Renal/urology

Question 1

fluid balance (normal input and output, formula for fluid mls needed in 24hrs for adult or child, rate you’d worry about central pontine myelinolysis, 5 causes of abnormal fluid loss)

Answer 1

normal: input 1000mL from drink, 650 from food, 350 water of oxidation; output 500mL by skin, 100mL each lungs and faeces, 1000mL urine (but variable)
for adults with no other fluid intake give 25-30ml/kg/24 hours, along with 50-100g glucose a day to limit starvation ketosis
for children: 100ml/kg/day for first 10kg, 50ml/kg/day for second 10kg, 20ml/kg/day for weight over 20kg
after working out per 24hr amount can convert that to a per hour amount to give eg nbm pt awaiting surgery etc
sodium: giving water alone affects osmolality so 1mmol/kg/24 hours; pontine myelosis will occur if na rises too fast in hyponat (ie >0.5-1mmol/l/hr or >10mmol/l in 24 hrs)
abnormal fluid loss can be via d&V, a hidden bleed, stoma, inappropriate urine loss, pancreatic or biliary drain
assess volume status through ABCDE approach of resp rate, pulse, bp inc postural hypotension, cap refill, jvp, pulm oedema, skin turgor, eyes and mucous membranes inc mouth; check if theyre feeling thirsty or have felt dizzy, had syncope
always get help if: Na <120, ongoing uncontrolled fluid loss, pulm oedema dev, if given >2000ml fluids, whenever you feel you need help

Question 2

algorithms for fluid assessment (6 indicators for resus and resus protocol inc 2 times you need expert help, 3 cases where give 250ml bolus, when to go to routine mx; 5 things to check before starting maintenance fluids, daily water/na/k cl/glucose needs, what to do if electrolyte or fluid issues, what to do for obese ppl; 4 times need expert help)

Answer 2

assess for fluid resus: volume status bearing in mind context, indicators for therapy: sysBP<100, HR >90, cap refill >2s or cool peripheries, resp rate >20, NEWS >/= 5, 45deg passive leg raising test pos
if anything suggests fluid resus then: high flow O2, large bore iv cannula access, bolus of 500ml crystalloid stat; reassess with ABCDE/fluid status for indicators as above, if still needed give further 250-500ml bolus if <2000ml given, repeat until >2000ml in which case expert help needed (inotropes); if at any point signs of shock dev, even if no more fluids needed, seek help; if not needed and not signs of shock then go to routine fluid management; seek help earlier or give 250 rather than 500ml in second bolus onwards if pt elderly or has renal/heart failure
if initial assessment says no fluid resus need then can pt meet fluid/electrolyte needs orally/enterally, if so then ensure these needs are met and monitor volume status; if they cant then move to routine fluid management
look at history for things affecting fluid intake or abnormal losses, examine for fluid status, check fluid balance chart and weight, NEWS score, any lab results; are there any fluid or electrolyte issues? if no cont with routine management: 25-30ml/kg/day of water, 1 mmol/kg/d each Na, K, Cl; 50-100g/d glucose; keep monitoring and stop when you can, NG or enteral preferable esp if maintenance needed for > 3 days
again if elderly, heart/renal failure, or malnourished w/ risk of refeeding syndrome go for 20-25ml/kg/d
if there are electrolyte or fluid issues: estimate deficit or excess and add/subtract from the maintenance requirement; check for abnormal losses or other causes of the deranged electrolytes: treat cause if poss, if abnormal loss ongoing/waiting for treatment then add extra fluid/electrolytes to prescribed amount to compensate for measured loss, monitor and reassess
if complex issues: sepsis, gross oedema, hyper/hyponat, organ impairment, then seek expert help
prescription should include type of fluid, volume to give, rate at which to give, any adjuncts; can get pt to look out for symptoms etc to help with their fluid balance monitoring
adjust calculations for obese pt - give the fluids as for their ideal body weight, and seek help if bmi >40; >3L fluid rarely needed
your initial crystalloid for resus should be NaCl 0.9% or hartmanns (hartmanns similar but less nacl and has K and HCO3, both solutions are isotonic, hartmanns maybe better if risk of losing k/hco3 eg vomiting)

Question 3

iv fluid therapy types and amounts

Answer 3

if patient cannot take fluids orally or because disturbance is severe enough to warrant rapid correction
3 basic types: plasma (expanders) or whole blood, aka colloids, given when vascular volume reduced after eg bleeding; 0.9% NaCl, isotonic NaCl, confined to ecf and given if that compartments volume reduced eg Na depletion; 5% dextrose (as pure water would haemolyse cells), with the dextrose rapidly metabolised and water redistributed across all comps so for those with reduced total body water eg hypernatraemia
generally per day: water losses of 2-3L, sodium of 100-200mmol, potassium of 20-200mmol; beware though that insensible losses inc when on artificial ventilation or with excessive sweating
after trauma of surgery: AVP secretion, K redistribution due to tissue damage, physiological stress response; so good iv treatment perioperatively per day may be: 1-1.5L fluid containing 30-50mmol Na and no K
do not raise serum Na by more than 10-12mmol/L per day, as otherwise may get osmotic demyelination, esp in pons, giving disability or death
when adjusting regimens, must assess fluid and electrolyte status: besides biochemistry, consider care records, exam of patient (JVP, CVP, ABP, pulse, oedema, skin turgor, chest sounds), nursing charts (inc fluid input/output)

Question 4

dehydration vs volume depletion, autotrans and imp of rapid vs gradual fluid loss, isoton vs hypoton fluid loss (inc which is better at depleting blood vol and showing clinical signs and why inc %s), what maintains rbf and gfr in vol depletion and when this fails (quant, inc ecf vol loss giving cr rise), what causes inc’d risk of gfr decline at lower level of vol depletion

Answer 4

dehydration= loss of total body water producing hypertonicity; vs volume depletion which is deficit in ecf volume
as blood volume falls, ecf autotransfuses via transcap refill; vascular refill rate is maximal immediately after a volume loss, recouping
about 50% of lost fluid within 2 hours with an eventual plateau at 24 hours after about 75-80% of lost vascular volume is recovered
Rapid losses of blood volume draw primarily from blood volume alone, while slower losses recruit from about 75% of the ECF (plasma volume
plus interstitial fluid volume) requiring 3 to 4-fold greater deficits to produce equivalent hemodynamic compromise.

Non-hemorrhagic fluid losses such as gastrointestinal, renal, or third spacing initially derive from the plasma volume but are usually slow
enough to distribute across much of the ECF compartment
When net fluid loss is isotonic, it draws completely from the ECF and thus the volume of fluid loss exactly equals the volume deficit.
Conversely, when there is pure water loss, ECF tonicity rises causing rapid translocation of water from the larger intracellular compartment
to establish a new elevated level of body tonicity
the concept of isotonic or pure water loss is attractive, but such losses rarely occur in isolation. Most non-hemorrhagic fluid losses are
hypotonic, but can be partitioned into isotonic and pure water components

Orthostatic changes in heart rate or blood pressure do not become evident in normal subjects until 15-20% of blood volume is removed acutely
Assuming a 15% fall in blood volume as a minimal threshold for clinically detectable volume depletion, a non-hemorrhagic, isotonic loss of
about 15% of ECF amounting to 7% of TBH2O is required. In contrast, a pure water deficit equivalent to 15% of TBH2O is needed to reach the
same hemodynamic threshold. Consequently, isotonic losses are about 2-fold more potent than pure water losses at depleting blood volume.
Indeed, isotonic losses alter systemic hemodynamics, reduce blood volume and GFR, and leave body tonicity unchanged. Conversely, an
equivalent pure water deficit does not measurably alter blood volume or GFR, while hypernatremia and hypertonicity are prominent

As blood volume and ECBV fall, initial intrarenal events maintain renal blood flow (RBF) and GFR primarily through prostaglandin effects on
afferent arteriolar tone despite systemic vasoconstriction. As ECBV declines further, angiotensin II-mediated efferent arteriolar
vasoconstriction reduces renal blood flow, but preserves GFR leading to a rise in filtration fraction, which contributes to enhanced
proximal tubular sodium and urea reabsorption. Eventually the mechanisms combating afferent arteriolar vasoconstriction fail leading to a
precipitous fall in RBF and GFR; RBF begins to fall at around 10% blood loss and GFR falls at about 20% blood loss
Thus, a rise in serum creatinine or oliguria related solely to non-hemorrhagic hypovolemia anticipates a 15-20% deficit in ECF. Vascular
disease from hypertension or diabetes, cardiac dysfunction, chronic kidney disease, or medications interfering with compensatory
angiotensin or prostaglandin systems, will exhibit GFR declines at lower levels of volume depletion

Question 5

cell adjustments to hypertonicity and action of ADH

Answer 5

cells acclimate to hypertonicity by accumulating electrolyte osmoles initially followed by organic osmoles chronically
If the progression of hypertonicity eclipses intracellular osmolyte accumulation, severe neurologic symptoms ensue with
seizures, coma, and central pontine myelinosis as the most dreaded complications. If hypertonicity develops slowly, neurons acclimate,
maintain cell volume, and patients exhibit only mild neurologic symptoms or may even present asymptomatically. However, rapid correction
of chronic, compensated hypertonicity may precipitate cerebral edema when osmotic entry of water into brain cells outstrips their
short-term ability to shed accumulated organic osmoles
cerebral oedema gives raised icp (headache, n&v, low consciousness, visual disturbance, cushing reflex)

ADH to improve water reabsorb and also increases distal nephron reabsorption of urea and recycling to improve the efficiency of water
reabsorption

Question 6

iv fluid giving inc mmol in 0.18% saline 1L bag, how many bags a day, na and cl content in normal saline relative to plasma, when to inc glucose and what %

Answer 6

Sodium Chloride 0.18% and Glucose 4 % Solution: Each ml contains 1.8 mg sodium chloride and 40 mg glucose (as monohydrate)
mmol/l (approx): Na+: 30 Cl-: 30; give it always as 1L (multipled by N) eg normal 2L requirements + 70mmol Na a day you could prescirbe 2; normal saline has slightly more na and 50% more cl than is in plasma
bags each to be given over 12 hours; this is if eg dehydrated (glucose included if nbm)

Question 7

shock vs dehydration (3 signs shock more likely, 4 things seen in both, 4 signs of decompensated shock, how tongue may be in dehydration)

Answer 7

Shock vs dehydration: clinical shock rather than just clinical dehydration as he has the following signs:
pale/mottled and cold extremities
prolonged capillary refill time

Note: tachycardia, tachypnoea, reduced skin turgor and reduced urine output can be seen in both early shock and clinical dehydration
Late (decompensated) shock has low BP, acidotic breathing, absent urine output, blue extremities

dehydration may have white tongue due to build up of debris

Question 8

7 factors increasing risk of dehydration in children

Answer 8

children younger than 1 year, especially those younger than 6 months
infants who were of low birth weight
children who have passed six or more diarrhoeal stools in the past 24 hours
children who have vomited three times or more in the past 24 hours
children who have not been offered or have not been able to tolerate supplementary fluids before presentation
infants who have stopped breastfeeding during the illness
children with signs of malnutrition

Question 9

5 features suggesting hypernat dehydration

Answer 9

jittery movements
increased muscle tone
hyperreflexia
convulsions
drowsiness or coma

Question 10

children losing fluid (eg d&v) mx if shocked x1, dehydrated (sign that might indicate this with tongue, main mx inc parameters, 2 other steps), not dehydrated x3 (plus advice x2 if vomiting)

Answer 10

if clinical shock is suspected children should be admitted for intravenous rehydration.

For children with no evidence of dehydration
continue breastfeeding and other milk feeds
encourage fluid intake
discourage fruit juices and carbonated drinks
if theyre vomiting can do more freq smaller feeds of same overall volume, and reintroduce plain food (plain boiled white rice is good option) as tolerated

If dehydration is suspected (inc if white tongue):
give oral fluid challenge (eg 1ml/kg per 10 mins of water, dilute apple juice, ORS, breastmilk)
continue breastfeeding
assess response, consider need for NGT or IV

Question 11

paediatric fluid prescribing (for over what age, how to work out what volume to give for maintenance dose, then when to adjust to 50% or 2/3; when to add more and how to estimate a fluid deficit (2 ways), 5 red flags for fluid depletion; normal fluid choice and when to add K x2, what if hyper or hyponat and dehydrated)

Answer 11

for those over 28 days old:

first what volume? 100ml/kg for first 10kg, 50ml/kg for next 10, 20ml/kg for every kg after that
can do full maintenance dose if no oral intake or eg half maintenance or 2/3 maintenance if drinking some but eating/drinking is reduced
can also add more to make up for a fluid deficit in eg DKA
to estimate a deficit work out percentage dehydration ([well weight-current weight/well weight] x100), or assume 5% if sx/signs of dehydration and 10% if red flags; then do % dehydration x current weight x 10
red flags: needed fluid resus, tachycardic/pneoic, irritable/lethargic, reduced skin turgor, sunken eyes

then what fluid? normally 0.9% sodium with 5% glucose; can add 10mmol/L K if losing that due to d&v or salbutamol therapy for eg asthma

Question 12

fluid responsiveness and resus - what influences, best sign, what causes greater SV variation (inc in who is this valid) and what other parameter varies, straight leg raise how to do and 3 times not to do, 2 other egs of predictors)

Answer 12

strongly influenced by starling curve: gradient decreases with increased preload until point reached where curve peaks and then begins to fall, so boluses will have less effect closer to the peak of the curve the pt’s preload sits

best sign ultimately is improvement on admin of a fluid bolus

also note that the lower you are on the frank starling curve (and therefore the greater the change in SV for diff preloads), the higher the variation in SV in different phases of ventilation - thus greater SV variation when more underfilled, however this is only valid for mechanically ventilated pts (same for pulse pressure variability, as in both cases only way to control enough confounding parameters), however is one of the best predictors of fluid responsiveness in these pts; you aim for SVV/PPV of <10%/12% respectively

straight leg raise is essentially a reversible fluid challenge; can’t do if hip trauma, post angiography, any worries of raised ICP; raise legs by 45deg, keep them up for 1 min; this one is well validated

other weird ones like PAWP (pulm art wedge pressure), IVC diameter variability etc; more of an ITU thing and often not v good

Question 13

enzyme inducers (mnemonic + 3)

Answer 13

PC BRAS – phenytoin, carbamazepine, barbiturates, rifampicin, alcohol (chronic excess) sulphonylureas (gliclazide). Others: topiramate, St John’s Wort, and smoking.

Question 14

enzyme inhibitors (mnemonic + 4)

Answer 14

AO DEVICES – allopurinol, omeprazole, disulfiram, erythromycin, valproate, isoniazid, ciprofloxacin, ethanol (acute intoxication), sulphonamides (antivirals). Others: azole antifungals, grapefruit juice, amiodarone, and SSRIs (fluoxetine, sertraline).

Question 15

5 cannula colours and their gauge + flow rates

Answer 15

Orange 14g 270ml/min
Grey 16g 180ml/min
Green 18g 80ml/min
Pink 20g 54ml/min
Blue 22g 33ml/min

Question 16

describe body fluid comps

Answer 16

ICF/ECF, ECF divided into IF and plasma, with transcellular fluid in specialised compartments like synovial fluid, digestive juices, CSF; ICF 25L, IF 13L, plasma 3L and TCF 1L; kidney regulates plasma which influences IF by staring forces and diffusion; blood is 55% plasma, 45% cells; plasma 91% water, 7% proteins, 2% electrolytes and separated from IF by capillary membranes

Question 17

4 functions of the kidney, gfr in infants

Answer 17

fluid/electrolyte homeostasis, excretion of waste products and drugs, production of vitD/EPO/renin/prostaglandin, acid-base hom

all nephrons produced by birth but gfr at birth only 20ml/min/1.73m2, with adult value of 120 reached between first and second years of life

Question 18

kidney structure/blood supply

Answer 18

2% body weight recieving 25% CO thus large renal arteries dividing into interlobar running up renal columns to corticomedullary junction where they feed arcuate arteries running along this border and branching into interlobular arteries then afferent arterioles, glomerular capillaries, efferent arterioles, peritubular capillaries or vasa recta then veins in reverse from interlobular; vasa recta gets 1% of blood flow (long and thin so high resistance, small flow), supplies inner medulla, medulla recieves little blood favouring generation of hyperosmotic gradient; 20% plasma filtered but 99% renal filtrate reabsorbed so venous composition almost identical to arterial; 90% blood to cortical peritubular, 9% to outer medulla peritubular, 1% to vasa recta

Question 19

describe basic renal mechanisms

Answer 19

blood filtered at glomerulus, filtrate into bowman’s capsule undergoing secretion and reabsorption and remaining fluid excreted as urine; plasma flow is (blood flow x (1-haematocrit)) 600 ml per min, of which around 20% (120ml) is filtered, most of this must be reabsorbed or entire plasma volume would rapidly end up in urine; filter and selectively reabsorb so anything you don’t recognise is got rid of

Question 20

nephron stucture

Answer 20

proximal tubule (convuluted then straigh - PT) reabsorbs 70% filtrate, essentially all aa and glucose, vary isotonic reabsorption to regulate EFC volume, cells have large surface area and many mitochondria; loop of henle LOH has thin descending, thin ascending and thick ascending limbs (tDL, tAL, TAL), separates absorption of water and solutes so fluid leaving is hypoosmotic to plasma, inner medulla is hyperosmotic and loop central to producing conc/dilute urine; distal convoluted tubule DCT important to potassium and pH control, and absorbs water in concentrating kidney so fluid leaving is isotonic to plasma, water impermeable in diluting kidney so filtrate remains hypoosmotic; cortical, outer and inner medullary collecting ducts allow water reabsoprtion into isoosmotic cortex and hyperosmotic medulla allowing hyperosmotic urine production; urine then follows minor calycles to major then enter renal pelvis and ureter; juxtamedullary nephrons have LOH that extends into inner medulla, cortical LOH only into outer, but all join collecing ducts running through inner medulla so all can use the hyperosmolarity of inner medulla to produce conc urine

Question 21

ultrafiltration (what size molecules can pass filter, why albumin doesn’t, why ions not affected by this) and filtration fraction (how to calculate, what it normally is, what happens when it increases and why, effect on FF of constricting aff art, eff art, raised plasma protein conc, decreased plasma protein conc, constriction or blockage of a ureter, low volume states like dehydration, and effect of catecholamines)

Answer 21

filtration movement of water and solutes through filter due to pressure gradient, ultra refers to small (molecular) scale of filter; molecules with diameter >4nm completely blocked and 2-4nm restricted so water and inorganic ions (diamter <1nm) freely pass through, albumin 3.5nm diameter but negatively charged so very little passes through; charge irrelevant for small anions as not sufficiently large to interact with charges in filter

The filtration fraction (FF) is the ratio between the glomerular filtration rate (GFR) and renal plasma flow (RPF). A healthy individual has a GFR of around 120 ml/min (milliliters per minute, or about ⅓ ounce per minute) and an RPF of around 600 ml/min. This results in a FF of 0.2 or 20%.

When the filtration fraction increases, the protein concentration of the peritubular capillaries increases. This leads to additional absorption of fluid in the proximal tubule and tubular pressure decreases which favours Na reabsorption in distal nephron

Afferent arteriole constriction leads to decreased GFR and decreased RPF, resulting in no change in FF. During efferent arteriole constriction, GFR is increased, but RPF is decreased, resulting in increased filtration fraction.
During a state of increased plasma protein concentration such as during multiple myeloma, GFR is decreased with no change in RPF, resulting in decreased FF. However, during a state of decreased plasma protein concentration such as during nephrotic syndrome, GFR is increased with no change in RPF, resulting in increased FF.

Constriction of a ureter such as during nephrolithiasis may lead to decreased GFR with no change in RPF, resulting in decreased FF. Finally, during low-volume states as in dehydration, GFR is decreased, but RPF is decreased to a much larger extent. This results in an increased FF.

Catecholamines (noradrenaline and adrenaline) increase filtration fraction by vasoconstriction of afferent and efferent arterioles,

Question 22

filter at glomerulus

Answer 22

3 layer with podocyte diaphragm most restrictive part: fenestrated capillary membrane with large 70nm pore preventing cell passage; basement membrane negatively charged and restricts large solutes; podocytes line Bowman’s capsule, have foot processes separated by filtration slits with thin diaphragms containing pores 4 by 14nm that also carry negative charge; extracellular domains of integral membrane proteins nephrin, NEPH1 interact with podocin and other proteins to form slit diaphragm; genetic absence of nephrin gives Finnish type congenital nephrotic syndrome with severe proteinuria and oedema due to albumin loss

Question 23

control of GFR

Answer 23

wide range of ABP, GFR stays relatively constant so regulation must be in place to stop increased ABP increasing renal plasma flow and so GFR; myogenic response, constriction of afferent arteriole when stretched and relaxation when released due to stretch activated cation channels allowing calcium influx through depolarisation to decrease or increase RPF and Pc as approriate; tuboglomerular feedback as GFR increases so increased NaCl delivery to macula densa between LoH and DCT suggesting flow rate too high for reabsorption, NKCC2 co-transporter imports Cl into cells (blocking this protein prevents TGF) and triggering paracrine release of adenosine and ATP (which decays to adenosine) which bind to adenosine A1 receptors on adjacent vascular smooth muscle of afferent arteriole to constrict it and lower RPF so GFR; autoregulation helps protect glomerular capilaries and ensure constant filtration load
bigger GFR but same RPF so bigger filtration fraction, COP rises in peritubular capillary which drives isoosmotic water reabsorption in the PCT via the interstitium; ECF volume can alter this: volume expansion gives increased pressure and decreased COP so less fluid reabsorbed into capillaries, backflow and raised pressure into tubule to aid excretion (so less than 67% Na reabsorbed etc), reverse with volume contraction as well as angiotensin 2 etc, plus increased NHE3 means more bicarbonate reabsorbed giving contraction alkalosis

Question 24

PT reabsorption and secretion

Answer 24

PT reabsorbs ~70% filtrate in total, water permeable, aa and glucose almost entirely reabsorbed but most substances conc’s remain roughly same; Na and anion movement (not Cl) generate favourable gradient for water to follow (water permeable so isotonic reabsorption = concs stay same, amounts change), helped by high COP in peritubular capillaries as just left glomerulus; basolateral Na pump establishes Na gradients from lumen to cell, IF to PT cap, Na gradient drives cotransporters of glucose (SGLT2), aa, lactate, phosphate; Na proton exchange to acidify lumen

PT secretion: secretion of protons for bicarbonate reabsorption; organic ion transporters important for clearing NTs, drugs, hormones inc anions like penicillin, cGMP, cAMP, prostaglandins and cations like NA/A, dopamine, creatinine and morphine; like charged ions can compete for carriers which often have max rate

Question 25

renin-angiotensin system (renin secreted by what (where) and 3 things that trigger release including how pos feedback happens; what renin does and how active angiotensin is made, 4 ang2 effects at AT1 receptors (inc how FF change causes what it does), 1x effect of binding AT2 receptors)

Answer 25

renin is a proteolytic enzyme secreted by juxtaglomerular cells (modified smooth muscle cells) in afferent arteriole; RSN NA on beta1, fall in pressure of blood in afferent arteriole, decreased Na load at macula densa trigger release (last one could be due to reduced flow rate or renin increasing Na reabsorption, thus positive feedback) catalyses decapeptide angiotensin1 production from plasma protein angiotensinogen, then ACE makes octapeptide angiotensin2 giving normal circulating level of 500-600pM which can rise tenfold in severe Na depletion a2 is powerful vasopressor, acting via AT1 receptors to increase vascular tone; stimulates N/H exchange and constricts arterioles to raise GFR which increases Na reabsorption via increased FF: raised GFR raises peritubular capillary COP to assist fluid reabsorption and reduces tubular pressure to favour Na reabsorption in collecting duct; a2 also stimulates thirst/Na appetite binds to AT2 receptors at adrenal glands to promote aldosterone synthesis in zona glomerulosa

Question 26

aldosterone in volume reg

Answer 26

acts on TAL and distal nephron (mainly CCD) to promote Na reabsorption and H and K secretion (some K reabsorption due to H/K exchanger but net secretion); increases density of ENACs, SK, Na pump (provide more K) but as it acts by increasing protein expression it has a slow effect; distal nephron parts reabsorb smaller percentage of Na so fine tune to give accurate volume control

Question 27

atrial natriuretic peptide and BNP - inc effect on renal blood flow, 2 things ANP inhibits, 2x effects on Na reabsorption, effects on vascular resistance; BNP affinity and half life vs ANP (inc why this better target)

Answer 27

ANP: granules of its precursor in atrial myocytes, released when increased ECF stretches atria; causes Na loss so water loss constricts efferent, relaxes afferent so higher GFR, more Na filtered inhibits renin, ADH secretion raises cGMP in cells to inhibit Na reabsorption in MCD/CCD, causes dopamine secretion by PCT cells to inhibit Na reabsorption in PCT can raise cGMP in vascular smooth muscle to relax it BNP is secreted attached to an N-terminal fragment in the prohormone called NT-proBNP, which is biologically inactive. Once released, BNP binds to and activates the atrial natriuretic factor receptor NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing. The physiologic actions of BNP are similar to those of ANP and include decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis BNP was first identified in brain but primarily released from ventricles of heart

Question 28

haemorrhage physiology

Answer 28

hypovolaemia leading to hypotension; kidney reduces Na excretion to reduce water excretion; decreases GFR and renal interstitial hydrostatic pressure down to favour PCT fluid reabsorption; tubular hydrostatic pressure down to reduce flow of fluid in lumen to give more time for reabsorption; blood COP usually remains same as lose plasma proteins, severe gives decreased GFR meaning decreased COP in peritubular capillaries decreased ABP > arteriobaroreflex > inc symp discharge; mechanotransduction by carotid/aortic baroreceptors and medulla (carotid via glossopharyngeal, aortic via vagus) to increase peripheral vasoconstriction to raise TPR, positive chrontropic/inotropic effects to raise CO with supporting venoconstriction to raise VR and preload; retention of Na due to inc RSNA increased [a2] act via AT1 receptors to bring about vasoconstriction, raised TPR and reduced blood loss. promotes Na retention, via AT2 receptors stimulates aldosterone release to further promote Na retention a2 stimulates thirst and Na appetite (so fluid retained as more Na more osmoreg)

Question 29

ADH (storage and release, 2 receptors and effect of action on each inc differential affinity, major stimulus of release + 2 ways drinking inhibits release, how blood volume links to release; what happens after binding to V2r x2)

Answer 29

aka vasopressin made in supraoptic SON and paraventricular PVN and stored in neurohypophysis nerve terminals to be released in Ca mediated exocytosis following an AP, with amount released influenced by AP frequency from SON; vasopressin acts on V1 receptors to promote vasoconstriction and V2 to promote water reabsorption/permeability and urea reabsorption in kidney where it is called ADH; V2 higher affinity so V1 only acted on when [ADH] well above normal osmoreg/cardiovascular systems both influence release, major stimulus osmolality of plasma at sensors near SON; organum vasculosum of lamina terminalis is circumventricular (outside blood brain barrier) and may have some osmoreceptors projecting to SON/PVN; additional reflex from gut/liver eg drinking (liver) and water absorption (gut) inhibit ADH release and water absorption dilutes plasma to inhibit ADH release so water loss promoted; blood volume increase sensed by arterial (via ABP) and low pressure baroreceptors which inhibit ADH release as volume increases to promote water loss binds basolatereal V2 receptors, cAMP signalling pathway, PKA phosphorylates proteins so vesicles containing AQP2 fuse with apical membrane; AQP3/4 always present basolaterally so basolatereal water permeability always high, the apical membrane thus the rate limiting step; ADH stimulates insertion of vasopressin regulated urea transporters VRUT into apical membrane of IMCD allowing urea handling for more concentrated urine

Question 30

drivers of thirst

Answer 30

driven by hypertonicity, hypovolaemia, hypotension, with hypertonicity most important factor: 2-5% change gives strong osmotic thirst but pressure/volume must fall 10%; thirst centre in hypothalamus near organum vasculosum of lamina terminalis, has different sensors to osmoreceptors but they also respond to cellular shrinkage; circulatory stretch receptors in baroreceptors inhibit hypovolaemic thirst centre, this is disinhibited when volume falls; ang2 powerful thirst stimulus (a dipsinogen), when injected near organum vasculosum of lamina terminalis causes immediated increase in water intake mediated by AT1 receptors; intake in next 15 minutes can exceed normal 24 hour intake

Question 31

ecf volume and Na balance

Answer 31

relates to plasma volume so MSFP so VR so CO so ABP, slower to regulate volume than osmolality, taking hours to days, with changes from -10% to +20%, thus volume control subordinate to osmoregulation; Na is main extracellular ion and Na content determines volume, control through varying Na loss in urine (important) and Na appetite (less important, mainly in extreme situations), changes in osmotic pressure can promote changes in volume so ABP, with hypernatraemia promoting hypertension and vice versa; 4 factors affect Na balance: physical, neural, endocrine, behavioural

Question 32

neural RSNA influence of Na balance (3 things)

Answer 32

dose dependent increase in renal sympathetic nerve activity with decreased ABP: NA acts on alpha1 adrenoreceptors to increase Na/H exchange, thus has an antinatriuretic and thus antidiuretic effect also constricts afferent/efferent arterioles to reduce renal blood flow and thus GFR and Na/water excretion, high density of alpha1 on afferent gives greater constriction with intense stimulation also promotes renin secretion to promote Na retaining hormones

Question 33

kallikrein-kinin system in the kidney - which part of kidney contains bradykinin precursors and which bit receptors, what triggers bradykinin formation in kidney, and what happens x2 to the kidney in response (inc signalling paths)

Answer 33

DT contains kininogen and kallikrein and collecting duct kininogen and bradykinin B2 receptors normally the system has minimal role but if very high Na reaches DT then kallikrein released, bradykinin formed from HMW kininogen and Na reabsorption inhibited (via PLC decs open prob of ENaC), renal vessels vasodilate (afferent arterioles in biphasic manner as under PGI2, PGE2, NO from macula densa and bradykinin incs PGI2 and NO production and selectively more efferent)

Question 34

bradykinin (formation/activation, inactivation, 2 receptors inc signalling pathway, differential expression, how they lead to vasodilation (so one way ACEi work), what else receptor activation drives, role of C1EI and what if mutated; 2 types of this + drug form, and 2 things that treat this)

Answer 34

bradykinin first identified as slow contractor of ileal smooth muscle; formed by kallikrein on kininogens (can be HMW or LMW); hageman factor (factor XII) activated by contacting -ve charged surface (collagen, BM, LPS) after leaking out of blood vessels during inflam, then converts prekallikrein to kallikrein which clips HMW kininogen to bradykinin and LMW kininogen to kallidin; bradykinin further clipped to inactivate by eg ACE B1r and B2r both Gq coupled with B1r upregulated during inflam by cytokines like IL1, B2r constitutively expressed and potently activated by bradykinin/kallidin; activating these r in vascular endothelium causes increased Ca which activates cytosolic phospholipase A2, causing prostacyclin (PGI2) production and eNOS activity; PGI2 and NO diffuse to smooth muscle, increase cAMP and cGMP respectively and mediate vasodilation (ACEi cause more bradykinin which thus causes vasodilation via this mechanism); activating Br also drives nociception (activates and sensitises) as Gq -> PKC -> phospho of ion channels involved in pain sensation kallikrein inhibited by C1-esterase inhibitor and in hereditary angioedema (HAE) mutation in C1INH causes excessive bradykinin leading to periods of severe/painful swelling; type I HAE compromises synthesis/secretion, type II allows inactive HAE to be produced; ACEi angioedema has 5x higher prevalence in african americans, possibly linked to variation in genes that control immune system; ecallantide is inhibitor of kallikrein that can treat HAE, as is recombinant C1INH, may also treat ACEi angioedema

