Week 1 (Path Stuff) Flashcards
Diabetes Mellitus is a ___ disease (microvasculature) manifestations
Systemic hypertension is a vascular disease (arteriolar) manifestations (aka ____ disease)
Glomerular
Tubulointerstitial
Increased BUN and creatinine levels related to DECREASED GFR is _____ and can be classified as
1) ____ azotemia which occurs after hypoperfusion of the kidneys that impairs renal function in the absence of renal parenchymal damage
2) ____ azotemia which is when urine flow is obstructed distal to the calyces and renal pelvis
____ is azotemia PLUS a constellation of clincal findings and biochemical abnormalities resulting from renal damage
Azotemia
Prerenal azotemia
Postrenal azotemia
Uremia
AKI (Acute kidney injury aka Acute renal failure) is often associated with acute ____ necrosis aka acute tubular injury (ATI) (BUT NOT ALL OF THEM) and is characterized by a rapid ___ in GFR and CAN be reversible, or progress to ____
** So just to clear up some terms, there is AKI (Acute kidney injury, sometimes called ARF), ATI (Acute tubular injury, sometimes called ATN)
AKI is when there is a loss of renal function that develops within 7 days and therefore associated with decreased GFR, increased BUN and Creatinine (azootemia)
ATI is when the epithelial cells in the renal tubules necrosis and this can present WITH AKI, or it can turn INTO AKI and the necrosis is either due to ischemia or toxins
CKD (Aka chronic renal failure) is mild to clinically silent at first and overtime it progresses with azotemia, and then to the clinical signs and symptoms which then are called UREMIA and the GFR is extremely ___ (Less than 60ml/min for at least 3 months) and/or persistent albuminuria is seen
^** Also this is generally irreversible
ESRD (End stage renal disease) is when the GFR is less than ____ of normal and is the end stage of uremia
Tubular, decline, CKD (Chronic kidney disease)
^**CKD is also referred to as CRF (Chronic renal failure)
Decreased
5%
____ syndrome is glomerular disease characterized by SEVERE proteinuria aka MORE than ____gms per day
^** The protein lost is mainly ____, so you get HYPOalbuminemia, severe generalized edema, hyperlipidemia, and lipiduria
^** Manifestations of lipids is due to the fact that the liver is stressed and goes into compensatory mode that produces lipoproteins
*** SO NEPHROTIC SYNDROME IS LARGELY ASSOCIATED WITH ____
Nephrotic syndrome, 3.5
Albumin
PROTEINURIA
____ syndrome is glomerular disease dominated by acute onset of visible HEMATURIA, mild/moderate proteinuria, and hypertension…. Proteinuria and edema is common, but not as severe as nephrotic syndrome
*** SO NEPHRITIC SYNDROME IS LARGELY ASSOCIATED WITH ____
Nephritic
HEMATURIA
____ has signs of nephritic syndrome (hematuria) AND rapid decline in GFR (aka acute renal failure) and implies very severe glomerular injury
Isolated urinary abnormalities present with subnephrotic range proteinuria (aka protein in the urine, but less than 3.5 gm/day) and possibly some degree of hematuria
RPGN (Rapidly progressive glomerulonephritis)
Prototypical localizations of immune complexes in the glomerulus include
1) ____ seen in acute post-infectious glomerulonephritis
2) ____ deposits seen in Membranous nephropathy or Heymann Glomerulonephritis
3) ___ deposits seen in Lupus nephritis or Membranoproliferative Glomerulonephritis
4) ___ deposits seen in IgA nephropathy
5) Basement membranes
1) Subepithelial humps
2) Epimembranous
3) Subendothelial
4) Mesangial
The glomerulus can be injured via Humoral-mediated immune injury (aka Abs), Cell mediated immune injury, and activation of alternative complement pathway
The humoral (antibody) immunity can have:
1) ___ immune complex deposition with Fixed or Planted Ags
2) ____ immune complex deposition with Endogenous (native to body) or Exogenous Ags
^** Bacterial endocarditis is an example of an exogenous circulating Ag
In situe deposition on FOOT processes is seen in ____
In situ complex nephritis (Heymann) AND Circulating immune complex has a ___ pattern and Anti-GBM has a ___ pattern
1) In-situ
2) Circulating
Heymann
Granular, linear
Acute Diffuse Proliferative Glomerulonephritis (which can be post-streptococcal or Postinfectious)
Is an immune complex injury triggered by exogenous bacterial, viral, or fungal Ags
More importantly, we think of this Post-infectious glomerulonephritis is due to ____
This is characterized by marked _____ (involves everything in the glomerulus) AND leukocyte infiltration (aka inflammatory cell infiltration) with exudation within the glomerular tuft
Electron microscopy will show ____ immune complexes and these deposits fluoresce (IgG, IgM, and C3 in the mesangium and along the GBM which correspond to these humps)
This is generally seen in ___ (adults or children?) following pharyngitis or skin infections and associated with the strep pyogenic exotoxin ___ elaborated by Group A Beta-hemolytic strep
Also these patients present like ___ syndrome with hematuria, fever, malaise, nausea, and oliguria and also dysmorphic red cells or RBC ___ are seen
**Children tend to get ____, and adults tend to ____
^** You ____ (should or should not?) do a renal biopsy on a child since they tend to clear in 6-8 weeks… So just maintain sodium and water balance
Group A Beta-hemolytic strep
Hypercellularity, exudation (aka interstitial edema)
Subepithelial hump
Children, B (Strepotococcal pyogenic exotoxin B aka SpeB)
Nephritic, Casts
Better, NOT get better
Should NOT
Rapidly Progressing Glomerulonephritis (RPGN) aka Crescentic Glomerulonephritis
Characterized by ____/compacted glomerular tufts, ____ shaped mass of proliferating visceral and parietal epithelial cells, rapid obliteration of the urinary space, and infiltration of macrophages and leukocytes
RPGN also presents with nephritic syndrome and rapid decrease in GFR (if untreated)
^** Realize that this is NOT a single disease, but rather a feature of various diseases with the common denominator in ALL types being SEVERE glomerular injury
******* So once again, lets say a patient has goodpastures syndrome. Ok, so they have that disease. Now lets say that during the course of Goodpastures syndrome, the GFR declines 50% within 3 months and nephritic syndrome is seen along with crescent formation and linear anti-GBM Abs…. Now the patient’s disease would be called _____
Collapsed, Crescent
RPGN Type 1
RPGN can be classified as Type 1, Type 2, or Type 3
1) Type 1 is also called ____ and is associated with pulmonary or renal hemorrhage such as in ____ syndrome
^** IgG deposits in the GBM can be seen and ______ can be used to treat the patients aka Type 1 DOES respond to plasmapheresis, but type 2 and 3 DO NOT!!!
** So if you see Anti-IgG localized to the GBM with diffuse ____ staining deposits, think goodpasture syndrome
2) Type 2 is also called ____ and biopsy shows IgG and C3 deposits in the GBM
^** ___ pattern of staining, which is characteristic of immune complex deposition
Name the 4 important Type 2 associated diseases
3) Type 3 is also called ____ and associated with ____ antibodies, skin rash, upper respiratory granulomas, etc.
^** There is NO anti-GBM antibodies or immune complexes seen (pauci = few)
Name if these diseases can become Type 2 or Type 3
A) Lupus nephritis B) IgA nephropathy C) Granulomatosis with poluangiitis (Wegners) D) Henoch-Schonlein purpura E) Microscopic polyangiitis F) Post infectious glomerulonephritis
*****Dont be confused, realize the Acute Diffuse Post-infectious glomerulonephritis does not present with cresents… It simply means that OVER TIME, it can progress to CRESENTIC Glomerular disease
Same idea with the other shit….
