Renal Pathology Flashcards
1
Q
What are the different types of casts?
A
- CELLULAR casts - e.g. epithelial, RBC, WBC
- GRANULAR casts - breakdown of cellular casts
- HYALINE casts
- FATTY casts
2
Q
Where are cellular casts formed?
A
Within the tubular lumen
3
Q
What are casts primarily composed of?
A
Tamm-Horsfall protein - secreted from the renal tubular cells
4
Q
What do hyaline casts indicate?
A
Usually nothing, tend to be of little diagnostic significance. May be seen in volume depleted states
5
Q
From what are granular casts derived?
A
The breakdown of cellular casts, especially epithelial cell casts
6
Q
What do epithelial cell casts indicate?
A
- Acute tubular necrosis
- Heavy metal poisoning
- Acute rejection of the transplant graft
7
Q
What do RBC casts indicate?
A
- Glomerulonephritis
- IgA nephropathy
- Post streptococcal glomerulonephritis
- Goodpasture syndrome
- Malignant HTN
- Vasculitis
- Renal ischaemia
8
Q
What do WBC casts indicate?
A
- Pyelonephritis
- Interstitial nephritis
- Lupus nephritis
9
Q
What do granular casts indicate?
A
- Acute tubular necrosis
- Chronic renal failure
- Nephrotic syndrome
10
Q
What do fatty casts indicate?
A
Nephrotic syndrome
11
Q
What is the structure of fatty casts?
A
Maltese-cross configuration of cholesterol
12
Q
What are the different types of glomerular disease?
A
- Nephrotic syndromes
2. Nephritic syndromes
13
Q
What causes nephrotic syndrome?
A
Increased filtration barrier permeability
14
Q
What are the nephrotic syndromes?
A
- MCD
- Focal segmental glomerulosclerosis
- Membranous glomerulopathy
- Membranoproliferative glomerulonephritis
- Diabetic nephropathy
- Renal amyloidosis
- Lupus nephritis
15
Q
What causes nephritic syndrome?
A
Inflammatory damage to the glomeruli
16
Q
What are the nephritic syndromes?
A
- Acute proliferative glomerulonephritis
- RPGN
- Anti-GBM disease
- Goodpasture syndrome
- IgA nephropathy (Berger disease)
- Alport syndrome (hereditary nephritis)
- Lupus nephritis
17
Q
What are the characteristic symptoms of nephrotic syndrome?
A
Puffiness around the eyes
Pitting edema of the legs
Pleural effusion
Ascites
18
Q
What are the hallmarks/signs of nephrotic syndrome?
A
Proteinuria Hypoalbuminaemia Edema Hyperlipidaemia Urinary fatty casts Hyper-coagulation
19
Q
Why is there an increase in the permeability of the filtration barrier?
A
Mononuclear cells release cytokines.
These cytokines cause podocyte fusion + obliterate the -ve charge of the GBM
20
Q
What is the definition of the proteinuria?
A
Urinary protein >3.5g/24hrs
21
Q
What is the definition of hypoalbuminaemia?
A
Plasma albumin <3g/dL
22
Q
What is the physiology of the edema in nephrotic syndrome?
A
Albumin loss = lower oncotic pressure
Lower oncotic pressure = loss of fluid from the circulation into the interstitial space
= activation of RAAS, increased sympathetic activity, release of vasopressin, decreased ANP release
All these changes^ = increased electrolyte and water retention
23
Q
Why does hyperlipidaemia occur in nephrotic syndrome?
A
Increased production of lipoproteins by the liver in order to attempt to main the falling oncotic pressure in nephrotic syndrome
24
Q
Why does hypercoaguability occur in nephrotic syndrome?
A
Loss of antithrombin III from the damaged glomeruli
= increased risk of renal vein thrombosis
25
What is the most common cause of nephrotic syndrome?
MCD
26
How is MCD diagnosed?
Renal biopsy + microscopy (specifically electron microscopy)
27
When is a definitive diagnosis not required for MCD?
Children with a typical presentation of MCD may be given an empiric steroids without a renal biopsy
28
What is seen on an electron microscope in MCD?
Effacement (fusion) of the visceral epithelial foot processes
29
What is seen on a light microscope in MCD?
Lipoid nephrosis - lipoid appearance of cells in proximal tubules
30
How is MCD treated?
