Renal Flashcards

Question

Cystinosis

Answer 1

**definition**: AR lysosomal storage disorder, most common cause of Fanconi's **clinical:** FTT, rickets, cystine deposits (cornea, renal, pancreas, thyroid, cardiac, muscle) - normal intelligence **treatment:** very treatable with cysteamine caps and eye drops

Answer 2

**definition:** XLR of renal tubules due to defect Cl Channel CLC-5 **clinical:** nephrocalcinosis, hypercalciuria, calculi, renal failure, renal rickets, proteinuria

Answer 3

**genetics:** point mutation WT1 gene chromosome 1 **clinical: (triad)** 1. progressive renal disease (early nephrotic sx then mesangial sclerosis) 2. undifferentiated genitals 3. Wilm's tumour (90%)

Answer 4

hypo-osmotic overhydration **diagnosis:** - hyponatraemia/low plasma osm - urine Na output inappropriately high \>50mmol/day - urine osm inappropriately high relative to serum: 350-400mosmol - no evidence hypovolaemia - increasing plasma osm in response to restriction of water

Answer 5

**indications:** acidosis, hyperkalaemia, uraemia \>80, fluid overload **effectiveness:** - conventional HD/PD: 15% normal function - short daily HD: 25% normal function - home nocturnal HD: 50% normal function \*\*peritoneal dialysis preferred in children

Answer 6

**genetics:** sporadic or associated syndrome **pathology:** small cysts in cortex, sometimes duplex kidney/GUT abnormalities **associations:** tuberous sclerosis, Zellweger, trisomy 13

Answer 7

**defect:** inability to excrete acid 1. failure NH₃ concentration in medullary interstitium 2. failure of distal H⁺ secretion **causes:** genetic, drugs, carbonic anhydrase def (OP), AI, obstructive uropathy **complications:** - calculi: no citrate in urine and Ca/PO₄insoluble at high pH - assoc deafness **diagnosis:** alkaline urine (low K⁺, high NH₃) **treatment:** correct acidosis, K citrate

Answer 8

**reabsorption:** 5% Na and 3% bicarb - variable water reabsorption in collecting ducts depending on ADH **tubular absorption:** Na absorbed via channel coupled to K excretion **tubular secretion:** ammonium, H+, K+ under influence of aldosterone

Answer 9

**Dimercaptosuccinic acid (radio-labelled)** 1) Scarring: sticks to PT and outlines cortical mass to detect cortical scarring 2) Differential function of each kidney= time taken to uptake

Answer 10

**potent vasocontricting peptides produce various tissues** **types:** endothelins 1- 2- 3- interactive with 2 G protein receptors type A and B - increased iCa and stimulate protein kinase C **function:** modulate vasomotor tone, cell proliferation, hormone production **endothelin 1:** - produced in endothelial and vascular smooth muscle cells - most potent vasoconstrictor - role in heart failure, renal failure

Answer 11

**definition:** repetitive voiding or urine into clothes/bed - at least twice/week for 3 months in child \>4yrs **epidemiology:** 5yrs (7% boys, 3% girls), 18yrs (1% men, 1% girls) **risk factors:** low SE, large families, institutionalised children, family hx **subtypes:** _diurnal_ _nocturnal can be:_ - monosymptomatic: no assoc daytime sx - nonmonosymptomatic (more): 1 subtle daytime sx _- primary enuresis_ (85%): never dry _- secondary enuresis:_ resumption post dry 6 month **voiding** - bladder vol= (age x 30) + 30 - frequency: 3-8 x **resolution:** 15% spontaneous cure rate annually

Answer 12

**causes** _diurnal/nocturnal:_ renal (CKD, UTI), endo (DM, DI), GI (constipation), sleep (OSA), neuro (SC disorder/GDD) _nocturnal:_ primary rousability, genetic component, nocturnal polyuria (low ADH night), psychological _diurnal:_ MOST overactive bladder, voiding postponement, bladder dys, giggle incontinence, vaginal voiding **treatment:** _1. Conservative_: education, charting, void before bed _2. Alarm (best treatment):_ 75-95% success at 3 months _(NOT \<7 yrs)_ _3. Medications:_ DDAVP (high relapse when ceased), imipramine (\<50% respond) _diurnal:_ + oxybutinin, tolteridone - refer to urology IF: diurnal, abnormal voiding, UTIs, genitals abnormal

Answer 13

**definition:** generalised proximal tubular dysfunction **causes:** - _genetic_: cystinosis, Lowe's, Dent's disease, galactossaemia, tyrosinaemia, Wilson's, heredity fructose intolerance - _acquired:_ interstitial nephritis, drugs, heavy metals, frusemide, aminoglycosides, cyclo, tacro, amphotericin, ifosfamide **clinical:** vomiting, FTT **diagnosis:** urine osm \<300, glycosuria, phosphaturia, low PO₄, amnioaciduria, tubular proteinuria

Answer 14

**DTPA:** isotope purely excreted like creatinine **MAG 3:** 20% isotope secreted at the tubules so always dye even if GFR is 0 (better images) **functional scans show:** 1. contribution of each kidney to overall function 2. obstruction **process:** - baseline image then dye injected - 2nd image at 2-3 mins to assess uptake/% contribution to function of each kidney - frusemide given at peak uptake (20-30 mins) - measure for washout time: if \<15 mins then no obstruction, if \>20 mins obstruction

Answer 15

**site:** distal tubule **age:** teens/adults **defect:** NaCl in distal collecting duct - causes thiazide like effect - hypovolaemia/hypotension, high renin/aldosterone, K/Mg wasting, low urine Ca, high urine Cl **clinical:** low growth, salt craving, muscle cramps, tetany, hypotension, fatigue, polyuria **diagnosis:** hypokalaemic met alkalosis, high urine Cl, low serum Mg, high serum Ca - NORMAL urine concentrating capacity **treatment:** KCl, Mg, spironolactone, fluid