Question 35

loop diuretics (acts where, main types (inc conversion between them and PO to IV), blocks what, why more concentrated at target site, why lose effect over time, how long to act, second mechanism of action, 4 things lost in urine (not Na/water) and one thing you lose less of)

Answer 35

act on LoH; main 2 are furosemide and bumetanide which are types of sulphonamides and 1mg bumet = 40mg furo, and you need to halve furo oral dose to get IV equiv; furosemide blocks NKCC2 in apical membrane of TAL cells, with loop diuretics beings actively secreted into PT giving conc in TAL 10-30x that in plasma repeated admin gives reduced effect as decreased ECF volume enhances reabsorption, hence why shouldn't space doses too far apart; IV furosemide acts in 10 mins (or after 1-1.5 hrs if given orally) furosemide also causes venodilation to reduce atrial filling pressure (maybe by inc prostaglandin synthesis) can cause hypokalaemia, with K replaced by exogenous K releasing compounds given in conjunction with the diuretic, or by combining loop diuretics with K sparing diuretics as in co-amilofruse; increased H loss (partly due to enhanced Na/H exchange and partly due to stim of NH3 renal synthesis/NH4+ secretion) can cause metabolic alkalosis; Ca/Mg loss increased; uric acid excretion in urine decreased which can result in gout

Question 36

metolazone (what it is, how it works, starting freq and important thing to remember when prescribing, indication x2 and what needs to be monitored, what can also be added, 4 biochem s/e)

Answer 36

a diuretic related to the thiazide class. Metolazone works by inhibiting sodium transport across the epithelium of the renal tubules (mostly in the distal tubules), decreasing sodium reabsorption, and increasing sodium, chloride, and water excretion start 2-3x a week, then alternate days, can go up to every day; need to prescribe by brand adjuvant therapy for treating severe CHF to produce diuresis in patients refractory to loop diuretics monotherapy; together they can produce profound diuresis (and so you need to keep close eye on U&Es) can be used to treat edema associated with nephrotic syndrome alone or in combination with spironolactone s/e: hyperuricemia, hyponatremia, hypokalemia, and hypomagnesemia

Question 37

thiazides (what cant you use them with and k sparing diuretics)

Answer 37

thiazides - most common are hydrochlorothiazide and bendroflumethiazide; indapamide for thiazide-like diuretics partly inhibit formation of dilute urine (but not conc urine); act in cortical segment of TAL and early DT by blocking Na-Cl cotransport (prob by binding at Cl site); also have vasodilator effects like loop diuretics, used to treat hypertension: short term by diuretic action, long term directly acting on blood vessels hypokalaemia/metabolic alkalosis; fall in K means can't use with digoxin as potentiates their action as they compete with K at Na pump; increase Mg excretion but decrease Ca excretion; uric acid excretion decreased; also danger with flecainide of long qt -> torsades k sparing - 3 main drugs: amiloride, triamterene and spironolactone; diff mechanisms of action but all depend on Na entering cells in DT through apical PM channel using gradient made by basolateral Na pump, with Na movement creating gradient that draws K into lumen so it's lost; first 2 drugs block the apical Na channels (diff from ones in excitable tissues: not VG and have diff structure) with weak diuretic effect but K loss decreased spironolactone: antagonist for aldosterone; aldosterone would bind with cytoplasmic steroid receptor, complex translocates to nucleus and induces Na channel/pump synthesis; spironolactone metabolised in liver to canrenone which accounts for some (but not all) effects of the drug; K-canrenone salt on its own works as a diuretic; spiro/canren compete with aldosterone for binding site on receptor so effect only significant when DT under effect of aldosterone; rate of onset low as determined by turnover of Na channels

Question 38

are diuretics nephrotoxic? why does cr rise? what if they're overloaded? how to escalate diuretics (urine output targets, 4 diuretic steps based on prev amount having) problem with using cr (and eGFR)

Answer 38

not directly cr rises for 2 reasons: 1. A transient increase in creatinine during the first day or so of diuresis due to an increase in serum creatinine due to loss of volume of fluid (no actual change in renal function or renal damage) or alternatively 2. if you are hypovolaemic/ dehydrated, addition of a diuretic can decrease your intravascular volume further -> lower BP -> less renal perfusion -> higher cr/ur -> AKI. If persisting, this can cause damage due to hypoperfusion of kidneys (ATN). check the haematocrit -> if also rising this is strongly suggestive of increasing concentration due to effective diuresis and associated with better outcomes if overloaded then diurese them - if BP is okay kidneys are being perfused, so rise in cr is due to becoming more concentrated; if not overloaded and on diuretics then they may be making things worse, or if third spacing when offloading if urine output aim for 100-150ml/hr, and double dose if this not reached within an hour; note also furo lasts 6hrs (why it's called lasix) and has a ceiling effect beyond which higher doses won't work (though they will last longer) how to start based on pt regular dose: if < 80furo a day then bolus 40 and infuse 5mg/hr (or can first try eg 40 and 40) if 80-160 a day then do 80mg bolus and 10mg/hr and consider metolazone 5mg OD if 160-240 do 80mg bolus and 20mg/hr + metolazone 5mg BID if >240 do 80mg and 30mg/hr + 5mg metolazone BID cr should rise giving a pseudo worsening of renal function when offloading - be guided by urine output, natriuresis

Question 39

diuretic resistant oedema

Answer 39

Diuretic resistance implies a failure to increase fluid and sodium (Na+) output sufficiently to relieve volume overload, edema, or congestion, despite escalating doses of a loop diuretic Furosemide diuresis normally lasts about 4 hours. Bumetanide is somewhat shorter and torsemide somewhat longer ormal ceiling daily dose of furosemide above which little further natriuresis occurs is 80 mg once or twice daily, increasing to 160 and 240 mg in patients with chronic kidney disease (CKD) stages 3 and 4 or nephrotic syndrome or 80 to 160 mg in patients with cirrhosis or HF with preserved GFR. Very high doses of circa 500 mg of furosemide may be required in patients with end-stage renal disease higher furosemide doses required for patients with CKD are a consequence of many factors including a decreased diuretic delivery to the kidney because of decreased renal blood flow (RBF), an increased volume of distribution of the protein-bound diuretic because of hypoalbuminemia, a decreased proximal tubule (PT) secretion of the diuretic by the organic anion transporters because of competition by urate and other organic anions that are retained in the plasma in patients with CKD, and a decreased filtered load of Na+ because of a decreased GFR for diuretic-resistant patients, the daily Na+ intake should be less than the acute Na+ loss with the diuretic to ensure a negative Na+ balance. This value is 120 to 150 mmol in normal subjects but is reduced in those with CHF to about 50 to 100 mmol rine from proteinuric patients contains sufficient proteases such as plasmin to hydrolyze the luminal peptide loops of the epithelial sodium channel, thereby opening the Na+ channel and promoting Na+ reabsorption - this can be blocked by amiloride as it blocks ENaC in cases of diuretic resistance collect 24 hr urine sodium, if >100 then dietary reduction; if not, or diet measures fail, then increase diuretic dose up to your ceiling given pt factors; if still not working measure 24 hour urine protein, if >1g add amiloride and if not add metolazone, if still not working consider continuous diuretic infusion or dialysis

Question 40

ACE inhibitors + which receptor losartan works on, benefit from combining ACEi with diuretic, why hypotension + ACEi dangerous combo

Answer 40

major egs are captopril, ramipril, enalapril antagonises the renin-angiotensin system; non-peptide ang2 antags (angiotensin receptor blockers ARBs) also developed, first one losartan but several available; losartan etc act on AT1 receptor which is the receptor that mediates ATIIs cardiorenal effects ACEi used for hypertension and heart failure (most benefit in heart failure with high renin levels); ACEi alongside diuretics almost always, with reduced aldosterone helping avoid hypokalaemia hypotension dangerous with ACEi as blocking constriction of efferent glomerular arteriole increases risk of renal failure

Question 41

diuretics and acei in hypertension

Answer 41

thiazides are most common first-line therapy in elderly patients, initially reducing blood volume before causing vasodilation with full antihypertensive effect taking up to 12 weeks to develop; ACEi (captopril) decrease circulating ang2, so dec aldosterone secretion, so less Na reabsorption - also increased bradykinin plays a minor role; side effects of ACEi minimal, most common is dry cough which can be severe, also can get angioedema so ARB; ACEi used when plasma renin high and 50-75% mild-moderate antihypertensives respond to them; effect is increased when used in conjunction with a diuretic, and ARBs can be used if patients intolerant of ACEi like losartan, aliskiren inhibits renin to stop A1 synthesis; spironolactone in people with high aldosterone (1 in 100) though cochrane review found bad side effects at high dose, low dose ineffective in many people

Question 42

hypernatraemia (top 3 dd, 3 causes of salt poisoning, 2 big hormonal causes, how to tell whether Na and water or pure water lost (inc why less apparent volume depletion in latter) and when to suspect Na poisoning, 2 other conditions may see with Na gain; if managing Na poisoning then water fluids to use and what not to use/why)

Answer 42

inc in serum Na above 133-146mmol/L so your top 3 diffs: dehydration, HHS/DM, DI sodium gain (aka salt poisoning) much rarer; can arise from sodium bicarb solution given to treat acidosis, where possible use a solution with lower Na conc (1.26%); another cause is near-drowning in salt water; a third is if infants given high Na feed, salt to a newborn also Conn's syndrome/primary hyperaldosteronism; may get similar findings in Cushings patients if mild and patient has signs of dehydration then likely loss of Na and water if more severe (150mmol/L+) then pure water loss more likely, especially if dehydration symptoms mild (depleted from all comps) relative to the hypernatraemia suspect salt poisoning if no signs of dehydration, especially if the level is 190mmol/L+ salt gain may be accompanied by pulmonary oedema and raised icp if dehydration signs then give water and Na if salt poisoning then water or hypotonic fluids given - iv dextrose in these patients can exacerbate ecf expansion leading to inc'd risk of pulmonary oedema and critically high icp, specialist help needed in eg PICU

Question 43

hypernatremia algorithm - 3 things to think first, 11 initial ix inc something to assess and something to calculate, 4 ix during mx, interpreting tests: increased volume x4 dd, then decreased in 2 different ways 4:4(inc role of Fena); mx based on volume status

Answer 43

think osmotic (HHS) and DI first (+dehydration for various causes) assess volume status and get blood and urine osmolality, U&Es, bone profile, Mg, glucose, blood gas, urine electrolytes, urine ur/cr and calculate FENa while correcting need strict input/output chart, and paired serum/urine osmol and electros every 6 hours to adjust therapy; in a child/baby you can also do daily weights increased volume suggests Na overload - salt poisoning, iatrogenic, cushing syndrome, conn syndrome decreased with hypersmolar urine: kidney is concentrating appropriately; low Na suggests GI loss (D&V, malabsorption, colostomy), otherwise eg poor intake, insensible losses through pyrexia or tachypnoea decreased with hypoosmolar urine: kidney is not concentrating appropriately; raised urine Na in osmotic diuresis, diuretic therapy (FENa high), intrinsic renal disease; low in diabetes insipidus (FENa low) if you can replace with enteral route (inc via NGT) this is best if not severe/symptomatic, and you do it by giving more free water -> calculate the amount of free water needed to get from current to target Na conc (MD calc can do this) and then you can divide that volume of free water into eg 4-hourly flushes/boluses down NGT or a volume for them to drink; if can't take this route or unwell/severe go straight for IV dex; your target BTW should be up to a 12mmol drop per day, and older ppl (with shrunken brains) could tolerate even more than this as risk of cerebral oedema is lower, risk also lower in acute setting as takes 48hrs for brain to adapt to hypernat - one case man drank quart of soy sauce Na up to 196 and hadd 6L water in 20mins to help normalise without causing cerebral oedema; note even 146-148 conc can make ppl thirsty, and hypernat tends not to get better by itself, so act hypovol gets balanced crystalloid resus then possibly 5% dex later, euvol gets 5% dex, hypervol 5% dex + loop diuretic (may also require thiazide-like to ensure a more conc urine produced, and K supplementation also often required) if poor renal function discuss with nephrologists/ITU as may need dialysis to help remove Na without giving loads of water that they can't then pee out also consider if becoming severely hypernat due to dehydration from not eatind and drinking as result of eg advanced dementia -> this is a common, painless mode of dying and consideration should be given to ACP, family wishes etc about whether to treat or not

Question 44

SIADH 14 causes and 5hypo/4eu/3hypervol hyponat

Answer 44

SIADH: MIND Malignancy (small cell lung cancer, also: pancreas, prostate) Infections (tuberculosis pneumonia) Neurological (stroke SAH SDH meningitis/encephalitis/abscess) Drugs - SIADH cannot void PP S: SSRIs (Sertaline) I: Indomethacin (Analgesics) A: Antidepressants (Tricyclics), ACEi D: Diuretics (Thiazides) H: Haloperidol + other antipsychs Cannot: Cyclophosphamide, Carbamazepine Void: Vincristine Other causes PEEP, porphyrias generally restrict fluids to treat Hyponatremia occurs if there is persistent ADH stimulation which is seen in following situations. Normal but persistent ADH secretion-In volume depletion the effect of decreased volume counteracts the effect of hypoosmolality and ADH stimulation continues to occur. Effective arterial blood volume depletion occurs by two mechanisms: True volume depletion; and in edematous patients with heart failure or cirrhosis in whom tissue perfusion is reduced because of a low cardiac output or arterial vasodilation, respectively. The reduction in tissue perfusion is sensed by baroreceptors at three sites: (i) In the carotid sinus and aortic arch that regulate sympathetic activity and, with significant volume depletion, the release of antidiuretic hormone; (ii) In the glomerular afferent arterioles that regulate the activity of the renin-angiotensin system; and (iii) in the atria and ventricles that regulate the release of natriuretic peptides. As a result there is water retention Abnormal ADH secretion e.g. Syndrome of inappropriate ADH release hypovol hyponat: cerebral salt wasting syndrome (after SAH, pitu surg, infection etc), thiazide diuretics (loops not so much as they act in loop which reduces countercurrent generation and so reduces how much water ADH can reabsorb), mineralocorticoid (adrenal) insuff (may see high K too but dont have to) euvol hyponat: SIADH, polydipsia (inc exercising and not replacing electrolytes), poor diet (not enough na), hypothyroid (CO down, ADH release therefore up), glucocort def (*key SIADH diff - must rule out this and hypothyr before diagnosing - pathology is cortisol inhibits ADH release so less cort more ADH, exacerbated by cort reduction meaning lower BP) hypervol hyponat: CHF, cirrhosis, nephrotic syndrome, CKD

Question 45

hyponatremia algorithm (2 qs to ask, 4 things to look for with assessing volume status, 8 ix, interpreting the above to classify 2:2:1:4:4:3:5:3 - order hyper hypo eu; mx based on volume status inc 2 options for SIADH; what if seizures/drowsy? including where they should be and what if also overloaded; how to calculate how much Na required; what is the max 24hrs rate of change (inc what this means per hour and what the exception is)

Answer 45

are they on meds that can cause it? any signs of endo or renal/resp/liver disease, or a cause of SIADH? look at fluid balance and assess fluid status - comment on JVP, skin turgor, get l/s BP, and look for oedema/ascites Ix: (U&Es, Mg, Glu, LFTs, Paired Osmolalities, Urine Na, TFTs, 9 am Cortisol) - note urine/serum osmol unreliable if diuretics given high osmolality hyponat may be hyperglyc or presence of eg glycine/mannitol - use calculator to correct for raised BMs normal osmo hyponat is pseudohyponat from hyperlipidaemia or hyperproteinaemia - this is a laboratory artefect that can be corrected for if low osmolality look at volume status, urine osmol, and urine Na; can be difficult to assess volume status esp hypo vs eu so another way to think is is RAAS on (aka urine na low) and is ADH on (urine osmol > serum osmol), RAAS is on if EABV is low (hypovol or hypervol w pathology), ADH is appropriately on if RAAS is also on, if RAAS off (urine Na high) but ADH on (urine osmol > serum osmol) then inappropriate ADH secretion or else DI overtreatment hypervol: is urine Na >20 then CKD, if <20 then CCF, cirrhosis, nephrotic syndrome, or other cause of hypoalbuminemia hypovol: urine Na >20 then diuretics, addisons, proximal RTA, salt-wasting nephropathy; urine Na <20 then vomiting, diarrhoa, or third spacing (pancreatitis, SBO/LBO, burns) euvol: urine osmol <100 then water intoxication (primary polydipsia, ecstasy, marathon runner or beer drinkers potomania -> low solute content of beer, and suppressive effect of alcohol on proteolysis result in reduced solute delivery to the kidney) or tea and toast syndrome, if >100 then hypothyroid, glucocorti def, SIADH (or overtreatment of DI with desmopressin) also note hypokal causes hyponat due to altered renal handling of Na -> correct K before correcting Na if you can, or correct Na cautiously -> small pt with hypokal and hyponat will correct fast and higher risk of osmotic demyelination hypervol gets fluid and salt restriction, furo too if severely overloaded; if hypvol treat cause and give 0.9% NaCl gradually if euvol find and address cause, water restrict to < urine output - if SIADH and resistant you can give demeclocylcine or ADHr antags if seizures or drowsy aim to bring Na up by 1-2mmol/hr for first 2-3 hours by giving 1.8% NaCl 300ml over 30 mins and repeating if needed; if overloaded also give some furosemide IV; will need to monitor U&Es 1-2hrly and pt will need to be in ICU; to work out exactly how much do Na conc of the fluid (154 for 0.9%, 308 for 1.8%) minus conc in plasma all divided by 1 + total body water (body weight x 0.6 if young man, 0.5 if old man or young woman, 0.4 if old woman)) and remember you're aiming for 1-2mmol/hr in first 3 hours (but then need to reduce to ensure 24hr max isn't breached do not increase by more than 10-12mmol/L in 24 hrs (ie 0.4-0.5mmol/hr - with exception only for the seizures/drowsiness above)

Question 46

interpreting ADH and RAAS in hyponat

Answer 46

RAAS activates before ADH system if low effective arterial blood volume, and is measure by urinary Na - so urinary Na will be low in low EABV states and so you need to see this to judge that ADH secretion is appropriate; if urine osmolality is raised (ADH secretion on) but UNa high (RAAS off) then the ADH secretion is inappropriate volume status is clinically tricky to assess (esp euvolemia) It's better to go sOsm for tonicity -> uOsm to determine whether ADH is on our off and then if on -> evaluate uNa to determine whether RAAS is on or off and whether ADH is appropriate. If ADH is off, you can consider primary polydipsia, tea and toast, beer potomania, etc. If ADH is on and RAAS is off, it's more consistent with SIADH (also thyroid/adrenal problems). If ADH and RAAS are both on, then EABV is low either due to hypervolemia (heart failure, cirrhosis etc) or hypovolemia UNa doesnt measure RAAS if on diuretics - in this case you can use FeUrea and if <55% RAAS is on uric acid can be used as a proxy for ADH due to complex renal mechanisms -> if serum uric acid low then ADH is on (eg can support diagnosis of SIADH)

Question 47

correcting hypokal and hyponat at same time

Answer 47

hypokalemia shifts sodium intracellularly and enhances vasopressin release, thereby worsening hyponatremia over-correction of sodium levels carries a risk of osmotic demyelination and permanent brain damage potassium is just as osmotically active as sodium, so if replacing it then intracellular sodium will move out into the extracellular fluid in exchange for potassium, and ADH release will fall -> thus sodium conc will rise as potassium conc rises therefore if sx allow replace K first, then Na afterwards to avoid over-correcting and increasing risk of osmotic demyelination

Question 48

assessing and managing hyponat (good threshold for concern, hyponat sx result from what and include 6sx and what threshold for 2 more; signs for Na depletion (5 inc first sign) vs water retention and why the difference, why do oedematous pts oft become hyponatremic (and what is their body Na status), general mx principle based on volume status)

Answer 48

120mmol/L good threshold as risk sharply incs below this conc and decs above it - but other factors too eg how fast is it falling hyponatraemia symptoms result from hypoosmolality leading to cell oedema and include: nausea, headache, malaise/lethargy, then bad mood/irritability and/or muscle cramps, then reduced consciousness - and typically below 115mmol/L seizures, coma Na depletion will give symptom of ecf compartment depletion: soft/sunken eyeballs, dry mucous membranes, raised pulse, decrease urine output/skin turgor, and postural hypotension postural hypotension typically first sign probably wont see signs of water overload if water retention as evenly distributed in all body comps, and rise is gradual patients with oedema often become hyponatraemic because the various causes trigger hyperaldosteronism, retaining Na and water but water more so due to ADH due to hypovolaemia; thus despite hyponatraemia also have Na overload if hypovolaemia (Na depleted) then give Na, if normovolaemic restrict fluids instead diuretic and fluid restriction for oedematous patient if seems serious (<120mmol/L), then hypertonic saline may be indicated; diuretics may be needed if hypervol

Question 49

sodium correction for hyperglycemia

Answer 49

Hyperglycemia causes osmotic shifts of water from the intracellular to the extracellular space, causing a relative dilutional hyponatremia, so you need to correct for this MDCalc can do this as glucose falls corrected Na should rise, aiming for >5 in first 8 hours; if it doesn't rise there is a risk of cerebral oedema

Question 50

management of hyponatremia

Answer 50

you might only investigate if <130 correct by no more than 0.1-1mmol/L every hour, and no more than 8-10mmol/day (10mmol/day for first day then no more than 8mmol/day after this) if unsure whether hypovol or euvol then can treat with IVF as for hypovol, if it stays same or gets worse then that suggests euvol SIADH (you pee out the electrolytes, but retain some of the water further diluting the Na); if hypovol due to sepsis but also hyponat (with possible SIADH contribution) and v large volumes of fluid needed then 1.8% sodium chloride is an option but try 0.9% first hypovol gets IVF, but if dehydrated and Na 130-134 then consider ORS instead (checking to make sure Na improves) fluid restrict for euvol, aim is 500ml < 24 hour urine output, can start with eg 1.5L, tricky if urine output low -> if <1500ml/day then more likely to fail; in kids instead of 1.5L as starting point due 0.5 or 0.75 of maintenance volume; monitor Na 4 hourly until 125+ then every 12 hours until >130; antidiuresis from fluid restriction may work against you severe hyponat, esp if accompanied with sx, needs correction with hypertonic 3% sodium chloride, which will be given by ITU so speak to them theory behind salt tablets eg slow sodium: more osmoles into plasma, this helps kidney remove more water as excess Na removed with water, but makes pt thirsty, not a good idea if HTN or heart failure, and needs to accompany fluid restriction (tricky if you're making pt thirsty); volume of slow sodium needed may also not be effective if Na <125 and urine osmol >500 more protein works similarly (boosting solute to help renal excretion) without making pt thirsty so high protein intake or eg protein supplement is best option here (works via protein induced ureagenesis, more urea = better water removal) urine volume produced = solute load (mmol)/urine osmolality -> note that IV fluid generally contain more free water by volume than the volume that would be removed by the solute load they contain (1L normal saline gives 1L water and causes 500mL water removal in urine) - hypertonic saline overcomes this and will correct hyponat regardless of aetiology demeclocycline induces nephrogenic DI, takes 72 hrs with sig Na rise in 5-7 days (can be used in chronic SIADH) tolvaptan is V2r antag and can be used in SIADH if Na <125 not responding to fluid restriction alone (or fluid restriction not practical) SGLT2i have also been shown to help correct hyponatremia (osmotic diuresis) furosemide is another option, and IV saline (or slow sodium if you must) can then be used to replace lost Na (must be hypertonic) if all other measures failed, or urgent need to correct due to symptoms, or dual diagnosis requiring lots of fluids (eg hypovol and SIADH) then hypertonic saline -> 1.8% or 3% depending on urgency and monitoring availability; former can be given via peripheral cannula on ward as 500ml over 10 hours (need to check U&Es after before any more); if <110 or severe sx then ITU and 3% -> note that hyponat seizures often don't respond well to anticonvulsants so giving 3% saline is the priority, while ideally should be given via central line can be done peripherally in large proximal vein if monitor closely for extravasation; check Na after each bag and switch to different fluid once >125mmol/L or Na icreased by 5mmol/L or seizures stopped, whichever comes first

Question 51

hypoalbuminemia (how common, 6 basic mechanisms causing, albumin half life, common reason to see, decreased production cause x1, renal loss x2, gut loss causes (5:8:4), 3rd space loss x2, 4 reasons why seen in critical illness, 3 reasons why seen in heart failure, general mx, 6 reasons to replace)

Answer 51

one of the most prevalent disorders in hospitalized and critically ill patients may be a result of decreased production (rare) of albumin or increased loss of albumin via the kidneys, gastrointestinal (GI) tract, skin, or extravascular space or increased catabolism of albumin or a combination of these mechanisms half-life of 21 days Note albumin is negative acute phase reaction, ie if acute phase inflam going on with CRP etc rising then albumin might fall as part of this Decreased production of albumin is a rare cause of hypoalbuminemia. Significant and severe chronic hepatic impairment is required before a noticeable decrease, as in advanced cirrhosis renal loss: nephrotic syndrome, CKD (ESRD) gut loss: erosive loss (IBD, malignancy, carcinoid, peptic ulcers, c. diff), non-erosive (celiac, sprue, parasites, SIBO, whipples, SLE, amyloidosis, AIDS), raised lymphatic pressure (heart failure, cirrhosis or liver outflow obstruction, thoracic duct obstruction, mesenteric TB) 3rd space loss: burns, sepsis seen in critical illness as cytokines suppress hepatic production (acute phase response) and capillaries leaky allowing 3rd spacing, plus some protein losing enteropathy and dilution from IV fluids seen in heart failure due to haemodilution, liver dysfunction, protein losing enteropathy treat cause generally highest-quality evidence exists for the use of albumin in patients with cirrhosis, particularly for the treatment of SBP, HRS, and large-volume paracentesis For patients with sepsis or ARDS and undergoing ECMO, the evidence for albumin therapy is not robust enough to allow for a general recommendation. Albumin should be considered when hemodynamic stability cannot be achieved with crystalloids alone or you have volume shift with oedema; raising albumin may also help improve diuretic efficacy

Question 52

K distribution and conc in plasma - inc why is moving into the intracellular compartment appropriate (short term)

Answer 52

kidneys control amout but <2% in ECF, 5.5 moles 98% in cells so short term change in distribution between compartments, kidneys regulate total amount and respond to changes in [K]plasma, maintaining it at 3.5 to 5mM, intracellular is 125mM; cell membrane, critical for excitable cells so halving or doubling conc gives severe disturbances to function of skeletal/cardiac muscle; volume maintenance, pH control, enzyme control; extracellular space is smaller than intracellular space so change in amount in extracellular compartment causes larger conc change and has a larger effect, thus short term control by moving between compartments is appropriate

Question 53

stress to K balance and hom mechanisms related to this

Answer 53

K intake which is sporadic and can vary from day to day meaning the regulatory system should be able to adjust, K transiently stored in cells and slowly excreted and thus should be added to IV fluid to balance losses; insensible losses of ~10mmoles in faeces/sweat, can vary considerably eg vomit, diarrhoea, sweating; controlled loss, with kidneys excreting 1-80% of filtered K allowing control despite varying intake/insensible losses; APs can shift K from intracellular to extracellular with skeletal muscle containing up to 70% of body's K; dehydration causes cells to shrink so [K] increases so some is excreted into IF; cell lysis releases K which is significant in burns, trauma, compartment syndrome, tumor lysis syndrome (excessive tumor death after chemo), acidosis causing H/K exchange with cells taking up lots of H as well buffered; hyperhydration can cause cells to take up K, adrenaline and insulin increase Na pump activity which means more K into cells

Question 54

K and acidosis/hyperglyc (inc organic acids, non-organic acidemias, and link to kidney)

Answer 54

low pH in IF inhibits Na/H exchange and Na/HCO3 cotransport which lowers pHi and [Na]i, the decreases pHi compromises Na pump and NKCC2, lowered [Na]i contributes to lowered Na pump activity, thus K remains outside cell leading to hyperkalaemia; high IF pH or [HCO3] enhances Na/H exchange and Na/HCO3 cotransport thus enhancing Na pump activity and inducing hypokalaemia; the reverse also holds true with hyperkalaemia causing acidosis/cell alkalosis and hypokalaemia alkalosis and cell acidosis; severe hyperglycaemia can induce cell shrinkage to give increased IF [K] like dehydration note: in metabolic acidosis caused by organic anions the OAT allows organic acids such as lactic acid or ketones to enter the cell. As the H+ concentration increases intracellularly, there is more Na+-H+ exchange and more influx of Na+ into the cell. More available Na+ intracellularly means more Na+ is pumped out by Na+K+ATPase, and more K+ is brought into the cell Concurrent hyperkalemia and lactic acidosis or diabetic ketoacidosis may of course still occur. However, in such cases, hyperkalemia is often due to an epiphenomenon related to complicating factors. In the case of lactic acidosis, this may be related to concurrent renal dysfunction while in diabetic ketoacidosis it may be related to hyperosmolarity or insulin deficiency so when you see a patient who has hyperkalemia and lactic acidosis, ask yourself “What else am I missing that can explain the hyperkalemia? in non-organic acidosis plasma potassium concentration may rise by up to 0.6 mmol/L for every 0.1 reduction in pH; smaller shifts in resp acidosis as CO2 enters cells (lipid soluble) and acidifies inside so Na/H exchange up, though you can still get hyperkalemia Renal K+ excretion will be acutely inhibited by acidemia but ultimately enhanced by the increased distal Na+ delivery and flow rate caused by metabolic acidosis and osmotic diuresis in the setting of high aldosterone (due to volume depletion from the above). Indeed, the patient may present with marked K+ depletion if osmotic diuresis has been going on for some time - see RTA

Question 55

insulin adr and kidney in k control (why would there otherwise even hyperkal if those hormones don’t work, what receptors they use and effect of this, 2 pts who may thus dev transient hyperkal, which cell is K in kidney regulated at and by what hormone, is K normally secreted or resorbed and how can you tell)

Answer 55

feedforward response to eating/exercise with insulin/adrenaline acting on receptor and GLUT4/ receptor then cAMP cascade respectively to increase Na pump as well as increase in [Na]i from glucose transport or APs; aldosterone acts on mineralocorticoid receptor and stimulates Na pump as well as K excretion by kidney, released by cells in adrenal cortex in response to elevated plasma [K]; poorly treated diabetics can thus develop transient hyperkalaemia after eating and patients taking beta blockers for eg hypertension can develop it after exercise 67% reabsorbed in PT, 20% in TAL, 3% in DCT, 9% in CCT; 50% secreted in DCT and 30% in CCT though that can change; K freely filtered 13% of filtered K reaches DCT due to unregulated reabsorption with more unregulated reabsorption in type A intercalated cells of DCT/CCT and regulated secretion from principal cells; thus all regulation is essentially at principal cells which can produce net reabsorption or secretion (usually the latter as dietary intake far greater than insensible losses); secretion must occur sometimes as urine can contain more K than the amount filtered

Question 56

more kidney handling of K (NKCC2, aldos mechanism, flow rate)

