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# Statistics

Positive likelihood ratio (likelihood of a pos result if you DO have the disease) / (likelihood of a pos result if you
DON‟T have the disease)

Pharmacology

Trial phases 0 = subtherapeutic doses for pharmokinetics/dynamics
1 = healthy volunteers; determine safe dose, safety, tolerability
2 = diseased pts for therapeutic effect + safety
3 = RCT for efficacy comparison
4 = post marketing monitoring
Bioequivalence AUC and Cmax (max conc) within 80-120% of each other
Clearance Cl = 0.7 x Vd ÷ t(1/2)

clearance also = dose/AUC
T(1/2) t1/2 = 0.693 x Vd/CL
Elimination clearance x plasma concentration
*Higher plasma concentration = more rapid elimination (but clearance is constant)
Hysteresis curves anticlockwise = takes time for distribution
clockwise = tachyphylaxis

Renal + Metabolic

Formulae

Normal GFR ⓝat birth: ≤15mL/min/1.73m². Adult: >120mL/min/1.73m²
GFR estimation Schwartz formula: K*height ÷ serum creatinine
 K = 0.45 in infants, 0.55 in children, 0.7 in adolescents
Creatinine clearance (⁵ ¹Cr EDTA) = “best”
FENa Sodium (urine) x Creatinine (plasma) x 100
Sodium (plasma) x Urine creatinine

= “Suc P/ Spu C”

Interpretation:
< 1% = conserved concentrating ability e.g. prerenal dz
>1-2% = intrarenal e.g. ATN with ↑ Na loss or hypervolaemia with
appropriate Na loss
Intermediate = either
In obstruction, FENa can be low OR high
Spot urine Pr:Cr ratio
 For proteinuria evaluation
Should be < 0.2 (<0.5 in younger kids)
0.2-2 = proteinuria. >2 = nephrotic range
Urine Ca²⁺ :Cr ratio > 0.2mg/mL suggests hypercalciuria (assoc with persistent haematuria)

Acidosis + Alkalosis

Anion gap Na – (HCO₃ ⁻ + Cl)
Normal is <12
Excess anion gap = total AG – normal AG (12)
add this value to measured bicarb
if > 30 (i.e. > ULN bicarb), suggests an underlying metabolic alkalosis
if < 24 (i.e. < LLN bicarb), suggests ANOTHER non-AG metabolic
acidosis
Osmolal gap
- Useful to identify another
osmolal agent in serum
(measured serum osmolality) – [ (2xNa) + glucose + urea]
normal is < 10
Urine anion gap
 Rough index of ammonium
excretion
 Used to differentiate renal
vs GI cause of
hyperchloraemic (normal
AG) metabolic acidosis
1. you have a metabolic acidosis
2. calculated anion gap is <12 ∴ there is no extra acid; base is
being lost somewhere
3. calculate (Urine Na + Urine K) – Urine Cl

If base (bicarb) is being lost in the gut; kidney will lose H⁺ (in the form of
NH₄ ) to compensate → UAG will be negative (<0) = GIT

If base is being lost by the kidney (e.g. RTA), it won‟t be able to
compensate → UAG will be positive (≥0) = RTA
Emesis vs diarrhoea Emesis:
- Loss of HCl and NaCl in vomitus → kidney saves Na²⁺ at the
expense of H⁺ → metabolic alkalosis (e.g. pyloric stenosis)
Diarrhoea
- Loss of HCO3⁻ in diarrhea → normal AG met acidosis
- Except for congenital chloride diarrhea, where there is inadequate
bicarb secretion and a metabolic alkalosis with diarrhoea
Metabolic alkalosis

CAUSES:
1. Volume contraction:
a. Chronic dehydration
b. diuretic use or abuse,
c. Bartter's or Gitelman's syndrome.
2. Loss of acid:
a. Pyloric stenosis, NG tubes to suction, vomiting.
i. PS: hypochloraemic metabolic alkalosis with
(trying to preserve K)
3. High mineralocorticoid states:
a. Hyperaldosteronism, black licorice use.
DIAGNOSIS
• ↑pH with ↑ HOC3
• Urine chloride and BP can be used to narrow the differential.
• Urine chloride can distinguish subtypes:
• Chloride responsive (urine Cl < 10): GI losses, dehydration,
diuretic use.
• Chloride resistant (urine Cl > 20): Mineralocorticoid states
(HTN); Bartter's or Gitelman's syndrome (both normotension)
Metabolic compensation in respiratory
acidosis
1. ACUTE COMPENSATION
In acute respiratory acidosis (resp failure), HCO3 can rise by 1mmol for
every 10mmHg risk in pCO₂ above 40mmHg, to max of bicarb ~38
Expected HCO3 = 24 + [(actual pCO₂ - 40)/10]

2. CHRONIC COMPENSATION
Bicarb will rise by 4mmol/L for every 10mmHg rise in pCO₂ ∴ expected
HCO3 = 24 + 4[(actual pCO₂ - 40)/10]
Metabolic compensation in respiratory
alkalosis
1. ACUTE COMPENSATION FOR RESP ALKALOSIS
△ HCO3 = 0.2 x △ pCO₂

2. CHRONIC COMPENSATION FOR RESP ALKALOSIS
△ HCO3 = 0.5 x △ pCO₂
Respiratory compensation in
metabolic acidosis
pCO₂ will drop in metabolic acidosis

expected pCO₂ = [△ in bicarb from normal] x 1.2

Fluids & Nutrition

Calculating fluid
deficit
e.g. 5% dry, weighs 10kg
= 10 x 5 x 10 = 500mL deficit
Fluid distribution ICF = 60% (K⁺ main cation)
ECF = 40% (Na²⁺ main cation)
 16% ¾
 plasma ¼
Insensible losses 1/3 from lungs, 2/3 from skin
= 40% of maintenance in infants, 25% in adolescents

Prems lose 2-3 mL/kg/hr
Normal UO 2-3mL/kg in young children
Day 2-3: 90mL/kg
Day 4-6: 120mL/kg
Day 7: 150mL/kg
Aim for:
 If <33wks or <10th centile: 180mL/kg/day
 If >33wks and BW > 10th centile: 150mL/kg/day
Calories Human breast milk: 20kcal/30mL
Fortifier: 24kcal/30mL
10% lipids = 1kcal/mL
10% dex = 0.4kcal/mL
Energy + growth 0-1mo: 120kcal/kg/day
<1yo: 90-100 kcal/kg/day
1-6: 75-90
6-12 60-75
12-18: 30-60

Electrolyte disorders

Correct Na in
hyperglycaemia
measured sodium + 0.3(glucose – 5.5)
Approach to
hyponatraemia
1. Check serum osmolarity
a. If normal, consider pseudohypoNa e.g.
hyperlipidaemia/hyperproteinaemia
b. If high, consider hyperglycaemia (translocational hypoNa)
c. If low, check volume status + UNa
2. Check volume status
3. Hypovolaemia + hypoNa
a. UNa < 10 = extrarenal (D/V, 3
rd
spacing, CSW)
b. UNa > 10 = renal wasting (thiazides, nephritis, RTA, hypoaldosteronism)
4. Euvolaemia + hypoNa
a. UNa < 10 = 1° polydipsia, low salt intake
b. UNa > 10 = SIADH, hypoaldosteronism
5. Hypervolaemia + hypoNa
a. UNa < 10 = CCF, nephrotic sy (intravasc depletion – trying to conserve
Na)
b. UNa > 10 = ARF, CRF (kidneys wasting salt)
6. Management
a. Seizure
i. Aim to increase serum Na by 5mmol/L
ii. Use 3% NaCl (513mmol/L = 1mmol in 1.95mL)
iii. Recall TBW = 0.6
iv. Give 0.6 x 1.95 x 5 x wk(kg)
v. Then aim to ↑ Na by 3mmol/L in 24h for total 8mmol/L increase
in 24 (0.3mmol/L/hr)
b. Asymptomatic – aim to increase by
Osmotic
demyelination
syndrome
In chronic hypoNa, brain cells lose solutes to maintain equilibrium w ECF
When rapidly corrected, cells swell as they were hypotonic
Damages myelin → cranial nerve sx, lethargy, coma
Dx: MRI
Acidosis:
- Could be laxative abuse, diarrhea
Alkalosis
- Vomiting (UNa < 10) or diuretic (UNa > 10)

Diabetes insipidus water deprivation test:
1. pt empties bladder, calculate weight
2. weigh q2h while water deprived
3. endpoint = serum osm > 300 (dehydrate) or > 4% wt loss
a. If urine osm < 700 despite serum osm > 295 = DI
b. Give DDAVP: if improves, = central DI, if not = nephrogenic

Hypernatraemia Mx Drop Na by max 0.5mmol/L/hour
Too rapid = risk cerebral oedema
If severe (>169) – use 0.9% NaCl + 5% dex; if moderate, can use 0.45% NaCl + 5% dex
Hypokalaemia ECG: prolonged PR, flat TW, TWI, STD, U waves (esp precordial leads)
Low urine K (24h K < 30) – GI bicarb loss, skin (sweating, burns)
High urine K (24h K > 30) – renal e.g. diuretics, tubular transport defects (all 3), dRTA,
hyperaldosteronism

Drugs: adrenaline, B-agonists, thiazides, amphotericin, cisplatin
Hyperkalaemia TTKG: < 10 = insufficient renal K+ excretion

Renal scans

Ultrasound Obstruction
MCUG Indications:
 Dilatation or hydronephrosis on US (e.g. post-UTI)
 Atypical, recurrent or hard-to-treat UTI (perform in 4-6mo)
 Abnormal urine flow
 FHx of VUR
 Enuresis

 Voiding dysfunction
Looks at
 Anatomical problems, voiding
 Can see enlarged abnormal bladder
MAG3 = DTPA Radioactive tracer injected IV
- 40-50% of MAG3 is excreted by PCT; can measure clearance. Need to give
frusemide.
- ~20% of DTPA is excreted by glomerulus, can estimate GFR but MAG is
better (higher extraction fraction)
- Counter-intuitive: maG is PcT, while dTPa is Glomerular
BOTH used to assess:
- Function of kidneys e.g. differential function
- Perfusion
- Obstructive pathology
DMSA Looks at cortical morphology e.g. SCARRING
Part of post-UTI work-up
IVP Rarely performed
Obstruction
Ectopic ureter
CT Stones (procedure of choice)
Masses, cysts
MRI Renal artery stenosis
Masses
NB: gadolinium is nephrotoxic; deposits in interstitium
Angiogram Definitive for vascular abnormalities e.g. fibromuscular dysplasia vs RAS

Renal Physiology

Sodium Reabsorption:
 60% in PCT (coupled to glu/AA/PO₄ ; Na/K/ATPase; NHE₃ exchange
(coupled to H⁺ excretion)
 25% in LOH (NKCC2 (side of frusemide); NHE₃ ; ROMK
 15% in DCT (NCCT- thiazide site – NaCl cotransport); ENaC (epithelial
Na channel – site of amiloride action)
 Immature kidney has ↓ Na²⁺ K⁺ ATPase & NHE₃
Regulation
 Angiotensin II ↑ Na reabsorption in PCT
 Aldosterone ↑ Na reabsorption in DCT /CD via Na/K pump (pushes 3Na
out, 2K in, leading to gradient so Na is reabsorbed, K is excreted), also
upregulates ENaCs
 ANP ↑ Na excretion & suppresses RAA axis; ↑GFR
Potassium  65-75% reabsorbed in PCT (Na/K/ATPase); rest in TAL via NKCC2, small
amt in DCT via H+K+ exchanger
 Excreted via ROMK in CD
 Excretion ↑ by aldosterone, urine flow, ↑ urine anions
 Fetus needs ↑K+ for growth ∴ 6.5mmol/L is normal in neonate; ↓ to 5.2 by
day 5
Calcium Active maternal transport in utero
70% reabsorbed in PCT via passive paracellular transport
PTH/1,25-OHD will ↑ epithelial Ca transporters in DCT/CD → total 98% reabsorbed
↑Reabsorption with PTH, calcitonin, vitamin D, thiazides, volume depletion
↑ excretion with volume expansion, ↑Na intake, mannitol, frusemide (hence stones)
Phosphate 80% reabsorbed in PCT
↑ excretion w vol expansion, PTH
↓ excretion w GH, volume contraction
99% reabsorbed in neonate
Other Mg: 25% reabsorbed in PCT, 75% in TAL (paracellular)
Glucose: >99% reabsorbed in PCT, Na coupled

