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110 Cards in this Set

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A patient presents with polyuria and nocturia. He is found to be pale and tachycardic, and his blood pressure when measured is 160 on 90. What is happening to this man? What could precipitate worsening of his condition?
Polyuria and nocturia = inability for the tubules to concetrate urine = tubular dysfunction. Acute renal insufficiency. Not presenting with uremic symptoms yet (failure), but kidneys struggling. Hypertension and anemia are also features of renal insufficiency.
Any nephrotoxin could precipitate uremia in this patient: aminoglycosides, cisplatin, NSAIDS, iodine contrast etc.
What are the clinical features of Autosomal dominant polycystic kidney disease?
Firstly, association with liver cysts and berry aneurysms.
Presentation is in 40's-50's: flank pain, haematuria, UTI's, hypertension.
What are the features of childhood/ autosomal recessive polycystic kidney disease?
- Enlarged, cystic kidneys at birth.
- Death in infancy or childhood.
- Also causes hepatic fibrosis.
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What are the mechanisms of Antibody-Mediated glomerular injury? (Note: 2 major divisions).
Mostly immune mediated.
Antibody mediated broken up into 2 types:
1.In Situ IC formation: circulating Ig react to intrinsic tissue antigen in the glomerulus.
a) anti-GBM antibody induced nephritis. IgG deposit in response to goodpasture's antigen, collagen IV). The ICs form linear deposits along the glom basement membrane.
b) Heymann nephritis: reaction to basal surface of visceral epithelial cells (Heymann antigen) - cause a membranous nephropathy.
c) Planted antigen, can be exogeneous (infectious eg post-strep GN, drugs), or endogenous (DNA, nuclear proteins, IgA).

2. Second mechanism and the most common, is Circulating Immune Complex deposition. The difference here is that the Ag-Ab reactions occur in the circulation, forming immune complexes that then get trapped within glomeruli. The possible antigens are the same as above: endog (SLE dna), tumor antigens) or exog (infectious products eg strep, HBsAg). May be cleared by local neutrophils/ macrophages if only a transient increase in the circulating IC, but if a continous shower of Ag is provided (eg Viral hepatitis, SLE), reaction may lead to a chronic membranous/ membranoproliferative GN.
Injury to the glomerular cells is not always anti-body mediated (In-situ IC, or Circulating IC). What are the other mechanisms?
Cell mediated immune injury eg sensitised Cytotoxic T cells. May be involved in the progression to chronic GN.

Activation of alternative complement pathway: activated by endotoxins, bacterial polysaccharides, IgA.... result in decrease in serum complement levels, and deposition of C3 in the glomeruli. Seen in nephrotic syndrome: membranous, FSGS. And in nephritic syndromes: RPGN type II (Immune complex), Post-strep GN, ,and mesangial proliferative eg Berger's/ IgA nephropathy.
What are the 2 major mechanisms of progression of glomerular disease?
1. FSGS.
2. Tubulo-interstitial nephritis.

FSGS: compensatory hypertrophy of remaining glomeruli --> haemodynamic changes that increase glomerular blood flow, filtration and BP --> glom HTN. Damages endothelium- increased permeability of the wals - protein leak and accumulation in the mesangium. Increased ECM production --> focal and eventually global sclerosis = further reduction in nephron mass.

2. Tubulo-interstiital nephritis: A result of ischemia, or downstream to sclerotic areas. Amplified massively by proteinuria - the proteins (such as Fe, Ig, other) activate the tubular cells, which when activated, secrete pro-inflammatory cytokines such as VEGF, TGF-b, ET-1 --> activate macrophages and fibroblasts --> FIBROSIS.
What are the 5 purely nephritic snydromes?
1. IgA nephropathy
2. Anti-GBM
3. Idiopathic RPGN.
4. Membranoproliferative GN
5. Mesangial proliferative GN (APSGN)
What are the 3 pathological changes that can occur in IgA nephropathy (Berger's Disease).
1. Mesangioproliferative GN (mesangial widening and proliferation due to deposition of polymeric IgA, that activates the alternative complement pathway and expands mesangium).
2. Focal proliferative: segmental proliferation.
3. Crescenteric GN (rare)
How does Berger's present, who getis it, and what 5 conditions is it associated with?
Bergers, most common GN worldwide, predominantly affects kids and young adults.
Presents as recurrent haematuria, typically gross haematuria after a respiratory infection. It usually lasts several days, and then subsides, only to recur within a few months.

