nephrology Flashcards

Question

definitions and classification of UTI

Answer 1

Definitions Bacteriuria: bacteria in urine, symptomatic or asympto UTI: symptomatic c¯ +ve culture or dipstick Urethral Syndrome: symptomatic but no bacteriuria Classification Uncomplicated: normal GU tract and function Complicated: abnormal GU tract, outflow obstruction, decrease renal function, impaired host defence, virulent organism Recurrent: further infection c¯ new organism Relapse: further infection c¯ same organism

Answer 2

Definitions Bacteriuria: bacteria in urine, symptomatic or asympto UTI: symptomatic c¯ +ve culture or dipstick Urethral Syndrome: symptomatic but no bacteriuria Classification Uncomplicated: normal GU tract and function Complicated: abnormal GU tract, outflow obstruction, decrease renal function, impaired host defence, virulent organism Recurrent: further infection c¯ new organism Relapse: further infection c¯ same organism

Answer 3

``` Pyelonephritis Fever, rigors Loin pain and tenderness Vomiting Oliguria if ARF ``` ``` Cystitis Frequency and urgency Polyuria Haematuria Dysuria Suprapubic tenderness Foul smelling urine ``` ``` Prostatitis Flu-like symptoms Low backache Dysuria Tender swollen prostate on PR ```

Answer 4

``` Organisms E. coli in 80% of cases Staphylococcus saprophyticus Proteus (alkaline urine causes struvite renal stones) Klebsiella ``` Ix Dipstick MSU for MCS Bloods: FBC, U+E, blood cultures (if systemic signs) US: children, men, recurrence, pyelonephritis Positive Culture >104 CFU/ml pure growth >103 CFU/ml pure growth of E. coli or S. saprophyticus >105 CFU/ml mixed growth c¯ one predominant organism Rx General Drink plenty, urinate often Uncomplicated lower UTI Trimethoprim PO Nitrofurantoin PO Duration = 3 days in ♀, 7 days in ♂ Lower UTI in pregnancy Cefadroxil PO Nitrofurantoin PO in 1st trimester Trimethoprim PO in 2nd and 3rd trimester Duration = 7 days Avoid Co-amoxiclav in 2nd and 3rd trimester Pyelonephritis Cefuroxime IV Ciprofloxacin PO Duration = 7 days for Cipro, 10 days for all other Add Gent if hypotensive or shock Cannot use Nitrofurantoin or Trimethoprim Pyelonephritis in pregnancy Cefuroxime IV Switch to Amox or Ciprofloxacin PO Duration = 7 days for Cipro, 14 days for all other Add Gent if hypotensive or shock (lower dose) Positive catheter specimen urine asymptomatic - no treatment symptomatic - take into account previous Rx and culture results ``` children Lower UTI Co-amoxiclav PO PenA: Nitrofurantoin PO if culture sensitive use Trimethoprim PO Duration = 3 days ``` Upper UTI or if under 1 year of age or unwell cefuroxime iv penA: ciprofloxacin iv duration 7-10 days

Answer 5

``` Sterile Pyuria: TB Treated UTI Appendicitis Calculi TIN Papillary necrosis Polycystic Kidney Chemical cystitis (e.g. cyclophosphamide) ```

Answer 6

Features Group of disorders resulting from glomerular damage Can cause proteinuria ± haematuria Can cause AKI or ESRF Presentations Asymptomatic haematuria Nephrotic syndrome Nephritic syndrome ``` Causes Idiopathic Immune: SLE, Goodpastures, vasculitis Infection: HBV, HCV, Strep, HIV Drugs: penicillamine, gold Amyloid ```

Answer 7

Ix ``` Blood Basic: FBC, U+E, ESR Complement (C3 and C4) Abs: ANA, dsDNA, ANCA, GBM Serum protein electrophoresis and Ig Infection: ASOT, HBC and HCV serology ``` ``` Urine Dipstick: proteinuria ± haematuria Spot PCR MCS Bence-Jones protein ``` Imaging CXR: infiltrates (Goodpasture’s, Wegener’s) Renal US ± biopsy General Mx Refer to nephrologist Rx HTN aggressively (at least 130/80) Include and ACEi / ARA

Answer 8

Causes 1. IgA Nephropathy 2. Thin BM 3. Alport’s

Answer 9

1. IgA Nephropathy / Berger’s Disease Commonest GN in developed world Features Young male c¯ episodic macroscopic haematuria occurring a few days after URTI. Rapid recovery between attacks increaseIgA Can occasionally cause nephritic syndrome Biopsy: IgA deposition in mesangium Rx: Steroids or cyclophosphamide if decrease renal function Prognosis: 20% ESRF after 20yrs Basics also called Berger's disease or mesangioproliferative glomerulonephritis commonest cause of glomerulonephritis worldwide 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 Differentiating between IgA nephropathy and post-streptococcal 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 Presentations young male, recurrent episodes of macroscopic haematuria typically associated with mucosal infections e.g., URTI nephrotic range proteinuria is rare renal failure Associated conditions alcoholic cirrhosis coeliac disease/dermatitis herpetiformis Henoch-Schonlein purpura Management steroids/immunosuppressants not be shown to be useful Prognosis 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

Answer 10

2. Thin BM Disease Autosomal dominant Commonest cause of asymptomatic haematuria Features Persistent, asymptomatic microscopic haematuria V. small risk of ESRF

Answer 11

3. Alport’s Syndrome 85% X-linked inheritance dominant ``` Features Haematuria, proteinuria cause progressive renal failure Sensorineural deafness Lens dislocation and cataracts Retinal “flecks” Females: haematuria only ``` 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 A favourite question is 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 Alport's syndrome usually presents in childhood. The following features may be seen: 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 *in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing

Answer 12

Nephritic Syndrome / Acute GN Haematuria (macro / micro) + red cell casts Proteinuria cause oedema (esp. periorbital) Hypertension Oliguria and progressive renal impairment Causes 1. Proliferative / post-streptococcal 2. Crescentic / RPGN

Answer 13

1. Proliferative / Post-streptococcal Features Young child develops malaise and nephritic syndrome c¯ smoky urine 1-2wks after sore throat or skin infection. increased ASOT decreased C3 Biopsy: IgG and C3 deposition Rx: Supportive Prognosis 95% of children recover fully Minority develop RPGN

Answer 14

Nephrotic Syndrome Proteinuria: PCR >300mg/mM or >3g/24h Hypoalbuminaemia: 3.5g/24h (>350mg/mmol) Oedema, salt & water retention due to reduction of plasma oncotic pressure Increase in cholesterol and triglycerides due to increased hepatic synthesis Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.

Answer 15

2. Crescentic / RPGN Most aggressive GN which can cause ESRF in days ``` Type 1: Anti-GBM (Goodpasture’s) – 5% Ab to NC domain of collagen 4 Haematuria and haemoptysis CXR shows infiltrates Rx: Plasmapheresis and immunosuppression ``` Type 2: Immune Complex Deposition – 45% Complication of any immune complex deposition Berger’s, post-strep, endocarditis, SLE Type 3: Pauci Immune – 50% cANCA: Wegener’s pANCA: microscopic polyangiitis, Churg-Strauss Even if ANCA+ve, may still be idiopathic i.e. no features of systemic vasculitis

Answer 16

Nephrotic Syndrome Proteinuria: PCR >300mg/mM or >3g/24h Hypoalbuminaemia:

Answer 17

``` Ix As for GN, check lipids Biopsy All adults Steroids 1st c¯ children: mostly minimal change ```

Answer 18

Secondary to Systemic Disease DM: glomerulosclerosis SLE: membranous Amyloidosis 1. Minimal Change Glomerulonephritis Commonest cause of nephrotic syndrome in children Assoc.: URTI Biopsy: normal light micro, fusion of podocytes on EM Rx: steroids Prog: 1% cause ESRF 2. Membranous Nephropathy 20-30% of adult nephrotic syndrome Associations commonest cause of proteinuria in later life Ca: lung, colon, breast AI: SLE, thyroid disease Infections: HBV Drugs: Penicillamine, gold Biopsy: subepithelial immune complex deposits Rx: immunosuppression if renal function declines Prog: 40% spontaneous remission 3. FSGS - focal segmental glomerulosclerosis. Commoner in Afro-Caribs Idiopathic or Secondary: VUR, Berger’s, SCD, HIV Biopsy: focal scarring, IgM deposition Rx: steroids or cyclophosphamide/ciclosporin Prog: 30-50% cause ESRF (may recur in transplants) 4. Membranoproliferative / Mesangiocapillary GN Rare May cause nephrotic (60%) or nephritic (30%) syndrome Asooc. c¯ HBV, HCV, endocarditis Prog: 50% cause ESRF

Answer 19

Mx Monitor U+E, BP, fluid balance, wt. Treat underlying cause Symptomatic / Complication Rx: Oedema: salt and fluid restrict + frusemide Proteinuria: ACEi / ARA decrease proteinuria increase Lipids: Statin VTE: Tinzaparin Rx HTN

Answer 20

Definition | Significant decline in renal function over hrs or days manifesting as an abrupt and sustained increase in Se U and Cr

Answer 21

Causes (Pre-renal and ATN account for ~80%) Pre-renal: commonest cause Shock or renovascular compromise (e.g. NSAIDs, ACEi) ``` Renal ATN: Ischaemia: shock, HTN, HUS, TTP Direct nephrotoxins: drugs, contrast, Hb Acute TIN: drug hypersensitivity Nephritic syndrome ``` ``` Post-renal: SNIPPIN Stone Neoplasm Inflammation: stricture Prostatic hypertrophy Posterior urethral valves Infection: TB, schisto Neuro: post-op, neuropathy ```