Diuretics

Loop Act on NKCCT channel in TAL
Most potent diuretic; ↑ excretion of up to
25% of filtered Na, and inhibits
reabsorption
Eliminated via kidney/liver
SE: ↓ BP, nephrotoxic, ototoxic, hypoK,
hypoMg, alkalosis, hyponatraemia,
hypercalciuria (stones)
Thiazide Act on NCCT (NaCl cotransport) at DCT
Inccrease excretion of Na, K, Mg
Decrease excretion of Ca
SE: hypoK, hyperglycaemia, hyperuricaemia,
hyperlipidaemia, hypocalciuria can →
hypercalcaemia
K+ sparing Act at CD ENaC (amiloride) or MR
(spironolactone)
SE: hyperK, teratogenicity, GI upset, PUD
Spironolactone = anti-androgen:
gynaecomastia, nausea, lethargy, cramps
Osmotic e.g. mannitol: ↑ plasma osm to draw water
out of tissues

Carbonic anhydrase
inhibitors
Act on PCT to inhibit Na, HCO3 and
water reabsorption

Glomerulonephritis

Low
complement
GN
PSGN (should resolve; usually C3 only; IgG in mesangium/BM. CH50 also initially low)
SLE (IF: + IgG, IgA, IgM, C3, C1q)
MPGN (type 1 = IgG pos, classical complement pathway; type 2 = alternate pathway, IgG neg)
Bacterial endocarditis, shunt nephritis, cryoglobulinaemia
Alport CAUSE: 80% XL; Type 4 collagen mutation (makes up GBM also in ears/eyes)
CLIN: Episodic gross haematuria, SNHL, FHx of renal failure
LM: mesangial proliferation > 10yo, thin BM thick cap wall, scalloped epitheilum
IHC: absent α-5 chain of collagen IV, Anti-GBM Ab stain negative
PROG: persistent haematuria or nephrotic = bad
RPGN Subacute nephritic syndrome with rapid ↓ renal function
Macrohaematuria, nephrotic proteinuria, oedema
LM: crescents (fibrin → fibrosis)
DDx:
- immune complex (PSGN, SLE, MPGN, HSP, IgA neph, mixed cryo, idiopathic immune
complex)
- anti GBM Abs (goodpasture, idiopathic)
- ANCA med (Wegeners, MPAN)
- Idiopathic
Mx = methylpred
CLIN: Persistent or intermittent microhaematuria
Ix: Don‟t need biopsy – would show isolated thin BM on EM, otherwise normal
Mx: usually nil, only if proteinuria (rare)
Minimal △ Nephrotic syndrome
Podocyte effacement on EM
PSGN CLIN: Micro/macrohaematuria, HTN, oliguria, renal failure
IX: ↓C3 (occ ↓C4), resolves within 2m
IF: starry sky IgG/C3 in GBM + mesangium
LM: endocapillary proliferation, PMNs
EM: subepithelial dense deposits, inflammation, proliferation
IgA neph CLIN: Synpharyngitic haematuria (latency 1-2wk)
PATH: Abs vs galactose-def IgA1 → immune complexes in mesangium + mesangial proliferation →
LM: mesangial proliferation, IgA deposition, ± crescents/tubulointerstitial dz
IF: granular IgA + C3 deposits
EM: mesangial deposits
HSP CLIN: Nephritic (90% have haematuria) or nephrotic. Renal dz 12 wks after initial presentation.
Features: purpuric rash (100%), arthritis (66%), abdo pain (50%), intussusception (5%), GN (25-
50%). Assoc w HLA DRB1*01, FMF, IBD
IX: ↑WCC, ↓Hb, ↑PLT, ↑ESR, ↑ IgA/IgM in 50%, ASOT ⊕in 30%
LM: mesangial proliferation
IF: granular IgA, IgM, IgG, C3
HUS CLIN: Triad = microangiopathic haemolytic anaemia (↓Hb), thrombocytopenia, ARF. Also HSM.
CAUSE:
 D+: 80% assoc with ETEC (0157:H7 = shiga toxin producing). Other: shigella, salmonella,
campylobacteria, S. pneumonia, Bartonella, viruses, OCP, cyclosporine, SLE, radiation
nephritis
 D-: complement defect
IX:
 ↓Hb, ↓PLT, ↑WCC, ↓haptoglobin, ↑retics
 IgA ± IgM ↑ in 50%
 PBF: schistocytes (helmet- fragments), burr (spiky from uraemia)
 DAT neg (vs AIHA)
 UA: haematuria, proteinuria
 LM: mesangial proliferation
 IF: granular IgA, IgM, IgG, C3
 Coags normal
 Renal US for RVT
AntiGBM dz
(Goodpasture)
CLIN: Pulm haem + RPGN. Nephritic OR nephrotic
IX: Normal C3, Anti-GBM IgG +
FSGS CAUSES: idiopathic, hereditary, severe obesity, reflux nephropathy, renal dysplasia, DM, von
Gierke, interferon
CLIN: nephrotic sy ± haematuria/HTN/↑Cr
IF: IgM + C3 in sclerotic segment. EM: foot process fusion
Prog: 1/3 improve, 1/3 persistent proteinuria, 1/3 ESRF early
Membranous CLIN: Nephrotic sy (#1 cause in adults)
IX:
 IgG and C3 on epithelial side of BM
 No cellular infiltrate
 + extracellular substance
 serum C3 normal (unless SLE)
neonatal membranous: mat anti-neutral endopeptidase Abs (mum has no NEP)
Causes: SLE, ITP, sarcoidosis, neuroblastoma, gonadoblastoma, HBV, HCV
Prog: 40% active dz
SLE Onset in adolescence, affects 30-70% of kids w SLE
Classes:
1. Normal LM
2. Hypercellular (mesangial expansion): haematuria, normal renal Fn, mild proteinuria
3. Focal proliferative (nephrotic)
4. Diffuse proliferative (nephrotic)
5. Membranous (nephrotic)
6. Sclerosing
Mx pred → AZT, cyclophosphamide
MPGN PATH: circulating immune complexes deposit → cellular infiltrate + complement activation
CAUSES
- Type 1: IgG +, complement + (infection, autoimmune, rheumatologic)
- Type 2: IgG - , complement + (alternative complement pathway problem)
- C3 Nephritic factor = IgG or IgM that binds & stabilizes C3 convertase →ongoing
complement activation
IF: granular IgG, IgM, C3 in types 1 and 3.
Type 2: C3 stains either smooth or granular, NO Ig
Type 1:
- Classical complement pathway
- Discrete deposits in mesangium/subendothelium
- Cryoglobulins (HCV 70-90%), other infections, SBE, HBV, SLE, Sjogren, NHL, CLL
- No cryoglobulins: endocarditis, abscess, shunt nephritis, viruses
Type 2
- Alternate complement pathway
- Intramembranous dense deposits – ribbon like thickened cap wall
Type 3
- - Discrete deposits in mesangium/subepithelium
Acute severe
nephritis
SLE
RPGN (many causes)
ANCA + (PAN, Wegener, Churgh-Strauss)
Some HSP
Anti-GBM dz
Nephrotic sy DDx:
MCD, FSGS, MPGN, Membranous
Congenital: Inf (TORCH, HIV, HBV), DenysDrash (WT1 mut), Pierson sy (LAMB2 mut)

1. proteinuria = >3+ on UA (not definitive); >1g/m²/day [>3.5g/d in adult]
Urine Pr: Cr >200mg/mmol on a first morning sample
2. hypoalbuminaemia (<25g/L)
3. generalised oedema
4. thrombotic disease (loss of factors), hyperlipidaemia (↑hepatic lipoprotein synth)
5. loss of Ig, reduced vaccine take, risk w encapsulated orgs
6. malnutrition, loss of TBG and other relevant proteins

PATHOPHYS: usually problem with podocyte function or endothelial/GBM/podocyte interface

MX
- low sodium diet to reduce oedema
- ACEi
- steroids (start at 60mg/kg/m2/day)

SAFE TO START STEROIDS WITHOUT BIOPSY
- age 2-12, no macrohaematuria, normal BP/Cr, no systemic dz

STEROID RESPONSIVENESS = better indicator of long term outcome vs histology
- 95% will achieve remission after an 8wk course of pred (60mg/m²/day x 4 weeks, then 40mg/m² alt
daily x 4 weeks)
- in minimal change - 75% achieve remission by 2 wks

STEROID RESISTANCE: no remission within 4 weeks→ biopsy (likely to be FSGS)
1. levamisole: antihelminthic, immunomodulator, useful for freq relapses; SE = neutropenia, rash,
vasculitis
2. cyclophosphamide
3. calcineurin inhibitors (Cyclo or tac)
4. MF
5. rituximab

SIGNS OF HYPOVOLAEMIA
Ur Na < 10mmol/L
↑ Hb, ↑ PCV

IV FLUIDS
IF shocked - give 4% albumin 10mL/kg and NO diuretics
No shock - consider 20% albumin infusion ± diuretics, give 5mL/kg (1g/kg) over 4-6h
Albumin not given for hypoalbuminaemia alone

HYPERTENSIVE EMERGENCY
give nifedipine 0.25-0.5mg/kg/dose
persistent HTN: amlodipine
look for features of hypovolaemia + give volume resus if present

DIURETICS
if overloaded - frusemide 0.5-1mg/kg daily or BD
IV frusemide 1mg/kg for emergency Mx

INFECTION
= main cause of death
loss of complement + Ig
high risk esp of ENCAPSULATED orgs
cellulitis: give 20% albumin + frusemide along with ABx to reduce oedema
VZV: treat aggressively with IV aciclovir then PO valacilovir. If exposed - give VZIG. Shingles also
gets IV aciclovir (d/t immunocompromise)

RENAL VEIN THROMBOSIS
d/t loss of proteins e.g. AT-3 (anticoagulant), plus hypovolaemia
CLUES: ↓Hb/PLTs, macrohaematuria, ↑Cr, HTN, palpable firm kidney
prophylaxis (LMWH) only in severe NS or of other RF

MEDICATIONS
Pred 60mg/m²/day x 6/52 then wean
Penicilin prophylaxis if asplenic, or other RF e.g. ATSI
Consider PPI to protect vs steroid gastric irritation
Consider anticoag prophylaxis in v. severe nephrotic sy

VACCINES
give all vaccines + 24ppv

DIET
low salt
normal protein (not high)

RELAPSED DZ
often d/t intercurrent illness
restart pred
2nd line: no data - cyclophosphamide, ciclosporine, MMF, rituximab

ARF, ATN, TIN

CKD
STAGE DESCRIPTION GFR (mL/min/1.73 m
2
)
1 Kidney damage with normal or increased GFR >90
2 Kidney damage with mild decrease in GFR 60-89
3 Moderate decrease in GFR 30-59
4 Severe decrease in GFR 5-29
5 Kidney failure <15 or on dialysis