So as another example: Only SOME IgA nephropathys progress overtime to where they become a cresentic glomerulonephritis and at this point, are classified as a TYPE ___ RPGN
Also 50% of PRIMARY renal diseases associated with RPGN have type ___ patterns
1) Anti-GBM Antibody, Goodpasture syndrome
Plasmapheresis
Linear
2) Immune complex
Granular
Post-infectious, IgA nephropathy, Lupus, and Henoch-Schonlein Pupura
3) Pauci-immune, ANCA
A) 2 B) 2 C) 3 D) 2 E) 3 F) 2
2
3
Nephrotic syndrome
Remember, this is where Proteinuria is seen (Proteinuria > 3.5gm in 24 hour period)
^** Occurs due to the GMB becoming diffusely leaky or porous to proteins, especially albumin… And remember we also usually don’t see hematuria
The serum albumin, which is the main protein being excreted, is therefore ____ aka hypOalbuminemia (usually less than 3gm)
Also severe generalized ____ is commonly seen along with hyperlipidemia and lipiduria
In children younger than 17 that exhibit Nephrotic Syndrome, 95% of these cases are ascribable to ___ glomerular disease caused by ____
In adults, Nephrotic Syndrome is more associated with ____ diseases in contrast to children (specifically, ___ or ___ diseases), but realize still 60% of the adult cases are still Primary glomerular disease
^** so just to recap, BOTH adults and kids more often have nephrotic syndrome due to a primary disease. However, compared to kids, adults have a greater likelihood of getting it from a systemic disease
^** In adults, the primary forms are caused by ____ or ____
Decreased
Edema
PRIMARY, Minimal-change disease (aka nill disease)
Systemic (aka secondary), Diabetes Mellitus or Systemic Lupus Erhthematosus
FSGS (Focal segmental glomerulosclerosis) or Membranous glomerulopathy
So once again, there are usually 3 PURE protein disorders aka Primary renal diseases for nephrotic syndromes which are
1) Minimal change disease (nil disease)
2) Membranous glomerulopathy
^** Realize this is the SAME thing as membranous nephropathy
3) FSGS (Focal segmental glomerulosclerosis)
^** Of the 3 however, ___ is the most likely to have some degree of hematuria
** Realize the # 2 and 3 can be either a pattern OR a diagnosis, but Minimal change disease is ALWAYS a diagnosis
FSGS
Membranous Glomerulopathy (aka nephropathy)
75% of the cases are primary are characterized by Abs to the renal autoantigen _____ receptor with involvement of complement (MAC) and IgG4
Often secondary causes of Membranous Glomerulopathy (describing the pattern, not diagnosis) include ___ like malaria, syphilis, hep B and C, or HIV along with malignant diseases like carcinomas/lymphomas and others, or drugs
85% of Membranous Glomerulopathy cases have ____ syndrome (proteinuria) and one way to contrast Membranous Glomerulopathy with Minimal change disease, is that MG has _____ proteinuria (which means large serum proteins are equally part of the exhibited proteinuria as well as smaller proteins like albumin)
**Another way to contrast MG with MCD is that in MCD, children respond ____ to steroids, and in MG they respond ____*
^** So if a patient has MCD, they ALWAYS respond well to steroids… And if they don’t do well, they probably have some other glomerular pattern like GM or FSGS
** Also patients with Mg do not have kidney transplants because this problem often re-accurs
Upon microscopy, the diffuse ___ of the capillary walls with NO increased cellularity and ___ are often seen projecting from the basement membrane towards the urinary space
** So if you see the word SPIKE and DOME, the answer it ____****
*****There patients are at highest risk for ____
**Also realize you can tell the difference between MN and MPGN due to the fact that MN involves ONLY the basement membrane and MPGN involves BOTH the basement membrane AND mesangial cells***
PLA2
Infections
Nephrotic syndrome, non-selective
Well, poorly
Thickening, spikes
Membranous Glomerulopathy
Renal vein thrombosis
In membranous glomerulopathy 3 things occur:
1) The foot processes of the epithelial cells will be ___
2) The basement membrane will be ___ (5-20x)
3) ____ deposits of dense IgG aggregates will be seen
^** Realize you see foot processes fusion in ANY disorder with nephrotic syndrome, but the only disorder where you see ONLY foot process fusion is ____*****
Immunofluorescences will show granular ____ IgG deposits along the GBM (But realize Lumpy-Bumpy is NOT chracterisitc of this, it is seen in other problems)
1) Effaced (aka removed/fused/simplified),
2) Thickened
3) Sub-epithelial
Minimal change disease (MCD)
Lumpy-Bumpy
Minimal Change Disease (MCD) also presents as nephrotic syndrome with edema (similar to MG), but remember ALL YOU SEE IS ____ and most common incidence is between 2-6 years of age and commonly follows a VIRAL ____ infection or viral immunizations…. Be careful because IgA nephropathy also commonly follows a respiratory infection
^** AKA the principle lesion is in the VISCERAL epithelial cells which shows a uniform and diffuse effacement of foot processes
Remember, unlike MG which is ____ proteinuria, this is highly ____ proteinuria (aka mainly composed of albumin)
Last but not least, remember, they respond well to ____, unlike MG
***** So if you see effacement with NORMAL glomeruli, think MMD
Foot process fusion (FPF), Respiratory
Non-selective, selective
Steroids
FSGS (Focal segmental glomerulosclerosis)
^** Can sometimes be confused with Rapidly Progressing Glomerulonephritis (RPGN) aka Crescentic Glomerulonephritis but it does NOT just involve bowmans capsule, instead it is a sclerosing pattern that extends deep into the glomerular tufts
FSGS presents with Neph___ syndrome and more common in ___ (kids or adults?), but in a child who has nephrotic syndrome and does NOT respond to steroids, they most likely have a childhood manifestation of FSGS
Also remember, this is the one that has a higher incidence of hematuria, decreased GFR, and HT
50% of patients progress to ESRD
^** So realize that FSGS can be a primary diagnosis (idiopathic cause) OR it can be descriptive of other diseases but is important for these other diseases because it implies a ___ prognosis due to the fact that most progress to CKD and ESRD
There is also a collapsing variant of FSGS, aka a secondary FSGS, which is called ____ where proliferation and ____ of the glomerular visceral epithelial cells is seen AND ___ within endothelial cells (which are NOT see in idiopathic/primary FSGS and therefore can be diagnostic… These are seen in SLE though)
^** Common in Black people
In contrast to MCD, proteinuria is ____ (selective or non-selective?), there is ___ response to steroids, and higher incidence of hematuria and decreased GFR and HT
^** Realize these are similar to MG, but the difference is that MGs have basement membrane thickening whereas FSGS has sclerosis and hyalinosis… Also ___ and C3 is often seen on microscopy in FSGS
(All 3 MG, FSGS, and MCD have loss of foot processes)
Nephrotic, adults
Poor
HIV nephropathy, hypertrophy, tubuloreticular inclusions
Non-selective, poor
IgM
MPGN (Membranoproliferative Glomerulonephropathy)
Mostly associated with a PATTERN of immune-mediated injury, rather than a specific diagnosis
Primary MPGN is broken down further into 2 different categories
1) Type 1 MPGN
^** Type 1 has _____ deposits seen on electron microscopy and IgG and C3 (complement); along with and C1q and C4 is seen on immunofluorescence, which is not seen in Type 2
^** Realize this is involved with the classic complement pathway AND alternative complement pathway
2) Type 2 MPGN (aka DDD)
^** Type 2 has ____ deposits seen on electron microscopy and is a _____ glomerulopathy (aka Autoantibody alternative complement) aka the C3 complement is NOT inside the dense deposits, instead it is outside
^** So in Type 2, ____ IgG autoantibodies bind to C3 convertase which leads to continuous and excess activation of the ____ complement pathway and this causes C3 to be deposited as granular or linear foci in the BM on either side, but NOT within and also C3 is often seen in the Mesangium in characteristic ___
BOTH of these present with ___ syndrome, but of these 2, Type ___ MPGN is most likely to present also with PROTEINURIA aka Type 1 presents as MIXED
MPGN 1 and 2 characteristics include alterations in the GBM that include thickening and ____ of the BM aka “tram-trak” appearance, ____ cell proliferation (this is why sometimes MPGN can be called Mesangiocapillary glomerulonephritis), and leukocyte infiltration (like neutrophils)
In Type 1 and Type 2 MPGN, one would see GBM thickening and ___ due to an increased mesangial matrix that dissects (aka interposes) and splits the GBM
Most commonly these occur in ____ (children or adults?) and 50% of patients with MPGN Type ___ develop chronic renal failure over a 10 year span but type 2 is a worse prognosis
1) Subendothelial
2) Dense Deposits, C3
C3NeF (Nephritic factor), alternative, mesangial rings
Nephritic, Type 1
Splitting, Mesangial cell
Splitting
Children, 1
Secondary MPGN Type 1 occurs ONLY in ____ (children or adults?) and is associated with chronic ____ from an infection, autoimmune disease, or neoplasia
MPGN Type 2 can NOT be a secondary disease, it is ONLY primary and presents mainly in children (Type 1 primary also presents mainly in children)
Which type of MPGN has a worse prognosis and generally these patients have severe renal disease?