Answer 16

**GFR=** no. nephrons X single nephron GFR **Normal GFR=** 100ml/min/m² **Newborn GFR=** 15ml/min/m² **renal blood flow (20-30% CO):** renal perfusion pressure (BP)/ renal vascular resistance **filtration fraction:** GFR/RBF **filtration of plasma:** 20X/hour

Answer 17

**mesangial cells:** connective tissue that controls pressure in glomerula **filtration (3 layers):** endothelium, GBM, podocytes with foot processes **macula densa:** epithelial cells in DCT, sense change in BP **juxtaglomerular apparatus:** sits next to afferent arteriole and responds to signals from macular densa to secrete renin

Answer 18

**incidence:** uncommon **clinical:** present in neonatal period - 10% liver fibrosis **pathology:** large echogenic kidneys, microscopic glomerular cysts

Answer 19

**pathophysiology:** preformed immune complexes or insitu immune complex formation with secondary injury via complement cascade and coagulation **clinical:** - haematuria +/- proteinuria - AKI with oliguria, hyperkalaemia - _nephrotic syndrome_ with 2 types: SLE and membranous **diagnosis:** - GN screen: C3/C4, ANA, dsDNA, ANCA, antiGBM, ASOT/DNAse B, urine - granular and red blood cell casts - renal biopsy

Answer 20

**definiition:** symptoms haematuria, proteinuria, oedema, HTN caused by glomerular injury accompanied by inflammation **pathogenesis:** immunologic response to several biological processes - may be isolated to the kidney or part of a systemic disorder _- primary disease:_ humoral response to inciting agent with Ig deposition and complement activation _- secondary disease:_ primary disease activates complement, coagulation and leukocyte systems that cause disease **presentations:** _- acute GN_: PSGN, HSP, post bacterial endocarditis _- RPGN:_ anti-GBM, IgA nephropathy, MPGN, SLE, PSGN, HSP, granulomatosis with polyangitis _- recurrent macroscopic haematuria:_ IgA nephropathy, Alport syndrome _- chronic GN:_ MPGN, IgA , antiGBM, SLE, granulomatosis **evaluation**: light microscopy, immunofluorescence, electron microscopy

Answer 21

**type:** focal **cause:** unknown **pathogenesis:** anti-GBM to type IV collage of GBM of lung/glomeruli **clinical:** rare in childhood, smokers **diagnosis:** - antiGBM, normal C3 - biopsy: linear deposition of anti-GBM IgG Ab **treatment:** IV steroid, immunosuppressants, IvIg - ALL progress to ESKD

Answer 22

**definition**: \>500 RBC/ml **incidence**: asymptomatic haematuria in 0.5-2% children **RBC casts/dysmorphic**: glomerular pathology

Answer 23

**advantage:** rapid correction of fluid overload/electrolyte abnormalities, removes burden from carer **disadvantage:** big central venous access (CVC/AV fistula), blood in fillter at all times **mechanism (counter-current)** - dialysate flows opposite direction to blood through cylinders maintain concentration gradient for exchange of solutes - fluid removes by hydrostatis pressure of dialysate fluid **complications:** hypotension, renal ischaemia, dysequilibrium syndrome (rapid shifts in urea) **contraindications:** haem instability, severe coagulopathy

Answer 24

**definition:** simultaneous microangiopathic haemolytic anaemia, thrombocytopaenia and AKI **pathophysiology:** post gastroenteritis then thrombotic microangiopathy causing fibrin/clot in glomerulus and secondary poor filtration/acute renal failure **clinical:** renal failure, hepatomegally, CNS (30%) with irritability, pancreatitis (\<10%), myocarditis - similar to TTP but more renal/neurological symptoms **diagnosis:** anaemia, thrombocytopaenia, Coomb's negative, fragments/schistocytes on film, raised transaminases **subtypes:** _primary causes_ - complement gene mutations - antibodies to complement factor H _secondary causes_ - infection: shiga toxin producing ecoli (STEC), strep pneumo, HIV - inborn error of cobalamin C metabolism - drug toxicity

Answer 25

**type:** focal IgA (similar to IgA vasculitis) pathogenesis: small vessel vasculitis with IgA deposits in glomeruli **clinical:** - purpuric rash, abdo pain, arthritis - 50% renal often weeks to months post initial symptoms **diagnosis:** - normal C3 **treatment:** - no evidence for steroids in HSP to prevent renal injury - steroids, immunosuppressants **prognosis:** worse if acute renal involvement at diagnosis

Answer 26

**7% filtered potassium is excreted with almost all reabsorbed PCT** **regulation K excretion:** aldosterone, serum [K] **causes:** _pseudohyperkalaemia:_ haemolysis _redistribution:_ met acidosis, DKA, familial hyperkalaemic periodic paralysis _true hyperkalaemia_ - low GFR: poor clearance, increased K load, decreased K excretion - normal GFR/low aldosterone: low renin (diabetic nephropathy, interstitial nephritis, obstructive uropathy), normal renin (adrenal insuff, drugs ACEi/ARB) - normal GFR/high aldosterone: pseudohypoaldosteronism, drugs (K sparing), obstructive uropathy/sickle cell nephropathy, post renal transplant **clinical:** arrhythmia if \>8.5mmol/L **diagnosis:** - ECG: small p waves, prolonged PR, wide QRS, peaked t waves **management:** _acute:_ cardiac monitor, ECG, calcium gluconate, salbutamol, insulin/dextrose, frusemide, resonium, dialysis _chronic:_ low K diet, loop diuretic