ATN Ischaemic or
Toxic: heavy metals, drugs (gent, NSAIDs, antivirals, diuretics, iodine, pesticides)
PCT: flat, ↓brush border, necrosis, sloughed cells obstruct tubule
Brown/orange casts = key feature (myoglobin/haemoglobin)
CLIN: loss of conc ability; oliguria (epithelial loss – can‟t excrete water etc.), diuresis
in recovery
TIN DEF: inflammation of interstitium with lymphocytes
CAUSES: idiopathic, infection, hypersensitivity, drugs (ABx, AEDs, loop/thiazide
diuretics), immune (IgA neph, SLE, sarcoid), Tx rejection, lymphoma.
LM: eosinophils if HS. Inflammation. Normal glom
CLIN: HS: ~15d post exposure → triad of fever, rash, arthralgia, with ↑Cr.
Otherwise: polyuria, HTN, proteinuria
IX:
Eosinophilia, eosinophis/WBCs on UA, ↑Ur/Cr, WC casts, haematuria, proteinuria
Radiolucent: cysteine, xanthine, uric acid (hence non con CT)
Stones management

Hypercalciuria
- Reduce dietary Na⁺
- Normal dietary Ca intake
- Thiazides (reduce Ca excretion)
- K+ citrate
- Neutral phosphate
Hyperoxaluria
- Reduce dietary oxalate
- K+ citrate
- Mg, neutral PO4, pyridoxine
Hypocitric acidura: K+ citrate, bicarb
Hyperuricosuria: alkalinize urine; allopurinol
Cystinuria: reduce Na intake; alkalinize urine

Tubular transport defects
Bartters Gitelmans LIddle
NKCC2 (frusemide site)
Or other – ROMK, combined Cl ch
NCCT (thiazide site) ENaC (amiloride site)
Hypokalaemic metabolic alkalosis Hypokalaemic metabolic alkalosis Hypokalaemic metabolic alkalosis
Dehydration, polyuria, FTT, stones
±SNHL, FLK
Milder symptoms of dehydration Severe hypertension, FTT, polyuria
↑ urine K, Cl, Ca, PGE2
↓ serum K, Cl, Mg (20%)
↑ urine Cl, Mg
↓ urine Ca
normal urine PGE2

Activation of RAA axis (↑Na delivery
to DCT)
Activation of RAA axis Supression of RAA axis
(↓renin/aldosterone)
“Pseudo-Bartter” = CCD, which has
faecal Cl < 90
DDx: RAS, where renin may be ↑,
aldosterone ↑; or
hyperaldosteronism where renin ↓,
aldosterone ↑

Post Renal Transplant Complications

Hypertension In 80% of those w decreased donor, 60% post living
CMV 1-6mo post Tx
Pneumonitis, GI dz (oesophagitis, gastro), hepatitis, pancreatitis
EBV Reactivation usually ASx
PTLD (polyclonal B cell expansion)
Mx: decrease immunosuppression. Use rituximab
BK virus Ubiqutious, found in uroepithelium
5% will get BK nephropathy, of which 50% get graft failure
Hyperacute rejection Within hours
D/t pre-formed Ab against donor antigens e.g. HLA, Abo
Irreversible → nephrectomy
Accelerated acute 1
st
week
T cell mediated
Mx = anti-T cell Abs, CTS
50% salvaged
Acute Tubulointerstitial cell rejection
1-2 week
2
nd
most common after chronic
T cell mediated w tubular injury
↑Cr + HTN = rejection til disproven. Other: fever, malaise, oliguria, tenderness
mx: CTS, anti-T cell Abs
Chronic >3mo
T cell mediated
Involves tubules, capillaries, intersitium
Main cause of allograft loss
Small kidneys
Reduce risk of rejection Younger age, HLA matching, use induction immunosuppression
GVHD Rare after renal Tx

Metabolic Ix Summary

FBC: looking for cytopenias [organic acidaemias] or evidence of sepsis/infection as a trigger
ABG: high anion gap suggests organic acidaemia; resp alkalosis suggests UCDs

BG: hypoglycaemia typical of FAODs or other dz of ketogenesis, GSDs and DCM e.g. disorders of fructose
metabolism
Ammonia: high in UCDs+++, also in organic acidaemias
EUCs, BUN: calculate anion gap, hyponatraemia/hyperkalaemia suggests salt wasting
Uric acid: high in pts with GSD, can be abnormal in chronic IEM (low in purine metabolism, raised in Lesch-Nyhan)
Ketones: HIGH in amino acidopathy, organic acidaemia. LOW in FAOD, hyperinsulinaemia. Normal in UCDs
Hypoglycaemia + ketosis = GSD (can't use glycogen but can make glucose), organic acidaemia, MSUD
Hypoglycaemia WITHOUT ketosis: FAOD, disorders of ketogenesis (HMG-CoA lyase def)

Galactosaemia – LOW ketones

Immunology

Post Transplant Complications (General)

Timing Week 1-2:
- Ultra-rapid or acute rejection (T cell mediated –
fever, hypertension, ↑Cr)
- N&V, mucositis, diarrhoea
- VOD (1-3 weeks)
Week 2 – 3months
- Acute GVHD (T cell mediated)
- Viral hepatitis reactivation
- CMV (highest risk = 2-3mo post Tx)
- N&V, diarrhoea from drugs, infection

>Day 100
- Chronic GVHD
- Chronic rejection

PCP Low grade fever, ↑RR, non-productive cough, can be
insidious

CXR: bilat perihilar interstitial infiltrates
HRCT: ground glass opacities in central lung

DX: need microscopy of lung fluid e.g. BAL, biopsy
?black on silver stain

MX: bactrim

CMV post
BMT
greatest cause of transplant failure
timing: 1-3 month post transplant (i.e. NOT EARLY)
can be asymptomatic
pneumonia 80-90% mortality
hepatitis
colitis
fever, encephalitis, retinitis, BM failure
15% get pneumonitis
overall 15-20% mortality
Highest risk time = 2-3mo post Tx
VOD Onset: 1-3 weeks post BMT
?Endothelial cell problem  obliteration of
venules/sinusoids  hepatocellular necrosis  fibrosis
throughout liver

Sx: hepatomegaly, RUQ pain, jaundice, ascites, no fever

TA-GVHD 1-2 weeks post transfusion
Fever, rash, diarrhea, pancytopenia, deranged LFTs
Unlike BMT-GVHD, TA-GVHD leads to marrow aplasia,
mortality > 90%

Cause: R is HLA heterozygous, D is homozygous

Ix: skin biopsy, HLA

Mx: supportive, CTS

Prevention: γ irradiation of blood e.g. PLTs (stops
proliferation of WBCs)

GVHD RF: HLA mismatch, unrelated donor, older age

Timing: 2-3 wks post Tx (>100d = chronic)

PATHOPHYS: conditioning ↑ host cytokines/MHC
upregulation → activation of donor T cells → inflame

GIT: “crypt cell necrosis”
Liver: “vanishing bile ducts”

Clin:
1. Rash (erythematous MP, palms, soles, nape,
trunk)  bullae, desquamation
2. GIT: secretory diarrhea, haematochezia,
cramping, PLE, N&V
3. ↑ conjugated bili, ↑ALP, cholestasis (bile duct
epithelium damaged  cholangitis)

Immunosuppressants

Glucocorticoids Block TNFα, IL2, IL6, T cells, IFN-γ
Arrest cell cycle
Cyclosporin Binds immunophili/cyclophilin & inhibits calcineurin phosphatase
Inhibits IL-2
SE:
 Hypertrichosis
 Gingival hyperplasia
 Coarse facies
 Hypertension
 Seizures/CNS
 Hypomagnesaemia
 Hyperlipidaemia
 Nephrotoxic (ARF, TIN)
 No myelotoxicity
 Levels will ↓ with CYP inducers, ↑ with CYP inhibitors
Tacrolimus More potent than cyclosporine
SE:
 Tremor
 Hyperglycaemia
 Hypertension
 Hypomagnesaemia
 Post-Tx lymphoproliferative sy
 Alopecia
 Nephrotoxic
 Hyperkalaemia
 ↓ wound healing
 NO: cosmetic se, NO hyperlipidaemia
Sirolimus MTOR inhibitor
Blocks cytokine driven cell proliferation + maturation
SE:
 Thrombocytopenia
 Hyperlipidaemia
 PTLD
Antiproliferatives e.g. AZT, MMF Inhibit DNA synthesis
AZT:
 Converted to 6-MP, requires TPMT (thiopurine methyltransferase)
 10% of population don‟t have TPMT
 Blocks protein synthesis w fraudulent base
 SE = BM suppression, liver damage, PTLD
MMF
 Antimetabolite; prodrug of pruine synthesis inhibitor
 Prevents B and T cell activation
 SE: leukopenia, anaemia, infection, ARF, gastritis, diarrhoea, PTLD
Anti-TNFα e.g. infliximab TNF secreted by TH1 cells
Used in Crohn‟s, psoriatic arthritis
SE:
 TB reactivation (therefore always test)
 Nausea
 Allergic reaction
Methotrexate Folate antagonist
SE:
 Transaminitis
 N&V
 Renal toxicity (precipitates in tubules)
 Some haem toxicity
 Hypersensitivity pneumonitis
 Neuro: encephalopathy (resolves)
 Derm – 15% get rash
Anakinra Anti-IL-1 antibody
Sulfasalazine MOA unknown
Basiliximab IL-2 antagnost
Can prevent acute transplant rejection
SE = hypersensitivity to it
Imatinib Used in CLL with Philadelphia chromosome

T cell summary

Th0 Immature T helper (CD4) cell
Th1 Differentiation triggered by IL-12, IFN-γ
Interacts with MHC/HLA 2
(NB: CD8 cells interact with
MHC/HLA1)
Produces IL-2, TNFα
IFN-α: activates macrophages, stimulates B cells to make Ab
TNF-ß: activates neutrophils
Targets virally infected cells, intracellular pathogens
Th2 Differentiation triggered by IL-4, IL-2 Triggers B cells to produce IgE
IL-3: mucus production
IL-5: activates eosinophils
Produces IL-4,5,7,10,13
Ab mediated immunity; extracellular parasites; asthma;allergy
Th17 Differentiation triggered by TGF-ß, IL-6 Produces IL-17, IL-21, IL22
IL-17 stimulates IL6,8 + neutrophil recruitment
Implicated in Crohns + other autoimmune disease
Extracellular bacteria, fungi, autoimmunity
T-reg Differentiation triggered by TGF-ß, IL-12 Produces TGF-ß, IL-35, IL-10
Involved in immune tolerance, regulation of immune
response

Immune cells + cytokines

Released by Actions Drugs
IL-1 Macrophages
Monocytes (which △
into DCs or
Pyrogen
Pro-inflammatory
Activates lymphocytes, leukocyte
IL-1ß = anakinra
Used in inflammatory disorders
macrophages)
DCs
Regulates haematopoeisis
IL-2 TH1 cells
NK cells
Drives cell division
T cell growth factor
Targeted e.g. by steroids,
calcineurin inhibitors
IL-3 Released by activated T
cells
Stimulates BM
IL-4/IL-13 Th2 cells, CD8 cells,
mast cells, basophils
Stimulates IgE class switching
IL-5 Th2 cells, eosinophils,
mast cells
Differentiation of eosinophils
IL-6 Monocytes, Th2 cells Production of plasma cells
Inflammation
Pyrogen

IL-12 Activates NK cells
Inhibits IgE response

macrophages
↑vasc permeability, fever, shock, CD8
killing
SHOCK

Interferons IFNγ made by Th1 cells Antiviral, anti-tumour
↑macrophages/NK cells
IFN α/β: protects cells adj to viral
cells e.g .use in hepatitis
IFNγ enhances specific + innate
immunity

OTHER COMPONENTS
Opsonins IgG bound to antigen
C4b + its fragments
Neutrophil
chemotaxis
C5a, LTB4, IL5, Il8
PAMPs Pathogen assoc. molecular patterns e.g. LPS
Recognised by APCs (e.g. by TLRs)
TLRs Bind PAMPs, act via NF-kappa-beta
Involved in sepsis
MBL “universal antibody”, opsonin
ON activation, cleaves C1r and C1s
NK cells Granular lymphocytes, 5-15% of blood lymphocytes
Initial response to virally infected cells
CD56/16 pos, CD3 negative
Deficiency  herpesvirus infections
IL-15 triggers development
BM derived (non-thymic)
Kill cells which have lost their MHC expression e.g. d/t virus, tumour
Release IFNγ to activate macrophages
Kill via performin-granzyme or Fas pathway (induction of apoptosis)
Eosinophils Have IgE receptor
Target helminths via degranulation + release of toxic proteins

