99 ‫محاضرة‬

‫ حممد بركات‬: ‫اجلزء األول‬

Slide 61
..: Benign Nephrosclerosis :..
Previously, We talked about ATN, where some patients present with either Acute Renal Failure or other
presentations like Chronic Renal Failure (which can go for a long period of time before being diagnosed; where they
present very late) or (some patients may present young with their presentation is led by HTN, Anemia, Serositis)

- Subsequently when these patients go for lab investigations you’ll find that they’ve advanced kidney disease
manifested by Elevated BUN & Creatinine as well as anemia & HTN
- If biopsy is done, there’ll be Benign Nephrosclerosis; where Patient go undetected/undiagnosed
until eventually they’re going to present to us with:
o Glomerulosclerosis,
o Arteriolar hyalinzation,
o Interstitial fibrosis,
o Tubular atrophy

Biopsy is not indicated in these cases; because it doesn’t help us in the diagnosis of the
original disease and it’s not going to guide us to further therapy

It’s Referred to as benign because;

o Process goes for long period of time before being diagnosed

o Usually, not associated with dramatic clinical presentation – unlike the Malignant
Nephrosclerosis (where patients have manifestation at a short period of time)

Causes of Undetected Renal failure Over a long period of time without being Diagnosed (cause of Benign
Nephrosclerosis):

- HTN (Benign course); at the level of the small arterioles HTN is associated with the exudation of proteins
into their walls, walls become thickened, with deposition of hyaline material (Arteriolosclerosis)
o This process can affect the glomeruli & blood vessels  further Ischemia of the kidney and
eventually a Nephrosclerosis
- Diabetes Mellitus
o It affects the glomeruli, the vessels, the interstitium, and the papillae along with Chronic
inflammatory processes
- Focal Segmental Glomerulo-sclerosis
- Amyloidosis
o Primary; due to Multiple myeloma
o Secondary; due to other diseases (TB, Rheumatoid Arthritis)
- Autoimmune Connective Tissue diseases
- Chronic Pyelonephritis (whatever the cause is)
As the condition goes on [it won’t matter whether that process started from the glomeruli or from tubules and the
medulla (Chronic inflammatory processes)] this is due to the fact that at the end, all are present as Chronic renal
failure.
And these advanced cases are going to display:

- Arterioles show: Thickening & Hyalinization

- Glomeruli show: Sclerosis
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 - Tubules show: Diffuse Atrophy (but other tubules are going to be abnormally dilated lined by flattened
epithelium and they contain proteinaceous material)
- Interstitium show: Fibrosis
In Ultrasound (US) Kidneys looks  Small & shrunken

If a patient is having primarily a vascular pathology (e.g. HTN), you get to see also Hyalinization of the
Arcute arteries (b/w the medulla & cortex of kidney)  and this might complicate the HTN itself (where the
patient would develop Nephrosclerosis -making HTN even worse-)

So this condition goes for long period and patient might not be aware that he’s having continuously deteriorating
kidney function (A normal looking person might present with BUN =150, Creatinine= 2 this means that patient
had already advanced kidney disease without being aware of it)

Other patients might have Malignant HTN (Doesn’t respond to treatment, acute & rapid end organ damage;
Diastolic usually >120!)

That can be complicated by what we call >>>

Slide 65 ..: Malignant Nephrosclerosis :..

End-organ damaged organs include (Kidney, Heart, Brain, Eyes)

All of these organs might be affected rather simultaneously and over a short period of time; these patient are going
to have very prominent clinical presentation, they might present with:

 MI
 CVA
 Retinopathy
 Rapidly deteriorating Kidney function

Morphologically/Pathogenesis

The severely elevated pressure will be associated with:

