Renal

Question 1

Obstructive uropathy - causes?

Answer 1

Kidney - calculus, chronic infection granulomatous, neoplasm, necrotising papillitis

Ureter - stricture, stenosis, kinks, chronic infection, congenital valve, retrocaval ureter, neoplasm, calculus, compression (nodes, tumour, abscess, haematoma), ureteritis cystica, ovarian vein syndrome, trauma

Bladder - ureterocele, neoplasm, diverticulum, calculus, foreign body, congenital neck obstruction, schistosomiasis,

Urethra - neoplasm, stricture, diverticulum, papilloma, meatal stenosis, BPH (men), prostatitis (men), prostate Ca (men), strangulation (men), phimosis (men)

Question 2

Presentation of renal colic

Answer 2

Loin to groin pain

Question 3

Types of renal calculi?

Answer 3

75% Ca Oxalate (phosphate)
15% Mg ammonium phosphate
10% uric acid or cysteine

Question 4

Risk factors for renal calculi?

Answer 4

Concentrated urine, hereditary, diet, co-morbidities (sarcoidosis, inflammatory bowel disease, cancer)

Question 5

Common sites of obstuction of ureter by kidney stone?

Answer 5

1. Ureterovesical junction
2. Crossing of iliac artery (mid ureter)
3. Ureteropelvic junction

Question 6

Possible routes of kidney infection?

Answer 6

Haematogenous vs Ascending

Question 7

Predisposing factors in acute pyelonephritits

Answer 7

Anomalies of kidney or ureter, calculi, obstruction at any level, DM, pregnancy, neurogenic bladder, instrumentation

Question 8

Clinical features of acute pyelonephritis

Answer 8

Bacteriuria (>100000/ml3)
Proteinuria absent or minimal
White cell casts and leukocytes

F>M
Tenderness at costovertebral angle
Tenesmus, pain/burning on urination
? Haemodynamic compromise

Question 9

Renal fusion types

Answer 9

1. Crossed ectopia with fusion.
2. S shaped sigmoid hidney
3. Pelvic cake/lump kidney
4. Horseshoe kidney - developing kidneys fuse usually with lower lobes, anterior to aorta, lies low in abdomen,. Most common fusion.

Fused kidneys are close to midline, have multiple renal arteries and are malrotated. Obstruction, stone formation and infection are potential complications.

Question 10

Wilm’s tumour

Answer 10

Nephroblastoma, characterisctic variegated structure with pseudocapsule. Almost exclusive to infants. Mass in loin/abdomen (ddx single cyst/PKD, large hydronephrosis, neuroblastoma).
Loss of weight, anaemia, haematuria, HTN
Mets late but LN, lungs, liver
In contrast to neuroblastoma where bone mets +++

Question 11

Surgical approach to the kidney

Answer 11

Lumbar - extraperitoneal, non muscle-splitting vertical incision on lateral back. For removing pelvic and upper urethral stones.

Lateral (flank) - extraperitoneal, patient positioned in lateral flexed position. For retrieving renal stones. Stressed skeleton and resp system as pt is in uncomfortable position

Anterior - midline, paramedian (extraperitoneal or transperitoneal), chevron

Question 12

Embryology - development of the urinary system

Answer 12

Initially intermediate mesoderm differentiates into nephrogenic tissue and forms a pronephros (doesn’t work and degenerates) and mesonephros (functions briefly) retroperitoneally. Definitive kidney develops from metanephric tissue into which ureteric bud grows and differentiates into renal pelvis, calyces and collecting duct.

Kidneys ascend from deep in the pelvis to posterior abdominal wall (always retroperitoneal). Hilum faces anterioly at first, but rotates 90* so that renal pelvis faces medially and renal vessels connect at the hilum

Question 13

Definition: Renal Hilus

Answer 13

Medial aspect of kidney containing the entrance to renal artery, vein and the renal pelvis

Question 14

Gross kidney anatomy - relation to outside

Answer 14

Stretch from T12 - L3
Right K lower then L because of liver

Kidney –> Fibrous capsule –> Perinephric fat –> Perinephric/Perirenal fascia (also encloses andrenal gland)

Renal cortex - outer bit which contains all glomeruli and medulla contains loops of hence, vasa recta and final collecting ducts

Question 15

Innervation of the bladder

Answer 15

S3 S4 S5

Question 16

Cortical vs Juxtamedullary Nephrons

Answer 16

Cortical nephrons occur throughout renal cortex and have short loops of hence
JM nephrons begin need corticomedullary junction and have long loops of hence descending deep into medulla which can highly concentrate urine.
Cortical > JM 7:1

Question 17

In which cell is EPO made?

