **S**pironolactone (hypoaldosteronism)
* **S**aline infusion
72
What is Winter's Formula?
PCO2 = 1.5 (HCO3) +6-10
73
Anion Gap Formula
* AG= Na - (HCO3 + Cl)
74
What can cause a low Anion gap?
* albumen is low
* Unmeasured cations are high such as due to light chain excess (multiple myeloma)
75
Distal Renal Tubular Acidosis Type 1
* Distal tubule can't get rid of hydrogen ion
* Can't acidy the urine so the urine pH is very high (alkaline)
* Defect in ability to alpha intercollated cells to secrete H+
* Alpha intercolated cells can't reclaim K+ resulting in hypokalemia
76
Distal Renal Tubular Acidosis Type 4
* Hypoaldosteronism reuslting in hyperkalemia thus causing increased NH3 synthesis in Proximal convoluted tubule and decreased urine buffering of H+
* Will have high urine pH
* No aldosterone so can't exchange H+ ion to reabsorb in Na+
77
Type II Renal Tubular Acidosis
* Problem with HCO3 reabsorption in proximal convoluted tubule
* Classically caused by Franconi Syndrome