1) Remarkable exudation of proteins and fibrinogen into the wall of the blood vessels themselves and that
large amount of fibrin will get deposited obscuring the underlying architecture giving us the impression of
Fibrinoid material weakening out the normal architecture = Fibrinoid necrosis [[[[So we don’t have an actual
necrosis but we have deposition of that material hiding the normal architecture of the blood vessels and the nearby
tissue]]]]
2) Severe/Remarkable endothelial activation (in part due to endothelial damage) associated with activation of
the coagulation cascade and Thrombosis –almost everywhere; particularly in organs of higher pressure and
of narrower arteries; as in the case of Kidney. [[Thrombotic Micro-Angiopathy]]
3) Proliferation of smooth muscles leading to plexiform musculopathy  referred to as Onion-Skinning
appearance of the blood vessels themselves.
[[This is how Malignant HTN affect arterioles around different organs of body]]

So in these cases, when kidney is affected, the blood to the kidney will diminish; because of the arteriolosclerosis; so
that might be associated with switching on of compensatory mechanisms of the kidney itself that will make that
condition even worse [[resulting from occlusion of Afferent arterioles: Marked stimulation of RAS + Bad HTN +
Aldosterone increased + Renin increased++…
(BP is going to be really elevated not responding to hypotensive drugs)

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Changes in the kidney (when it’s affected by malignant HTN):

 Cortical small tiny foci of hemorrhage; called petechial hemorrhage [1](or called flea bitten kidney); due
to rupture of small capillaries.
 Changes mentioned before can be seen not only in the vessels but also in the Glomeruli [2] (Fibrinoid
exudation, Endothelial activation, small thrombosis all occur over the blood vessels –especially in
Glomeruli) and that will be associated with the petechial hemorrhage & disruption of the glomeruli
themselves
And the condition in which we get to see wide spread thrombosis in those tiny blood vessels (& arterioles) is
referred to as Thrombotic Micro-Angiopathy [3]

Why Micro-Angiopathy?
 It occurs in small vessels because it have high resistance and high pressure, smaller endothelial cells that can be
affected by that elevated pressure – and that will be associated with a condition similar to DIC; where you get to see
small thrombosis widely spreading all over the body especially in the organs with high-level of circulation  so this
will be associated with crapping of the RBC’s and hemolysis in addition to the Intravascular thrombosis along
with thrombolysis)

- And since the affected vessels are the small ones  causes End-organ damage affecting the Kidneys, Heart,
Brain, others…
o CNS manifestation
o Liver involvement
o Kidney involvement; which might sometimes progress to Acute Renal Failure [4] manifested by
Hematuria & Proteinuria
o Retinal involvement
o Papilledema
o Encephalopathy
o Coagulopathy
o Vascular abnormalities
- Acute Renal failure in these cases (malignant HTN) isn’t going to be due to Renal Causes (not pre-
renal/post-renal causes), but not all are due to Glomerular or Tubular injury but due to Vascular injury in
these cases…
- Moreover, these patients present with those manifestations:
o Severe headache, Nausea, Vomiting (Due to increased Intracranial pressure & sometimes due to
hemorrhage)
o Scotomas (scattered Blind spots in the retina)
 Whenever you’re going to hospitalize a patient like this  you have to go for BUN & creatinine,
Urine analysis!!  whenever Proteinuria, Hematuria along with Oliguria are seen then the
patient is getting into Acute Renal Failure due to Thrombotic Micro-Angiopathy [Fatal outcome]

Similar in some aspects to DIC, however, pathogenesis & treatment are different

Differences from DIC:

- In this case, there’s HTN in contrast to low BP in DIC (because DIC patients are usually in states near shock or
due to septicemia –which cause endothelial activation other than HTN–)
- Elevated D-dimer in DIC

Difference from Heparin-Induced Thrombocytopenia (HIT syndrome):

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 - Result from administration of unfractionated heparin; where heparin is associated with formation of
antibodies against the endothelium as well as against certain platelets factors..
This will be associated with plt’s activation, consumption, and then Thrombocytopenia

Another condition similar to Thrombotic Micro-Angiopathy (TMA) is Thrombotic Thrombocytopenic Purpra