Adults, chronic antigenemia (Ags in the blood)
Type 2
IgA nephropathy
Presents with characteristic deposition of ____ in the mesangium upon immunofluorescence and acute, ____, mesangial cellular proliferation along with an increased mesangial matrix is seen
There are mesangial and paramesangial dense deposits
IgA nephropathy is often a cause of ____ gross or microscopic ____… So if you see recurrent hematuria, consider this in your diff dx
Recurrent episodes of hematuria with NO progression of renal disease occurs in most patients, but the disease progresses to CHRONIC renal failure in 15-40% of patients over a 20 year period
**This disease is more common in whites and asians, male, family histories, and older children/young adults… Often IgA nephropathy follows ____ (respiratory or less common, GU), and the infection occurs at the same time as the hematuria*********
^** Note that MCD also commonly follows a respiratory infection (don’t confuse, should be easy)
IgA, focal
Recurrent, Hematuria
Infections
There are two diseases associated with IgA nephropathy and include
1) ____ disease which is a Renal IgA nephropathy that is NOT systemic
2) ____ disease which is an IgA nephropathy that IS systemic, often exhibiting skin (purpuric) manifestations and involvement of the abdominal viscera other than the kidney
^** So HSP is an IgA mediated systemic vasculitis syndrome but if you are considering IgA nephropathy as the diagnosis, rather than a pattern, than it is a PRIMARY Renal-glomerular disease aka ____ syndrome
1) Berger disease
2) HSP (Henoch-Schonlein purpura)
Berger
Primary glomerular diseases progressing to CGN (Chronic Glomerulonephritis) occurs in 90% of patients with _____, 50-80% of patients with ____, and then various percentages in other diseases
CGN is pretty much end stage glomerular disease and usually arises from a known disease (like we just explained with the primary renal glomerulonephritis), but sometimes it can arise from a patient with NO history of any recognized forms of glomerulonephritis (so either these were asymptomatic forms, unknown/unrecognized/ or uremia)
It presents with a ___ cortex, glomeruli obliteration leading to acellular eosinophilic masses, and due to the HT that occurs with it there is arterial and arteriolar ____ and MOST importantly, there is diffuse ____ scaring
^** The symmetrical scaring is important, because it contrasts that from Chronic Pyelonephritis which presents with IRREGULAR scarring
Crescentic GN, FSGS
Thinned, sclerosis, symmetrical
Hereditary nephritis with glomerular involvement consists of two major diseases ____ or ____ and 80% of patients with a family history of hematuria or recurrent hematuria during childhood have one of these disorders
___ has irregular THICKENING of the basement membrane, lamination of the lamina dense, and foci of rarefaction aka “moth eaten” or “frayed”
___ has irregular THINNING of the basement membrane due to mutations in the Alpha3 or Alpha4 chains of ____
Most patients with TBMD are ___ inheritance and Alport syndrome patients are _____ for an ____ inheritance pattern
^** Alport is usually ___-linked and due to defective ____ from one of it’s ___ chains being mutated so if you stain for antibodies to these alpha chains, it will come up NEGATIVE
So once again, if you see “basket weave” or “moth-eaten” thickened basement membranes, think ____
**** AUDITORY AND EYE PROBLEMS CAN DEVELOP IN ___ SYNDROME
Alport syndrome or TBMD (Thin basement membrane disease aka Benign familial hematuria)
Alport syndrome
TBMD, Type 4 collagen
Heterozygous, homozygotes, autosomal recessive
X-linked, Type 4 collagen, alpha
Alport syndrome
Alports
******______ associated with glomerulonephritis is NOT a septic embolic phenomenon, instead it is an immunological phenomenon *******
Bacterial Endocarditis
Diabetic Nephropathy
First, realize diabetic patients usually have an increased ___ levels in their urine
Two major causes for diabetic glomerular lesions to develop
1) Metabolic defects linked to ____ and advanced ____ of end products, which causes the GBM to thicken and the mesangial matrix to increase (sclerosis)
2) Hemodynamic effects associated with glomerular ____ (aka they are under increased pressure)
In diabetic patients, there is DIFFUSE ___ning of the basement membranes in both the tubules and the glomerulus and DIFFUSE mesangial ____ aka increased mesangial matrix
***** So you might be thinking, how do you differentiate diabetic nephropathy vs MPGN since they both involve basement membrane thickening and mesangial cell proliferation… Well thats easy, first off MPGN also has basement membrane ____ and MOST IMPORTANTLY OF ALL, if the patient is a DIABETIC, they probably have DIABETIC nephropathy
Albumin (aka albumineria)
1) Hyperglycemia (to much glucose in blood), glycosylation
2) Hypertrophy
Thickening, sclerosis
Splitting
Like we said, in a patient with Diabetic Nephropathy, there can be glomerulosceleoris, which is either ___ OR ____
In diffuse diabetic glomerulosclerosis, there is an increase in the mesangial matrix (aka mesangial sclerosis) and diffuse capillary basement membrane thickening ** This was discussed on previous not card**
In nodular diabetic glomerulosclerosis, there is also thickening of the GMB and characteristic ACELLULAR ____ nodules
Diabetic patients will also have advanced renal _____ (thickened, tortuous vascual portions) similar to the presentation seen in HT in the kidney since remember, most diabetic patients are hypertensive
Diffuse or Nodular
PAS+
Hyaline Arteriolosclerosis
Diabetes often progresses to CKD so in end stage diabetic nephrosclerosis, there is a ___ appearance to the cortical surfaces of the kidneys which signifies that the patient was hypERtensive (not necessarily that they were diabetic)
Also realize that 50% of patients have cysts, that have nothing to do with the case
Also Diabetics can have ___ necrosis (but this is also seen in UTIs/obstructions and Analgesic nephropathy)
Granular
SLE (Systemic Lupus Erythematosus)
Presents with a ___ rash on the face
Characterized by ____ upon light microscopy, _____ dense deposits in the glomerular capillary basement membrane and also in the mesangium
There is FOCAL and DIFFUSE proliferative lupus nephritis
Diffuse has increased cellularity, immunofluorescence will show anti-IgG Abs
^** Remember, if RPGN develops it’s a Type ___ RPGN
Butterfly
Wire-loops, Subendothelial
Type 2
_____ is the most common cause of acute renal failure (AKI) and is characterized by focal tubular epithelial cell ____ which can become detached and sloughed off into the tubular lumen leading to ___s that obstruct flow
^** So if you see RBC casts in the urine, think of this for a differential. Remember, casts are also seen in acute proliferative glomerulonephritis and leukocyte (neutrophil) casts will be seen in acute pyelonephritis
It can be classified as either:
1) ____ due to decreased or interrupted blood flow from hypotension/shock (decreased Effective Circulating Blood Volume) or involvement of intrarenal blood vessels like ____ or microangiopathies like HUS, TTP, or DIC
2) ____ due to toxic injury to the tubules from drugs or other toxins
One way to tell Ischemic vs Toxic apart is ____ has the PST and PCT continuous necrosis and in ____ there is only patchy PST and PCT necrosis (aka SKIP lesions… Just think about the fact that ischemia would cause profusion problems causing skipping wheras toxins fuck the entire thing up)
In ATI, the ____ epithelial cells are susceptible to injury leading to swelling, vacuolization, and destruction
ATI (Acute Tubular Injury old term being Acute Tubular Necrosis), necrosis, Casts
1) Ischemic, malignant hypertension
2) Nephrotoxic
Toxi, Ischemic
PCT (Proximal tubule)
ATI has various phases
1) Initiation
2) Maintenance with oliguria (aka decreased urine output 40 - 400 ml with 800-2000ml being normal) and ____ as the clinical problem
3) Recover phase which has ___ output urine volume (3L), ____ as the clinical problem and susceptibility to ____
2) Hyperkalemia
3) High, Hypokalemia, infection
Azotemia (increased BUN, which can progress to uremia) and the inability to concentrate urine (polyuria) can be seen in Primary ____ (this is simply a form of nephritis aka inflammation of the kidneys, that affects the interstitium of the kidneys that surround the tubules)
It is mainly associated with ____ and these can be either acute or chronic, with chronic most closely associated with ____
One way you can tell Acute Vs Chronic tubulointerstitial nephritis apart is that Acute has a RAPID clinical onset, interstitial ___, and leukocyte infiltration (mainly ____ and ____ Aka granulocytes)
Chronic has infiltration (but mainly ____ leukocytes aka agranulocytes aka macrophages, B cells, T cells, NK cells) ____ and tubular ____
Tubulointerstitial nephritis
INFECTIONS, VUR (Vesicoureteral reflux)
Edema, eosinophils and neutrophils
Mononuclear, Fibrosis, atrophy
Nephritic/nephrotic syndromes, tubular
___ is inflammation affecting the tubules, interstitium, and renal pelvis and can be Acute or Chronic, with Acute being caused by a ____ infection that has spread up the urinary tract aka ASCENDING INFECTION (or the infection could have come from the blood stream, but usually UTIs are more often cause it)
UTIs are mostly caused by ___
Bladder inflammation (aka ___) is commonly caused by bacteria
So once again, acute pyelonephritis is an acute bacterial infection of the kidney parenchyma
Chronic pyelonephrtitis is recurrent or long term infection of the kidney, which damaged the pelvis AND ____ system and parenchyma resulting in anatomical distortion and broad based scars on the renal cortex (commonly associated with obstruction or VUR)
^** THIS IS IMPORTANT, ONLY CHRONIC PYELONEPHRITIS and ANALGESIC NEPHROPATHY affects the calyx
Once again, 95% of pyelonephrtitis are ___ infections from the bladder and NOT hematogenous infections
Pyelonephrtitis, bacterial
Enteric bacteria (specifically, Gram - bacilli bacteria like E. coli)
Cystitis
Calcyeal
Ascending
Acute Pyelonephrtitis has ____ interstitial ____ inflammation (such as diffuse abscesses or wedge like areas aka exudative purulent localized inflammation that can cause interstitial abscesses), intratubular aggregates of ____ (since this is an suppurative necrosis that produces pus), and neutrophilic tubulitis and tubular necrosis
3 complications of ACUTE pyelonephritis can occur, which include ___ necrosis (ischemic coagulative necrosis that occurs in the pyramids), Pyogenic abscess formation associated with the kidney itself called ___ (due to complete obstruction HIGH in the urinary tract that causes renal pelvis and ureters to fill with pus), and ___ abscesses which are associated with the capsule and into the perinephric tissue
Commonly can occur during pregnancy and associated with ___
Also seen in patients with indwelling catheters
Acute pyelonephritis is almost ALWAYS associated with an ascending cystitis infection (aka bacterial infection that moves into the bladder) combined with a predisposing ___ defect (aka defective vesicoureteral junction)
*** If you see leukocyte ____ (like a neutrophil cast), then it MUST mean the kidney is involved since those are only formed in the tubules
Patchy interstitial suppurative inflammation, neutrophils
Papillary necrosis, pyonephrosis, perinephric abscess
VUR (Vesicoureteral reflux)
anatomical
Casts
Most children with UTIs have reflux due to a defective ____ (which is partial or complete lack of an oblique entry/angle of the intravesical portion of the ureter)
^** This becomes a problem when urinary stasis (urine sitting around) leads to infections that can involve the ureter and kidney
Adults might have bladder outlet obstruction due to prostatic hypertrophy that can cause the reflux
Vesicoureteral Junction (aka a valve malfunction)
In Acute pyelonephrtitis, there is acute inflammation in the tubules
The cortical surface of the kidney will show multiple foci of ____ areas of acute inflammation and abscess formation
Pyogenic (Pus aka yellow-gray)
Papillary necrosis can be seen in
1) DM
2) Analgesic nephropathy
3) Obstruction (like UTIs)
A) Which one of the 3 is more common in males?