Answer 17

Fibroblast-like interstitial cells of the kidney

Question 18

What is the role of mesangial cells in the glomerulus?

Answer 18

Provide a scaffold to support the many capillaries in Bowman’s capsule. Have contractile and phagocytic properties

Question 19

What are the 3 components of the glomerular filtration barrier?

Answer 19

1. Endothelial cells - thin with 70nm pores filled with -ve charges podocalyxin
2. GBM - specialised capillary basement membrane. 2 layers made up of type IV collagen, fibronectin, heparin sulphate proteoglycans, lamina, podocalyxin. TIV collage forms helical strands arranged into 3d framework to which everything else is attached.
3. Epithelial cells of Bowman’s capsule (podocytes) - long projections with foot processes which attach to GBM. Foot processes form mesh with filtration slits of 25-65 nm. Key selective barrier preventing passage of large molecules

Question 20

Renal Hx and Examination

Answer 20

Esp –> Drugs, FHx, Infection, PMHx
Urine appearance
Exam –> Abdo/Cardiac. (Note BP, JVP, Fundoscopy, Renal bruit, oedema)

Question 21

Urine microscopy - casts

Answer 21

Microscope with phase contrast to examine fresh urine. Centrifuge if possible .
RBC - Can arise from anywhere in tract but deformed (dysmorphic) indicates glomerular bleeding (glomerulonephritis)
RBC casts - glomerulonephritis
WC - inflammation. Polymorphonuclear cells - infection. Eosinophils/lymphocytes - interstitial nephritis
WC casts - acute bacterial infection
Waxy casts - large, occur in dilated tubules in CRF
Hyaline casts - normal
Granular casts - normal
Crystals - variable significance as can form after collection. Ideally ASAP >37*C

Question 22

At what eGFR level do you expect urea and creatinine to rise?

Answer 22

About 30mL/min

Question 23

Why does creatinine clearance slightly overestimate GFR?

Answer 23

GFR (vol of filtrate formed in 1 minute) estimated by measuring plasma and urine concentration of a substance and the urine flow rate per minute.
Tubular creatinine secretion overestimates GFR when creatinine clearance is used to estimate GFR
Inulin is better, as is very inert, but only used for research purposes.
eGFR often estimated with algorithms using plasma Cr, age, weight, gender

Question 24

Renal anti-immune profile

Answer 24

ANCA - vasculitis
Anti-GMB Goodpasture’s
ANA/anti ds-DNA, low complement levels - SLE

Question 25

What is the approach for renal biopsy?

Answer 25

Percutaneous biopsy performed with long cutting needle through back under US guidance. Tissue examined by light microscopy, immunostaining, electron microscopy

Question 26

Causes of ARF (in %), mortality, prognosis

Answer 26

Pre-renal, inadequate perfusion (50-65% cases) Renal, intrinsic renal disease (20-35% cases) Post-renal, obstructive (15% cases) Overall mortality 30-70% Prognosis --> 60% regain normal renal function, 15-30% have impairment, 5-10% ESRF

Question 27

What is the pathophysiology of ATN?

