Nephrology

Question 1

Normal anion gap ( = hyperchloraemic metabolic acidosis)

Answer 1

gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula
renal tubular acidosis
drugs: e.g. acetazolamide
ammonium chloride injection
Addison's disease

Question 2

Raised anion gap

Answer 2

actate: shock, sepsis, hypoxia
ketones: diabetic ketoacidosis, alcohol
urate: renal failure
acid poisoning: salicylates, methanol

Question 3

Metabolic acidosis secondary to high lactate levels may be subdivided into two types:

Answer 3

lactic acidosis type A: sepsis, shock, hypoxia, burns

lactic acidosis type B: metformin

Question 4

IgA Nephropathy

what is it?

Answer 4

(also known as Berger’s disease) is the commonest cause of glomerulonephritis worldwide. It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection.

Question 5

IgA Nephropathy

associated diseases

Answer 5

alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura

Question 6

Pathophysiology of IgA Nephropathy

Answer 6

thought to be caused by mesangial deposition of IgA immune complexes
there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

Question 7

IgA Nephropathy presentations

Answer 7

young male, recurrent episodes of macroscopic haematuria
typically associated with a recent respiratory tract infection
nephrotic range proteinuria is rare
renal failure is unusual and seen in a minority of patients

Question 8

Differentiation between igA nephropathy and post-streptococcal

Answer 8

glomerulonephritis
post-streptococcal glomerulonephritis is associated with low complement levels
main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur)
there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis

Question 9

Management of IgA Nephropathy

Answer 9

Isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate (GFR)
no treatment needed, other than follow-up to check renal function
persistent proteinuria (above 500 to 1000 mg/day), a normal or only slightly reduced GFR
initial treatment is with ACE inhibitors
if there is active disease (e.g. falling GFR) or failure to respond to ACE inhibitors
immunosuppression with corticosteroids

Question 10

Prognosis of IgA Nephropathy

Answer 10

25% of patients develop ESRF
markers of good prognosis: frank haematuria
markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD

Question 11

Post streptococcous glomerulonephritis

Answer 11

typically occurs 7-14 days following a group A beta-haemolytic Streptococcus infection (usually Streptococcus pyogenes). It is caused by immune complex (IgG, IgM and C3) deposition in the glomeruli. Young children are most commonly affected.

Question 12

Post streptococcous glomerulonephritis

features

Answer 12

general
headache
malaise
visible haematuria
proteinuria
this may result in oedema
hypertension
oliguria
bloods:
low C3
raised ASO titre

Question 13

Post streptococcous glomerulonephritis

Renal biopsy features

Answer 13

post-streptococcal glomerulonephritis causes acute, diffuse proliferative glomerulonephritis
endothelial proliferation with neutrophils
electron microscopy: subepithelial ‘humps’ caused by lumpy immune complex deposits
immunofluorescence: granular or ‘starry sky’ appearance

Carries a good prognosis

Question 14

histology of IgA nephropathy

Answer 14

histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

Question 15

membranoproliferative glomerulonephritis (type I)
histology

Answer 15

Subendothelial immune complex deposits with ‘tram-track’ appearance on electron microscopy

Question 16

membranous glomerulonephritis histology

Answer 16

Thickened basement membrane with subepithelial electron dense deposits creating a ‘spike and dome’ appearance

Question 17

Mechanism of action: Spironolactone

Answer 17

aldosterone antagonist which acts in the cortical collecting duct.

Question 18

Indications for Spironolactone

Answer 18

ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used
hypertension: used in some patients as a NICE ‘step 4’ treatment
heart failure (see RALES study below)
nephrotic syndrome
Conn’s syndrome

Question 19

adverse effects of spironolactone

Answer 19

hyperkalaemia

gynaecomastia

Question 20

Aetiology of Faconi’s syndrome

Answer 20

Generalised disorder of renal tubular transport in the proximal convoluted tubule

Question 21

Features of Anti-Glomerular Basement Membrane Disease

Answer 21

pulmonary haemorrhage
rapidly progressive glomerulonephritis
this typically results in a rapid onset acute kidney injury
nephritis → proteinuria + haematuria