Answer 27

**mechanism:** 1. aldosterone deficiency - eg. CAH, pseudoaldosteronism with UTI 2. tubular aldosterone resistance 3. drugs that impair aldosterone - eg. heparing, NSAIDs, calcineurin inhibitors, trimethroprim 4. interstitial nephritis **diagnosis:** decreased Na, increased K acidic urine, increased renin, low aldosterone **treatment:** mineralocorticoids

Answer 28

**type:** focal **incidence:** sporadic (family hx uncommon), linked 6q22-23, assoc HSP **pathophysiology:** mesangial deposits IgA complexes (glomerulus not involved) **clinical variable presentations:** - synpharingitic episodes of haematuria - persistent micro haematuria - acute nephritis - nephrotic syndrome **diagnosis:** biopsy (IgA levels not helpful) **treatment:** BP control, +/- steroids, immunosuppressants **prognosis:** often benign, 20% CKD

Answer 29

**acute interstitial nephritis** **mechanism:** inflammatory infiltrate in kidney interstitium with immune mediated inflammation of the tubules **cause:** - drugs: NSAIDs, antibiotics - infections - TINU: tubulointerstitial nephritis and uveitis syndrome - systemic disease: SLE, sarcoidosis **clinical:** usually 1-2 weeks post exposure - nausea, vomiting, abdo pain **diagnosis:** non oliguric, no proteinuria, increased Cr - biopsy if severe or systemic cause suspected **management:** removal of offending agent, supportive, ?steroids

Answer 30

**causes:** - vascular disease: HUS, thromboses - glomerular disease: GN - CAKUT (congenital): cystic - tubular disease - interstitial disease

Answer 31

**genetic:** AR, 3 mutations, also NHPH gene defect **clinical:** - renal: variable cystic - cerebellum: vermal aplasia - eye: coloboma, retinitis pigmentosa - congenital hypotonia - ocular-motor apraxia

Answer 32

**genetics:** rare AD **pathogenesis:** increased activity luminal membrane sodium channels **diagnosis:** low aldosterone/renin **clinical:** present at young age with HTN, hypokalaemia, metabolic alkalosis **treatment:** amiloride

Answer 33

**mechanism:** acts on thick ascending limb to decrease Na reabsorption via Na/Cl/2K transporter **effect:** excretion 25% filtered Na and increases Ca excretion **side effects:** - high glucose/TG/cholesterol - low uric acid/Ca/Cl/K/Mg/Na - metabolic acidosis

Answer 34

**Counter current multiplier system establishes osmotic gradient in interstial tissue from cortex to medulla** - _descending tubule_: impermeable solute, loses water, increasing concentration - _ascending tubule_: impermeable to water, loses solutes, more dilute **Na absorption:** Na/Cl/2K co transport - inhibited by frusemide

Answer 35

**definition:** oculorenal syndrome **genetics:** OCRL1 gene defect **clinical:** presents like Dent's disease _- renal:_ PT failure (type 2 RTA), nephrocalcinosis, renal calculi, renal osteodystrophy - congenital cataracts - mental retardation

Answer 36

**mechanism:** non reabsorbable sugar alcohol - acts as osmotic diuretic inhibiting sodium and water reabsorption in PT and LOH

Answer 37

**investigation**: obstruction, VUR **process:** catheterise, fill bladder with radiolabelled material, scan with voiding **diagnosis:** shows bladder wall thickening/trabeculation **VUR** grade 1: reflux into ureter grade 2: into collecting system w/o dilation grade 3: into collecting system with mild dilation grade 4: moderate dilation but still impression of calyces grade 5: severe dilation - _note_: prophylactic AB\> grade 2

Answer 38

**incidence:** AR, rare **clinical:** neurosurgical and renal problems

Answer 39

**genetic:** AD rare **clinical:** - progressive decline in kidney function from adolescence - polyuria, enuresis, anorexia, pallor - ESKD in adulthood (or earlier if juvenille form) **pathophysiology:** tubulointerstitial kidney disease **biopsy:** cortico-medullary cystic changes **US:** normal/small kidneys **diagnosis:** elevated uric acid/creatinine

Answer 40

**incidence**: adolesence/teens **type of GN with:** - characteristic light microscopy changes: mesangial hypercellularity, endocapillary proliferation and double-contour glomerular capillary walls - histological changes: thickened GBM, increased mesangial/endocap cellularity **immune-complex mediated:** most common with chronic antigenemia/circulating immune complexes - associated chronic infections (eg HBV, HCV, fungus, parasites), AI diseases (eg SLE, Sjorgens, RA), monoclonal gammopathies (eg multiple myeloma) **complement-mediated MPGN:** less common from dysregulation and persistence of alternative complement p/w - deposition of complement along capillaries in mesangium **classification with electron microscopy** _MPGN I:_ immune deposits mesangium/subendo space _MPGN II (worst prognosis):_ dense deposits along GBM, tubules, bowman's capsule _MPGN III:_ type I with subepithelial deposits **diagnosis:** low C3, normal C4 **treatment:** prednisone, immunomodulators, Ig, recurs post transplant **prognosis:** ESKD 50% in 10 yrs

Answer 41

**type:** focal non proliferative **pathogenesis:** subepithelial immune deposits (not cellular) - secondary to SLE, HepB, tumours **clinical:** nephrotic syndrome - haematuria common **diagnosis:** - normal C3 - biopsy: thick BM, spikes on silver stain **treatment:** steroids if nephrotic, ACEi if non nephrotic