1. Viral or bacterial inflammation of mucosal surface, esp URT (membranous infection/ inflammation; where sIgA is stimulated).
2. Crohns
3. Coeliac.
4. Chronic Bronchitis (be aware in a smoker)
4. Liver disease (failure to clear IgA complexes.

Complications:
- 5-10% develop acute nephritic GN.
- 15-40% progress to CRF over 20 years.
What are the clinical features of crescenteric GN?
= Severe glomerular injury, rapid loss of renal faunction with SEVERE OLIGURIA +
- Haematuria
- Moderate proteinuria.
- Variable hypertension and oedema

Goodpasture's syndrome may also have recurrent haemoptysis.
What are 6 compplications of nephrotic syndrome?
1. Massive proteinuria --> loss of Ig --> Infections.
2. Loss of antithrombin III etc --> coagulation. 10-40% --> venous thrombosis, pulmonary embolism.
3. Periorbital oedema, ascites, peripheral oedema, pleural effusion.
4. Decreased GFR (loss of intravascular oncotic pressure)
5. Frothy urine due to proteins.
6. Xanthelasma and xanthomata (hyperlipidemia).
What are the 2 main causes of membranous glomerulonephropathy?
1. Idiopathic (80%)
2. Secondary to systemic condition eg SLE, drugs, tumors.
What is the pathology/ pathogenesis behind membranous GN? (nephrotic).

How does it present? (adult)
IC deposition along subepithelial side of BM- eg travel through endothelial fenestrations, through the basement membrane, and then sit just bwn the BM and the visceral epithelium/ foot processes. Sit here, and eventually get engulfed by membane --> membrane thickening. The membrane thickening can encroach on the capillary lumen, and sclerosis of the mesangium may also occur.

Presentation: insidious onset of nephrotic syndrome, in a previously healthy individual.
What are the 4 pathological changes of diabeic nephropathy/ Glom sclerosis?
1. Bilateral enlargement of the kidneys at the beginning- feel for it ina adiabetic patient presenting with nephrotic syndrome.
2. Capillary BM thickening, and mesangial expansion/ sclerosis.
3. Focal Nodular Glomerulosclerosis (ovoid nodules of matrix at the periphery of the glomerulus, can enlarge over time and obliterate glomerular tuft).
4. HYALINE arteriosclerosis, of the afferent and efferent arterioles, due to leakage of plasma componenets across the damaged vascular endothelium, and increased ECM production by SMCs.
3 and 4 account for the severe proteinuria.

( 1. BM thickening. 2. Mesangial sclerosis.
3. Nodular glomerulosclerosis. 4. Hyaline arteriosclerosis.)
Broadly speaking, glomerular disease manifests as 1 or more of :
decreased GFR, haematuria, proteinuria.... hypertension, oedema.
What are the three clinical manifestations of RPGN?

What are the three signficant causes?
1. Proteinuria.
2. Acute nephritis.
3. Acute renal failure.

Type I; Anti-GBM
Type II; Immune complex disease eg SLE, IgA nephorpathy.
Type III: Pauci Immune (ANCA) eg Wegener's.
What are 5 causes (1 renal, 4 secondary) of asymptomatic haematuria/ proteinuria.
Renal: IgA Nephropathy.
Secondary:
- Exercise induced haemoglobuinuria.
- SLE
- Henoch-Scheinlenn
- Bacterial endocarditis.
What is Wegener's Granulomatosis?
- Vasculitis, affecting nose, lungs kidneys, others.
- Life-threatening, requires long term immuno-suppression.
- Common feature is auto-immune attack by ANCAs; attack small and medium sized blood vessels.

Initial symptoms:
- Rapidly progressive glomerulonephritis (75%), leading to chronic renal failure.
- Upper airway pathology eg nosebleeds, hearing loss, gingiivitis, scleritis...
- Lungs can also form pulmonary nodules ('coin lesions), often interpreted as pneumonia, that can cause hemoptysis.