Hypersensitivity

Type 1 Antigen + IgE → mast cell, basophil
activation → histamine/leukotriene release
→ urticarial, bronchospasm, anaphylaxis

mediated by Th2/IgE/mast cells
e.g. anaphylaxis
Confirm with tryptase

Late phase: mediated by eosinophils + neutrophils
Type 2 IgG/IgM/complement mediated – cytotoxic
Ab reaction
IgG or IgM recognises antigen → coats cell
→ recognised by complement → destroyed
e.g. AIHA
Transfusion reaction
Goodpastures (anti-GBM disease)
Haemolytic disease of newborn (anti-Rh)
Autoimmune thrombocytopenia
Type 3 Insoluble immune complexes e.g. serum
sickness, RA, SLE
Mostly IgG, some IgM
Sx 1-3 wks after last dose
e.g. SLE, GN, serum sickness (cefaclor)
Type 4 T cell mediated, delayed
Th1, Th17, CD8 cells
e.g. allergic contact dermatitis, Mantoux test, drug
exanthems

Haematology

Approach to positive DAT

VWD vs Haemophilia A

Diamond
Blackfan
Macrocytic
Retics ↓
HbF↑
BM: ↓ RBC precursors
Craniofacial, thumb
abnormalities
Mx: CTS
TEC Normocytic TEC vs IDA: check MCV: low
PLT normal or ↑
~2yo at onset
in IDA, but normal/high in
TEC

Mx: nil
Parvovirus B19 Retics ↓
LM of BM: nuclear inclusions, loss of erythroid precursors
Mx: transfuse if needed
Anaemia of
chronic disease
Low serum iron
normocytic, normochromic
Low retics (or normal)
High WCC common
TIBC normal or low (vs IDA: high)
Ferritin may be high (APR)
BM: ↑ haemosiderin
May have concurrent IDA
Mx = control disease, EPO
Anaemia of
renal disease
TIBC normal
Fe studies normal
EPO low
MCV normal
Retics normal or low

Physiologic
anaemia of
infancy
@ age 2-3mo
Megaloblastic
anaemia
High MCV
hypersegmented PMNs
BM erythroid hyperplasia
Giant vacuolated metamyelocytes (megaloblasts)
Retics low
Nucleated RBCs
Normal Fe
LDH ↑↑ (marks ineffective erythropoiesis)
Goats milk is folate deficient
Folate def in coeliac,
diarrhea, phenytoin, MTX

B12 deficiency e.g. deficiency
Pernicious anaemia – IF deficiency e.g. atrophic gastritis
HIGH MCV
Hypersegmented neutrophils
Hypercellular BM
LDH high

schilling test: give labeled
BV12 to check its absorption
+ exc in urine
Sideroblastic
anaemia
Impaired haem synthesis  iron ring around nucleated RBCs
Pearson sy = variant with hypoplastic anaemia
Congenital form
Acquired forms e.g. idiopathic, drugs,

Haemolytic
anaemia
Retic index
normal is 1
Acute HA: 2-3
Chr HA: 4-6
↓ RBC survival time
↑ indirect bilirubin
↓ haptoglobin
↑ urobilinogen
Hct low if severe

Spherocytosis Hb normal or low
MCV normal
MCH high (d/t less membrane)
HyPERchronic, microcytic, LESS central pallor than normal
Usually >15-20% of RBCs are spherocytes
Retics present – polychromatophilic
BM: eythroid hyperplasia
XR: marrow expansion
Haptoglobin: LOW (binds to free Hb)
Pigment gallstones
Osmotic fragility test
RBC membrane protein electrophoresis
DNA analysis
DAT NEG
Indirect bili UP
Mx
?splenectomy for all or >5y
folic acid
PO penicillin after
splenectomy + vaccinate
against encapsulated
organisms
Elliptocytosis Abnormal spectrin (vs spherocytosis: abnormal spectrin &
ankyrin)
Anaemia, jaundice, splenomegaly
Elongated RBCs
High retics
BM: erythroid hyperplasia
Indirect bili Up
Protein separation + analysis: cells lyse @ 45-46 degrees

PNH

RBCs susceptible to complement mediated damage
60% have BM failure (panycotpenia)
Also get thrombosis
Mx: CTS
Anticoagulaiton
HA
BM failure
Thrombosis
Ham test (alternate complement pathway), sucrose lysis test
(classical pathway)
Haemosiderinuria  Fe loss
Flow cytometry
Thalassaemia

Cardiology

Formulae + physiology
Bazzett formula QT
_____
R R

Use preceding RR

Should be < 0.49s in infants, < 0.44s in older children
Fick principle Works out CO when given O₂ consumption
CO (in L/min) = VO₂ (in mL/min) / (arterial sat) – (venous sat)
Poiseulle‟s law Calculate PVR:
P1 – P2 (pressure difference) = flow x resistance
∴ PVR = (mean PA pressure – LA pressure)/pulmonary flow
Inotropes summary of receptors:
 presynaptic α₂ - negative feedback for norad
 post-synaptic α₁ - INOTROPIC (contractility e.g. septic shock, arrest)
 post-synaptic α₂ - vasoconstrictor (e.g. anaphylaxis)
 β₁ : positive inotropic, chronotropic, dromotropic (↑AV conduction)
 β₂ : vasodilation of vasc sm muscle

KEY: think α₁ /β₁ are similar (both inotropic, β₁ is chronotropic + dromotropic), α₂ /β₂ are
opposites (vasoconstriction vs vasodilatation)
dopaminergic Ⓡs:
- peripheral D1 receptors: vasodilatation of renal, coronary and mesenteric circulation. also
natriuretic
- presynpatic D2 receptors: inhibit norad release

INOTROPES MOA:
activate cardiac β₁ Ⓡs + ↑cAMP via G protein → ↑ opening of L-type Ca2+ channels → more Ca
influx → more forceful contraction

- acts on α, β₁ , β₂ , NOT dopaminergic
- low dose = 2nd line inotropic (e.g. in sepsis - EXAM QN)
- high dose = vasopressive e.g. anaphylaxis, arrest

- acts on α, β₁ , less so on β₂ , nil on dopaminergic

ISOPROTENEROL
- acts on β₁ , β₂

DOPAMINE: dose dependent
- low dose: ↑ renal perfusion (dopaminergic Ⓡs)
- intermediate: cardiac stimulation, renal vasodilatation (β₁ , dopaminergic)
- high dose: vasoconstriction, hypertension (α)

DOBUTAMINE
Stimulates β₁ i.e. inotropic/chronotropic only
weak β₂ effect

Cardio clues

Infarct patterns LMCA: STE in aVR

INFERIOR
- RCA occlusion

LATERAL
- LCA (left circumflex)
- I, aVL, V5, V6

ANTERIOR

POSTERIOR
- RCA
- reciprocal changes in ant leads, esp. V1

LUSB murmur
(pulm area)
PS: harsh systolic murmur, wide split S2, click/thrill
ASD: fixed split S2, mid-systolic murmur, ±heave
PDA: continuous LUSB murmur
VSD: can cause LUSB or LLSB murmur. Small: murmur stops early. Large: pansystolic. Very
large: no turbulence, no murmur
LLSB (tricuspid
area)
VSD
Still‟s murmur: musical/buzzing, diminished with standing, mid-systolic, soft
HOCM: mid-systolic murmur, ↑ with valsalva, ↓ with handgrip, laterally displaced
TS: mid diastolic murmur, assoc with ARF
Mitral area (apex) MS: mid diastolic murmur, assoc with ARF
MR: pansystolic, assoc. with Marfan‟s, EDS
AR: mid-diastolic, with bounding pulses, can cause relative MS
Pansystolic murmur VSD
MR
TR
Continuous murmur PDA (machine line, check below L clavicle)
Venous hum: R subclavian, resolves when supine
AV fistula
Late systolic
murmur
MVP
Early diastolic
murmur
AR (3
rd
LICS)
PR (3
rd
RICS)
Mid diastolic
murmur
Turbulence across MV/TV
MS, TS, atrial myxoma, L->R shunt, Austin flint (AR with regurgitant jet causing diastolic
murmur)
Bounding pulses PDA, AR, LR shunt e.g. large AVM (e.g. V of Galen), truncus
Fixed split S2 ASD (usually)
Occ. Another L-> R shunt that increases flow across PV
Wide split S2 = delayed PV closure
pulmonary stenosis
RBBB (slow to move)
Paradoxical split S2 S2 splits in expiration rather than inspiration
d/t very delayed AV closure, e.g. AS, LBBB
Prostaglandin
infusion
INDICATIONS (duct dependent CHD):
2. Inadequate PBF e.g. PA + IVS, TA + IVS, critical PS
3. Inadequate systemic BF e.g. critical CoA, interrupted arch, HLHS
For duct-dependent lesions: aim sats 75-85%

CHF by age
Newborn with cardiomegaly, tachypnoea,
hepatomegaly
5 “A”s – AV valve (Ebstein‟s), AV block, AVM, Anaemia, Arrhythmia
0-4wk w ↑HR, ↑RR, hepatomegaly HLHS
TGA
TAPVR
AV fistula
Critical AS/PS
Coarctation
1-4mo: ↓feeding, ↑RR, FTT, sweating,
hepatomegaly
Large L→R shunts (VSD, PDA, AVSD)
SVT

ECG S2 Murmur CXR Other
D-TGA normal single or split none or sys – from
LV (pulm) flow
egg on string
↑PBF
Cyanosis (mixing), ↑w
PDA closure
Mx: balloon septost.
L-TGA abnormal p
waves
abnormal Q in 3,
aVF, aVR, V1
upright TW in
precord.
heart block
none
RVH strain
single long loud ESM
LUSB
Boot shaped
↓ PBF
<6m: BT shunt to ↑
PBF (subclav-PA)
>6m: corrective

single loud Ø unless VSD ↑PBF
cardiomeg
↓ sats then pulm
oedema
↓LV forces
Norwood (PA→Ao;
palliative)
Glenn: SVC→PA
PA-IVS 30-90
LVH
RAE
single sys cardiomeg +
RVH
RAE
single or split ESM LUSB (2
nd
/3
rd

LICS) ± click
cardiomeg ± post
sten dilat.