(TTP); which is considered the another cause of Thrombotic Microangiopathy…
- An acute condition where the patient presents with a near shock state and with CNS manifestation, evidence of Liver
and kidney damage, in addition to hemolysis within the blood vessels themselves ( Intravascular Hemolysis – this is
also seen in TMA)
- The mechanism is similar to TMA; where these patients are going to have widespread thromboses within
the blood vessels, and these thromboses are going to consume the platelets and they’re going to lead to
RBC’s hemolysis  Hemolytic (Intravascular) Anemia & Thrombocytopenia (overshadowing or
complicating the DIC)
- However, the mechanism in this case is different in that, in this case the patient is going to have vWF
resistant to degradation this again can be associated with something like Disseminated Thrombosis
within those blood vessels = this is referred to as TTP
- Presentation
Adult patient with No history of HTN or Septicemia or Toxic shock (may happen after some
inflammatory processes) presenting to you with CNS, Liver, & Kidney damage/manifestation and
Hemolysis
- Diagnosis:
Peripheral blood (blood film); you get to see Thrombocytopenia & Schistocytes (in an adult; it denotes
intravascular hemolysis

As opposed to extravascular hemolysis [ex. thalassemia+ they don’t have Schistocytes though there’s hemolysis –
but that hemolysis is extravascular [within the spleen; where it’s fragments are not going to get out from it+ )

Another condition similar to it in terms of clinical and morphologic changes (but not same mechanism and causes),
and that more frequent in children is: Hemolytic Uremic Syndrome

- Hemolytic; because we have intravascular hemolysis due to Fibrinoid activation within the small blood
vessels; especially within the glomeruli
- Uremic: it’s a misnomer; because these patients are not yet uremic
- When that process affects the glomeruli:
o Glomeruli get clod (all are going to have Fibrinoid within the glomeruli) associated with thrombosis
within of some of these glomeruli, the circulation within the glomeruli will become very disturbed 
leading to decreased GFR, and those damaged glomeruli will leak RBCs, as:
- Presentation:
A child (patient) that presents to you with Hematuria, Hematemesis, or Melena and Oliguria and Micro-
angiopathic Hemolytic Anemia (associated with Acute Renal Failure)
o Like if the patient is getting into Acute Renal Failure; which is characterized by azotemia (Hence
metaphorically called Uremic!) – though it’s not uremia by convulsion
o Urema indicates the Chronic renal failure not the acute renal failure

- Etiology/Causes:
GIT inflammatory process; due to Shiga-producing E.coli;

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 Shiga toxin will be associated with massive endothelial activation  massive thrombosis especially within glomerular
capillaries  so these patients are also going to present to us with signs of acute renal failure [[As if they have Rapidly
Progressive]]

Difference from TTP:

- TTP usually affects adults

- Mechanism is different (vWF Resistant to degradation)
- Treated with: [1] Anticoagulants –to prevent further thrombi formation–, [2] Plasmapheresis –especially in
Good-Pasteur syndrome; to remove Ab’s–

If biopsy is taken from a patient with Oliguria & Hematuria, & anemia, what would you see? [[[Biopsy is
not really needed nor indicated]]]

- Biopsy is not really needed; because *Oliguria & Hematuria+ are indicators that there’s -maybe- Transient
Acute Renal Failure, which can be caused by (causes of ARF)
1. Pre-renal
 Look for Shock; (unlikely in children!)
2. Renal
 RPGN; especially after streptococcal infection in these children ..
 Dx: Anti-Streptolysin lysine Antibodies (ASLO) & Hypo-complementemia
 Complement level gets down when it’s ongoing highly activated throughout the body; if
that’s associated with renal failure; then the causes are limited:
o Post-streptococcal
o Mmebrano-proliferative (Hypo-complementimic Glomerulonephritis); who
have C3 nephritic factor or deficiency of the complement inhibitor H  those
patient are going to have also overwhelming activation of the complement
 Even though, it’s not complement-mediated pathology
 IgA nephropathy; Diagnosed by simple blood and urine test
3. Post-renal
 Look for obstruction

Slide 75 The cystic Diseases of the Kidneys

These diseases are of a variety of conditions that are associated with the formation of single or multiple, unilateral or
bilateral, cortical or medullary cysts that are associated with normal or abnormal kidney function and even renal
failure (So these are going to pose a diagnostic dilemma!)

