Nephrology Flashcards
1
Q
What is the pathophysiology of minimal change disease?
A
T cell and cytokine mediated damage to glomerular basement membrane, causing polyanion loss and reduction in electrostatic charge, leading to increased glomerular permeability to serum albumin.
2
Q
What are the features of minimal change disease?
A
- Nephrotic syndrome
- Normotension
- High selective proteinuria (intermediate proteins loss only)
3
Q
What are the findings on renal biopsy in minimal change disease?
A
- Normal glomeruli on light microscopy
- Fused podocytes and effacement of foot processes on electron microscopy.
4
Q
What are the causes of minimal change disease?
A
- Usually idiopathic
- NSAIDs, rifampicin
- Infectious mononucleosis
- Hodgkin’s lymphoma, thymoma
5
Q
What is the management of minimal change disease?
A
1st line: oral corticosteroids
2nd line: cyclophosphamide
6
Q
What are the causes of membranous glomerulonephritis?
A
- Idiopathic: anti-phospholipase A2 antibodies
- Infections: Hep B, malaria, syphilis
- Malignancy: prostate, lung, leukaemia, lymphoma
- Drugs: gold, penicillamine, NSAIDs
- Autoimmune: SLE class V, thyroiditis, rheumatoid
7
Q
What are the renal biopsy findings of membranous glomerulonephritis?
A
Thickened basement membrane with sub epithelial electron dense deposits
‘spike and dome’ appearance
8
Q
What is the management for membranous glomerulonephritis?
A
- ACEIs or ARBs
- Immunosuppression in severe/progressive disease (not corticosteroids on their own)
- Anticoagulation in high risk patients
9
Q
What are good prognostic factors of membranous glomerulonephritis?
A
- female
- early age at presentation
- asymptomatic proteinuria of modest degree at presentation
10
Q
What are the features of type 1 membranoproliferative glomerulonephritis?
A
- 90% cases
- causes by cryglobulinaemia or hep C
- electron microscopy = sub endothelial and mesangium immune deposits of electron dense material resulting in ‘Tram-track’ appearance.
11
Q
What are the features of type 2 membranoproliferative glomerulonephritis?
A
- ‘dense deposit disease’
- caused by partial lipodystrophy (loss of submit tissue from face) or factor H deficiency
- persistent activation of alternative complement pathway
- low circulating C3
- C3b nephritic factor in 70% (antibody to alternative pathway C3 convertase C3bBb, stabilises C3 convertase).
- electron microscopy = intramembranous immune complex deposits ‘dense deposits’
12
Q
What are the causes of Type 3 membranoproliferative glomerulonephritis?
A
Hep B and C
13
Q
What are the causes of focal segmental glomerulosclerosis?
A
Generally presents in young adults
- Idiopathic
- Secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
- HIV
- Heroin
- Alport’s syndrome
- Sickle cell
14
Q
What are the renal biopsy findings in focal segmental glomerulosclerosis?
A
Light microscopy = focal and segmental sclerosis and hyalinosis
Electron microscopy = effacement of foot processes
15
Q
What is the management of focal segmental glomerulosclerosis?
A
Steroids +/- immunosuppressants
16
Q
What is the prognosis of focal segmental glomerulosclerosis?
A
If untreated <10% have a chance of spontaneous remission.
17
Q
What is IgA neuropathy?
A
- Commonest cause of glomerulonephritis worldwide
- Mesangial deposition of IgA immune complexes
- Presents with macroscopic haematuria usually in young people following a recent respiratory infection.
- Associated with alcoholic cirrhosis, Henoch-Schonlein purpura and coeliac disease/dermatitis herpetiformis
18
Q
What are the histology findings in IgA nephropathy?
A
mesangial hypercellularity, positive immunofluorescence for IgA and C3
19
Q
What are the features of IgA nephropathy?
A
- Typically young males
- Recurrent episodes of macroscopic haematuria
- Recent upper Respiratory tract infection
- Nephrotic range proteinuria is rare
- renal failure is unusual and only seen in minority
20
Q
What is the management for IgA nephropathy?
A
Isolated haematuria with no or minimal proteinuria and normal GFR = no treatment.