RAE
split sys ⓝor cardiomeg
(snowman)

Obstructed TAPVR: cyanosis, ↑RR, ↓ response to PGE
Incomplete obstruction: CHF, pulm HTN
NO obstruction: L→R shunt, mild/no cyanosis, no pulm HTN
Tricuspid
atresia
LVH
RAE
single sys cardiomeg Need ASD for R→L
BT shunt, Fontan
(RA→PA)
Truncus
arteriosus
LVH, RVH, BVH
single sys/±dias cardiomeg, R Ao
arch in 50%
“torrential” PBF
Ebstein's RAE + RBBB =
classic
± WPW (40%)
split sys
cardiomeg+ Early cyanosis
Prostaglandin
AS ⓝor LVH, mid-sys RUSB ⓝor prom LV,
post sten.
dilatation

CoA RVH/RBBB in
infants
(obstructed/sym
patomatic type)
Older: LVH
Single, loud Ø in 50%
or ESM (b/w
scapulae)
cardiomeg
↑PBF
± lower postductal
sats
Alcapa ↓Q I, aVL usually ø cardiomeg Angina 2-3mo
± RBBB
sup axis
fixed split ESM LUSB (flow) cardiomeg
↑PBF
↑ pulm a.
mx: close age 4-5y or
when Qp:Qs > 2:1
VSD ±RVH ⓝor loud PSM (small)
short SM (small)
ø murmur (large)
parasternal thrill
±cardiomeg
(large)
↑PBF

PDA RVH sys LSB
older: cont <clav
cardiomeg if large

↑ PBF: TGA, TAPVR, truncus [all have lots of flow]
↓PBF (oligaemia): TOF, PA-IVS, PS, TA, Ebstein‟s [all R heart obstruction]
↑ pulm venous congestion: HLHS, TAPVR

vc = venous congestion

Higher preductal sats: pulmonary HTN (e.g. mec asp, CDH - >5% difference from pre- to post- due to RL shunt),
↓ sys pressure e.g. AS, CoA
Higher post-ductal sats: TGA with CoA

key points:
- max LV volume is at end of isovolumetric contraction

Endocrinology

Hormones
MOA: bnds G-protein coupled receptors: V1 in liver (glycogenolysis, vasoconstriction), V3 (ant pit
↑ACTH), V2 basolat membrane of CD cells → G protein dissociation → adenylate cyclase activation →
↑cAMP → protein kinase 4 activated → aquaporin 2 inserted
↑ release with:
 Osm > 283
 8% ↓ intravasc volume
 25% ↓ BP
 nausea, pain, hypoglycaemia, stress, alcohol
↓ release with
 glucocorticoids

Rickets

Type Ca PO4 ALP PTH 25
OHD
1,25
(OH)2D
Urine
calcium
↓Ca
rickets
Vitamin D deficient
rickets
↓ or N ↓ or N ↑ or ↑↑ ↑ ↓ ↑ or N* ↓ or N
Vitamin D
dependent rickets
type 1
↓ ↓ or N ↑↑ ↑ N ↓ ↓
Hereditary vitamin D
resistant rickets
(vitamin D
dependent type 2)
↓ ↓ or N ↑↑ ↑ N ↑↑ ↓
↓ PO4
rickets
hypophosphatemia
N ↓↓ ↑ N or sl↑ N N or ↓ ↓
Hereditary
hypophosphatemic
rickets with
hypercalciuria
N ↓ or ↓↓ ↑ N or ↓ N ↑ ↑
Nutritional
phosphate
deprivation
↑ or N ↓ ↑ or ↑↑ ↓ or N N ↑ ↑ or N
Calcipenic rickets refers to disorders in which intestinal absorption of calcium is too low to match the calcium
demands imposed by bone growth.
* In vitamin D deficient rickets, 1,25(OH)2D usually is increased or normal. Occasionally, it may be deceased.

Vitamin D deficiency Inadequate stores, nutritional, sun,
Mx = vitamin D
Serum: ↓ 25-OHD, ⓝ/↑ 1,25-OHD, ↓Ca,
↑PTH, ↓PO4, ↑ALP
Urine: ↑PO4 (need vit D to reabsorb it),
↑Ca
Type 1 vitamin D
dependent rickets = 1-α
hydroxylase def
Low 1α reductase
Mx = high dose vitamin D
Serum: ⓝ25-OHD but ↓1,25OHD,
otherwise similar picture to vitamin D
deficiency, Ca ⓝ/↓, PTH ⓝ/↑
Type 2 vitamin D
dependent rickets = XLD
hypophosphataemic rickets
= vitamin D resistant
rickets
Kidneys can‟t reabsorb PO4 → ↓
conversion of 25-OHD to 1,25-OHD
Females get fasting hypophosphataemia

Mx = vitamin D, phosphate
ⓝPTH, ⓝCa, ↓PO4, ↑ ALP, ↓/ⓝ1,25-
OHD (usually low PO4 would upregulate
1,25-OHD)
Urine: ↑PO4
Renal osteodystrophy PO4 retention → binds Ca → hypoCa →
stim PTH
Also, renal damage → 1α hydroxylase
falls → worsening hypoCa 2° hyperpara,
trying to ↑Ca → bone resorption
Autonomous (tertiary) hyperpara

Hypoparathyroidism Autoimmune, absence, 22q11.2, CASR
mutation (see below)

Familial hypercalciuric
hypocalcaemia
* Ca sensing ® mutation Serum: ↓ PTH (since thinks Ca is high),
↓Ca,
Pseudohypoparathyroidism e.g. Albright hereditary osteodystrophy =
resistance to PTH function
↑ PTH, ↓Ca, ↑ PO4 (PTH isn‟t working)
Fanconi syndrome Renal phosphate wasting 
hypophosphataemia  ↓ △ 25-OHD to
1,25-OHD

T1DM autoantibodies

Islet cell antibodies (ICA) Positive in 80-90% with new dx T1DM
Insulin autoantibodies (IAA) Positive in 30-40% with new dx
After Rx, all pts will develop these
Appears 1
st

Anti-GAD antibodies Present in 80% of newly dx (most likely
to be found in newly diagnosed?)
Appears 2
nd

IA-2 antibodies (insulinoma
assoc)
Present in 60%
Anti-21-hydroxylase Abs 1.7% of pts
Significance

1 pos → 30% get DM
2 pos → 70% get DM
3 pos → 90% get DM
Higher risk with ↑ titre

Thyroid disease

Hashimotos
autoimmune lymphocytic infiltration -
-> goitre

90% anti-peroxidase Abs
70% anti-thyroglobulin Abs
initial rise in thyroid stimulating Abs
Graves Thyroid stimulating antibodies
Neonatal dz Maternal Hashimotos → thyroid blocking antibodies cross placenta [rarely can
cause thyrotoxicosis from stimulating antibodies]
Maternal Graves Thyroid stimulating Abs  neonatal transient
hyperthyroidism
Thyroid scan
results
Thyroid agenesis (85% of
congenital hypothyroidism)
Cold scan
Fetal radioiodine exposure ↓ uptake, small thyroid
Maternal lithium in pregnancy Cold scan (lithium competes w iodine)
Thyroid organification defect
(dyshormogenesis)
Normal or ↑ uptake in normal or enlarged thyroid
Untreated maternal Graves‟ Cold scan

Rheumatology – Antibodies

ANA TESTING:
Staining pattern - correlates to different disease but many confounders e.g. speckled =
smith, RNP, Ro, La.
Rim pattern = ds DNA

Titre: low is < 1:80, high is > 1:640
normal is less than 1:40
titre refers to dilutions until no Abs detected

Drug induced lupus (100%)
SLE (93%)
Mixed CT disease (90%)
Scleroderma (85%)
Oligoarticular JIA (70%)
Polymyositis/dermatomyositis (60%)
Sjogren‟s (50%)
Rheumatoid arthritis (40%)
Discoid lupus (15%)
Other: Hashimoto‟s, Graves, autoimmune hepatitis, PBC
Anti ds-DNA Specific for SLE
Best to monitor disease activity: more sens/spec than C3/C4
C4 drops more than C3 – also reflects flare
Anti-histone Drug induced lupus
ENA: Anti-SM Most specific for SLE, but only pos in 25%
ENA: anti-Ro/La Sjogrens
40% of SLE
Discoid SLE
Neonatal SLE:
 Ab ransferred between wk 12-16 of gestation
 90% have anti SSA, also SSB, U1-RNP
 Annular scaly rash, haemolytic anaemia, TP, neutropenia, congenital heart
block, HSM, jaundice
Anti U1-RNP Pos in 10% of SLE
Pos in other mixed CT disease
Anti-Scl-70 Scleroderma
Antiphospholipid Ab Lupus anticoagulant (doesn‟t correct on mixing studies, causes A/V thrombosis)
Anticardiolipin
Anti ribosomal P SLE
99% spec, only 21% sens
assoc with depression + psychosis
CRP Should be normal in SLE – if not, think sepsis
ESR Correlates with flare of disease in SLE

Oncology – chemotherapy

Chemo by cell
cycle stage
Gap 0 Resting phase (senescence)
Interphase G1, S, G2
Gap 1 ↑ Cell size L-asparaginase (starves cells of this
AA that they can‟t produce)
Synthesis DNA replication Cytarabine
Steroids
Methotrexate
6-MP
Gap 2 Continued cell growth Topoisomerase II inhibitors
Anthracyclines
Mitosis Division into daughter cells
PMAT:
Prophase (DNA condenses, spindle
forms)
Metaphase (chromosomes LINE UP,
spindles attach)
Anaphase (division + migration)
Telophase (membranes form,
cytoplasm splits)
Vincristine
Paclitaxel
Phase non-
specific
Alkylating agents
Antibiotics
Platinating agents
Alkalyting
agents
e.g ifosfamide, cyclophosphamide
MOA: alkylates guanine ∴ inhibits DNA synthesis by forming irreversible cross-links in DNA
Phase non-specific

SE:
 AML
 TCC
 Haemorrhagic cystitis (prevent w mesna)
 Pulmonary fibrosis
 Delayed puberty
 Infertility
 Ifosfamide: Fanconi sy
 N&V, dark skin/nails, metallic taste, SIADH, anaphylaxis

Requires hepatic activation ∴ less effective if liver dysfunction
Etoposide Topoisomerase inhibitor (regulates DNA winding)
Gap 2 phase

SE:
N + V
Myelosuppression
Secondary AML [also occurs with alkalyting agents]

Anthracyclines e.g. doxorubicin, daunorubicin, BLEOMYCIN
Gap 2 phase

MOA: prevents DNA double helix from rewinding after unwinding by binding to topoisomerase
II ∴ prevents replication

SE:
N+V
Cardiomyopathy (often refractory) or arrhythmia
Red urine
Myelosuppression
Extravasation injury
BLEOMYCIN - pulmonary fibrosis
Methotrexate MOA: folic acid antagonist; inhibits dihydrofolate reductase
Synthesis phase

SE:
Myelosuppression
Mucositis
Hepatitis
Long term: osteopenia/bone #s
High dose: renal, CNS toxicity
Intrathecal: arachnoiditis, ❉leukoencephalopathy❉
Exudative pulmonary effusion

Result therapy: leucovorin (folinic acid – already reduced ∴ don‟t need DHFR)

INTERACTIONS:
bactrim also inhibits DHFR
delayed clearance with: salicylates, penicillins, ALLOPURINOL
↑ conc with NSAIDs
displaced from protein binding sites by: PHT, salicylates

L-
asparaginase
MOA: depletion of l-asparagine which is an AA that leukaemic cells can't produce, unlike normal
cells
Gap 1 phase

PEG-asparaginase catalyses L-asparagine → ammonia
PEG = polyethylene glycol

SE:
allergic reaction
pancreatitis*** - NB if abdo pain**
hyperglycaemia
PLT dysfunction + coagulopathy
Encephalopathy
Venous thrombosis

Carboplatin,
Cisplatin
alkylating-like agents; no alkyl but do form cross-links
platinum agents
phase non specific

inhibit DNA synthesis

SE:
N+V
renal dysfunction***
myelosuppression
↑ risk leukaemia - which has a poor outcome
ototoxic *** (SNHL)
tetany
neurotoxic
HUS
anaphylactoid
peripheranl neuropathy (vincristine more likely)
seizures

Vincristine Inhibits microtubule formation (spindle stage)
= during mitosis

SE:
cellulitis
peripheral neuropathy
jaw pain
constipation
ileus
Seizures
ptosis
MINIMAL MYELOSUPPRESSION
most likely to cause delayed nausea

Cytarabine Pyrimidine analogue but main action is to inhibit DNA polymerase
AKA cytosine arabinosine, Ara-C
Synthesis phase

'cy' = 'py'rimidine
vs. mercaptoPUrine

Indications: ALL, AML, NHL, HL

SE
N+V, myelosuppression, mucositis, conjunctivitis
Liver dysfunction
CNS/cerebellar dysfunction
Intrathecal complications (arachnoiditis, leukoencephalopathy, leukomyelopathy)
Renal dysfunction