High dose oral glucocorticoids (prednisolone). Alkylating agents (e.g. cyclophosphamide or chlorambucil) in failure to respond to steroids
31
What is the prognosis of MCD in an adult vs. children?
```
Adult = 50% response
Children = 90% response to treatment
```
32
What proportion of cases of nephrotic syndromes does focal segmental glomerulosclerosis account for?
1/3 in adults; 50% of cases in African Americans
33
What is the most common glomerular disease in HIV patients?
Focal segmental glomerulosclerosis (FSGS)
34
What are the differences in presentation between FSGS and MCD?
FSGS = non-selective proteinuria (whereas MCD = selective proteinuria of albumin)
Patients with FSGS also have HTN and mild haematuria on top of the usual symptoms of nephrotic syndrome
35
What is seen on light microscopy in FSGS?
FOCAL accumulation of hyaline material
| SEGMENTAL sclerosis
36
What is the prognosis of FSGS?
Poor - 50% develop ESRD within 10 years
37
What is the leading cause of nephrotic syndrome in adults?
Membranous glomerulopathy (30-40% of cases)
38
What are the demographics of membranous glomerulopathy?
More often seen in men - 2:1 ratio
| Peak incidence = 30-50y/o
39
Is the proteinuria in membranous glomerulopathy selective or non-selective?
Non-selective
40
What systematic diseases are glomerulopathy associated with?
```
SLE
RA
Hep B
Hep C
Syphillis
Schistomiasis
Malaria
Leprosy
Drugs - e.g. gold and penicillamine
```
41
How do sub-epithelial deposits appear under the electron microscope?
'Spike' = extensions of GBM around the deposits + 'Dome' = deposits in the GBM
42
How is membranous glomerulopathy USUALLY treated? How otherwise might it be treated?
High rate of spontaneous remission, therefore no treatment needed. Otherwise, in severe disease, immunosuppressive therapy of cyclophosphamide + cyclosporine + glucocorticoids = used
43
What are the 2 types of membranoproliferative glomerulonephritis?
Type I - 2/3 of cases - type III hypersensitivity, deposition of immune complexes
type II - 1/3 of cases - associated with C3 nephritic factor. C£ present, but no IgG deposits
44
How does type I membranoproliferative glomerulonephritis appear under the electron microscope?
Subendothelial deposits of IgG + C3 + tram-track appearance from mesangium ingrowth into the GBM
45
How does type II membranoproliferative glomerulonephritis appear under the electron microscope?
Intramembranous deposits + increased glomeruli size + tram-track appearance
46
In whom with membranoproliferative glomerulonephritis may PE be useful?
In patients with circulating C3NeF
47
How does the prognosis differ between type I and II membranoproliferative glomerulonephritis?
Type I = 70-85% = no chronic decline in GFR
| Type II = worse prognosis. Majority of patients progress to ESRD after 5-10 years
48
In which type of DM is diabetic nephropathy more common?
Type I
49
After how long of microalbuminaemia do other symptoms develop?
5-10 years
50
What is the leading cause of ESRD in the West?
Diabetic nephropathy
51
What is a complication seen in DM nephropathy?
Arteriosclerosis of the real artery
52
What is seen under the light microscope in DM nephropathy?
Thickening of GBM
Expansion of the mesangium
Kimmelstiel-Wilson lesions
53
How should DM nephropathy be treated?
Good glucose control + ACE inhibitors at onset of microalbuminaemia
54
What are the characteristics of amyloidosis?
Fibrous, insoluble proteins in a beta-pleated sheet confirmation in the extracellular space of the organs. = a multi-system disorder
55
What are the different types of amyloidosis that affect the kidney?
1. Amyloid L (AL)
| 2. Amyloid A (AA)
56
What happens if the chains are not beta-pleated? What is the disease called then?
Light-chain deposition disease
57
From where may a biopsy be taken for diagnosis of amyloidosis?
Renal, abdominal fat pad, rectally
58
Which stain is used to identify amyloidosis? What is seen upon the staining being +ve?
Congo red stain will show apple-green bifringence in amyloidosis
59
How is amyloidosis treated?
Melphalan + prednisone
60
What are the classes of lupus nephritis?
```
I - no evidence of disease
II - mesangial involvement
III - focal proliferative nephritis
IV - diffuse proliferative nephritis
V - membranous nephritis
```
61
How is each class of lupus nephritis treated?
```
I - general SLE treatment
II - corticosteroids
III - high doses of corticosteroids
IV - corticosteroids + immunosuppressants
V - attend to general symptoms
```
62
What are the hallmarks of nephritic syndrome?