Answer 22

``` Presentation Uraemia / Azotaemia Acidosis Hyperkalaemia Fluid overload Oedema, inc. pulmonary increase BP (or decrease) S3 gallop increase JVP ```

Answer 23

Ix Bloods: FBC, U+E, LFT, glucose, clotting, Ca, ESR ABG: hypoxia (oedema), acidosis, increase K+ GN screen: if cause unclear Urine: dip, MCS, chemistry (U+E, PCR, osmolality, BJP) ECG: hyperkalaemia CXR: pulmonary oedema Renal US: Renal size, hydronephrosis NB. in pre-renal failure, urine is concentrated and Na is reabsorbed cause increase osmolality, Na

Answer 24

Clinical Assessment 1. Acute or chronic? Can’t tell for sure: Rx as acute Chronic features Hx of comorbidity: DM, HTN Long duration of symptoms Previously abnormal bloods (GP records) ``` 2. Volume depleted? Postural hypotension decrease JVP increase pulse Poor skin turgor, dry mucus membranes ``` ``` 3. GU tract obstruction? Suprapubic discomfort Palpable bladder Enlarged prostate Catheter Complete anuria (rare in ARF) ``` 4. Rare cause? Assoc. c¯ proteinuria ± haematuria Vasculitis: rash, arthralgia, nosebleed

Answer 25

RIFLE Classification 3 grades of AKI and 2 outcomes Classification determined by worst criteria Classification GFR UO ``` Classification: stage 1 = increase Cr x1.5 or decrease GFR >25% or urine output 50% or urine output 75% or urine output 3mo ```

Answer 26

Ix Bloods: FBC, U+E, LFT, glucose, clotting, Ca, ESR ABG: hypoxia (oedema), acidosis, increase K+ GN screen: if cause unclear Urine: dip, MCS, chemistry (U+E, PCR, osmolality, BJP) ECG: hyperkalaemia CXR: pulmonary oedema Renal US: Renal size, hydronephrosis NB. in pre-renal failure, urine is concentrated and Na is reabsorbed cause increase osmolality, Na

Answer 27

``` Rx General Identify and Rx pre-renal or post-renal causes Urgent US Rx exacerbating factors: e.g. sepsis Give PPIs Stop nephrotoxins: NSAIDs, ACEi, gent, vanc Stop metformin if Cr > 150mM ``` ``` Monitor Catheterise and monitor UO Consider CVP Fluid balance Wt. ``` Hyperkalaemia: ``` ECG Features (in order) Peaked T waves Flattened P waves increase PR interval Widened QRS Sine-wave pattern causes VF ``` Mx 10ml 10% calcium gluconate 100ml 20% glucose + 10u insulin (Actrapid) Salbutamol 5mg nebulizer Calcium resonium 15g PO or 30g PR Haemofiltration (usually needed if anuric) ``` Pulmonary Oedema: Sit up and give high-flow O2 Morphine 2.5mg IV (± metoclopramide 10mg IV) Frusemide 120-250mg IV over 1h GTN spray ± ISMN IVI (unless SBP 10 ```

Answer 28

Indications for Acute Dialysis (AEIOU) 1. Persistent hyperkalaemia (>7mM) 2. Refractory pulmonary oedema 3. Symptomatic uraemia: encephalopathy, pericarditis 4. Severe metabolic acidosis (pH

Answer 29

1 - Resuscitate and Assess Fluid Status A: drop GCS may need airway Mx B: pulmonary oedema – sit up, high flow O2 C: Assess fluid status: cv = postural BP, JVP, HR tissues = CRT, cold/warm hands, skin turgor, mucus membranes end organ = mental state, urine output. 2 - Rx Life-Threatening Complications Hyperkalaemia Pulmonary oedema Consider need for rapid dialysis 3 - Rx Shock or Dehydration Fluid challenge 250-500ml over 30min Repeat as necessary: aim for CVP of 5-10cm Once replete, continue @ 20ml+UO/h ``` 4 - Monitor Cardiac monitor Urinary catheter Consider CVP Start fluid balance chart ``` ``` 5 - Look for Evidence of Post-Renal Causes Palpable ± tender bladder Enlarged prostate Catheter in situ Complete anuria ``` ``` 6 - Hx and Ix Hx: Evidence of Acute vs. Chronic RF Duration of symptoms Co-morbidities Previous blood results ``` ``` Ix Bloods, ABG Urine dip + MCS + chem ECG CXR and Renal US ``` 7 - Rx Sepsis Blood cultures and empirical Abx 8 - Further Mx Call urologists if obstructed despite catheter Care with nephrotoxic drugs: e.g. gentamicin

Answer 30

Acute Interstitial / Tubulointerstitial Nephritis Immune-mediated hypersensitivity c¯ either drugs or other Ag acting as haptans ``` Causes Drug hypersensitivity in 70% NSAIDs Abx: Cephs, penicillins, rifampicin, sulphonamide Diuretics: frusemide, thiazides Allopurinol Cimetidine Infections in 15% Staphs, streps Immune disorders SLE, Sjogren’s ``` Presentation Fever, arthralgia, rashes AKI causes olig/anuria Uveitis

Answer 31

``` Complications: CRF HEALS Cardiovascular disease Renal osteodystrophy Fluid (oedema) HTN Electrolyte disturbances: K, H Anaemia Leg restlessness Sensory neuropathy ``` Sodium & water Impaired excretory & conservatory mechanism for sodium and water. Thirst & and nocturia reflect diminished capacity of the kidney to concentrate urine and loss of normal diurnal variation of production of urine. Urine tends towards a fixed osmolality. Potassium Well maintained until GFR

Answer 32

Ix increase IgE, eosinophilia Dip: haematuria, proteinuria, sterile pyuria Rx Stop offending drug Prednisolone Prognosis: Most recover renal function

Answer 33

Chronic TIN - Tubulointerstitial Nephritis Fibrosis and tubular loss Commonly caused by: Reflux and chronic pyelonephritis DM SCD or trait

Answer 34

Analgesic Nephropathy Prolonged heavy ingestion of compound analgesics Often a Hx of chronic pain: headaches, muscle pain Features Sterile pyuria ± mild proteinuria Slowly progressive CRF Sloughed papilla can cause obstruction and renal colic Ix: CT w/o contrast (papillary calcifications) Rx: stop analgesics

Answer 35

Acute Urate Crystal Nephropathy AKI due to urate precipitation Usually after chemo-induced cell lysis Rx: hydration, urinary alkalinisation

Answer 36

Nephrocalcinosis Diffuse renal parenchymal calcification Progressive renal impairment ``` Causes Malignancy increased PTH Myeloma Sarcoidosis Vit D intoxification RTA ```

Answer 37

Nephrocalcinosis Acute Urate Crystal Nephropathy Analgesic Nephropathy Chronic TIN - Tubulointerstitial Nephritis Acute Interstitial / Tubulointerstitial Nephritis

Answer 38

Nephrotoxins Either directly toxic via ATN Or cause hypersensitivity via TIN (Tubulointerstitial Nephritis)

Answer 39

Endogenous Haemoglobin, myoglobin Urate Ig: e.g. light chains in myeloma

Answer 40

Features Kidney damage at least 3mo indicated by decreased function involving loss of both glomerular and tubular function. Retention of nitrogenous waste products. Symptoms usually only occur by stage 4 CKD stage GFR range 1 Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD) 2 60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD) 3a 45-59 ml/min, a moderate reduction in kidney function 3b 30-44 ml/min, a moderate reduction in kidney function 4 15-29 ml/min, a severe reduction in kidney function 5 Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed

Answer 41

``` Pathogenesis Skeletal muscle breakdown causes release of: K+, PO4, urate Myoglobin, CK increase K and AKI ``` Causes Ischaemia: embolism, surgery Trauma: immobilisation, crush, burns, seizures, compartment syndrome Toxins: statins, fibrates, ecstasy, neuroleptics Clinical Muscle pain, swelling Red/brown urine AKI occurs 10-12h later Ix Dipstick: +ve Hb, -ve RBCs Blood: increase CK, increase K, increase PO4, increase urate ``` Rx Rx hyperkalaemia IV rehydration: 300ml/h CVP monitoring if oliguric IV NaHCO3 may be used to alkalinize urine and stabilise a less toxic form of myoglobin. ```

Answer 42

Features Kidney damage at least 3mo indicated by decreased function Symptoms usually only occur by stage 4 ``` stage 1 GFR at least 90 2 60-89 3a 45-59 3b 30-44 4 16-29 5 less than 15 ``` Syndrome of persistent renal impairment involving loss of both glomerular and tubular function. Retention of nitrogenous waste products.

Answer 43

Causes Common DM HTN ``` Other RAS GN Polycystic disease Drugs: e.g. analgesic nephropathy Pyelonephritis: usually 2O to VUR SLE Myeloma and amyloidosis ``` ``` Hx Past UTI HTN, DM FH DH Symptoms ```

Answer 44

Ix Blood decrease Hb, U+E, ESR, glucose, decrease Ca/increase PO4, increase ALP, increase PTH Immune: ANA, dsDNA, ANCA, GBM, C3, C4, Ig, Hep Film: burr cells Urine: dip, MCS, PCR, BJP Imaging CXR: cardiomegaly, pleural/pericardial effusion, oedema AXR: calcification from stones ``` Renal US Usually small ( ```