Answer 27

Most AKI results from ATN, usually 2* to renal hypo perfusion, often in the context of sepsis / nephrotoxic drugs 1. Renal ischaemia causes swelling of tubules 2. Tubular cell death and shedding into lumen causes blockage, raising tubular pressure, stopping glomerular filtration. 3. Swollen tubules compress nearby vasa recta, further reducing perfusion Ischaemia alos results in production of free radicals which further damage cells and mitochondria, used up ATP means Ca cannot be explode from cells, and high IC Ca interferes with cell metabolism. Apoptosis and necrosis of tubular cells are common

Question 28

Pre-renal causes of ARF

Answer 28

Inadequate cardiac function, circulatory volume depletion, obstruction of arterial blood supply. Resulting renal ischaemia causes ATN

Question 29

Name 10 nephrotoxic agents

Answer 29

Aminoglycosides - tubular toxin NSAIDs - inhibit Pg mediated vasodilation ACEi/ARB - reduce efferent arteriole tone Cephalosporins - tubular toxin Amphotericin B - vasoconstriction and membrane damage Aciclovir/Indinavir - precipitate in tubules Ciclosporin/Tacrolimus - indirect vasoconstriction Radiocontrast - vasoconstriction PPIs - allergic tubulointerstitial nephritis

Question 30

RIFLE criteria for ARF

Answer 30

Classification of severity of ARF looking at serum Cr and UO. To be used after optimal state of hydration achieved and easily reversible causes (obstruction) excluded RISK - Cr increase x1.5 baseline OR UO <0.5mL/kg/h >6hours INJURY - Cr increase x2 baseline OR UO <0.5mL/kg/h >12h FAILURE - Cr increase x3 baseline OR UO <0.3mL/kg/h x24h or anuria >12h LOSS - persistent failure >4 weeks ESRD Correlates well with length of stay in ICU, hospital, mortality, renal recovery

Question 31

Name some tubular toxins

Answer 31

Heavy metals Contrast media Haemoglobin Myoglobin

Question 32

How does acute hypercalcaemia cause AFR?

Answer 32

Renal vasoconstriction and calcium phosphate precipitation in tubules

Question 33

How does myeloma cause ARF?

Answer 33

Light chain precipitation in tubules can cause case nephropathy and AKI

Question 34

What can cause crystals to form in tubules causing ARF?

Answer 34

Gout (hyperuricaemia), aciclovir, indinavir

Question 35

How do NSAIDs cause kidney damage?

Answer 35

Normally, tonic prostaglandin induced vasodilation or renal arterioles. NSAIDs inhibit Pg synthesis, leading to vasoconstriction. When coupled with volume depletion, vasoconstriction can be intense.

Question 36

What are the RF for NSAID induced kidney injury?

Answer 36

Volume depletion, diuretic use, pre-existing renal impairment, oedematous state (CCF, liver cirrhosis, nephrotic syndrome)

Question 37

Why is renal artery stenosis an absolute CI for ACEi?

Answer 37

In RAS, angII causes efferent arteriolar constriction to maintain GFR. ACEi/ARB block this constrictive drive, and cause a large fall in GFR

Question 38

Common features of AKI in hospital

Answer 38

BP dropping with time HR increasing with time Urine output falling Weight falling Drug chart contains NSAIDS, amino glycosides, ACEi/ARB, radiocontrast Most common culprits are fluid depletion, sepsis, drug toxicity (esp after surgery, trauma or burns)

Question 39

AKI in viva - investigations and basic management

Answer 39

1. Bloods tests - K levels, CK, anaemia, WCC, inflammatory markers, kidney function, immunology incl complement, ANCA, antiGBM, ANA & dsDNA, cultures 2. Urine - culture, microscopy, dipstick, Bence Jones proteins 3. USS KUB and Doppler 1. Electrolytes - U&E daily, restricted K, diuretics to prevent hyperkalaemia 2. Acid - severe acidosis with inadequate renal function must be treated with renal replacement therapy 3. Volume - regularly reassess, if necessary invasive monitoring, Daily insensible losses are 500ml + 500ml for every point of fever. Daily weights 4. Pulmonary oedema - sit patient up, high flow O2, if renal function give diuretics

Question 40

CI for renal replacement therapy

Answer 40

Hyperkalaemia, acidosis, pulmonary oedema, severe uraemia. Haemodialysis can be poorly tolerated by haemodynamically unstable patients. Continous haemofiltration is slower and better tolerated.

Question 41

Stages of CKD

Answer 41

1. eGFR >90 2. eGFR 60-80 3A. eGFR 45-59 3B. eGFR 30-44 4. eGFR 15-29 5. eGFR <15

Question 42

What are general management principles for CKD?