Haematuria
Oliguria
Azotemia
HTN
63
What is azotemia?
Increased blood urea nitrogen (BUN) and creatine
64
How do the symptoms of nephritic syndrome come about?
```
Haematuria = due to destruction of glomerular capillaries
Oliguria = obstruction of glomerular capillary lumen decreases the GFR leading to oliguria (<400ml/day) and azotemia
HTN = secondary to the increased fluid retention by the kidney due to decreased GFR
```
65
Which type of nephritic syndrome is most likely to affect children?
Acute proliferative glomerulonephritis (poststreptococcal)
66
After what does acute proliferative glomerulonephritis usually occur?
2-3 weeks after either pharyngeal or skin infections with GABHS
67
What are the diagnostic signs of acute proliferative glomerulonephritis?
Serum chemistry - ANCA and anti-GBM Ab's are -ve, C3 = usually low, ASO tigers or other streptococcal Abs are elevated
Urinalysis - smoky brown urine, RBC casts
Pathology - renal biopsy
Light microscopy - enlarged glomeruli
Electron microscopy - subepithelial deposits - 'humps'
Immunofluorescence - 'bumpy appearance' of IgG and C3 deposits
68
What is RPGN also known as?
Crescentic RPGN
69
What are the 3 types of RPGN?
Type I - Goodpastures
Type II - Post-streptococcal, SLE, IgA nephropathy, Henoch-Schonlein purpura
Type III - Wegener's
70
Which types of RPGN are ANCA -ve?
Type I - Goodpastures
| Type II - Post-streptococcal, SLE, IgA nephropathy, Henoch-Schonlein purpur
71
Which types of RPGN are ANCA +ve?
Type III - Wegener's
72
What feature characterises Goodpastures syndrome?
Ab's against proteins in the GBM
73
What is seen upon immunofluorescence in Goodpastures?
Linear, ribbon-like deposits of IgG
74
Aside from nephritic symptoms, what other symptoms are seen in Goodpastures?
Pulmonary haemorrhage - presenting with haemoptysis
75
What is the treatment of Goodpastures?
Emergency plasmapheresis performed daily until anti-GBM titers become negative. Prednisone + either cyclophosphamide or azathioprine are also started to prevent the formation of new GBM Abs
76
What is the most common form of glomerulopathy worldwide?
IgA nephropathy
77
If IgA nephropathy is associated with external symptoms, what might the condition be?
Henoch-Schonlein purpura
78
What are the external symptoms of Henoch-Schonlen Purpura?
Skin - puerperal lesions on the extensor surfaces
GI - abdominal pain/interstitial bleeding
Musculoskeletal - joint pain
79
How does IgA nephropathy typically present?
Painless haematuria following infection
80
What is seen on immunofluorescence in IgA nephropathy?
Granular IgA deposits
81
How is Alport syndrome acquired?
X-linked recessive
82
What is Alport syndrome caused by an error in?
Synthesis of the alpha-5 chain type IV collagen
83
Aside from nephritic syndrome, what other symptoms do people with Alport's have?
Nerve deafness
Lens dislocation
Cataracts
84
What are the diagnostic findings in Alport's?
Serum chemistry - ANCA and anti-GBM -ve, C3 = normal
Urinalysis - gross haematuria + mild proteinuria
Pathology - renal biopsy
Light microscopy - glomerular + mesangial proliferation. Foam cells - interstitial cells with accumulation of lipids
EM - splitting of the GBM
85
A combination of what 3 symptoms indicates Wegener's?
1. Chronic sinusitis
2. Haemoptysis
3. Haematuria
86
What are the 3 C's of Wegener's?
C-ANCA
Corticosteroids
Cyclophosphamide
87
What are the different types of kidney stones?
Calcium oxalate/phosphate
Struvite
Uric acid
Cystine
88
In what season do kidney stones most commonly form?
Summer - due to insufficient fluid intake
89
How do calcium oxalate/phosphate stones appear on XR?
Radiopaque
90
How do struvite stones appear on XR?
Radiopaque
91
How do uric acid stones appear on XR?
Radiolucent
92
How do cystine stones appear on XR?
Faintly opaque/ground glass
93
Stones under what size are likely to pass 'naturally'?
<9mm
94
What is the characteristic pain of kidney stones?