Neurology – AEDs

CARBAMAZEPINE

Blocks Na channels
Narrow therapeutic index
Hepatic metabolism
CYP inducer
#1 SE = MP rash
High risk SJS
Idiosyncratic agranulocytosis
Neurotoxic
Nausea, dizziness
Drowsiness
Ataxia
DRESS (MP rash, exfoliative dermatitis,
oedema, LNs, fever, eosinophilia)
Phenytoin Blocks Na channels
Narrow therapeutic index (?needs most
monitoring)
Hydroxylated in liver
 Saturable system – small △ can →
toxicity
Zero order kinetics
Ataxia
Drowsiness
Gum hypertrophy
Acne
Coarse facies
Hirsutism
CYP inducer
DRESS
Teratogenic (cleft)
Lamotrigine Blocks Na channels Rash in 5-10%
SJS/TEN (1:50-300)
↑ risk SJS with valproate
Dizziness, ataxia, diplopia
GI symptoms
Valproate Blocks Na channels, GABA-ergic
Therapeutic monitoring
CYP inhibitor
Drowsiness
Wt gain
Pancreatitis
Alopecia
Liver dysfunction
Teratogenic (?5% risk major defects)
Phenobarbitone Blocks Na channels
GABA-ergic
Drowsiness, sedation
Tolerance
Sudden withdrawal can → status
Topiramate GABA-ergic
Carbonic anhydrase inhibitor
Nausea, abdo pain, anorexia
Nephrolithiasis
Hypochloraemic met acidosis
Myopia, closed angle glaucoma
Cognitive dysfunction
Wt loss
Vigabatrin GABA-ergic (↓ GABA breakdown) Optic neuritis
Concentric vision loss
Retinal atrophy
Drowsiness
Benzodiazepines GABA-ergic Sedation
Tolerance
Levetiracetam MOA unknown
Partial & generalized seizures
Behavioural disturbance
Sleep disturbance
Psychosis
Gabapentin GABA analogue
Partial seizures
Weight gain
CI in myoclonus
Ethosuximide ↑ seizure threshold (non-GABA), ↓ nerve
conduction in CNS
Absence seizures ONLY
Ataxia
BM suppression

Neurodegenerative diseases – MRI findings

XL ALD Parieto-occipital WM changes (towards the back)
+ may suggest pigment changes, deterioration at school

Metachromatic leukodystrophy Periventricular + deep WM (UMN + LMN signs)

NCL Periventricular rim of mildly abnormal tissue

Krabbe Symmetric ↑ densities in caudate nucleus, thalami
Leigh Deep grey matter symmetric lesions: brainstem, BG, subthalamic nuclei
PKU WM changes, initially central
MSUD Deep gray matter changes + WM
MPS Cortical GM + WM changes

CSF findings in ADEM, MS, GBS, ACA, TM
ADEM Post viral encephalitis, myelitis (weakness, long tract
si.) MRI: BG, thal, brainstem T2 enhancing lesions
CSF monocytic/lymphocytic pleocytosis ± ↑
protein
MS MRI: T2 multifocal lesions in periventricular WM Mild ↑ CSF WCC, IgG1 oligoclonal bands
GBS CSF ↑ protein without pleocytosis
ACA Isolated ataxia, or may have other cerebellar signs CSF not needed – may have ↑WCC
Transverse
myelitis
dysfunction
CSF ↑WCC, ↑protein

Weakness

General clues  Proximal usually muscular (except SMA)
 Distal usually neuropathy (except myotonic dystrophy)
 Muscle hypertrophy common in myopathy
 Distal atrophy/wasting common in neuropathy
 Floppy weak
o Neuromuscular
o ↓ tone, ↓ power, ↓ reflexes
o Myopathy, dystrophy, myasthenia gravis, SMA
 Floppy strong
o Central
o ↓ tone, ⓝstrength, ⓝ/↑ reflexes
o CP, genetic (Down syndrome), metabolic
GBS Symmetric ascending paralysis
Neuropathic pain
↓DTRs
Urinary retention
50%  bulbar involvement
CSF protein ↑ (cells usu < 10)
NCS ↓ CV , dispersion
MRI: thick/enhanced n. roots, thick cauda
equina
CIDP (>2mo) Symmetrical prox & distal weakness
Motor > sensory {glove/stocking}
↓DTRs
Rarely: CN/bulbar
CSF ↑ protein without pleocytosis
CMT Distal weakness 1
st
, calf pseudohypertrophy
↓DTRs distally
Mostly motor, but some sensory involvement
EMG ↓ CV
Normal CSf
Myotonic
dystrophy
Distal > proximal weakness
Normal DTRs/↑
Involves face, tongue, speech

SMA Proximal weakness
↓ DTRs
ⓝface, ⓝcognition, bell-shaped chest
Fibrillation on EMG
Spont AP
Denervation/renervation
Biopsy: alt ⓝ/atrophic muscle

Malformations
Dandy-Walker  Complete or partial agenesis of cerebellar vermis
 with retrocerebellar cyst
 that communicates with 4
th
ventricle
MRI: enlarged post fossa ± absent CC ± polymicrogyria or heterotopia
Chiari 1 Inferiorly displaced cerebellar tonsils through foramen magnum
± hydrocephalus or hydrosyringomyelia
Chiari 2 Small posterior fossa
Tonsils + 4
th
ventricle + brainstem enter cervical canal
Myelomeningocoele
Syringomyelia Cystic cavity in spinal cord, ± communication with CSF
Spina bifida Midline defect of VBs/arches/laminae ± protrusion of SC/meninges (occulta vs
cystica)
Diastematomyelia Bony burr splits cord @ L1-L3

Obstructive hydrocephalus Aqueductal stenosis – dilated 3
rd
+ lateral ventricles, normal 4
th
ventricle
Porencephalic cyst Lined by WM
Schizencephaly Not lined by WM

Neuro injuries

CONGENITAL BRACHIAL PLEXUS INJURIES
Erb‟s palsy C5 + C6
Deltoid, infraspinatus (C5)
Biceps (C6)
Forearm extended
PRESERVED hand/wrist movement
Erb‟s palsy plus C5-C7 Arm adducted, int rotated, forearm extended &
pronated, “waiter’s tip” flexion of wrist/fingers
Flail arm C5-T1 Whole upper limb weak
± Horner sy
Klumpke‟s C8-T1 Isolated hand paralysis + Horner syndrome

Nerve Motor DTRs Sensory Mechanism
Axillary
nerve
teres
minor/deltoid
lateral upper arm (inf half deltoid) surgical neck humerus, ant/inf
shoulder dislocation

Median
C5-T1
LOAF (lat lumb,
OPB, APB,
FPB)
Finger
jerk

#, Colles #, CTS
n.
C7-C8
elbow ext
(triceps,
wrist ext, MCP,
supination
Triceps
Supinato
r jerk

Causes: # humeral shaft, sat night
palsy
Ulnar
C8-T1
Medial 2
interossei,
hypothenar
muscles (claw
hand)

pressure
AIN Thumb IP
flexion
IF DIP flexion
“OK sign”
Supracondylar #
MSK n
C5-C6
Biceps,
brachialis
(elbow flexion)
Biceps
jerk

FEMORAL L2,3,4 Hip flexion, knee extension, knee jerk

OBTURATOR

L2,3,4 (same as femoral)

SCIATIC

L4,5, S1,2,3

Hip extension, knee flexion (opposite of femoral) + all peroneal/tibial
supplied muscles/sensory areas
Splits in mid thigh to common peroneal + tibial
TIBIAL

L4,5, S1,2,3

Supplies plantaris, gastrocnemius, popliteus, soleus, tibialis POSTERIOR,
FDL, FHL, toe muscles
INJURY --> intrinsic foot weakness
**tibialis posterior inverts the foot ∴ in sciatic lesions you can't invert,
but in common peroneal lesions you can
PERONEAL

L4-S2

Superficial peroneaL: peroneus longus/brevis, med/lat cutnaneous n
Deep peroneaL; tibialis ANTERIOR, EDH, EHL
SURAL

originates from branches of tibial + common peroneal
supplies cutaneous innervation to lateral calf + foot
purely sensory

Tracts

PAIN/TEMP

Lateral spinothalamic
Fibres decussate 1-2 levels higher ∴ lesion @ site → contralat loss of pain/temp 2
levels below

LIGHT
TOUGH/PRESSURE

Anterior spinothalamic + medial lemniscus

VIBRATION

Medial lemniscus

PROPRIOCEPTION

Spinocerebellar, medial lemniscus

MOTOR

Corticospinal: decussates @ foramen magnum
Corticobulbar: decussates @ C7 + C12 level

Infectious diseases
Antibiotics

Drug MOA + spectrum of activity NOTES
Aminoglycosides Covers gram negs incl. Pseudomonas
NO gram pos cover
Concentration dependent killing
Nephrotoxic (usually ATN) – 5-7d lag
Ototoxic
Resistance from altered binding sites
Beta-lactams Binds PBPs
GPOs (not enterococcus)
Anti-staph have anti- beta-lactamase
Aminopenicillins have some GNO cover
e.g. E. coli
Ticarcillin/piperacillin are anti-
pseudomonal, anti-anaerobe, and are
combined with a beta-lactamase
inhibitor to maximise spectrum
SE: low incidence „true allergy‟
10% cross-reactivity w cephalosporin allergy
Carbapenems Use for ESBLs e.g. enterobacter (a
GNO)

Cephalosporins Bind PBPs
1
st
gen: strep, staph (not MRSA), some
GNOs (Kleb, Proteus, E. coli – PECK)

2
nd
GPOs, better for GNOs: PeCK,
Haemophilus, Enterobacter, Neisseria
Cefaclor – serum sickness
[HEN PECK]

3
rd
gen: better CNS penetration. Still
covers strep (but some resistance
therefore vanc in meningitis), better
GNO. Ceftazidime covers Pseudomonas

4
th
gene: good GPO and GNO coverage,
good CNS penetration
LIncosamides (e.g.
clindamycin)
Covers most GPOs, good anaerobe
cover, covers MRSA
NOT enterococcus

Macrolides 50S ribosomal subunit, reducing protein
synthesis
Erythromycin: CYP inhibitor, LQTS,
Metronidazole
(imidazole)
Inhibits nucleic acid synthesis (DNA
damage)
Anaerobes e.g Bacteroides, Clostridium,
Gardnerella
Parasites e.g. Giardia (no eosinophilia),
Entamoeba (no eosinophilia),
Trichomonas

Common organisms

Gram positive
cocci
Catalase pos clusters= staph
 Coagulase pos = aureus (grapelike)
 Coag neg = epidermidis, saphrophyticus
Catalase neg diplo/chains = strep
 α-haemolytic (partial/green) = S. pneumonia (capsulated), S. viridans (no capsule)
 β-haemolytic (clear) = S. pyogenes, S. agalactiae
 γ-haemolytic (no haemolysis) = Enterococcus, Pseudopeptostrep
Gram positive
rods
Aerobic:
 Bacillus (spores)
 Nocardia (branching)
 Listeria (motile)
 Corynebacterium
Anaerobic
 Clostridium (spores)
 Actinomyces (branching)
Gram negative
rods
Aerobic: Legionella, Bordetella, Haemophilus, Campylobacter, Pseudomonas, Vibrio,
Escherichia, Klebsiella, Enterobacter, Serratia, Salmonella, Shigella, Proteus
Anaerobic = bacteroides
Gram negative
cocci
Neisseria = bean shaped diplococci
E. Coli gastro EHEC (0157:H7) = shiga toxin, causes HUS. don’t treat with ABx
ETEC: watery secretory diarrhea
Enteroinvasive: inflammatory
Enterohaemorrhagic: inflammatory
Enterococcus Gram pos diplococci (like strep)

Causes sepsis, necrotising enterocolitis

Ampicillin, vancomycin, linezolid, rifampin,
quinolones
NOT cephalosporins
Listeria Gram pos rod

Clues: nodules on placenta, mat fever

Ampicillin, penicillin
Chlamydia C. pneumoniae causes conjunctivitis (>d5),
staccato cough, pneumonia. GNO.
Intracellular anaerobe. Intracytopalsmic
inclusion bodies; PCR. Mx = macrolide