Answer 45

``` Complications: CRF HEALS Cardiovascular disease Renal osteodystrophy Fluid (oedema) HTN Electrolyte disturbances: K, H Anaemia Leg restlessness Sensory neuropathy ```

Answer 46

Features Osteoporosis: decreases bone density Osteomalacia: decreases mineralisation of osteoid (matrix) secondary/ tertiary HPT causes osteitis fibrosa cystica -Subperiosteal bone resorption -Acral osteolysis: short stubby fingers - Pepperpot skull May get spinal osteosclerosis causes Rugger Jersey spine Sclerotic vertebral end-plate c¯ lucent centre Mechanism: decreased 1alpha-hydroxylase causes decreased vit D activation causes decreased Ca and increased PTH Phosphate retention causes decreased Ca and increased PTH (directly) increased PTH causes activation of osteoclasts ± osteoblasts Also acidosis causes bone resorption

Answer 47

Mx General Rx reversible causes Stop nephrotoxic drugs ``` Lifestyle Exercise Healthy wt. Stop smoking Na, fluid and PO4 restriction ``` CV Risk Statins (irrespective of lipids) Low-dose aspirin Rx DM Hypertension Target

Answer 48

Treatment of choice for ESRF ``` Assessment Virology status: CMV, HCV, HBV, HIV, VZV, EBV CVD TB ABO and HLA haplotype ``` Contraindications Active infection Cancer Severe HD or other co-morbidity

Answer 49

Immunosuppression Pre-op: campath / alemtuzumab (anti-CD52) Post-op: prednisolone short-term and tacro/ciclo longterm Prognosis t½ for cadaveric grafts: 15yrs

Answer 50

Complications ``` Post-op Bleeding Graft thrombosis Infection Urinary leaks ``` ``` Hyperacute rejection (minutes) ABO incompatibility Thrombosis and SIRS due to pre-existent antibodies against donor HLA type 1 antigens (a type II hypersensitivity reaction) rarely seen due to HLA matching ``` Acute Rejection (under 6mo) usually due to mismatched HLA. Cell-mediated (cytotoxic T cells) other causes include cytomegalovirus infection Interstitial fibrosis + tubular atrophy Gradual rise in Cr and proteinuria Not responsive to immunosuppression Causes of chronic graft failure (> 6 months) both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy) recurrence of original renal disease (MCGN > IgA > FSGS) Ciclosporin / tacrolimus nephrotoxicity Acute: reversible afferent arteriole constriction cause decrease in GFR Chronic: tubular atrophy and fibrosis Immune Function increased risk of infection: opportunists, fungi, warts increased risk of malignancy: BCC, SCC, lymphoma (EBV) Cardiovascular Disease Hypertension and atherosclerosis The human leucocyte antigen (HLA) system is the name given to the major histocompatibility complex (MHC) in humans. It is coded for on chromosome 6. ``` Some basic points on the HLA system class 1 antigens include A, B and C. Class 2 antigens include DP,DQ and DR when HLA matching for a renal transplant the relative importance of the HLA antigens are as follows DR > B > A ``` Graft survival 1 year = 90%, 10 years = 60% for cadaveric transplants 1 year = 95%, 10 years = 70% for living-donor transplants

Answer 51

``` Differential of Rising Cr in Tx pt. Rejection Obstruction ATN Drug toxicity ```

Answer 52

Diabetic Nephropathy Causes ~20% of ESRF Advanced / ESRF occurs in 40% of T1 and T2 DM Pathology Diabetic nephropathy describes conglomerate of lesions occurring concurrently. Hyperglycaemia causes renal hyperperfusion causes hypertrophy and increases renal size Hypertrophy and metabolic defects inc. ROS production causes glomerulosclerosis and nephron loss Nephron loss causes RAS activation causes HTN Clinically Microalbuminuria (30-300mg/d or albumin:creatinine >3). Strong independent RF for CV disease Progresses to proteinuria (albuminuria >300mg/d) Diabetic retinopathy usually co-exists and HTN is common

Answer 53

Renal Tubular Acidosis Impaired acid excretion causes hyperchloraemic met acidosis Both cause RAS activation causes K+ wasting and hypokalaemia ``` Type 1 (Distal) Inability to excrete H+, even when acidotic May complicate other renal disorders ``` Causes Hereditary: Marfan’s, Ehler’s Danlos AI: Sjogren’s, SLE, thyroiditis Drugs Features Rickets / osteomalacia (bone buffering) Renal stones and UTIs Nephrocalcinosis causes ESRF Dx Failure to acidify urine (pH >5.5) despite acid load Type 2 (Proximal) Defect in HCO3 reabsorption in PCT Tubules can reabsorb some HCO3 so can acidify urine in systemic acidosis when HCO3 drop Usually assoc. c¯ Fanconi syndrome Dx Urine will acidify c¯ acid load (pH Type 4:most common. May get decreased renin or resistance to aldos. Normal anion gap. - hyporeninaemic hypoaldosteronism. aldosterone not produced

Answer 54

Screening | T2DMs should be screened for microalbuminuria 6moly

Answer 55

Rx Good glycaemic control delays onset and progression BP target 130/80 Start ACEi/ARB even if normotensive Stop smoking Combined kidney pancreas Tx possible in selected pts

Answer 56

Amyloidosis Renal involvement usually caused by AL/AA amyloid Features: Proteinuria Nephrotic syndrome Progressive renal failure Dx Large kidneys on US Biopsy

Answer 57

Infection GN: post-strep, HCV, HBV, HIV, SBE/IE, visceral abscess Vasculitis: HBV, HCV, post-strep TIN: bacterial pyelonephritis, CMV, HBV, toxo

Answer 58

Pathology Excess production of monoclonal Ab ± light chains (excreted and detected in 60% as urinary BJP). Light chains block tubules and have direct toxic effects ATN. Myeloma also assoc. c¯ greatly raised Ca2+ Presentation ARF / CRF Amyloidosis

Answer 59

Rx Ensure fluid intake of 3L/d to prevent further impairment Dialysis may be required in ARF

Answer 60

RA NSAIDs cause ATN Penicillamine and gold cause membranous GN AA amyloidosis occurs in 15%

Answer 61

SLE Involves glomerulus in 40-60% causes ARF/CRF Proteinuria and increases BP common Rx Proteinuria: ACEi Aggressive GN: immunosuppression

Answer 62

Diffuse Systemic Sclerosis Renal crisis: malignant HTN + ARF Commonest cause of death Rx: ACEi if increase increase BP or renal crisis

Answer 63

Haemolytic Uraemic Syndrome (HUS) E. coli O157:H7: verotoxin causes endothelial dysfunction Features Young children eating undercooked meat (burgers) Bloody diarrhoea and abdominal pain precedes: microangiopathic haemolytic anaemia Thrombocytopenia Renal failure Ix Schistocytes, decrease plats decrease Hb Normal clotting Rx Usually resolves spontaneously Dialysis or plasma exchange may be needed

Answer 64

``` Cause Atherosclerosis in 80% Fibromuscular dysplasia Thromboembolism External mass compression ``` Features Refractory hypertension Worsening renal function after ACEi/ARB Flash pulmonary oedema (no LV impairment on echo) Ix US + doppler: small kidney + decrease flow CT/MR angio Renal angiography: gold standard Rx Rx medical CV risk factors Angioplasty and stenting

Answer 65

Haemolytic Uraemic Syndrome (HUS) E. coli O157:H7: verotoxin causes endothelial dysfunction Features Young children eating undercooked meat (burgers) Bloody diarrhoea and abdominal pain precedes: MAHA Thrombocytopenia Renal failure Ix Schistocytes, decrease plats decrease Hb Normal clotting Rx Usually resolves spontaneously Dialysis or plasma exchange may be needed

Answer 66

Thrombotic Thrombocytopenia Purpura (TTP) Genetic or acquired deficiency of ADAMTS13 causes giant vWF multimers Features Adult females ``` Pentad Fever CNS signs: confusion, seizures MAHA Thrombocytopenia Renal failure ``` Ix: As HUS Rx: Plasmapheresis, immunosuppression, splenectomy

Answer 67

Renal Tubular Acidosis Impaired acid excretion causes hyperchloraemic met acidosis Both cause RAS activation causes K+ wasting and hypokalaemia ``` Type 1 (Distal) Inability to excrete H+, even when acidotic May complicate other renal disorders ``` Causes Hereditary: Marfan’s, Ehler’s Danlos AI: Sjogren’s, SLE, thyroiditis Drugs Features Rickets / osteomalacia (bone buffering) Renal stones and UTIs Nephrocalcinosis causes ESRF Dx Failure to acidify urine (pH >5.5) despite acid load Type 2 (Proximal) Defect in HCO3 reabsorption in PCT Tubules can reabsorb some HCO3 so can acidify urine in systemic acidosis when HCO3 drop Usually assoc. c¯ Fanconi syndrome Dx Urine will acidify c¯ acid load (pH

Answer 68

Fanconi Syndrome Disturbance of PCT function causes generalised impaired reabsorption: amino acids, K+, HCO3, phosphate, glucose Causes Idiopathic Inherited: inborn errors, Wilson’s Acquired: tubule damage (drugs, myeloma…) Features Polyuria (osmotic diuresis) Hypophosphataemic rickets (Vit D resistant) Acidosis, decrease K

Answer 69

Prev: 1:1000 caucasians Age: Adults 40-60yrs Genetics PKD1 on Chr16, polycystin 1 (80%): cell-cell and cell matrix membrane receptor, presents with renal failure earlier PKD2 on Chr4, polycystin 2: Ca2+ channel that interacts c¯ polycystin 1 Path Large cysts arising from all parts of nephron Progressive decline in renal function 70% ESRF by 70yrs Genetic testing is still not routinely recommended for screening family members

Answer 70

Bartter’s Syndrome | Gitelman Syndrome

Answer 71

Bartter’s Syndrome Blockage of NaCl reabsorption in loop of Henle (as if taking frusemide) Congenital salt wasting causes RAS activation causes hypokalaemia and metabolic alkalosis Normal BP

Answer 72

Gitelman Syndrome Blockage of NaCl reabsorption in DCT (as if taking thiazides) Congenital salt wasting causes RAS activation causes hypokalaemia and metabolic alkalosis + hypocalciuria Normal BP

Answer 73

Prev: 1:1000 Age: Adults 40-60yrs Genetics PKD1 on Chr16, polycystin 1 (80%): cell-cell and cell matrix membrane receptor PKD2 on Chr4, polycystin 2: Ca2+ channel that interacts c¯ polycystin 1 Path Large cysts arising from all parts of nephron Progressive decline in renal function 70% ESRF by 70yrs

Answer 74

Presentation: MISSHAPES ``` Mass: abdo mass and flank pain Infected cyst Stones SBP raised Haematuria or haemorrhage into cyst Aneurysms: berry causes SAH Polyuria + nocturia Extra-renal cysts: liver Systolic murmur: mitral valve prolapse ```

Answer 75

``` Rx General increase water intake, decrease Na, decrease caffeine (may decrease cyst formation) Monitor U+E and BP Genetic counselling MRA screen for Berry aneurysms ``` Medical Rx HTN aggressively:

Answer 76

Auto Rec Polycystic Kidney Disease Prev: 1:40,000 Infancy Renal cysts and congenital hepatic fibrosis

Answer 77

Medullary Sponge Kidney Multiple cystic dilatations of the CDs in the medulla Typically presents in 20-30s Commoner in females Often asymptomatic, but predisposes to: Hypercalciuria and nephrolithiasis Recurrent UTIs and pyelonephritis Haematuria Renal function is usually normal