So we have to determine whether these are simple cysts or whether are going to be associated with renal failure,
whether these are neoplastic or non-neoplastic cysts, this is in order to determine our next
therapeutic/interventional approach

These are common; sometimes seen in renal failure patients as either a cause or a consequence of renal failure [1]…
and most of them are going to be due to a defect in diffusion between different nephron components [2].

The nephron though it’s an integrated functional unit, however, it’s made up of embryologically different
components; Glomeruli, Distal tubules, Proximal Tubules, collecting tubules… each of these arise from different
embryonic component – and all of these component have to fuse, and their fusion is going to be determined by

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certain genes that will determine the migration and the fusion of these tubules, if they fail to do that (as in cases of
failure of certain Microtubules-associated mechanisms – e.g. Centrosome & cilia- ) this leads to Blind-ended
nephrons and that component will continue to become cystic until eventually it might destroy the entire kidney
parenchyma itself,

Types include:

1) Simple cyst
2) ADPKD: Autosomal Dominant Polycystic Kidney Disease
3) ARPKD: Autosomal Recessive Polycystic Kidney Disease

 Simple cysts
Innocent cysts, however, their size might become very prominent (usually <5cm; but can be 10 or even 15
cm)
 Large cysts are really annoying to the patient; can be associated with pain
- Most common in Adults; most of them are accidental finding in the Ultrasound or CT
[[Cystic kidney is more possible as the patient gets older, however, it’s frequent in young]]
- By Ultrasound, cyst location must be determined and it’s usually:
o 1 or 2 in cortex either unilateral or bilateral (without affecting the medulla); where the cortex and
the cortico-medullary junction are still preserved [SIMPLE CYST]
- Tx; nothing; unless large & annoying go for aspiration to relieve the pressure and symptoms & Just make
sure this is simple non-neoplastic cyst

- Another of common occurrence are simple cysts seen in end-stage kidneys (which is a bilateral process
associated with shrinkage of both kidneys, whose management is either Dialysis or Transplantation)
o So going for chronic dialysis might be associated later on with cyst formation of those native non-
functional kidneys; and this again has no clinical significance (called trans-stygian kidney ‫ما بعد الجحيم‬
- ‫ موت الكلية‬-); we don’t have to anything except making sure that this entity is trans-stygian kidney

 ADPKD
In most of the cases (85-90%) is a Genetic condition due to inheritance of polycystin 1 (PKD1) gene
defect

PKD1 gene normally codes for (Polycystin 1) protein, a cell membrane associated protein that is largely
extracellular, involved in cell to cell adhesion and interaction between cells making up those nephrons and involved
in tubular cilia

- In these cases, there’re Cysts that are gradually growing and enlarging in size and in number (both kidneys)
 so process is going to be diffuse & to a certain extent symmetric; affecting the cortex as well as the
medulla [if you cut through that kidney; there’ll be not of much of left cortex ]
- Complications/Consequences…
As that process goes on and on; more functional nephrons are lost (patients are going to lose gradually their
nephrons)  until eventually they’re going to present to us with renal failure (at 40-50 yrs of age) [[
Before that he might have complaints -such as abdominal pain, hematuria, HTN, UTI- and these
complaints are non-specific being none of which is diagnostic  might be referred to Ultrasound  find
multiple bilateral Cysts ]]
- Management; tell the patient that at the age of 40-50; he’s going to have Renal failure (There’s nothing to do
about that); in order to Let him prepare himself for Kidney transplantation at that time
 This condition is inherited as AD