Clostridium Anaerobe, gram pos
C. tetani – tetanus
C. botulinum – infant botulism (inhibits
release of Ach into synapse)
Debridement, tet Ig, metronidazole OR penicillin
Botulism: supportive +/- antitoxin
C. diptheriae Gram pos rod
H. flu “pleomorphic” on gram stain
Strep GP diplococcic (or chains) – blue on stain

Alpha = viridans, pneumonia

Beta:
GAS (pyogenes)
Pharyngitis: ABx do not shorten illness, don‟t
prevent PSGN, but do prevent ARF
- Pharyngitis (risk ARF, PSGN)
- Peritonsillar abscess (deviated uvula;
cover for anaerobes too)
- Retropharyngeal: usually younger,
neck hyperextended (vs tripod in
epiglottitis)
– pyogenes (pharyngitis, oral abscess, skin,
PSGN)
GBS
- Give intrapartum penicillin if: PROM >
18h; previous positive screen in same
pregnancy; unknown status +
complicated OR <37/40

Impetigo (less bullous than staph)
TSS
Enterobacter GNO
Can be ESBL – use carbapenem

Echinococcus Cestode (parasite)
E. granulosus  cystic disease
E. multilocularis  alveolar disease
In kids #1 site = lungs: CP, cough, haemoptysis
#2 = liver – abdo distension, pain, hepatomeg
other: bone
can have anaphylaxis from cyst rupture
US shows fibrous capsule +/- internal
membranes
Bloods show eosinophilia
Mx: albendazole + aspirate if accessible
EBV In B cells
CMV in monocytes
HIV in follicular dendritic cells
Toxin mediated Staph scalded skin
S. aureus phage 11, type 71
Exfoliative toxin  epidermis peels off
Peri-orificial (no intra-oral lesions, vs EB where
there are; also in EB the lesions may be
present at birth)
Benign
Staph toxic shock
TSST1
S aureus phage 1, type 29

Tender erythroderma
Oedema
Late desquamation
oral + genital mucosa red
Can  fulminant shock, multi org failure
10% mortality
d/t suprantigen  >30% T cells activated
Mx: fluclox + clindamycin, IVIG in severe shock
GAS toxic-shock like syndrome
GAS with exotoxin A
Erythroderma
Late desquamation
Sepsis more likely
Oral mucosa involved
30-50% mortality
Mx: benpen + clinda/linco (to improve tissue
penetration) + IVIG if shock
STIs Chlamydia 75% no symptoms
May have urthritis, bleeding
Dx: 1
st
pass urine PCR
Endocervical swab  Culture, IF, NAATs
Mx: azithromycin stat dose, or doxy x 7 days
Gonorrhoea Purulent/copious discharge
Dysuria, bleeding
Dx: urine pCR or endocervical swab
Mx: ceftriaxone IM or IV
PID Polymicrobial
ABdo pain, d/c, bleeding, fever, N&V
Mucopurulent d/c
Mx: ceftriaxone + flagyl + azithromycin
Trichomoniasis Itchy, yellow-green discharge
mx: metronidazole stat dose

Incubation + contagious periods

Incubation Contagious period
Varicella 10-21 days from 5 days before rash appears
until all lesions crusted (~5-7days)
Parvovirus 4-14 days from 7 days before rash appears
until rash appears – then don‟t
need to isolate
HFM 3-6 days (short) from onset of mouth ulcers until
fever is gone
Impetigo 2-5 days (short) onset of sores until has had 24h of
antibiotic (don‟t need to isolate)
Lice 7 days onset of itch until one treatment
Measles 8-12 days from 4 days before rash until 5 days
after rash appears
Meningitis 3-6 days (short) from onset of symptoms and lasting
1-2 weeks
roseola 9-10 days onset of fever until rash disappears
(2 days)
Rubella 2-3 weeks from 7 days before rash until 5 days
after rash appears (similar to
measles)
Scabies ~1 month onset of rash until treatment
scarlet fever 3-6 days onset of fever or rash until 24h
treatment
shingles ~2 weeks onset of rash until all sores crusted
(~7 days) – don‟t need to isolate, just
cover lesions
warts 1-9 months
bronchiolitis ~5 days from onset of cough then for 7 days
colds 2-5 days from onset of rhinorrhoea until
afebrile
cough, croup 2-5 days onset of cough until afebrile
influenza 1-3 days onset of symptoms until afebrile
strep throat 2-5 days onset of sore throat until on ABx 24h
viral sore throat 2-5 days onset of sore throat until afebrile
TB 6mo – 2y until 2 wks on treatment
pertussis 7-10 days from onset of rhinorrhoea until 5
days treatment
EBV 30-50 days from onset of fever until afebrile
viral conjunctivitis

Streptococcal antibodies
ASOT - recent GAS pharyngitis < 2mo
- useful in diagnosing ARF
- rises from 3wk on
- severe strep: only ↑ in 70-80%
- pyoderma: ↑ in 30-40%
- PSGN: ↑ in 50%
- MPGN: ↑ in 20%
Anti-DNAse B

- superior for skin infections, less FPs, longer period of reactivity
- useful in ARF, skin infections and PSGN
- rises from 6-8wk on – stays up for 6-9mo
Anti-hyaluronidase Follows GAS infection + rheumatic fever
Anti-fibrinolysin
(antistreptokinase)
↑ In rheumatic fever + recent haemolytic strep infections

TORCH + other congenital infections

Toxoplasmosis
(protozoan)
1. Chorioretinitis
2. Hydrocephalus
3. Intracranial calcifications (Scattered)

Other: ASx, HSM, ↑LNs, ↓IQ, visual defect, jaundice,
anaemia, ↓PLTs, abnormal CSF findings, seizures,
hearing loss

DIAGNOSIS IN UTERO
1. Serology: IgG/IgM
2. PCR amniotic fluid
3. US: hydrocephalus, IC calcifications, microcephaly,
IUGR, ascites, HS

Acquired 1
st
trimester: 10-25% risk +
more severe
Consider abortion if < 16wk
Acquired 3
rd
trimester: 60-90% risk
but less severe

PREVENT transmission w spiramycin
in pregnancy
If confirmed – use pyrimethamine _
st
trimester
Add leukovorin (folinic acid) to ↓ BM
suppression
Treat infant with
x 1-2y
Syphilis
(spirochetal
bacteria – T.
pallidum)
CLIN - everything

DIAGNOSIS
Mat; VDRL titre, plasma rapid regain
If positive --> agglutination + fluorescent treponemal
1°/2°/early latent disease: 50% risk
Established latent disease: 10% risk

MANAGEMENT
Penicillin x 10 days
antibody absorption tests

Neonate:
- IgM POS in 90% with congenital syphilis
- If antibody titre ↑ 4-fold in 3mo = diagnostic (if mat
Ab, will decline)
- Dark ground microscopy can show organism from
skin, placenta
- Check CSF for evidence of neurosyphilis

HIV PRESENTATION
AIDS defining illnesses:
 PCP (median age 5mo) – perihilar infiltrates
 Lymphoid interstitial pneumonia/pulmonary
lymphoid hyperplasia – older age,
reticulonodular bibasilar infiltrates + hilar
 Recurrent bacterial infections e.g. strep,
staph, salmonella
 Pseudomonas later
 Wasting sy (>10% wt loss, crossing 2
centiles, <5
th
centile)
 Candida oesophagitis
 HIV encephalopathy (DD, microcephaly)
 CMV pneumonia, colitis, retinitis

Dx: Mat Ab will persist for 18mo ∴ check HIV DNA
PCR @ 3-4wk, 1-2m and 4-6m (± @ birth), then
ELISA/western blot @ 18m
Usually hypergamma, 10% hypogamma
↓CD4:CD8 (normal is 2:1)
Lymphopenia
↓ Mitogenic response

Exclude HIV: 2 neg PCRs @ >1mo and >4mo
No treatment: 25-30% risk
With testing, counsellling, ARTs,
LSCS, no BF: <2% risk

Bactrim prophylaxis for PCP

PROG: ø Rx → death by 5
RNA conc predicts prog (so does CD4
count – best used together)

PREVENT
ART in pregnancy; IV zidovudine in
labour; LSCS if ↑ viral load; infant gets
ZDV x 6wk, BF CI

MX: combination ART:
 2x NRTIs (nucleoside
reverse transcriptase
inhibitors)
 PLUS a PI or NNRTI
 NRTI e.g. zidovudine,
lamivudine (neutropenia,
lactic acidosis)
 NNRTI e.g. efavirenz

Give inactivated vaccines
MMR/VZV only when CD4 > 15
HCV (RNA virus),
genotype 1 =
worst
TRANS: blood, sexual, transplacental
CLIN: jaundice rare. Nausea, pain, anorexia, episodic
transaminitis
IX: RNA PCR, HCV Abs after 4-6wk, LFTs, fibrosis on
biopsy
Check baby PCR @ 2mo, anti-HCV @ 18mo (when
mat is gone)

Mum RNA pos → 5-10% risk

↑Clearance if young

α-interferon & ribavirin clears in 50%

CAN breastfeed

Ribavirn SE: haemolytic anaemia,
teratogenicity
HBV (DNA virus) TRANS: vertical, parenteral, sexual, BM (v low)
Incubation 60-90 days
Prodrome of fever, malaise, vomiting, then RUQ pain,
jaundice, rash, ±arthritis, haematuria
Cirrhosis in 20%, of which 10% →malignancy
US + αFP to screen for HCC q6mo

Neonate: check serology @12mo if mum positive
If mum HBeAg pos: check LFTs, HBeAg + refer ID

Perinatal infection: usually ASx, but 90% → carriers,
risk HCC later

Screening: screen all for HBsAg, if pos then HBeAg
Mum HBeAg pos: 90% risk
Mum HbeAg neg, HBsAg pos: 10%

PREVENT:
Vaccine + Ig @ birth prevents >90%

Acquired in infancy: 90% → chronic
dz
Acquired in childhood: 30-90%

Mx: if abⓝLFTs→ α-interferon,
nucleoside analogues (e.g.
lamivudine)
CMV 0.2-2.4% of all live births

CMV syndrome: HSM, jaundice, petechiae, purpura,
microcephaly, seizures, chorioretinitis, IUGR/SGA,
periventricular calcifications

Risk: 1% of non-immune women get CMV in
pregnancy, of which 10-20% will have congenital
CMV. Most ASx, but 15% of these will develop
hearing loss

DX: check mat IgM, IgG (high anti-CMV IgG avidity
suggests 1° >6mo, low avidity = recent infection)
US for periventricular calcifications
Highest risk = new infection in 1
st

trimester (50% risk fetal infection,
20% congenital, 10-15% mortality –
but majority still normal)

Reactivation: IgG protects ∴ only 10%
have deafness or neuro probs

Mx: ganciclovir x 6 wks if severe dz,
chorioretinitis, SNHL, microcephaly
Neonatal cord blood IgM
Neonatal urine viral culture, throat swab/NPA PCR,
neuroimaging
Rubella CRS: IUGR, microcephaly, eye stuff: cataracts,
chorioretinitis, microphthalmia, heart stuff: pulm
stenosis, PDA, SNHL, HSM, LNs, anaemia, blueberry
muffin rash, pneumonitis, renal anomalies

Dx: Mat IgG/IgM, neonatal cord blood IgM, higher
than expected neonatal IgG, PCR, viral culture
<12 wks: CRS in > 90% (♥/eye)
12-18wk: SNHL in 20%
>18wk: infection rare

Supportive Mx
Varicella Syndrome: cicatricial (scarred) skin, limb hypoplasia,
↓IQ, seizures, chorioretinitis, cataracts, microcephaly,
IUGR
?30-50% mortality

DX: amnio for varicella PCR
Week 8-20: highest risk
<20
th
week: 1-2%
>20
th
week: very low risk

Mx: give mum ZIG within 72h of any
exposure if she‟s seroneg. If mum had
dz > 5d before delivery, no Rx for
neonate if well, even if lesions.