Persistent proteinuria, normal or slightly reduced GFR = ACEIs
If active disease e.g. falling GFR or failure to respond to ACEIs then immunosuppression with corticosteroids
21
Q
What are poor prognostic factors in IgA Nephropathy?
A
- Male
- Proteinuria
- HTN
- Smoking
- Hyperlipidaemia
- ACE genotype DD
22
Q
What is a good prognostic factor in IgA Nephropathy?
A
Frank haematuria
23
Q
What are the features of Henoch-Schonlein Purpura?
A
- palpable purpuric rash with localised oedema over buttocks and extensor surfaces of arms/legs
- Abdominal pain
- Polyarthritis
- Features of IgA nephropathy may occur
24
Q
What is Henoch-Schonlein Purpura?
A
- IgA mediated small vessel vasculitis
- Overlaps with IgA nephropathy
- Usually seen in children following infection
25
What is the management for Henoch-Schonlein purpura?
Analgesia for arthralgia
Supportive treatment of nephropathy
26
What is the prognosis of hence-schonlein purpura?
Excellent, usually self limiting and no renal impairment
1/3 relapse
27
What is post-streptococcal glomerulonephritis?
Immune complex deposition in glomeruli 7-14days following group A beta haemolytic streptococcal infection.
Usually strep pyogenes
Young children most commonly affected
28
What are the features of post-streptococcal glomerulonephritis?
- General malaise and headache
- Visible haematuria
- Proteinuria
- HTN
- Oliguria
- Increase in anti-streptolysin O titre to confirm recent strep infection
- low C3
29
What are the renal biopsy findings in Post-streoptococcal glomerulonephritis?
Endothelial proliferation with neutrophils
Electron microscopy = sup epithelial 'humps' caused by lumpy immune complex deposits
Immunofluorescence = granular or 'starry sky' appearance
30
What is diabetes insipidus?
Deficiency in action of anti-diuretic hormone (ADH).
31
Where is ADH synthesised and stored?
Synthesised: Magnocellular neurons in supraoptic and paraventricular nuclei of hypothalamus
Stored: posterior pituitary
32
What is the difference between cranial and nephrogenic DI?
Cranial DI = deficiency in ADH secretion
Nephrogenic DI = insensitivity of kidney to ADH
33
What are the causes of cranial DI?
- idiopathic
- post head injury
- pituitary surgery
- craniopharyngiomas
- infiltrative: histiocytosis X, sarcoidosis
- DIDMOAD (association of cranial DI, diabetes mellitus, optic atrophy and deafness. Also known as Wolfram's syndrome)
34
What are the causes of nephrogenic DI?
- genetic: vasopressin receptor abnormality most common, mutation in gene that codes for aquaporin 2 channel
- Hypercalcaemia
- Hypokalaemia
- Lithium
- Demeclocycline
- Tubulo-interstitial disease
- Haemochromatosis
35
What are the symptoms of diabetes insipidus?
Polyuria
Polydipsia
36
What are the investigations for diabetes insipidus?
- High plasma osmolality (>295mOsm/kg)
- Low urine osmolality (<300mOsm/kg)
- Water deprivation test
- Desmopressin test may be used to differentiate cranial from nephrogenic (increase in urine osmolality suggest cranial)
A urine osmolality >700 rules out DI.
37
What is the management of diabetes insipidus?
Nephrogenic: Thiazides, low salt/protein diet
Cranial: desmopressin
38
What is amyloidosis?
- Extracellular deposition of insoluble fibrillar protein called amyloid.
- Derived from many different precursor proteins.
- Leads to tissue/organ dysfunction.
- Can be systemic or localised
- Further classified by precursor protein type.
39
How is amyloidosis diagnosed?
- Congo red staining: apple green birefringence.
- Serum amyloid precursor (SAP) scan
- Biopsy of skin, rectal mucosa or abdominal fat
40
What are the features of AL amyloidosis?
- Most common type
- Light chain fragment
- Due to myeloma, MGUS, Waldenstrom's
- Features: nephrotic syndrome, cardio/neuro involvement, macroglossia, periorbital ecchymoses.
41
What are the features of AA amyloid?
- precursor serum amyloid A protein
- chronic infection/inflammation e.g. TB, RA, bronchiectasis
- renal involvement most common
42
What are the features of Beta-2 micro globulin amyloidosis?