Answer 78

``` Tuberous Sclerosis (Bourneville’s Disease) AD condition c¯ hamartomas in skin, brain, eye, kidney ``` Skin: nasolabial adenoma sebaceum, ash-leaf macules, peri-ungual fibromas Neuro: decrease IQ, epilepsy Renal: cysts, angiomyolipomas

Answer 79

Renal Enlargement Differential: PHONOS ``` Polycystic kidneys: ADPKD, ARPKD, TS Hypertrophy 2O to contralateral renal agenesis Obstruction (hydronephrosis) Neoplasia: RCC, myeloma, amyloidosis Occlusion (renal vein thrombosis) Systemic: early DM, amyloid ```

Answer 80

``` Pre renal causes e.g. loss of blood Tubules functional and producing high quality urine urine sodium 500mmol/l U/P osmolality 1.5 i.e hypoperfusion ``` Renal causes e.g. heavy metal toxicity of tubules Tubular function impaired leading to poor quality urine urine sodium >20mmol/l Fractional excretion of sodium >1% urine urea

Answer 81

Urine Albumin/creatinine ratio (ACR): formerly known as ‘microalbumin’ More sensitive indicator of renal damage than PCR ( ratio of protein to creatinine i.e. PCR)

Answer 82

Demeclocyline blocks ADH effects used for inappropriate ADH secretion Tolvaptan; ADH receptor blocker (V2 receptors) also used for inappropriate ADH secretion

Answer 83

``` 1 - ACEI 2 - penicillamine 3 - gentamicin, amphotericin 4 - NSAIDS 5 - lithium ```

Answer 84

Avoid nephrotoxic drugs Drugs may be ineffective in kidney failure e.g. thiazide diuretics Sensitivity to a drug may be increased; e.g., opiates, hypnotics, sedatives, antiepileptics Adverse effects more likely in patients with kidney failure; NSAIDs, metformin, K-sparing diuretics, ACE inhibitors, anticoagulants Drug may accumulate so reduce dose or dose frequency; vancomycin, penicillins, cephalosporins, statins, beta blockers, ACE inhibitors, digoxin, sulphonylureas

Answer 85

``` uraemia - need GFR below 15ml/min protein loss and Na retention acidosis hyperkalaemia anaemia vit d deficiency ```

Answer 86

Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.

Answer 87

Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.

Answer 88

Causes of chronic graft failure (> 6 months) both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy) recurrence of original renal disease (MCGN > IgA > FSGS)

Answer 89

Cytomegalovirus is the most common and important viral infection in solid organ transplant recipients

Answer 90

Causes of chronic graft failure (later than 6 months) both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy) recurrence of original renal disease (MCGN over IgA over FSGS)

Answer 91

Cytomegalovirus is the most common and important viral infection in solid organ transplant recipients Ganciclovir is the treatment of choice in such patients.

Answer 92

Cytomegalovirus is the most common and important viral infection in solid organ transplant recipients Ganciclovir is the treatment of choice in such patients.

Answer 93

Features of renal cell carcinoma: classical triad: haematuria, loin pain, abdominal mass pyrexia of unknown origin left varicocele (due to occlusion of left testicular vein) endocrine effects: may secrete erythropoietin (polycythaemia), parathyroid hormone (hypercalcaemia), renin, ACTH 25% have metastases at presentation

Answer 94

Features of Chlamydia asymptomatic in around 70% of women and 50% of men women: cervicitis (discharge, bleeding), dysuria men: urethral discharge, dysuria

Answer 95

Features of Chlamydia asymptomatic in around 70% of women and 50% of men women: cervicitis (discharge, bleeding), dysuria men: urethral discharge, dysuria

Answer 96

Haemolytic uraemic syndrome is generally seen in young children and produces a triad of: acute renal failure microangiopathic haemolytic anaemia thrombocytopenia ``` Causes post-dysentery - classically E coli 0157:H7 ('verotoxigenic', 'enterohaemorrhagic') tumours pregnancy ciclosporin, the Pill systemic lupus erythematosus HIV ``` Investigations full blood count: anaemia, thrombocytopaenia, fragmented blood film U&E: acute renal failure stool culture Management treatment is supportive e.g. Fluids, blood transfusion and dialysis if required there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients the indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea

Answer 97

Haemolytic uraemic syndrome is generally seen in young children and produces a triad of: acute renal failure microangiopathic haemolytic anaemia thrombocytopenia ``` Causes post-dysentery - classically E coli 0157:H7 ('verotoxigenic', 'enterohaemorrhagic') tumours pregnancy ciclosporin, the Pill systemic lupus erythematosus HIV ``` Investigations full blood count: anaemia, thrombocytopaenia, fragmented blood film U&E: acute renal failure stool culture Management treatment is supportive e.g. Fluids, blood transfusion and dialysis if required there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients the indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea

Answer 98

Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults. The majority of cases are idiopathic, but in around 10-20% a cause is found: drugs: NSAIDs, rifampicin Hodgkin's lymphoma, thymoma infectious mononucleosis Pathophysiology T-cell and cytokine mediated damage to the glomerular basement membrane → polyanion loss the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin ``` Features nephrotic syndrome normotension - hypertension is rare highly selective proteinuria* renal biopsy: electron microscopy shows fusion of podocytes ``` Management majority of cases (80%) are steroid responsive cyclophosphamide is the next step for steroid resistant cases Prognosis is overall good, although relapse is common. Roughly: 1/3 have just one episode 1/3 have infrequent relapses 1/3 have frequent relapses which stop before adulthood *only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus

Answer 99

Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults. The majority of cases are idiopathic, but in around 10-20% a cause is found: drugs: NSAIDs, rifampicin Hodgkin's lymphoma, thymoma infectious mononucleosis Pathophysiology T-cell and cytokine mediated damage to the glomerular basement membrane → polyanion loss the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin ``` Features nephrotic syndrome normotension - hypertension is rare highly selective proteinuria* renal biopsy: electron microscopy shows fusion of podocytes ``` Management majority of cases (80%) are steroid responsive cyclophosphamide is the next step for steroid resistant cases Prognosis is overall good, although relapse is common. Roughly: 1/3 have just one episode 1/3 have infrequent relapses 1/3 have frequent relapses which stop before adulthood *only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus

Answer 100

Over 50% of renal transplant patients have a significant infection within the first 12 months of having a renal transplant. At the time of transplant the CMV-serological status of the donor and recipient are noted. The highest risk is seen in CMV-seronegative recipients who receive a kidney from a CMV-seropositive donor. These patients are usually given antiviral prophylaxis. Cytomegalovirus tend to be seen after four weeks as before this time the immune system has not been fully affected by the immunosuppressants.

Answer 101

Congenital CMV infection features include growth retardation, pinpoint petechial 'blueberry muffin' skin lesions, microcephaly, sensorineural deafness, encephalitiis (seizures) and hepatosplenomegaly CMV mononucleosis infectious mononucelosis-like illness may develop in immunocompetent individuals CMV retinitis common in HIV patients with a low CD4 count (

Answer 102

Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media. Risk factors include known renal impairment (especially diabetic nephropathy) age > 70 years dehydration cardiac failure the use of nephrotoxic drugs such as NSAIDs Prevention the evidence base currently supports the use of intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the use of isotonic sodium bicarbonate N-acetylcysteine (usually given orally) has been shown to reduce the incidence of contrast-nephropathy in some studies but the evidence base is not as strong as for fluid therapy

Answer 103

Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media. Risk factors include known renal impairment (especially diabetic nephropathy) age > 70 years dehydration cardiac failure the use of nephrotoxic drugs such as NSAIDs Prevention the evidence base currently supports the use of intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the use of isotonic sodium bicarbonate N-acetylcysteine (usually given orally) has been shown to reduce the incidence of contrast-nephropathy in some studies but the evidence base is not as strong as for fluid therapy

Answer 104

an ACE inhibitor

Answer 105

Henoch-Schonlein purpura (HSP) is 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. Features 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 Treatment analgesia for arthralgia treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants Prognosis usually excellent, HSP is a self-limiting condition, especially in children without renal involvement around 1/3rd of patients have a relapse

Answer 106

Henoch-Schonlein purpura (HSP) is 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. Features 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 Treatment analgesia for arthralgia treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants Prognosis usually excellent, HSP is a self-limiting condition, especially in children without renal involvement around 1/3rd of patients have a relapse

Answer 107

``` WHO classification class I: normal kidney class II: mesangial glomerulonephritis class III: focal (and segmental) proliferative glomerulonephritis class IV: diffuse proliferative glomerulonephritis class V: diffuse membranous glomerulonephritis class VI: sclerosing glomerulonephritis ``` Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings: glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance if severe, the capillary wall may be thickened secondary to immune complex deposition electron microscopy shows subendothelial immune complex deposits granular appearance on immunofluorescence Management treat hypertension corticosteroids if clinical evidence of disease immunosuppressants e.g. azathiopine/cyclophosphamide

Answer 108

``` WHO classification class I: normal kidney class II: mesangial glomerulonephritis class III: focal (and segmental) proliferative glomerulonephritis class IV: diffuse proliferative glomerulonephritis class V: diffuse membranous glomerulonephritis class VI: sclerosing glomerulonephritis ``` Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings: glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance if severe, the capillary wall may be thickened secondary to immune complex deposition electron microscopy shows subendothelial immune complex deposits granular appearance on immunofluorescence Management treat hypertension corticosteroids if clinical evidence of disease immunosuppressants e.g. azathiopine/cyclophosphamide

Answer 109

Cardiovascular events account for 50% of the mortality in patients receiving dialysis.

Answer 110

Cardiovascular events account for 50% of the mortality in patients receiving dialysis.