Answer 42

Weight loss (to a correct BMI), aggressive BP management, low salt intake, exercise, avoiding NSAID painkillers, reduced alcohol intake all beneficial

Question 43

What is the most commonly used formula to calculate eGFR, and in which patients do you need a correction

Answer 43

MDRD formula | Black african ethnicity patients have higher plasma Cr levels with equivalent renal function so eGFR multiplied x1.2

Question 44

What tests would you do if you suspected proteinuria?

Answer 44

Urine Dip At low levels urine albumin:creatinine ratio. In non DM pts, ACR .30mg/mmol indicated significant proteinuria. In DM, ACR >2.5mg/mmol in men or 3.5mg/mmol in women is significant At higher levels PCR can be used

Question 45

Define uraemic syndrome in ESRF

Answer 45

Refers to complications of CRF including anaemia, confusion, coma, asterixis, seizures, pericardial effusion, itch, renal bone disease. Requires renal replacement therapy

Question 46

What is the biochemical profile of renal bone disease?

Answer 46

Low Ca, high PO4, high PTH *Plasma Ca typically low in CRF unless tertiary hyperparathyroidism develops USS - small atrophied fibrotic kidneys

Question 47

Presentation of renal bone disease

Answer 47

Can cause bone pain, esp lower back, hips, legs. | Proximal myopathy and soft tissue calcification

Question 48

Differentiate high turnover vs low turnover renal bone disease and the causes

Answer 48

Most renal bone disease is high turnover. High PTH stimulating bone resorption and new bone has disordered collagen. Caused by inadequate fit D production and net renal phosphate retention. High PO4 further lowers Ca through CaPO4 deposition in soft tissue. Hypocalcaemia results in 2* hyperparathyroidism, which can become 3* In low turnover renal bone disease low PTH, causing osteomalacia with poorly mineralised bone. If Ca intake and plasma Ca high enough to suppress PTH.

Question 49

What will a radiograph of high turnover renal bone disease show? What will low turnover bone disease show?

Answer 49

High turnover - Subperiosteal resorption in the phalanges, erosion of phalangeal tufts, erosion of clavicle heads. Low turnover - multiple fracture or pseudo fractures (radiolucent cortical zones perpendicular to bone surface)

Question 50

What is the treatment of high turnover renal bone disease?

Answer 50

Reduced PO4 intake through diet modification and binding agents containing calcium, lanthanum or synthetic resins. High dose Vitamin D inhibits PTH secretion and bone turnover while increasing gut Ca absorption. Should reduce PTH to normal levels. If PTH does not fall, surgical removal of parathyroid glands. Dialysis may help to reduce acidosis

Question 51

Complications of ESRF - top to bottom

Answer 51

Anxiety, depression, seizures Anaemia, high BP, hypervolaemia, LVH, pericarditis, hyperlipidaemia, sexual dysfunction Vomiting, oesophagitis, pancreatitis Infertility Proximal myopathy, muscle cramps Peripheral neuropathy Immune dysfunction, tissue calcification, bleeding, itch, bone pain

Question 52

ESRF - general management

Answer 52

Dialysis / Transplantation Intake --> K restriction, PO4 restriction, Na restriction, H2O resriction PO4 binding agents, Vitamin D, EPO, BP control

Question 53

ESRF - haematological

Answer 53

Anaemia due to lack of EPO EPO replaced SC or IV, along with monitoring Fe, B9, B12 Increased bleeding time due to impaired platelet function. DDAVP increases vWf level and can be used to transiently reduce bleeding time. Efficient dialysis needed.

Question 54

ESRF - vascular Disease

Answer 54

Major cause of death. HTN due to Na and H2O retention leading to hypervolaemia. Dietary restriction. If renal function sufficient, furosemide. If not, control with dialysis. HTN which does not respond to reduction in body volume in 2* to +++ renin, and so ACEi/ARB or vasodilators may be useful.

Question 55

ESRF - skin

Answer 55

Pruritus is a very common complaint. Often with 2* or 3* hyperparathyroidism with CaPO4 crystal deposition under the skin. Control of PO4 levels and moisturising creams. Uraemic frost - precipitation of urea crystals on skin in severe uraemia.