- precursor Beta-2 microglobulin (part of major histocompatibility complex)
- associated with patients of renal dialysis
43
What is Goodpasture's syndrome?
Rare small vessel vasculitis associated with pulmonary haemorrhage and rapidly progressive glomerulonephritis.
Anti-GBM antibodies against type IV collagen.
M>F 2:1
Peak 20-30yrs and 60-70yrs
Associated with HLA DR2
44
What are the features of Goodpasture's syndrome?
- Pulmonary haemorrhage
- Rapidly progressive glomerulonephritis
- AKI
- Proteinuria
- Haematuria
45
What are the investigation findings for Goodpasture's syndrome?
- Renal biopsy - linear IgG deposits along basement membrane
- Increased transfer factor secondary to pulmonary haemorrhages.
46
What is the management of Goodpasture's syndrome?
- Plasma exchange (plasmapheresis)
- Steroids
- Cyclophosphamide
47
What are the risk factors for developing pulmonary haemorrhage in Goodpasture's syndrome?
- Smoking
- LRTI
- Pulmonary oedema
- Inhalation of hydrocarbons
- young males
48
What are the risk factors for BPH?
- Advancing age
- Ethnicity; Black > white > Asian
49
What are the features of BPH?
- Voiding sx:
* weak/intermittent flow
* straining
* hesitancy
* terminal dribbling
* incomplete emptying
- Storage sx:
* urgency
* frequency
* urge incontinence
* nocturne
- Post-micturation
* dribbling
- UTI
- Retention
- Obstructive uropathy
50
What are the investigations for BPH?
- urine dipstick
- U+Es
- PSA
- Urinary-frequency-volume chart (3 days)
- International prostate symptom score (IPSS).
51
What is the management of BPH?
- watchful waiting
- Alpha-1 antagonists e.g tamsulosin and alfuzosin (reduce smooth muscle tone of prostate/bladder)
- 5-alpha reductase inhibitors e.g. finasteride (blocks conversion of testosterone to dihydrotestosterone, reduces prostate volume to slow disease)
- Antimuscarinic drugs e.g. tolterodine, darifenacin
- surgery (TURP)
52
What are the features of hyper acute organ rejection?
- occurs almost immediately
- macroscopic features (mottled, dusky, thrombosis) manifest before vascular anastomosis/removal of clamps
- major HLA mismatch and ABO compatibility are risk factors
- Rx = removal of graft
53
What are the features of acute organ rejection?
- occurs within 6 months of graft
- mononuclear cell infiltrates predominate
- occurs in 50% of cases
- most medically managed
54
What are the features of chronic organ rejection?
- occurs after 6 months of graft insertion
- vascular changes most predominant with myointimal proliferation leading to organ ischaemia
- Organ specific changes e.g. loss of acinar cells in pancreas or coronary artery disease in cardiac graft.
55
What is cystinuria?
- Autosomal recessive disorder
- formation of recurrent renal stones. - defect in the membrane transport of cystine, ornithine, lysine, arginine (mnemonic = COLA)
56
What are the genetic abnormalities in cystinuria?
chromosome 2: SLC3A1 gene, chromosome 19: SLC7A9
57
What are the features of cystinuria?
- recurrent renal stones
- classically yellow and crystalline, appearing semi-opaque on x-ray
58
How is cystinuria diagnosed?
cyanide-nitroprusside test
59
What is the management for cystinuria?
- hydration
- D-penicillamine
- urinary alkalinization
60
What is Fanconi syndrome?
Generalised reabsorptive disorder of renal tubular transport in the proximal convoluted tubule resulting in:
- type 2 (proximal) renal tubular acidosis
- polyuria
- aminoaciduria
- glycosuria
- phosphaturia
- osteomalacia
61
What are the causes of Fanconi syndrome?
- cystinosis (most common cause in children)
- Sjogren's syndrome
- multiple myeloma
- nephrotic syndrome
- Wilson's disease
62
What is haemolytic uraemia syndrome (HUS)?
Triad of AKI + microangiopathic haemolytic anaemia + thrombocytopenia
Usually seen in young children
63
What are the secondary causes 'typical' of HUS?