Pathophys: inflammation, with granuloma formation, against a non-specific inflammatory background. ANCA's can activate neutrophils, increasing their adherence to endothelium, and induce their degranulation, damaging the ECs. However in vivo, it is not known that this is the cause of the vasculitis. Exact mechanism unknown.
40 yo white male, presents with rapidly deteriorating renal function: oliguric, with gross haematuria.
Also has been coughing up blood over last few days. What are the differentials, to include both symptoms?
- RPGN + haemoptysis: classic presentation of Goodpasture's syndrome.
- Type III RPGN is ANCA mediated, a component of Wegener's Granulomatosis patients (75%). WG also often has pulmonary involvement, with pulmonary nodules, infiltrates, and haemorrhage causing haemoptysis. WG also typically presents in middle age, and 90% of the patients are white.

Other causes: Tumors can cause a continous shower of Ag.
- Membranous Glomerulonephropathy (secondary) can be in association with tumors eg a bronchial carcinoma causing haemoptysis. However membranous GN typically presents as insidious onset of nephrotic syndrome.. less likely in this patient.
Henoch Schonlein Purpura? What is it, what is the "classic triad" and what renal condition is it associated with?
Purpura, Arthritis, and Abdominal Pain.
40% have kidney involvement- may be small amounts of blood and protein in the urine, usually goes unnoticed (asymptomatic haematuria and proteinuria).

HSP is a childhood disease, a small vessel vasculitis in which IgA complexes and C3 are deposited in arterioles, capillaries and venules. It is often preceded by an infection such as pharyngitis. It is a systemic vasculitis, characterised by immune complexes containing IgA. It usually resolves within sevreal weeks, and requires no treatment: may relapse in a third, irreversible kidney damage in 1/100.

The Purpura is raised, and typically on the legs and buttocks.
The abdominal pain is colicky, may have nausea/ vomiting. May cause GI haemorrhage by intussusception.
Arthritis, typically of the ankles, knees and elbows. Non-erosive, no permanent damage.
What are pitfalls of serum creatinine as an indicator of renal function?
It only manifests as increased serum creatinine when there is signficiant renal damage eg only starts to rise when GFR is ~30ml/min (as per diagram), or 20% of normal function (normal is ~120).
Creatinine also varied by age, mass, gender.
It is ideal however for tracking the trend of kidney function in an individual over time, as a measure of deterioration/ improvement.
Stages of CKD:
Measured in relation to GFR:
1. >90, but slight kidney damage.
2. 60-90, mild decrease in function.
3. 30-60, moderate decrease in function.
4. 15-30, severe decrease in function.
5. <15, kidney failure.
What component of the cockcroft gault equation is not included in MDRD calculation of eGFR?
Cockcroft & Gault: = (140-age) * Wt * 0.85 if female / 72*serum creatinine.

MDRD does not adjust for body mas.

Serum creatinine in a bigger person is going to be higher... A falling eGFR might be masked by higher production of Cr.

Cockcroft Gault should not be used for kids, patietns at extremes of body habitus, amputees, the elderly/ overtly cachectic.

So for a heavy person, MDRD not including weight will cause an underestimation of GFR. and thin people will have their GFR over-estimated.
Risk factors for CKD?
Modifiable:
- Smoking
- Diabetes
- Obesity
- HTN

Non-Modifiable:
- Age >50yo
- Fam Hx of kidney disease.
- ATSI
Relationship between kidney and cardiovascular disease?
CKD patients have a 2-3 fold greater risk of cardiac death than other invidviduals.
20 times more likely to die from CV event than end up on dialysis.
Even early CKD is a significant risk factor.
When is it advised to cease renally excreted medications?
When GFR < 60ml/min.
Drugs that should be avoided include digoxin, famcyclovir, gabapentin (GABA analogue in treatemnt of epilepsy), Lithium, Sotalol, Metformin, Erythromycin, NSAIDS, ACE-Is, radio contrast, aminoglycosides.
What is the 'triple whammy' of drugs in renal failure?
- NSAIDS
- ACE-I
- Diuretic.
What are some major symptoms of uremia?
- Ano, naus, vom.
- Confusion, lethargy.
- Muscle twitching, convulsions,
- Coma.
What are the 5 functions of the kidney, and the corresponding consequences of chronic renal failure...
1. Nitrogenous waste excretion --> accumulation/ uremia.
2. Electrolyte balance --> imbalance.
3. Salt and water balance --> fluid overload or depletion.
4. Acid Base Balance --> acidosis.
5. Hormonal: Vitamin D, EPO --> bone disease, anemia.