Answer 56

paracellular diffusion due to water reabsorption at TAL and transcellular movement by NKCC2 then basolateral K channels, diuretic furosemide reduces NKCC2 activity to decrease K reabsorption and increase distal tubular flow, increasing K excretion and possibly causing hypokalaemia; DCT and CCT reabsorb via ATP driven K/H exchanger at type A intercalated cell, very pH sensitive so more reabsorbed in acidosis principal cells of DCT/CCT have basolateral Na pump which creates an electrochemical K gradient with K diffuses through basolateral K channels to enable Na reabsorption and secreted into lumen through apical SK (small Ca activated K channel); apical ENaC provides Na for pump and prevents excessive Em developing increases tubular flow rate increases K secretion as removes secreted K to renew gradient, in hypovolaemia increased Na reabsorption would be expected to increase K secretion but opposite happens due to decreased flow rate, increased flow rate also delivers more Na to be reabsorbed to increase Na pump activity; high plasma conc means high IF conc means more transported ino principal cells to enhance secretory gradient aldosterone from cortex due to increased K plasma conc to increase activity of Na pump, ENaC, SK by stimulating protein synthesis, its actions thus taking at least 30mins, if adrenal glands removed in animal less sharp relationship between urine K and plasma K as aldosterone infused at constant rate, however aldosterone in hypovolaemia doesnt increase secretion as offset by decreased flow rate; ADH promotes water reabsorption to decrease flow which should decrease K secretion but it avoids regulating K by increasing luminal K conductance in principal cells to balance effect; increased plasma K also potentiates K excretion by decreasing Na/fluid reabsorption in PCT leading to increased flow rate

Question 57

hyperkalaemia (ecg changes, symptoms, causes, management)

Answer 57

normal is 3.5-5.3mmol/L immediately life threatening if >7mmol/L, may cause cardiac arrest ECG changes seen inc: tall tented T waves and widening of QRS complex may see muscle weakness and paraesthesia, palpitations almost all have decreased excretion due to renal failure leading to reduced GFR and exacerbated by concurrent metabolic acidosis; or due to hypoaldosteronism reducing GFR, often seen with ACEis and ARBs, or adrenal insufficiency can also be due to redistribution out of cells: during rhabdomyolysis, trauma, or tumour lysis syndrome; metabolic acidosis also causes; as does insulin deficiency (insulin stims uptake of K, so you may see it in eg diabetic ketoacidosis) recurrent attacks of weakness/paralysis, often precipitated by rest after exercise, can be due to rare autosomal condition hyperkalaemic periodic paralysis increased intake is 3rd major cause: esp a risk in patients with impaired renal function; eg the K included in many drugs; iv K shouldnt be given at more than 20mmol/hr unless extreme circumstances; blood products may also cause as RBCs release K when stored so use blood less than 5 days old or wash prior to transfusion calcium gluconate 10ml over 10 mins counteracts the effects on Em of cells 5-10u actrapid insulin in 250ml dex 10% + 5-10mg salbutamol neb given to promote K uptake by muscle nebs/insulin can be given if >6 but <7 and no ecg changes, w/o also giving the ca gluc correct reduction of GFR if possible, if not then give dialysis cation exchange resins only useful in modest, slow increases in K

Question 58

hyperkal periodic paralysis syndrome (mutation in what gene, result of mutation and how this leads to weakness and paralysis, usual presentation inc muscles commonly affected and 3 common triggers, how long attacks last, another muscle sx, 4 parts of diagnosis, mx x2)

Answer 58

caused by a point mutation in the SCN4A gene; channels malfunction by allowing too much sodium into skeletal muscles by staying open too long or not staying closed long enough. This additional influx of sodium triggers a release of intracellular potassium from the skeletal muscles; impairs a muscle's ability to contract, leading to weakness or paralysis typically present in the first or second decade of life with intermittent bouts of weakness or paralysis in the hips, shoulders, and back. Common triggers are potassium-rich foods, a cold environment, and rest after physical activity Attacks are generally intermittent and last 15 minutes to 1 hour. Affected individuals may also present with myo/paratonia (muscle stiffness or inability to relax muscles); Diagnosis is based primarily on several criteria, which include a history of transient episodes of weakness, ictal serum potassium levels, electromyography, and exclusion of secondary causes Treatments include behavioral interventions directed at avoidance of triggers, modification of potassium levels through diet, diuretics, and carbonic anhydrase inhibitors

Question 59

hypokalaemia causes, sx

Answer 59

reduced intake is rare cause as renal retention of K when levels fall means intake must drop a lot but consider when patient having hypocaloric diet eg for weight loss redistribution into cells: metabolic alkalosis, insulin treatment (for eg diabetic ketoacidosis), refeeding syndrome (after starvation, fed with lots of carbs, seen in eg POWs; phosphate/Mg/K falls due to insulin release for raised glucose; anorexia patients may get, also at risk those with: cancer, alcoholism, post-op; beta agonism (inc stress through b2r); treatment of anaemia with folic acid/vit B12 due to new cells taking up K heritable hypokalaemic periodic paralysis resembles refeeding syndrome, can be preciptated by rest after exercise, and may also be acquired by thryotoxicosis (esp in males of chinese descent) poss due to inc'd catacholamine sensitivity GIT: vomiting/diarrhoea, esp see in eg cholera, or chronic laxative abuse (but rule out other causes first for the latter) urinary: loop and thiazide diuretics, mineralocorticoid excess, hypomagnesaemia (if less than 0.6mmol/L Mg then get impaired renal tubular absorption, at higher levels and generally more likely if also using PPIs); tubulopathies, often due to platinum containing drugs, rare mutations too note alcoholic patients esp prone to hypokal for various reasons is cause obvious? vomiting/diarrhoea/diuresis no - is there evidence of redistribution into cells eg high bicarb, low phosphate/glucose; also check Mg no - check urine K as could be cushings, Conns, low Mg causing loss in urine no - rarer gut causes: villous adenoma, laxative abuse no - drugs that could explain: diuretics, amphotericin, salbutamol, dobutamine, vit B12, folate no - rarer causes: inherited tubulopathies can give oral K salts in enteric coating for prophylaxis, or iv K up to 20mmol/hr to treat if bad (unless extreme, but in this case must have ecg monitoring) in terms of sx: mild may have none, perhaps arrhythmia; severe can cause muscle weakness, myalgia, tremor, and muscle cramps (owing to disturbed function of skeletal muscle), and constipation (from disturbed function of smooth muscle). With more severe hypokalemia, flaccid paralysis and hyporeflexia may result. can get resp depression, rhabdomylosis

Question 60

hypokalemia causes - 4 broad overview reasons, dd based on urinary potassium (7:3:8 and for final of those 1:3:4), explaining effect of abx; 10 ix and one thing to calculate; mild, mod, severe, critical and how to mx based on this; 3 oral replacement options inc sando-k mmol content and how many bananas or cups of orange juice needed; IV concentrations and max rate, how to give on ward and what if fluid restricted, how to monitor)

Answer 60

hypokal: compartment shift, renal loss, GI loss, inadequate intake low urinary potassium: lower GI loss eg diarrhoea, laxative abuse, insulin, beta agonists, methylxanthines, bicarb therapy, periodic hypokal paralysis high urinary potassium with acidosis: RTA t1/t2, DKA high urinary potassium with alkalosis: vomiting, NG suction, bartter, gitelmans, diuretics, beta-lactams (anionic, in tubular fluid cause retention of cationic K by electrical effect), hypomag, deranged renin aldosterone axis (low r high a in primary hyperaldost; high both in heart failure, RAS, renin-secreting tumours; low both in cushing syndrome, steroid use, licorice, adrenal hyperplasia get urine and serum K and osmolality, measure magnesium, calculate transtubular potassium gradient TTKG, establish acid base status and BP; then think about renin, aldosterone levels; get an ECG mild is 3-3.5, moderate 2.5-3, severe 2-2.5, critical <2; if 3-3.5 then oral replacement, if <3 then IV route if symptomatic or ECG changes, if <2.5 then definitely IV oral options: sando-K first line (1 tablet is 12mmol); alternatives include K syrup (kay-cee-l); slow-K tablets another option but v irritant and can cause ulcers, esp if motility problems; a banana has 12-15 mmol, so 5-6 bananas a day could be an option, one cup of orange juice has similar amount so could do eg 2x cups orange juice and 2-3 bananas depending on size IV can give 20 (levels normal, for prophylaxis) or 40 mmol/L (<3.5), not at a rate higher than 10mmol/hr; give in NaCl or 5% dex over minimum 4 hours (can do 20mmol/hr so over 2 hours if you need to); can be in 500ml or in 100ml in ITU with cardiac monitoring, if eg fluid restricted; should use large peripheral vein or a central vein so as not to cause sclerosis of the vessel whenever you're replacing, but esp if <3, you need daily U&Es to monitor

Question 61

hypokal periodic paralysis syndrome - channel types affected, acquired cases associated with what, mean age of presentation; 2 common triggers and possible explanation of this; how freq are attacks; history including which muscles tend to be affected and ictal K levels, features of prodrome x3, which limbs more and 3 groups spared, another uncommon feature; initial mx and 2 further steps

Answer 61

Most cases of the HypoKPP are hereditary or familial. The familial form of HypoKPP is a rare channelopathy caused by the mutation in either of the calcium (usually) or sodium ion channels; acquired cases known, associated with hyperthyroidism; mean age of presentation of attacks is the first or second decade of life, usually the late childhood or teenage years most consistent triggering factors are rest following strenuous exercise and consumption of diets rich in carbohydrates -? rise in insulin/adr causes K shift into muscles maybe; attacks may be frequent, or one and done usually present with attacks of generalized severe muscle weakness, with proximal muscle involvement more marked than distal and a profound decrease in serum potassium level - often go to bed normally and then wake with profound weakness; may have prodrome (fatigue, paresthesias, behavioral changes a day before an attack); lower limbs oft more than upper, and Bulbar, ocular, and respiratory muscles are usually spared; myotonia is uncommon initially lifestyle modifications, then K supplements and acetazolamide if that doesn't control

Question 62

hypokalemia algorithm

Answer 62

K+ is freely filtered across the glomerulus and then avidly reabsorbed by the proximal tubule and thick ascending limb of the kidney. Only a small amount of K+ reaches the distal nephron. K+ reabsorption in the proximal tubule is primarily through the paracellular pathway and is in rough proportion to the amount of Na+ and water reabsorbed In the thick ascending limb, K+ reabsorption occurs by both transcellular and paracellular pathways. Transcellular movement is mediated by the Na+-K+-2Cl− cotransporter located on the apical membrane. A component of K+ that enters the cell back diffuses into the lumen through the ROMK (renal outer medullary K+) channel, leading to the generation of a lumen positive charge which, in turn, drives a component of K+ reabsorption through the paracellular pathway K+ secretion begins within the early distal convoluted tubule and progressively increases in magnitude into the cortical collecting duct. Physiological needs regulate the secretory component of K+ handling Electrogenic secretion through the ROMK channel is the major K+ secretory mechanism in the distal nephron. Maxi-K+ or BK channels are a second type of channel that also mediates K+ secretion under conditions of increased flow. In addition to stimulating maxi-K+ channels, tubular flow also augments electrogenic K+ secretion by diluting luminal K+ concentration and stimulating Na+ reabsorption through the epithelial Na+ channel (ENaC). This stimulatory effect can be traced to a mechanosensitive property whereby shear stress increases the open probability of the ENaC channel for hypokal, first check either 24 urine K or spot urine K:creatinine ratio, if either is low suggests extrarenal cause (cell shift or loss via other means eg gut, or poor intake) -> if still in doubt caculate TTKG, if <3 then extrarenal if EABV up (hypertensive) check renin and aldos levels (both high RAS or renin tumour, aldos only high then hyperaldos, both low then cushing or liddle syndrome or CAH if EABV normal/low check serum bicarb -> if low then RTA, if high check urine Cl; if urine Cl low then vomiting or niche things, if high then loop/thiazide diuretics, gitelman or bartter syndromes, Mg def

Question 63

Ca hom intro (hyper and hypo symptoms)

Answer 63

Ca has structural role in bones, roles in signalling, exocytosis, ECC, stability of excitable cell membranes hypocalcaemia lowers AP threshold giving spontaneous activity, motor nerves especially vulnerable and may give tetany with death resulting from tetanic contraction of muscles in larynx hypercalcaemia raises AP threshold giving sluggish CNS function, muscle weakness, arrhythmia, kidney stones from precipitating calcium phosphates but not dangerous in short term ~99% in bones, relatively stable; 1kg of Ca in bones locked up as hydroxyapatite, 1g lines surfaces of canals in bone with fluid available for exchange, another gram in the ECF; plasma [Ca] is 2.5mM, around half bound to proteins, just under half free and the remainder complexed with anions; ionised Ca should be 1-1.4; pseudohypo if albumin levels low as bound to that, so labs correct (give result if alb levels normal) mass balance is the key regulatory feature with amount ingested = amount in faeces/urine, achieved via bone remodelling, inc Ca output by kidneys and balancing distribution between gut and ECF

Question 64

PTH and vit D link to Ca levels

Answer 64

PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation most important action of 1,25-dihydroxy-vitamin D is to increase the active absorption of Ca2+ from the intestinal lumen of the gut by increasing expression of Ca binding proteins vitamin D also increases uptake of phos and Mg2+ from the gut; Within bone, 1,25-dihydroxyvitamin D has an effect synergistic with that of PTH stimulating bone resorption and, thereby, raising circulating Ca2+ concentrations. If pth is low, Ca will be low; pth may be high due to vit D and Ca levels being low (sec hyperpara) PTH stimulates bone resorption, releasing Ca and phos; the phos is rapidly removed from the circulation because the most dramatic effect of PTH on the kidney is to inhibit reabsorption of Pi in the proximal tubule and markedly increase its excretion. At the same time, PTH also enhances Ca2+ reabsorption in the ascending loop of Henlé and the distal convoluted tubule; it also incs vit D synthesis in kidney

Question 65

hypocalcaemia investigations + mx

Answer 65

healthy serum calcium is approx 2.4mmol/L, half bound to plasma proteins (less in acidosis and more in alkalosis) if albumin falls, total serum Ca will also fall but will have normal unbound Ca levels as this is the regulated part, thus not hypocalcaemic many labs thus reported a calcium figure adjusted for this, reporting what the total would be if normal albumin present after the initial test for ca ask: renal disease? measure urea and creatinine, and if fine then measure Mg and phosphate - > low suggests vit D deficiency and high hypopara; vit D def even more likely if PTH levels appropriately elevated, other rare causes and pseudohypopara; if PTH is inappropriately low may be due to post-surgery, Mg deficiency, or else idiopathic chronic renal failure affects synthesis of vit D metabolites giving hypocalcaemia quite commonly, and from that bone disease and hyperparathyroidism in acute give iv ca gluconate 10% boluses to stabilise then infusion in dilated iv fluids (need ecg monitoring for both); in chronic can give oral ca and vit D supplements

Question 66

early and late neonatal hypocalcemia

Answer 66

early onset: within the first 72 h of life more common in preterm infants, infants with intrauterine growth retardation, infants with perinatal asphyxia, and the infants of diabetic mothers, as well as seen in infants with severe vit D deficient mothers, sepsis, maternal use of anticonvulsants and high dose antacids causes varied: causes of hypocalcemia in premature infants include early discontinuation of calcium transfer through the placenta, an exaggerated decrease in the serum calcium level that physiologically occurs postpartumly, the reduced response of target organs to PTH, and increased calcitonin levels. The main causes of hypocalcemia in infants with asphyxia include increased phosphate load due to cellular damage, increased calcitonin production, renal failure, and decreased PTH secretion. The main cause of hypocalcemia in the infants of diabetic mothers is hypomagnesemia in the mother and the infant due to increased maternal urinary excretion of magnesium during pregnancy causing functional hypoparathyroidism in the infant. The increased maternal calcium due to maternal hyperparathyroidism passes to the infant through the placenta and suppresses fetal PTH synthesis late onset occurs after the first 72 h and generally by the end of the first week of birth. The most common causes of late-onset hypocalcemia include excessive phosphate intake (eg feeding with cows milk), hypomagnesemia, hyper calciuric hypocalc, hypoparathyroidism (inc syndromic eg DiGeorge syndrome and secondary due to mat hyperpara), PTH resistance (aka pseudohypopara) and vitamin D deficiency, or iatrogenic (diuretics, bicarb, phosphate etc) ionized calcium, phosphate, alkaline phosphatase, magnesium, albumin, and creatinine levels should be checked +/- PTH, 25-hydroxyvitamin D, and, if necessary, 1,25-dihydroxyvitamin D, urine calcium/cr sequence: albumin (if low check ionised Ca or adjusted Ca to confirm true hypocalc), if confirmed or albumin normal then urine ca (if high hypercalciuric hypocalc), if low check phos (if low rickets or Vit D def), if high check PTH (low/normal hypopara and high pseudohypopara) check an ECG and examine for signs of hypocalc

Question 67

hypercalcaemia clinical (inc when life threatening, 3 options for mx, first ix when find it, 15 sx, how much fluid commonly needed, bisphos choice and when to repeat, how long to normalise and monitoring bloods)

Answer 67

if >2.8mmol/L, non-specific symptoms so may find in any ward - still treat with rehydration if >3.5 after adjusted for albumin then life threatening and treat immediately - rehydration, consider bisphosphonate + calcitonin if >4; if still up after 5 days give second dose of bisphosphonates if over 2.8 but <3.5 then measure PTH: if undetectable then why has Ca become high enough to suppress it? suggests malignancy or other cause of high Ca; if detectable/high then suggests primary hyperparathyroidism (often adenoma) More frequent urination and thirst. Fatigue, bone pain, headaches. Nausea/vomiting, constipation, decrease in appetite. Forgetfulness. Lethargy, depression, memory loss or irritability. Muscle aches, weakness, cramping and/or twitches shortened QT interval < 3 - watch/wait, rx if sx troublesome. >3: recommend treatment to reduce distressing sx : Rehydration with 1-2L IV normal saline. Commonly need 4L. IV bisphosphonates. (Zoledronic acid) If don’t respond can repeat bispho after 5 days, and consider denosumab - particularly for bony mets. Maintain hydration and repeat Ca/U+Es at 48h. Normalisation can take 3 days or more

Question 68

hypercalciuria and nephrocalcinosis

Answer 68

Nephrocalcinosis (NC) describes the deposition of calcium salts in the tubules, tubular epithelium and/or the interstitial tissue of the kidney. It may be detected incidentally (e.g. ultrasound for another indication) without evidence of kidney dysfunction, or it may result in acute or chronic kidney injury as well as being a risk factor for nephrolithiasis Hypercalciuria (which may occur in the context of hypercalcaemia or normocalcaemia): Idiopathic hypercalciuria – the most common cause of hypercalciuria Increased sodium/salt intake (leads to increased distal tubular secretion of calcium) Vitamin A, C and D excess or intoxication Prolonged immobility leading to increased bone resorption leading to resorptive hypercalciuria Hyperparathyroidism Hypophosphatasia Hypophosphataemia Ketogenic diet Malignancy with paraneoplastic effects Sarcoidosis and other granulomatous diseases Milk-alkali syndrome – hypercalcaemia and metabolic alkalosis secondary to high intake of calcium and absorbable alkali Inherited disorders affecting the renal tubules (type 1 RTA, bartter syndrome and many others) loop diuretics, steroids, acetazolamide, topiramate, Ca/vit supplements and more USS (diagnostic/rule out stones) bloods: (U&Es, bone profile, VBG, PTH, vit D level, uric acid) urine: (M&S, pH, creat ratio to (citrate, oxalate, urate, calcium, protein), urine amino acids and organic acids, tubular reabsorption of phosphate 24 hour urine collection for Ca would be useful if possible Any causative agent (e.g. furosemide) should be stopped if possible. Liberal fluid intake (>1.5 L/m2/day) is likely to be of benefit in helping reduce the risk of stone formation. Dietary advice for those with hypercalciuria and/or hypocitraturia: Adding fresh lemon juice to water as a source of citrate Avoiding carbonated drinks Salt restriction of 2-6 g/day depending on age Maintaining normal calcium intake of between 350 mg/day for children and 1000 mg/day for adolescents Thiazide diuretics can be started if not hypovolaemic +/- potassium citrate supplementation

Question 69

blood phosphate - causes of (6) high and (9) low levels, symptoms of hypo, mx of hypo

Answer 69

phosphate (mono and dihydrogen) usually maintained at 0.8-1.4mmol/L; usually reciprocal relationship with Ca so things which change it often also change phosphate (but both raised in tert hyperpara) so high in hypopara and sec hyperpara (CKD) but note: acidosis decreases metabolism, so utilisation of phosphate, thus its levels inc; also inc'd by tissue damage, tumour lysis, rhabdomyolysis etc as released from cells low levels become severe around <0.3mmol/L and needs iv correction; modest impairment more common causes inc alcohol use disorder, prim hyperpara, hypothyroid, cushings, burns, alkalosis (eg hypervent), refeeding syndrome, ingestion of non-absorbable antacids like aluminium hydroxide which prevent its absorption; and certain congenital defects and tumours sx: get muscle weakness (inc low CO and resp depression, and diplopia), tremors, white blood cell dysfunction worsening infections, mental status changes (ie confusion), seizures mx: oral replacement usually sufficient but if <0.05 with sx or <0.3 w/o then IV correction - 20-40mmol per day; monitor U&Es, Ca, Mg

Question 70

blood magnesium

Answer 70

hypomagnesaemia usually due to dietary deficiency (main source is chlorophyll ie green veg) may also get it though from diuretics, PPIs, ciclosporin, cisplatin and some cytotoxic drugs, osmotic diuresis as in eg diabetes mellitus, malabsorb, diarrhoea or prolonged nasogastric suction/stoma/fistula, alcoholism <0.6mmol/L in serum suggests patient is very deficient and would benefit from treatment; 0.8-1 is normal range causes hypoparathyroid (lowering ca too), hypokalemia (causes inc'd excretion by kidney, hence hypokalemic and failing to respond to k supp check mg), and symptoms like hypocalc (long qt, tachycard, weakness, tiredness, cramps, temors/paraesthesia, spasticity, seizures if mild then oral replacement, otherwise iv uncommon to see hypermagnesaemia but can get in renal failure

Question 71

roles of Mg in medical rx

Answer 71

Magnesium is involved as a cofactor in more than 300 enzyme systems Oral magnesium promotes defecation via osmotic retention of fluids Magnesium acts as a natural calcium channel blocker, and it is a cofactor of the Na-K-ATP pump. Magnesium helps control atrioventricular node conduction. Therefore, hypomagnesemia can cause myocardial excitability resulting in arrhythmias such as ventricular tachycardia and torsades de pointes Magnesium depresses the central nervous system (CNS) while producing anticonvulsant effects. At neuromuscular junctions, it inhibits the release of acetylcholine, thus blocking peripheral neuromuscular transmission (CaV antag -> NT release down): patients with neuromuscular disease, such as myasthenia gravis need to be closely monitored if they are given magnesium. Magnesium is a cofactor of parathyroid hormone (PTH) synthesis. With hypomagnesemia, concurrent hypoparathyroidism will ensue. Hypoparathyroidism can lead to decreased calcium and eventually lead to osteopenia or osteoporosis Magnesium administration can cause bronchial smooth muscle relaxation. The cause of smooth muscle relaxation is unclear. It is thought to be either by inhibiting calcium, histamine, or acetylcholine release. There may also be a synergist effect with the concurrent use of beta-agonists. Hypermagnesemia: Serum Magnesium Concentration Greater Than 2.6 mg/dL - normally if too much given too quickly, or overuse of OTC Mg therapies (antacids, laxatives), or in AKI Symptoms include vasodilation causing flushing, hypotension, hyporeflexia, and respiratory depression. With a magnesium concentration above 6 mg/dL, ECG changes can consist of PR prolongation, widening of QRS, and peaked T waves. Cardiac arrest occurs whenever levels are above 15 mg/dL

Question 72

electrolyte disorders causing seizures/status that may or may not be responsive

Answer 72

hyponat, hypocalc, hypomag rarely hypernat or hypercalc can Generalized tonicclonic, focal motor, and (less frequently) atypical absence or even akinetic seizures may occur in patients with hypocalcemia even without muscular tetany; can also get all seizure kinds with other electrolyte disorders

Question 73

zinc and copper (Zn bound where x2, when serum level not useful, Cu binding and when not reliable and where else to measure it x2, who to ix for Wilson’s, how does ZN influence Cu, Cu deficiency 5sx and 3 causes, 9 sx of low zinc)

Answer 73

90% zinc bound to albumin and 10% to a2 macroglobulin serum zinc conc not useful when CRP >20mg/L as decreases during acute phase response can look for serum copper, though 90% bound to caeruloplasmin, which is greatly increased in the acute phase response can also look for urinary copper concentration patients with Wilsons disease will have serum copper <10micromol/L, caeruloplasmin <0.15g/L, urinary copper 5-15micromol/24hrs, liver copper microg/g >250 investigate all young adults with unexplained neurological signs and hepatic disease prolonged Zn supplementation is common cause of copper deficiency, ask patients with unexplained marrow suppression or neuropathy about dietary supplements hypocupremia: anemia, neutropenia, myelopathy, periph and optic neuropathy (gradual vision, colour loss); think after bariatric surg, malabsorb, zing ingestion (inc coin eating) zn def: Delayed wound healing, impaired taste, loss of appetite, hair loss, fertility issues (inc low testosterone), rashes/stomatitis, lethargy/depression, delayed growth, and increased susceptibility to infection

Question 74

management of paediatric electrolyte emergencies

Answer 74

hyperkal: stop RBC infusion and any meds/fluids that inc K; attach cardiac monitor, blood gas every 30 mins until safe level (+ lab confirmation but dont wait for this) if ECG changes Ca gluconate 10% 0.5ml/Kg max 20mL, and rpt after 5 mins if ECG doesn't improve insulin + glucose via same cannula, infusion and if in arrest bolus + infusion -> check guidelines for amounts also salbutamol nebulised, or if not SVIA then IV; if in arrest then adrenaline (dont give both due to synergism at beta2 receptor) can give bicarb if pH <7.3: 8.4% 1mmol/kg, can't give in same line as Ca, need to rx hypocalc before giving as otherwise risk of severe hypocalc and tetany then remove K with furosemide IV 1mg/kg max 10mg (takes 4 hours to work) if haemodynamically stable, or else do dialysis; Ca resonium is another option hypokal <3: continuous ECG monitor, recheck gas every 30 mins until safe leverl; correct Mg to >0.7; give KCl 1mmol/kg IV over 2 hours, in arrest give KCl neat central/IO or peripheral hypermag >2 bolus CaGlu as per hyperkal, replete with 10-20ml/kg IVF boluses until euvol then diurese with furo 1mg/kg max 10mg, check Mg hourly, dialyse if refractory hypomag <0.6 magsulf 50% 200mg/kg bolus then infusion until >0.7; bolus neat if torsades; max 2g hypercalc iCa >3 fluid replete with 10-20ml/kf boluses until euvol then force diuresis with furo as above; check gas every 30-60 mins; if refractory dialyse; in less emergent situation bisphos is a good option hypocalc iCa <0.8 Correct Mg >0.7, if phosphate <1 give CaGlu as above; if >2 risk of precipitation -> discuss with PICU/renal in arrest immediately give CaGlu as above and check every 30-60 mins until 1-1.4

Question 75

biochem patterns: adrenal insuff (5), hyperaldo(3), phaeochromocytoma(1), sarcoidosis(2), carcinoid syndrome(3), refeeding syndrome(4), sequelae of parenteral nutrition(3), rhabdomyolysis (5), tumour lysis syndrome (6), toxic alcohols (ethylene glycol as eg)(3), lithium toxicity (2), salicylate toxicity (3)

Answer 75

Adrenal insufficiency Hyponatraemia Hyperkalaemia Normal anion gap acidosis Hypoglycaemia Hypercalcaemia Hyperaldosteronism Hypokalemia Hypernatremia Metabolic alkalosis Phaeochromocytoma Hypokalemia (due to β-2 effect) Sarcoidosis Hypercalcemia Hypercalciuria Carcinoid syndrome Hypokalemia Hypomagnesemia Normal anion gap acidosis (all due to secretory diarrhoea) Refeeding syndrome Hypophosphataemia Hypokalaemia Hypomagnesaemia Hyperglycaemia Sequelae of parenteral nutrition Hyperglycaemia Hyperlipidiaemia Normal anion gap metabolic acidosis Rhabdomyolysis Hyperkalemia Hyperphosphataemia Myoglobinuria Raised serum CK and LDH Tumour lysis syndrome Hyperphosphataemia Hyperkalaemia Hypocalcaemia Hyperuricaemia High anion gap metabolic acidosis Raised serum LDH Toxic alcohols, eg. ethylene glycol High anion gap metabolic acidosis High serum osmolar gap Hypocalcaemia Lithium toxicity Negative anion gap Hypernatremia Salicylate toxicity High anion gap metabolic acidosis Hypokalemia High urinary potassium

Question 76

AKI staging, causes (inc 8 nephrotoxins), who's at risk

Answer 76

rapid fall in GFR (hrs to days) causing retention of urea, creatinine etc and disordered electrolytes, fluid, acid base balance RIFLE classification: risk, injury, failure, loss, end stage kidney disease; we use KDIGO classification: stage 1 is serum creatinine 1.5-1.9x baseline, 2 is 2-2.9x baseline, 3 is 3x or more baseline scr not good for early diagnosis as takes time to rise so some other biomarkers being investigated can be pre-renal (RBD down secondary to hypovolaemia, vasodilation in sepsis, falling CO, intrarenal vasomotor changes due to ACE-i or NSAIDs) which is reversible if RBD restored; intrinsic renal AKI (parenchyma damage from acute tubular necrosis due to ischaemia or nephrotoxic insult, acute glomerulonephritis, acute TIN, hypertensive emergency or vasculitis) post renal (obstruction of urine outflow leading to back pressure in kidney and tubular function compromised, needs patient to only have one working kidney or else both to be compromised for AKI) those at risk: old, diabetes, trauma or burns, vascular or hepatic surgery, volume depletion (NBM, vomiting), on NSAIDs ACEi or ARBs; other common nephrotoxins: iv contrast agents, chemo like cisplatin, immunosuppresants like ciclosporin or tacrolimus, antibiotics like aminoglycosides (gentamicin), vancomycin, amphotericin

Question 77

investigating AKI (inc minimum bloods and ix, telling CKD from AKI - visually or in blood results)

Answer 77

patients may be asymp in early stages despite kidneys working v poorly; usually will see urea and scr up and urine output down (<400mL/d often); freq also volume overload giving pulm oedema, hyperkalaemia leading to arrhythmia or arrest or non-specifically sick/deteriorating patient in all acutely unwell patients check renal function and serum K !!! esp if oedema, ecg changes, nausea, comatose/drowsy, risk factors for AKI to tell AKI from CKD, check patient records or ask them to see if they have CKD; failing that USS to look for CKD kidneys; also PTH can help: secondary hyperpara if chronic assume AKI unless proven otherwise assess ABC, K and volume status and stabilise patient as priority, then can consider the cause: pre, post, intrinsic? look at drug chart and stop all nephrotoxic drugs if poss urine dipstick, LFTs, CRP, CK (for rhabdomyolysis as myoglobin is nephrotoxic); STOP: sepsis/hypoperfusion, toxicity, obstruction, parenchymal disease to check volume status: BP and heart rate (lying and standing if poss), peripheral perfusion: warm w bounding pulse suggests vasodilation and cold with cap refill down suggests poor CO or hypovolaemia, check urine output and for oedema, look for dec'd jvp (patient can lie down to make it obvious) asses for sources of emboli (valves, AF etc) urine dipstick is key! also full bloods: FBC to look for anaemia which devs early, signs for clotting eg d dimers and any infection, U&Es esp raised K, CRP, CK, lactate to assess tissue underperfusion, bicarb to check for metabolic acidosis (venous sample, ABG if it is low) so min: FBC, U&Es, ca, phosphate, CRP, CK, LFT, albumin, urine dipstick, venous bicarb or ABG; check patients drug history renal USS to exclude obstruction and CKD; CXR may help with info on heart, pericardial effusion, pulm oedema renal biopsy only really needed if unexplained and if non-ATN intrinsic cause suspected