Answer 111

NICE urgent cancer referral guidelines of any age with painless macroscopic haematuria patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care aged 40 years and older who present with recurrent or persistent urinary tract infection associated with haematuria aged 50 years and older who are found to have unexplained microscopic haematuria

Answer 112

foods: beetroot, rhubarb drugs: rifampicin, doxorubicin

Answer 113

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. Features abdominal mass (most common presenting feature) flank pain painless haematuria other features: anorexia, fever unilateral in 95% of cases metastases are found in 20% of patients (most commonly lung)

Answer 114

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. Features abdominal mass (most common presenting feature) flank pain painless haematuria other features: anorexia, fever unilateral in 95% of cases metastases are found in 20% of patients (most commonly lung)

Answer 115

Questions regarding which drugs to avoid in renal failure are common ``` Drugs to avoid in renal failure antibiotics: tetracycline, nitrofurantoin NSAIDs lithium metformin ``` Drugs likely to accumulate in chronic kidney disease - need dose adjustment most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin digoxin, atenolol methotrexate sulphonylureas furosemide opioids Drugs relatively safe - can sometimes use normal dose depending on the degree of chronic kidney disease antibiotics: erythromycin, rifampicin diazepam warfarin Many drugs need dose adjustment in renal disease due to changes in drug metabolism and also pharmacokinetics. Often this dose adjustment is made on the level of the estimated glomerular filtration rate (eGFR) which is a calculated surrogate of renal function using the serum creatinine. Stages of chronic kidney disease are classified according to the eGFR; stage 3 CKD equates to an eGFR of 30-59ml/min.

Answer 116

Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors). Management may be categorised by the aims of treatment Stabilisation of the cardiac membrane intravenous calcium gluconate Short-term shift in potassium from extracellular to intracellular fluid compartment combined insulin/dextrose infusion nebulised salbutamol Removal of potassium from the body calcium resonium (orally or enema) loop diuretics dialysis

Answer 117

Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors). Management may be categorised by the aims of treatment Stabilisation of the cardiac membrane intravenous calcium gluconate Short-term shift in potassium from extracellular to intracellular fluid compartment combined insulin/dextrose infusion nebulised salbutamol Removal of potassium from the body calcium resonium (orally or enema) loop diuretics dialysis

Answer 118

The majority of patients with chronic kidney disease (CKD) will require more than two drugs to treat hypertension. ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, although any rise should prompt careful monitoring and exclusion of other causes (e.g. NSAIDs). A rise greater than this may indicate underlying renovascular disease. Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then consideration should be given to temporarily stopping the drug *the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min

Answer 119

The majority of patients with chronic kidney disease (CKD) will require more than two drugs to treat hypertension. ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, although any rise should prompt careful monitoring and exclusion of other causes (e.g. NSAIDs). A rise greater than this may indicate underlying renovascular disease. Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then consideration should be given to temporarily stopping the drug *the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min

Answer 120

Peritoneal dialysis (PD) is a form of renal replacement therapy. It is sometimes used as a stop-gap to haemodialysis or for younger patients who do not want to have to visit hospital three times a week. The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves four 2-litre exchanges/day. Complications peritonitis: coagulase-negative staphylococci such as Staphylococcus epidermidis is the most common cause. Staphylococcus aureus is another common cause sclerosing peritonitis

Answer 121

Treatment of hypokalaemia depends on severity. Any causative agents should be removed. Gradual replacement of potassium via the oral route is preferred if possible. Mild to moderate hypokalaemia 2.5 - 3.4 mmol/l can be treated with oral potassium provided the patient is not symptomatic and there are no ECG changes. Treatment If mild: (over2.5mmol/L, no symptoms) give oral K+ supplement (at least 80mmol/24h, eg Sando-K® 2 tabs/8h). Review K+ after 3 days. If taking a thiazide diuretic, and K+ over 3.0 consider repeating and/or K+ sparing diuretic. If severe: (under 2.5mmol/L, and/or dangerous symptoms) give IV potassium cautiously, not more than 20mmol/h, and not more concentrated than 40mmol/L. Do not give K+ if oliguric. Never give K+ as a fast stat bolus dose

Answer 122

There are two main types of anti-neutrophil cytoplasmic antibodies (ANCA) - cytoplasmic (cANCA) and perinuclear (pANCA) For the exam, remember: cANCA - Wegener's granulomatosis pANCA - Churg-Strauss syndrome + others (see below) cANCA most common target serine proteinase 3 (PR3) some correlation between cANCA levels and disease activity Wegener's granulomatosis, positive in > 90% microscopic polyangiitis, positive in 40% pANCA most common target is myeloperoxidase (MPO) cannot use level of pANCA to monitor disease activity associated with immune crescentic glomerulonephritis (positive in c. 80% of patients) microscopic polyangiitis, positive in 50-75% Churg-Strauss syndrome, positive in 60% primary sclerosing cholangitis, positive in 60-80% Wegener's granulomatosis, positive in 25% Other causes of positive ANCA (usually pANCA) inflammatory bowel disease (UC > Crohn's) connective tissue disorders: RA, SLE, Sjogren's autoimmune hepatitis

Answer 123

``` SHAPE: Sclerderma HIV nephropathy Amyloidosis Polycystic kidney disease Endocrinophathy (diabetes) ```

Answer 124

"S#!T": Stones/ Systemic disease (SLE)/ Structural lesions (UPJ obstruction) Hematologic disease (sickle cell, coagulopathy)/ Hypercalciuria/ Hereditary (Alport nephritis)/ HSP/ HUS Infectious and Immunologic (PSGN)/ IgA nephropathy (Berger nephritis)/ Interstitial disease (interstitial nephritis)/ Idiopathic conditions (thin glomerular basement membrane disease or benign familial hematuria) Trauma/ Tumor/ TB/ Toxins

Answer 125

``` DAVID: Diabetes mellitus Amyloidosis Vasculitis Infections Drugs ```

Answer 126

proteinuria over 3g in 24 hrs | hypoalbuminaemia

Answer 127

visible haematuria is basically never glomerular damage, much more likely to be renal tract e.g. bladder cancer. glomerular damage will usually cause microscopic haematuria.

Answer 128

Pre-renal renal failure (70%) Causes: hypovolaemia/sepsis (most common AKI cause), renovascular disease Suggested by: history, hypotension, ↑urea greater than ↑creatinine Investigation: Fluid volume assessment Renal artery Doppler (if suspect renovascular disease) Treatment: IV fluid resuscitation Complications: acute tubular necrosis (ATN)

Answer 129

Intrinsic renal failure (20%) Causes: ATN (ischaemic or nephrotoxic), acute interstitial nephritis, acute glomerulonephritis Suggested by: causative drugs, renal hypoperfusion, other glomerulonephritis symptoms, haematuria & proteinuria Investigation: - Urine dipstick blood +++ protein +++ in glomerulonephritis in ATN, urine is usually bland - Urine protein-creatinine ratio (PCR; to quantify & monitor proteinuria if dipstick protein +ve; under 15mg/mmol = normal; over 300mg/mmol = nephrotic) NB. Urine PCR (mg/mmol) X 10 ≈ 24h protein loss (mg) Possible further tests - Nephritic screen (if suspect glomerulonephritis): ANA, ANCA, anti-GBM, complement, RhF, hepatitis serology, anti-phospholipid Ab - Renal biopsy (if: unexplained AKI; glomerulonephritis suspected; positive nephritic screen; persistent ATN; suspected tubule-interstitial nephritis) - Urgent renal biopsy (if suspect rapidly progressive glomerulonephritis – suggested by rapid loss of kidney function & worsening severe proteinuria and haematuria & nephritic syndrome) Myeloma screen (if old) Creatinine kinase (if suspect rhabdomyolysis) Serum bicarbonate Treatment: - Treat cause (e.g. hypoperfusion) + sodium bicarbonate (protects kidney) in ATN - Stop causative agent for acute interstitial nephritis - Immunosuppressants for glomerulonephritis Complications: irreversible renal damage

Answer 130

Post-renal renal failure (10%) Causes: urinary tract obstruction (prostate, stones, structure, tumour, blood clot etc) Suggested by: history, ↑urea = ↑creatinine Investigate: Renal tract USS Treatment: relieve obstruction e.g. catheterise (urinary/suprapubic) if urethral or nephrostomy if ureteric Complications: pyelonephritis (can progress to irreversible renal damage)

Answer 131

Commonest causes 1. Diabetes (secondary glomerular disease) 2. Chronic hypertension 3. Chronic glomerulonephritis diseases (e.g. vasculitidies) 4. Others e.g. PKD, drugs ``` Determining cause History Urine dipstick Renal USS Renal biopsy if required ``` Management Manage cause General measures: fluid restriction, reduce protein intake, ACE-inhibitor Treat complications: hypertension, oedema, anaemia, renal bone disease, hyperkalaemia, hyperlipidaemia Dialysis (when GFR under15) When to refer ITU: refractory hyperkalaemia, refractory metabolic acidosis, pulmonary oedema, worsening uraemia Nephrologist: AKI ?cause, AKI grade 3/4, suspected glomerulonephritits, not improving, CKD grade 4/5, previous renal transplant Urologist: urinary tract obstruction

Answer 132

``` When to dialyse Mnemonic: AEIOU Intractable…. Acidosis pH under 7.1 Electrolyte abnormalities (hyperkalaemia, hyponatraemia, hypercalcaemia) K+over 6.5 or ECG changes ``` Intoxicants (methanol, lithium, salicism) Overload Acute pulmonary oedema Uraemia urea over 60 or pericarditis or uraemic syn In chronic renal failure, regular dialysis is required when the GFR is under15ml/minute

Answer 133

divide by hypovolaemic, euvolaemic, oedematous. 1 - hypovolaemic . sodium has been lost and water follows. - divide causes by urinary sodium - if urinary sodium is over 20 then the sodium has been lost from the kidneys = diuretics, addisson's (increase K), kidney injury, osmotic diuresis. - if urinary sodium is under 20 then the sodium has been lost from elsewhere - D and V, fistulae, burns 2 - euvolaemic - water has been gained but the sodium load has remained the same. - divide by urinary sodium/osmolality - if urine sodium is over 40 or osmo over 100 then the H2O has been gained from the kidneys. = SIADH, hypothyroidism, glucocorticoid insufficiency. - if urine sodium under 40 or osmo under 100 then H20 has been gained from elsewhere. = H2O intoxication. 3 - oedematous - LOW Na+ CAUSED BY EXCESS ADH RELEASED SECONDARY TO INTRAVASCULAR FLUID DEPLETION (DUE TO EXTRAVASATION) Congestive cardiac failure Hypoalbuminaemia (i.e. liver disease or nephrotic syn)

Answer 134