+ impaired clotting (decreased plately aggregation)... pruritis/ dry skin... infection (abnormal antibodies).
What are some EARLY signs of uremia?
Weakness, fatigue. Naus/ anorexia.
METALLIC taste. Pruritis/ dry skin.
Pallor.
Nocturia/ polyuria.
Platelet dysfunction --> thrombocytopenia/ bruising-bleeding.
Pericarditis.
What is dialysis?
Removal of toxic wastes and excess water from the blood, across a semi-permeable membrane.
What are the four components required for dialysis?
Dialyzer (membrane)
Dialysate (fluid)
Tubes for transport of blood and dialysate.
Machine, to power and mechanically monitor the procedure.
What are the three factors affecting diffusion (eg in dialysis?)
1. Concentration of solute.
2. Size of slute/ molecular weight.
3. Membrane resistance/ permeability.

Utra filtration in haemodialysis also uses positive pressure on the blood side, or negative pressure on the dialysate side.
Ultrafiltration in peritoneal dialysis relies on the osmotic gradient:
Can creatinine cross the dialysing membrane?
Can bacteria?
Creatinine can- high creatinine on patient blood, returns to the patient with low creatinine.
Bacteria can NOT cross the membrane, however endotoxin fragments (LPS), peptidoglycans etc CAN.
What are the 5 types of dialysis?
HD:
- in centre
- satelllite
- home
PD:
- CAPD;continuous ambulatory PD
- APD; automated PD.
What is the 'kidney check screen'?
BP
eGFR
Urinarlysis for albuminuria.
What is the definition of CKD?
GFR< 60 for 3 months, with or without evidence of kidney damage.
Or evidence of kidney damage for >3 months, with or without decreased GFR.
Evidence of KD includes:
- Micro or macro albuminuria.
- Persistent haematuria
- Pathological evidence eg renal biopsy.
- Radiological evidence eg scarring or PKD on US.
What are some implications regarding kidney disease in the indiginous population?
Between 9-30 times increased risk of ESRD.
- Less likely to get a transplant (comorbidities, advanced disease on presentation, less likely to find a suitable donor, cultural factors.
- High cost of treatment, out of reach
- Impact on QOL, both patient and carer.
- Death from ESRD also much higher rate (5x rate of non-indiginous).
List 5 contributing factors to the prevalence and poor prognosis of kidney disease in indiginous communities?
1. Low birth weight- linked to fewer nephrons.
2. Poor perinatal nutrition.
3. Increased incidence of diabetes
4. Late presentation
5. Inequalities of access to health survices eg 100s of km's from nearest hospital.
What are the three most common causes of CRF, and three others.
1. Diabetes (30%)
2. GN (25%)
3. HTN (15%)
+ polycystic kidneys (10%), vesicoureteric reflux, analgesic nephropathy.
How does sickle cell disease cause renal pathology?
Painful crises: where the abnormal sickle proteins aggregate, and cause vessel occlusion, resulting in painful ischemia of the supplied region. Vessel occlusion in the kidney produce glomerular HTN, FSGS, interstitial nephritis and renal infarrction. Associated wtih hypothenuria, microscopic and even gross haematuria. Treatment is directed at reducing frequency, and AC-Is to delay progressive declione of renal functions. By the second or third decade of life, persistent vasoocclusive disease in the kidney leads to varying degreees of renal failure, and some patients end up on dialysis.
What 2 systems are schistosomiasis associated with, and what is the name of the organism?
Renal and GI manifestations> Affects more than 300 million people worldwide.
Schistosomiasis mansoni is associated with renal problems. 4 distinct syndromes, including mesangioproliferative, membranoprolifeaerative, FSGS and amyloidosis.
What component of the GBM are antibodies directed at in anti-GBM disease?
The alpha-3 NC1 domain of collagen IV.
Are the kidneys often involved in lupus? Who has the worst prognosis. What are the 6 stages of lupus nephritis?
Up to half of patients with SLE will have renal involvement with symptoms at diagnosis. :Iupus nephritis results from deposition of circulating ICs, which activate the complement cascade, cause leukocytic infiltration, and secrete pro-inflammatory cytokines. In situ IC formation may also play a role in renal injury. Most common clinical sign is proteinuira, but haematuria and hypertension can present.
The lupus nephritis is most severe in YOUNG BLACK FEMALES.
What are the 2 most common causes of gross haematuria, as a consequence of glomerular injury?
- IgA nephropathy (recurrent gross haematuria, for several days and then subsides- usually after an upper respitary tract infection).
- Sickle-cell disease.