Answer 42

**Increased anion gap**'MUDPILES' **M**ethanol **U**remia **D**iabetic Ketoacidosis **P**aracetamol **I**ron, Inhalants (CO, cyanide, toluene), Isoniazid, Ibuprofen **L**actic acidosis **E**thylene glycol, ethanol ketoacidosis **S**alicylates, starvation ketoacidosis, sympathomimetics

Answer 43

**renal compensation** - HCO₃ reabsorption: 85% in PCT - regeneraton of HCO₃ by excretion of NH₄ in DCT - NH₃ + H⁺ and NH₄ excreted

Answer 44

**Normal AG acidosis 'USED CARP'** **U**reteric diversion **S**mall bowel fistula **E**xcessive Cl **D**KA resolving **C**arbonic anhydrase inhibitors **A**ddisons **R**enal tubular acidosis (Types 1, 2 & 4) **P**ancreatic fistula

Answer 45

**cause:** diuretic use, diarrhoea **mechanism:** chloride loss causes alkalosis 1. impaired HCO3 secretion 2. fall in ECF volume: decreased GFR, decreased filtered HCO₃, increased Na reabsorption, increased NaHCO₃ reabsorption, increased K excretion, increased NH₄excretion, increase HCO₃ **chloride responsive: renal cause (Ur Cl\>40)** - Barttner's, Giltelman's, diuretics **chloride responsive: non renal cause (Ur Cl\<25)** - vomiting, diarrhoea, CF **chloride resistant** (volume overload/hypertensive) - mineralocorticoid excess or impaired Cl- excretion

Answer 46

**incidence:** 1:3000, sporadic not inherited **pathogenesis:** failure of ureteric bud to fuse metanephros - renal parenchyma replaced non-communication cysts - non functioning kidney with atretic/obstructed ureter **clinical:** - 30% abnormal contralateral side, PUJ obstructions 15%, VUR 10% - usually normal renal function **treatment:** nephrectomy if symptoms **prognosis:** cysts involute 5 yrs, malignant change possible, RF uncommon

Answer 47

**hyponatraemia:** - early: excess TBW and normal Na - later: renal causes **hypernatraemia:** - almost always hypovolaemic hypernatraemia - preterm: insensible losses - term: poor feeding **hypokalaemia:** - excess renal loss K **hyperkalaemia:** - renal failure, haemolysis, tissue destruction

Answer 48

**antenatal** - urine from week 10 gestation - small volume but 60% AF - oligohydramios: eg. PUV - polyhydramnios: eg. nephrogenic DI, Bartter's - Cr crosses placenta: neonatal Cr= maternal Cr **postnatal:** - relative renal insufficiency: low BP, high SVR, poor tubular reabsorption Na/HCO₃ - initially low urine vol, poor urine concentration, GFR 10-15ml/min

Answer 49

**'Ho Hum'** **H**aematuria **O**liguria **H**ypertension **U**raemia **M**ild proteinuria

Answer 50

**definition:** laying down of calcium in the kidney in nondiscrete locations **incidence:** common \<1 week and disappears with urine production **pathology:** lays around renal pyramids first **causes:** same as for metabolic calculi - hyperoxaluria - hypercalciuria

Answer 51

**definition:** partial or complete renal resistance to ADH **cause:** hereditary or acquired **pathophysiology:** urine output determined by solute intake/excretion **treatment:** - low salt/protein diet \*\*protein highest renal solute load, best control UO - diuretics (increase proximal Na/H₂O reabsorp and reduce distal water delivery) - NSAIDs (inhibit renal PG synthesis/afferent vasodilation) - exogenous ADH (only for non hereditary) - water q2 hourly day and night

Answer 52

**incidence:** most common cause of genetic cystic disease, **incidence:** 1:50,000 **genetics:** AR, chromosome 2, NHPH1-6 **pathogenesis:** ciliary defect causing problem with apotosis causing tubular BM thickening/wrinkling with tubular atrophy/fibrosis and few cysts at CM junction **3 variants:** 1. infantile: 1yr with ESKD 2. juvenille (most): 13yrs ESKD 3. adolescent: 19yrs ESKD **clinical:** - _renal_ (due to tubular injury): polyuria/polydipsia, reduced concentrating ability, Na loss, renal failure, anaemia \* normal BP **US:** loss of CM differentiation, normal/small size **treatment:** nil specific, renal transplant

Answer 53

**4 criteria** **1.** proteinuria \>50mg/kg/day **2.** hypoalbuminaemia \<25 **3.** oedema **4.** hyperlipidaemia: liver compensation for decreased albumin so increased other protein production **incidence:** M\>F 2:1, \<6 yrs usually MCNS, \>6yrs FSGN **clinical:** - usually present with oedema first - then anorexia, abdo pain, cool peripheries **pathophysiology:** effacement of podocyte foot processes **causes:** _- steroid sensitive:_ no known cause _- steroid resistant:_ associated with genes for proteins podocin, nephrin, WT1 **associated:** _- infections_: encapsulated, urinary loss Ig and C3 precursor _- thrombosis:_ 2-5% in children due to hypercoagulable state from stasis, haemconcentration, increased factor production, urinary loss anticoagulants _- hyperlipidaemia_

Answer 54

**primary causes:** _minimal change disease (85%)_: - EM effacement foot processes - 90% sensitive to steroids and rarely ESKD _focal segmental glomerulosclerosis (most severe):_ - LM mesangial proliferation/segmental scarring - IF +ve IgM/C3 - EM segmental scarring of glomerular tufts/obliteration capillary lumen - 20% respond to steroids and most ESKD _mesangial proliferation:_ - LM increased mesangial cells/matrix - IF mesangial IM/IgA staining - EM increaesd mesangial cells/effaced epithelium - 50% respond to steroids **secondary causes:** - any of GN: SLE, HSP, membranoproliferative, PSGN - malignancy (immune complexes with tumour Ag deposit in glomeruli - drugs: lithium, gold, phenytoin, NSAIDs - infection: HIV, hepatitis, malaria, syphillis