Question 22

Investigation findings in Anti-glomerular basement membrane disease (Goodpasteurs)

Answer 22

renal biopsy: linear IgG deposits along the basement membrane
raised transfer factor secondary to pulmonary haemorrhages

Question 23

Management of Anti-glomerular basement membrane disease

Answer 23

plasmaphoresis
steroids
cyclophosphamide

Question 24

Risk factors for pulmonary haemorrhage in anti-glomerular basement membrane disease

Answer 24

smoking
lower respiratory tract infection
pulmonary oedema
inhalation of hydrocarbons
young males

Question 25

urine sodium in acute tubular necrosis

Answer 25

>40mmol

Question 26

metabolic abnormalities caused by ammonium chloride injection

Answer 26

normal anion gap metabolic acidosis

Question 27

normal anion gap metabolic acidosis causes

Answer 27

``` gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula renal tubular acidosis drugs: e.g. acetazolamide ammonium chloride injection Addison's disease ```

Question 28

raised anion gap metabolic acidosis

Answer 28

lactate: shock, sepsis, hypoxia ketones: diabetic ketoacidosis, alcohol urate: renal failure acid poisoning: salicylates, methanol

Question 29

raised anion gap metabolic acidosis

Answer 29

lactate: shock, sepsis, hypoxia ketones: diabetic ketoacidosis, alcohol urate: renal failure acid poisoning: salicylates, methanol

Question 30

typical history: minimal change disease

Answer 30

a 15-year-old presents with nephrotic syndrome. Their blood pressure and renal blood tests are normal

Question 31

typical history IgA nephropathy

Answer 31

a 25-year-old man presents with visible haematuria. He also complains of having a bad sore throat at the current time

Question 32

Features of Henoch-Schonlein purpura

Answer 32

palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs abdominal pain polyarthritis features of IgA nephropathy may occur e.g. haematuria, renal failure

Question 33

what is Henoch-Schonlein purpura

Answer 33

An IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger's disease). HSP is usually seen in children following an infection.

Question 34

treatment of Henoch-Schonlein purpura

Answer 34

analgesia for arthralgia treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants

Question 35

typical histories of streptococcus pyogenes

Answer 35

a 10-year-old boy boy presents after passing 'brown' urine. Two weeks ago he had a severe sore throat. On examination his blood pressure is high for his age and there is periorbital oedema a 10-year-old presents with fever. They complain of fleeting large joint pain and 'jerking' movements of the hand and face. On examination a murmur is noted and subcutaneous nodules on the wrists a 10-year-old presents with fever and a sore throat. Today they have a developed a fine, erythematous, 'sand-paper' rash which is more prominent in flexural areas.

Question 36

Type 1 Membranoproliferative glomerulonephritis

Answer 36

accounts for 90% of cases cause: cryoglobulinaemia, hepatitis C renal biopsy electron microscopy: subendothelial and mesangium immune deposits of electron-dense material resulting in a 'tram-track' appearance

Question 37

Type 2 Membranoproliferative glomerulonephritis

Answer 37

- 'dense deposit disease' causes: partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face), factor H deficiency caused by persistent activation of the alternative complement pathway low circulating levels of C3 C3b nephritic factor is found in 70% an antibody to alternative-pathway C3 convertase (C3bBb) stabilizes C3 convertase renal biopsy electron microscopy: intramembranous immune complex deposits with 'dense deposits'

Question 38

Type 3 Membranoproliferative glomerulonephritis

Answer 38

causes: hep B and C

Question 39

What is Alport's syndrome

Answer 39

Alport's syndrome is usually inherited in an X-linked dominant pattern*. It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in males with females rarely developing renal failure.

Question 40

typical question around Alport's syndrome

Answer 40

an Alport's patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture's syndrome like picture

Question 41

Features of Alport's syndrome

Answer 41

microscopic haematuria progressive renal failure bilateral sensorineural deafness lenticonus: protrusion of the lens surface into the anterior chamber retinitis pigmentosa renal biopsy: splitting of lamina densa seen on electron microscopy

Question 42

minimal change histology:

Answer 42

Effacement of foot processes on electron microscopy

Question 43

CKD bone disease- basic problems

Answer 43

low vitamin D (1-alpha hydroxylation normally occurs in the kidneys) high phosphate low calcium: due to lack of vitamin D, high phosphate- due to reduced excretion secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D

Question 44

CKD bone disease - clinical manifestations

Answer 44