Other common causes of haematuria include UTI, Kidney stone/ ureteric stone, BPH, Schisto,
A man presents with shortness of breath, and red urine in the mornings.... Dx?
What is the main complication to be wary of in this patient?
PNH; paroxysmal nocturnal haemoglobinuria. Complement induced intravascular haemolysis of RBCs due to an ACQUIRED defect in the cell membrane; deficiency of GPi, leading to absence of protective mechanism to prevent complement destruction- similar to ITP.
Causes anemia, and red urine due to the excessive haemoglobin in the urine.
Can be primary, or secondary to myelodisplastic disorders such as aplastic anemia.

Thrombosis: 40% develop a clot at some point in their illness = main cause of severe complications/ death. Clots can be in common sites such as DVT - PE. But in PNH can also form in more unusual sites, such as the hepatic vein (Budd-chiari syndrome), the portal vein of the liver (portal vein thrombosis), or the SM/IMV (mesenteric ischemia). Cerebral venous thrombosis is also more common in PNH.
What is the clinical approach to haematuria?
What points you towards a glomerular origin?
Consider the most common causes first.
Then exclude anatomic lesions such as malignancy of the urinary tract, particularly in older men. Or may be at the onset of BPH, interstitial nephritis, renal stones, Cystic kidney disease or renal vascular injury. Dysmorphic RBCs point you towards a glomerular origin, such as glomerulonephritis.
How will a patient present with proteinuria eg what will their complaint be?
Notice that they are more puffy than usual, carrying extra weight. May notice 'foamy urine' on voiding.
What are some causes of transient proteinuria?
Fever (all the extra inflammatory proteins), exercise, sleep apnea, obesity, emotional stress, congestive heart failure.

N.b proteinuria in adults is largely non-selective, cf children, where proteinuria is selective, largely composed of albumin.
Acute nephritis is proteinuria, haematuria, pyuria, hypertension, and a rise in serum creatinine. The serum creatinine rises over a few weeks, if the inflammation develops slowly. If the serum creatinine rises acutely over a few days, what is this then referred to?
Rapidly Progressive GlomeruloNephritis.
What is nephrotic-range proteinuria?
Large amounts of protein in the urine, without clinical manifestations. The GFR in these patients may initiially be normal, but with persistent hyperfiltration, the proteinuria will initate nephron loss, and GFR will decline.
What are some ways to distinguish acute from chronic renal failure?
- How the patient feels; Patients who develop RF quickly are often tired, weak, miserable; have uremic symptoms eg ano/ naus/ vom, pruritis, metallic taste, confusion/ somnolence..... Chronic development, may be asymptomatic.
- Renal ultrasound: small kidneys, more likely to be chronic.
How long does it usually take for APSGN to develop, after a) skin infection/ impetigo and b) throat infection/ strep pharyngitis.
a) 2-6 weeks for impetigo.
b) 1-3 weeks for skin. (throat has better access to central blood supply- think of the throat closest to aorta, more rapidly disseminated to the kidneys).
What are some renal complications of bacterial endocarditis?
IC deposition, causing endocarditis associated GN. The kidneys have subcapsular haemorrhages with a flea-bitten appearance = immune-cell foci, with necrotic surrounds.
- Can also get embolic infarction.
- And septic abscess formation.
What is IgA nephropathy, in simple terms (one sentence).
Deposition of IgA in the mesangium, causing recurrent episodes of haematuria.