Loin to groin
95
What are the intervention options when stones are >9mm?
Extracorporeal shockwave lithotripsy (ESWL) or nephrolithotomy
96
Which type of stone is most common?
Calcium oxalate and calcium phosphate
97
What causes calcium stones to form?
```
Hypercalcaemia
Cancer
Elevated PTH
Increased vitamin D
Idiopathic
```
98
What is the composition of struvite stones?
Magnesium ammonium phosphate
99
In which patients are struvite stones occuring?
Patients with persistently alkaline urine, e.g. from UTIs caused by urease +ve organisms - e.g. proteus vulgaris, klebsiella, pseudomonas and staphylococci
100
When is it a stag horn kidney stone?
When the stone forms a cast of the renal pelvis and calyces system
101
What conditions are associated with uric acid stones?
```
Hyperuricaemia
Gout
Tumour lysis syndrome
Leukaemia
Myeloproliferative disease
```
102
What are the most common UTI causing bacteria in women?
E coli
| Staphylococcus saprophyticus
103
What should be assessed for in children with recurrent UTIs?
Vesicoureteral reflux (VUR) + child abuse
104
What are the antibiotic options for an uncomplicated UTI?
Trimethoprim
Sulfamethoxazole
Ciprofloxacin
Nitrofurantoin
105
What may underly chronic pyelonephritis?
Obstructions - e.g. stones
| VUR
106
What systematic processes are associated with cortical necrosis (causing DCN)?
Diffuse or patchy infarction of the cortices of the kidney secondary to ischaemia
107
What conditions are associated with diffuse cortical necrosis (DCN)?
Abruptio placentae
Eclampsia/pre-eclampsia
Septic shock
Haemolytic-uremic syndrome
108
What conditions are associated with renal papillary necrosis?
DM
Acute pyelonephritis
Chronic analgesic use
Sickle cell disease
109
In what condition may nephrocalcinosis be seen?
Renal papillary necrosis
110
What are the characteristics of pre-renal, renal failure?
Urine osmolality - >500
Urine sodium - <10
Fractional excretion of sodium - <1%
Blood urea nitrogen/creatine ration - >20
111
What are the characteristics of renal, renal failure?
Urine osmolality - <350
Urine sodium - >20
Fractional excretion of sodium - >2%
Blood urea nitrogen/creatine ration - <15
112
What are the characteristics of post-renal, renal failure?
Urine osmolality - <350
Urine sodium - >40
Fractional excretion of sodium - >4%
Blood urea nitrogen/creatine ration - >15
113
What are the 5 indications for dialysis?
1. Severe uraemia
2. Hyperkalaemia unresponsive to treatment
3. Metabolic acidosis
4. Refractory fluid overload
5. Pericarditis
114
What is the most common cause of acute renal failure (ARF)?
Acute tubular necrosis (ATN)
115
What is normal GFR?
115-125ml/min
116
What is the definition of polyuria?
Urine output >3L/24hrs
117
What is the definition of oliguria?
Urine output <500ml/24hrs
118
What is the definition of anuria?
Urine output <100ml/24hrs
119
In ATN what is seen on microscopy?
Muddy brown casts
120
What are the pre-renal causes of CKD?
1. Renal artery stenosis
| 2. Embolism
121
What are the renal causes of CKD?
1. DM
2. SLE
3. HTN
4. Amyloidosis
5. Adult PCKD
6. Renal cancer
7. Chronic glomerulonephritis
122
What are the post-renal causes of CKD?
Chronic urinary tract obstruction
123
When is dialysis indicated in CKD?
GFR =20ml/min
124
When is transplant indicated in CKD?
GFR <20ml/min
125
What are the possible long term sequelae of renal failure?
Congestive heart failure (CHF)
| Pulmonary edema
126
What are the consequences of renal failure?
1. Uremic syndrome
2. Hyperkalemia
3. Metabolic acidosis - when GFR<50%, there is impaired renal production of HCO3-, H+ cannot be excreted
4. Sodium and water retention
5. Anaemia
6. Renal osteodystrophy
7. HTN
8. Fanconi syndrome
127
What occurs during uremic syndrome?
Lethargy, seizures, myoclonus, asterixis, pericardial friction rub, hyperammonemia
128
What are the consequences of hyperkalemia?
Peaked T waves on ECG, which can lead to ventricular fibrillation
129
How does anaemia occur in renal failure?
There is failure of EPO production, causing decreased hematocrit
130
What is autosomal dominant PCKD caused by?