Question 78

managing AKI (general and hyperkal specific)

Answer 78

give fluids to restore volume if needed; if ecg changes give insulin and glucose plus nebulised salbutamol (unless ihd/tachycardic), give bicarb too if it's low and no fluid overload; for pulmonary oedema sit patient up and give O2, if haemodynamically stable also furosemide and GTN (sys BP >90mmHg); patient may have uraemic coma so be prepared to manage airway etc besides ecg changes, urgently lower serum K if >6.5mmol/L also give ca gluconate to stabilise the Em of the heart; beware giving bicarb means giving na which can cause a volume overload furosemide helps make sure max loss of K too so good to give if safe AKI will give metabolic acidosis with raised anion gap anaemia may not be part of uraemic syndrome, it might mean there is a bleed you havent spotted (consider abdo, pelvis, thorax, back) also note if liver is cirrhotic, portal hypertension incs shear stress producing local vasodilators, get splanchnic and systemic vasodilation, sensed as underfilling of arterial system, so response as for falling blood volume; excess catecholamine, angiotensin II, adenosine, thromboxane A2, and endothelin gives renal artery constriction and RBF down, this is thus entirely pre-renal in nature as a cause of AKI tumour lysis -> uric acid stones, can give AKI hyperkal: treat if >6.5 or ecg changes. stabilise membrane (10mmol 10% ca gluc), stop exacerbating drugs. short term shift into cells (5-10u actrapid insulin in 250ml dex 10% (5 units if poor renal fucntion and want to be safe, but usually do 10 even if bad renal function)/5-10mg salbut neb - latter for really rapid lowering) but will come back out in hours so: removal of k from body (ca resonium - may get constipation, alternatives exist like sodium zirconium SZC but that can cause fluid reabsorb; in general onset of exchange resins takes days so in acute emergency setting dialysis is preferred - if >6.5 or ecg changes), diuretics, or dialysis if v high or not responding, or acute emergency eg ECG changes of hyperkal); ion exchange resin alone may be used if mild/mod hyperkal <6.5 and no ecg changes; if acidotic then giving some rapid bicarb can also help with shifting into cells

Question 79

AKI staging, intrinsic causes, inc'd sens to prerenal, prerenal vs ATN, 4 ATN and 6 AIN causes, lupus nephritis

Answer 79

creat x1.5 is stage 1, creat 2x is stage 2, creat 3x is stage 3 urine output <0.5ml/kg/hr x 6hr stage 1, if x12 is stage 2, x24hr or anuria x12hr then stage 3 go with the worst figure (creat lags behind urine output) intrinsic renal causes inc ATN (ischaemic 50% toxic 35%), AIN, acute GN autoregulation impairment leading to (or increasing sensitivity to) prerenal eg NSAIDs, ACEI/ARBs - stop these drugs if pt has sepsis as big risk of AKI (ACEI/ARBs act on efferent bit) ATN: ischaemia, toxins, rhabdo, myeloma AIN: NSAIDs, omeprazole, antibiotics, post-infective, pyelonephritis, granulomatous (TB, sarcoidosis) pre-renal AKI respond to fluid resus almost immediately, whereas intrinsic remain oliguric severity/prognosis doesnt come from histo as only small sample of kidney, base on clinical picture lupus nephritis has 6 classes of severity from minimal mesangial to advanced sclerosing and inc mesangioprolif can tell prerenal uremia from ATN as better response to fluid challenge, low urine Na (kidneys still reabsorb, in ATN urine will have high Na and also brown granular casts); takes ~48hrs for untreated prerenal to become ATN

Question 80

general approach to AKI, indications for dialysis

Answer 80

is this acute or chronic? has obstruction been excluded? is the patient euvolaemic? is there evidence for renal parenchymal disease identify and correct pre and post renal factors; review drugs (stop nsaids/acei/arbs); identify and treat complications hyperkal >6.5mm is absolute ind for rrt, or vol overload -? pulm oedema, or encephelopathy/pericarditis (uraemic)

Question 81

AKI bundle

Answer 81

hold meds: ACE inhibitors and ARBs NSAIDS Other antihypertensives Diuretics especially if potassium sparing Metformin Gentamicin (consider also suspending if risk factors for AKI eg sepsis, hypovolemia, D&V, heart failure exacerbation etc) dose adjust meds: Penicillins Cephalosporins Vancomycin Opiates Gabapentin Aciclovir LMWH assess for risk factors, urological sx, rheum sx, volume status, signs of vasculitis check urine dip: absence of significant haematoproteinuria virtually excludes glomerulonephritis while the presence of leucocytes and nitrites suggests urinary tract infection (note elderly pt will need culture sending for UTI dx) FBC, film, U&Es, LFTs, bone profile, urine culture, urine PCR (if protein present on dip), renal USS, CXR (pulm oedema, sepsis screen), blood cultures (if sepsis possible) also consider: CK, CRP, myeloma screen, LDH, HIV screen, HBV/HCV, and if GN possible then ANA, ANCA, anti-GBM, complement, Ig levels (and liaise with renal team and phone abto ask for urgent processing) Mx fluid balance chart with input/output monitoring (catheter may be helpful) consider daily weights screen for sepsis, treat if present if hypovol poss then bolus, repeat BP to check response, repeat bolus if no response, if still no response discuss with seniors -> may be cardiogenic or need vasopressors if volume unresponsive then pulmonary oedema is a risk -> CCOT discussion and close monitoring would be appropriate, may need dialysis treat hyperkal, consider diuresis for acidosis, treat pulm oedema (sit up, s/l GTN or GTN infusion, IV furosemide (high doses 160mg+ may be needed), dialysis), if uraemic then needs dialysis discuss with renal team if: dialysis indicated, progress to AKI 3 despite treatment, CKD 4/5 or known renal disease, haemoptysis or otherwise suspect vaculitis or autoimmune diease, rhabdomyolysis, haemolysis on film or bloody diarrhoea, myeloma, ++ blood and protein on dipstick

Question 82

nephrotoxic drugs (4 forms of damage with corresponding drugs 3:6:9:1)

Answer 82

membranous GN: gold, penicillamine, captopril (acute) interstitial nephritis - penicillins, cephalosporins, NSAIDs, allopurinol, phenytoin, PPIs renal tubular damage - amphotericin, heavy metals (gold, mercury), cisplatin, aminoglycosides, vancomycin, contrast (maybe), NSAIDs, acyclovir, lithium ciclosporin/tacrolimus do various ways

Question 83

11 ciclosporin s/e

Answer 83

nephrotoxic, may make it hard to tell apart from rejection of renal transplant also hypertension, hypertrichosis, periph neurop, headaches, diarrhoea/nausea, raised LDL and triglycerides, tremor, gingival hypertrophy, liver inhibitor, and immunosuppression

Question 84

drugs to stop during AKI (inc nuance about the first)

Answer 84

DAMN drugs diuretics + dapagliflozin, ACEi/ARBs, metformin, NSAIDs although note: you can give loop diuretics in AKI, you just might need to give higher doses; Cr may rise when you do this as you offload some fluid, or may rise as AKI worsens - needs judgement; furosemide doesn't cause AKI, but if it causes hypovolaemia (ie you've over-diuresed someone) then that can cause/worsen AKI, hence the need to sometimes discontinue in AKI; essentially if overloaded ad AKI keep diuresing until offloaded, then (or if not hypervol) discontinue

Question 85

nephrotoxicty due to contrast media (inc time course, 5 risk factors, 2 procedures where might happen, 2 protective steps)

Answer 85

Contrast-induced nephropathy peaks 2 -5 days after administration - cr often begins to rise within 24 hrs. Risk factors include known renal impairment (especially diabetic nephropathy) age > 70 years dehydration cardiac failure the use of nephrotoxic drugs such as NSAIDs Examples of procedures that may cause contrast-induced nephropathy includes: CT with contrast coronary angiography/percutaneous coronary intervention (PCI) 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 Patients who are high-risk for contrast-induced nephropathy should have metformin withheld for a minimum of 48 hours and until the renal function has been shown to be normal. This is due to the risk of lactic acidosis

Question 86

contrast induced nephropathy - historical perspective, modern dyes, recent specialty statement

Answer 86

concept of contrast nephropathy was born in the 1950's, when it was observed that some patients developed renal failure following injection of IV contrast dye for intravenous pyelography contrast dye used at that time probably was poisonous, but studies not well done modern contrast dyes (with lower osmolarity) don't seem to cause renal failure; numerous studies and meta-analyses have emerged which don't detect any relationship between contrast dye administration and elevation of creatinine RCEG have put out a statement addressing this There is now a significant body of evidence supporting the use of iodinated contrast agent for CT scans in the emergency setting even if baseline renal function is abnormal or the patient is taking metformin. The evidence for the routine use of fluid therapy prior to intravenous contrast in the emergency setting is weak. In the emergency setting the balance of risk of CI-AKI is highly likely to be offset by the risk of delay in diagnosis (delayed scan waiting for blood results) and in some cases (especially the elderly and those with known heart failure) the requirement for pre-hydration Measurement of renal function should not be considered a pre-requisite prior to scanning (the electronic requesting system should reflect this). * Pre-existing renal disease, diabetes mellitus or medication such as metformin should not delay scanning (the electronic requesting system should reflect this). * Age is not an independent risk factor for CI-AKI and should not delay scanning * Intravenous fluid administration should not be considered a pre-requisite prior to scanning

Question 87

ATN

Answer 87

presents as AKI and progresses to strictural injury to renal parenchyma; on biopsy would see loss of brush border, tubular cell vacuolation and sloughing into the lumen due to drop in renal perfusion (hypotension, shock, block of blood supply) or nephrotoxicity from drugs etc

Question 88

acute interstitial nephritis (2 causes, 4 features/sx)

Answer 88

there are both acute and chronic forms of interstitial nephritis (aka tubulointerstitial nephritis) presents with acute kidney injury and hypertension. There is acute inflammation of the tubules and interstitium. This is usually caused by a hypersensitivity reaction to: Drugs (e.g. NSAIDS, omeprazole/PPIs or antibiotics + many more) Infection Other features of a generalised hypersensitivity reaction can accompany the acute kidney injury: Rash Fever Eosinophilia Joint pain May also see nausea/vomiting, flank pain (caused by inflam -> oedema -> stretching of renal capsule), haematuria - esp in chronic form, which may also be asymp or have just progressive features of renal failure CIN due to chronic tubular insults giving fibrosis and dysfunction; include damage by heavy metals, nephrocalcinosis, chronic hypokalemia, meds inc analgesics and chinese herbs, chronic pyelonephritis, reflux inc VUR; note many of these cause AIN also

Question 89

ascites surgical - hepatorenal syndrome path and common root cause (plus 3 causes of that), other acute cause, chronic form

Answer 89

besides portal hypertension from compression by scarred tissue or general venous congestion, liver function may be down (hypoalbuminaemia); also cirrhosis causes splanchnic vasodilation as vasodilators accumulate in the circulation when liver fails; systemic hypotension and renal hypoperfusion thus renin-ang activation, aldosterone release giving salt and water retention; sometimes this exacerbates as renal vasocons cant compensate so renin-ang system stays activated, inc'g renal vasocontriction until AKI; hepatorenal syndrome is result as renal hypoperfusion continues, this has high mortality via AKI; initial stabilisation via volume expansion, pos inotropy, vasocontrictors usually HRS is due to acute decompensation of cirrhosis due to infection eg spont bacti peritonitis, GI bleed, alcohol intake; may have a slower form with diuretic resistant ascites (as kidney function unable to excrete enough sodium to clear the fluid, liver transplant needed and dialysis needed to support until you can get it; this slower kind of HRS may be the end stage of ascites HRS can also occur due to an acute liver failure

Question 90

urea:creatinine ratio

Answer 90

both freely filtered by the glomerulus, but urea reabsorbed by the tubules in a regulated manner, and cr is not reabsorbed urea primary metabolite derived from dietary protein and tissue protein turnover, creatinine is product of muscle creatine catabolism in prerenal AKI urea:cr >110:1 due to hypoperfusion of kidneys; may also be increased by inc'd dietary protein including GI bleeding; an elevated baseline is possible in patients with reduced muscle mass eg elderly pts postrenal AKI or normal situation is ratio of 40-110:1 intrarenal AKI reduced the reabsorption of urea so ratio falls <40:1, may also be due to liver disease (dec'd urea formation), or malnutrition

Question 91

azotemia, uraemia (inc sx); azotemia causes (6 prerenal, 2 renal, 1 postrenal); management of both

Answer 91

azotemia precedes, has raised blood urea but not yet high enough for symptoms; see progressive weakness, easy fatigue, n&v causing loss of appetite, muscle atrophy, tremors and periph neuropathy, cramps, insulin resistance, altered cognitive function, metabolic acidosis; progress to stupor, coma, death; - may also see uremic fetor, encephalopathy, pericarditis, itching, uremic frost, impotence, amenorrhoea, stomatitis, parotitis, xerostomia symptoms begin to manifest as GFR falls below 60 azotemia may be prerenal (heart failure, shock, dehydration) or increased urea production in liver due to high protein diet/GI bleed or inc'd protein catabolism (stress, fever, corticosteroid use, major illness); renal are AKI and CKD; postrenal due to outflow obstruction dialysis or kidney transplant, or palliative (latter two if coming from renal cause) prerenal azotemia causes BUN to rise out of proportion with creatinine, unlike intrinsic AKI like ATN, and can be treated with saline unlike ATN; prerenal azotemia may progress to ATN if untreated (or may not)

Question 92

cockcroft-gault formula (function, caveat regarding renal function, what weight to use)

Answer 92

to provide reliable approximation of residual renal function in patients with CKD, by providing an estimate for creatinine clearance renal function should be stable it has been used for working out drug dose to give in pt with poor renal function, but nowadays eGFR measured in more modern ways is preferred nevertheless it's on mdcalc if you need/want to use it/estimate creatinine clearance; weight should be ideal weight if pt obese or has fluid retention

Question 93

what causes a high urea?

Answer 93

low GFR (hypotension, renal obstructive disease, glomerular disease), high protein diet, catabolic states like infection/trauma/surgery, steroid use large reserve of renal function means plasma urea and creatinine conc wont rise until 50% reduction in GFR

Question 94

signs of chronic liver vs chronic kidney disease

Answer 94

liver: jaundice, palmar erythema, clubbing, leuconychia, spider naevi, foetor hepaticus, hepatomeg, splenomeg, ascites, caput medusae, periph oedema kidney: pallor, poss uraemic lemon tinge to skin, pulm and periph oedema, pleural effusions, pericarditis, scars relating to renal surgery, peritoneal dialysis scars +/- AV vascular access (oft tunnelled line on right side of chest); children may be smaller; you should check the BP and urine

Question 95

CKD clinical (inc how hyperglyc -> CKD), signs of renal disease (inc conc where get ureamic sx)(also staging by eGFR and ACR)

Answer 95

2 main parameters: eGFR (ml/min/1.73m2) Calculator – race, sex, age Urinary Albumin:Creatinine Ratio – ACR 24hr is gold standard – can do random sample Diabetic Nephropathy – 44% Hypertensive nephropathy – 27% (more common in Afro-Caribbean populations) Glomerulonephritis – 8% Cystic disease – 2% Urological – 2% 17% = other Malaria most common in sub-Saharan Africa Schistosomiasis most common in Middle East Screening for Diabetic patients – annual ACR and eGFR Glomerular disease: Hyperglycaemia = hyperfiltration (glucose increases ATII release – efferent vasoconstriction) Tubulointerstitial disease: - Uric acid and ROS from fructose metabolism = tubular damage Asymptomatic especially in early disease But as kidneys begin to fail, waste products begin to accumulate (uraemic toxins) Uraemic Sx (When serum conc exceeds 40mmol/L) Malaise, weight loss, insomnia, Nocturia/Polyuria (loss of concentrating ability) NB – urine volume not good marker of renal function in CKD (oliguria is good marker of AKI) Itching Nausea/vomiting Paraesthesia / tetany / bone pain (CKD-MBD) Severe stage 5: Mental slowing / myoclonic twitching / seizures Other signs: Mitral regurgitation = calcification Aortic / pulmonary regurgition = volume overload Glove and Stocking peripheral sensory loss Pigmentation = Poor excretion of beta-MSH stage 1 (G1) – a normal eGFR above 90ml/min, but other tests have detected signs of kidney damage stage 2 (G2) – a slightly reduced eGFR of 60 to 89ml/min, with other signs of kidney damage stage 3a (G3a) – an eGFR of 45 to 59ml/min stage 3b (G3b) – an eGFR of 30 to 44ml/min stage 4 (G4) – an eGFR of 15 to 29ml/min stage 5 (G5) – an eGFR below 15ml/min, meaning the kidneys have lost almost all of their function Your ACR result is given as a stage from 1 to 3: A1 – an ACR of less than 3mg/mmol A2 – an ACR of 3 to 30mg/mmol A3 – an ACR of more than 30mg/mmol

Question 96

CKD investigations (4 things in urine and what they suggest, 6 bloods, 3 imaging, other helpful ix; how anemia devs (histo appearance and other ix needed, mx), general mx in early and late disease, link to GH and what age to transplant im children + why this is x3

Answer 96

Urine: Microscopy: White cells – UTI (unlikely cause of CKD) or TB Eosinophiluria – Tubulointerstitial nephritis Granular casts – Sign of active renal disease Red-cell casts – Glomerulonephritis Bloods: U&Es (eGFR calculated from creatinine) Electrophoresis (if myeloma suspected) HbA1C and blood glucose Complement and Autoantibodies if SLE / vasculitidies suspected Imaging Ultrasound of renal tract (look for renal size, obstruction and hydronephrosis) APCKD and Diabetic nephropathy = enlarged kidneys CT-KUB Calculi, cortical scarring MR-angiography Renovascular disease Renal Biopsy: Helps confirm cause of CKD Kidney damage in CKD destroys Peritubular Interstitial Fibroblasts Low EPO = Low Erythropoiesis = Anaemia (normochromic, normocytic) Diagnosis of exclusion – test for other causes (haematinics and DAT EPO or ESA (Erythropoietic stimulating agent). Target Hb>100 Management of CKD involves blood pressure management (in early disease) and renal replacement (in advanced disease) + managing cause CKD in children is state of GH resistance, thus giving small stature, transplant before 6yo has most benefit for being close to peers later on; this is due to dec'd GH receptors, altered intracell signalling, and inc'd IGF1 inhibitor conc; recombinant GH is something that can be considered

Question 97

CKD and bone disease (inc phos)

Answer 97

1-alpha hydroxylation normally occurs in the kidneys → CKD leads to low vitamin D the kidneys normally excrete phosphate → CKD leads to high phosphate This, in turn, causes other problems: the high phosphate level 'drags' calcium from the bones, resulting in osteomalacia low calcium: due to lack of vitamin D, high phosphate secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D aim is to reduce phosphate and parathyroid hormone levels. Overview reduced dietary intake of phosphate is the first-line management phosphate binders vitamin D: alfacalcidol, calcitriol parathyroidectomy may be needed in some cases Phosphate binders aluminium-based binders are less commonly used now calcium-based binders problems include hypercalcemia and vascular calcification sevelamer a non-calcium based binder that is now increasingly used binds to dietary phosphate and prevents its absorption

Question 98

renal replacement therapy (access options, subtypes, 9 complications inc dialysis disequib syndrome and some from av fistula, 6 sx during/after session, when perit recommended)

Answer 98

may be good to start earlier, as waiting until pt shows uraemic symptoms may mean pt develops nutritional deficiencies which are then hard to overcome; however bear in mind dialysis has huge impact on qol so many pts resistant to starting on it 2 access options for chronic situation: arteriovenous fistula in nondominant hand (dont take blood from it or do blood pressure reading on that arm, will have red bracelet); or tunneled dialysis line, oft if fistula formation fails or systemic vascular disease means fistula wont work haemodialysis: solutes diffuse across semiperm membrane separating blood from dialysis fluid haemofiltration: uses convection via pressure in the blood comp to force water and solutes, this is more technical and expensive but ensures larger solutes removed better than in haemodialysis haemodiafiltration: does both usually 4 hours 3x a week complications: stenosis or thrombosis of fistulae, line infection (systemically unwell eg, or pus or inflam around line), steal syndrome (av fistula leads to ischaemia in the hand); hypotension, arrhythmias, dialysis disequilibrium syndrome (cerebral oedema from urea dropping too fast giving headache, focal neurology, dec consciousness, esp common on first session), anaphylaxis (breathless etc on starting first dialysis session usually, due to reaction to dialysis membrane); qol effects, cardiac injury peritoneal dialysis uses the peritoneum as the semiperm membrane; cloudy bag or abdo pain may be peritonitis; can also get exit site infection, constipation etc generally can get dizziness, nausea, cramps, headache during and for a bit after due to fluid shifts as fluid removed (ckd pt pass little urine); fatigue generally, itchy skin, altered libido or sleep can do home dialysis peritoneal needs to be done every day but easier than haemodial to do at home (anyone can); oft recommended if no cardio comorbs or have some residual renal function; hernias and abdo scars may mean not do; pt lifestyle wishes may also support doing perit

Question 99

CRRT (2 pt groups, main difference from dialysis and benefit of that, 2 common types, 2 places where access can be and anticoag used, 7 indications)

Answer 99

CRRT: continuous renal replacement therapy, for critically unwell pt with AKI or normally dialysis dependent, especially if haemodynamically unstable; slower type of dialysis over 24 instead of 4 hours, less haemodynamic shifts so less strain on heart common types are continuous venovenous haemofiltration (CVVH) and continuous venovenous haemodialysis provide solute clearance and volume removal, generally with double lumen catheter in IJV, or more rarely femoral vein - catheter tip at junction of SVC and RA; citrate often used as anticoagulation so extracorporeal circuit doesn't clot indications include pulm oedema/pericard effusion refractory to diuresis, pH <7.2, hyperkalemia >6/6.5, or eg severe hypo/hypernat or hyperphos; also uraemic sx and possibly hyperammonaemia if severe eg infants with IEM

Question 100

renal hypertension (2 big causes and differentiating them, other 2 causes; 2 main causes of the second of the big causes; 4 ix)

Answer 100

renal artery stenosis and primary hyperaldosteronism; aldosterone high in both, renin high in former and low in latter; ras usually fibromusc dysplasia in kids primary hyperaldost may be adenoma (2/3 times) or adrenal hyperplasia also consder chronic renal failure and renal tumours ix must include urinalysis, urine MC&S, serum U&Es, and renal USS

Question 101

13 hyperuricaemia causes

Answer 101

gout, lesch-nyhan syndrome, myeloprolif disorders, tumor lysis syndrome, high purine diet, hyperpara, lead poisoning, down syndrome, exercise, starvation, thiazide diuretics, low dose salicylates, alcohol ingestion

Question 102

body pH buffering systems (inc pH equation)

Answer 102

static systems inc protein, haemoglobin, hydrogenphosphate - quickly depleted; dynamic system bases on bicarbonate, acid reacts to make sodium salt, CO2, water - H/H equation 6.1 + log([HCO3]/0.03*pCO2) 0.03 is solubility constant to make it a conc based on Henry's law, lungs keep pCO2 constant (some compensation) so non-volatile acids deplete bicarbonate, kidneys replace

Question 103

bicarbonate handling in the kidney

Answer 103

80% in PCT, 10% in TAL, 6% in DCT, 4% in collecting ducts; reabsorption decreased and some secretion by type b intercalated cells of DCT in alkalosis lumen acidified and apical membrane CA produces CO2 which diffuses into cell, intracellular CA generates proton/bicarbonate (acidified lumen forces reaction right, alkaline cell forces it left), bicarbonate reabsorbed basolaterally with bicarbonate/chloride exchanger and NBC1 (3 bicarbonate, 1 Na); PCT/TAL acidify with NHE3 Na/H exchanger and H-ATPase, DCT/ducts have type A cell with H/K exchanger reabsorption insufficient to replace lost bicarbonate, actively produced in PCT and proton secreted into lumen; urine min pH 4.5, otherwise will damage cells and because that's 1000-fold difference from [H], max gradient H-ATPase can work against; acid load > than what min pH allows (50 to 100 mmol a day) so buffer by something body can afford to lose (not bicarbonate) - hydrogen phosphate and some creatinine buffer not enough, especially when big acid load, so glutamine made from waste aa in liver by transamination enters PCT cells undergoes ammoniagenesis making alpha ketoglutarate and ammonium, plus bicarbonate which is reabsorbed; ammonium dissociates in cell, ammonia crosses PM, is protonated in tubule to act as buffer important control point as more trapping if low plasma pH so more excreted in urine, higher plasma pH and more enters blood from interstitium, goes to liver to become urea

Question 104

regulating renal pH control - effect of low blood pH, effect of high paCO2, paracrine signal, 4x hormones

Answer 104

No single hormone, lots of intrinsic methods: low pH enhances H secretion and bicarbonate reabsorption/creation high pCO2 means more CO2 into cells to breakdown into bicarbonate and H for secretion possibly autocrine/paracrine effects of endothelin increases activity/expression of transporters with low pH cortisol released with low pH increases transcription of NBC1/NHE3 prolonged acidosis gives PTH which promotes secretion of H in TAL/DCT and reduces phosphate reabsorption which increases buffering capacity of tubular fluid Ang2/aldosterone increase Na/H (PCT) and K/H (DCT) exchange respectively

Question 105

anion gap

Answer 105

Na + K - (Cl + HCO3) <12 is normal raised if organic acid accumulates or proton secretion fails (both of which mean you lose bicarb) Causes (CATMUDPILES) CO, CN Alcoholic ketoacidosis and starvation ketoacidosis Toluene Metformin, Methanol Uremia DKA Paracetamol, propylene glycol Iron, Isoniazid, IEM Lactic acidosis Ethylene glycol Salicylates Normal is due to hyperchlor acidosis (via strong ion effect) or HCO3 depletion if Cl replaces the HCO3 or Na down with HCO3; diarrhoea by far most common cause, is bc more Na than Cl secreted into gut fluid hence something like lactated ringers is better than saline to avoid Na:Cl ratio decreasing Causes (CAGE) Chloride excess Acetazolamide/Adrenal insuff GI causes – diarrhea/vomiting, fistulae (pancreatic, ureters, biliary, small bowel, ileostomy) Extra – RTA

Question 106

strong ion difference and acidosis: what are strong ions (commonest in blood and what their concs are), what is the remaining charge difference and 3 things that contribute to this inc conc of the biggest and what kind of ion it is (and why) and what the implication of this is, what the conc of misc anions are, and how all of this explains normal anion gap acidosis; limitation to theory; reasons for normal anion gap despite cause that would lead to raised (and vice versa 3:1)

Answer 106

Strong ions fully disassociate in water. The common strong ions in blood are Na, K, Cl Na+ = 145 K+ = 5 Total = 150 Cl- = 105 That leave 45 mmol/L of unaccounted for negativeness. Part of that is lactate, albumin and a few other non significant things. But by far the biggest additional contributor is bicarbonate. HCO3- (about 28) Bicarb is NOT a strong ion. It can exists as HCO3 and as CO2. That means if there is a large change in one of the other strong ions (Na, K and Cl), it’s always Cl btw, the other massive contributor to your body being electrically neutral (HCO3) must change. So if you raise your Cl to 120. 150 - 120 = 30 We have about 15mmol/l of other ions floating around (alb, lac etc). Therefore we only have 30-15 = 15 mmol/l left. The bicarbonate is going to drop to 15 to compensate for the raised Cl, driven by electrochemical effect on the bicarb dissociation equation. This is how to understand normal anion gap acidosis note limitation to the theory is it models serum as a single comp instead of dynamically linked to others like ICF -> so doesnt consider the role of gibbs-donnan equilibria across eg RBC membrane and hamburger effects etc increase in anions may not be enough to push gap out of normal range, lactate can exchange for Cl giving appearance of NAGMA, hypoalbuminemia masks; in other situation may expect NAGMA but see raised gap due to other cause occurring at same time

Question 107

interpreting the anion gap (normal, adjusting for albumin, causes of high gap w/o acidosis, causes of negative anion gap); osmolar gap and interpretation

Answer 107

normal is 12 if K not used, 16 if used; "normal" expected value decreases by 1mEq/L for every 4g/L decrease in serum albumin high anion gap in absence of acidosis: other anions present eg Gamma-globulinaemia High serum paraprotein in myeloma High serum phosphate or sulfate negative anion gap: Increase in unmeasured cations (lithium, Ca, Mg), pseudohyponay (hyperlipidemia, hyperprot) Osmolar gap: measured osmolality - calculated osmolality (which is 2× Na+ + glucose + urea) - should be <10; use uncorrected sodium normal anion gap w high osmolar gap: any substance administered into the bloodstream which does not dissociate at physiologic pH eg mannitol, glycine, ethanol high anion gap w high osmolar gap: methanol, ethylene glycol, salicylate, lactic acidosis, alcoholic KA or DKA

Question 108

consequences of acidosis: resp acidosis x4; met acidosis x16

Answer 108

RESP ACIDOSIS Right shift of the oxyhaemoglobin dissociation curve (except with chronically raised PaCO2, a decrease in 2,3-DPG drives the curve back to the left) inc'd symp tone -> inc'd CO, BP, vasodilation; cerebral vasodilation giving raised ICP and headache CNS depression and coma may get hypochloremia due to hamburger shift acidosis will begin to decrease contractility and so SV etc like metabolic over time MET ACIDOSIS Increased respiratory stimulus -> increased work of breathing Right shift of the oxyhaemoglobin dissociation curve Decreased responsiveness to catecholamines Decreased cardiac output Increased propensity to arrhythmias Decreased systemic vascular tone and arterial vasodilation Pulmonary vasoconstricition Cerebral vasodilation Hyperkal, hypercalc Increased renal ammonia production and secretion, so inc'd renal O2 demand; diuresis from added anions Decreased stomach emptying Nausea and vomiting Decreased splanchnic perfusion Coagulopathy

Question 109

uraemic acidosis - 2 different forms and which aspect of kidney isn't working in each, impact of the strong ion difference on pH, role of ammonium and how it interacts with strong ion difference and when this becomes a problem; when do you start to retain acidic by-products?