N.b is the most common GN, male preponderance, 20's-30's.
How would you differentiate IgA Nephropathy, and Henoch-Schonlein Purpura.
HSP: distinguished by prominent systemic symptoms eg arthritis, gi pain, purpura, + preceding infection + younger age (<20yo).
When do symptoms of CKD usually present?
Stage 3: (90, 90-60, 60-30) --> GFR between 30-60.
Each stage usualy has hypertension.
What is isothenuria?
When the GFR drops below 15ml/min (stage 5), the urine output and osmolarity becomes fixed = isothenuria.
A young man has just begun a course of ampicillin for a skin infection.Over the next few days, he finds running a fever, and feeling really dizzy when he stands up. He is also breathing wierdly- very fast, deep and sighing. What might be going on with this patient? What other signs might you look for to support this diagnosis?
Volume depletion and acidosis are complications of tubulo-interstitial nephritis. Interstitial disease can cuase salt wasting due to the poor urinary concentrating ability. The volume depletion is manifested by his postural hypotension, and the acidosis by the hyperventilation/ Kussmaul's breathing.
TIN is also consistent with his recent intake of beta-lactam antibiotics. The three main groups of causes of TIN are allergic (drugs), infectious, and idiopathic.
Would also look for an allergic rash/ eiosinophilia.
Skin infection with GAS can progress to acute post-strep GN, but this usually takes 3-6 weeks, rather than a few days.
What is the most common cause of CHRONIC tubulo-interstitial nephritis?
Chronic urinary tract obstruction.
Other causes include persistent acute TIN, nephrotoxins (analgesics, metals, radiation), or infections (renal TB, chornic bact pyelonephritis).
What size must a renal papillary adenoma be to be considered benigin?
<5mm. >5mm = malignant carcinoma.
What is tuberous sclerosis?
An inherited multi-system disease, that causes non-malignant tumors to grow in the brain and other organs.
In the brain, grow as hard/ swollen 'tubers', that cause seizures, developmental delay, behavioural abnrormalities and sometimes autism/ self-injury (10%).
Over half have involvement of the kidneys- get AngioMyoLipoma''s (blood vessels, smooth muscle, fat) tumors, that can rupture causing haematuria/ catastrophic haemorrhage if >4mm.
These can be solitary in non-TSC patients, but are usually multiple and bilateral in TSC patients.
Also get cystic lung involvement, and rhabdoymoma's (benign tumors of striated muscle).
Skin abnormalities in nearly all patients: get facial angiofibroma's, a rash of reddish spots or bumps, which appear in a butterfly distribution. This embarrassing rash starts in childhood, adn can be removed using dermabrasion. etc etc.
What is the most common benign renal tumor?
The renal fibroma/ hamartoma/ angioma. = Fibroblast like cells + collagenous tissue. No malignant potential.
Which of the benign renal tumors can grow to a considerable size- the most common.
Oncocyotoma- benign, growth from intercalating cells of the collecting duct. Homogenous, large eosinophilic cells, with many mitochondria. Can grow up to 12cm.
What is the classical triad of RCC?
Haematuria, costovertebral pain, palpable mass.
Who gets RCC?
Older patients usually in 60s and 70's. Main RF is tobacco (doubles risk), + obesity, hypertension, unopposed oestrogen therapy, asbestos and heavy metals.
Chronic Renal failure also increases likelihood, as does acquired (dialysis-related) cystic disease: 7% develop papillary RCC in the walls of the cyst over 10years.
What is Von Hippel-Lindau disease?
A rare AD genetic condition, in which haemangioblastoma's form in the cerebellum, spinal cord, kidneys and retina. Associated with RCC and phaeochromocytoma too (20%).
What are the 2 main classifications of RCC tumor?
1. Clear cell carcinoma: most common (80%)- have clear or granular cytoplasm, non-papillary growth. Develop in the proximal tubule.
Macroscopically: big, soft, yellow (fat accumulation), with necrosis and haemorrhage.
2. Papillary carcinoma: 10-15%, have papillary growth pattern. Develop in the distal tubule.
A big yellow-ish, spherical neoplasm is seen in one pole of the kidney. There is extension of the tumor into the dilated renal vein. What is likely Dx?
Large, unipolar, yellow tumor with renal vein extension = Clear cell RCC.
Where in the kidney is RCC usually, and where does it spread?
Upper pole.
Spreads to renal vein, growing as column of cells.
Can also extend into perinephric fat, or bulge into calyces, penetrate the ureter.
Metastasises early (a quarter at dx): lung 50%, bone 30%, liver and ln's.
What are the paraneoplastic syndromes that develop with RCC?
Renin secretion - HTN
EPO secretion - polycythemia
ATCH - Cushing's
PTH - Hypercalcemia.
How does RCC MOST OFTEN present?
NOT haematuria, flank pain & palpable mass. 90% present with just recurrent, sometimes microscopic haematuria.
Patient then is most likely to present with constitutional symptoms: fever, malaise, weight loss.
Since a quarter have mets at diagnosis, could even present with lung mets eg haemoptysis. Easy metastasis when IVC in such proximity to an extending renal tumor.
Poor prognosis.
What is Wilm's Tumor/ Nephroblastoma?
Who gets it?
Prognosis?
Nephroblastoma- a tumor of the primitive metanephros. CHILDHOOD; 1-4years old, M=F. Presents with abdominal mass and pain, occasionaly haematuria. They are aggressive tumors, often presenting with metastatic disease of the lung. Long term survival is still good though (>80%).
SCARY- young child with abdominal pain and mass.... check them out! renal cancer!
Which of the renal carcinoma's presents the earliest?