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 - During the process of proliferation or regeneration of some of those endothelial cells, they’ll form those
blind-ended spaces or cavities that will become later on cystic and eventually Chronic Renal Failure
o So the only solution is Kidney transplantation (Doesn’t recur after transplantation)
- Morphologically; the cysts will develop in all segments of the corpuscle of the kidney itself and sometimes
you get to see remaining kidney parenchyma or cortex in between those dilated spaces; which might sustain
the normal kidney function for a period of time
o Later on the cysts will become larger; filled with yellowish (sometimes hemorrhagic blood) fluid;
can also be associated with symptoms (mentioned before) but not necessarily; most of them are
accidently found
- Because these are of congenital GENETIC abnormality; other cystic structures can be seen elsewhere:
particularly Berry aneurysms of the Circle of Willis (in 15-20%) - Pay attention to these patients! Some
of them, especially if they’ve HTN, they can develop subarachnoid hemorrhage because of the rupture of the
berry aneurysm-
Or they may have Liver cysts (in 30%, usually asymptomatic and not problematic), pancreas, spleen, pineal
gland, seminal vesicles and lung
[[Some factor might complicate the progress of PKD such as: Hematuria, HTN, UTI]]

Another, rather interesting, manifestation is Multi-cystic Renal Dysplasia; these patients are going to have cysts
of different sizes in both kidneys (Unilateral or Bilateral). However, these are going to present very early in life (not
like Adult polycystic Kidney type) usually in newborn as an abdominal/flank mass associated with renal failure
(Most common cystic disease in children)

- Here, nomenclature could be confusing; because Dysplasia doesn’t mean premalignant condition, But it
indicates abnormal maturation/formation of the kidney from the embryologic and histologic point view
- Sometimes it might be associated with formation of alien stroma (such as cartilage!); that’s why it’s
referred to as being dysplastic
- These patients might have other congenital abnormalities that are associated with aggravation of the renal
disease, such as Ureteral atresia, Obstruction of ureteropelvic junction, or Urethral obstruction (last
2 contributing to obstructive uropathy)
- Grossly; enlarged kidneys, might be palpable in the neonatal period
- Microscopically; abnormal epithelium, immature stroma (Cartilage, Fibro-muscular tissue, Disorganized
tubules Renal failure)
- Fortunately, the expression might not be bilateral (due to some micro-environmental factors)
 ARPKD
In childhood, incidence is rare (about 1/10,000)
- Associated with gene defect in Gene PKHD1.

Gene PKHD1 codes for fibrocystin, a form of membrane receptor protein involved in the function of cilia (which
will the final integration of the components of the tubules themselves)

- Because this gene is needed for other tissues maturation; that condition (also as the ADPKD) can be
associated with other extra-renal involvement; particularly the liver where there’ll be von Meyenburg
complex of the liver (which is a bile duct hamartoma in the liver manifested as benign tumour-like
malformation of the liver) and this might be associated with congenital cyst  that might lead to Hepatic
Fibrosis or bile duct ectasia or Bile ductules atresia
o We used the term fibrosis rather than cirrhosis; because there isn’t much regeneration (having
fibrous tissue in the liver but the remaining parts of it are of normal architecture)

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 - It may also involve Lung abnormality that is associated with underdevelopment of the lungs
(Pulmonary/Lung Hypoplasia) which might be associated with death in the early stages of that
disease ** If patient didn’t die in early life due to respiratory failure; he dies from Renal failure ]]
 Usually manifests at birth, large abdominal mass with Potters sequence (Pulmonary hypoplasia,
joint deformity, characteristic facies)

Previous conditions (abnormal makeup of cilia) differ from Kartagener’s Syndrome that results from immotile cilia;
meaning that their -motor- events are missing (which is the dynein);

Moreover, Microtubules, involved in Kartagener’s syndrome, are necessary for cellular migration in the
embryogenesis (having problem at this level causes the Situs Inversus; which is not usually associated with APKD;
where the problem is not in the movement of the cilia but rather in their interaction)

ARPKD, it’s going to be:

- Diffuse
- Bilateral
- Characterized (by ultrasound) in that most of those cysts are going to be located within Cortex and mostly
within the medulla  having small cysts filling the kidney in nearly homogenous pattern importing to it a
Sponge-like appearance (Lot of fenestrae –cysts–)
- So Bilateral, variously sized, increasing in number and in size kidney cysts in adults-renal failure at age
40 .
- These patients are going to have normal kidneys, then at age 20 they will form these cysts, and at age of 40
they will develop renal failure.