``` Investigation Plasma osmolality (to confirm if true hyponatraema) Low = true Normal = false (‘pseudohyponatraemia’ due to high lipids/protein) High = dilutional (due to high glucose/ alcohols/ mannitol) ``` Urinary sodium and osmolality (to confirm if the problem is occurring in the kidneys or elsewhere) Specific tests to confirm specific causes e.g. Addison’s disease: Synacthen (synthetic ACTH) test or 9am cortisol screening test SIADH: confirmed by combination of low plasma osmolality (under275) and high urine osmolality (over100) Hypothyroidism: TFTs Management Treat cause Sodium correction Seizures/coma: senior could give hypertonic saline Hypovolaemic: replace lost fluid with 0.9% saline Euvolaemic: correct cause ± slow 0.9% saline IV, e.g. 1L/8-10hours If SIADH or oedematous: fluid restrict to 1 litre/day (excess H2O causes dilutional hyponatraemia) and consider demeclocycline for fluid restriction-resistant SIADH NB. correct chronic hyponatraemia slowly (risk of osmotic demyelination

Answer 135

Causes Normovolaemia = iatrogenic (e.g. excess IV crystalloids, sodium containing drugs) Hypovolaemia - Producing small volumes of concentrated urine (normal response to hypovolaemia) = Fluid loss (i.e. diarrhoea/vomiting, burns) - Not producing small volumes of concentrated urine (abnormal response to hypovolaemia) = Diabetes insipidus (urine osmolality under 750 + serum osmolality over 300) (i.e. kidneys not reabsorbing any H2O) or = Osmotic diuresis (e.g. DKA) or hypoaldosteronism (kidneys loosing H20 and solutes) Investigation Urine & serum osmolality Fluid deprivation test to confirm diabetes insipidus Management Treat cause Sodium correction Hypovolaemic (high sodium usually due to fluid loss): 0.9% saline 1L/6hours to correct hypovolaemia Euvolaemic: 5% dextrose 1L/6hours NB. correct chronic hypernatraemia slowly (risk of osmotic demyelination)

Answer 136

Management Severe (under 1.9mmol/L or symptomatic): calcium gluconate 10ml 10% IV over 30mins – should be diluted: 1ml 10% calcium gluconate to 4ml normal saline or 5% dextrose – may be repeated until asymptomatic and can be followed by an infusion if required (100ml 10% calcium gluconate in 1L dextrose or saline at 50-100ml/h) Mild (over 1.9mmol/L and asymptomatic): calcium supplements (e.g. Sandocal 1000 BD) Treat cause e.g. in vitamin D deficiency, load with 100,000 units colecalciferol STAT and give Adcal-D3 maintenance

Answer 137

Management Treat cause Replace fluid deficit and keep patient very well hydrated (continuous 0.9% saline at 1L/4-6h) If severe (over 3.5mmol/L or symptomatic – a medical emergency): also bisphosphonate e.g. pamidronate 30-90mg IV depending on severity (one off dose)

Answer 138

``` Causes: Excess loss: - Diuretics - Severe diarrhoea - DKA ``` Poor nutrition / alcoholism Most in bone and cells, therefore tends to reduce if calcium or potassium are low Management: 5grams (20mmol) IV magnesium in 50ml 0.9% saline over 5 hours Poor evidence base for oral replacement Dealing with concurrent electrolyte abnormalities - Correct hypomagnesemia before concurrent hypokalaemia, hypophosphatemia and hypocalcaemia if possible - Do not give IV magnesium and IV phosphate at the same time (can precipitate as magnesium phosphate)

Answer 139

``` Causes Vitamin D deficiency Refeeding syndrome Primary hyperparathyroidism Poor nutrition / alcoholism ``` Management PO: phosphate-sandoz 2 tablets TDS x 3/7 IV: sodium glycerophosphate 10mmol in 500ml over 12 hours Do not give if hypercalcaemic or oliguric

Answer 140

Acute kidney injury (AKI) = rise in serum creatinine over 50% from baseline, or urine output under 0.5ml/kg/h for 6 hours Determine if it is pre-renal, renal or post-renal ``` ALL patients need: Urine dipstick (interpreted in context of history) ``` Bloods (including FBC ± haematinics, U&Es, CRP, Ca2+, PO4 3-, PTH) VBG (check for: metabolic acidosis & low bicarbonate – may need weak bicarbonate infusion; and hyperkalaemia) Accurate fluid balance chart (requires catheterisation) Stopping of any renal-excreted drugs

Answer 141

Differentiating between IgA nephropathy and post-streptococcal 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 less complement less blood longer interval

Answer 142

The patient in this scenario has post-streptococcal glomerulonephritis. The GP in this scenario correctly diagnosed impetigo in this patient. Impetigo is most commonly caused by either Staphylococcus aureus or Streptococcus pyogenes. Streptococcal infections, most commonly of the skin or pharynx, can result in a condition known as post-streptococcal glomerulonephritis. The exact mechanism is unclear, but it is believed to be a type III hypersensitivity reaction, wherein immune complexes become lodged in the glomerular basement membrane and compliment activation results in destruction of this membrane. There is usually a classical clinical presentation in these patients, so renal biopsy is not needed in the majority of cases. Other investigations may reveal there to be an elevated Anti-streptolysin O titre and low complement levels (C3) in the blood. ``` Signs and symptoms may include: Haematuria Oliguria Oedema Hypertension General symptoms such as fever, headache, anorexia, nausea and vomiting, pallor etc ``` Post-streptococcal glomerulonephritis Post-streptococcal glomerulonephritis 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 most commonly affected. ``` Features general: headache, malaise haematuria nephritic syndrome hypertension low C3 raised ASO titre ``` Renal biopsy features 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

Answer 143

Over 50% of renal transplant patients have a significant infection within the first 12 months of having a renal transplant. At the time of transplant the CMV-serological status of the donor and recipient are noted. The highest risk is seen in CMV-seronegative recipients who receive a kidney from a CMV-seropositive donor. These patients are usually given antiviral prophylaxis. Cytomegalovirus tend to be seen after four weeks as before this time the immune system has not been fully affected by the immunosuppressants. Cytomegalovirus Cytomegalovirus (CMV) is one of the herpes viruses. It is thought that around 50% of people have been exposed to the CMV virus although it only usually causes disease in the immunocompromised, for example people with HIV or those on immunosuppressants following organ transplantation. Pathophysiology infected cells have a 'Owl's eye' appearance due to intranuclear inclusion bodies Patterns of disease Congenital CMV infection features include growth retardation, pinpoint petechial 'blueberry muffin' skin lesions, microcephaly, sensorineural deafness, encephalitiis (seizures) and hepatosplenomegaly CMV mononucleosis infectious mononucelosis-like illness may develop in immunocompetent individuals CMV retinitis common in HIV patients with a low CD4 count (

Answer 144

Ultrasound is the screening test for adult polycystic kidney disease Genetic testing is still not routinely recommended for screening family members Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively The screening investigation for relatives is abdominal ultrasound: Ultrasound diagnostic criteria (in patients with positive family history) two cysts, unilateral or bilateral, if aged 60 years