Answer 55

**treatment** 1. _high dose steroids tapered 4 months_ - 6 weeks 60mg/m2/day then 4 weeks 40mg/m2/day and taper - high dose and long course prevents relapse - 40 % relapse, 90% respond to steroids in 3 weeks _2. frusemide_ _3. fluid restrict_ _4.albumin_ _5. antihypertensives_ **definition of relapse:** 3x \>3+ protein in urine **treatment of relapse:** 60mg/m2/day until remission (urine negative 3/7) **steroid dependent:** relapse on alternate days or within 28 days ceasing **steroid resistant:** ongoing proteinuria at 8 weeks, 80% FSGN, need biopsy - consider cyclosphospamide, rituximab **prognosis:** - steroid responsive: most have repeated relapses, decreased frequency with age - steroid resistant: poorer prognosis, renal insufficiency

Answer 56

**causes:** PUJ obstruction, renal calculi, thrombi, tumours **Ureteric stricture** - congenital with extrinsic compression where the right ureter sits behind IVC **Ectopic ureter** - F\>M, ureter enters urethra/cervic/uterus - reimplantation if renal function is preserved otherwise nephrectomy **ureterocele** - cystic dilation at end of ureter - surgical resection/correction

Answer 57

**calculated plasma osmolarity**= 2[Na+Ka] + glucose + urea **plasma osmolarity**= 280-295 mosmol/l

Answer 58

**osmolality**= no. of osmoles/kg of solutes (mosmol/kg) **osmolarity**= no. of osmoles/L of solution (mosmol/L)

Answer 59

**incidence:** RARE. genetic **mechanism:** overproduction oxalate in liver due to primary or secondary disease **clinical:** reccurent nephrolithiasis and progression to ESKD **treatment:** pyridoxine, fluids, transplant

Answer 60

**mechanism: anticholinergic** **-** prevents muscarinic recepter activation by anticholine on bladder smooth **use:** decreases bladder spasm to prevent incontinence

Answer 61

**dialysate contains:** osmotic agent, electrolytes, acid buffer **ultrafiltrate:** fluid removed from patient **volumes:** 10-50ml/kg each cycle **contraindications:** intraabdominal pathology, peritonitis **advantages:** gentle, less fluid shift, higher peritoneal SA in children, no central venous access devise **disadvantages:** infection (IP ceftazidime/ceftriaxone or if \<2yrs IP ceftaxidime/vancomycin with continuous PD), peritoneal fibrosis, career burnout

Answer 62

**incidence:** 5-15% HUS, younger 1-2yrs **pathophysiology:** pneumococcus produces neuroaminidase and exposes T antigen on RBC/platelets (cryptantigen considered FB) causing haemolysis **clinical:** pneumonia (70%) with empyema/effusion, meningitis (20-30%) - more severe initial disease - complications: pancreatitis, purpura fulminans, cholecystitis, cardiac dys, hearing loss **treatment:** supportive

Answer 63

mechanism: obstruction **pathophysiology:** 1. collecting tube dysfunction (type 4 renal tubular acidosis) - water/Na loss, H/K retained 2. more proximal dysfunction - RAAS, reduced GFR, ATN 3. ATN assoc sepsis - poor outcome

Answer 64

**type:** diffuse proliferative glomerular injury with inflammation **incidence:** 5-12 yrs, 15% post GAS infections, increased with family history **pathophysiology:** GAS infection, diffuse mesangial cell proliferation, glomerular inflammation - usually GAS but also EBV, CMV, HepB, endocarditis **clinical:** 1-2 weeks post throat infection/3 weeks post skin infection - gross haematuria, flank pain, oliguria, HTN, oedema, hyperkalaemia, hypocalcaemia - MRI can show reversible posterior leukencephalopathy **diagnosis:** - low C3, normal C4, ASOT+ (throat 90%, skin 50%), AntiDNAse B+ (95% spec) _- urinalysis:_ protein, casts _- biopsy:_ IgG/C3 deposits, diffuse proliferation **treatment:** dialysis, fluid restrict, frusemide - NO STEROIDS **prognosis:** 95% fully recover - micro haematuria may persist for 1 yr - 5% relapse or ESKD

Answer 65

**pathophysiology:** - embryological remnant: a valve with leaflets with only a slit like opening at a point along the urethra **clinical:** severe obstructive uropathy - poor urinary stream, trabeculated bladder, ESKD 30% **diagnosis:** often diagnoses antenataly with hydronephrosis, oligohydramnios, pulmonary hypoplasia **associations:** VUR, dysplastic kidney **treatment:** antenatal decompression, IDC/vesicostomy, valve ablation, prophylactic AB, monitor renal function

Answer 66

**mechanism:** act on cortical collecting duct - amiloride: directly decreases Na channel activity - spironolactone: inhibits aldosterone receptor and decreases number of Na/Cl cotransporters **effect:** weak natriuretic activity with only 2% filtered Na excreted **side effects:** hyperkalaemia, gynaecomastia - amiloride: hyperchloremic met acidosis, hyponatraemia