‫ ليان ملحم‬، ‫ آيه جابر‬: ‫اجلزء الثاني‬

Slide 85  Multicystic renal dysplasia:

 The patient present with abdominal mass and if you go for biopsy, you will get to see abnormal tissue within
the kidney itself.
 Note: this dysplasia has no precancerous connotation, because dysplasia in this case is totally different (not
acquired due to carcinogenesis dysplasia), but it is abnormal maturation leading to abnormal tubules in
these patients.

Slide 87  Autosomal recessive polycystic kidney:

 Occurs in children
 These patients are not going to have just this disease, but also other organs are going to be affected,
especially the lung.
 So these patients might die either of lung failure or kidney failure.
 If you go for biopsy, you will see cysts that are mostly going to be located within the medulla, leading
eventually to degradation of the kidneys at an earlier age.

Slide 90  Medullary cystic kidney:

 When we get to see cysts mostly in the medulla, imparting to it what we refer to as sponge appearance
 Two groups:
1. Medullary sponge kidney : very benign, more than one cyst setting in the medulla, and not associated with
disorganizations of nephrons .Some of these patients may have hemihypertrophy( part of the body is larger
than the other ) as an association with that condition (1_4%) and when you get to see that, it is usually with
no clinical significant.

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 2. Nephronothesis( uremic medullary cystic disease) : associated with renal failure
 Why we didn’t consider it autosomal recessive polycystic kidney?
 Different genes are going to be incorporated as well as extrarenal manifestations, for example:
retinitis pigmentosa, liver fibrosis, mental retardation as well as cerebellar malformations.
 In most of the cases, the cause is autosomal recessive NPH1 ( nephronothesis medullary cystic disease gene)
that also has something to do with the movement and the motility of the cilia itself
 This is really common, and might be considered as one of the most common genetic diseases leading to
renal failure (Remember that the most common cause of renal failure worldwide is diabetes) .

Slide 92  Renal stones ( renal colic)

 Severe abdominal pain radiating to the external genetalia
 Can be associated with dysuria, sometimes with mild hematuria
 1% of population clinically significant
 Higher percentage -> asymptomatic
 Males more than females and some of them might have genetic tendency
 So these patients are going to have different presentation, either they are going to present to us
with renal colic, or with UTI or with renal failure!
 If we are talking about renal colic, then the stones are going to besmall and located within the
ureters, the ureter will have peristaltic waves trying to move or squeeze that stone down to the
bladder, and that will be associated with erosion, ulcerations, inflammation and traumatization of
the ureter itself leading to severe pain
 Usually those who have renal colic are going to have small stones within the ureter while larger
stones within the pelvis are not going to be associated with renal colic( may obstruct the ureter from
above causing hydronephrosis or even renal failure

 What lead to the formation of these stones?

o Genetic
o Inflammation
 Most of these stones are going to contain calcium oxalate and phosphate (more than 80%)And that
what makes them radio opaque by X-ray .
 So, most of these stone are going to be seen using ultrasound
 But if a patient came to the ER with severe abdominal pain, we do what we call plain abdomen or
KUB (diagnostic medical imaging technique of the abdomen and stands for kidneys, ureters, and
bladder) .
 What causes this calcium-containing stones?
1. Idiopathic hypercalciuria
2. Hypercalcemia which is going to be associated with hypercalciuria

 When the patient passes the stone, you analyze it to know its chemical makeup
 If it contains calcium you have to know if the patient has hypecalcemia or idiopathic hepyrcalciuria, by
measuring the serum calcium
 If serum calcium was high then it is hypercalcemia
 If not, you have to collect the urine for 24 hours and measure the excretion of
calcium in the urine to know if your patient is having hypercalciuria
 Some patients may have hyperuricosuria; high levels of uric acid in the urine that on top of which calcium can be
deposited causing stones even though calcium levels are normal)
 In some patients (especially young children), these stone will contain oxalate due to
hyperoxalateuria or hyperuricosuria.