- Shiga toxin-producing E.coli 0157:H7 (accounts for 90% cases in kids)
- pneumococcal infection
- HIV
- Rare: SLE, drugs, cancer
64
What is the cause of primary 'atypical' HUS?
complement dysregulation
65
What are the investigation findings in HUS?
- Blood film: Coomb's test negative, schistocytes
- Anaemia
- Thrombocytopenia
- U+Es: AKI
- Stool culture: look for presence of shiga toxin
66
What is the management for HUS?
- Supportive e.g. IVF, blood transfusions, dialysis
- no role for antibiotics
- plasma exchange reserved for severe cases of HUS not associated with diarrhoea
- Eculizumab (C5 inhibitor monoclonal antibody) in adult atypical HUS
67
What is the most common cause of peritonitis secondary to peritoneal dialysis?
Coagulase-negative Staphylococcus
68
What is ADPKD?
Autosomal dominant polycystic kidney disease
Most common inherited cause of kidney disease.
PK1 and PKD2 types.
PK1 - 85% of cases, chromosome 16, renal failure earlier
PK2 - 15% cases, chromosome 4
69
What is the diagnostic criteria for ADPKD?
Diagnosis on AUSS.
- 2 cysts on either kidney if <30yrs
- 2 cysts on both kidneys if 30-59yrs
- 4cysts on both kidneys if 60+yrs
70
What are the features of ADPKD?
- flank pain
- haematuria
- HTN
- recurrent UTIs
- palpable kidneys
- renal impairment
- renal stones
Extrarenal manifesations:
- liver cysts (70% may cause hepatomegaly)
- berry aneurysms (8% may burst and cause SAH)
- Cardiac (mitral valve prolapse, aortic root dilation, dissection)
- cysts in other organs e.g. pancreas, spleen
71
What is the management of ADPKD?
- Tolvaptan (vasopressin receptor 2 antagonist) if they have CKD 2/3 at start of rx, evidence of rapidly progressing disease and company provides discount on patient access scheme.
72
What is Alport's syndrome?
- X-linked dominant condition (85% cases)
- defect in gene that codes of type IV collagen leading to abnormal glomerular basement membrane
- more severe in males
- usually presents in childhoodW
73
What are the features of Alport's syndrome?
-microscopic haematuria
- progressive renal failure
- bilateral sensorineural deafness
- lenticonus: protrusion of lens surface into anterior chamber
- retinitis pigmentosa
- renal biopsy: splitting of lamina densa on electron microscopy
74
How is Alport's syndrome diagnosed?
- molecular genetic testing
- renal biopsy: longitudinal splitting of lamina densa of GBM resulting in 'basket-weave' appearance
75
What are the causes of a normal anion gap metabolic acidosis?
- GI bicarb loss: ureterosigmoidostomy, fistula, diarrhoea
- renal tubular acidosis
- drugs e.g. acetazolamide
- ammonium chloride injection
- Addison's disease
76
What are the causes of a raised anion gap metabolic acidosis?
- Lactate: shock/hypoxia
- Ketones: DKA, alcohol
- urate: renal failure
- acid poisoning: salicylates, methanol
- 5-oxoproline: chronic paracetamol use
77
What is ARPKD?
- Autosomal recessive polycystic kidney disease
- defect in gene located on chromosome 6which encode for the fibrocystin, protein important in renal tubule development.
78
What are the features of ARPKD?
- Diagnosed on prenatal US or in early infancy with abdominal masses and renal failure
- New-born's may also have sx of Potter's syndrome secondary to oligohydramnios
- ESRF develops in childhood
- Liver also involved with portal and interlobular fibrosis
- renal biopsy: multiple cylindrical lesions at right angles to cortical surface
79
What are the risk factors for transition cell bladder cancer?
- Smoking
* most important risk factor in western countries
* hazard ratio is around 4
- Exposure to aniline dyes
* for example working in the printing and textile industry
* examples are 2-naphthylamine and benzidine
- Rubber manufacture
- Cyclophosphamide
80
What are the risk factors for squamous cell bladder cancer?
- Schistosomiasis
- Smoking
81
What is erythropoietin?
- haematopoietic growth factor that stimulates the production of erythrocytes.
- secreted by the kidney in response to cellular hypoxia.
- used to treat anaemia associated with chronic kidney disease and cytotoxic therapy.