Answer 67

**Respiratory compensation** 1 CO₂: 1 HCO₃ - 30 mins-24 hrs _met acidosis_: decrease pCO₂ 1.3 for decrease 1 HCO₃ _met alkalosis:_ increase pCO₂ 0.6 for increase 1 HCO₃ **Metabolic compensation** - 1 to 5 days _resp acidosis ACUTE_: increase HCO₃ 1 for increase 10 CO₂ _resp acidosis CHRONIC_: increase HCO₃ 3.5 for increase 10 CO₂ _resp alkalosis ACUTE_: decrease HCO₃ 2 for decrease 10 CO₂ _resp alkalosis CHRONIC:_ decrease HCO₃ 3 for increase 10 CO₂

Answer 68

**cause:** hypovolaemia, poor perfusion, sepsis, CV failure **pathophysiology to counter hypovolaemia:** 1. intrarenal PG release: dilation afferent arteriole and improve filtration 2. decreased pressure at macula densa, increase renin/ATII, selectrive vasoconstriction efferent arteriole, increased hydrostatic pressure across glomerulus 3. further increase renin/ATII, systemic vascoconstriction afferent/efferent arterioles, ATN and oliguric RG

Answer 69

**definition**: \>4mg/m²/hr **diagnosis**: early morning protein to creatinine ratio most reliable **dipsticks**: most sensitive for albuminuria and miss other proteinurias - 1+ 30mg/dl - 2+ 100mg/dl - 3+ 300mg/dl - 4+ 2000mg/dl **non-pathological**: exercise, fever, posture **pathological:** tubular, glomerular, tumour, drugs, stone, infection

Answer 70

**definition:** inability to reabsorb HCO₃(and Na) **cause:** can be isolated or generalised proximal dysfunction _ie Fanconi's syndrome: genetic or acquired_ - decreased PO4, renal glycosuria, aminoaciduria, tubular proteinuria, T2 RTA _causes of isolated proximal RTA_ 1. idiopathic 2. cystinosis 3. ifosfamide **diagnosis:** acidic urine \<5.5, NH₄ in urine, NO calculi (citrate present) **treatment:** BICARB

Answer 71

**iso-osmotic reabsorption of 2/3 glomerular filtrate** **active reabsorption:** Na, K, glucose, galactose, fructose, AA, Ca, uric acid, Vit C **passive reabsorption:** urea and water due to osmotic gradient generated by solute reabsorption **active secretion:** organic acids eg. PAH, diuretics, salicylates, penicillin, probenicid

Answer 72

**incidence:** most common obstruction, M:F 2:1 **pathophysiology:** congenital instrinsic stenosis (90%) and less commonly extrinsic compression (10%) causing partial obstruction of the ureter resulting in thin ureter and dilated kidney - 60% left, 10% bilateral **diagnosis:** _US:_ hydronephrosis _MCUG:_ detect VUR (10%) _DTPA:_ diagnose obstruction **management:** AB prophylaxis, pyeloplasty (91-98% success)

Answer 73

**causes of increased renin:** - decreased BV/Na concentration - catecholamines - standing **causes of decreased renin release:** - angiotensin II, ADH, hypernatraemia, hypokalaemia - indomethacin/beta blockers/ACEi

Answer 74

**hydrogen:** secretion 85% PCT, 10% distal tubules, 5% CD in exchange for Na - via 3 mechanisms **chloride:** moves passively with Na except for active transport in LOH **sugar/AA:** completely reaborbed in PT via Na dependent active transport - glucose is saturable: at 10mmol/l glycosuria occurs **urea:** 87% filtered reabsorbed (50% in PT) **water:** passively reabsorbed 80% PT, 15% LOH, distal tubule via ADH

Answer 75

**Renal H⁺ excretion** - minimal H⁺ excretion but excrete H⁺via NH₄ **Urine anion gap** - urine ammonia can be estimated by the UAG: UAG= (urine Na + urine K) - urine Cl - usually Na + K \> Cl **Acidosis** - increased excretion of NH₄ combines with Cl to make ammonium Cl and increases renal Cl so Cl\> Na + K **Urine pH** - if high: bicarb in urine - if low: H⁺present

Answer 76

**1. Renal bicarb reabsorption** - H+ secretion tubular cells binds HCO₃- to form H₂CO₃ that divides to CO₂/H₂0 with reabsorption of CO₂ into tubular cells **2. Ammonium secretion** - NH₃ in tubular cells accepts H+ to form NH₄+ which is then excreted **3. Dihydrogen phosphate** - exchange H for Na converts monohydrogen phosphate to dihydrogen phosphate (acid) \*\*Excess H+: 2/3 excreted as annium, 1/3 excreted as dihydrogen phosphate

Answer 77

**incidence:** most common benign tumour kidneys - 1/10 in patients with TS **pathogenesis:** benign tumour of blood vessels **clinical:** retroperitoneal haem with sudden pain, nausea, vomiting, shock **renal US:** bilateral multiple echogenic foci

Answer 78

**differention:** - proliferative vs non proliferative - diffuse vs focal - segmental vs global - crescenteris: cellular vs fibrous types **specific patterns:** - cresenteric= RPGN - tram tracking= MPGN - wire loops= SLE - spikes on special stains= membranous - starry sky= PSGN - subepithelial humps (immune complexes on GBM)= PSGN **immunofluorescence:** c3, IgA/M/G, C1q - granular= immune complex - pauci immune= ANCA assoc - linear IgG at GBM= antiGBM - gull house pattern (all present)= SLE **electronmicroscopy:** good for the site of immune deposition