``` Osteitis fibrosa cystica aka hyperparathyroid bone disease Adynamic reduction in cellular activity (both osteoblasts and osteoclasts) in bone may be due to over treatment with vitamin D Osteomalacia due to low vitamin D Osteosclerosis Osteoporosis ```

Question 45

Atypical haemolytic uraemic syndrome

Answer 45

encompasses many diseases with microangiopathic haemolytic anaemia with schistocytes and thrombocytopenia No DIARRHOEAL syndromes

Question 46

Haemolytic uraemic syndrome triad

Answer 46

Acute kidney injury microangiopathic haemolytic anaemia thrombocytopenia

Question 47

Secondary causes of HUS

Answer 47

classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7 ('verotoxigenic', 'enterohaemorrhagic'). This is the most common cause in children, accounting for over 90% of cases pneumococcal infection HIV rare: systemic lupus erythematosus, drugs, cancer

Question 48

Investigations of HUS

Answer 48

``` full blood count: anaemia, thrombocytopaenia, fragmented blood film U&E: acute kidney injury stool culture looking for evidence of STEC infection PCR for Shiga toxins ```

Question 49

Management of HUS

Answer 49

Largely supportive | eculizumab (a C5 inhibitor monoclonal antibody) may be more beneficial than plasma exchange

Question 50

Alports syndrome

Answer 50

hereditary nephritis due to a basement membrane disorder resulting in haematuria as a renal manifestation. Microscopic hematuria is persistent and invariable in males affected by Alport's disease. Haematuria may present with/without bilateral anterior lenticonus and sensorineural hearing loss.

Question 51

Genetics of Alports syndrome

Answer 51

X-linked dominant inheritance | Type IV collagen defect that leads to abnormal basement membrane

Question 52

Features of Alport syndrome

Answer 52

microscopic haematuria progressive renal failure bilateral sensorineural deafness lenticonus: protrusion of the lens surface into the anterior chamber retinitis pigmentosa renal biopsy: splitting of lamina densa seen on electron microscopy

Question 53

Diagnosis of Alport syndrome

Answer 53

molecular genetic testing renal biopsy electron microscopy: characteristic finding is of the longitudinal splitting of the lamina densa of the glomerular basement membrane, resulting in a 'basket-weave' appearance

Question 54

mechanism of action: Calcium resonium

Answer 54

Calcium and sodium cations are exchanged for hydrogen ions in the stomach. These hydrogen ions are then exchanged for potassium ions in the large intestine and the potassium ions are excreted from the bowel as part of the resin comple

Question 55

What is cystinuria

Answer 55

Cystinuria is an autosomal recessive disorder characterised by the formation of recurrent renal stones. It is due to a defect in the membrane transport of cystine, ornithine, lysine, arginine (mnemonic = COLA)

Question 56

Features of cystinuria

Answer 56

recurrent renal stones | are classically yellow and crystalline, appearing semi-opaque on x-ray

Question 57

Diagnosis of cystinuria

Answer 57

cyanide-nitroprusside test

Question 58

Management of cystinuria

Answer 58

hydration D-penicillamine urinary alkalinization

Question 59

Glomerulonephritis and low complement

Answer 59

post-streptococcal glomerulonephritis subacute bacterial endocarditis systemic lupus erythematosus mesangiocapillary glomerulonephritis

Question 60

Glomerulonephritis with normal complement | levels

Answer 60

Goodpastures syndrome rare condition associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis. It is caused by anti-glomerular basement membrane (anti-GBM) antibodies against type IV collagen

Question 61

Complications of nephrotic syndrome

Answer 61

Anti-thrombin III deficiency (and plasminogen)- lost through glomerular basement membrane --> DVT/PE/renal vein thrombosis Hyperlipidaemia CKD Increased infection risk - loss of urinary immunoglobulin loss hypocalcaemia

Question 62

Rapidly progressive glomerulonephritis

Answer 62

Rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli. Causes Goodpasture's syndrome Wegener's granulomatosis others: SLE, microscopic polyarteritisR

Question 63

Urine dip - protein positive

Answer 63

intra-renal AKI

Question 64

Bacterial infections in Peritoneal dialysis

Answer 64

Coagulase-negative Staphylococcus species e.g. Staphylococcus epidermidis and Staphylococcus capitis peritonitis remains a common complication of peritoneal dialysis. Empiric antibiotic therapy usually aims to cover both gram-positive and gram-negative organisms.

Question 65

Goodpastures accronyms

Answer 65

IgG deposits on renal biopsy | anti-GBM antibodies

Question 66

Features of Goodpastures/anti-glomerular basement membrane disease

Answer 66

pulmonary haemorrhage rapidly progressive glomerulonephritis this typically results in a rapid onset acute kidney injury nephritis → proteinuria + haematuria

Question 67

Investigations in Goodpastures/ anti-glomerular membrane basement disease

Answer 67

renal biopsy: linear IgG deposits along the basement membrane raised transfer factor secondary to pulmonary haemorrhages

Question 68

Management of Goodpastures

Answer 68

plasma exchange (plasmapheresis) steroids cyclophosphamide

Question 69

Risk factors for pulmonary haemorrhage in Goodpastures disease

Answer 69