Mutations in PKD1 or PKD2
131
At what age does autosomal dominant PCKD present?
40s
132
How should autosomal dominant PCKD be managed?
Anti-HTNs + diuretics + low-salt diet
133
What condition is autosomal dominant PCKD associated with?
Saccular aneurism of the Circle of Willis = high incidence of subarachnoid haemorrhage
134
What is autosomal recessive PCKD caused by?
PKHD1 mutation
135
How do neonates with autosomal recessive PCKD present?
Enlarged kidneys
136
How do we distinguish between autosomal recessive and autosomal dominant PCKD?
In autosomal recessive PCKD, parents will NOT have cysts
137
What is the prognosis of autosomal recessive PCKD?
50% of neonates die
Of the 50% that survive, 1/3 will develop ESRD within 10 years
Other will develop liver cysts, and then congenital hepatic cirrhosis
138
What causes Liddle syndrome?
Autosomal dominant gain of function mutation in the collecting duct ENaC channels
139
How does Liddle syndrome present?
Children = tend to be asymptomatic
Adults = weakness, fatigue + palpitations
Hypokalemia
Metabolic alkalosis
HTN (severe)
140
How is Liddle syndrome treated?
ENaC antagonists
141
What causes Bartter syndrome?
Autosomal recessive mutations in any of the transporters of the thick ascending limb of Henle
142
How does Bartter syndrome present?
Presentation in early life with growth + mental retardation
```
Hypochloremic metabolic alkalosis
Hypokalemia
HYPERcalciuria
Hypomagnesia (in many, but not all)
No HTN
```
143
How is Bartter syndrome treated?
K+ supplements + spironolactone (to increase serum K+)
144
What causes Gitelman syndrome?
Autosomal recessive defect in thiazide-sensitive Na+-Cl- cotransporter in the distal tubule
145
How does Gitelman syndrome present?
Cramps + severe fatigue
```
Hypochloremic metabolic alkalosis
Hypokalemia
HYPOcalciuria
Hypomagnesia (in many, but not all)
No HTN
```
146
How is Gitelman syndrome treated?
K+ supplements + spironolactone (to increase serum K+)
147
What is the most common primary renal tumour?
Renal cell carcinoma
148
What are the different types of renal cell carcinoma?
1. Clear-cell carcinomas
2. Papillary renal cell carcinomas
3. Chromophobe renal carcinomas
149
What are the RFs for renal cell carcinoma?
1. Smoking
2. Cadmium
3. Petroleum
4. Gasoline
5. Asbestos
6. Lead
150
What is the classic RCC triad?
1. Painless hematuria
2. Palpable flank mass
3. Flank pain
151
From what does RCC arise?
Tubular epithelium
152
What proportion of RCCs are clear cell carcinomas?
80%
153
What proportion of RCCs are papillary renal cell carcinomas?
15%
154
What proportion of RCCs are chromophore renal carcinomas?
<5%
155
What genetics defects are associated with RCCs?
Clear cell carcinomas - VHL gene (tutor suppressor gene on chromosome 3)
Papillary renal cell carcinomas - MET gene (photo-oncogene on chromosome 7)
Chromophobe renal carcinomas - loss of entire chromosome (frequently 1, 2, 6, 10, 13, 17 and 21)
156
What are the paraneoplastic syndromes associated with RCCs?
Hypercalcemia
| Polycythemia (excess EPO production)
157
How may RCCs spread?
Hemataogenous spread via renal vein and IVC to the bones or lungs
158
How are RCCs treated?
Radical nephrectomy with removal of LNs
159
How are RCCs with mets treated?
+ interleukin-2
160
Where do transition cell carcinomas tend to occur?
Bladder
161
In whom are bladder tumours associated?
1. Smokers
2. Cyclophosphamide
3. Phenacetin
4. Beta-naphthylamine
162
How may bladder tumours be treated?
Transurethral resection and/or BCG injection
163
What causes Wilms tumours?
Two-hit mechanism - mutation of one copy of WT1 on chromosome 11 in the gremlin, followed by an acquired mutation in the second copy of WT1
164
What syndromes are associated with Wilms tumours?
Beckwith-Wiedemann
Denys-Drash syndrome
WAGR complex
165
How is a Wilms tumour treated?
Nephrectomy with chemotherapy
Vincristine, actinomycin D and doxorubicin if lung mets are found