Answer 109

the acidosis of renal failure Failure to acidify urine (which occurs with tubular dysfunction) Failure to excrete non-volatile acidic anions (which occurs with decreased glomerular filtration) kidney handles the acid-base balance of the body by excreting chloride, which increases the strong ion difference. When there is less strong anion (Cl-) but strong cations (Na+ and K+) are retained, the equilibrium favours a decrease in the amount of weak cations (which are mainly H+) and an increase in the amount of weak anions (mainly HCO3-). The whole focus on ammonium excretion is probably wrong – ammonium is merely a weak cation which is co-excreted with chloride to maintain the electrical charge neutrality of the tubular fluid; BUT a failure of ammonia excretion reduces the capacity for chloride excretion, and the “trapped” chloride in the body fluids decreases the strong ion difference, resulting in acidosis this occurs when enough nephrons lost that remaining can't upreg their ammonium secretion anymore to compensate with eGFR <20 or so retain acidic by-products of metabolism as well as hidden anions like phosphate, urate etc

Question 110

D-lactate acidosis - AKA, what kind of acidosis caused, 4 pts who might have and what test is normal, pathophys, where can and can't metabolise it, 6 sx, suspect when x4 and how to ix

Answer 110

aka D-lactic encephalopathy rare cause of high anion gap metabolic acidosis (HAGMA) typically occurs in patients with short bowel syndrome or following jejuno-ileal bypass surgery (or eg SIBO, not taking pancreas enzyme replacements properly) usual L-lactate assay is normal malabsorbed carbohydrate is fermented by an abnormal bacterial flora in the colon this produces excessive amounts of D-lactate acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, giving rise to a vicious cycle; it competes with pyruvate for absorption but can't be metabolised, seems to be a problem in brain and heart but not liver hepatic metabolism of lactate does not discriminate between isoforms and so can metabolise it well unless lots produced Get neurological symptoms altered mental status, slurred speech, and ataxia, coma (often may appear “drunk”) “brain fogginess”; can get arrhythmias, heart block suspect if sx and blood gas suspicious, risk factors present, no other apparent cause; check D-lactate level specifically

Question 111

sodium bicarb indications x4 and dose calculation

Answer 111

Hyperkalaemia Treatment of sodium channel blocker overdose with ECG features (e.g. tricyclic overdose) Urinary alkalinisation (salicylate poisoning) Normal anion gap metabolic acidosis inc RTA debated to give in other causes of acidosis body weight × 0.3 × (desired HCO3- - measured HCO3- )

Question 112

rationale for giving bicarb or not in acidosis

Answer 112

risks of bicarb: decreased availability of oxygen at the tissue level due to a leftward shift in the oxygen dissociation curve, akalemia if over aggressive causing hypocalcemia, due to the hyperosmolar nature of the solution sodium load associated with these preparations, patients may experience fluid shifts, notably pulmonary and cerebral edema, and important to note that the use of sodium bicarbonate relies on the ability of the patient to have effective ventilation. The bicarbonate anion combines with hydrogen ions to ultimately form CO2 - if minute ventilation is restricted, preventing adequate exhalation of CO2, excessive administration of sodium bicarbonate may inadvertently cause hypercarbia and paradoxically lower the pH (note this mechanism is challenged by some) lactic acidosis: Acidemia has been implicated in contributing to cardiovascular instability and decreased responsiveness to catecholamines and severe lactic acidosis is associated with increased mortality leading to general belief you should give bicarb if severe acidosis eg pH <7.1, however there is no mortality benefit or demonstrated improvement in hemodynamics with use of sodium bicarbonate in lactic acidosis, although emerging data suggest patients with persistent metabolic acidosis <7.2 and acute kidney injury may benefit from an infusion of bicarbonate after initial resuscitation arrest: Pushes of sodium bicarbonate are not recommended for use in undifferentiated cardiac arrest for adult or pediatric patients (may even have inc'd mortality, but may be selection error as only giving bicarb to sickest ppl). However, they are recommended in selected cases, including suspected hyperkalemia or sodium channel blockade toxicity (eg TCA overdose, maybe cocaine) DKA: Sodium bicarbonate therapy in the initial resuscitation or recovery phase of DKA is not recommended and may cause harm in pediatric patients (through inc'd cerebral oedema risk), although data in patients with severe acidosis (pH < 7.0) and hyperkalemia are lacking rhabdomyolysis: primary theorized benefit of bicarbonate therapy in patients with rhabdomyolysis is alkalinization of urine. In animal models, it has been observed that precipitation of myoglobin complexes is worsened in acidic urine, thereby further damaging renal tubules, but this is not recommended based on the available evidence; however, if AKI w metabolic acidosis then may benefit NAGMA: occurs by direct loss of bicarbonate in the gastrointestinal or urinary systems, direct or indirect chloride administration, or impaired ammonia excretion with chronic kidney disease. The role of bicarbonate therapy in NAGMA depends largely on the mechanism by which the acidosis occurred. Renal tubular acidosis may cause a decrease in serum bicarbonate concentration by inadequate proton excretion in the distal tubules (type 1), inadequate bicarbonate resorption in the proximal tubules (type 2), or reduced sodium resorption in the collecting ducts (type 4), which causes hyperkalemia and hyponatremia in addition to NAGMA. Direct loss of bicarbonate in the gastrointestinal or urinary systems most often occurs through secretory diarrhea, enteric fistulae, or ureteroileostomy. Concomitant hyponatremia, hypokalemia, and volume depletion may occur. Hyponatremia and decreased extracellular fluid volume stimulate the renal retention of both Na+ and Cl−. Retained Cl− replaces the lost HCO3−, generating a relative excess of chloride. Bicarb supplementation is recomended in these cases reasons not good in cardiac arrest: CO2 release is controlled by both ventilation and perfusion of the lungs. Because a heart is not pumping in cardiac arrest, we are rate limited in the amount of CO2 that can be released by the minimal perfusion of our chest compressions. This means A) there is no value in hyperventilating an arrest patient and B) bicarbonate cannot buffer out acid because the body cannot release the CO2 (even if ventilate, the Q part of VQ won't be very good so poor gas exchange - reverse is why abrupt rise in ET CO2 can indicate ROSC) Bicarbonate actually worsens lactic acidosis. This is because the temporary and aggressive increase in pH (reduction in acidity) up-regulates the production of pyruvate (acidosis down-regulates glycolysis). Without the availability of oxygen for aerobic metabolism (citrate cycle, electron transport chain), pyruvate undergoes lactic acid fermentation, worsening the acid problem. Also, you're not treating the underlying problem -> at best temporising

Question 113

renal tubular acidosis -t1 problem + general treatment, t2 problem + general treatment, t4 problem and 6dd + general treatment

Answer 113

Type 1 renal tubular acidosis is due to pathology in the distal tubule. The distal tubule is unable to excrete hydrogen ions. Treatment is with oral bicarbonate Type 2 renal tubular acidosis is due to pathology in the proximal tubule. The proximal tubule is unable to reabsorb bicarbonate from the urine into the blood. Excessive bicarbonate is excreted in the urine. Fanconi’s syndrome is the main cause. Oral bis again Type 4 renal tubular acidosis is caused by reduced aldosterone. This is probably the most common cause of renal tubular acidosis Besides prim mineralocort def or MRAs consider any disruption in RAAS eg diabetic nephropathy, glomerulonephritis, ACEi, ARBs Management is with fludrocortisone

Question 114

type 1 RTA pathophys - key molecule (2 places it comes from), what would happen if membrane between tubular lumen and cap destroyed, what happens if ammonia not excreted properly and where does the problem tend to lie x2; 14 causes; key finding in urine biochem and how to confirm; mx required for pH

Answer 114

key feature of the renal tubular mechanisms involved here is the import of systemic ammonia, as well as the de novo synthesis of ammonia from glutamine within the renal tubule one can completely destroy the water-impermeable membranes which separate the peritubular capillary and the tubular lumen. This would lead to an equilibration of bicarbonate and chloride, with the resulting failure to excrete one and retain the other Any defect of ammonia excretion would decrease the concentration of chloride anions in the tubular fluid. This chloride would have to be retained (otherwise would be balancing the charge of the trapped ammonium ions) main defect in this case seems to be a problem with ATP-powered H+ secretion; another mechanism is the overactivity of a chloride-bicarbonate exchange protein (genetic causes often gain of function mutation of this) besides genetic, causes inc Cu deposition in DT (wilsons, PBC), SLE, sjogrens, hypercalciuria (hyperPTH, sarcoid, vit D tox etc), toxins (amphotericin, toluene, cyclophos, cyclospor), pyelonephritis, obstructive nephropathy characteristic finding in distal renal tubular acidosis is a positive urinary anion gap, which demonstrates a failure to upregulate renal ammonium excretion (this is intact in type 2); confirm by giving bicarb bolus, which will be reabsorbed in PT and not change urine pH (unlike type 2 where it will raise pH); 1-2mmol/kg/day of bicarbonate replacement is required

Question 115

renal acid-base handling: how much filtered bicarb usually reabsorbed in PCT and how much in DCT, what happens to the secreted protons, what else is secreted; what happens in type 1 RTA, why Na and K lost; 5 sx + 2 mechanisms by which chronic met acidosis gives hypercalciuria and 2 conditions from this + what happens to bones; type 1 causes x11; mx x2 and two main reasons for this mx

Answer 115

usually 85% filtered bicarb reabsorbed in PCT in exchange for hydrogen ions, remaining 15% reabsorbed by DCT again in exchange for hydrogen ions secreted H+ combine with urine buffers ammonia and H2PO4; Cl also secreted, allowing more bicarb to exist via electroneutrality effect distal (type 1) rta is due to DCT failing to secrete H+, thus no bicarb reabsorb either; Na would be reabsorbed as H secreted thus Na lost, intravasc vol depleted, aldos release -> K lost see failure to thrive, and the hypokal can cause weakness, lower reflexes, polyuria/dipsia chronic met acidosis -> bone resorption, and renal ca reabsorption impaired, together giving hypercalciuria and thus renal stones common and nephrocalcinosis, may get rickets from bone buffering the acid type 1 causes may be idiopathic, familial, amphotericin toxicity, sickle cell, sjogrens, SLE, nephrocalcinosis caused by hyperpara, hypercalciuria, vit D intoxication; also by chronic pyeloneph or obstructive nephro correct acidosis with small doses of bicarb 1-4 mmol/kg/day to allow growth normally and prevent nephocalcinosis, beware correcting before supplementing K as might provoke life threatening hypokal

Question 116

type 2 RTA (problem, where new conc equib is found, how K is affected and comparison to t1; 7 causes; test to show difference from type 1; mx x2

Answer 116

reduced prox reabsorption of bicarb, new equilb found at 15-20mmol/L plasma conc; some K lost to try and hold on to H but hypokal not as bad as in type 1 while can be isolated/idiopathic more usually part of global proximal renal tubular dysfunction aka Fanconi syndrome; can also be due to heavy metal poisoning, wilsons disease, various inherited disorders, renal transplant, RVT note unlike in type 1 urine can still be acidified, demonstrated with ammonium chloride loading test -> if pH falls <5.5 then type 2 likely; bicarb meanwhile will raise urine pH in this case correct acidosis with bicarb and give K supplements but give larger dose of bicarb eg 10 mmol/kg/day (as bicarb reabsorption is less effective so need to overcome this)

Question 117

type 2 RTA physiology - normal upper limit of renal bicarb reabsorb, normally what happens and how this effects tubular Cl, so what therefore happens if CA fails; 2 causes in elderly, common cause in kids, 4 drugs that can cause

Answer 117

decreases the strong ion difference by interfering with bicarbonate resorption in the proximal tubule; 26mmol/L is the upper limit of renal bicarbonate reabsorption, but this is lowered so you reabsorb less Normally carbonic anhydrase converts the filtered bicarbonate into easily resorbed CO2, and then traps it again inside the cell. The filtered bicarbonate is essentially completely reabsorbed. The concentration of chloride in the tubule is therefore expected to increase- if the bicarbonate has been reabsorbed, more chloride must remain in the tubule to maintain electroneutrality; the failure of carbonic anhydrase results in bicarbonate remaining trapped in the urine, and Cl that would have been excreted is retained in the elderly thinks MGUS, amyloidosis; may be a syndrome in kids; or drug toxicity - acetazolamide, topiramate, aminoglycosides, heavy metals

Question 118

fanconi (7 things not reabsorbed, 5 sx) and bartter syndromes (what not absorbed where, result in kidney and hormone changes, how to distinguish from other causes of similar hormone changes, 4 biochemical features, 6sx, 3 mx)

Answer 118

former inherited or acquired: reabsorption of glucose, phosphate, bicarb, K, Na, water and amino acids decreased; presents as failure to thrive, polyuria/dipsia, hypophos rickets, hypokal (weakness/constipation), and prox RTA latter due to Na Cl reabsorption fault in LoH (NKCC2) giving JGA hyperplasia, thus raised renin -> raised aldos; BP normal despite this, and is one way to distinguish from other causes of hyperaldos; Na, K, Cl levels lower, metabolic alkalosis; failure to thrive, polyuria/dipsia, weakness, constipation, salt craving, tetany (alkalosis means less ionised Ca); treated with K supplementation, Na supplementation, and spironolactone or amiloride to reduce K loss (don't always need to replace Ca as will rise as alkalosis resolves)

Question 119

9 causes of hypochloraemic hypokalaemic metabolic alkalosis

Answer 119

bartter/gitelman syndrome, diuretic abuse or chronic use, recovery after chronic hypercarbia (CLD/BPD in premies), extra-renal Cl loss eg pyloric stenosis, persisting d&v, CF, chloridorrhoea; with high BP consider cushing syndrome, hyperaldosteronism

Question 120

bartter and gitelmans syndromes (inheritance, 5 metabolic things shared, 7 shared sx; subtypes and common cause of BS and what overproduced; defect in GS; 6 common sx in BS, how GS usually picked up and 4 other sx; 2 ways to tell conditions apart and why one avoided in kid; 3mx for both, 3mx for BS, 1mx for GS and 2 times to modify it)

Answer 120

inherited autosomal recessive conditions resulting in defects of renal tubular excretion and reabsorption share some characteristic metabolic abnormalities such as hypokalemia, metabolic alkalosis, hyperplasia of the juxtaglomerular apparatus with hyperreninemia and hyperaldosteronism as a result common sx may include (from the kypokal): fatigue, dizziness, constipation, muscle cramps and weakness, and if severe then rhabdomyolysis, prolonged QT interval, life-threatening arrhythmia; despite hyperreninemia don't see HTN defect of NaCl reabsorption in the thick ascending limb for BS, often NKCC2, but there are 5 subtypes with each affecting a different transporter, and you tend to get overproduction of prostaglandin E2 depending on the type; GS meanwhile is NaCl reabsorption in the DCT due to mutation in the thiazide-sensitive NaCl cotransporter and prostaglandin plays less of a role in BS may see antenatal manifestations such as polyhydramnios secondary to fetal polyuria may occur. As transepithelial voltage gradient cannot be maintained to absorb calcium and magnesium, hypercalciuria and hypermagnesiuria occur and may result in nephrocalcinosis; history is often polyuria and polydispsia with growth failure if untreated GS often asymp, picked up with incidental hypokal finding as an older kid or maybe an adult, where BS is usually in first few years; may have sx from kypokal, or the hypomag inc failure to thrive and paraesthesias, maybe even tetany; persistent hypokal may lead to chronic interstitial nephritis, adults may have chondrococalcinosis phenotypic variation can make it hard to tell; you can give a thiazide like diuretic to tell apart, as if no change in fractional excretion of Cl then is GS; however risk of volume depletion means don't do in kids where BS is possible; genetic tests required to be sure amiloride and spironolactione for hypokal in both (GS may not need this if asymp) + K supplementation; ACEi, NSAIDs, and GH supplementation for BS; GS needs lifelong Mg supplements (higher doses when unwell, and IV if tetany develops)

Question 121

metabolic alkalosis algorithm - 6 steps (4 conditions to exclude prior to ix, then 4ix; interpreting these ix for remaining dd: 4:5:4:3:3)

Answer 121

milk alkali, CF, recent alkali admin, refeeding alkalosis? if none of these then check urine Cl, BP, renin, aldos if urine Cl <20 then diuretics, gastric Cl loss (d&v), post-hypercapnea, villous adenoma if urine Cl >20 and no hypertension then bartter, gitelmans, diuretics, hypomag, hypokal if hypertens and renin high then diuretics, renin secreting tumour, RAS, malignant hypertension if renin low and aldos low then cushing, licorice, CAH if renin low and aldos high then adr adenoma, bilat adr hyperplasia, aldo synthase hyperact

Question 122

orthostatic proteinuria

Answer 122

the most frequent cause of isolated proteinuria in children, especially adolescents defined as normal urinary protein excretion during the night but increased excretion during the day, associated with activity and upright posture urinary albumin:creatinine ratio from overnight and daytime urine samples can be compared. Normal night-time protein excretion with increased protein excretion during the day are indicative of orthostatic proteinuria. However, a further assessment of other causes of proteinuria is essential if there is any doubt It is essential to rule out any other cause of persistent proteinuria and this will often require referral/discussion with a nephrologist. Other causes of proteinuria include: Physical exercise. Fever. Pregnancy. Urinary tract infection. Nephrotic syndrome. Renal tubular disease. Nutracker phenomenon Chronic renal disease - eg, diabetic kidney disease, glomerulonephritis, reflux nephropathy, systemic lupus erythematosus and amyloidosis

Question 123

nephrotic syndrome (6 features, 2 things needed for diagnosis, metabolic sx secondary to what, causes x7, 9ix to get, 6 ix panels to consider; 5 mx

Answer 123

proteinuria w/ hypoalbuminaemia, oedema, hyperlipidaemia, (and thrombotic tendency + immunodef as proteins lost); diagnosis needs protein loss (urine dipstick) and hypoalbuminemia Hyperlipidaemia is caused by inc hepatic lipoprotein synthesis secondary to reduced plasma oncotic pressure in descending freq order, causes are: membranous nephropathy, minimal change, SLE, FSGS, MCGN, amyloidosis, IgA GN investigate: FBC, U&Es, albumin and total plasma protein, LFTs, lipid panel, urine microscopy, urine sodium, urine protein:creatinine ratio; consider HIV, hepatitis, syphillis, autoimmune, myeloma, amyloidosis ix many cases steroid responsive, esp in kids, else treat cause if known; restrict fluid and salt, use furosemide; ACEi or ARB as have anti-proteinuric effect and also treat the raised BP; note breathlessness may be an embolism from hypercoagulability not just oedema - heparin or warfarin/DOAC if patient at high risk of clotting

Question 124

membranous nephropathy (peak incidence age, how common, pathophys, commonest cause, secondary causes x14, mx x3)

Answer 124

GN, one of the commonest worldwide causes of nephrotic syndrome; peak incidence in 40-60s and 2:1 men:women; 2nd most common adult GN after FSGS immune deposits on GBM, recruit complement, podocytes injured 85% idiopathic; secondary due to many infections HBV, HCV, HIV, malaria, schistosomiasis, syphilis, leprosy, lung/colon cancer, leukaemia and lymphoma; autoimmune disease inc MG, SLE, IBD etc; nephrotoxic drugs symptomatic relief, treat cause, immunosuppression

Question 125

nephrotic syndrome 3 complications (and acr); nephrotic syndrome 7 mx, 4 options for mem neph if not remitting, mem GN prognosis x3, 4 broad causes

Answer 125

nephrotic syndrome urinary protein >3.5g/24hr, ACR >220 complications: VTE, pneumococcal infection (Ig loss), hypercholesterolaemia generally to manage nephrotic syndrome: diuretics and fluid restrict for oedema, ACEi/ARB (reduce protein loss), aspirin, anticoagulate if severe hypoalbu <20g/L, statin if no remission of nephrotic syndrome due to mem GN after 6mo then give cyclophosphamide, steroids, or tacrolimus; or b cell biologics In pts with mem GN, 25% have spont remission, 25% partial remission or stabilise, 50% have progressive renal impairment membranous GN see thickened BM; 25% full remission, 25% partial, 50% progress 66-85% membranous GN is idiopathic, rest due to SLE, infection (HBC/HCV, malaria), drugs (penicillamine, NSAIDs, gold)

Question 126

nephrotic syndrome paediatric

Answer 126

Proteinuria  Low plasma albumin (<25 g/l)  Oedema  Hyperlipidaemia is typically also present Remission:  No proteinuria for 3 consecutive days Relapse:  Proteinuria 3+ or greater for 3 consecutive days  Oedema and proteinuria – this may be how a relapse presents if regular urine testing has not been done at home Frequently Relapsing:  2 or more relapses within 6 months of the initial response, or  4 or more relapses within any 12 month period Steroid Dependent:  relapsing clinical course whilst on alternate day steroids or clinical relapse within 2-weeks of cessation of steroids Classification: Idiopathic (primary) NS: – Steroid responsive – Steroid resistant – no remission after 4 weeks of full-dose prednisolone Secondary NS (post-streptococcal nephritis, HSP, SLE, MPGN) Congenital NS – presents in first 3 months after birth Typical features are aged 1-10yo with normal BP, normal Cr, +/- microscopic haematuria; atypical if outside of these parameters; >90% of typical cases are steroid responsive and won't need a biopsy Children with atypical features:  should be discussed with paeds nephrology as soon as possible, before commencing any treatment  are more likely to be unresponsive to steroid treatment  are likely to undergo renal biopsy, when the main histological types are  Minimal change  Focal segmental glomerulosclerosis (FSGS)  Mesangioproliferative glomerulonephritis at presentation get: height, weight, BP, U&Es, bone profile, liver profile, FBC, C3/4, VZV IgG titre, measles IgG titre, urine dip, urine protein:creatinine ratio (and discuss atypical with paeds nephro ?further ix) during inpatient stay will need: twice daily weight, 4 hourly BP, daily urine dip, and input/output fluid monitoring; rpt bloods won't normally help besides atypical presentation, discuss with paeds nephro if: low C3/4, poor urine output, no remission despite 28 days of pred, marked s/e when on steroids Consider admission if first presentation  Always admit if child is hypertensive, oedematous or has raised creatinine.  Most children who have relapsed can be managed at home unless the above apply Give pred: 60 mg/m2 orally daily, to a maximum daily dose of 60 mg, for 28 days irrespective of whether the child goes into remission before 28 days then 40 mg/m2 orally on alternate days for 28 days then 30 mg/m2 orally on alternate days for 14 days then 20 mg/m2 orally on alternate days for 14 days then 10 mg/m2 orally on alternate days for 14 days then 5 mg/m2 orally on alternate days for 14 days Then stop Give PenV whilst the child is nephrotic with oedema and low plasma albumin (this advice varies between departments so check yours). Discontinue once in remission Give ranitidine during prednisolone treatment in order to reduce gastritis related symptoms. It can usually be discontinued once the prednisolone dose has reduced to 10 mg/m2 on alternate days. Low salt diet to help prevent excess thirst and fluid retention. Fluid restriction is only considered if the child continues to gain weight despite a low salt diet and is clinically euvolaemic. If relapse: Come straight to CED if the child: – becomes unwell e.g. with abdominal pain or fever – has worsening oedema – has reduced urine output Treatment with prednisolone can usually be commenced immediately at home: Prednisolone dose: 60 mg/m2 orally daily, to a max daily dose of 60mg, until remission; then wean using same doses as above but one week instead of 28 days and follow above advice for pred/ranitidine/low salt diet Their consultant MUST be told about the relapse Levamisole may be beneficial for children with frequent relapses. It is less useful in those who are steroid dependent. After treatment has been established for 4 weeks, steroids can be tapered. FBC check monthly for first 3 months, then at 6 months and 4-6 monthly thereafter. Occasionally cyclophos, ciclosporin, tacrolimus, mycophenolate, rituximab may be used if steroid unresponsive or frequently relapsing 20% HAS 5ml/kg over 4-6 hours can be given after discussing with paeds neph for: Hypovolaemia: – cool fingers and toes – poor urine output – abdominal pain – raised urea, raised Hb/Hct Severe oedema: – causing immobility – scrotal swelling and ascites causing discomfort – skin breakdown Low urinary sodium can help to confirm intravascular volume depletion if clinically not obvious. <10mmol/L consistent with volume depletion Monitor oxygen saturation, pulse, blood pressure, respiratory rate every 30 minutes regularly during and for 2 hours post infusion.  Accurate fluid balance measurement essential  Beware of intravascular fluid overload due to fluid shift: o rising pulse, BP, respiratory rate; visible JVP o development of oxygen requirement  If overload develops: o Stop 20% albumin infusion o consider furosemide Besides infection with encapsulated organisms, there is a risk of SBP: Any child with NS presenting with abdominal pain and tenderness +/- fever should be commenced on IV antibiotics (amoxicillin, gentamicin & metronidazole as per protocol for peritonitis) and discussed with the Paediatric ID team Consider intravascular thrombosis as a cause of symptoms such as – altered behaviour or headaches / vomiting (intracranial thrombosis) – cough and breathlessness (pulmonary thrombo-embolism) – peripheral vascular changes suggesting DVT or arterial ischaemia – renal vein thrombosis (signs can include macroscopic haematuria, palpable kidney, loin tenderness, raised creatinine, hypertension) Patients on prednisolone and negative for varicella antibodies should be given VZIG if in contact with chicken pox Avoid live vaccines whilst on steroids o Aim to administer vaccine when steroids and/or other immunosuppressive drugs have been stopped for at least 12 weeks o Pneumococcal recommended for all children with NS  routine pneumococcal vaccine (Prevnar 13) should be supplemented with Pneumovax 23 for over 2 year olds

Question 127

congenital nephrotic syndrome - finnish type (3 signs in the mum, 2 thing in first few weeks of life then 2 things that build up and prognosis), dd name, biochem and prognosis vs finnish type, mx x2 and what is no help

Answer 127

finnish type - more common, maternal serum and amniotic fluid AFP up, large placenta; early proteinuria and normal renal function presenting in first few days to weeks of life; gradual nephrotic picture onset with rec infections and declining renal function, death by 4-5yo diffuse mesangiosclerosis - normal maternal AFP but proteinuria at birth, more rapid decline than finnish type dialysis for mx, consider transplant when child old enough; steroids and immunosuppression no help

Question 128

what causes abdo pain in nephrotic syndrome? what happens to BPx2? what negative spiral can occur?

Answer 128

splanchnic ischaemia BP may be low due to hypovol (fluid lost to extravascular spaces as oncotic pressure falls), or high as underperfused kidney releases renin - fluids will improve the BP in this case also get negative spiral of dec oncotic pressure -> oedema but low intravasc volume so raised FF, thirst, ADH, renin -> Na and water retained, worsening oedema

Question 129

5 proteins lost in nephrotic syndrome and result (inc specific bacti class problem)

Answer 129

albumin loss -> hypoalbuminemia immunoglobulins and complement loss inc's susceptibility to encapsulated bacti eg pneumococcus and HiB, sepsis of former esp a problem acquired thrombophilia due to loss of clotting factors like antithrombin loss of vit D binding globulin -> rickets thyroid binding globulin -> hypothyroid

Question 130

RVT (2x causes, 5x sx, ix, mx)

Answer 130

occurs in state of severe dehydration (eg neonate not having sufficient fluids and febrile) or hypercoag state (nephrotic syndrome, polycythaemia, protein C deficiency) renal enlargement, flank pain, irritability in baby, haemat (micro or macro), and declining renal function renal uss can diagnose if develop breathlessnes as well may have developed secondary PE treatment with hydration and anticoag

Question 131

neonatal RVT

Answer 131

Suspect RVT in any newborn infant with haematuria. 3. Look for classic triad of RVT: (1) haematuria; (2) flank mass; (3) thrombocytopenia Consider the following questions to identify potential risk factors for thrombosis * Is it spontaneous? * Is it secondary to UVC placement? * Is it secondary to risk factors associated with hyperosmolar state such as perinatal asphyxia, coagulopathy, maternal diabetes mellitus, dehydration, polycythaemia, acute blood loss, sepsis, shock? Obtain intravenous access and perform FBC, UEC, coagulation profile (APTT, PT) and other blood tests as appropriate. Perform abdominal ultrasound with colour Doppler Consult renal and haematology team urgently. Perform prothrombotic risk factor screening: protein C, protein S, plasma antithrombin III activity, lipoprotein (a), factor V Leiden mutation, prothrombin gene mutation and MTHFR thermolabile mutation. Ensure close monitoring of urine output (including catheterisation in case of macroscopic haematuria due to risk of blood clots blocking urination) and fluid balance. Ensure good hydration (guide: 20 ml/kg/day more than regular volume requirement) Discuss the specific thrombolytic and anticoagulant management with renal and haematology; generally will be LMWH, bilateral RVT with renal compromise will likely need thrombolysis with alteplase Perform colour Doppler daily for the first week of hospitalisation. This is to check for: * Extension of thrombosis * Re-permeabilisation (defined as reappearance of renal vein patency and regression of nephromegaly and hyperechogenicity) Closely monitor blood pressure (minimum 6 hourly) for the first week of hospitalisation to evaluate any transient hypertension. Closely monitor platelets, EUC, urine output and fluid balance Closely monitor for central nervous system complications by regular cranial ultrasounds as intraventricular haemorrhage can occur with thrombolytic/heparin therapy

Question 132

nephritic syndrome - 6 poss sx/signs (inc histo for the diff causes - 4 in kids, 7 more in adults); IgA mx in adults (5 associations, control hyper, control condition)

Answer 132

hypertension, haematuria, gfr down, oedema, flank/abdo pain, maybe AKI kids/teens: IgA neph (1-2 days after urti), PSGN (2-3 weeks after strep inc urti), HSP (purpura, abdo pain, arth, plus maybe nephritic symptoms, also often post-infectious and IgA associated), HUS (after diarrhoea, thrombocytopen, haem anaem, AKI or neph) in adults: maybe above but also goodpastures, SLE, RPGN, MPGN, inf endocard, cryoglobulinemia, anca vasculitides (egpa, micro poly, gpa) many will have crescentic GN appearance on histo, stain for IgG in antiGBM disease, IgA in IgA neph/hsp, IgM/G complement in lupus, IgG and complement + starry sky in post infectious, pauci-immune if anca associated IgA -> hypercellular mesangium IgA most common GN in adults, systemic IgA doesnt have to be raised, 5% have AKI, exercise may worsen, infection/vaccination, associated with coeliac; associated with infections -> pharyngi, tonsil, pneumonia, gastroent; control hypertension (acei), consider tonsillectomy if that's triggering immunosuppression eg steroids, 20-40% progress to esrf; male, older age, crescentic appearance some risk factors for worse progression

Question 133

types of GN (IgA neph, post-infectious, mesangiocap, minimal change, FSGS)

Answer 133

IgA nephropathy: most common, often idiopathic but sometimes eg GI disorders, cirrhosis etc; 30-50% will progress to CKD IgA complexes deposit in mesangium activating them to make PDGF and other cytokines by Fc receptors, they proliferate and make matrix and recruit inflam exudate; suggested genetic influence and maybe hypersensitivity or an infection triggers but not always consider in young adults esp with unusual urine, may have CKD but not always; raised BP common; 50% cases will have raised serum IgA post infectious: usually after strep but any infection can cause in theory; beware a concealed source of infection eg endocarditis or abscess; parasites, fungi, viral infections can cause too classic is in kids <7yo and mediated by immune complexes, often after an infection eg sore throat, cellulitis, otitis media, impetigo, tonsilitis etc has resolved; varies on spectrum from micro haemat to AKI, oedema etc; often self limiting mesangiocapillary GN: defined histologically with BM splitting and mesangial IC deposits as cytoplasm from mesangial cells pours between endothelium and BM; complement attacks the ICs; idiopathic usually in peeps ages 8-30 and more common in men; poor prognosis of 50% -> ESRD at 10 yrs minimal change disease: less common in adults, common in kids; suspected due to altered T cell activity resulting in podocyte dysfunction atopy in 30% of patients with this, other poss causes inc infection, malignancy (haemtological often), NSAIDs and many other drugs odema often massive with facial and periorbital swelling, ascites, pericardial effusion etc; foamy urine as protein has detergent effect; normal appearance under LM, EM shows podocytes displaced remits rapidly with steroid treatment focal and segmental glomerulosclerosis: may be secondary if other glomerular damage, altered haemodynamics damage remaining nephrons; may also be primary/idiopathic which is more common in men and black people (is 2/3 of causes of nephrotic syndrome in black people) presents with nephrotic syndrome, signs of GN; secondary often after infection like HIV associated nephropathy, after reflux, after drug toxicity, after morbid obesity, sickle cell, pre-eclampsia, diabetic nephropathy or various types of GN; linked to prog CKD treat underlying cause and relieve symptoms, if prim immunosupp can be considered

Question 134

henoch-schonlein purpura (Ig involved, normal ages, aetiology and general pathophys inc form of vasculitis, 4 triggers and commonest season, 3 features of prodrome, 12 sx and classic tetrad, 14 complications 6 dd, 9 ix, 4 mx, 2 reasons to admit; 8 dd for non-blanching purpura; 4 steps for follow up and process if nephritic features inc x2 reasons to consider biopsy)