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  If your patient is a stone-former, you have to investigate him, but if not you just have to tell him how
to avoid forming these stones.
 Struvite stones: high levels of ammonium, and mostly is going to be due to infection (in patients with
repeated UTI, for example, the debris will be deposited with ammonium forming struvite stone)
 Hyperuricosuria in patients with hyperuricosemia as in the case of gout. Uric acid stones:
 Others like cysteine, oxalate is going to be seen in children who have some sort of metabolic
diseases.
 Stag horn stones: very large stones in the pelvis, which will lead to destruction of the kidney with
no pain!

Slide 98  Hydronephrosis:
 Distension and dilation of the renal pelvis and calyces, filled with urine, and the cortex is atrophic
 Causes:
1. The most important cause is obstruction, and depending on the underlying causes, it might be
congenital due to absence of the urethra or valves or the kidney may be abnormally located, and
sometimes that can be associated with retroperitoneal fibrosis .
o If the obstruction is at the level of prostate or lower, this will be associated with bilateral
Hydronephrosis. But if it is going to affect one of the ureters, then it is going to be
unilateral.
o The only solution is nephrectomy
2. Other acquired causes: calculi, tumors, inflammatory processes, neurogenic relaxation of the
ureter and pregnancy induced.
Congenital valve abnormality: formation of valves in wrong places .
 the backflow will be associated with increased pressure on the glomeruli, causing irreversible
damage of the glomeruli and later on atrophy of the cortex , and if we have inflammation , that can
be associated with inflammatory process leading to pyonephrosis ( pus in the kidney ).

Slide  Renal cell carcinoma

102  Most of them arise from the epithelium of the tubule and collecting ducts , virtually we have no
tumors that arise from glomeruli , very occasionally you see primary tumors arising from the interstituim
(Angiolipoma , fibroma , fibrosarcoma , angiosarcoma … ) .
 Earliest manifestation of RCC is nothing .
 Increased risk in
 Smoking
 Exposure to cadmium
 Acquired polycystic disease in dialysis
 genetic
 Mostly 6th to 7th decades, M:F 2:1 ; That’s the age when these patients are going to have the characteristic
manifestation of RCC that includes .
 What’s good about RCC is that they may achieve large sizes without metastasizing , so the staging here is
different ( when these tumors are less than 7cm , most likely they haven’t metastasize yet .
 RCC are divided into different morphologic types because they have different underlying oncogenes , the
response to treatment and prognosis is also different .
Clear cell carcinomas
 The cytoplasm will be clear, because the contents of it is glycogen , which will be washed up during routine
tissue processing .
 This cans be sporadic ( mostly ) , or it can be due von Hipple –Lindau disease (we talk about it in 1st semester
, these patients are going to have increseed proliferation due to hypoxia that has to be inhibited by von
Hippel- lIndau gene , these patients are not going to have inhibition , so this can be associated with excessive

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 proliferation of these cells leading to clear RCC , It is Also associated with hemangioblastoma of the
cerebellum and Numerous bilateral renal cysts )
 Treatment is different for these patients , sometimes we give them Interferons.
Papillary renal cell carcinoma
 Papillary projection
 Over expression of Met gene.
 Sporadic forms .
Chromophobe renal cell carcinoma
 5%
 Arise from cortical collecting ducts
 Mutation are different from those with clear type .
Oncocytoma :
 A cell Characterize by the presence of many mitochondria within the cytoplasm , and those large numbers of
mitochondria will impart to that cytoplasm eosinophilic granular appearance .
 Most of the oncocytomas are Grade 1 , stage 1 tumors , so previously it was considered as benign tumors ,
but nowadays we consider them as low grade metastasizing RCC that have to be treated the same way .
 Slide 106 : this is the characteristic appearance , all of these is hemorrhagic yellowish tumor that tends to be
surrounded by capsule or the “ Gerota’s fascia “ .
 Renal cell carcinoma likes to invade renal veins and sometimes reach vena cava