``` smoking lower respiratory tract infection pulmonary oedema inhalation of hydrocarbons young males ```

Question 70

Poor prognostic factors in IgA Nephropathy

Answer 70

male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD

Question 71

Management of IgA nephropathy

Answer 71

isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate (GFR) no treatment needed, other than follow-up to check renal function persistent proteinuria (above 500 to 1000 mg/day), a normal or only slightly reduced GFR initial treatment is with ACE inhibitors if there is active disease (e.g. falling GFR) or failure to respond to ACE inhibitors immunosuppression with corticosteroids

Question 72

Differentiating between IgA Nephropathy and post streptococcous glomerulonephritis

Answer 72

post-streptococcal glomerulonephritis is associated with low complement levels main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur) there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis

Question 73

Pathophysiology of IgA Nephropathy

Answer 73

thought to be caused by mesangial deposition of IgA immune complexes there is considerable pathological overlap with Henoch-Schonlein purpura (HSP) histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

Question 74

What is diabetes insipidus

Answer 74

a condition characterised by either a decreased secretion of antidiuretic hormone (ADH) from the pituitary (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI)

Question 75

Causes of cranial diabetes insipidus

Answer 75

``` idiopathic post head injury pituitary surgery craniopharyngiomas histiocytosis X DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome) haemochromatosis ```

Question 76

Causes of nephrogenic diabetes insipidus

Answer 76

genetic: the more common form affects the vasopression (ADH) receptor, the less common form results from a mutation in the gene that encodes the aquaporin 2 channel electrolytes: hypercalcaemia, hypokalaemia lithium lithium desensitizes the kidney's ability to respond to ADH in the collecting ducts demeclocycline tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis

Question 77

Features of HSP

Answer 77

palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs abdominal pain polyarthritis features of IgA nephropathy may occur e.g. haematuria, renal failure

Question 78

Pre-renal or ATN - AKI

Answer 78

In prerenal uraemia think of the kidneys holding on to sodium to preserve volume Pre-renal = urinary sodium excretion = 20%

Question 79

Mechanism of action: Spironalactone

Answer 79

aldosterone antagonist which acts in the cortical collecting duct.

Question 80

Indications for spironolactone

Answer 80

ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used hypertension: used in some patients as a NICE 'step 4' treatment heart failure (see RALES study below) nephrotic syndrome Conn's syndrome

Question 81

Adverse effects of spironolactone

Answer 81

hyperkalaemia | gynaecomastia: less common with eplerenone

Question 82

Prevention of calcium renal stones

Answer 82

``` high fluid intake low animal protein, low salt diet (a low calcium diet has not been shown to be superior to a normocalcaemic diet) thiazides diuretics (increase distal tubular calcium resorption) ```

Question 83

prevention of oxalate renal stones

Answer 83

cholestyramine reduces urinary oxalate secretion | pyridoxine reduces urinary oxalate secretion