Answer 79

**incidence:** M\>F, 1% children, 60% metabolic risk factor - variables: diet, geography, race, family history **diet:** increased protein/cereal, high or low calcium, high salt **stone composition:** - calcium oxalate 60-90% - calcium phosphate 10% - struvite 1-14% - urate 5-10% - cystine 1-5% **formation:** forms in tubules at site of injury usually in medulla **clinical:** flank pain (50%), renal colic (7%), haematuria (10% macro, 90% micro), passage of stone, UTI, CKD - chance of passing stone \<5mm high, 5-7 mm 50%, \>7mm review **diagnosis:** - US: detects stone, shows obstruction - urine/stone analysis **complications:** UTI (FTT and intermittent urosepsis), functional impairmonet, decreased bone density

Answer 80

**clearance_x=** [urine_x] x urine volume/[Plasma_x] - if clearance\>GFR: secretion of solute - if clearance

clearance of solute

- ideal solute: freely filtered at glomerulus, no metabolism/secretion/reabsorption ie. inulin

creatinine: small endogenous product muscle metabolism

- secreted in tubules so can overestimate GFR

urea:

- 40-50% passively reabsorbed in proximal tubule

- can underestimate GFR

cystatin C: small molecule produced nucleated cells in body

- metabolised in tubules so can't measure clearance

- BUT serum cystatin C may correlate better with GFR

Answer 81

**pathogenesis:** problem non-motile cilia from tubular epithelial cells facing lumen - loss of tubule orientation causing dilation and cysts **polycystic:** ARPKD, ADPKD, MCDK **CAKUT:** renal agenesis, dysplasia, aplasia **tubulointerstitial:** renal tubular dysgenesis, nephronopthisis, medullary cystic disease, Bardet-Biedl **neonplasms:** cystic nephroma/nephroblastoma/RCC, von Hippel Lindau, lymphangioma, hygroma renalis **other:** simple corticol cyst, medullar sponge kidney, localised renal cystic disease

Answer 82

**genetics:** AD, HNF1B activates polycystin/uromodulin **clinical:** DM (20-40yrs), gout, bicornuate uterus, hypomagnesiua, LFTs

Answer 83

**timing:** 5 weeks gestation, glomerulus development at 9 weeks, urine output 10 weeks **_phases_** **1st: Pronephros day 22** **2nd: Mesonephros** - mesoderm in thoracolumbar region develops into glomeruli/tubules **3rd: Metanephros week 5** - outpouch of mesonephros forms ureteric bud branches into the ureter and collecting duct system **completion:** weeks 32-36 all nephronic units complete

Answer 84

**Na reabsorption** (99% of filtered) - 60% PCT: Na/H exchanger (H provided by HCO₃ absorption and carbonic anhydrase) - 25% LOH (thick ascending limb): Na/Cl/2K co transported - 10% DT: epithelial Na channel coupled to K - 2% CT **Na regulation** by Aldosterone/ANP - mediate plasma volume **NOT** Na **Fraction excretion** of Na: % of Na filtered by kidney excreted in urine - (FE_Na)= 100x (Na_u x Cr_p)/(Na_p x Cr_u) - \<1%: prerenal disease, 1-2%: ATN or prerenal, \>2%: ATN

Answer 85

**prevalence:** very common early on with CKD **pathogenesis:** **-** decreased renal mass causes decreased renal 1 alpha-hydroxylase and 1, 25 vitamin D3 production - decreased GI calcium absorption and hypocalcemia, and increased PTH activity - excessive PTH secretion corrects hypocalcemia by increased bone resorption - later mechanisms to enhance phosphate excretion inadequate causing hyperphosphatemia with further hypocalcemia and increased PTH **4 types:** _1. Osteitis fibrosa cystica:_ increased bone turnover due to secondary hyperPTH - increased PTH due: increased Ph, decreased Ca/VitD _2. Adynamic bone disease:_ decreased bone turnover - most common renal bone disease - decreased osteoblast/osteoclast activity - over suppression of PTH (vit D tx, Ca based phosphate binder) _3. Osteomalacia:_ decreased bone turnover and more undermineralised bone - common when Al would deposit in bone with Al based Ph binders **diagnosis:** PTH, ALP, BMD testing, bone biopsy **management:** control of PTH and PO₄

Answer 86

**PCT (65%):** site of signficant reabsorption (NaCl, water, HCO3, nutrients) and excretion (H, drugs) **LOH (25%):** countercurrent mechanism, descending limb impermeable to solutes and reabsorbs water, ascending limb impermeable to water and Na/Cl/K reabsorbed **DCT (8%):** electrolyte reabsorption in smaller shifts **CD (1.5%):** site ADH/aldosterone action - Aldosterone: Na/water retention, K/H secretion, stimulates ADH - ADH: acts on cortical part of CT NB. % Reabsorption of solutes

Answer 87

**types:** preemptive, living related donor, deceased donor **graft survival:** approx 15 years **immunosuppresants:** steroids, basiliximab for induction (anti CD25 monocloncal Ab), tacrolimus/cyclosporine (calcineurin inhibitors), azathioprine/MMF (antiproliferative agents), sirolimus/everolimus (mTOR inhibitors) **complications:** _rejection: creatinine best indicator of rejection_ - hyperacute: preexisting HLA Ab, occurs anytime - acute: T cell medicated, interstitial inflammation/arteritis, treat with methylprednisone/anti-thymocyte globulin - chronic: donor specific antibiodies, CD4 staining on biopsy, glomerulitis/vascular thrombosis, optimise immune suppression _infection:_ EBV, CMV, BK _NODAT (new onset diabetes after transplant):_ same as DM2, increased BMI/steroids _PTLD (post transplant lymphoproliferative disease):_ related to infection, treat with reduced immunosuppression, monitor EBV levels _malignancy:_ most adults, skin (SCC/BCC), increased all types due to immune suppression