B) Which one of the three is NOT often associated with infections
C) Which one of the three does NOT have calcifications
____ has pale gray necrosis limited to the papilla (aka papillary necrosis)
____ has red-brown necrotic papilla sloughed into the calyx
A) Obstruction
B) Analgesic Nephropathy (this is associated with drugs)
C) DM
DM and obstructive (UTIs)
Analgesic nephropathy
Chronic Pyelonephrtitis (more common than acute)
Associated with renal scarring and tubulointerstitial inflammation
This, along with analgesic nephropathy are the ONLY 2 diseases that damage the ___
^** Remember, AN has red-brown necrotic papilla sloughed into the calyx
VUR in chronic pyelonephritis results in ___ scarring
*** So if you see a pyelonephritic scar (aka inflammation, fibrosis, and deformation of the ____ and pelvis), then think CHRONIC Pyelonephritis
You can tell chronic PYELONEPHRITIS vs chronic GLOMERULONEPHRITIS due to the fact that pyelo has ____ scarring and glomerulo has diffuse and ___ scarring
Calyces (calyx)
Polar
Calyx
Irregular, symmetrical
Xanthogranulomatous pyelonephritis often presents as big shaggy yellowish orange masses and accumulation of foamy (lipid-laden) macrophages and this infection is associated with ___ species
Granulomatous interstitial inflammation can be seen in ___ forms of pyelonephritis like that from Candida
Viral forms can be from polyomavirus
Proteus
Fungal
Remember, Primary tubulointerstitial nephritis is mainly due to infections (acute or chronic), but can also be due to toxins and is the 2nd most common cause of acute kidney injury (behind pyelonephrtitis)
** One example of a toxin induced tubulointerstitial nephritis is analgesic nephropathy
**These patients will have FEVER and ___, along with infiltrates in the renal parenchyma (mainly mononuclear cells like lymphocytes and macrophages) *******, and 25% have a ___
Remember that you can tell a tubulointerstitial nephritis from that of a glomerulonpehritis since they DONT have nephortic/nephritic syndrome but analgesic nephropathy is an exception since it often presents with hematuria, mild proteinuria, and leukocyturia
^** Edema will also be seen histologically
^** Ig___ might be elevated since this is most likely a late phase reaction of an IgE-mediated type 1 hypersensitivity
Eosinophilia, rash
IgE
Other tubulointerstitial diseases aka renal disease related to nonrenal neoplasms (aka problems that don’t stem from tjhe kidneys) include
1) Direct or metastatic tumor invasion of the renal parenchyma
2) Hypercalceima
3) Hyperuricemia
4) Amyloidosis
5) Multiple myeloma is a non-renal malignant tumor that stems from hematopoietic origin that affects the kidneys
^** Multiple myeloma patients have overt renal insufficiency due to ____ proteinuria (which occurs in 70% of patients with multiple myeloma)
The presence of _____ nephropathy is characteristic of this disease, with bence jones tubular casts appearing as pink to blue amphorus masses
** The bence jones proteins combined with glycoproteins to form tubular casts that obstruct the tubular lumen and cause an inflammatory reaction
6) Glomerulopathies
5) Bence-jones, Light chain cast nephropathy
Renal vascular diseases can be classified as either small vessel disease, large vessel disease, or thrombotic microangiopathies
Or they can be classified as
1) Benign Nephrosclerosis
^* Nephroscelrosis (benign or malignant) is sclerosis of the renal arterioles and small arteries and associated with ____ in that it can be caused FROM hypertension, or it can cause hypertension itself and due to the thickened walls and narrow lumens, causing ischemia to develop
^* This is a general process, not a specific diagnosis
Benign is associated with medial and intimal ____, and ___ arteriosclerosis (aka hyalinization of the arteriolar walls) of the renal arterioles and ___ arteries and causes multi-focal ____ of the kidney prenchyma supplied by the vessels which can lead to atrophy
^** This actually seems like a similar presentation to Diabetes, but remember, that patient WILL HAVE diabetes if it is diabetic nephropathy… If the patients have diabetes, HT, or are ____ descent then these patients have an INCREASED incidence and severity of nephrosclerosis leading to renal failure (malignant nephro can lead to renal failure, or benign in black people…. But benign in non-blacks does NOT lead to renal failure)
^** Often accompanying hyaline arteriolosclerosis is ____ which is simply the narrowing of the lumen due to the interlobular and arcuate arteries and their morphological changes
The size of the kidney becomes slightly decreased, and cortical surfaces have a fine, granular, ____ grain look
^** So in other words, medial and intimal thickening and these hyaline protein depositions in SMALL vessels characterize this problem
Benign nephrosclerosis is usually not associated with renal insufficiency, EXCEPT for ___ populations
HT
Thickening, Hyaline, Small , Ischemia
African american
Fibroelastic hyperlasia
Leather
African american
2) Malignant nephrosclerosis (is a morphological analogue) to malignant arteriolosclerosis
Malignant arteriolosclerosis is a renal vascular disorder associated with malignant ____, which is a clinical syndrome and emergency
Ischemic kidneys and increased ____ is seen with gross manifestations as ____ renal hemorrhage (which are petechial hemorrhages)
This is also a SMALL artery disease, and the two characteristic histology changes are ____ (proliferation of smooth muscle cells of the arterial wall that are arranged concentrically) and ___ (Smudgy eosinophilic appearance due to fibrin deposition), infracts, and ischemic atrophy and ALL of these can cause renal failure
^** So unlike benign which had not all nephrosclerosis progress to CKD, here, malignant nephro CAN progress
Early symptoms are due to increased ____ and papilledema, retinal hemorrhages, CV abnormalities, and renal failure are seen
Hypertension
Renin, Flea-bitten
Hyperplastic arteriolitis and Fibrinoid necrosis
ICP
Renal artery stenosis is also referred to as ___ vessel disease and these HT patients CAN BE CURED
The most common cause is ____ often at the origin of a renal artery from the abnormal aorta
____ dysplasia is the second most common cause for large vessel disease
Which occurs more commonly in men? And which in women?
Also which occurs at a younger age? And which at an older age?
This diagnosis is hard to differentiate from a patient with essential HT, since the stenosis usually causes HT. You can differentiate due to renal scans, ___ will be elevated and therefore problems should get better with a angiotensin converting enzyme inhibitor that decreases renin, and the kidney will be ___ in size due to ischemia
Large
Atherosclerosis (accumulation of WBCs or fatty plaques)
Fibromuscular (looks like a string-of-beads caused by areas of stenoses alternating with small aneurysms)
Sclerosis = Men and Old
Fibromuscular dysplasia = Women and younger
Renin, decreased
Thrombotic microangiopathies results when thrombosis in the capillaries and arterioles occurs due to endothelial cell injury
Thrombi in the capillaries and arterioles of ___ vessels due to a ___ platelet count (thrombocytopenia) and this can lead to ischemic effects
The two diseases related to thrombotic microangiopathies include ___ which is usually triggered by endothelial cell injury and eventually causes platelet activation and thrombosis, and ___ which has its triggering event as platelet aggregation
^** In other words, these 2 diseases LEAD to thrombotic microangiopathies
SMALL, decreased
HUS, TTP
If a child recently visited a fast food restaurant and now has DIARRHEA, they most likely have ____ which is associated with ___-like toxin (mainly E.coli)
^** The shiga like toxin causes endothelial cell injury
There is also a ATYPICAL HUS, which is due to an INHERITED mutation of protein that regulates ___ activation and seen mainly in ____ (kids or adults?), commonly during pregnancy
^**Excessive inappropriate activation of complement causes endothelial cell injury
*******TTP presents usually in ADULTS, with a fever, thrombocytopenia, microangiopathic hemolytic anemia, and the most prominent feature is ___ involvement (seizures, LOC, confusion, etc…) and is usually inherited as a defective ____ (a protease that regulates the function of von Willebrand Factor
^** With ADAMTS13 defective, vWF continues to be expressed causing platelets to aggregate
*** So just a recap, HUS has its initiating event as ____ leading to platelet activation and thrombosis and TTP has its initiating even as ____ leading to platelet activation and thrombosis
Typical HUS, Shiga
Complement, Adults
Neurologic, ADAMTS13
Endothelial injury, Platelet aggregation (from a defective ADAMTS13 that controls vWF)
____ are commonly seen in patients with atherosclerosis and if these patients have theirs repaired, they are at risk for developing ___ renal disease
Atheroembolic renal disease (AERD) presents with atrophy, fibrosis, hemorrhage, and necrosis aka infarcts with the characteristic feature being ___ crystals which appear as ____
^** Infracts are mainly due to ___ with the most common source being mural thrombosis from the left side of the heart
AAA (Abdominal aortic aneurysm)
Atheroembolic
Cholesterol crystals, Rhomboid clefts
Embolism
Hematuria and the inability to concentrate urine (polyuria) with patchy papillary necrosis is seen in ____
^** THIS IS VERY SIMILAR to a Tubulointerstitial nephritis, except instead of ____ and polyuria, this patient has ____ and polyuria
** Both have patchy papillary necrosis
Also note these Sickle cell patients have hyposthenuria and possible proteinuria
Sickly cell nephropathy
Azotemia + polyuria, Hematuria + polyuria
If the cortex is pale due to a massive ischemic necrosis, commonly due to hypovolemic shock, it is referred to as ____
Diffuse cortical necrosis
Fusion of the lower poles is called a ___ kidney and is a congenital problem
Horseshoe
ADPKD (Adult polycystic kidney disease) presents with ____lateral, ___ in size (3-4cm), cysts in the kidneys and liver and brain ____ with common clinical features including ____ (due to cyst enlargement and hemorrhage), flank pain, UTIs, diverticular disease of the colon, mitral valve prolapse, etc.