Question 56

ESRF - GIT

Answer 56

Nausea and Vomiting, anorexia, heartburn, oesophagi tis, angiodysplasia common. Higher incidence of pancreatitis Taste disturbance - urine like smell to breath

Question 57

ESRF - Endocrine

Answer 57

Loss of libido, impotence, low sperm count and motility, reduced ovulation Loss of muscle mass in adults, growth retardation in children

Question 58

ESRF - Neurological and Psychiatric

Answer 58

Fatigue, diminished consciousness, coma if untreated. Neurological irritation - tremor, asterixis, agitation, meningism, myoclonus, inreased tone, ankle clonus, extensor plantars, seizures. Peripheral neuropathy - sensory and muscle. Usually symmetrical but can be single cranial nerve palsy. Sleep disturbance Restless legs Depression and anxiety and suicide

Question 59

ESRF - Immunological

Answer 59

Infection common as immune system depressed. Uraemia suppresses function of most immune cells, and dialysis can activate complement.

Question 60

ESRF - Lipids

Answer 60

Hyperlipidaemia common, especially hypertriglyceridaemia from decreased TG catabolism. Statins

Question 61

ESRF - Cardiac Disease

Answer 61

Pericarditis mor likely if urea/PO4 levels high. Fluid overload and HTN can cause LV hypertrophy or dilated cardiomyopathy. Large AV fistula can use up a lot of CO

Question 62

Haemodialysis - principles

Answer 62

1. Dialysis - removal of unwanted solutes by diffusion. Blood separated from suitable fluid with semipermeable membrane. Diffusion until equilibrium reached. Can be done with a synthetic membrane (haemodialysis) or peritoneal membrane. 2. Hemofiltration - removal of water which carries with is unwanted soluble substances. If blood pumped at higher hydrostaticic pressure than fluid on other side of membrane, then water in blood forced through membrane by ultrafiltration.

Question 63

Why, in a renal patient who needs a cannula, should you always start with back of hand?

Answer 63

To avoid damage to arm veins that may be later needed for fistula construction

Question 64

How does haemodialysis look like in practice? What makes up the dialyse fluid?

Answer 64

2 points of access - one to take blood, one to return blood. Blood pumped past one side of semipermeable membrane while dialyse fluid pumped opposite way. Membranes arranged within a cartridge as hollow fibres. Amount of fluid removed controlled by altering pressure. Essential constituents of plasma - Na, K, Cl, Ca, Mg, glucose, buffer (bicarb, lactate) Blood and dialyse reach equilibrium. [K] in dialyse lower vs plasma to promote K removal. Heparin used in circuit to prevent clotting.

Question 65

Haemodialysis access

Answer 65

In short term acute - wide bore dual lumen central venous catheter tunnelled under skin Artificial AV fistula created, usually joining radial/brachial artery to vein, in a side to side or side to end manner. Over time the fistula dilates to allow 2 wide bore cannulas.

Question 66

What are the acute complications of haemodialysis?

Answer 66

Hypotension Over aggressive initial dialysis can cause disequilibrium, and result in osmotic changes in brain as plasma urea falls, results range from nausea to coma Itch during or after Cramps as electrolytes shift across muscle membranes Hypokalaemia and dysrythmias Air embolism - place pt head down on left side with 100% oxygen

Question 67

What are the chronic complications of haemodialysis?

Answer 67

Fistula thrombosis Aneurysm formation Infection Blood borne infection transmission is a risk.

Question 68

In what forms of poisoning can haemodialysis be useful?