82
What are the side effects of erythropoietin?
- accelerated hypertension potentially leading to encephalopathy and seizures (blood pressure increases in 25% of patients)
- bone aches
- flu-like symptoms
- skin rashes, urticaria
- pure red cell aplasia* (due to antibodies against erythropoietin)
- raised PCV increases risk of thrombosis (e.g. Fistula)
- iron deficiency 2nd to increased erythropoiesis
83
Why may a patient fail to respond to erythropoietin?
- iron deficiency
- inadequate dose
- concurrent infection/inflammation
- hyperparathyroid bone disease
- aluminium toxicity
84
What are the features of fibromuscular dysplasia?
- most common cause of the remaining 10% of renal vascular disease following renal artery stenosis which accounts for 90% cases.
- hypertension
- chronic kidney disease or more acute renal failure e.g. secondary to ACE-inhibitor initiation
- 'flash' pulmonary oedema
- 90% female
85
Which conditions are associated with glomerulonephritis and low complement levels?
- post-streptococcal glomerulonephritis
- subacute bacterial endocarditis
- systemic lupus erythematosus
- mesangiocapillary glomerulonephritis
86
What are the 5 main features of HIV associated nephropathy?
- massive proteinuria resulting in nephrotic syndrome
- normal or large kidneys
- focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy
- elevated urea and creatinine
- normotension
87
What are the causes of renal papillary necrosis?
- chronic analgesia use
- sickle cell disease
- TB
- acute pyelonephritis
- diabetes mellitus
88
What are the features of papillary necrosis?
- fever, loin pain, haematuria
- IVU - papillary necrosis with renal scarring - 'cup & spill'
89
What is the recommended treatment for bacterial infection secondary to peritoneal dialysis?
- vancomycin (or teicoplanin) + ceftazidime added to dialysis fluid OR vancomycin added to dialysis fluid + ciprofloxacin by mouth
- aminoglycosides are sometimes used to cover the Gram negative organisms instead of ceftazidime
90
Which conditions are an indication for plasma exchange?
- Guillain-Barre syndrome
- myasthenia gravis
- Goodpasture's syndrome
- ANCA positive vasculitis if rapidly progressive
- renal failure or pulmonary haemorrhage
- TTP/HUS
- cryoglobulinaemia
- hyperviscosity syndrome e.g. secondary to myeloma
91
What are some complications of plasma exchange?
- hypocalcaemia: due to the presence of citrate used as an anticoagulant for the extracorporeal system
- metabolic alkalosis
- removal of systemic medications
- coagulation factor depletion
- immunoglobulin depletion
92
What are some causes of raised PSA?
- prostate cancer
- BPH
- prostatitis/UTI (wait 6/52 post rx to check)
- ejaculation
- vigorous exercise
- urinary retention
- instrumentation of urinary tract
93
What are the management options for localised prostate cancer/
- watch and wait
- radical prostatectomy
- radiotherapy (external beam and brachytherapy)
94
What are the management options for localised advanced prostate cancer?
- hormonal therapy
- radical prostatectomy
- radiotherapy (external beam and brachytherapy)
95
What is an example of a synthetic GnRH agonist?
Goserelin
May cause flare phenomenon as testosterone initially increases for 2-3weeks before decreasing to castration levels
96
What is an example of GnRH antagonist used in prostate cancer treatment?
Degarelix
97
What is the mechanism of action of cyproterone acetate?
Steroidal anti-androgen
prevents DHT binding from intracytoplasmic protein complexes
98
What is the mechanism of action of Abiraterone and when is it utilised?
Androgen synthesis inhibitor
Used when other androgen therapy has failed and before chemo is started.
99
Which chemotherapy is used in prostate cancer?
Docetaxel
100
What is the most common type of primary renal neoplasm?
renal cell cancer (85%)
arises from proximal renal tubular epithelium
Most common histological subtype is clear cell
101
What are the risk factors for renal cell cancer?
- middle aged men
- smoking
- HTN
- obesity
- von-Hippel-Lindau syndrome
- tuberous sclerosis
- ADPKD (marginal increase)
102
What are the features of renal cell cancer?
- haematuria
- loin pain
- abdominal mass
- pyrexia of unknown origin
- endocrine effects: may secrete erythropoietin (polycythemia), PTH (hypercalcaemia), renin or ACTH.