Answer 134

IgA autoimmune vasculitis of childhood peak 4-6yo, 90% cases under 10yo, rare in infants Etiology is unclear. More than 75% of patients report previous upper respiratory or gastrointestinal infections  Many bacteria, viruses, drugs and vaccinations have been associated  Thought to be IgA-mediated autoimmune phenomenon with an unknown antigenic stimulant. Antigen-antibody complexes deposit throughout the body and activate pathways leading to necrotizing vasculitis often history of prev infection inc pvB19, EBV, campylobacter etc; vaccination may be trigger most common in autumn/winter, look for preceding urti/GIT disease Prodrome of headache, anorexia, fever is followed by a rash, abdominal pain, and/or arthritis low fever, sym erythematous macules on (back of) legs, buttocks, ulnar side of arms evolving over 24hrs to raised red or purple non-blanching purpura; preceding/along rash abdo pain, bloody diarrhoea, n&v; joint pain, esp knees and ankles, may be swollen/tender; renal involvement within 3mo of disease starting: micro haemat, some proteinuria, maybe nephrotic syndrome - rarely nephritic syndrome and <1% progress to ESRD - sometimes ckd progresses up to 10yrs after initial flare; scrotal involvement may mimic test torsion with swelling +/- pain; sometimes headaches/seizures; classic tetrad of palp purpuric rash, joint pains, GI symptoms, renal symptoms Gastrointestinal complications include intussusception (usually ileo-ileal), bowel infarction, bowel perforation, hydrops of the gallbladder, pancreatitis, massive GI bleed & protein losing enteropathy Cardiac: Coronary artery vasculitis resulting in myocardial infarction (MI)  CNS: Headache, CNS bleeding, subtle encephalopathy, seizures  Other: Pulmonary haemorrhage, Orchitis which may lead to surgical exploration of the scrotum consider intussusception, meningitides and thrombocytopenia, other GN causes, IBD, SLE urinalysis, FBC, U&Es, crp + esr, ASOT, monospot, autoantibody screen (ANA, RF, C3/4), consider abdo uss; note if clinically diagnosed and urine dip obtained and you're not admitting then other ix may not be needed (except ?check renal function) self limiting within 4 weeks: water, paracetamol (nsaids but caution if renal/GI involvement eg proteinuria or hypertension); In children with severe abdominal or joint pain not responding to simple analgesia, a course of prednisolone 1mg/kg daily for 1-2 weeks may be considered after discussion with treating consultant Provided there is no frank haematuria, and no severe abdominal tenderness or severe joint pain, the child may be discharged with paracetamol or Ibuprofen If frank haematuria is present initially, admit for observation, urine output measurement, and BP checks. If severe abdominal pain is present or if symptoms suggest intussusception or GI bleeding occurs, discuss with consultant, admit for observation and consider surgical assessment differentials for nonblanching purpura: meningococcal sepsis, HSP, ITP or other cause of low plats (inc leukaemia and aplastic anemia), DIC, HUS, forceful coughing/vomiting (if theyre in head/neck/shoulders), NAI HSP should remain in the differential diagnosis of any patient presenting with abdominal pain with or without a skin rash. This is one of the reasons why urinalysis in children presenting with non-specific abdominal pain is so important. Reg review clinic at 48-72 hours and at 2 weeks (for BP, EMU dipstick).  GP to review weekly in weeks 1-4 (for BP, EMU dipstick), then fortnightly in weeks 5-12 (for BP, EMU dipstick).  OPD Appointment at 3 months with Consultant. If, at that time, there has been no renal involvement, discharge to further GP follow up.  GP should see child at 6 months (for BP, EMU dipstick) and discharge if no renal involvement.  If at any time there is hypertension, macroscopic haematuria or proteinuria, GP should refer urgently to a paediatrician for ix and possible discussion with neph following below plan (also used for nephritic syndrome features at any point): rpt all ix as above/do for first time; any nephritic syndrome or nephrotic syndrome persisting for 4-6 weeks will require consideration of renal biopsy by paeds neph

Question 135

HUS

Answer 135

gastroenteritis, often with bloody diarrhoea. The symptoms of haemolytic uraemic syndrome typically start around 5 days after the onset of the diarrhoea. Signs and symptoms of HUS may include: Reduced urine output Haematuria or dark brown urine Abdominal pain Lethargy and irritability Confusion triad: haem anaemia, AKI, thrombocytopenia supportive management; renal dialysis may be needed pneumococcal HUS - rarely, HUS can be a complication of invasive strep infection (5% of HUS, 0.4% of invasive strep infection)

Question 136

haemolytic uraemic syndrome - triad, associations x5 inc commonest, 5sx, 7ix, 5mx

Answer 136

haemolytic anaemia, thrombocytopenia, and AKI triad associated commonly with e coli O157; sometimes strep pneumoniae, coxsackie virus, cancers, lupus profuse diarrhoea turning bloody 1-3 days later most common presenting feature, history of fever (though oft afebrile by time reach doctors), marked abdo pain and painful defaecation often if suspect (ie has bloody diarrhoea), then FBC and film, U&Es, LFTs, lactate (high is early hus indicator), stool culture, urinalysis notifiable, supportive treatment with fluids - must keep circulating volume up to minimise AKI risk; dialysis, antihypertensives, blood transfusions may be needed

Question 137

HUS anaemia histo finding (why) and what kind of anemia and 9 poss complications, mx x4

Answer 137

DAT -ve haemolytic anaemia w schistocytes seen as rbcs shredded through fibrin mesh complications: abdo pain, perforation, strictures, encephalitis or persistent neuro sequelae, myocarditis or cardiomyopathy, diabetes or pancreatitis, hepatitis, retinal haemorrhages control hypertension, maintain fluid and electrolyte balance, transfuse blood/platelets, dialyse if needed

Question 138

7 rash then renal failure possibilities (inc 3 ix)

Answer 138

HSP, sometimes HUS, streptococcal disease or IgA neph, SLE; also vasculitides, inf endocard consider therefore autoimmune screen, ASOT, plus complement levels (C3/4 reduced by strep and SLE)

Question 139

pulmonary renal syndrome (7 causes, what kind of autoimmune disease depletes complement, anti-GBM histo and antibody type + 3mx,

Answer 139

esp goodpastures, ANCA vasc, lupus, crygoglobulinaemia, HSP (though skin, joint, bowel commoner than lung) also maybe nephrotic syndrome ->RVT -> PE; infection with resp and kidney (AIN, ATN) involvement IgG complexes deplete classical complement C4 C3 (so in eg lupus etc) anti-GBM disease: IgG staining linearly along the BM, crescentic GN histo; aka goodpastures; look in blood for anti glomerular BM antibodies plasma exchange to remove antibody, iv -> oral steroids, cyclophosphamide

Question 140

CH50 assay

Answer 140

screening assay for the activation of the classical complement pathway and it is sensitive to the reduction, absence and/or inactivity of any component of the pathway tests the functional capability of serum complement components of the classical pathway to lyse sheep red blood cells (SRBC) pre-coated with rabbit anti-sheep red blood cell antibody (haemolysin). When antibody-coated SRBC are incubated with test serum, the classical pathway of complement is activated and haemolysis results. If a complement component is absent, the total complement activity / CH50 level will be zero; if one or more components of the classical pathway are decreased, the CH50 will be decreased Common egs: Low C3 and C4 levels can be seen in active SLE. Very low C3 in isolation can be seen in post streptococcal glomerulonephritis and C3 nephritic factor related disease. Very low C4 in isolation can be associated with C1 inhibitor deficiency. A decrease in both C3 and C4: --- commonly seen when the classical pathway is activated --- immune complex-mediated diseases such as systemic lupus erythematosus / SLE --- consumption of the complement components (sepsis) -- low synthesis due to liver disease. C3 is decreased and C4 is normal: --- commonly seen when the alternative pathway is activated (Gram-negative sepsis) --- post-streptococcal glomerulonephritis --- C3 nephritic factor. C3 is normal and C4 is decreased: ---cryoglobulinaemia ---C1 inhibitor deficiency ---active SLE ---genetic deficiency if and individual has normal C3/C4 values but a decreased CH50, that can indicate a terminal complement pathway deficiency (deficiencies of C5, C6, C7, and C8 - not C9 as not required for cell lysis) Increased CH50 values means that their complement is hyperfunctional relative to normal, and this may be seen in cancer and other inflam states

Question 141

post-strep vs IgA neph

Answer 141

Post-streptococcal glomerulonephritis occurs 1 – 3 weeks after a β-haemolytic streptococcus infection, such as tonsillitis caused by Streptococcus pyogenes. Immune complexes made up of streptococcal antigens, antibodies and complement proteins get stuck in the glomeruli of the kidney and cause inflammation. This inflammation leads to an acute deterioration in renal function, causing an acute kidney injury management supportive; may see haematuria but proteinuria bigger symptom; complement levels may be low IgA nephropathy (also known as Berger's disease) is the commonest cause of glomerulonephritis worldwide. It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection 1-2 days after, mesangial IgA deposition so mesangial cell prolif

Question 142

HSP vs HUS vs TTP - inc management for all (itp in kids inc management)

Answer 142

HSP vs HUS vs TTP: HSP is primarily seen in kids. It's a leukocytoclastic vasculitis that primarily affects the skin (palpable purpura on the buttocks and lower extremities w/o thrombocytopenia, platelet count may even be raised), joints, kidneys (proteinuria and hematuria), and the GI tract (abdominal pain). may have n&v; also if young and abdo pain + bloody diarrhoea make sure to rule out intus It often follows a GI illness or URI and is usually self-limiting but oral steroids can help. sometimes associated with IgA neph so check BP and urine regularly over 6-12mo; if rash only on legs not butt consider thrombocytopenia which can inc HUS HUS is often associated with EHEC and Shigella and is seen most often in kids. (There's also 'atypical HUS', which is much rarer.) It often presents (on exams) as a microangiopathic hemolytic anemia (i.e., anemia, schistocytes, low haptoglobin, normal coags) with thrombocytopenia and AKI (oliguria, hematuria, elevated creatinine, etc). Most kids will recover from this illness but may need supportive therapies (e.g.fluids, if bad aki dialysis, plasma exchange); esp if 6mo-5yo, may have recent exposure to farm animals shiga toxin damages endothelium (esp in glomerulus) causing microthrombus formation TTP is a life-threatening disorder usually seen in adults. As others have stated, primary TTP is caused by large wWF multimers that lead to widespread clot formation. The classic pentad is fever, thrombocytopenia, microangiopathic hemolytic anemia, AKI, and altered mental status (and other neurologic manifestations). Coags will be normal, which helps to distinguish this disorder from DIC. (If you see thrombocytopenia with MAHA but normal coags and no real signs of sepsis or sources of infection, think TTP.) Treatment relies on plasmapheresis; may be idiopathic (oft antibodies directed against ADAMTS13 which breaks down vWF), can be genetic with mutation in ADAMTS13 gene can be sec to bacti infection, pregnancy, SLE, bone marrow transplant, antivirals, chemo, immunosup, HRT/COCP; steroids can help, dont give platelets; HUS more common in kids vs TTP more common in adults, TTP will oft have low/altered ADAMST13 in lab tests, also note ITP often follows viral prodrome in kids, may have epistaxis or purpuric rash; oral pred, then IVIg/ritux, then splenectomy but usually self resolving and treatment not needed if plat count >50; rule out HIV and HCV as triggers for low plat count alongside other causes

Question 143

paediatric nephritic syndrome guideline

Answer 143

Patients may present with:  Macroscopic or microscopic haematuria  Signs of fluid overload such as hypertension and oedema  Renal dysfunction. In the paediatric age group, the most common cause (about 80% of cases) is acute post-infection glomerulonephritis (APSGN). Streptococcal infections represent most of this post-infectious acute GN; other infections include Staphylococcus aureus or Staphylococcus epidermidis and gram-negative bacteria symptoms usually develop:  1-2 weeks after a throat infection (Pharyngitis).  Alternatively, 3 – 6 weeks after skin infection (Impetigo). The prognosis for APSGN is good, with 95% of patients making a full recovery Ix: Urine for:  Dipstick urinalysis  Urine culture  Urine microscopy for casts (often not seen unless extremely fresh specimen)  Urine protein: creatinine ratio (confirm with early morning specimen) (B) Blood for:  Paediatric renal profile to include urea, electrolytes, creatinine, calcium, phosphate, chloride, bicarbonate, and albumin  Full blood count  Antistreptolysin titre (ASOT)  Ask lab to store blood for Anti-DNase B titres if ASOT negative  C3 and C4 levels  Anti-nuclear antibody (ANA) (C) Throat or skin (if infected) swab (D) CXR if hypertensive or fluid overloaded discuss with paeds neph if: estimated GFR <90 ml/min/1.73m2 – see Appendix 1 * electrolyte imbalance (especially hyperkalaemia)  hypertension  nephrotic syndrome or protein: creatinine ratio >50 mg/mmol  normal C3 and/or low C4 (low C3 would be consistent with PIGN)  signs/results suggestive of systemic vasculitis (rash, arthralgia, other organ involvement, positive ANA) . Further investigations to consider after discussion:  Renal Ultrasound  Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane antibody (antiGBM antibody) if renal dysfunction or signs suggestive of vasculitis  General viral titres plus Hep B and C, HIV, Hantavirus  C1q and C1q antibodies if SLE suspected  Cryoglobulin titre (cryoglobulinemia is a small vessel vasculitis, rare in childhood, associated with chronic infections especially hepatitis C, autoimmune disorders, and B-cell lymphoproliferative diseases) Post streptococcal acute glomerulonephritis usually remits spontaneously and treatment is supportive only. Children without fluid overload, hypertension or electrolyte imbalance may be managed as outpatients providing they are reviewed frequently .2 Fluid Balance  Fluid input and urine output should be closely monitored.  All children should be weighed daily.  All patients should be on a no added salt diet.  If oliguric (<0.5 ml/kg/hr) restrict fluid input to replacement of insensible losses (400 ml/m2/day) plus previous days urine output  If overloaded (i.e., Hypertensive, raised JVP, oedematous) give furosemide 1 – 2 mg/kg up to twice daily to induce a negative fluid balance If hypertensive: Treat fluid overload which is the usual cause (see above)  If euvolemic, use Amlodipine (nifedipine an option but only IP as short acting + rebound)- no ACEi unless proteinuric and paeds neph say so, no beta blockers as can worsen hyperkal mx hyperkal in normal fashion on d/c will need OP review minimum 3mo and 6mo Normal urinalysis and normal BP on at least 2 visits + normal eGFR, C4, C3, albumin at 3mo then d/c from follow up -> otherwise paeds neph ddx: IgA neph - will have normal complement MPGN - low C3 and proteinuria persist beyond 3mo vasculitides (in general will have systemic sx): IgA nephritis (HSP), SLE (rash, raynauds, arthropathy, alopecia, pleuritis), ANCA positive vasculitis (nasal ulceration, sinusitis, cough, haemoptysis) Alport syndrome: family history of deafness or kidney disease also suspect above if has had previous episodes of visible haematuria

Question 144

amyloidosis

Answer 144

a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue about 36 different types of amyloidosis, each due to a specific protein misfolding; 19 are grouped into localized forms, 14 are grouped as systemic forms, and 3 proteins can identify as either protein misfolding ca be genetic or acquired 4 most common types: light chain (AL), inflammation (AA), dialysis-related (Aβ2M), and hereditary/old age People with conditions such as multiple myeloma or a bone marrow illness called Waldenström’s macroglobulinemia are more likely to have AL amyloidosis - it starts in plasma cells AA amyloidosis can complicate chronic diseases characterized by inflammation, such as rheumatoid arthritis (RA) or inflammatory bowel disease (IBS) ATTR (aka inherited/old age) due to transthyretin protein amyloid deposition in kidneys can cause nephrotic syndrome, 20% AL and 40-60% AA type get esrf; deposition in heart can give heart failure, AV block or SAN dysfunction don't get CNS involvement but PNS and ANS giving sym sensory neuropathy or autonomic dys from GI involvement can get weight loss, diarrhoea, abdo pain, reflux, GI bleeding, jaundice, fat malabsorp, splenic dysfunction; may get hypothy, hypoadr, joint pain (esp knee, hands, wrists, hip) can dev purpura w bruising around eyes; can also get enlarged tongue so general signs and sx: Feeling very weak or tired Losing weight without trying Swelling in the belly, legs, ankles or feet Numbness, pain or tingling in hands or feet Skin that bruises easily Purple spots (purpura) or bruised-looking areas of skin around the eyes Bleeding more than usual after an injury Increased tongue size Shortness of breath

Question 145

amyloidosis 7 ix and 3 mx

Answer 145

A urine test and a blood test may be followed by one or more imaging procedures to take a look at body’s internal organs, such as an echocardiogram , nuclear heart test or liver ultrasound . A genetic test may be necessary to see identify the familial form of amyloidosis. might undergo a biopsy, where the doctor takes a small sample of bone marrow or another organ to examine under the microscope mx - aim to slow progression and reduce sx impact; depends on type but eg chemo or autologous bone marrow transplant for AL, special meds that target the TTR gene or stabilise the protein various clinical trials too

Question 146

12 causes of combined renal and neuro signs

Answer 146

wilsons - fanconi plus basal ganglia/periph neuro renal HTN - may cause seizures and hypertensive enceph renal biochem disturbance - esp plasma Na may cause seizures if altered HUS SLE - enceph, stroke/cvst, perip/autonomic neurop, headache, mood disorder, seizures alport syndrome - GN, sensorineural deafness esp in high freq range, and vision changes; micro/macro haemat common ADPCKD - associated with berry aneurysm sickle cell - pap necrosis and neuro features lead poisoning - fanconi syndrome and raised icp tuberous sclerosis - angiomyolipoma can lead to htn and aki, can get renal cysts NF - linked to renal artery stenosis PRES - post reversible enceph syndrome, causing seizures (+/- status), delirium, and/or visual changes oft in context of HTN during CKD/AKI or if on drugs post-renal transplant drug ingestion always poss

Question 147

enuresis (sx to ask about, when to consider mistreatment; how to assess primary inc 2 things to rule out if daytime too, 6 things to look for if secondary; 6 initial things to manage primary w/o daytime wetting, what if those fail (or for short term protection), when to refer primary to paeds and 2 meds they can try; how to use desmo, 3 times to be cautious with it; how to mx secondary (simple) and when to refer to sec care

Answer 147

if <5yo ask if trained for daytime toilet use ask about urgency, freq, daytime wetting, dysuria, poor stream, pass <4times a day, prev been dry at night for >6mo; consider child mistreatment if persists despite adequate treatment, or child reported to be doing it deliberately ask children if they think there is a problem, what they think the problem is, what they want from treatment if primary assess when happens, fluid intake, access to toilet, reason for consultation - if under 5 then assess for constipation as this is common cause; congen malforms (spina bifida) and UTI if daytime too if sec look for constipation, diabetes, uti, behavioural problems, family problems, maltreatment, and assess pattern explain it isnt childs fault, and punishing them wont help prim w/o daytime wetting - reassure that oft resolves; advice on fluid intake, avoid caffeine, toilet 4-7 times during day, easy toilet/potty access, waterproof pads etc for bed; positive rewards for dry nights, drinking right amount; short term control for sleepovers or school trips with desmopressin; enuresis alarm long term if other methods failed, desmopressin can be used if alarm wont work (eg shares room with sibling, <7yo so not mature enough etc); each treatment for 4 weeks, if working use for 3mo trial a week w/o to see if worked if not can keep going for 6mo; wait and see if <2x wet nights a week if no response to 2 complete courses with alarm or desmo refer to paeds, may use TCA (imipramine) or antimuscarinic (oxybutynin) sips only (1 glass total) from 1hr before to 8hr after desmo to avoid fluid overload, take it at bedtime, caution if sickle cell or CF, avoid nsaids; if revert after stop treatment can start again for second attempt if daytime wetting refer to sec care; if secondary try to identify and manage cause, if cant find or manage refer to paeds or enuresis clinic

Question 148

enuresis definition

Answer 148

Enuresis may be defined as the 'involuntary discharge of urine by day or night or both, in a child aged 5 years or older, in the absence of congenital or acquired defects of the nervous system or urinary tract (ie still v common at age 4, tho most children achieve nightime continence by 3-4yo)

Question 149

haematuria (inc what tming of blood relative to pee and what pain level tells you)(general ix)(also inc initial mx if catheterised haemat)

Answer 149

kidney: tear, stone, tumour, parenchymal disease, GN, infarction, infection, PCKD ureter: stone bladder: tear, tumour, cystitis, stone urethra: bleeding from prostate/dilated veins over prostate, prostate cancer, BPH, tear if accompanied by pain in flanks renal origin more likely, terminal w/pain bladder likely, initial or terminal but painless prostate likely, dribbling indy of micturition suggests urethral origin; painless and symptomless suggestive of tumour somewhere in tract; acute nephritis poss if recent sore throat, esp in child also bleeding disorders (TCP, on anticoag med), but usually underlying path which bleeding disorder just unmasks ballot kidneys, feel for bladder and prostate can do microscopy (rbcs to exclude haemoglobinuria or beeturia, casts suggests GN, pus and organisms infection), cytology, USS renal, CT renal tract (with contrast), flexible cystoscopy TB can infect the kidneys with granulating lesions in parenchyma giving haemat, pyoneph, and can spread down ureter to give cystitis in cathetrised pt firts send ix and see if resolves over 24 hours, if not can do 3 way catheter and bladder irrigation, and consider 2ww for CT renal tract and flexi cystoscopy

Question 150

additional haematuria (8 transient causes, 2ww when, best 3 imaging tests in order you want them)

Answer 150

check for transient causes: UTI, period, beetroot, exercise, rifampicin, penicillins, cyclophosphamide, hep/warf refer to urology on 2 week wait for >45yo with VH that is not explained by UTI etc, or if after treating the UTI still present; also any non visible H if >60yo if elevated WCC or dysuria any transient causes ruled out renal USS combined with cystoscopy best initial investigation of nonVH, CT scanning can be next stage if bladder cancer, need to CT scan for staging and to see if upper urinary tract cancer too

Question 151

urine colour and tests (causes 6:2:2, why red in first days of life; 2 kinds of urine dipstick(

Answer 151

red: haematuria, haemoglobinuria, myoglobinuria, beeturia, acute intermittent porphyria, urates black urine: alkaptonuria, also oft seen in melanotic sarcomas which secrete melanin in urine urine that darkens on standing: porphobilinogen or urobilinogen, both colourless compounds that turn dark orange-brown when exposed to air note - brick red urate staining in first days of life common, due to high urate conc due to dehydration as breastmilk still coming through while breastfeeding clinistix is urine dipstick specific for glucose; clinitest is urine dipstick that detects reducing sugars (glucose, lactose, fructose, galactose) but not sucrose

Question 152

16 ix for haematuria

Answer 152

MC&S of urine, U&Es, FBC, coags, CRP, ASOT, antinuclear factor, C3/C4; if painful include Ca, phos, urate levels and send urinary electrolytes and Ca; consider abdo x-ray/CT-KUB, uss, flexible cystoscopy, renal biopsy

Question 153

BFH and idiopathic hypercalciuria

Answer 153

benign familial haematuria kids have persistent microhaemat, this tends to run in families and renal function may worsen over time; biopsy to diagnose definitively, shows reduced thickness of glom BM idiopathic hypercalciuria in 2% of children can lead to ca stone production; reduce salt and ca in diet, high fluid intakes, consider thiazide diuretics that dec ca excretion

Question 154

renal colic (5 risk factors, 4 stone types and relevant radiodensity, and causes for each of those, how crystals form)

Answer 154

inc risk: male (testosterone inc liver production of oxalate), genetic (family history, more common in white and asian peeps), drinking less (conc urine has lower pH inc risk of cystine and uric acid stones) also thus more common in summer as urine more conc; high animal protein incs urine oxalate and thus stone risk as does other high oxalate foods like spinach 80-85% are ca oxalate stones,5-10% uric acid, 2-20% struvite mixed ca phosphate/oxalate up to 10%; radiodensity is ca phos > ca oxalate > cystine (1%) > struvite > uric acid > rarer types; uric acid and below cant be seen on x ray or CT so IVU to investigate when conc of these various minerals is above a saturation point they precipitate as crystals, there are some inhibitors of crystallisation meaning this doesnt happen immediately (eg citrate, women have more of this in their urine); crystals nucleate on epithelial surfaces of other crystals and then aggregate to form calculi hypercalciuria due to bone resorption inc (hyperparathyroidism), inc'd GIT ca absorption etc or hyperoxaluria (liver makes more or colon absorbs more as more bile reaches it if short bowel syndrome or malabsorption/IBD), hypocitrauria all inc risk for ca oxalate stones uric acid risk inc'd by gout, cell necrosis (nucleic acids released and converted to uric acid) esp after treatment of myeloproliferative disorders with cytotoxic drugs ca phos stones in people with RTA due to high urine pH struvite stones from urease producing bacti (breakdown urea to form ammonia which raises urine pH), this is esp proteus, klebsiella infection cystine from cystinuria

Question 155

renal colic presentation and investigation (2 risk factors in history, vs peritonitis, when to suspect lucent stones, what if gold standard test not available, mx basics)

Answer 155

history, noting risk factors and eg low activity level means inc'd risk of bone resorption, corticosteroids inc gut absorption of Ca may be found incidentally; presentation is loin to groin colicky pain, very bad, with haematuria; patient will move around trying to find position to relieve pain unlike with peritonitis where they will lie fully still struvite stones lead to recurrent UTIs or infective complications (pyonephritis or perinephric abscess, septicaemia); urine dipstick inc pH but radiograph for radiodense, lucent suspected on history and urine pH being low take U&Es and CRP as well as FBC gold standard is CT-KUB (CT showing kidneys, ureter, bladder) except indanivir stones which use IVU; allows determination of stone size and location; if not immediately available use abdo USS imaging to rule out AAA or other serious thing if patient >50yo often can watch and wait as will pass if <5mm, can give NSAIDs to relieve pain, alpha blockers as second line - tamsulosin can relax ureter smooth muscle, but recent large study suggests it has no benefit so guidelines changing; can try to break up stone with various techniques if wont pass or if large, if patient needs to get back to work etc, if infection suspected or kidney function affected surgery in certain circumstances; high fluid volumes won't 'flush' it out

Question 156

reducing risk of renal stones x3

Answer 156

Stay hydrated animal proteins = uric acid, raised urine ca; veggie diet not only avoids these problems but has less aa like tryptophan, tyrosine, phenylaline which lead to oxalate formation, so is extra protective if ca intake remains normal potassium citrate supplements protect against stones but too much can bring urine pH up allowing ca phos stones to form so urine pH must remain acidic for benefit

Question 157

renal stones (Ca phos usually in what, 3 things that act as nidus, 3 ways presents based on location, ix - 2 choices, mx - analgesia, 4 options for stones, 4 other bits)

Answer 157

ca phos stones almost always found in infected urine (proteus raised urine pH) sutures, ureteric stents, sloughed cells (pap/tub nec, infection) act as nidus for stone formation in parenchyma stone may be symptomless, in calyx system dull pain, in ureter renal colic (cont pain with sharp exacerbations, sweating, vomiting) low dose non-contrast CT imaging modality of choice, but USS first for pregnant, child/teen im or pr diclofenac; Stone burden of less than 2cm in aggregate Lithotripsy Stone burden of less than 2cm in pregnant females Ureteroscopy Complex renal calculi and staghorn calculi Percutaneous nephrolithotomy Ureteric calculi less than 5mm Manage expectantly if anuria (either bilat block or block of solitary kidney) then percut nephrostomy to drain, renal replacement therapy temp may be needed, then remove stone as above (percut nephros is also used to drain pyonephrosis or renal abscess) try to determine and eliminate cause (eg rec ca stones may be due to hyperpara from tumour etc); always encourage pt to drink a lot so dilute urine produced

Question 158

cystinuria (cause, inheritance pattern, presentation (what happens and 3 resulting sx), 2 initial ix (something else that makes one of these positive) and confirmatory ix, mx)

Answer 158

caused by impaired renal and GI transport of dibasic aa COAL (cystine, ornithine, arginine, lysine) inherited in AR fasion clinical effect is production of cystine renal stones in 3% of sufferers; typically bilat and staghorn; can lead to infections, haematuria, renal obstruction -> failure urinalysis will have yellow/brown hexagonal crystals, pos urine cyanide nitroprusside test, also pos in fanconi syndrome and other things causing aa loss in urine urine chromatography/electrophoresis confirms mx high fluid intake, alkanise urine with bicarb/citrate

Question 159

evaluation of paediatric urinary tract stones

Answer 159

Nephrolithiasis (kidney stones) or nephrocalcinosis (increased calcium content in the kidneys, which may be focal or generalised) are often a sign of underlying disease/anatomical anomalies and not the disease itself Classic symptoms of stones (e.g. renal colic and haematuria) are uncommon in children. More commonly they present with abdominal pain, vomiting, fever, signs of UTI, micro or macroscopic haematuria. Small children often present with non specific signs. Some children may have sterile pyuria, dysuria, voiding problems, urine retention, enuresis, frequent voiding or history of passage of stones or gravel. Some stones are detected incidentally. Nephrocalcinosis is mostly asymptomatic and often detected incidentally. They might rarely present with renal colic (passage of tiny calculi), haematuria (gross or microscopic) or sterile leukocyturia Infection related stones are composed of struvite and are caused by urease producing organism i.e proteus; they are radio-opaque; staghorn stones are generally struvite Ca stones are radio-opaque; they're associated with disorders of hypercalciuria & hypercalcemia Cystine stones seen in cystinuria are radio-opaque Oxalate stones seen in hyperoxaluria (idiopathic, IBD) are radio-opaque Uric acid stones are radio-lucent; associated with chronic diarrhoea, tumour lysis syndrome, and inborn errors of purine metabolism U&Es, bicarbonate, venous gas, liver function, bone profile, magnesium, urate, PTH, plasma oxalate Urine sample for dipstick, and one for microscopy and culture; also will need to check protein:cr ratio, cystine:cr ratio, ca:cr ratio, urate:ca ratio, pH (lab value), oxalate:cr ratio, magnesium, osmolality, electrolytes, amino acid screen get renal tract USS; CT scan if small/suspected ureteric stones * MAG 3 if suspected obstruction If stone passed or retrieved, should be sent for complete quantitative analysis If suspected obstruction due to stone, hospitalise, urgent referral to urologist, check kidney function, may require urgent intervention. If no obstruction, proceed for metabolic work up, consult urologist and nephrologist. Manage conservatively with adequate fluid intake and analgesia. Treat underlying metabolic disorder. If stone does not pass spontaneously definitive treatment is needed in the form of extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy or endoscopic removal depending on size, location and type of stone General recommendations * Increased fluid intake (minimum125% of normal maintenance volume) and avoidance of fizzy drinks * Decreased intake of animal protein * Restricted salt intake * Normal calcium intake (not in excess of or less than recommended amount) * Reduce intake of food rich in oxalate Specific recommendations For calcium stones – oral potassium citrate, thiazide diuretics to reduce hypercalciuria Uric acid stones- allopurinol, potassium citrate Oxalate stones- no specific drug. Consider vit B6 Cystine stones- alkanisation with potassium citrate, consider specific agents like mercaptopropionylglycine or d-penicillamine. Struvite stones – prompt treatment of infection.