Answer 145

``` Drugs to avoid in renal failure antibiotics: tetracycline, nitrofurantoin NSAIDs lithium metformin ```

Answer 146

Drugs likely to accumulate in chronic kidney disease - need dose adjustment most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin digoxin, atenolol methotrexate sulphonylureas furosemide opioids

Answer 147

Drugs relatively safe - can sometimes use normal dose depending on the degree of chronic kidney disease antibiotics: erythromycin, rifampicin diazepam warfarin

Answer 148

lenticonus: protrusion of the lens surface into the anterior chamber seen in alport

Answer 149

Collecting an ACR sample by collecting a 'spot' sample it avoids the need to collect urine over a 24 hour period in order to detect or quantify proteinuria should be a first-pass morning urine specimen if the initial ACR is greater than 30 mg/mmol and less than 70 mg/mmol, confirm by a subsequent early morning sample. If the initial ACR is greater than 70 mg/mmol a repeat sample need not be tested Interpreting the ACR results in non-diabetics an ACR greater than 30 mg/mmol is considered clinically significant proteinuria in diabetics microalbuminuria (ACR greater than 2.5 mg/mmol in men and ACR greater than 3.5 mg/mmol in women) is considered clinically significant

Answer 150

Factors which may affect the result pregnancy muscle mass (e.g. amputees, body-builders) eating red meat 12 hours prior to the sample being taken

Answer 151

systematic reviews have yielded some guidelines on pain relief: 1 - single doses of NSAIDS and opioids provide pain relief in acute renal colic. 2 - NSAIDS have a greater effect and reduce the likelihood of needing further analgesia 3 - opioids esp pethidine are associated with higher risk of vomiting 4 - NSAIDS are therefore recommended above opioids. 5 - if opioids need to be used e.g. due to NSAID CIs or ease of titratability then pethidine should be avoided. the scenario here used diclofenac 100mg PR

Answer 152

In the acute phase after the relief of an obstruction, the kidneys kick back into action by producing a lot of urine: up to 1L within the fi rst hour. It is therefore essential to provide concurrent rehydration therapy to avoid immediate dehydration. During this phase of diuresis, sodium and bicarbonate will also be lost in large quantities, so it is also important to keep a close eye on electrolyte levels and replace where necessary. If the catheter does not relieve his distended abdomen, then imaging would be required ( A and E ). Given his chronic prostate problem, it would also be important to perform a rectal examination ( B ) and, once the catheter has been in situ for some time, to check serum prostate surface antigen. One-off doses of antibiotics ( C ) can be given at the time of catheterization as prophylaxis but should not be continued without good reason.

Answer 153

Whilst the serum creatinine is important in the assessment of renal functionit does not tell the whole story. For renal physicians, much more vitalare the urine output, the serum bicarbonate, and the creatinine clearance(CrCl). CrCl gives a truer picture of renal function as it takes into account the patient’s age and weight. It is important to remember that creatinineis a breakdown product of creatine phosphate in muscle and is thereforedependent on the patient’s muscle mass. Therefore, when trying to makesense of the serum creatinine, always pay attention to the build of the patient: 115 μ mol/L may produce a CrCl within the normal range for a young man who weighs 120kg, but in this woman with an eating disorder who weighs only 25kg, it actually refl ects moderate renal impairment

Answer 154

This, unfortunately, is an all too common scenario in clinical practice. A fall with subsequent prolonged immobility is enough to cause considerable muscle breakdown in an older person. This can be measured via serum creatine kinase on a standard biochemistry blood test. One of the breakdown products of muscle, myoglobin is particularly harmful to kidneys and in a poorly hydrated older person who may already be unwell— hence the fall—is highly likely to precipitate an acute kidney injury. If the renal failure can be directly attributed to the raised CK, the diagnosis is rhabdomyolysis. ``` A serum troponin ( E ) will be hard to make sense of as it will be falsely elevated in renal failure. If in the setting of diarrhoea and renal failure then it is important to consider clotting ( D ) and platelet function, as haemolytic- uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are both rare but important diagnoses not to miss. An ESR ( C ) would add little to this case—a CRP would be more useful in assessing the intercurrence of an acute infection. In all cases of acute renal failure it is important to measure and correct electrolytes, but the level of calcium ( B ) does not hold the key to the diagnosis here. ```

Answer 155

IgA nephropathy is the commonest explanation for macroscopic haematuria in the western world. Most commonly aff ecting young men, it happens due to overproduction of IgA (classically in response to a throat infection), which then forms immune complexes that lodge in mesangial cells. in the glomerulus. This man has developed haematuria after an upper respiratory tract infection, a classical way for IgA nephropathy or Berger’s disease—the commonest glomerulonephritis in the world, characterized by IgA deposition in the mesangium—to take hold.

Answer 156

A Antibodies binding the kidney’s basement membrane. A This is the process behind Goodpasture’s disease, which is very rare and also presents with haemoptysis (as antibodies also bind alveolar membranes).

Answer 157

This would be the biopsy fi nding in a rapidly progressive glomerulonephritis. It would present with acute renal failure following either vasculitic or infective processes E Necrotizing granulomatous inflammation in Bowman’s capsule

Answer 158

Nephritic syndrome is proteinuria, haematuria, oliguria, and hypertension with rising urea and creatinine. In this case, it is most probably due to a post-streptococcal glomerulonephritis

Answer 159

Acute tubular necrosis is due to either ischaemia, drugs, or toxins, and presents as acute renal failure.

Answer 160

Interstitial nephritis can occur secondary to drugs or infections and presents with either progressive renal impairment, acute renal failure, or hypertension.

Answer 161

PC - intermittent right-sided abdominal pain for the last 5 days. It has struck several times for short periods, always focused on the right side of the back, before moving towards his groin. When it comes, it is severe—enough to wake him from sleep on one occasion—and causes him to roll around to try to get comfortable This is a typical history of colic in the distribution of the right ureteric system. Supportive evidence should be sought via haematuria on urinalysis and a plain X-ray to screen for any obvious calculi before proceeding to an intravenous urogram (IVU).

Answer 162

Amylase + CT scan of the abdomen

Answer 163

Digital rectal examination + abdominal X-ray

Answer 164

After basic blood tests and a convincing history, the only way to diagnose an acute appendicitis is to proceed to theatre. Full blood count + laparotomy

Answer 165

Liver function tests + liver ultrasound scan

Answer 166

The consultant is concerned that his patient has been receiving metformin while her kidneys are potentially poorly perfused: it is in this setting that the drug is very occasionally known to cause lactic acidosis (displayed by the laboured Kussmaul breathing, which tries to blow off the excess acid). An arterial blood gas should be performed immediately with the anion gap calculated (lactic acidosis causes a metabolic acidosis with a raised anion gap).

Answer 167

The skeleton history along with the urine dip result is suggestive of systemic lupus erythematosus (SLE) with concurrent lupus-induced nephritis. In cases such as this where there is proteinuria, it is the glomerular fi ltrating apparatus that has been damaged, leading to a chronic leak of protein and/or blood. The treatment is threefold: reduce proteinuria with angiotensin-converting enzyme (ACE) inhibitors (and/or angiotensin II receptor blockers), manage hypertension (proteinuria is an independent risk factor for hypertension), and slow the renal disease process via immunosuppression (steroids ± cyclophosphamide).

Answer 168

This is an enzyme inhibitor and potentiates the eff ects of warfarin. It is widely used as fi rst-line treatment in urinary tract infections but is often forgotten as a source of important drug interactions. Although studies have failed to demonstrate an interaction with coumarin anticoagulants (such as warfarin) and penicillins, experience from anticoagulant clinics suggests that the INR can be altered by broad-spectrum antibiotics such as amoxicillin.

Answer 169

Although low-molecular-weight heparin ( B ) can be given in severe renal impairment, monitoring of anti-factor Xa would be required because the patient would be at increased risk of bleeding. Therefore, unfractionated heparin would be a more appropriate choice.

Answer 170

Although all of this man’s parameters have deteriorated slightly, it is only the anaemia that needs investigation at this stage. NICE guidance states that management of anaemia should be considered in chronic kidney disease (CKD) in those with Hb

Answer 171

This man is describing visible or macroscopic haematuria. Any one single episode of macroscopic haematuria should be considered significant. It is important to rule out transient causes (urinary tract infection or drug side eff ects) and to then test for urea and electrolytes and urinary protein:creatinine ratio before referring to either a urologist or a nephrologist. He has developed haematuria soon after what sounds like an upper respiratory tract infection—this is classical for IgA nephropathy in which overproduction of IgA leads to immune complexes that deposit in mesangial cells. A If this man were older, then bladder carcinoma would be the most likely diagnosis. It presents with painless macroscopic haematuria and becomes more likely with age, especially if certain environmental risk factors are in place (smoking; amines in some dyes, paints, solvents, and textiles). It would need to be excluded in this case (via an ultrasound scan and cystoscopy) but is not the most likely diagnosis. C Nephrotic syndrome is by defi nition proteinuria (>3g/24h), hypoalbuminaemia (

Answer 172

In this case, given the vomiting and the rapid increase in urea, a gastrointestinal (GI) bleed is the most likely cause. Although a rising urea usually represents dehydration ( A ), this would normally be accompanied by a rising creatinine. The fact that it rises on its own suggests an increase in circulating protein levels—i.e. by digested blood—rather than failure of the kidneys. Even without a past medical history of GORD or stomach ulcers, GI bleeds are common after periods of physiological stress such as surgery or time in intensive care. Although the haemoglobin is stable, it often takes longer for this to fall than it does for the urea to rise. However, he needs to be crossmatched for at least 2 units of blood and listed for an endoscopy. Most surgical teams would be keen to perform a CT abdomen in this situation, as a post-operative collection ( B ) would necessitate further emergency surgery or at the least a radiologically inserted drain. Both PEs ( D ) and chest infections ( C ) are common after surgery, but other than the tachycardia there are no real indications of either in this case.

Answer 173

Microalbuminuria should be tested for every 6 months in type 2 diabetes for two reasons: it gives early warning of impending renal disease and is an independent risk factor for cardiovascular disease. Therefore, regardless of the blood pressure, those who have it should start immediately on an angiotensin-converting enzyme (ACE) inhibitor. These days it can be accurately assessed by sending a single urine sample for albumin:creatinine ratio testing.

Answer 174

This is a diffi cult but common scenario. As the woman has no capacity, she cannot refuse treatment (unless there is formal documentation in the form of an advance directive). The doctors need to weigh up what is in her best interests. In the short term, that should normally include relieving pain by the minimal restraint possible: in this case, this may entail giving low-dose sedation in order to insert the catheter. In the medium term, contacting her relatives comes in to play: to guide the doctors as to what may more generally be in the woman’s best interests, it would be useful to know how she had been over the preceding months, whether she had expressed thoughts about medical interventions, whether she was depressed or indeed suicidal. Armed with this information, they would have some basis for withholding treatment further down the line should she continue to oppose it.

Answer 175

This type of glomerular damage is associated with autoimmune conditions such as rheumatoid arthritis, as well as some of the drugs used to treat them. It tends to present in adults with nephrotic syndrome.

Answer 176

This is damage to the glomerulus (actually an infl ammatory reaction) occurring classically 1–12 weeks after a streptococcal infection of the skin or throat. It presents as nephritic syndrome but in most cases requires only supportive therapy.

Answer 177

This man with currently untreated HIV infection is presenting with nephrotic syndrome. This is most likely to herald scarring of certain areas of glomeruli. In the setting of HIV, focal segmental glomerulosclerosis is known as HIV-associated nephropathy (HIVAN), a serious complication of advanced HIV that will need some or all of highly active anti-retroviral treatment (HAART), angiotensin-converting enzyme (ACE) inhibitors, steroids, and immunosuppression, but may still result in end-stage renal failure.

Answer 178

This young man has varied symptoms—epistaxis with nasal crusting, sinusitis, and scleritis—which are suggestive of a vasculitic process. Concurrent with acute renal failure, this raises the possibility of rapidly progressive glomerulonephritis, the most aggressive of all glomerular diseases, with the potential to progress towards end-stage renal failure in a matter of days. If these kind of symptoms are present in a young person with acute renal failure, it is vital to perform a full autoimmune screen prior to involving the renal physicians, who may opt for an urgent biopsy.

Answer 179

IgA nephropathy (commonly occurring after virus infection) features immune complex deposition in mesangial cells, which respond by proliferating.

Answer 180

Plasma potassium levels are regulated by a number of factors including aldosterone, acid-base balance and insulin levels. Metabolic acidosis is associated with hyperkalaemia as hydrogen and potassium ions compete with each other for exchange with sodium ions across cell membranes and in the distal tubule. ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRS leading to a sinusoidal pattern and asystole ``` Causes of hyperkalaemia: acute renal failure drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers, spironolactone, ciclosporin, heparin** metabolic acidosis Addison's rhabdomyolysis massive blood transfusion ``` ``` Foods that are high in potassium: salt substitutes (i.e. Contain potassium rather than sodium) bananas, oranges, kiwi fruit, avocado, spinach, tomatoes ``` *beta-blockers interfere with potassium transport into cells and can potentially cause hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are sometimes used as emergency treatment **both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is thought to be caused by inhibition of aldosterone secretion

Answer 181

This patient is hyperkalaemic and has associated ECG changes (peaked T waves in the anterior leads and bradycardia). Bradycardia in such patients is a worrying sign as asystole may occur. The first priority in this patient is to stabilise the myocardium with intravenous calcium gluconate. Hyperkalaemia: management Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors). Management may be categorised by the aims of treatment Stabilisation of the cardiac membrane intravenous calcium gluconate Short-term shift in potassium from extracellular to intracellular fluid compartment combined insulin/dextrose infusion nebulised salbutamol Removal of potassium from the body calcium resonium (orally or enema) loop diuretics dialysis

Answer 182

Parathyroid hormone levels are useful as malignancy and primary hyperparathyroidism are the two most common causes of hypercalcaemia. A parathyroid hormone that is normal or raised suggests primary hyperparathyroidism. Hypercalcaemia: causes The most common causes of hypercalcaemia are malignancy (bone metastases, myeloma, PTHrP from squamous cell lung cancer) and primary hyperparathyroidism ``` Other causes include sarcoidosis* vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: thiazides, calcium containing antacids dehydration Addison's disease Paget's disease of the bone** ``` *other causes of granulomas may lead to hypercalcaemia e.g. Tuberculosis and histoplasmosis **usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation

Answer 183

In 2014 NICE updated their guidelines on lipid modification. This proved highly controversial as it meant that we should be recommending statins to a significant proportion of the population over the age of 60 years. Anyway, the key points of the new guidelines are summarised below. Primary prevention - who and how to assess risk A systematic strategy should be used to identify people aged over 40 years who are likely to be at high risk of cardiovascular disease (CVD), defined as a 10-year risk of 10% or greater. NICE recommend we use the QRISK2 CVD risk assessment tool for patients aged = 85 years are at high risk of CVD due to their age. QRISK2 should not be used in the following situations as there are more specific guidelines for these patient groups: type 1 diabetics patients with an estimated glomerular filtration rate (eGFR) less than 60 ml/min and/or albuminuria patients with a history of familial hyperlipidaemia NICE suggest QRISK2 may underestimate CVD risk in the following population groups: people treated for HIV people with serious mental health problems people taking medicines that can cause dyslipidaemia such as antipsychotics, corticosteroids or immunosuppressant drugs people with autoimmune disorders/systemic inflammatory disorders such as systemic lupus erythematosus

Answer 184

Measuring lipid levels When measuring lipids both the total cholesterol and HDL should be checking to provide the most accurate risk of CVD. A full lipid profile should also be checked (i.e. including triglycerides) before starting a statin. The samples does not need to be fasting. In the vast majority of patient the cholesterol measurements will be fed into the QRISK2 tool. If however the patient's cholesterol is very high we should consider familial hyperlipidaemia. NICE recommend the following that we should consider the possibility of familial hypercholesterolaemia and investigate further if the total cholesterol concentration is > 7.5 mmol/l and there is a family history of premature coronary heart disease. They also recommend referring people with a total cholesterol > 9.0 mmol/l or a non-HDL cholesterol (i.e. LDL) of > 7.5 mmol/l even in the absence of a first-degree family history of premature coronary heart disease.

Answer 185

Interpreting the QRISK2 result Probably the headline changes in the 2014 guidelines was the new, lower cut-off of 10-year CVD risk cut-off of 10%. NICE now recommend we offer a statin to people with a QRISK2 10-year risk of >= 10% Lifestyle factors are of course important and NICE recommend that we give patients the option of having their CVD risk reassessed after a period of time before starting a statin. Atorvastatin 20mg should be offered first-line.

Answer 186

Special situations Type 1 diabetes mellitus NICE recommend that we 'consider statin treatment for the primary prevention of CVD in all adults with type 1 diabetes' atorvastatin 20 mg should be offered if type 1 diabetics who are: → older than 40 years, or → have had diabetes for more than 10 years or → have established nephropathy or → have other CVD risk factors Chronic kidney disease (CKD) atorvastatin 20mg should be offered to patients with CKD increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved and the eGFR > 30 ml/min. If the eGFR is

Answer 187

Secondary prevention All patients with CVD should be taking a statin in the absence of any contraindication. Atorvastatin 80mg should be offered first-line.

Answer 188

Follow-up of people started on statins NICE recommend we follow-up patients at 3 months repeat a full lipid profile if the non-HDL cholesterol has not fallen by at least 40% concordance and lifestyle changes should be discussed with the patient NICE recommend we consider increasing the dose of atorvastatin up to 80mg

Answer 189

Lifestyle modifications These are in many ways predictable but NICE make a number of specific points: Cardioprotective diet total fat intake should be

Answer 190

This patient has developed xanthelasma secondary to hypercholesterolaemia. Hyperlipidaemia: xanthomata Characteristic xanthomata seen in hyperlipidaemia: Palmar xanthoma remnant hyperlipidaemia may less commonly be seen in familial hypercholesterolaemia Eruptive xanthoma are due to high triglyceride levels and present as multiple red/yellow vesicles on the extensor surfaces (e.g. elbows, knees) Causes of eruptive xanthoma familial hypertriglyceridaemia lipoprotein lipase deficiency Tendon xanthoma, tuberous xanthoma, xanthelasma familial hypercholesterolaemia remnant hyperlipidaemia Xanthelasma are also seen without lipid abnormalities ``` Management of xanthelasma, options include: surgical excision topical trichloroacetic acid laser therapy electrodesiccation ```

Answer 191

Out of the list above sertraline is the medication known to cause hyponatraemia. Other common drug causes of low sodium include: chlorpropramide, carbamazepine, selective serotonin reuptake inhibitor (SSRI) antidepressants, tricyclic antidepressants, lithium, MDMA/ecstasy, tramadol, haloperidol, vincristine, desmopressin, fluphenazine. Hyponatraemia Hyponatraemia may be caused by water excess or sodium depletion. Causes of pseudohyponatraemia include hyperlipidaemia (increase in serum volume) or a taking blood from a drip arm. Urinary sodium and osmolarity levels aid making a diagnosis Urinary sodium > 20 mmol/l Sodium depletion, renal loss (patient often hypovolaemic) diuretics Addison's diuretic stage of renal failure Patient often euvolaemic SIADH (urine osmolality > 500 mmol/kg) hypothyroidism Urinary sodium

Answer 192

* Bone metastases | * Hyperparathyroidism

Answer 193

* Osteomalacia | * Renal failure

Answer 194

5. Metabolic component: What is the bicarbonate level/base excess? bicarbonate under 22 mmol/l (or a base excess under - 2mmol/l) suggests a metabolic acidosis (or renal compensation for a respiratory alkalosis) bicarbonate over 26 mmol/l (or a base excess over + 2mmol/l) suggests a metabolic alkalosis (or renal compensation for a respiratory acidosis)

Answer 195