Slide107 this is how they look under microscope

Slide108 clinical manifestations

 Painless hematuria
 Palpable mass and flank pain
 Painless hematuria and flank pain! How come?!
 Painless or painful hematuria while the pt. is urinating. So when pt. has pain during urination, this denotes
nephrolithiasis or UTI while if the pt. doesn’t have pain during urination with isolated flank pain, this might
denote cancer.
 Fever
 Polycythemia due to increase erythropoietin
 Hepato-renal syndrome (Stauffer syndrome) = Hepatomegaly even with normal liver function test. The
mechanism unknown! What we know is: when we remove kidney tumor the liver will get back to normal.
 Other hormone like substances cause hypercalcemia, hypertension
Slide109 Wilms tumor (nephroblastoma)
 Wilms is the author who describes this tumor.
 Nephroblastoma Is misnomer, it actually means that we have abnormal maturation of the kidney.
 Very common among children before age of 10and. they will have this tumor b/w age 2 and 5
 Associated with wilms tumor dislocation on chromosome11
 So, what’s lead to this tumor is genetic that might be inherited or mutated.
 When it is mutated might be associated with other abnormality elsewhere, e.g.:
o WAGR syndrome is a combination of (Wilms tumor, Aniridia(the absence of iris), Genital
abnormalities and mental Retardation)
o Denys- Drash syndrome: the patients are going to have renal abnormalities as well as gonadal
dysgenesis.
o Beckwith-Wiedermann syndrome these patients are going to have increase sizes of adrenal cells as
well as hemyhypertrophy.
 What characterizes that tumor is its tendency for multicentricity and bilaterality
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 ‫وهاي مشكلته! ٌعنً ممكن ٌٌجً بأكثر من محل بالكلٌة والمشكلة األكبر انه ممكن ٌٌجً بالكلٌتٌن‬
Synchronous wilms tumor when there is tumor in both kidneys
Slides 111-112 morphology
 It looks whitish, firm tumor that is going to be made up of multiple components.
 Most of the cases there is three components –even the is a dominant one but all of them are present- .
These components are:
o Blastem,
o Stroma,
o Epithelium.
So all components of kidney will make neoplastic proliferation

 Epithelial cell type will form abortive tubule and glomeruli

 Stoma—might form myxoid tissue, skeletal and cartilage within kidney
 Blastemal which means undifferentiated cells
Slide114 presentation
 Abdominal mass- mothers or fathers usually feel it.
 Some will have fever, hematuria
 Prognosis is good
Tumors of urinary bladder- Slide115
 Urothelial tumors which means these tumors are going to arise from urothelium (transitional epithelium
that lines the pelvis, ureter and bladder). That Epithelium might be affected by the same carcinogenesis in
all parts so sometimes we call it a common field theory- imagine that this is a field lined by urothelial cells
that affected by the same environment which is urine. So u expect to see these tumors along that field
allover but mostly it will be seen in bladder because in bladder there is time of contact b/w epithelium and
carcinogens present in urine.
 These tumors might grow in the form of papilla or they might form that solid below the pelvic.
Slide117
 In the case of papillary type it might be classified into begin papilloma- we don’t use this term any more-
instead we use Low grade of low potential malignant tumors.
 They grow as cornflower mass within the bladder.
 Grading today we use low / high grade instead of grade 1, 2 ,3
 Staging In situ \invasive. The treatment is going to vary:
o In situ- we remove them and give the patient intravesical BCG which will activate the immune
system and that might be associated with a decrease recurrence.
o Invasive we have to go for cystectomy and chemotherapy
 The only manifestation is painless hematuria
Remember: Painless hematuria with no cast =this is tumor.
If there is cast=glomerular hematuria.
... ‫ وٌنتهً المساق‬، ‫الطالب ٌقومون بالتصفٌق للدكتور على جهوده‬

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