How is this cancer diagnosed?
Urothelial carcinoma of the renal pelvis: presents early and when small, due to pelvic obstruction.
--> hydronephrosis and flank pain. Or/ fragmentation of the tumor --> haematuria.

Can affect any part of the urinary tract, from the renal pelvis to the urethra.

Gragments of the tumor can be detected in urine --> cytological diagnosis.
Poor prognosis.
In macroscopic examination of urine, match up the following colours to possible causes.
1. Red
2. Green
3. Black
4. Porphyria
5. TUrbid/ milky white.
1. Red: haematuria, haemoglobin/myoglobinuria, beets, senna or rifampicin.
2. Green - pseudomonas, amitryptilline (tricyclic antidepressants).
What two cancers commonly metastasise to the kidney?
Haematogenous spread; high fraction of cardiac output to kidneys (25%), get LUNG PRIMARIES and BLOOD CANCERS. eg B-cell lymphoma (burkitt's type).
A woman presents with oliguria and gross distension of the bladder. Dx?
Obstruction eg of the urethra. Most common primary of the urethra = transitional cell carcinoma.
Transitional cell carcinoma?
Most common cancer of the bladder, ureter, urehtra.
Second most common type of kidney cancer.

Causes:
Cyclophosphamide
long term analgesia
Radiation exposure
Cigarette smoke

Multifocal, often multiple at diagnosis. Can be papillary, sessile or CIS growth.
Most common met is to bone (spine mainly).
Patient presents with haematuria and lower back pain that wakes the patient at night. Dx?
Haematuria could be second to bladder cancer/ any TCC, which most commonly metastasises to bone.
What two locations to kidney cancer usually originate?
Renal tubules - RCC, clear cell adenocarcinoma.

Renal pelvis - Transitional cell carcinoma.
What is the most common sign of renal cancer?
palpable mass.
What is the treatment for RCC?
Not chemo and radio (ineffective in RCC), will usually consiste of nephrectomy alone.

If there are mets: targeted therapy such as Interferons, IL-2.
What is the most common kidney cancer of children?
WIlm's tumor (*nephroblastoma).
Aggressive but hightly responsive.
LUnilateral, encapsulated, vascularised.
What is the mesenchymal tumor (non-epithelial) that can arise in the urinary tract, typically of the female genital tract (can also occur in the bladder)?
Embryonal rhabdomyosarcome, childhood tumor, rare.
Is the bladder a common location for metastasis?
no.
What are most urinary calculi composed of?

What is an exception? What condiitons does this form under?
Calcium oxalate or phosphate.

Staghorn calculi: MAP/S
Magnesium ammonium phosphate/ struvite.
Form when urea-splitting organisms are present, increase pH, cause precipitation. Obstructive, predispose to persistent pelvicalyceal infection and pyonephrosis.
What conditions predispose to calculus formation?
Increases solute concentration or decreased solubility (abnormal pH)
Low fluid intake
Urinary stasis
Persistent obstruction/ UTI
Abnormal metabolic state eg gout (uric acid crystals).
Why might hydronephrosis occur in a pregnant woman?
Bilateral compression of the ureters by the enlarged uterus.
Large calculi like staghorn calculi, obstruct the renal pevlcis, forming pyeonephrosis and pelvicalyceal infection. What happens to smaller renal calculi?
Smaller calculi tend to pause down into the ureter, causing:
renal colic
haematuria
obstruction + secondary infection
What is the most serious consequence of calculi?
Chronic irritation can result in squamous metaplasia of the urotherlium --> SCC.
What mechanisms are used to disrupt a urothiliasis?
Ultrasound, using a lithotripter (allowing fragments to pass normally).