``` BMI Old classification NICE classification under 18.5 Underweight Underweight 18.5 - 24.9 Normal Normal 25 - 29.9 Overweight Overweight 30 - 34.9 Obese Obese I 35 - 39.9 Clinically obese Obese II over 40 Morbidly obese Obese III ```

Answer 196

The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days Other options include: calcitonin - quicker effect than bisphosphonates steroids in sarcoidosis There is a limited role for the use of furosemide in hypercalcaemia. It may be useful in patients who cannot tolerate aggressive fluid rehydration

Answer 197

Albumin levels are often reduced following an acute phase response Acute phase proteins ``` Acute phase proteins CRP procalcitonin ferritin fibrinogen alpha-1 antitrypsin caeruloplasmin serum amyloid A serum amyloid P component* haptoglobin complement ``` During the acute phase response the liver decreases the production of other proteins (sometimes referred to as negative acute phase proteins). Examples include: albumin transthyretin (formerly known as prealbumin) transferrin retinol binding protein cortisol binding protein *plays a more significant role in other mammals such as mice

Answer 198

Parathyroid hormone is the single most useful test in determining the cause of hypocalcaemia Hypocalcaemia: causes and management The clinical history combined with parathyroid hormone levels will reveal the cause of hypocalcaemia in the majority of cases Causes vitamin D deficiency (osteomalacia) chronic renal failure hypoparathyroidism (e.g. post thyroid/parathyroid surgery) pseudohypoparathyroidism (target cells insensitive to PTH) rhabdomyolysis (initial stages) magnesium deficiency (due to end organ PTH resistance) massive blood transfusion Acute pancreatitis may also cause hypocalcaemia. Contamination of blood samples with EDTA may also give falsely low calcium levels Management acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes intravenous calcium chloride is more likely to cause local irritation ECG monitoring is recommended further management depends on the underlying cause

Answer 199

Hyperlipidaemia: secondary causes Causes of predominantly hypertriglyceridaemia diabetes mellitus (types 1 and 2) obesity alcohol chronic renal failure drugs: thiazides, non-selective beta-blockers, unopposed oestrogen liver disease Causes of predominantly hypercholesterolaemia nephrotic syndrome cholestasis hypothyroidism

Answer 200

Acute intermittent porphyria (AIP) is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen. It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40 year olds. AIP is more common in females (5:1) ``` Features abdominal: abdominal pain, vomiting neurological: motor neuropathy psychiatric: e.g. depression hypertension and tachycardia common ``` Diagnosis classically urine turns deep red on standing raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks) assay of red cells for porphobilinogen deaminase raised serum levels of delta aminolaevulinic acid and porphobilinogen

Answer 201

Familial hypercholesterolaemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the gene which encodes the LDL-receptor protein. Clinical diagnosis is now based on the Simon Broome criteria: in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus: for definite FH: tendon xanthoma in patients or 1st or 2nd degree relatives or DNA-based evidence of FH for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels

Answer 202

Familial hypercholesterolaemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the gene which encodes the LDL-receptor protein. Management the use of CVD risk estimation using standard tables is not appropriate in FH as they do not accurately reflect the risk of CVD referral to a specialist lipid clinic is usually required the maximum dose of potent statins are usually required first-degree relatives have a 50% chance of having the disorder and should therefore be offered screening. This includes children who should be screened by the age of 10 years if there is one affected parent statins should be discontinued in women 3 months before conception due to the risk of congenital defects