Renal Flashcards
Obstructive uropathy - causes?
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)
Presentation of renal colic
Loin to groin pain
Types of renal calculi?
75% Ca Oxalate (phosphate)
15% Mg ammonium phosphate
10% uric acid or cysteine
Risk factors for renal calculi?
Concentrated urine, hereditary, diet, co-morbidities (sarcoidosis, inflammatory bowel disease, cancer)
Common sites of obstuction of ureter by kidney stone?
- Ureterovesical junction
- Crossing of iliac artery (mid ureter)
- Ureteropelvic junction
Possible routes of kidney infection?
Haematogenous vs Ascending
Predisposing factors in acute pyelonephritits
Anomalies of kidney or ureter, calculi, obstruction at any level, DM, pregnancy, neurogenic bladder, instrumentation
Clinical features of acute pyelonephritis
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
Renal fusion types
- Crossed ectopia with fusion.
- S shaped sigmoid hidney
- Pelvic cake/lump kidney
- 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.
Wilm’s tumour
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 +++
Surgical approach to the kidney
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
Embryology - development of the urinary system
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
Definition: Renal Hilus
Medial aspect of kidney containing the entrance to renal artery, vein and the renal pelvis
Gross kidney anatomy - relation to outside
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
Innervation of the bladder
S3 S4 S5
Cortical vs Juxtamedullary Nephrons
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
In which cell is EPO made?
Fibroblast-like interstitial cells of the kidney
What is the role of mesangial cells in the glomerulus?
Provide a scaffold to support the many capillaries in Bowman’s capsule. Have contractile and phagocytic properties
What are the 3 components of the glomerular filtration barrier?
- Endothelial cells - thin with 70nm pores filled with -ve charges podocalyxin
- 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.
- 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
Renal Hx and Examination
Esp –> Drugs, FHx, Infection, PMHx
Urine appearance
Exam –> Abdo/Cardiac. (Note BP, JVP, Fundoscopy, Renal bruit, oedema)
Urine microscopy - casts
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
At what eGFR level do you expect urea and creatinine to rise?
About 30mL/min
Why does creatinine clearance slightly overestimate GFR?
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
Renal anti-immune profile
ANCA - vasculitis
Anti-GMB Goodpasture’s
ANA/anti ds-DNA, low complement levels - SLE
What is the approach for renal biopsy?
Percutaneous biopsy performed with long cutting needle through back under US guidance. Tissue examined by light microscopy, immunostaining, electron microscopy
Causes of ARF (in %), mortality, prognosis
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
What is the pathophysiology of ATN?
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
Pre-renal causes of ARF
Inadequate cardiac function, circulatory volume depletion, obstruction of arterial blood supply. Resulting renal ischaemia causes ATN
Name 10 nephrotoxic agents
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
RIFLE criteria for ARF
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
Name some tubular toxins
Heavy metals
Contrast media
Haemoglobin
Myoglobin
How does acute hypercalcaemia cause AFR?
Renal vasoconstriction and calcium phosphate precipitation in tubules
How does myeloma cause ARF?
Light chain precipitation in tubules can cause case nephropathy and AKI
What can cause crystals to form in tubules causing ARF?
Gout (hyperuricaemia), aciclovir, indinavir
How do NSAIDs cause kidney damage?
Normally, tonic prostaglandin induced vasodilation or renal arterioles. NSAIDs inhibit Pg synthesis, leading to vasoconstriction.
When coupled with volume depletion, vasoconstriction can be intense.
What are the RF for NSAID induced kidney injury?
Volume depletion, diuretic use, pre-existing renal impairment, oedematous state (CCF, liver cirrhosis, nephrotic syndrome)
Why is renal artery stenosis an absolute CI for ACEi?
In RAS, angII causes efferent arteriolar constriction to maintain GFR. ACEi/ARB block this constrictive drive, and cause a large fall in GFR
Common features of AKI in hospital
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)
AKI in viva - investigations and basic management
- Bloods tests - K levels, CK, anaemia, WCC, inflammatory markers, kidney function, immunology incl complement, ANCA, antiGBM, ANA & dsDNA, cultures
- Urine - culture, microscopy, dipstick, Bence Jones proteins
- USS KUB and Doppler
- Electrolytes - U&E daily, restricted K, diuretics to prevent hyperkalaemia
- Acid - severe acidosis with inadequate renal function must be treated with renal replacement therapy
- Volume - regularly reassess, if necessary invasive monitoring, Daily insensible losses are 500ml + 500ml for every point of fever. Daily weights
- Pulmonary oedema - sit patient up, high flow O2, if renal function give diuretics
CI for renal replacement therapy
Hyperkalaemia, acidosis, pulmonary oedema, severe uraemia. Haemodialysis can be poorly tolerated by haemodynamically unstable patients. Continous haemofiltration is slower and better tolerated.