Surgically if this fails.
What pathological change will result with urethral stenosis?
Bladder trabeculation: contracting against an increased pressure.
A woman is oliguric 10 days before death, with blood urea concentration of 77mol/L.
post- renal failure eg bilateral ureteric obstruction.
A man is finds that he is struggling to initiate urination (hesitancy), has the need to strain, and produces only a weak dribble. Pathology?

If the man is 60- what likely cause.
If it is a 7 year old boy- what likely cause.
Partial urethral obstruction.

Man: BPH or less commonly, a stricture.
Boy- congenital narrow urethra.
Differentiate the causes of painless haematuria, and haematuria with pain.
Painless: more likely to be a glomerular dysfunction (eg nephritic syndrome: post-strep, IgA nephropathy, RPGN, secondary eg SLE, polyangitis, Wegener's).

Painful:
stone
(UTI) bladder, kidney, ureteric infection/ cancer
Blood clot passing through ureters.
What are some causes of ureteric obstruction?
Stones.
Strictures (post inflammatory?)
Torsion (eg horse shoe kidney, long tortuous ureters).
How do you differentiate between a cyst and a tumor on ultrasound-
Cyst:
Avascular
Fluid vs solid echo on US
Smooth contours.
What are the three main causes of renal failure?
1. Diabetes
2. Glomerulonephritis
3. HTN/ vascular
At what GFR do symptoms usually begin to present.
<15ml/min... (moderate/ severe renal failure).
normal GFR =~70.
what are the complications of CRF?
Electrolyte imbalance
Fluid overload
Loss of EPO --> anemia
Loss of anticoagulants --> clotting? (loss of anti-thrombin III)
Metabolic acidosis- no control of H+. Lose response to aldosterone?
Accumulation of nitrogenous wastes.
Impaired activation of vitamin D --> osteoporosis/ reanl osteodystrophy
RAS activation --> HTN.
How is salt handling affected in renal failure?
Simple kinetics. When the GFR drops to 10%, only 10% of the salt load is getting filtered. Normally, with GFR 125ml/min = 180L/ day... and [Na+] = 140mM = 140 x 125 = 25 000 mmol/ day.

This drops to 2 500mmol/day, and only 5% of the filtered fluid ever reaches the distal nephron to be "controlled" by control mechanisms --> cannot increase excretion.
--> fluid overload.

There is also an increased production of solutes for a fewer number of nephrons: the osmotic load is greater, keeping osmotically obliged water in the tubules.
What is isothenuria?
With a severely reduced GFR eg 10%, there is impaired ability to either concentrate or dlute urine, and to increase or decrease salt excretion.
They therefore have NO tolerance to variations in salt and water intake.
What are the three main causes of renal failure?
1. Diabetes
2. Glomerulonephritis
3. HTN/ vascular
At what GFR do symptoms usually begin to present.
<15ml/min... (moderate/ severe renal failure).
normal GFR =~70.
what are the complications of CRF?
Electrolyte imbalance
Fluid overload
Loss of EPO --> anemia
Loss of anticoagulants --> clotting? (loss of anti-thrombin III)
Metabolic acidosis- no control of H+. Lose response to aldosterone?
Accumulation of nitrogenous wastes.
Impaired activation of vitamin D --> osteoporosis/ reanl osteodystrophy
RAS activation --> HTN.
How is salt handling affected in renal failure?
Simple kinetics. When the GFR drops to 10%, only 10% of the salt load is getting filtered. Normally, with GFR 125ml/min = 180L/ day... and [Na+] = 140mM = 140 x 125 = 25 000 mmol/ day.

This drops to 2 500mmol/day, and only 5% of the filtered fluid ever reaches the distal nephron to be "controlled" by control mechanisms --> cannot increase excretion.
--> fluid overload.

There is also an increased production of solutes for a fewer number of nephrons: the osmotic load is greater, keeping osmotically obliged water in the tubules.
What is isothenuria?
With a severely reduced GFR eg 10%, there is impaired ability to either concentrate or dlute urine, and to increase or decrease salt excretion.
They therefore have NO tolerance to variations in salt and water intake.
What parts of the nephron constitute the countercurrent mechanism?
Since the fluid coming out of the proximal tubule is iso-osmotic (equal absorption of fluids and solutes ~60%), the descending LoH is the first component, and then the ascending loop.
Descending- permeable to water but not solutes.... loses alot of fluid.
Ascending- impermeable to water, but solutes move freely; absorption of solutes (Na/K/2Cl transporter- blocked by amiloride?).