This is an ____ inheritance pattern
^** Also these patients usually don’t realize they have this until 40ish, but by this time they are ALREADY in ____
*** So in other words, multiple expanding cysts of both kidneys (always BILATERAL) that eventually destroy the renal parenchyma and cause renal failure and these usually present with ___uria
_____ presents with SLIGHTLY enlarged (1-2cm) or normal kidneys that have cysts (commonly in the collecting ducts) at birth and unlike ADPKD, death occurs in infancy/childhood
^** So realize ADPKD have VERY enlarged kidneys (3-4cm) and ARPKD has less enlarged kidneys (1-2cm)
This is an ____ inheritance pattern
Also in almost all cases, these children have hepatic ____ (compared to hepatic cysts seen in ADPKD)
** Also note both ADPKD and ARPKD will cause abdominal pain, polyuria, polydipsia, abdominal mass, etc…
Bilateral, large, aneurysms, hematuria
AD
Chronic renal failure (aka ESRD)
Hematuria
ARPKD (Childhood polycystic kidney disease)
AR
Fibrosis
For patients with ADPKD, even though it is AD it, requires a mutation of both alleles of either PKD gene
There are 2 types of PKD genes, PKD 1 and PKD 2
PKD1 is the most common (85%), and it codes for ____ which is an integral membrane glycoprotein withy a role in cell-cell interactions or cell-matrix interactions
PKD2 (15%) codes for ___ and this causes problems with Ca2+ regulation
Which one has a better prognosis (aka which one is less likely to cause rend-stage renal failure?)
In patients with ADPKD, 40% have other cysts in the ___, **4-10% die from ____ (due to the fact that they have berry aneurysms)****, and 82% have diverticular disease of the ____
Don’t confuse the PKD gene with the ___ gene, that is the cause for ARPKD, which encodes for ____
**So dont confuse PKD and PKHD and dont confuse Polycystin and Fibrocystin**
Polycystin 1
Polycystin 2
PKD2 mutations
Liver, Subarachnoid hemorrhage, colon
PKHD 1, fibrocystin
____ is when cysts are seen in the medulla which can lead to recurrent ____ development, and also associated with UTIs; and these are benign
^** These usually occur in adults
Cysts localized to the corticomedullary junction and medulla are seen in _____
^** These usually occur in kids (although there is an adult onset form)
^** Both medullary sponge kidney and nephronophthisis are types of medullary cystic disease
Medullary Sponge Kidney, kidney stone
Nephronopthisis
Nephronopthisis (NPHP) is the most common cause of GENETIC end stage renal disease in ____ (children or adults?) and young adults and this occurs secondarily to progressive cortical and tubulointerstitial damage
^***** So realize the cysts don’t cause the ESRD, instead the cysts cause disruption of the cortical tubulointerstitum, which THEN cause problems that can lead to ESRD
The most common form is the familial ____ form, but there is also an adult-onset form considered as a separate entity
Both forms have cortiomedullary cysts and kidney size ____ and patients present with poly___ and poly___
^** Both forms also have ___ wasting
* Realize that this is one way you can tell NPHP vs ADPKD, since NPHP has a shrunken kidney size and ADPKD does not*****
Mutations in ____ are the cause of medullary cystic disease
Familial juvenile is an ____ inheritance and adult onset is ____
Children
Juvenile
Decreased (shrunken), Polyuria (large volumes of dilute urine) and Polydipsia (increased thirst)
Salt wasting
MCKD1 and MCKD2
AR, AD
There are 3 major ACQUIRED renal cystic diseases (aka not inherited)
1) ____ are seen as single cysts that occur on the renal CORTICAL surface filled with CLEAR fluid and these are benign… Usually no clinical significance
^** Can be confused with kidney tumors, but can be distinguished due to the fact that the cysts have ___ contours and almost ALWAYS ____ (also they give ___ rather than solid signals on ultrasonography)
** 2) A patient that was on dialysis, that presents with cysts located in the cortical and medullary locations with NUMEROUS clear fluid cysts and the kidney size is ___, it is most likely ____ disease
^** Clinical findings include hemorrhage, erythrocytosis, and neoplasias with the most common being ____ (12 to 18x higher)
^** The clear fluid cysts contain ____ crystals
3) ____ often presents as a common MASS in the perinatal period with extensive multiple cysts with intervening poorly-differentiated ____ of mesenchyme often with ___ formations and immature collecting ducts
^** So if you see no glomeruli and islands of CARTILAGE, think this
^** This is assocaited with other GU anomalies like agenesis (absent ureters), ureteropelvic obstruction, etc…
If ____lateral, renal failure will develop but if ____, it is surgically curable
1) Simple renal cysts
Smooth, avascular, fluid
2) Normal, Acquired renal cystic disease
Renal cell carcinoma
Calcium oxalate
3) Unilateral Multicystic renal dysplasia, Islands, cartilage
Bilateral, Unilateral
___ is when the renal pelvis and calyces are dialted along with atrophy of the kidney due to obstruction to the outflow of urine
If a 20-30 year old male with a history of kidney stone formation comes in, with unilateral pain they most likely have ____
These are made up of mainly ___ oxalate and ___ (aka calcium stones)
Predisposing factors include urinary pH changes, decreased urine volume, or presence of bacteria
Hydronephrosis
Kidney stones (nephrolithiasis)
Calcium oxylate, Phosphate
The most COMMON benign renal neoplasia is ___
Most benign neoplasias do NOT cause clinical problems and the majority are small
These renal papillary adenomas are DEFINED by size, so if it is LESS than ___ cm, it’s considered benign, but if it is greater than that, it is classified as a LOW GRADE ____
These neoplasias are ____ in nature, discrete, pale yellow-gray in color, small, and may be multiple
Morphologically, eosinophilic cytoplasms, papillae, and thin fibrovascular cores are seen
Renal papillary adenomas
1 cm, Low grade renal cell carcinoma
Coritcal
____ are primary renal epithelial neoplasms (-omas) that arise from TYPE ___ intercalated cells of renal cortical collecting ducts
These present as ___-____ color and are well circumscribed, often with central ___ sacr
** Remember, we said most benign renal neoplasias are small, but these CAN be large (10-15 cms)
Also these present similar to renal cell carcinomas (most commonly the non-clear cell aka chromophobe variant)… They are pretty much IMPOSSIBLE to tell apart**
Morphologically, they present with eosinophilic and granular cytoplasms, and often show a ___ pattern
It seems like you might be able to tell them apart based on the fact that oncocytomas have NO perinuclear clearing
Oncocytomas, Type A
Mahogany-brown, stellate
Nesting
In a patient with Tuberous Sclerosis, 80% of them have ___ due to the loss of the ___ tumor suppressor genes (which is an ___ inheritance pattern and causes tumors or lesions of the brain, skin, kidney, heart, lungs, or eyes)
Like oncocytomas, these can present as large masses (in contrast to most benign renal neoplasia) and these can often ____, leading to massive ____
^** Therefore, the initial presentation may be ____, secondary to massive retroperitoneal/intra-abdominal bleeding
Thick walled blood vessels, smooth muscle, and fat are seen microscopically
ANGIO (blood vessels) - MYO (smooth muscle) - LIPO (fat)
Angiomyolipomas, TSC1/TSC2, AD
RUPTURE, hemorrhage
Shock
Thick
Adenocarcinomas of the kidney (which arise from renal tubular epithelium) aka malignant renal tumors aka Renal Cell Carcinomas (RCC) are the most COMMON adult kidney cancers
___ is a huge risk factor
Most of these cases are sporadic, but 4% of them are hereditary as an ___ inheritance in younger patients
In ____ syndrome, most of these patients develop RCCs (inherited)
Cigarette smoking
AD
Von Hippel-Lindau
There are a few major classifications of RCCs, and some can be either sporadic or hereditary :
1) Clear cell carcinoma
^** This is the most common form of the 2 with CLEAR cytoplasm, NON papillary and BRIGHT ___ in color
Of the sporadic/hereditary cases of Clear cell carcinomas, 95% are ___ and of the 5% that are hereditary, almost ALL of them have a chromosome ___, ____ arm DELETION/TRANSLOCATION affecting the ___ tumor suppressor gene
^** The clear cytoplasm is due to GLYCOGEN and LIPID accumulation
2) Papillary carcinoma
^** This occurs less often than clear cell and characterized by papillary growth patters with foamy macrophages in the stalk
Here, ____ forms have genetics being trisomy 7, 16, 17; or a lost of the Y chromosome (activated ___ proto-oncogene)
Hereditary forms only has trisomy ___ and mutated, activated MET
Realize that Sporadic cases usually have a ____ lesion and Hereditary cases usually have ___ lesions
3) Chromophobe renal carcinoma
^** Less common than both Clear cell and Papillary and presents with pale eosinophilic cytoplasm and nuclear ____ along with the eosinophilic cells arranged in ___ sheets (rather than nests like in oncocytomas)
** These arise from Type ___ intercalated cells of renal cortex collecting ducts (remember, Oncocytomas which are similar to these chromophobe RCCs arise from Type A)
4) Medullary/collecting duct/sarcomatoid
^** Sarcomatoid RCC is composed of spindle cells simulating a mesenchymal neoplasm
** Collecting duct carcinoma shows branching tubules lined by highly atypical cuboidal cells
1) Yellow
Sporadic, Ch3, Short arm, VHL
2) Sporadic, MET
7
Single, Multiple
3) Halos, solid
Type B
What is the triad of RCC clinical presentation?