Answer 68

``` Water soluble drugs or metabolites Toxic alcohols - methanol, ethylene glycol, isopropanolol Lithium Metformin Salicylates Na Valproate Barbituates Theophylline ```

Question 69

Technical aspects of peritoneal dialysis

Answer 69

Soft Silastic catheter tunnelled through skin. Bag of sterile dialyse fluid drains into by gravity. When finished, catheter unclamped and fluid drained by gravity into bag. Called continuous ambulatory peritoneal dialysis (CAPD) Typically 2L every 4h, with high osmotic bag overnight for water. Intermittant peritoneal dialysis overnight is a less common approach. Any residual kidney function helps soooo much here. May not be possible if previous surgery or sepsis has caused adhesions or fibrosis in the peritoneal cavity.

Question 70

Complications of peritoneal dialysis

Answer 70

Peritonitis - Staph, Enterococci, E. Coli, Pseudomonas, Anaerobes, Fungi Exit site infection Protein loss - 5-10g loss/day compensated with protein intake Glucose absorption - important for DM patients Volume effects - hernias, back pain, breathing problems Sclerosing encapsulating peritonitis - intraperitoneal fibrosis which encases bowel and causes obstruction and malnutrition

Question 71

What is, and when would you use, continuous haemofiltration?

Answer 71

Venous blood pumped at high pressure onto highly permeable membrane producing large volumes of ultra filtrate, which is discarded and replaced with appropriate volume of balanced electrolyte solution. Slow and continuous, therefore avoids rapid solute changes of conventional dialysis. Good for unstable critically ill patients with ARF or ESKD. Anticoagulated with heparin or prostacyclin. Continous arterovenous haemofiltration also possible - uses arterial pressure as driving force.

Question 72

Define plasma exchange. When might it be appropriate?

Answer 72

Removal of antibodies or other large immunologically active molecules. Plasma filtered away and replaced with new fluid containing electrolytes, FFP and albumin.

Question 73

Roughly, how dos renal transplant look like?

Answer 73

Donor kidney implanted in RIF or LIF. Renal artery sutured to external or internal iliac artery and renal vein to external iliac vein. Ureter implanted in bladder wall.

Question 74

Which HLA types must be matched in transplants?

Answer 74

Blood type compatibility | HLA-A, HLA-B and HLA-DR molecules must be matched.

Question 75

Immunosupressants: steroids

Answer 75

Prednisolone or methyprednisolone Bind steroid receptor, inhibiting gene transcription and function of T cells, macrophages and neutrophils. SE - Cushingoid

Question 76

Immunosupressants: Cyclosporin

Answer 76

Forms complex with cyclophillin to inhibit calcineurin. Calcineurin normally dephosphorylates NFAT which promotes expression of cytokines. Therefore cyclosporin inhibits IL2 and TC activation SE - nephrotoxic (from vasoconstriction acutely, chronically from glomerular ischaemia and interstitial fibrosis), hyperkalaemia, hypermagnasaemia, HTN, gum hyperplasia CP450 inducers lower activity

Question 77

Immunosupressants: Azathioprine

Answer 77

Metabolised to 6-mercaptopurine which inhibits purine metabolism and therefore nucleic acid synthesis and cell proliferation, especially in lymphocytes and neutrophils SE - infection, pancreatitis, BM suppression, megaloblastic anaemia Degraded by xanthine oxidase! Never with allopurinol!

Question 78

Immunosupressants: Mycophenylate mofetil

Answer 78

Inhibits iodine monophosphate dehydrogenase - requires for nucleic acid synthesis. Inhibits BC and TC function SE - oesophagi tis, gastritis, diarrhoea

Question 79

Immunosupressants: Tacrolimus

Answer 79

Calcineurin inhibitor | SE - nephrotoxic and HTN, can cause IGF/DM

Question 80

Immunosupressants: Sirolimus

Answer 80

mTOR inhibitor, blocking protein translation, IL2 signalling and TC and TC proliferation SE - proteinuria

Question 81

Immunosupressants: Biologics

Answer 81

Basiliximab - CD25 (IL2r alpha chain) inhibitor Rituximab - anti CD20 (b cell depletor) Alemtuzuman - anti CD52 (general lymphocyte depletor)

Question 82

Early complications of transplantation

Answer 82

Poor renal function may indicate acute rejection, ciclosporin toxicity, or ATN due to ischaemia before kidney was revascularised. Cellular vs Vascular rejection CMV infection - fever, retinopathy, hepatitis, enteritis. Gancyclovir

Question 83

Chronic complications of transplantation

Answer 83

Loss of renal function - chronic rejection. Recurrent diease - esp. focal segmental glomerulonephritis, membranoproliferative glomerulonephritits or IgA nephropathy HTN Hyperlipidaemia OP and osteonecrosis of femoral head Skin cancer Post transplant lymphoproliferative disease (EBV causes a lymphoma like illness)