Question 160

polycystic kidneys (AD not a age range, progresses to what, 5 associated things, 8sx, 4 ix, mx (definitive x1 and initial x3, when else get, risk of what else increased

Answer 160

autosomal dominant condition, usually between ages 30 and 50; enormous fluid filled cysts make kidneys palpable; ischaemic atropy of surrounding parenchyma and obstruction of renal tubulues, often progressing by age 50 to end stage renal failure; 33% also have liver cysts, 30% berry aneurysm at circle of willis and also aortic root dilation and eg MR, TR present with: pos family history often, hypertension, flank pain, palpable masses, haematuria, oedema/sob, stones, UTIs, renal failure (lethargy, nausea/vomiting, anaemia, confusion, seizures) USS, CT, MRI useful to investigate; genetic testing (PKD1/2) for definitive; dialysis + transplant may be needed, prior manage blood pressure and stones etc a similar diseases is acquired during chronic or end stage renal failure found in over 1/3 patients after 3 yrs dialysis both have inc'd risk of adenomas

Question 161

ADPKD

Answer 161

PKD1/2 genes implicated; may be de novo or familial; esrf in late middle age; also intracranial aneurysms, mit valve prolapse giving regurg (maybe tricuspid regurg), aortic dissection, cysts in liver/spleen/ovaries etc, and diverticulae

Question 162

von hippel lindau (what it is and seven things you’re at risk of)

Answer 162

(VHL) syndrome is an autosomal dominant condition predisposing to neoplasia cerebellar haemangiomas: these can cause subarachnoid haemorrhages retinal haemangiomas: vitreous haemorrhage renal cysts (premalignant) phaeochromocytoma extra-renal cysts: epididymal, pancreatic, hepatic endolymphatic sac tumours clear-cell renal cell carcinoma

Question 163

sterile pyuria (5 inf, 7 non-inf causes)

Answer 163

differential diagnoses for infectious causes of sterile pyuria include perinephric abscess, urethral syndrome, chronic prostatitis, renal tuberculosis*, and fungal infections of the urinary tract Noninfectious causes of pyuria include lithium and heavy metal toxicity, renal stones*, sarcoidosis, interstitial cystitis, polycystic kidney disease, genitourinary malignancy*, and renal transplant rejection.

Question 164

ARPCKD

Answer 164

baby born with very enlarged kidneys, renal failure usually rapid onset at birth; pulm hypoplasia oft present due to reduced urine output often congen hepatic fibrosis giving hepatomeg and impaired liver function and bile duct ectasia leading to portal HTN poss; lack of differentiation between renal medulla and cortex poor prognosis but renal transplant might help

Question 165

how does presentation of uti vary with age in children?

Answer 165

* Neonates: Very non-specific symptoms; septicaemia can develop rapidly. * Infancy: Fever, lethargy, diarrhoea and vomiting (may mimic gastroenteritis), poor feeding, septicaemia and febrile convulsions. * Childhood: Fever, dysuria, frequency, urgency, loin/IF or abdominal pain, diarrhoea and vomiting, with febrile convulsions. NB In childhood, frequency and dysuria without fever are often due to vulvitis in girls and balanitis in boys

Question 166

UTIs - def for complicated x2, recurrent x2; 6 bacti causes; 4 things that make pyeloneph more likely

Answer 166

cytitis (bladder), pyelonephritis (kidney) or ureteritis or urethritis; originally >10^5cfu per ml but less than this may be clinically relevant; complicated have accompanying structural or functional abnormality, and most infections in men are complicated; most in women are uncomplicated; recurrent if >2 in past 6mo or 3 in 12mo due to reinfection, persistence (poss due to fistula, calculus, chronic prostatitis) e coli (g- bacillus) is 85% community and 50% hospital uncomplicated UTIs; other common ones are proteus mirabilis, staph saprophyticus, klebsiella; e coli up to 50% complicated UTIs others may be same as above or enterococci or other staph; usual route is bacti from large bowel to perineum thence urethera and up cyst to pyelo more likely if bacti have p pili, if pregnant, if ureter obstructed, if reflux to kidney from bladder

Question 167

investigation of UTIs (inc commonest cause of pyeloneph)

Answer 167

cystitis: cloudy pee (wbcs), burning or pain of urethra, freq, urgency, offensive urine, haematuria, fever, suprapubic pain; pelvic exam and check for palpable bladder; urine dipstick will show WBCs and nitrites but false negs for nitrites are quite common (eg low bacti numbers; microscopy of urine sample to look for bacti if pyelonephritis, recurrent infection, or woman pregnant then further investigations as below otherwise give nitrofurnatoin po 5 days or local guidelines pyelonephritis: fever, flank pain, microscopy/dipstick shows infection, also symptoms of cystitis usually; 80% secondary to p pili e coli but ent faecalis and the usual mix of UTI bugs can also cause, esp if ureteric peristalsis altered due to eg calculi; culture urine plus oral antibiotics (ceftriaxone/cefotaxime), renal USS to look for obstruction or stones, or site of rec infection; CT if needed; if doesnt respond then maybe pyonephrosis or perinephric abscess which should be drained prevention of UTIs: drink more fluids, drink cranberry juice, take d-mannose or lactobacillus supplements, pee quickly after sex (evidence not 100% on these though)

Question 168

childhood utis

Answer 168

any loin/iliac fossa pain/tenderness and fever in child suspect pyelonephritis; suspect lUTI if <3mo w/ fever, vomiting, lethargy, poor feeding, failure to thrive, maybe abdo pain, jaundice, haematuria; if >3mo w/ fever, freq, dys, abdo pain, vomiting, loin pain 38deg or loin pain/pyeloneph then urine sample for m&s, refer to paediatrics; 38deg + bacteriuria, or <38 but bacteriuria and loin pain, diagnose pyelo; otherwise lUTI suspect any uti <3mo m&s and urgent paeds treatment for parenteral antibiotics; suspect and >3mo dipstick, if nitrites and leucocytes treat, if leuc + nitrite neg then m&s, start antibiotics if <3yo or good evidence to suspect; if leuc neg nit pos treat as uti; for all uti if <3yo, rec, no response then send m&s cefalexin if uUTI, trimeth or nitro if lUTI atypical infection (poor urine flow, sepsis, non ecoli cause, bladder/abdo mass, failure to respond needs, recurrent needs uss of urinary tract; dmsa scan within 4-6mo if rec or atypical uti and <3yo, or >3yo w/ rec parents return if no response in 24-48 hrs; paracetamol pain relief

Question 169

atypical uti features (children)

Answer 169

poor urine flow, sepsis, non ecoli cause, bladder/abdo mass, failure to respond

Question 170

uti ix, DMSA and MCUG (children)

Answer 170

All children under 6 months with their first UTI should have an abdominal ultrasound within 6 weeks, or during the illness if there are recurrent UTIs or atypical bacteria Children with recurrent UTIs should have an abdominal ultrasound within 6 weeks Children with atypical UTIs should have an abdominal ultrasound during the illness DMSA (Dimercaptosuccinic Acid) Scan DMSA scans should be used 4 – 6 months after the illness to assess for damage from recurrent or atypical UTIs Micturating cystourethrogram (MCUG) should be used to investigate atypical or recurrent UTIs in children under 6 months. It is also used where there is a family history of vesico-ureteric reflux, dilatation of the ureter on ultrasound or poor urinary flow UTI + thrush treatment didnt help? consider vulvovaginitis

Question 171

different kinds of urinary casts and what they mean

Answer 171

hyaline casts dont mean anything on their own granular casts seen in glomerular and tubular disease, finely granular casts may be normal in children white cell casts in acute pyeloneph or interstitial neph, so if kid with UTI has white cell casts suspect pyeloneph red cell casts always pathological and almost always GN

Question 172

MCUG vs IVU; VUR (how common, cause, normal way it presents x2, ix inc 2 indications, severity grading, 3mx)

Answer 172

IVU outlines kidney within 5 mins of injection then down to bladder etc; may see eg duplication of renal collecting system or horseshoe kidney; MCUG will have dye-introducing catheter and is mainly used to exclude VUR VUR in 1-3% of infants, seems to be idiopathic; usually no sx until uti devs (cystitis or pyeloneph), or a hydronephrosis may be found; MCUG done to see, usually if uss suggests or <2yo with 2+ UTIs with fever; VUR graded 1-5: 1 is backup into nondilated ureter, 2 is into renal pelvis and calyces without dilation, 3 is mild-mod dilation, 4 is mod dilation, 5 is gross dilation inc loss of papillary impressions; consider observation, proph abx, surgery if severe Continuous antibiotic prophylaxis is recommended for the child less than one year of age with VUR with a history of a febrile urinary tract infection. This approach is based on the greater morbidity from recurrent urinary tract infections found in this population In the absence of a history of febrile urinary tract infections, continuous antibiotic prophylaxis is recommended for the child less than one year of age with VUR grades III–V who is identified through screening Continuous antibiotic prophylaxis is recommended for the child >1yo with bladder/bowel dysfunction and VUR due to the increased risk of urinary tract infection while bladder/bowel dysfunction is present and being treated Asymptomatic patients (PNH or sibling) with high-grade reflux and abnormal kidneys also get CAP; no CAP is asymptomatic with low grade reflux and normal kidneys General evaluation, including monitoring of blood pressure, height, and weight is recommended annually; Urinalysis for proteinuria and bacteriuria is indicated annually, including a urine culture and sensitivity if the urinalysis is suggestive of infection; Ultrasonography is recommended every 12 months to monitor renal growth and any parenchymal scarring. It is recommended that patients receiving continuous antibiotic prophylaxis with a febrile breakthrough urinary tract infection be considered for open surgical ureteral reimplantation or endoscopic injection of bulking agents Following the resolution of VUR, either spontaneously or by surgical intervention, general evaluation, including monitoring of blood pressure, height, and weight, and urinalysis for protein and urinary tract infection, is recommended annually through adolescence if either kidney is abnormal by ultrasound or DMSA scanning Faster resolution of VUR is more likely for age <1 yr at presentation, lower grade of reflux (grade I–III), and asymptomatic presentation; Resolution is nearly 80% for VUR grades I and II and 30–50% for VUR grades III–V within 4–5 yr of follow-up Circumcision during early infancy may be considered as part of the conservative approach because it is effective in reducing the risk of infection in normal children

Question 173

DMSA (role, when), DTPA, MAG3 scans (what both of these are and how they work, interpreting former)

Answer 173

DMSA taken up and retained by tubular cells, gives static image used to look for scarring as only taken up by functional tissue, better for this purpose than IVU; should be done at least 6 weeks post UTI other 2 are dynamic scans with MAG3 generally better pictures of tract when renal function impaired; both get iv injection then scan for emissions by excreted tracer with time/activity curve produced representing function of the kidney in DTPA scan, in normal kidney tracer count sharply rises as DTPA injected, then slower as tracer taken up, then count falls as is excreted; in obstructed kidney excretion fails so tracer count doesnt fall; then give furosemide, and if this washes out and tracer count falls suggests dilated but non-obstructed system, and if doesnt fall then true obstruction

Question 174

prescribing in renal impairment

Answer 174

for most drugs and for most adult patients of average build and height, eGFR (rather than CrCl) can be used to determine dosage adjustments. Exceptions to the use of eGFR include toxic drugs, in elderly patients (>75yo) and in patients at extremes of muscle mass; CrCl should be used as an estimate of renal function for direct-acting oral anticoagulants (DOACs), and drugs with a narrow therapeutic index remember serum creatinine levels lag behind the development of AKI and progress of recovery. As creatinine rises, estimates of GFR will overestimate renal function and as creatinine falls and kidney function improves, estimates of GFR will underestimate renal function Creatinine clearance or absolute glomerular filtration rate should be used to adjust drug doses in patients with a BMI less than 18 kg/m2 or greater than 40 kg/m2. Ideal body weight should be used to calculate the CrCl via cockroft-gault. Where the patient's actual body weight is less than their ideal body weight, actual body weight should be used instead. Meanwhile the absolute glomerular filtration rate is determined by removing the normalisation for BSA from the eGFR using the following formula: GFR (Absolute) = eGFR x (individual's body surface area / 1.73)

Question 175

posterior urethral valves (typical pt, up to what everyone usually and 2 severe things that might be alongside causing earlier presentation, 3 reasons for older kids to present, diagnostic ix finds what, what else will they often have)

Answer 175

condition found only in boy where urethra has a blockage in it near the bladder. This makes it difficult for a child to pass urine. As the bladder pushes hard to get the urine out, it causes pressure which may result in urine being pushed back from the bladder into the ureters and kidneys valves are actually obstructing membranous folds situated within the posterior urethral lumen About a third of children born with posterior urethral valves will progress to ESRD. Additionally, between 10% and 15% of all children who undergo kidney transplantation will have a history of posterior urethral valves. It is commonest obstructive cause of CKD in children symptoms include: spectrum from delayed voiding to severe retention an enlarged bladder, so that it can be felt through the abdomen as a lump abdominal or lower back pain urinary tract infections (UTIs) difficulty urinating with voiding sx such as a weak stream of urine unusually frequent urination In severe cases, inadequate urine output can lead to antenatal oligohydramnios and pulmonary hypoplasia. MCUG is gold standard ix; 50-60% will also have vur initially catheterise to drain bladder if needed and check renal function, monitor for post-obstructive diuresis (esp in neonates) and replace fluid and electrolytes as needed surgery to be conducted at the earliest possible time post-surgery, often long term intermittent self catheterisation and anticholinergics may be needed due to bladder dysfunction including high voiding pressures (due to changes in compliance from the initial distension)

Question 176

prune belly syndrome

Answer 176

absent ant abdo wall musculature + genitourinary abnorms like bilat cryptorchidism, non-obstructive dilation of renal tract, VUR, cystic renal dysplasia, poss pulmonary hypoplasia from antenatal oligohydramnios stasis leads to rec UTI also have cardiac and msk abnormalities

Question 177

causes of enlarged kidneys

Answer 177

unilat: hydronephrosis, cysts, tumour, RVT bilat: hydronephrosis, stones, ureterocoeles, cysts, tumours, infiltration sec to leukaemia/lymphoma

Question 178

VUR mx (inc how normally resolves and what else to consider, 2 complications of scarring, 5 mx of future infections, and monitoring when/how x4)

Answer 178

Most cases of reflux resolve as the child gets older. Surgery to reimplant the ureters might be considered if the relux does not resolve spontaneously, but is often unsuccessful. Renal scars from VUR may produce excess renin, which can cause hypertension. Serious, bilateral scarring can result in chronic renal failure. Therefore it is important to prevent further infection. Patient should be given long-term antibiotic prophylaxis, usually trimethoprim, until the reflux resolves, based on the grade and sx as per previous flashcard. You should also advise their parents on conservative measures to prevent UTIs, such as maintaining a high fluid intake, regular and complete voiding, avoiding constipation and good hygiene. should have a urine culture in any non-specific illness to exclude a UTI. If already has some renal scarring blood pressure should be checked twice a year and the ultrasound repeated in 2 years to check renal growth; if another UTI happens need to look for more scarring

Question 179

congenital urogenital malformations

Answer 179

renal agenesis 1 in 1-2000, usually asymp horseshoe kidney 1 in 600, prone to stones, UTI etc, maybe abdo mass and haematuria micropenis - hypogonad hypo eg kallmans, prader willi; hypergonad hypo eg gonadal dysgen; idiopathic hypospadius - association with low birth weight, 10% have undescended testis, up to 15% inguinal hernia above with bilat undes testes needs immediate endo investigation; if non retractile crypt orchidopexy needed, still have higher risk of fert problems and cancer; should be done by 6-12mo old

Question 180

congenital urogenital malformations

Answer 180

Congenital abnormalities of the kidney and urinary tract are fairly common. Most abnormalities seen on antenatal ultrasound resolve spontaneously Babies found to have any of the following, fall into a moderate risk group * Severe unilateral hydronephrosis ≥20 mm with pelvicalyceal dilatation * Bilateral hydronephrosis ≥7mm but less than 10mm * Complex duplex i.e. significant hydronephrosis or non-obstructing ureterocoele * Hydronephrosis ≥7mm and < 10mm in a single functioning kidney Babies found to have any of the following fall into a low risk group * Simple duplex kidney * Unilateral hydronephrosis <20mm with normal contralateral kidney * Unilateral MCDK with normal contralateral kidney * Unilateral renal agenesis with normal contralateral kidney * Unilateral renal dysplasia / hypoplasia with normal contralateral kidney * Other renal abnormality e.g. horseshoe kidney with no hydronephrosis, normal contralateral kidney and normal liquor volume for these babies: check they are passing urine normally, no need for routine U&Es, request an OP USS and refer to renal clinic, inform parents how to spot UTI and to bring child for assessment urgent IP USS needed in case of posterior valves; otherwise MCUG will often be done after the USS if any dilation shown, and DMSA sometimes needed -> seek advice from local nephrology team from find guidelines

Question 181

back pain (pyenoneph path, 3 complications, renal pap necrosis causes POSTCARDS, pyeloneph ix)

Answer 181

pyeloneph path: kidney will have yellow white cortical abscess of several mm diameter with surrounding hyperaemia; neutrophils will be in tubules and interstitium and in severe disease glomerulus will be involved tubular necrosis may occur leading to scarring other complications inc pyonephritis (calyces and ureter blocked with pus), perinephric abscess, papillary necrosis (constant pain) renal pap necrosis: distal 2/3 of pyramids have ischaemic coagulative necrosis; postcards for causes: pyelonephritis, obstruction, sickle cell disease, TB, chronic liver disease, analgesic (ab)use, renal transplant rejection, DM, systemic vasculitis lumbar disc pain very unlikely in person >60yo as discs dessicated and tend not to herniate, so if suspect that then think again and check for AAA; AAA may also present like renal colic due to effect of the haemtoma, and in men >65 renal colic rare but AAA not so suspect it; with pyeloneph, blood culture and msu urine culture needed - even if urine dip neg cipro for 7 days while awaiting susceptibility info

Question 182

renal tumours (most common malig type in adults and in kids, sx, 3 paraneoplastic syndromes, ind for doing bone scan)

Answer 182

adenomas and rarer benign ones poss, adenomas are symptomless rare for mets to go to kidney, sometimes from lymphoma, leukaemia, breast, lung primary: renal cell carcinoma in adults, nephroblastoma in kids RCC: 80% of all renal tumours, men 2x more likely to get, pt usually 40yo+; incidental diagnosis common but haematuria in 50% of cases, loin ache in 40%, loin mass in 25%; spread along left renal vein block test vein confluence, give left sided varicocele in 1% cases; anaemia, loss of weight, pyrexia of unknown origin; mets (bones, lungs); paraneoplastic syndromes inc hypertension (renin), polycythaemia (epo), hypercalcaemia (PTH) urinalysis, CT scan (can do staging too), if ALP or serum Ca up then bone scan

Question 183

renal cell carcinoma (inc how many renal cancers are this, most common subtype, 4 risk factors, rarer kind)

Answer 183

renal cell carcinoma >90% renal cancers (and 70% renal cell carcinoma is clear cell) smoking, obesity, hypertension are risk factors; alos eg von hippel lindau syndrome grade and stage (based on tumour size and local invasion) rarely can get urothelial cancer, treated similarly to bladder urothelial cancer in terms of staging etc

Question 184

nephroblastoma mrcpch (sx, derives from what, mets, ix, 5 associated syndromes)

Answer 184

abdo/flank mass/haematuria/hypertension between ages 1 and 4 derived from mesonephric mesoderm and m>f 20% inherited, rest sporadic hypertens as pressure on renal art leads to renin production; usually microscopic haemat not visible, but only in 1/3 cases prox spread of tumour through renal vein then IVC can cause tricuspid regurg and heart failure, or by blocking IVC distended veins over abdo cannon ball mets in 10% of cases iv pyelogram (no change in renal axis but calyces distorted), CT scan and biopsy associated with BW syndrome, NF, adrenal hypoplasia and horseshoe kidney, aniridia + 11p13 del

Question 185

neuroblastoma mrcpch (3 associations, where it occurs (overall plus 4 specifics), 10 sx in various places, 5 ix inc kidney sign, 2 ways to differentiate from wilm tumour)

Answer 185

usually before 2.5yo, associated with BW, NF, nesidioblastosis can occur anywhere along sympathetic nervous system but most commonly in adrenal gland, tho also eg mediastinum, neck, pelvis irregular flank mass which crosses midline (unlike nephroblastoma) oft presents late with mets (70% of cases), to eg bone, marrow, liver, lymph nodes thoracic tumour can cause horner syndrome or trach/vasc compression, may see heterochromia skin involvement may cause bluish tender nodules met to sphenoid bone can cause proptosis and periorbital bruising <1yo primary may be undetectable, just mets to skin, marrow, and liver and this form may spontaneously remit chronic watery diarrhoea possible if VIP secretion if of olfactory nerve may get nose bleeds and obstruction generally do IVP, CT scan, and biopsy - IVP shows drooping lily sign as kidney pushed down and laterally, and unlike wilm tumour, calyces not distorted plain AXR shows calcification in 50% of cases; catecholamine levels inc'd and sometimes HMA and CMA

Question 186

neuroblastoma (sx and signs of it I’m various places, 7ix, when to watch and wait, 3 diffs)

Answer 186

usually children <5yo, usually starts in abdo (adrenals) but can spread to liver, skin, bones lump/swelling in stomach which may be painful; may first be lump in neck; may be in spinal cord giving numbness/weakness of legs tiredness, fever, weight loss, anorexia pain/swelling of bone, if spread to marrow then pancytopenia, bruised looking skin, jaundice and hepatomegaly; hypertension or renal insuff from compression of renal artery, periorb bruising, horner's syndrome may produce catecholamines giving flushing, sweating, tachycardia, diarrhoea very urgent (within 48hrs) ref if palp abdo mass, unexplained enlarged abdo organ, or otherwise suspect: FBCs, ESR, coag screen, VMA and HVA (catecholamine products) in urine; CT if in abdo/pelvis or mediastinum, MRI if paraspinal; bone/MIBG scan; biopsy - microscopy, catecholamine levels raised or immunohistology if staged MS/4S (<18mo, not spread to bone, less than 10% marrow cells neuroblastoma) just monitor; otherwise surgery, chemo, radiotherapy, stem cell therapy consider rhabdomyosarcoma, eilms tumour, lymphoma,

Question 187

nephroblastoma (incidence, associations x3 and genetics x2, usually presents when, 9sx, surveillance how and for who, 5ix, 3 mx)

Answer 187

aka wilms tumour 1 in 10,000 children (3% of wilms tumours present in adults); 5-10% pts have both kidneys affected usually otherwise healthy but linked to overgrowth eg beckwith wiedemann, perlman etc, also edwards (ts18); some autosomal dom hereditary ones (WT1 or 2 gene mutated) but this is uncommon usually presents in first 5yrs of life usually asymp abdo mass; look for abdo pain, haematuria, UTI, fever, hypertension; lung mets may cause breathlessness; poss varicocele; anorexia renal uss every 3-4mo for surveillance if genetic or have associated condition from above until 5 (or 7 for BW and some familial pedigrees) very urgent (within 48hrs) ref if palp mass or unexplained vis haemat; FBC, urinalysis, U&Es; USS of mass then CT/MRI nephrectomy then chemo, maybe postop radiotherapy if stage 3+

Question 188

WAGR and denys-drash syndromes

Answer 188

aka WAGR complex, Wilms tumour-aniridia syndrome (+ genitourinary anomalies, and mental retardation) Some WAGR syndrome patients show severe childhood obesity and hyperphagia, and are categorised as WAGRO (adding obesity) caused by a mutation on chromosome 11 with deletion including the PAX6 ocular development gene and the Wilms' tumour gene (WT1) Diagnosis for WAGR syndrome can be made by confirming microdeletion of 11p13 need regular wilm tumour surveillance denys-drash syndrome: characterized by the triad of pseudohermaphroditism, mesangial renal sclerosis, and Wilms' tumor. The condition first manifests as early nephrotic syndrome and progresses to mesangial renal sclerosis, and ultimately CKD Males with Denys-Drash syndrome exhibit gonadal dysgenesis and undescended testes. Females with Denys-Drash syndrome typically have normal genitalia cause of DDS is most commonly an abnormality in the WT1 gene

Question 189

neuroblastoma: main ix, main imaging for staging and follow up (what is positive), normal age for neuroblastoma, normal age for nephroblastoma, both uncommon after what age, 2 sx resulting from the mass

Answer 189

urine catecholamines ix MIBG scan can be used for staging and follow up (highly intense (dark) uptake in the adrenal pos for neuroblastoma) neuroblastomas usually 1-2, nephroblastoma usually 3-4, both uncommon after 5 due to the mass may get leg oedema, hydroceles

Question 190

rhabdomyolysis - sx depend on what 2 things; mild form how diagnosed; more severe sx x3, and consequence if these severe; 7 more generalised sx; 16 causes; 4 blood results; 3mx; what other condition often coincides?

Answer 190

symptoms of rhabdomyolysis depend on its severity and whether kidney failure develops. Milder forms may not cause any muscle symptoms, and the diagnosis is based on abnormal blood tests in the context of other problems. More severe rhabdomyolysis is characterized by muscle pain, weakness and swelling of the affected muscles If the swelling is very rapid, as may happen with a crush injury after someone is released from under heavy collapsed debris, the movement of fluid from the bloodstream into damaged muscle may cause low blood pressure and shock. Other symptoms are nonspecific and result either from the consequences of muscle tissue breakdown or from the condition that originally led to the muscle breakdown. Release of the components of muscle tissue into the bloodstream causes electrolyte disturbances, which can lead to nausea, vomiting, confusion, coma or abnormal heart rate and rhythm. The urine may be dark, often described as "tea-colored", due to the presence of myoglobin. Damage to the kidneys may give rise to AKI cause extreme exercise inc delirium tremens, seizures/status, tetanus; crush/blast injury; arterial thrombosis/embolism; HHS, hypocalc/nat/kal/phos, statins, neuroleptic malig syndrome, serotonin syndrome, malig hypertens, poly/dermatomyositis CK, LDH will be elevated, K/phos maybe, myoglobin in urine/blood IV fluids (maybe even prophylactically if crush injury in eg trauma pt), correct electrolytes, haemodialysis if bad AKI comp syndrome often coincides so look for it and mx if needed

Question 191

phimosis in children - when normal, avoid what, how to mx and when to refer)

Answer 191

In children less than 2 years of age, phimosis (a non-retractable foreskin) is normal and will most likely resolve with time You should avoid forcible retraction of a phimosis as this can result in scar formation As this is likely physiological there is no need for an urgent or non-urgent referral to paediatrics or referral to paediatric surgeons; instead arrange to review at 2yo if not resolved

Question 192

hypospadias mx - inc what age intervention done, what mustnt happen before, who might not need

Answer 192

once hypospadias has been identified, infants should be referred to specialist services corrective surgery is typically performed when the child is around 12 months of age it is essential that the child is not circumcised prior to the surgery as the foreskin may be used in the corrective procedure in boys with very distal disease, no treatment may be needed

Question 193

bladder tumour (inc main type, 4 risk factors), 6sx, 3ix, 3 mx options, 3 options post bladder removal)

Answer 193

nearly always malignant; urothelial carcinoma in 90% cases, usually in middle aged + ppl cig smoking incs risk, and working in rubber/plastic or dye industries as beta-naphthylamine secreted in urine; long term catheterisation in eg paraplegic pts, schistosomiasis infections (these two metaplasia then SCC) spreads locally to pelvic viscera painless haematuria (micro or macro) and may cause freq, urgency, sometimes dysuria; retention, maybe hydronephrosis poss urinalysis, flexible cytoscopy good; CT-KUB or CT urogram for staging non muscle invasive have endoscopic resection then chemo; if high risk then cystectomy; if muscle invasive (often has bad pain and CT will show) then platinum chemo then cystectomy or radiotherapy with cytoscopic follow up and salvage cystectomy if recur after bladder removal options are: ileal conduit (piece of SI create tube, attach ureters through this to stoma, then wear bag over this), neobladder (using larger part of SI), or continent urinary reservoir (similar idea, needs draining with catheter several times a day)

Question 194

bladder stones (2 things that inc risk +3 things that cause the second thing), 3 sx inc when is pain worst (3 places it's felt) and freq worst

Answer 194

same types as renal, often from renal passing down; can arise in bladder due to foreign body (indwelling catheter) or stasis (outflow obstruction from stricture after infection, enlarged prostate, atonic bladder in paraplegic person) pain (suprapub, perineum, tip of penis) esp at end of micturition when bladder contracts, frequency (esp bad during day as upright position lets stone irritate trigone), terminal haematuria

Question 195

pneumaturia (common cause (4 reasons for this) and 2 other causes, what else can occur, 3 ix inc modification to prove, mx)

Answer 195

air or bubbles in urine or a history of sputtering passing of urine; urine may be foamy, beware similar word used to describe proteinuria; dysuria may also occur colovesical fistula is common cause, often a complication of diverticular disease (60%) but also crohns, CRC or bladder cancer; rare gas producing UTIs, or divers may also have faeces in urine may also occur USS, CT (per-rectal contrast to prove once other imaging indicates); colonoscopy to follow up then surgical resection and anastomosis

Question 196

acute scrotal pain - 2 key emergencies; torsion age range, time range for testes to be saved, 3sx and 3 exam findings, difference if late presentation, difference if testis undescended; ix, mx when is orchidectomy required; 2 other things that undergo torsion and how sx vary from testicular - mx x2; epidiymoorchitis 2x common bacti, 9 sx, 3ix, 4mx and 3mx if advanced or abx resistant; fournier's gangrene what it is, 2x common sources, mx x2

Answer 196

key emergencies are torsion and fournier's gangrene; if diagnosis unclear, get senior colleague to review urgently torsion: surgical emergency; commonest boys 10-15yo, rare in ppl >30yo, ischaemic injury oft within 4 hrs of onset of pain, but majority of testes can be saved if explored within 8 hrs, 4 ideally; sudden onset unilat test pain (+ nausea/vomiting oft) but pain may not localise, instead general abdo pain so always check external genitalia as part of routine abdo exam; tender swollen test oft high in scrotum with scrotal oedema and erythema, examination may not be tolerated in which case emergency scrotal exploration required; prolonged ischaemia may mean pt presenting late has little tenderness; if testis undescended may have tenderness or swelling along inguinal canal; investigation not really needed, USS can of groin and scrotum to diagnose/localise a torted inguinal testis; surgery within 1hr, consent for exploratory + orchidopexy +/- orchidectomy - if viable then both testes fixated, if torted unviable then remove to prevent locus of infection and formation of anti-sperm antibodies note 2 types of torsion: Intravaginal torsion: occurs within tunica vaginalis, only involves testis and spermatic cord. Most commonly seen in practice. Extravaginal torsion: involves twisting of testis, cord, and processus vaginalis as a unit; typically seen in neonates because the scrotal parietal tunica vaginalis hasn't fully adhered to the scrotum's outer tissues; typically occurs in or just below the inguinal canal hydatid cyst and epididymal appendix may also tort and these are mimics of torted testis, maybe a bit more gradual onset and tenderness localised to epididymis or upper pole of testis, or lump separate from testis; unless clear, scrotal exploratory surgery still warranted esp as later can get scrotal oedema and erythema, reactive hydrocele, and swollen tender testis; medical management with NSAIDs poss if clinically clear diagnosis acute epididymoorchitis - pathogens via urinary tract, usually chlamydia in younger men and e coli in older men; oft insidious onset pain + swelling but can be acute, oft unilat but eg mumps orchitis is bilat (and some others); viral cause in kids common and oft associated with concurrent URTI + lymphadenopathy; fever/rigors, dysuria, freq can all occur; initially epididymis tender and thickened, then hemiscrotum oedematous and erythematous; urinalysis (though oft clear), raised wcc on FBC, scrotal USS for hyperaemic engorged epidid; abx for 2 weeks, up to 6 weeks, NSAIDs, bed rest, get tested for STIs (partners too); advanced or antibiotic refractory cases admit, iv fluids and gentamicin, abscess may have dev'd and needs draining fournier's gangrene - nec fasc of scrotum, perineum, perianal region oft from urinary or anorectal infection; life threatening with immediate surgical debridement, suprapub catheter if penis involved