RCCs are great at causing various problems not related to the kidney and after they have already metastasized, they can cause non-specific symptoms like weight loss, malasia, weakness, fever, etc…
Hematuria, Costovertebral pain, Palpable flank mass
RCCs spread mainly through the BLOOD (renal vein), not lymph and papillary and chromophobe types have a ___ prognosis, clear cell is a ___ prognosis, and collecting ducts/sarcomatoids/medullary forms are the ____ prognosis
Gross features show yellowish, spherical neoplasms in one pole of the kidney would be most likely ____
Better, average, worse
Sporadic (since its in one pole) clear cell carcinoma (since it is bright yellow)
Urothelial (transitional cell) carcinoma of the kidney originates from the urothelium of the renal ___ with most patients have concomitant bladder tumors
It’s assocaited with Analgesic nephropathy and Balkan (tubulo-interstitial) aka Lynch nephropathy
Common clinical features include hematuria and can lead to hydronephrosis and flank pain and prognosis is generally ___
So if a patient has a tumor in both the bladder and renal pelvis, along with hematuria and possibly an associated disease like analgeic/balkan/lynch nephropathy, then possibly be thinking a ____ carcinoma
Pelvis
Poor
Urothelial
A large abdominal mass that may exhibit pain, microscopic hematuria, and HT in CHILDREN (2-5 year olds) and found most commonly in ASIANS is ___
^** These tumors, along with neuroblastomas are referred to as small round BLUE cell tumors
Also realize that Wilms tumor occurs age 5 and below and Neuroblastomas can occur up until age 10
___ mutations and other congenital or familial syndromes cause 10% of these tumors
^** These congenital/familail syndromes are classified as WAGR, Denys-Drash, or Beckwith-Weidemann
The other 90% of these tumors are in healthy kids with no congenital or genetic problems
If the tumor is bilateral, they ALWAYS have ____ as a precursor lesion
These tumors are WELL-circumbscribed, ___-___ in color, and often large/expansile tumors in the ____ pole of the kidney
Wilms tumor
WT1
Nephrogenic rests
Tan-gray, lower
There are 2 types of possible wilms tumor histomorphology, with the typic triphasic type having a _____ prognosis and the anaplstic type being an ____ prognosis
The triphasic has its histological features mimic the germinal development of the normal kidney with all 3 cell types present (blastemal, epithelial, and stromal)
**The anaplastic can be diffuse or focal with the ____ morphology ALWAYS being associated with a poor prognosis (the focal anaplasia doesn’t always)***
^**Anaplasia is associated with the ___ mutations and chemotherapy resistance
So once again, the presence or absence of DIFFUSE anaplsia is the most important feature of prognosis
Favorable, unfavorable
Diffuse
P53
Remember only 10% of congenital/familail syndromes are classified as WAGR, Denys-Drash, or Beckwith-Weidemann
1) WAGR (33% develop wilms tumor)
^** W = Wilms tumor, A = Aniridia (absence of iris), G = Genital anomalies, R = Retardation
These patients have 11p13 germline mutations that cause ___ and ___ to be lost
2) Denys-Drash (90% develop wilms tumor)
^** Present with gonadal dysgenesis and early-onset Nephropathy leading to renal failure and they are at increased risk for gonadoblastomas
These patients also have a WT1 mutation, but it affects the ____ region (dominant negative missense mutation)
3) Beckwith-Wiedemann syndrome (BWS)
^** Patients present with organomegaly, adrenal cytomegaly, omphalocele, etc
^** This is due to GENOMIC ___ at the ___ gene that affects ____
1) WT1 and PAX6
2) Zinc finger
3) Imprinting, WT2, IGF2
Neuroblastomas occur in kids
Most occur sporadically, but of those that are familial, they are often due to a ___ mutation
40% arise in the adrenal medulla
These might be confused with a Wilms tumor, but some defining characteristic features include ____rosettes, neuropils, dense core granules
Stages for neuroblastomas include ____s being favorable and ____s being unfavorable
Also children ___ than 18 months old have a better prognosis and if MYCN is amplified, they have a ___ prognosis
^** MYCN amplification AUTOMATICALLY bumps the kids into a high risk category
Sometimes these babies look like blueberry muffins and there is increased _____ in almost all neuroblastomas
ALK
Homer-Wright pesudorosettes
1, 2A, 2B, 4S = favorable ; 3, 4 = unfavorable
Less, worse
Catecholamines
The ureters lie in a ___ position so retroperitoneal tumors or fibrosis can entrap and obstruct them
The most common cause of hydronephrosis (excess fluid in kidney) is infants and children is ____ obstruction (which blocks the flow of urine from the renal pelvis to the proximal ureter)
^** Don’t confuse this with a UVJ and VUR problems, which is commonly associated with chronic pyelonephrtitis
Congenital anomalies include double and bifid ureters, UPJ obstruction, diverticulae, etc…
In adults, obstruction of the ureters can be acute (commonly from ___) or chronic (commonly from tumors)
^** There can also be an idiopathic cause called ____ which is IgG4 related and causes narrowing of the ureter
Retroperitoneal
UPJ (Uteropelvic junction obstruction)
Calculi (Aka stones)
Sclerosing retroperitoneal fibrosis
____ is a pouch-like evagination of the bladder wall and can be congenital, but most commonly are ACQUIRED via persistent ____
If the urethra is obstructed, most commonly from ____ enlargement which obstructs the urine outflow, the bladder wall will thicken and increased pressure causes out-pouching (diverticulae)
^** Since the urine just sits there, a large increased risk for infection and bladder ___ to form occurs
Diverticulae, Urethral obstruction (Note this is URETHRAL, not URETERs)
Prostate
Calculi (aka stones)
Exstrophy is a developmental failure in the ___ wall of the abdomen and bladder and the exposed mucosa can undergo colonic glandular ____ which often becomes infected and there is an increased risk for ____ arising in the bladder
^** Prognosis is good if surgery is done early
Anterior, metaplasia, adenocarcinomas
Sometimes, the bladder stays connected to the umbilicus via a fistulous urinary tract, which is referred to as a patent urachus
Urachal cysts occur when only the central region of the urachus persists and this can often lead to ____ arising from these cysts (occurs in 20-40% of BLADDER adenocarcinomas)
Carcinomas
____ presents with dysuria (pain upon urination), pelvi/abdominal pain in the region of the bladder, frequency peeing, and low grade fever, etc
Cystitis (which means inflammation of the bladder) can be acute or chronic and is often the same thing as a UTI (which is due to the bacteria, E.coli)… So if a culture comes back +, think bacterial cystitis
In an immune suppressed patient, ____ can cause cystitis
^** If it comes back -, but you still think its some form of cystitis then think about urethritis, genital tract disease, or some non-bacterial cause)
If a patient is on ___ therapy when the culture is obtained, it might come back as a false -
Cystitis
Candidia albicans
Antimicrobial
The most common agents for acute cystitis is ___ (along with Proteus, Klebsiella, or Enterobacter)
Much more common in women and most cases exhibit non-specific acute inflammation
Remember, if the bacteria stay to long in the bladder (cystitis) they can make their way up to the kidney and cause ___
Cystitis can also become hemorrhagic, often seen in patients receiving cytotoxic ___ drugs like cyclophosphamide
AKA cyclophosphamide can cause ____
^** ___ infection can also cause hemorrhagic cystitis
Acute cystitis shows ____ (increased blood flow) of the mucosa and ____ infiltrates
Chronic cystitis differs from acute cystitis in the nature of the inflammatory cell infiltrate and the clinical sequelae
AKA chornic cystitis has ____ inflammatory infiltrates
E. Coli
Pyelonephritis
Anti-tumor
Hemorrhagic cystitis
Adenovirus
Hyperemia, neutrophilic
Mononuclear
There are also some special forms of cystitis that include
1) _____ is a chronic, persistent, painful form of cystitis that occurs in women 30-40 with intermittent, sever suprapubic pain, urinary frequency and urgency, hematuria, and dysuria, but NOOOOOOOOOOO bacterial infection (culture nagative)
^***Mucosal ___ cells are characteristic of this disease
2) ____ has soft, yellow, slightly raised mucosal plaques (broad, flat plaques) that can involve the entire bladder and occurs due to chronic infection from E. Coli because ____ function is defective
^** Characteristic feature is ____ present in macrophages and the macrophages also have granular PAS+ cytoplasm
3) ___ commonly occurs from catheters and extensive submucosal edema causes polypoid urothelium
^** Commonly confused with ____
1) Interstitial cystitis (Hunner ulcer)
Mast
2) Malacoplakia, phagosome
Michaelis-Gutmann bodies
3) Polypoid cystitis, papillary carcinoma
In a chronic reaction/inflammatory condition where there is chronic irritation, the urothelium can proliferate into buds and down into the lamina propria, called nests of ____, which grow down into the connective tissue under the epithelium into the lamina propria and if the buds differentiate into cystic deposits, it causes ____ and if they differentiate into goblet cells (intestinal columnar mucin-secreting glands aka epithelial cells -> cuboidal/columnar cells) it is called ___