Answer 88

**definition**: normal AG acidosis but failure to acidify urine **types:** - distal (type 1) RTA - proximal (type 2) RTA - mixed (type 3) RTA - type 4 RTA **treatment:** treat underlying condition, sodium bicarb **complications:** lactic acidosis, hypernatraemia, volume overload, hypokalaemia, hypocalcaemia, alkalosis

Answer 89

**epidemiology:** 90% all cases usually \<5years, 3/100,000 **organism:** 6-9% STEC infections **pathophysiology:** microangiopathic anaemia by nonimmune RBC destruction due to shearing through platelet microthrombi - glomerular thrombotic microangiopathy with can extend to afferent arteriole **clinical:** preceded 5-10 days before with abdominal pain, vomiting, blood diarrhoea usually post exposure to undercooked beef - AKI 50% - neurological symptoms 25% and seizures assoc HTN - GI haemorrhagic colitis - also cardiac dysfunciton, pancreatitis, liver dysfunction, haem disorders **prognosis:** 30% CKD, 5% mortality **treatment:** fluids, dialysis, eculizumab (monoclonal complement Ig), plasma exchange

Answer 90

**incidence:** sporadic, M\>F 2:1 **cause:** unknown **diagnosis:** cortical, solitary, unilateral **clinical:** pain, haematuria, obstruction, rupture, infection

Answer 91

**type:** diffuse **epidemiology:** 25% SLE in children **pathogenesis:** minimal change (mild, haematuria/proteinuria), mesangial (mildest 25%, haematuria/proteinuria), FSGN (20%, + impaired RF), diffuse proliferative (most common/severe 40%, + impaired RF), membranous (15%, nephrotic syndrome), advanced sclerosis **diagnosis: (FULL HOUSE)** - low C3/C4, ANA+ve, ESR, dsDNA+ve - biopsy: wire loops, all stains positive: IgG, IgA, IgM, C3, C1q **treatment:** steroids, immunomodulators, IVIg, ACEi, statin **prognosis:** ESKD 20% at 10 yrs

Answer 92

**mechanism:** inhibit Na transport in DT via inhibition NaCl cotransported - also cause increased reabsorption of calcium **effect:** smaller proproportion of filtered load, so smaller natriuretic effect **side effects:** hyperglycaemia, hypokalaemia, hyperuricaemia, hypercalcemia, hypochloremic alkalosis

Answer 93

**ATN:** _cause:_ ischaemic 60%, nephrotoxic 40%: aminoglycosides, chemotherapy (cisplatin), IVIG, contrast _pathophysiology:_ oedema, sloughing of cells, Na/K pump dysfunction _management:_ hydration, nutrition, time **Contrast nephropathy/dermopathy:** _cause:_ CT contrast, MRI gadolinium (lower toxicity) _pathophysiology:_ rise Cr after 48 hours - MRI gadolinium associated nephrogenic systemic fibrosis if GFR\<3 _management_: hydration, ?NAC (free radial scavenger)

Answer 94

**causes:** disorders of purine metabolism (5-10%), uric acid overprod, tumour lysis, Lesch-Nyhan, gout, ketogenic diet, salicylates, glycogen storage 1 **treatment:** alkalinise urine, ?allopurinal, uricase

Answer 95

**specific gravity:** normal 1.010-1.035 **osmolality:** normal 300mosm (more accurate than SG) **microscopy** **urinary casts:** cylindrical structures produced by kidney (DCT/CD) and present in urine - _hyaline casts:_ transparent, most common, solidified Tamm-Horsfall mucoprotein secreted from the tubular epithelial cells of nephrons with dehydration/exercise, not pathological - _granular casts:_ 2nd most common, breakdown of cellular casts or inclusion of aggregated protein, glomerular/tubular disease _- white cell casts:_ indicate inflammation/infection ie. acute pyelonephritis, interstitial nephritis - _red cell casts:_ always pathological, usually glomerulonephritis - _fat globules:_ hyperlipidaemia - _glycosuria:_ steroids, FSGS

Answer 96

**incidence:** 7% febrile infants - \<12 months M=F, \<3 months M\>F **risk factors:** FHx, abnormal flow, constipation, abdo mass, antenatal dx renal abnormality, HTN **definitions:** - cystitis: bacteruria but no systemic symptoms - pyelonephritis: bacteriiuria + fever/pain **pathogens:** ecoli (\>80%), klebsiella, proteus, enterobacter, enterococcus **diagnosis:** - leuks+/nitrites+: AB - leuks-/nitrites+: AB - leuks +/nitrites-: AB IF clinical evidence - leuks-/nitrites-: DONT treat **treatment:** - \<6m or unwell: IV AB (benpen, gent) - \>6m and not unwell: PO AB (trimethoprim, bactrim, ceph)

Answer 97

**incidence:** 1/40,000, 95% male **triad: l**ack of abdominal muscles, undescended tests, antenatal urethral obstrution **clinical:** oligohydramnios, pulmonary hypoplasia - often assoc malrotation **prognosis:** dependes on pulm/renal dysplasia

Answer 98

**incidence:** usually adults with sinusitis/renal/skin involvement **pathophysiology:** focal segmental GN (may be crescenteric), NO immune deposits (oie. pauci immune) **clinical:** - systemic disease: ENT/pulmonary - microhaematuria, AKI with haematuria/casts, proteinuria below nephrotic range, RPGN common **diagnosis:** ANCA +ve - biospy: ANCA - immunofluorescence: pauci immune **treatment**: non specific - dialysis, steroids, immunosuppressants, IVIg

Answer 99

**CRITERIA:** - seriously ill/septicaemia - poor urine flow - abdominal mass - elevated creatinine - failure to respond to appropriate AB within 48 hours - non Ecoli organisms