- paraneoplastic hepatic dysfunction syndrome
- varicocele
- Stauffer syndrome: paraneoplastic disorder causing cholestasis and hepatosplenomegaly, felt secondary to increased levels of IL-2.
103
How is renal cell cancer staged?
T1 = <7cm tumour confined to kidney
T2 = >7cm tumour confined to kidney
T3 = tumour extends into major veins or perinephric tissues but not to ipsilateral adrenal gland or Gerota's fascia
T4 = tumour invades beyond gerota's fascia and into ipsilateral adrenal gland.
104
What is the management of renal cell cancer?
- Confined disease offered partial or total nephrectomy dependent on tumour size.
- Interferon alpha and IL-2 may be used to reduce tumour size and help with mets
- Tyrosine kinase receptor inhibitors e.g. sorafenib, sunitinib have superior efficacy than interferon alpha
105
What are the different types of renal stones and how do they present on XR?
- calcium oxalate (40% opaque)
- mixed calcium oxalate/phosphate (25% opaque)
- triple phosphate (10% opaque)
- calcium phosphate (10% opaque)
- urate stones (5-10% radiolucent)
- cystine stones (1% semi opaque ground glass appearance)
- xanthine (<1% radio-lucent)
106
What are the risk factors for renal stones?
- dehydration
- hypercalcinuria, hyperparathyroidism, hypercalcaemia
- cystinuria
- high dietary oxalate
- renal tubular acidosis
- medullary sponge kidney, polycystic kidney
- beryllium or cadmium exposure
urate specific:
- gout
- ileostomy
drugs:
- loop diuretics
- steroids
- acetazolamide
- theophylline
107
What is the management of renal stones?
- watchful waiting if <5mm
- 5-10mm shockwave lithotripsy
- 10-20mm shockwave lithotripsy or ureteroscopy
- >20mm percutaneous nephrolithotomy
108
What is the management of ureteric stones?
- <10mm shockwave lithotripsy and alpha blockers
- 10-20mm ureteroscopy
109
What is the prevention of renal stones?
Calcium:
- high fluid intake, add lemon juice
- avoid carbonated drinks
- limit salt intake
- potassium citrate may be beneficial
- thiazide diuretics
Oxalate:
- cholestyramine and pyridoxine
Uric acid:
- allopurinol
- urinary alkalinization
110
what are stag horn calculi usually formed of?
Ammonium
Magnesium
Phosphate
or triple phosphate
111
Where is the site of action of spironolactone?
Cortical collecting duct (distal convoluted tubule)
112
What conditions are associated with retroperitoneal peritoniti?s?
- Riedel's thyroiditis
- previous radiotherapy
- sarcoidosis
- inflammatory abdominal aortic aneurysm
- drugs: methysergide
113
What is calciphylaxis
Rare complication of end-stage renal failure.
Results in deposition of calcium within arterioles causing microvascular occlusion and necrosis of the supplied tissue. It most commonly affects the skin and presents with painful necrotic skin lesions.
Warfarin can induce this.
114
What is the electrolyte requirement per day for maintenance?
Sodium - 1mmol/kg
Potassium - 1 mmol/kg
Water - 30ml/Kg
Glucose - 50-100g
115
What is the mechanism of action of calcium resonium?
It increases potassium excretion by preventing enteral absorption'
116
What is Wilm's tumour?
Wilms' nephroblastoma is one of the most common childhood malignancies. It typically presents in children under 5 years of age, with a median age of 3 years old.
117
Which conditions are associated with Wilm's tumour?
- Beckwith-Wiedemann syndrome
- as part of WAGR syndrome with Aniridia, Genitourinary malformations, mental Retardation
hemihypertrophy
- around one-third of cases are associated with a loss-of-function mutation in the WT1 gene on chromosome 11
118
What are the features of Wilm's tumour?
- abdominal mass (most common presenting feature)
- painless haematuria
- flank pain
- other features: anorexia, fever
- unilateral in 95% of cases
- metastases are found in 20% of patients (most commonly lung)
119
What is the management for Wilm's tumour?
- nephrectomy
- chemotherapy
- radiotherapy if advanced disease
- prognosis: good, 80% cure rate
120