Often present with frequency, dysuria, urgency, and hematuria and therefore clinically mimic bladder cancer
Also associated with chronic infection, ____ is characterized by aggregates of lymphocytes in lymphoid follicles in the mucosa and underlying wall
_____ is manifested by infiltration of submucosal eosinophils
Nests of Von Brunn, CC (Cystitis cystica), CG (Cystitis glandularis)
Follicular cystitis
Eosinophilic cystitis
Most bladder neoplasias are EPITHELIAL in origin, with non-epithelial tumors (mesenchymal) being rare with the most common non-epithelial tumor being a ____ (commonly seen in adults and called leiomyosarcomas)
Other mesenchymal tumors include:
1) A malignant mesenchymal tumor (which is a small, round, blue cell tumor) seen in children is ____
^** These tumors present with sarcoma ____ and a ___ layer with clusters of tumor cells present right below the epithelium giving a ‘nevoid’ appearance are seen
2) Lipomas, Fibromas and Neurofibromas are all ___ in origin
Leiomyoma
1) Rhabdomyosarcoma
Botryoid, Cambium
Benign
2) A malignant mesenchymal tumor in adults is a ___
One more non-epithelial malignancy is a primary malignant ____ and seen in adults, more commonly females, and most have ____
Leiomyosarcoma
Lymphoma (more specifically, Non-Hodgkin lymphoma), chronic cystitis
The more common tumors in the urinary bladder (epithelial) are ____ tumors (90%), with squamous cell carcinomas and sarcomas making up the rest
^** So remember, non-epithelial (mesenchymal) are much more rare than epithelial tumors
Urothelial (aka transition cell)
Bladder neoplasia include:
_____ are attached to the mucosa by a stock and has a central core of loose fibrovascular tissue covered by the epithelium that is histologically IDENTICAL to the normal urothelium
____ have inter-anastomosing cords of cytologically bland urothelium that extend down into the lamina propria
_____ has the same features as papillomas, EXCEPT they have a clinical finding of THICK epithelium covering papillary projections
___ grade papillary urothelial carcinomas have a slightly thicker lining than papillomas and slight nuclear atypia like scattered hyperchormatic nuclei and mitotic figures. The architecture and cytologic appearances are ORDERLY
____ grade papillary urothelial carcinomas have dyscohesive cells with large hyperchromatic nuclei and high anaplastic cells, also loss of polarity
Flat tumors aka CIS are similar to High grade papillary urothelial carcinomas in that they have lack of cohesiveness, mucosal reddening, granularity, or thickening without evident intraluminal mass
^** Realize these are ALLLLLLLLL Non-invasive, but there is also Invasive urothelial cancers that has its prognosis based on the depth of invasion AKA stage… And if it goes into the detrusor muscle aka mucalris propria, it is a BAD outcome
Exophytic papillomas
Inverted papillomas
PUNLMP (Papillary urothelial neoplasia of low malignant potential)
Low
High
Urotherlial (transition cell) neoplasia starts off as a precursor lesion before they become invasive carcinomas
There are two main types (both are non invasive since they are just precursor lesions)
1) _____ urothelial carcinomas (aka papillomas)
This type of precursor lesion can be either low grade or high grade (sometimes the grades are 1, 2, and 3 instead of low/high)
Either way, these non-invasive papillary tumors originate from papillary urothelial ____so if the urothelium is normal or just thick, its a grade 1, if there is atypical hyperplasia it is grade 2 and if it a carcinoma in situ (CIS) it is grade 3
2) ___ urothelial carcinomas aka ____
^** These types of precursors lesions are ALWAYS ____ grade aka grade 3 since they are by deffiniton, CIS neoplasias
In papillary lesions, ____ is likely and the ONLY clinical finding****
In flat lesions, discomfort is likely
1) Papillary
Hyperplasia
2) Flat, CIS (Carcinomas in situ)
High
PAINLESS Hematuria
Various risk factors play a role in urothelial carcinomas such as cigarette smoking, industrial exposure to arylamines, SCC, etc…
Also genetics like a Chromosome ____ monosomy or deletion is often seen in both LOW and HIGH grades and if a loss of function mutations in____ is detected, it’s usually a bad prognostic sign and most likely means the tumor is a HIGH grade with likelihood to spread
Gain of function mutations in ___ or mutations in the ___ oncogene are usually seen in non invasive, LOW grade papillary carcinomas
9, Tp53 (or RB)
FGFR3, HRAS
One way to tell the difference between low grade papillary urothelial carcinomas and high grade, is that ___ grade has an orderly architectural and cytologic appearance but ____ grade ones have SEVERE cytologic atypia with hyperchormatic HUGE nuclei and a high N/C ratio
Low, High
The MAJOR prognostic issue that determines outcome of bladder cancer is the DEPTH of muscle invasion (____) more-so than histological grade because remember, most of them that turn into invasive cancers are of high grade anyway….
Ta, Tia, and T1 are ____ stage so the 5 year survival is very high
T___ is invasion into superficial muscle and T___a/b and T____ is ADVANCED stage (into deep muscle and perivascular fat) so these are all BAD
Stage
Low
T2, T3 and T4
Urethra can become inflamed (urethritis) or have tumor and tumor like lesions
Inflammation of the urethra is divided into
1) Gonococcal
2) Non-gonococcal with the major organism being ____
____ is painless and ____ is painful
3) Non-infectious like that seen in reactive arthritis which is associated with the clinical triad of arthritis, conjunctivitis, and urethritis
Tumors of the urethra are generally ____ in origin if proximal urethra and ____ if distal urethra origin
Another tumor, a ___ is an inflammatory lesion that presents as a small red painful mass in the external urethral meatus in older females
2) Chlamydia
Chlamydia, gonorrhea
urothelial, squamous cell
Urethral caruncle
The penis has 3 clinically significant congenital anomalies which include hypospadias (opening under dick), epispadias (opening over dick), or phimosis
Inflammation can also occur in the penis and includes:
____ Is an infection of glands and prepuce due to Candida albicans, anerobic bacteria, or Gardnerella and common in uncircumscribed males due to smegma accumulation (sweat, debri, epithelial cells, etc….) and can cause ___ aka small orifice to permit normal urination
Tumors can occur with the most common being a benign epithelial tumor called a ____ (due to ___) or carcinomas
^** Condyloma Acuminatum will present as single or multiple sessile or pedunculated, red papillary excrescences on the penis
^** Histologically, it presents with acanthosis (thickening of underlying epidermis) and superficial hyperkaratosis
^** All these tumors seem to have a strong association with HPV with the benign condyloma acuminatum being HPV type ___ and the malignant carcinomas being Type ___ for the CISs (Bowen disease and Bowenoid papulosis) AND invasive carcinomas
If you see ____ (cytoplasmic vacuolization of the squamous cells) then that is indicative of HPV infection… But realize it doesn’t differentiate what type of benign or malignant tumor it is
For the malignant tumors, the 2 important ones are both Carcinomas in situ (CIS) and include:
____ disease involves the skin of the shaft of the penis and scrotum, and is gray-white and opaque plaque OR shiny red and velvety plaques
^** The epidermis contains hyperproliferative and mitotic atypical cells that are hyperchromatic, dysplastic, and dyskeratotic epithelia cells with an INTACT basement membrane
The other CIS is ____ which presents as a MULTIPLE reddish brown papular lesion seen in younger patients that Bowens
^** Which of the 2 sometimes develops into a squamous cell carcinoma over the years? And which one NEVER develops into an invasive carcinoma and will spontaneously regress***
Balanoposthitis, Phimosis
Condyloma Acuminatum, HPV
Type 6, Type 16
Koilocytosis
Bowen’s disease
Bowenoid papulosis
Bowens, Bowenoid
_____ of the penis begin on the glans or inner surface and show Papillary AND Flat patterns
^** Eventually, an ulcerated infiltrative lesion will occur and possibly a cauliflower like fungating mass and epithelial thickening accompanied by graying and fissuring of the mucosal surface might occur
For the testis and epididymis the most common congenital anomaly is absence of a testi called ___ and causes an increased risk of testitcular cancer and ____ (aka placement into the scrotal sac) must be done before 1 year old age is reached
For inflammation, ___ and ___ (characterized by caseating granulomatous inflammation) usually affect the epididymis and ___ affects the testis first
Syphilis is characterized by the production of ____ and ___ associated with perivascular cuffing of lymphocytes and plasma cells
^** Realize that the epididymis usually is affected by inflammation, and the testis by tumors
There are also benign spermatic cord tumors (most commonly Lipomas) and benign paratesticular tumors (most commonly _____ tumors, which are characterized by small nodules that occur near the upper pole of the epididymis)
^** Realize the adenomatoid tumors are benign, but occur near the testis, so if you realize this then you dont have to remove the entire testis since it wont invade
