Renal/urology Flashcards
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)
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
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)
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)
iv fluid therapy types and amounts
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)
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
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
cell adjustments to hypertonicity and action of ADH
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
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 %
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)
shock vs dehydration (3 signs shock more likely, 4 things seen in both, 4 signs of decompensated shock, how tongue may be in dehydration)
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
7 factors increasing risk of dehydration in children
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
5 features suggesting hypernat dehydration
jittery movements
increased muscle tone
hyperreflexia
convulsions
drowsiness or coma
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)
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
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)
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
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)
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
enzyme inducers (mnemonic + 3)
PC BRAS – phenytoin, carbamazepine, barbiturates, rifampicin, alcohol (chronic excess) sulphonylureas (gliclazide). Others: topiramate, St John’s Wort, and smoking.
enzyme inhibitors (mnemonic + 4)
AO DEVICES – allopurinol, omeprazole, disulfiram, erythromycin, valproate, isoniazid, ciprofloxacin, ethanol (acute intoxication), sulphonamides (antivirals). Others: azole antifungals, grapefruit juice, amiodarone, and SSRIs (fluoxetine, sertraline).
5 cannula colours and their gauge + flow rates
Orange 14g 270ml/min
Grey 16g 180ml/min
Green 18g 80ml/min
Pink 20g 54ml/min
Blue 22g 33ml/min
describe body fluid comps
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
4 functions of the kidney, gfr in infants
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
kidney structure/blood supply
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
describe basic renal mechanisms
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
nephron stucture
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
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)
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,
filter at glomerulus
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
control of GFR
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
PT reabsorption and secretion
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
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)
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
aldosterone in volume reg
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
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)
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
haemorrhage physiology
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)
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)
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
drivers of thirst
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
ecf volume and Na balance
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
neural RSNA influence of Na balance (3 things)
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
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)
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)
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)
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
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)
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
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)
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
thiazides (what cant you use them with and k sparing diuretics)
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
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)
not directly
cr rises for 2 reasons:
- 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
- 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
diuretic resistant oedema
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
ACE inhibitors + which receptor losartan works on, benefit from combining ACEi with diuretic, why hypotension + ACEi dangerous combo
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
diuretics and acei in hypertension
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
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)
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
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
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
SIADH 14 causes and 5hypo/4eu/3hypervol hyponat
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
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)
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)
interpreting ADH and RAAS in hyponat
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)
correcting hypokal and hyponat at same time
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
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)
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
sodium correction for hyperglycemia
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
management of hyponatremia
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
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)
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
K distribution and conc in plasma - inc why is moving into the intracellular compartment appropriate (short term)
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
stress to K balance and hom mechanisms related to this
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
K and acidosis/hyperglyc (inc organic acids, non-organic acidemias, and link to kidney)
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
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)
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
more kidney handling of K (NKCC2, aldos mechanism, flow rate)
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
hyperkalaemia (ecg changes, symptoms, causes, management)
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
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)
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
hypokalaemia causes, sx
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
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)
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
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
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
hypokalemia algorithm
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
Ca hom intro (hyper and hypo symptoms)
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
PTH and vit D link to Ca levels
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
hypocalcaemia investigations + mx
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
early and late neonatal hypocalcemia
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
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)
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
hypercalciuria and nephrocalcinosis
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
blood phosphate - causes of (6) high and (9) low levels, symptoms of hypo, mx of hypo
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
blood magnesium
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
roles of Mg in medical rx
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
electrolyte disorders causing seizures/status that may or may not be responsive
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
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)
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
management of paediatric electrolyte emergencies
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
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)
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
AKI staging, causes (inc 8 nephrotoxins), who’s at risk
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
investigating AKI (inc minimum bloods and ix, telling CKD from AKI - visually or in blood results)
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
managing AKI (general and hyperkal specific)
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
AKI staging, intrinsic causes, inc’d sens to prerenal, prerenal vs ATN, 4 ATN and 6 AIN causes, lupus nephritis
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
general approach to AKI, indications for dialysis
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)
AKI bundle
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
nephrotoxic drugs (4 forms of damage with corresponding drugs 3:6:9:1)
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
11 ciclosporin s/e
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
drugs to stop during AKI (inc nuance about the first)
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
nephrotoxicty due to contrast media (inc time course, 5 risk factors, 2 procedures where might happen, 2 protective steps)
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
contrast induced nephropathy - historical perspective, modern dyes, recent specialty statement
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
ATN
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
acute interstitial nephritis (2 causes, 4 features/sx)
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