Stages of CKD
- eGFR >90
- eGFR 60-80
3A. eGFR 45-59
3B. eGFR 30-44 - eGFR 15-29
- eGFR <15
What are general management principles for CKD?
Weight loss (to a correct BMI), aggressive BP management, low salt intake, exercise, avoiding NSAID painkillers, reduced alcohol intake all beneficial
What is the most commonly used formula to calculate eGFR, and in which patients do you need a correction
MDRD formula
Black african ethnicity patients have higher plasma Cr levels with equivalent renal function so eGFR multiplied x1.2
What tests would you do if you suspected proteinuria?
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
Define uraemic syndrome in ESRF
Refers to complications of CRF including anaemia, confusion, coma, asterixis, seizures, pericardial effusion, itch, renal bone disease.
Requires renal replacement therapy
What is the biochemical profile of renal bone disease?
Low Ca, high PO4, high PTH
*Plasma Ca typically low in CRF unless tertiary hyperparathyroidism develops
USS - small atrophied fibrotic kidneys
Presentation of renal bone disease
Can cause bone pain, esp lower back, hips, legs.
Proximal myopathy and soft tissue calcification
Differentiate high turnover vs low turnover renal bone disease and the causes
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.
What will a radiograph of high turnover renal bone disease show? What will low turnover bone disease show?
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)
What is the treatment of high turnover renal bone disease?
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
Complications of ESRF - top to bottom
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
ESRF - general management
Dialysis / Transplantation
Intake –> K restriction, PO4 restriction, Na restriction, H2O resriction
PO4 binding agents, Vitamin D, EPO, BP control
ESRF - haematological
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.
ESRF - vascular Disease
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.
ESRF - skin
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.
ESRF - GIT
Nausea and Vomiting, anorexia, heartburn, oesophagi tis, angiodysplasia common. Higher incidence of pancreatitis
Taste disturbance - urine like smell to breath
ESRF - Endocrine
Loss of libido, impotence, low sperm count and motility, reduced ovulation
Loss of muscle mass in adults, growth retardation in children
ESRF - Neurological and Psychiatric
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
ESRF - Immunological
Infection common as immune system depressed. Uraemia suppresses function of most immune cells, and dialysis can activate complement.
ESRF - Lipids
Hyperlipidaemia common, especially hypertriglyceridaemia from decreased TG catabolism. Statins
ESRF - Cardiac Disease
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
Haemodialysis - principles
- 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.
- 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.
Why, in a renal patient who needs a cannula, should you always start with back of hand?
To avoid damage to arm veins that may be later needed for fistula construction
How does haemodialysis look like in practice? What makes up the dialyse fluid?
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.
Haemodialysis access
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.
What are the acute complications of haemodialysis?
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
What are the chronic complications of haemodialysis?
Fistula thrombosis
Aneurysm formation
Infection
Blood borne infection transmission is a risk.
In what forms of poisoning can haemodialysis be useful?
Water soluble drugs or metabolites Toxic alcohols - methanol, ethylene glycol, isopropanolol Lithium Metformin Salicylates Na Valproate Barbituates Theophylline
Technical aspects of peritoneal dialysis
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.
Complications of peritoneal dialysis
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
What is, and when would you use, continuous haemofiltration?
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.
Define plasma exchange. When might it be appropriate?
Removal of antibodies or other large immunologically active molecules.
Plasma filtered away and replaced with new fluid containing electrolytes, FFP and albumin.
Roughly, how dos renal transplant look like?
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.
Which HLA types must be matched in transplants?
Blood type compatibility
HLA-A, HLA-B and HLA-DR molecules must be matched.
Immunosupressants: steroids
Prednisolone or methyprednisolone
Bind steroid receptor, inhibiting gene transcription and function of T cells, macrophages and neutrophils.
SE - Cushingoid
Immunosupressants: Cyclosporin
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
Immunosupressants: Azathioprine
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!
Immunosupressants: Mycophenylate mofetil
Inhibits iodine monophosphate dehydrogenase - requires for nucleic acid synthesis. Inhibits BC and TC function
SE - oesophagi tis, gastritis, diarrhoea
Immunosupressants: Tacrolimus
Calcineurin inhibitor
SE - nephrotoxic and HTN, can cause IGF/DM
Immunosupressants: Sirolimus
mTOR inhibitor, blocking protein translation, IL2 signalling and TC and TC proliferation
SE - proteinuria
Immunosupressants: Biologics
Basiliximab - CD25 (IL2r alpha chain) inhibitor
Rituximab - anti CD20 (b cell depletor)
Alemtuzuman - anti CD52 (general lymphocyte depletor)
Early complications of transplantation
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
Chronic complications of transplantation
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)