Question 197

testicular trauma ix + 2 inds for surgery; idiopathic scrotal oedema age, 2x sx; 5 other causes of swollen scrotum that aren't infection/torsion related and ix to do

Answer 197

trauma: sutures may be needed, USS to check on testes following blunt trauma, if inconclusive or penetrating trauma then surgical exploration idiopathic scrotal oedema in boys <5yo: scrotal swelling + erythema spreading up inguinal canal, even abdo wall inguinal hernia, varicocele, hydrocele, testicular tumour or bleed into a testicular tumour: any uncertainty about masses, request USS

Question 198

scrotal pain/swelling

Answer 198

Acute scrotal pain in children may arise from many differential diagnoses; testicular torsion is the most important but is relatively uncommon with an incidence of between 3.5-4.5/100,000; Incidence peaks in the 1st year of life and again at puberty (ie most cases are in kids/teens) Sudden pain is the most common presenting symptom -may be more gradual in some cases. A history of previous transient scrotal pain is significant; may have abdo pain, nausea/vomiting, difficulty passing urine or dysuria, tender testis +/- unusual gait, oedema, swelling and redness to the scrotal area, progressively diffuse hemiscrotal involvement; high riding and transverse lie of affected testicle; absent cremasteric reflex ddx: Torsion of appendix testis/epididymis  Blue dot on upper pole of testis  Usually minimal pain at rest  Inflammation can develop with time  Nausea and vomiting uncommon Most common in pre-pubertal boys Idiopathic Scrotal Oedema  Common in younger children  Benign, self-limiting e.g. insect bite Mild discomfort, swelling and oedema beyond the scrotum usually into the perineum Hydrocele  Normally resolves by 2 years of age  Painless fluctuant swelling  Trans illuminates Scrotal Trauma  History of significant trauma  Local bruising and / or oedema and/or haematoma Epididymitis/orchitis  Older teen /adult with STI  Inflammation of the epididymis and/or testis due to viral infection (mumps, adenovirus) or chemical irritation caused by reflux (constipation)  Dysuria, increased frequency, malodourous urine.  Fever common  Gradual onset  Nausea and/or vomiting uncommon May have swelling if abscess formed - USS will pick up, and needs surgical mx in this case Testicular Tumours  Painless swelling  Gradual onset Vasculitis (Henoch-Schonlein Purpura)  Associated rash  Abdominal pain Also consider inguinal hernia If testicular torsion cannot be ruled out in presentations of scrotal pain, exploration is mandatory, this is a fundamental management principle o POCT urinalysis- if positive, further MC&S should be performed to evaluate for presence of infection. o Blood tests- not required for testicular torsion-but maybe useful if sepsis is an alternative diagnosis – if sepsis is considered, activate sepsis six o Nil By Mouth- for emergency surgery (following administration of analgesia) o Urgent referral to surgical team- general surgery or urology. Don't do USS if think it might be torsion - needs urgent surgical exploration ideally if ally,3yo and unable to mx locally; only transfer if eg <3yo and unable to mx locally if torsion not felt to be likely can get eg USS as might help identify eg abscess formation

Question 199

acute urinary retention - 3 sx, 3 precipitators, 4 ix, 4mx and what if this fails, when can send home (5 things to tick off), what med to start and how to TWOC, when to d/c with urology x2

Answer 199

suprapubic pain, difficulty passing urine; older patients may just be confused or agitated; may or may not be precipitating features eg constipation, UTI, clot/haematuria bladder scan, urine dip, FBC, U&Es, PSA only if prostate feels malignant but can be falsely elevated in acute retention so don't bother sepsis 6 if needed; urgent transurethral catheterisation, repeat bladder scan for post void residual volume and must document this; CSU for M C and S (microscopy, culture, sensitivity); suprapubic catheter if this fails if no sepsis or diuresis, residual volume <1000mL (above suggests chronic block), no renal impairment, adequate care at home can send home start Tamsulosin 400mcg od if not on any meds, TWOC in community in 7 days; if residual >1000 may be acute on chronic and needs urology discussion; if deranged U&Es needs admission and urol discussion

Question 200

catheter sizes - scale used (how to interpret), usual size for men women and kids, normal size for clear urine vs urine with debris vs urine with clots

Answer 200

measured on french scale where 1 french = 0.33mm in diameter (or roughly the size in french is the circumference in mm) Men are usually 14-16 Fr, women usually 12; children are usually 6-10 Fr Generally: 12FR –14FR for drainage of clear urine 14FR–16FR for urine containing debris or particles 18FR or above if blood clots are present in the urine Note that 3 way tends to be 22Fr (and remember to put a spigot in the third lumen when you insert one) Also bear in mind that male catheter's tend to be longer than female

Question 201

catheter management - what ix shouldn't be done and how to ix for UTI; what if urine colour or smell abnormal; prophylactic gent x6 reasons for and 4 reasons not

Answer 201

All catheterised patients will have abnormal urinalysis and routine dipstick testing is unreliable and unnecessary. If patient have symptoms indicating a catheter associated UTI a urine sample for MC&S should be taken from the catheter sampling port Antibiotics should NOT be prescribed just because of the appearance or smell of the urine, as this may represent colonisation rather than active infection - most catheters will be colonised within 7 days prophylactic gent 1.5 mg/kg if painless/chronic retention, when changing if discharge at meatus, if known UTI, if 2nd attempt or trauma occurs (haematuria post insertion), if 2+ of [male, immunosuppressed, multiple comorbidities, abnormal tract], insertion in 6 weeks after joint replacement to reduce risk of prosthesis infection; not needed for acute retention w/o UTI sx, if inserting for fluid monitoring nor have IE risk factors nor established graft or artificial joint

Question 202

catheter troubleshooting: blocked/bypassing 5 causes 7mx; debris causes x2 and mx x5; penile discomfort causes x3 and mx x5; traumatic hypospadias 3 causes and 1mx; recurrent UTI caused x3 and 4 mx; SPC displaced or fallen out mx, what to do if changing, what if multiple recent failures, if unable to change

Answer 202

Blocked/ bypassing urethral catheter or SPC causes: 1. Bladder spasm 2. UTI 3. Debris 4. Blood clot 5. Not in right place actions: Check catheter position - Flush catheter to check patency – if not change - If long term catheter, and it has been in for a long time, and there is some debris then AXR to check for bladder stones - Debris with neobladders is common –just needs to be flushed regularly with Urotainer® solutions -Antimuscarinics may help (if catheter patent) - If blood clot and patient has significant haematuria then will need bladder irrigation (and a 3 way catheter to facilitate this) - If problem persists ? urology rv Debris in urethral catheter/ SPC causes: 1. UTIs 2. Bladder stone actions: - Check for UTIs - Check catheter position - Flush catheter to check patency – if not change - If long term catheter and it has been in for a long time and there is some debris then AXR to check for bladder stones - If problem persists ? urology rv penile discomfort Causes: 1. Catheter irritation 2. Traumatic hypospadias 3. UTI Actions: - Examine penis and look for catheter trauma - Check for UTI - Instillagel - Antimuscarinics -urology r/v traumatic hypospadias causes 1. Longer term urethral catheter in men and women 2. Catheter tubing attached too tight on leg (there should be some slack) 3. No G-strap/stat lock to limit catheter movement Actions: - Refer to urology recurrent UTI 1. Long term catheter 2. Recent catheter change 3. Bladder stones Actions: - Treat with antibiotics ONLY if symptomatic (pain/ unwell/fever). By 7 days most catheters are colonised by bacteria. -Send urine sample, dont dip (likewise for anyone >65yo) - If symptomatic, and not due to bladder spasm, and has had a long term catheter also organise XRay KUB/ USS KUB to check for bladder stones. - If symptomatic and repeated infections for referral to Urology as OPD to discuss options such as SPC SPC fallen out / displaced - SPC needs to be replaced ASAP, most start closing over after an hour, making replacement difficult - If changing then ensure bladder full prior to change. Fill the bladder with 300mls N. saline. - If multiple recent SPC failures then consider bladder stones (XRKUB/USSKUB) - If unable to change please contact urology if catheter needed to monitor fluid balance but can't get it in overnight then leave for day team and in mean time used a convene or serial bladder scans

Question 203

autonomic dysreflexia (in which pts, 7 sx, 5 causes, 3mx)

Answer 203

in pt with SCI above T6 Severe headache * Flushing, blotching of skin or pallor below level of the injury * Hypertension * Slow pulse * Sweating * Palpitations * Blurred vision Bladder problems are the most common cause of autonomic dysreflexia eg: An overfull bladder * Bladder calculi * High pressure voiding * Urinary tract infection * Instrumentation eg cystoscopy, catheterisation remove stimulus (eg catheter) catheterise if bladder over full and pt not voiding, control BP

Question 204

bladder spasm - 3 sx, 5 causes, 2mx

Answer 204

uncontrolled, sometimes painful contractions of the bladder causing a sudden urge to urinate occasionally results in some leakage of urine or bypassing around the catheter Possible causes for bladder spasms can be:  A urinary tract infection (UTI)  A water filled balloon holding the catheter in place in the bladder  A catheter that is causing traction (pulling) on the bladder neck because it is not secured correctly.  A blocked catheter Catheter that is too large or inserted too far in so irritating the trigone can try oxybutynin or other antispasmodics, also look for and address cause

Question 205

acute penis problems (urethral trauma 4sx, 4x causes of venous priapism and 1 of arterial, 1ix and 3 mx of condition and sx diff between 2 types; paraphimosis 4mx, fracture common cause 4 sx, 2 anatomical sites that might be disrupted, 3mx)

Answer 205

urethral trauma may be indicated by blood at the meatus, bruising of shaft/perineum/scrotum; inability to void or macroscopic haematuria oft too priapism: venous congestion/low flow is most common type and usually linked to medication (various, inc recreationals), sickle cell, polycythaemia, malig and is increasingly painful and rigid; also arterial/high flow which is turgid and less painful, and usually from perineal trauma (may not have been noticed) leading to arterio-sinusoidal shunt; aspirate 10-20mL of blood and do blood gas analysis to find which type as treatment varies; ice pack, medical treatment (terbutaline 5-10mg po, if fails phenylephrine into cavernosa but be very cautious if ihd, hypertension etc) for venous type paraphimosis: penile block if v painful or swollen (but not inc epineph as risk of penile ischaemia worsened), otherwise lidocaine lube gel; gentle compression of foreskin to reduce oedema and attempt reduction, if fails then gauze tight wrap beneath band, hold in place, use both thumbs to ease glans through the ring; GA may be needed for kids; if still cant then call urologist, dorsal slit under GA fracture - blunt trauma to erect penis, almost always intercourse, oft loud snap/pop and sudden onset pain + bruising and swelling which can spread to scrotum and perineum if buck's fascia disrupted; might palpate the tun albu defect; blood at meatus etc might suggest urethral injury too - if in retention then suppub cath and retrograde urethrogram; call urologist for surgery

Question 206

priapism guidelines

Answer 206

can occur in childhood and is often under-reported. It often starts at night in association with a full bladder * Acute, fulminant (> 4 hours). * Stuttering (repeated painful erections lasting more than 30 minutes sickle cell is a common trigger in children * Ensure Haematology/ Haemoglobinopathy paediatric team is notified of admission immediately. * Rehydrate immediately (IV fluids) * Opiate analgesia - consider PCA, +/- sedation (diazepam) * Catheterisation, if necessary, to empty bladder * Urgent Paediatric urology opinion. Where a Consultant Paediatric Urologist is available and priapism persists he/she may decide to administer an intracavernous α-agonist, e.g. phenylephrine (monitor BP and HR) Get cross match, FBC, U&Es Where a Consultant Paediatric Urologist is unavailable, and priapism persists exchange transfusion is likely to be required but should be first discussed with the Paediatric Haematology Consultant. * If detumescence has not begun within 24 hours, penile aspiration or the Winter procedure (a spongiosum-cavernosum shunt) should be considered (patients will require exchange transfusion first). For stuttering priapism, increase oral fluids and ensure frequent bladder emptying Oral analgesia Drug treatments such as Anti-androgens (cyproterone), α-agonists (etilefrine 10 mg tds treatment or 5-10 mg bg prophylaxis) or oestrogens (diethyl stilbestrol) can be used in the short to medium term (on the advice of the Paediatric Urologists) to prevent spontaneous erections. * Consider exchange transfusion followed by a period of hypertransfusion * The patient should seek medical attention if an episode lasts > 3 hours Consider referral to a specialist sickle Urology service for patients with stuttering priapism or after admission with acute priapism

Question 207

balanitis (3 sx, 3 signs, 5 things to ask about, 5ix, 5 mx and what/when resistant)

Answer 207

Penile soreness and itch Bleeding from the foreskin and/or odour, which usually develops over a few days. Dysuria, difficulty passing urine, and/or dyspareunia. On examination, there may be: Redness and swelling of the glans penis (and often the foreskin) with exudate. Tightening of the foreskin or meatal stenosis (may suggest lichen sclerosus). An inability to retract the foreskin ask about hygiene, joint/eye problems, any new drugs or creams, any trauma, any other skin conditions swab for candida and culture if sx severe; STI screen if blisters, lymphadenopathy, high risk history; if severe consider testing for diabetes and HIV clean daily with water, avoid triggers, topical hydrocortisone and imidazole cream until sx settle or up to 14 days (if non-specific, if clearly irritant then only give the steroid, if confirmed candida only the imidazole), if suspected or confirmed bacterial then flulox for 7 days (clari if pen allergic), if persisting over 7 days stop the steroid, swab for culture and candida and test for DM +/- immunosuppression

Question 208

prostate enlargement - how many men have by age 70, 5 consequences, 6sx and 2 things UTI may cause, haematuria and 2 forms of retention, 5 sx of renal failure and so 2 things to check in elderly confused men, how benign vs malignant prostate feels

Answer 208

70% men have BPH by age 70 enlarged prostates of any cause obstruct bladder outflow with following consequences: diverticulae may form in bladder wall, bladder stones from urinary stasis, hydronephrosis if back pressure high enough, UTIs (esp risk after catheterisation), and renal failure (AKI or CKD) from progressive hydronephrosis clinically any prostatic hyperplasia will present with: bladder overactivity giving freq and urg, noct, sometimes urg incontinence; UTI may exacerbate this or precip acute retention voiding symptoms due to outflow obstruction: hesitancy or terminal dribbling, poor or intermittent stream; if prostatic veins enlarge can get haematuria at start or end of micturition (must exclude bladder/renal cancers before diagnose); eventually may get urinary retention (acute/painful, chronic is not/less painful and has overflow incontinence, higher risk of hydronephrosis) finally may have symptoms of renal failure eg confusion, vomiting, lethargy, headache, drowsiness; so in elderly men presenting with confusion wise to check for azotemia and enlarged bladder benign usually lat lobes big with median sulcus still, if cancer then hard nodule or craggy obliteration of sulcus; palpate again after catheterisation as enlarged bladder pushes prostate down and may make it seem bigger than it is; sometimes only middle lobe enlarged in which case prostate will feel normal

Question 209

enlarged prostate mx: 3 main presenting problems, few sx 2 mx; moderate then 2 initial mx and if these fail then ix (to check what) and if confirmed what mx; most likely complication + 5 others

Answer 209

nocturia, freq, urg often main presenting problems if few symptoms can try lifestyle: less caffeine, more or less fluid if moderate symptoms then alpha1 antag (tamsulosin) or 5a reductase inhib (finasteride, may take up to 6mo to work); if medical therapies fail then urodynamics to double check outflow obstruction and not poor detrusor contractility, and then if confirmed then surgery; surgery also if complications of outflow obstruction endoscopic prostatectomy (TURP), very safe operation, some risk of bleeding esp if pt on asp/clop etc; infection may occur so proph antibiotics; retrograde ejaculation highly likely; impotence in 5-15% ppl; bladder neck stenosis from stricture formation, presents as outflow tract obstruction; incontinence rare but poss

Question 210

prostate cancer

Answer 210

most common cancer in men in UK (rare before 50, incs rapidly after with maybe 80% >80yo have it - although only kills 4% of men, many others die with it rather than from it); usually ACC; may spread to bladder, urethra, sem vescs, rarely into rectum; locally to iliac and para-aortic nodes; blood borne to pelvis, spine, skull (osteosclerotic lesions) or to liver and lungs PSA screening or BPH presentation; sometimes symptoms from secondaries eg pain in back, spinal cord compression; weight loss, anaemia etc; after DRE if suspect then PSA (>20ng/mL suggests disseminated disease), transrectal USS biopsy; bone scan if any pain in bones or PSA >20; MRI to identify primary tumour and for staging; MRI is primary investigation if suspected, before biopsy treatment options are active surveillance, esp if tumour small and well differentiated and life expectancy <10yrs anyway; radical prostatectomy takes out prostate, sem vescs, lymph nodes in pelvis; risks of impotence and incontinence; or radical radiotherapy with less risk of both of those things but irritation of prostate, bladder, or bowel in met disease, gonadtrophin antags can provide symptomatic relief; radiotherapy to relieve bony pain

Question 211

prostate cancer clinical (gleason staging, low/int/high risk cut offs, first line ix and likert scale cut off, 4 things that can raise PSA (and for how long)

Answer 211

graded using gleason system based on architecture of tissue, levels 3,4,5, what is most prominent and what is highest? total them eg 3+4 is 7; then staging 6 is considered low risk 7 is intermediate risk (3 + 4 is lower risk than 4 + 3) 8 or above is deemed to be high risk Multiparametric MRI is now the first-line investigation for people with suspected clinically localised prostate cancer. the results are reported using a 5‑point Likert scale If the Likert scale is >=3 a multiparametric MRI-influenced prostate biopsy is offered men aged 50-69 years should be referred if the PSA is >= 3.0 ng/ml OR there is an abnormal DRE PSA levels may also be raised by*: benign prostatic hyperplasia (BPH) prostatitis and urinary tract infection (NICE recommend to postpone the PSA test for at least 1 month after treatment) ejaculation (ideally not in the previous 48 hours) vigorous exercise (ideally not in the previous 48 hours) also if DRE

Question 212

testis cancer (what dont you often do, most common germ cell type, most aggresive, 4 subtypes of NSGCT, what makes AFP, what makes bHCG)

Answer 212

oft dont biopsy testis tumour due to risk of staging - after USS, CT, serum markers often remove testis germ cell 95%; undescended testis, testicular dysgen, genetics or previous history of testis tumour are risk factors seminoma then half germ cell tumours; NSGCT more aggressive, with variegated appaearance, red, necrosis and haemorhage rather than smooth and pale like seminoma; NSGCT may be teratoma, yolk sac, choriocarcinoma, embryonal; often mixed yolk sac makes AFP; teratoma has all kinds of other tissues including glands etc; choriocarcinoma looks a bit like placenta and makes bHCG after type do staging rarely can get lymphoma in testis, usually in older

Question 213

varicocele (transillum? reduce when? when suspicious and 2 causes, ix, mx)

Answer 213

Does not transilluminate, reduces on lying supine Sudden-onset or varicocele which doesn’t drain when supine -> suspicion for obstructed venous drainage (E.g renal cell carcinoma with renal vein tumour throbus) Ix: USS with doppler Mx: conservative, surgery if painful/ infertility concerns

Question 214

The clinic nurse brings you the fi le for the next patient. It is only a temporary set, so you have no information other than the GP’s fairly brief referral letter: ‘Dear doctor, please could you review this lovely little boy who has a lump in his scrotum. It looks to me like a hydrocoele. I have explained to the parents that there may be a need for surgery.’ Ralph is nearly 10 months old. - dd, hist, ex, ix, mx

Answer 214

1 Hydrocoele. 2 Hernia. 3 Lymphadenopathy. 4 Haematocoele. 5 Tumour. It is important to keep an open mind until you have completed your own history and examination. how long has lump been there? does it come and go or get bigger when he cries? cause any pain? changed since they noticed it? any other lumps? recent illness? history of trauma? did testes descend normally and on time look for sys upset, ext genitalia, palpate cervical, axillary, inguinal lumph nodes and examine lump - size, site, colour, regularity, tethering, transillumination, temp, composition; is it tender? can it be reduced? impulse if cough/cries/you gently palpate abdo? can you get above it? feel for thickened spermatic cord, auscultate for bowel sounds if it might be a hernia, and if it is a hernia is it direct or indirect (tho hard in children to tell)

Question 215

paeds inguinal hernia

Answer 215

Before birth, a boy’s testicles have to travel from inside the body, down to the groin where they drop into the scrotum. This pathway normally closes up after the testicles have dropped. It is quite common, however, for the pathway to remain as a point of weakness so when there is an increase in pressure, like when kid starts crying, some of the bowel can get pushed through. This is thus an indirect hernia). About one in 50 boys experiences this and there are usually no problems. At the moment kids hernia reduces spontaneously. There is a small risk that bowel may become trapped and strangulate (i.e. lose its blood supply). There is also a risk (one in 10) that it may start to obstruct the gut - Risk of obstruction in a 6-month-old is > 50–60%. * Risk of obstruction in a 1-year-old is > 10%. * Risk of obstruction in a 2-year-old is > 2% if not reducible then try under analgesia/anaesthetic to reduce, if still cant then surgery is even more urgent surgery performed: The hernial sac (i.e. the processus vaginalis) is divided via an incision made in the inguinal skin crease. The bowel is replaced within the abdomen and a mesh fi xed over the defect. Ideally this is a day case procedure. However, if the child is very young, or there are complications, they may be admitted overnight note hydrocoele oft resolves spont before 18mo so surg only if not resolved after this time

Question 216

undescended testis mx

Answer 216

Unilateral undescended testis NICE CKS now recommend referral should be considered from around 3 months of age, with the baby ideally seeing a urological surgeon before 6 months of age Orchidopexy: Surgical practices vary although the majority of procedures are performed at around 1 year of age Bilateral undescended testes Should be reviewed by a senior paediatrician within 24hours as the child may need urgent endocrine or genetic investigation

Question 217

nutcracker syndrome - what it is, 5sx, 4 causes and ix

Answer 217

vascular compression disorder that refers to the compression of the left renal vein most commonly between the superior mesenteric artery (SMA) and aorta, although other variations can exist, giving renal venous hypertension -> haematuria may also see left flank pain, pelvic pain, gonadal varices; RVT is possible oft an anatomical variation, but can be compression by pancreatic cancer, retroperitoneal tumors, and abdominal aortic aneurysm; abdo CT is needed to ix further

Question 218

incontinence paediatric - bladder cycle, causes, risk factors

Answer 218

day wetting in a child over 5 years that occurs more than once a month for more than 3 months; daytime continence normally achieved by 4yo (and night-time by 7yo) 6 % of 7-year-olds are affected by urinary incontinence during the daytime. The rate of comorbid behavioural and emotional disorders in children with incontinence is high; 20-40% with urinary incontinence normal bladder cycle: During the filling phase, the bladder volume increases with very little change to the internal pressure; As the bladder fills it becomes spherical and then pear-shaped as it rises up out of the pelvic cavity. During filling, the detrusor is relaxed and the bladder neck and external sphincter are contracted maintaining continence. The first desire to void is usually experience at 150-200ml (about half full) capacity which can be suppressed by conscious inhibitory control Voiding is initiated voluntarily and can be delayed until a suitable time and place. The external sphincter and bladder neck relax and simultaneously the detrusor muscle contracts. This is co-ordinated via the spinal-pontine-spinal reflex which involves the micturition control centre in the pons. When the external sphincter relaxes the pressure in the urethra is lowered and the pelvic floor relaxes allowing the bladder neck to descend and open. This is known as funnelling. The parasympathetic nerves stimulate the detrusor contraction, thus increasing the intravesical pressure and the urine is expelled As emptying is completed the flow reduces and ends: External sphincter closes under voluntary control Urethra contracts forcing urine above the level of the external sphincter back up into the bladder Cortical micturition control centre takes control; this inhibition allows the filling cycle to start again causes: 1. Voiding postponement– habitually delayed urination, with overfilling and leakage 2. Overactive bladder- urgency or small bladder capacity 3. Underactive bladder– infrequent urination and overfilling leading to overflow incontinence. A large post-void residual is common 4. Dysfunctional voiding (non-neurogenic) – an inability to relax the urethral sphincter and/or pelvic floor musculature during voiding, resulting in an interrupted urinary flow and prolonged voiding time. 5. Incomplete emptying of urine Causes of urinary incontinence are mostly functional impairments risk factors: Developmental delay  Constipation, faecal incontinence  Psychosocial variables or behavioural disorders (inadequate toilet training, parental separation, conflicts within the family, the birth of a sibling, high anxiety level, depression, oppositional-defiant disorder, attention deficit hyperactivity disorder and autism)  Chronic Kidney disease  Diabetes mellitus or insipidus  Sickle Cell disease

Question 219

paediatric incontinence - ix/mx

Answer 219

establish in history: Pattern of wetting? (nights/days/continuous incontinence/dribbling)  When did wetting start? If recent, consider presentation of a systemic illness  History of toilet training, prior interventions for urinary incontinence and responses of family members and peers to voiding.  Previously dry without assistance? If so, enquire about any possible medical, emotional, or physical triggers Urgency, frequency, difficulty in passing urine  Previous urinary tract infections  Constipation/soiling  Motor delay  Any emotional or behavioural problems check: Growth, BP, abdo (for bladder, constipation), lumbar spine for features of spina bifida, sacral agenesis and occult spinal dysraphism, including sacral dimple, tuft of hair, naevus, lipoma, asymmetrical gluteal creases.  Neurologic examination: assessment of motor strength, deep tendon reflexes, perineal sensation, gait and coordination.  Genitalia: penile or meatal abnormalities in boys as well as labial adhesions in girls red flags: Voiding difficulties present- weak stream, need to strain to void  Polydipsia, polyuria and weight loss  Renal problems  Hypertension  Distended bladder on examination  Asymmetric gluteal cleft or neurological deficit on examination  Haematuria  Recurrent urinary tract infections  Loin pain  Signs or concerns of sexual abuse ix 2 days voiding and drinking diary - ix for polyuria if output >50ml/kg/day, urine dip, renal tract USS (check bladder wall thickness, post void residual, upper tract dilatation) mx behavioural interventions, rx constipation and any other underlying causes if not successful try anticholinergic eg oxybutynin or tolterodine, if successful try off medication every 3mo if still not successful refer to tertiary centre behavioural interventions: 1. Regular voiding habits (about every 2 hours - reward chart for trying) 2. Sound voiding posture 3. Do not rush urinating, make sure that the bladder is emptied completely, try and sit/stand still for 10-20 seconds after urinating or double voiding (wait 20 seconds, then try again) 4. Pelvic floor awareness and training to relax pelvic floor and avoid holding manoeuvres. 5. Standardisation of fluid intake (4-8yo should drink 1000-1400mL per day, 9-13yo 1200-2100 if girls and 1400-2300 if boys, 14-18yo 1400-2500mL if girls and 2100-3200 if boys) - too much can give polyuria, too little can give a small bladder that fills and so gives sensation of needing to go frequently 6. Avoid flavoured and fizzy drinks other reasons for tertiary referral: Voiding difficulties in boys  Spinal cord pathology  Severe daytime symptoms despite measures above  History of recurrent urinary tract infections  Known or suspected anatomical or neurological problems  Comorbidities such as diabetes mellitus

Question 220

multicystic dysplastic kidney

Answer 220

MCDK is a congenital developmental anomaly with an incidence of around 1:4,300 live births. A multicystic dysplastic kidney has no functioning renal tissue and bilateral involvement is incompatible with life over 40% of MCDK’s involute spontaneously with a further 30% involuting partially ontralateral kidney may show compensatory hypertrophy (77%) which is a normal finding. Alternatively, the kidney may be of normal size (6%), this may suggest dysplasia and requires long term follow up. Occasionally the contralateral kidney may show mild hydronephrosis (10%), or obvious dyplasia Contralateral renal anomalies, most commonly VUR (mostly mild and self resolving), but also vesicoureteric/ pelviureteric junction obstruction and ureterocoele may be found in up to 16% of cases. As the MCDK is non functional, any abnormality to the effectively solitary kidney needs more aggressive assessment and management Normal contralateral kidney - Routine renal ultrasound at 4-6 weeks & DMSA at 3 months to identify if there is any functioning renal tissue – MCDK is totally non-functioning Referral to the nephrology team should occur when: There is any abnormality of the contralateral kidney on ultrasound (i.e. dilatation or cysts) or DMSA – URGENT REFERRAL BY PHONE There is a remnant of MCDK present on postnatal ultrasound (i.e. involution has not occurred) Refer to nephrology non-urgently where compensatory hypertrophy is NOT demonstrated on USS If a single kidney is affected by MCDK but there are contralateral changes – eg parenchymal cysts or pelvicalyceal dilatation ≥15mm, OR if there are concerns about renal function due to the presence of oligohydramnios then the infant will require urgent investigation and close monitoring. This should include: Daily blood pressure; U&E; urine output and fluid balance. An early (48 – 72) USS should be arranged and the case should be discussed with the Nephrologists.

Question 221

paediatric renal transplant

Answer 221

treatment of choice for patients with ESRF transplant will be from living donor (relative) or deceased donor and carried out in specialised renal transplant centre choice of early steroid withdrawal (short course prednisolone-MMFtacrolimus-basiliximab, ‘TWIST’) or steroid maintenance (prednisolone-azathioprine-tacrolimusbasiliximab, ‘PAT-B’) ISD regimen should be made jointly by health professionals and parent and the young person children and young people should receive pneumocystis prophylaxis with cotrimoxazole for 6 months post transplant they should receive prophylaxis with valganciclovir for at least 3 months post transplant if the donor is CMV positive and recipient CMV negative should be monitored for CMV viral load at least monthly for 12 months post transplant if either donor or recipient are CMV positive increasing shortage of deceased donor kidneys and sensitisation of children due to blood transfusions and previous transplants have resulted in strategies with antibody removal to permit ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation in children; plasmapharesis is used to lower the titre of the offending anti-ABO antibodies pretransplantation, and then lowered levels are maintained for several weeks post engraftment, allowing allograft survival even when antibodies later return to predepletion levels, and despite the presence of normal levels of complement. This apparent resistance of a vascularized graft to humoral rejection despite the presence of antibodies directed against the donor endothelium is called accommodation; IVIg and early immunosuppression + rituximab also often given before the operation complications: Delayed graft function (DGF) is defined by the need for dialysis in the first week after transplantation. Its risk increases with prolonged WITs and CITs (warm and cold ischaemia times) therefore is relatively rare with living donor grafts). Whilst most DGF kidneys eventually function, there is a recognised association with increased rejection rates and decreased graft survival rates. Early complications comprise renal artery thrombosis (rare, 1%) and renal vein thrombosis (6%). They must be recognised promptly using a Doppler ultrasound and will require taking back to theatre urgently if identified. Aspirin and/or heparin are often started post-operatively to reduce this risk Late complications include renal artery stenosis, which usually presents several months post transplantation with uncontrollable hypertension and worsening graft function. Angiography confirms the diagnosis and the treatment of choice is typically angioplasty. Ureteric leaks occur from a breakdown of the ureteric-bladder anastomosis, presenting with a decreased urine output and increasing abdominal pain. They often require repeat surgical intervention. Urinary tract obstruction can also occur, through ischaemic strictures in the distal ureter (treated with dilatation) or extrinsic compression from a lymphocele or haematoma (treated via drainage). longer term complications are often related to the use of immunosuppressive agents, such as recurrent infections, diabetes mellitus, or malignancy

Question 222

erectile dysfunction management

Answer 222

oral phosphodiesterase-5 inhibitors like sildenafil are first-line therapy second line includes intracavernosal injection of alprostadil - a synthetic analog of prostaglandin E1, whihc promotes smooth muscle relaxation to increase blood flow into the penis