Question 84

prevention of uric acid renal stones

Answer 84

allopurinol | urinary alkalinization e.g. oral bicarbonate

Question 85

Genetic changes that cause nephrogenic diatbetes insipidus

Answer 85

the more common form affects the vasopression (ADH) receptor | the less common form results from a mutation in the gene that encodes the aquaporin 2 channel

Question 86

Fibromuscular dysplasia

Answer 86

Young female, hypertension and asymmetric kidneys

Question 87

Features of fibromuscular dysplasia

Answer 87

hypertension chronic kidney disease or more acute renal failure e.g. secondary to ACE-inhibitor initiation 'flash' pulmonary oedema

Question 88

Electron microscopy in minimal change disease

Answer 88

normal glomeruli on light microscopy | electron microscopy shows fusion of podocytes and effacement of foot processes

Question 89

Membranoproliferative glomerulonephritis type 1

Answer 89

accounts for 90% of cases cause: cryoglobulinaemia, hepatitis C renal biopsy electron microscopy: subendothelial and mesangium immune deposits of electron-dense material resulting in a 'tram-track' appearance

Question 90

Membranoproliferative glomerulonephritis type 2

Answer 90

causes: partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face), factor H deficiency caused by persistent activation of the alternative complement pathway low circulating levels of C3 C3b nephritic factor is found in 70% an antibody to alternative-pathway C3 convertase (C3bBb) stabilizes C3 convertase renal biopsy electron microscopy: intramembranous immune complex deposits with 'dense deposits'

Question 91

AL amyloidosis

Answer 91

the most common form of amyloidosis L for immunoglobulin Light chain fragment due to myeloma, Waldenstrom's, MGUS features include: nephrotic syndrome, cardiac and neurological involvement, macroglossia, periorbital eccymoses

Question 92

AA amyloidosis

Answer 92

A for precursor serum amyloid A protein, an acute phase reactant seen in chronic infection/inflammation e.g. TB, bronchiectasis, rheumatoid arthritis features: renal involvement most common feature

Question 93

Beta-2 microglobulin amyloidosis

Answer 93

precursor protein is beta-2 microglobulin, part of the major histocompatibility complex associated with patients on renal dialysis

Question 94

Magnesium ammonium phosphate, (also known as struvite) renal stones

Answer 94

caused by urea splitting bacteria e.g. proteus. | can cause staghorn calculi

Question 95

Causes of papillary necrosis

Answer 95

``` chronic analgesia use sickle cell disease TB acute pyelonephritis diabetes mellitus ```

Question 96

Features of papillary necrosis

Answer 96

fever, loin pain, haematuria | IVU - papillary necrosis with renal scarring - 'cup & spill'

Question 97

Nephrogenic diabetes insipidus

Answer 97

presents with polyuria and polydipsia. The kidneys are not responding to antidiuretic hormone (ADH) and so osmolality remains low post-water deprivation, as they fail to concentrate urine. Osmolality remains low after administering desmopressin, as the kidneys cannot res

Question 98

Tolvaptan mechanism of action

Answer 98

action of vasopressin at the V2 receptor. This receptor is found on the basolateral membrane of the principal cells in the collecting ducts of the kidney. This reduces water absorption (through decreased aquaporin 2) and increases aquaresis without sodium loss. Desmopressin is a synthetic analogue of vasopressin that exerts agonism at the V2 receptor.

Question 99

V1 receptors

Answer 99

found on vascular smooth muscle and when activated cause vasoconstriction. V3 receptors are expressed in the pituitary gland and modulate ACTH secretion.

Question 100

Mechanism of action Abiraterone acetate

Answer 100

selective androgen synthesis inhibitor that works by blocking cytochrome P450 17 alpha-hydroxylase. It blocks androgen production in the testes and adrenal glands, and in prostatic tumour tissue. Abiraterone is administered orally in combination with prednisolone

Question 101

paraneoplastic hepatic dysfunction syndrome

Answer 101

Also known as Stauffer syndrome. Typically presents as cholestasis/hepatosplenomegaly. It is thought to be secondary to increased levels of IL-6