^** Sometimes, orhcitis can present as a painless testicular mass that mimics a tumor (usually, it presents as a tender mass with sudden onset and fever), and it can be distinguished from a tumor due to the fact that granulomas are seen restricted to the _____ and this is an AUTOIMMUNE disease
^** So just to recap, if you see a mass limited to the seminiferous tubules, think _____
Squamous Cell Carcinoma
Cryptochidism, Orchiopexy
Gonorrhea and tuberculosis, syphilis
Gummas, obliterative endarteritis
Adenomatoid
Spermatic tubules (specifically, the seminiferous tubules)
Granulomatous orchitis
Testicular tumors are 95% ____ tumors, and 4% sex cord-stromal tumors and 1% non-hodgkin lymphomas
ALMOST ALL TUMORS OF THE TESTICLES CAUSE SWELLING OF THE TESTICLE (except pure choriocarcinomas)… So if you see or feel testicular swelling, include this in your diff dx
^** These germ cell tumors are further subdivided into
1) Seminomatous tumors aka seminomas and spermatocytic seminomas (resemble primordial germ cells or early gonocytes)
2) Non-seminomatous tumors aka NSGCTs (undifferentiated cells)
Germ cell tumors have different causes like environmental factors, genetics (KIT or BAK mutations), and origins from a ___ precursor lesion due to a re-duplication of the chromosome ___, ___ arm
Seminomas tend to stay localized, but NSGCTs don’t; aka NSGCTs are ___ aggressive and have a ___ prognosis
NSGCTs tend to metastisize via the ___ and seminomas tend to via the ____
Also elevated ___ indicates a mass of tumor cells and is a good biomarker for a germ cell tumor
Germ cell
ITGCN (Intratubular germ cell neoplasia), 12/short (aka 12p)
More, worse
Blood, lymph
Lactate dehydrogenase
1) Seminomatous tumors (resemble primordial germ cells or early gonocytes)
A) _____
^** Gray-white in color, there ____ (is or is not?) hemorrhage or necrosis, the cells are large and round to polyhedral, with a distinct cell membrane and clear to watery appearing cytoplasm with a large central nucleus with one or two prominent nuclei
^** Microscopically, they have sheets of uniform cells divided into poorly demarcated lobules by delicate fibrous septa containing a lymphocytic infiltrate
^** KIT, OCT4, and PLAP stain +
Sometimes ____ are seen if the patients HCG levels are elevated and also an ill-defined granulomatous reaction is seen (which is in contrast with the well-formed discrete granulomas seen in tuberculosis)
B) ____ seminoma
^** These are different from typical seminomas due to the fact that they have NO lymphocytes, No granulomas, NO Syncytiotrophoblasts, and have an admixture of other cells
^** Spermatocytic seminomas DO NOT come from the precursor lesion ITGCN (remember, the other one that also does not come from ITGCN is a yolk sack tumor)
A) Seminoma (typical)
Is NOT
Syncytiotrophoblasts
B) Spermatocytic
2) Non-seminomatous tumors (undifferentiated cells)
A) ____ carcinoma
^** These are smaller than seminomas and DO NOT replace the entire tesis. They are more aggressive than seminomas and cells grow in alveolar or tubular patterns, sometimes with papillary convolutions and more differentiated lesions may display sheets of cells
These are KIT ___, OCT3-4 and PLAP ___, and Cytokeratin and CD30 ____ aka only KIT is not seen… This is different from seminomas, which are KIT ___ and OCT3-4 amd NANOG +
There ___ (is or is not?) hemorrhage seen in these tumors -> Remember, seminomas DO NOT have hemorrhage
B) ____ (endodermal sinus) tumor have elevated ____ and often have ___ bodies (structures that resemble endodermal sinuses)
C) Choriocarcinoma have elevated ____
^** Cause NO testicular enlargement and are detected only as a small palpable nodule and contain 2 cell types (____ and ___) and also necrosis and hemorrhage is seen
So which one contains no testical enlargement? And which ones do NOT come from ITGCN precursor lesions?
A) Embryonal carcinoma
KIT -, OCT/PLAP/CD30/Cytokeratin +, KIT +
Is
B) Yolk sac, AFP, Schiller-Duval
C) HCG
syncytiotrophoblasts and cytotrophoblasts
Choriocarcinoma, Spermatocytic seminomas and Yolk sack tumors
Sex cord-gonadal stroma tumors which are 4% of testicaular tumors (remember, 95% are germ cell tumors) include
1) ____ cell tumors cause testicular swelling and in adults usually cause gynecomastia due to changes in hormone levels and in kids will cause sexual precocity
^** These have characteristic rod shaped ____ of ___
2) Sertoli cell tumors
The other non-germ cell tumors are non-hodgkin lymphomas, and even though these are only 1% of testicular tumors and much more rare, they are the MOST COMMON in patients aged ___ and older
^** So if a 60 year old male comes in with a testicular mass, consider this like a B-cell lymphoma or Burkitt lymphoma, etc…
1) Leydig cell tumor
Crystalloids of Reinke
60
The bladder has 4 regions, Peripheral, central, transitional, and periurethral
Hyperplasias arise usually in the ___ zone and carcinomas originate in the ___ zones
Transitional, peripheral
The prostate can become inflamed (prostatitis) due to:
1) Acute bacterial - usually is due to ___ or another gram negative bacteria
^** Presents with fever, chills and dysuria and when a rectal exam is performed, the prostate will feel tender and boggy. Also urine cultures will show a bacteria
2) Chronic bacterial
^** Hard to diagnosis but patient usually has recurrent UTIs and ____ in prostatic secretions and + bacterial cultures will diagnosis this
3) Chronic abacterial MOST COMMON
^** same presentation as chronic bacterial (leukocytosis upon prostatic secretions), except it does NOT have history of UTIs and bacteria cultures are negative … The cause is UNKNOWN and they ____ respond to antibiotics
4) Granulomatous
You ____ (should or should not?) get a biopsy if acute or chronic prostatitis is suspected since it can lead to sepsis
1) E. Coli
2) Leukocytosis
Do NOT
SHOULD NOT
_____ is another prostate problem that is common in men over 50 due to nodular hyperplasia of prostatic stromal and epithelial cells and often leads to urinary obstruction since the large, discrete nodules form in the ____ region
^** The major reason the cells overgrow is due to the androgen ____, which causes increased proliferation of ___ cells and decreased death of ___ cells leading to hyperplasia
Microscopically, the hyperplastic glands have 2 layers with one being an inner ____ layer and the other being an outer layer composed of ____ basal cells
BPH (Benign prostatic hyperplasia), periurethral (book says periurethral at first, but then explains that nodular hyperplasia originates in the TRANSITION zone… So idk which one it is)
DHT, stromal, epithelial
Columnar, flattened
Tumors of the prostate include the most common form of cancer in men, ____
^** Realize when the term “benign glands” are used, that simply is talking about the BPH which can prevent similar to a prostate gland cancer
On the X-linked AR gene, CAG repeats with the ___ stretches have the MOST sensitivity to androgens aka short stretches = more prone to development of cancer
Prostate cancers are common in men over 50 with ____s playing an important role with a mutation causing chromosomal rearrangement that juxtaposes the coding sequence of an ____ family transcription factor gene like ERG or ETV1 next to the androgen-regulated ____ promoter
Another epigenetic change that can occur is hyper methylation of ____ genes
Adenocarcinomas
Short
Androgens, ETS, TMPRSS2
GSTP1
Morphologically, most prostate cancers arise in the ___ zone of the gland (____ location)
Histologically, the lesions are well-defined and produce demonstrable gland patterns and if ____ invasion is seen on biopsy, it’s specific for prostate cancer
**In contrast to benign glands (aka BPH), Cancers of the prostate have a basal cell layer ____ (aka BPHs DO have an outer flattened BASAL cell layer, and cancers do NOT)*****
Also in contrast to benign glands, cancer glands are more crowded and LACK branching and papillary infoldings and they feel gritty and firm
^** Also, prostate cancers are ___ + and benign ones are not
Peripheral, posterior
Perineural
Absent
AMACR (Alpha-methylacyl-coenzyme)
Also realize ____ is a pre-cursor lesion found in 80% of prostate carcinomas and cytologically PIN and carcinomas are identical, but remember, carcinomas do NOT have a basal cell layer, and PIN WILLhave a patchy layer of basal cells and an intact membrane
^** AKA features of cancer, but basal cells = PIN and this has a high chance of turning into a cancer
Grading prostate cancer wise, grade 1 shows ___ differentiated tumors (neoplastic glands are uniform and round in appearance and packed into well circumscribed nodules) and grade 5 shows ____ glandular differentiation which will have tumor cells infiltrating the stroma and in the form of cords, sheets, and nests
^** Most well-differentiated = 2 and least-differentiated = 10 (since they get to grades) and 8/9/10 is no curable
PIN (High-grade prostatic intraepithelial neoplasia)
Well, No
____ is used to assist in the diagnosis and management of prostate cancer and another gene that can be helpful is the noncoding RNA, ____
^** Realize PSA can be elevated in BPH also
*************Also the findings of ____ metastases by skeletal muscle surveys or radionuclide bone scanning is diagnostic of prostate cancer since these cancers spread via the blood to the bones (lumbar spine, proximal femur, pelis, etc)
PSA, PCA3
Osteoblastic