If neonate exposed from 5d before to
2d after birth: give ZIG, give acyclovir
only if Sx.
HSV Vesicles in > 50% (skin, eyes, mouth)
Disseminated in 25% (sx @ 7-10d)
Encephalitis in 30% (d13-16)

“Syndrome”: vesicles, chorioretinitis, microcephaly,
microphthalmia

Ix: IgM takes 2 weeks to appear; IgG reflects mum.
Therefore tak swabs of throat/eye/lesions for IF
(quick) + PCR
CSF PCR, viral culture
EEG: temporal/parietal predilection
Mat 1°: 30-50% risk
Mat recurrence: 1-3% risk
↑ w scalp probe

Of those who got it:

5% was in utero
85% intrapartum (mostly HSV2)
10% postpartum

PREVENT: LSCS if active lesions
Swab infant @ 48h

Mx: acyclovir IV x 14d if sick
Neonatal
conjunctivitis
Gonococcal
 Gram neg coccobacillus
 D1-3
 Florid exudate, risk corneal ulcer, perforation, blindness

Chlamydia
 Day 5-14
 Purulent. May get pneumonia
 Mx = erythromycin x 2 weeks
HSV: presents day 4
Other bacterial : use topical tobramycin or chloramphenicol
Breastfeeding
contraindications
HIV, active TB, chemo, illicit drug use, radiation (temporarily), infant has galactosaemia

Teratogens

Warfarin Fetal warfarin syndrome
 Nasal hypoplasia, low
nasal bridge, groove b/w
nostrils + tip
 Stippled epiphyses
 Hypoplastic phalanges, △
 LBW
 C-spine abnormalities
 Airway compromise
Haemorrhage
6-8 weeks: fetal warfarin syndrome
up to 20 wks: CNS/ocular defects
e.g. Dandy Walker – likely from
haemorrhage

Phenytoin Fetal hydantoin syndrome
 IUGR, microcephaly, MR
 Metopic ridging,
epicanthal folds, ptosis,
flat nasal bridge
 Phalangeal hypoplasia
 Cleft lip

NSAIDs

- kernicterus
- 3rd trim: early closure of DA
- abortion (1st trim)

¹³¹IODINE

- 1st trim: severe hyperthyroidism
- other time: destroys thyroid

K IODIDE

- large goitre

TRIIODOTHYRONINE

- goitre

Lithium Heart/great vessel defects
Alcohol Fetal alcohol syndrome
 Low IQ
 Microcephaly
 Short palpebral fissures
 Maxillary hypoplasia
 Short nose
 Smooth philtrum
 Joint problems
 VSD > ASD
2 drinks per day → SGA
≥ 4-6 drinks per day → FAS
Androgens e.g. danazol Virilisation in female fetus
Methotrexate Skeletal malformations e.g. cranial
dysplaia
Low set ears
< 6 weeks can cause ToF
Retinoic acid Dysmorphism
CNS defects
♥ defects

VALPROATE

- 1.5% risk NTDs
heart - overall 5.7% risk major
malformation
- 9.1% risk major congenital
malformation if mum taking high
dose
- fetal distress, low apgars
- highest risk 1st trimester

ACE-inhibitors

- renal dysfunction, oligohydramnios
sequence

- highest risk 2nd/3rd trimester

AMINOGLYCOSIDES

- hearing loss (labyrinth damage)

BETA BLOCKERS

?IUGR

CARBAMAZEPINE, PHENOBARB

- haemolytic dz of newborn
carbamazepine --> NTDs, cleft
lip/palate, DD, nail hypoplasia

TRIMETHOPRIM

- NTDs

ORAL HYPOGLYCAEMICS

- neonatal hypoglycaemia

Tetracyclines stained teeth, enamel hypoplasia highest risk 2nd/3rd trimester
CHLORAMPHENICOL

- grey baby syndrome (vasomotor
collapse)

FLUOROQUINOLONES

- ?MSK defects

microcephaly, MR
- skeletal abnormalities

COCAINE

- GU, limb, CNS, ocular defects
(?poor evidence)

MARIJUANA

- gastroschisis (v rare?)

AMPHETAMINES

- IUGR, ↓ placental blood flow

HEROIN

- IUGR, w

drawal

DIGOXIN

- crosses placenta

NICOTINE

- IUGR, ↓placental blood flow

CCBs

- phalageal defects (1st trim), IUGR
(2nd/3rd trim)

THIAZIDES

- ↓ placental perfusion, IUGR

CHEMOTHERAPY

- malformations

BENZODIAZEPINES

- withdrawal, resp depression

OPIOIDS - withdrawal (6-8d of life)
- high dose: CNS depression,

SSRIs paroxetine - CHD
METHIMAZOLE - goitre, aplasia cutis
CTS Orofacial cleft 1
st
trimester
Vitamin K haemolysis
Pseudoephedrine Gastroschisis
Caffeine High dose: stillbirth, prem, LBW
Aspartame Avoid in PKU

Toxidromes

Drugs that cause
diaphoresis
Need „SOAP‟ to wash it off:
 Sympathomimetics
 Organophosphates + other
cholinergics
 Aspirin
 PCP (phenylcycline)

Drugs that cause
nystagmus
Alcohol
Lithium
AEDs
PCP

Charcoal useful for AAA Asthma meds (aminophylline, anti-muscarinics)
Aspirin, ibuprofen
Acetaminophen
Give within 1h

Charcoal
contraindicated
Unprotected airway
Risk aspiration e.g. hydrocarbons, oils
Not effective in: cyanide, caustic alkali, organic
solvents, iron, ethanol, methanol, lithium, mineral
acids

Gastric lavage
contraindicated
Hydrocarbons
Acid or base ingestions

Plant toxidromes Anticholinergic plants
 Jimson week (Datura)
Digoxin-like: oleander

Cholinergic poisoning CAUSES: organophosphates, carbamates, sarin,
physostigmine, pilocarpine, edrophonium

DUMBELS (respond to atropine)

Fasciculations, weakness (nicotinic – ø response
to atropine)
Mx:
Decontamination (charcoal)
ABCs, supportive care
Atropine
Anticholinergic
poisoning
diphenhydramine, TCAs (also cause SS), deadly

HOT as a hare
BLIND as a bat (mydriasis)
RED as a beet
DRY as a bone (xerostomia, ↓ secretions, urinary
retention)
FAST as a something fast

Mx: cholinergics, e.g. physostigmine
(anticholinesterase)
Paracetamol high risk: >200mg/kg; unknown quantity, or
repeated >100mg/kg/day

D1: N&V, sweaty, malaise, pallor, anorexia
D2: RUQ pain, oliguria, transaminitis, ↑SBR/INR
D3: risk multiorgan failure, death or resolves <d5
MX = NAC
Glutathione precursor
SE:
 anaphylactoid reaction
with wheeze, rash. Stop,
give antihistamines,

PATH: paracetamol → hepatic
sulfation/glucuronidation (kids use sulphation
more so have more reserve for glucuronidation in
OD) → non-toxic. 4% of dose → CYP450 →
NAPQI (toxic to kidney, pancreas, mitochondrial
injury, hepatocyte death) → combines w
glutathione → non-toxic

restart more slowly

Benzodiazepines Respiratory depression Flumazenil
Beta blockers Hypoglycaemia, ?bradycardia, ?hypotension Glucagon
Carbon monoxide Smoke inhalation, car fumes
constitutional sx
severe: seizure, coma, confusion
cyanosis ABSENT
CO has stronger affinity with Hb
Can have normal SpO2/pO2 (measures Hb-CO
as if it were Hb-O2)
100% O₂ via NRB
Hyperbaric O₂
CCBs Insulin, Ca salts
Cyanide Coma, seizures, apnoea, cardiac arrest Amyl nitrate, Na nitrate (these can
cause methaemoglobinaemia)
Ethylene glycol
(antifreeze)
Metabolic acidosis with ↑ AG, ↑ osmolal gap Fomipezole
Methanol ↑ AG met acidosis
Alcohol dehydrogenase breaks it down into toxic
metabolites
Fomipezole
Ethanol (competes for alcohol
dehydrogenase)
Heavy metals Dimercaprol
DMSA
EDTA
Iron Corrosive to GI mucosa
GIB, hepatotoxicity, coagulopathy, cardiac
dysfunction, gastric outlet obstruction
Uncouples oxidative phosphorylation → lactic
acidosis
Toxic @ > 40mg/kg elemental iron (FGF = 80mg
per tab)
V&D, abdo pain, shock
Desferrioxamine (doesn‟t drop level
but chelates)
WBI
Methaemoglobinaemia Congenital or from nitrates/sulphonamides
Cyanosis
Methylene blue 1%
Opioids naloxone
Organophosphates Atropine
Salicylates Early resp alkalosis (can miss this in kids), then
metabolic acidosis, tinnitus, vertigo, V&D, AMS,
diaphoresis, normal pupils
Zero order kinetics @ high dose
Supportive care
Charcoal or lavage
TCAs MOA: inhibit 5-HT, norad reuptake. Muscarinic
ACh blockade (anticholinergic sx), peripheral α-
OD: coma, convulsions, cardiac arrhythmia (wide
QRS), antichol sy
SE: dry mouth, blurred vision, constipation, urine
retention, tachycardia, postural hypoTN,
arrhythmia, sudden death, ↓sz threshold
Sodium bicarb (if QRS > 120)
Charcoal if early

Lead poisoning Constitutional Sx, microcytic anaemia,
Burton line: blue/black line on gum
Renal tubular dysfunction
↑serum lead leve, XR shows dense metaphyseal
line
Chelation
Copper N&V, blue/green vomit Supportive care
Arsenic V&D, colic
From contaminated food
Eosinophilia
Lavage, BAL
Mushrooms Short acting:
 V&D, salivation, sweating,
hallucinations, vision loss
Long acting
 Liver failure, renal failure
LSD = ergot (fungus). Not addictive. Mydriasis,
nausea, flushing ↑HR/temp
Supportive care
PCP Angel dust
Dissociative
Cramps, diarrhoea, haematemesis, miosis

Gastroenterology
Coeliac antibodies
IgA endomysial 88-100% sensitive (“moderate”)
91-100% specific = most specific
IgA anti-TTG 92-100% sensitive (highly sensitive)
91-100% specific
Highly sensitive AND specific
Present in 98% of biopsy proven CD
MOST USEFUL test for those >2yo, and correlates with mucosal damage
BUT:
 Disappears with treatment
 False + with IDDM, liver disease, heart failure
92-97% specificity
Not recommended – neither sens/spec are great, and poor PPV
45% specific: also found in CMPA, CD, tropical sprue
IgA anti-DGP 73% sens, 89% spec
APPROACH Always check IgA to r/o IgA deficiency (independently assoc. with CD)
In kids, IgA anti-TTG is the most useful, can also check IgA endomysial
If positive  biopsy (while ON gluten)
If negative  check HLA DQ2/DQ8 to try and RULE OUT CD. If these are positive,
consider modified gluten challenge + duodenal biopsy

Gastroenterology notes

Protein losing enteropathy Low IgG, IgA, IgM
Normal IgE d/t rapid turnover
Faecal osmolar gap serum osmolarity - [2 x (faecal sodium + potassium)]

normal = 50-100mosm/kg
osmotic diarrhoea = FOG > 100
secretory = FOG ≤ 100 (sometimes reported as <50)

estimate as 290 - [2x (stool Na + K)]

Autoimmune hepatitis ALT, AST ↑ 3-10X normal
↑ SBR (mostly direct)
Hypergammaglobulinaemia
Hypoalbuminaemia
± haemolytic anaemia, thrombocytopenia, leukopenia
Type 1:
 ANA pos, SMA pos
 Better steroid sensitivity + prognosis
 Can cause acute liver failure
Type 2:
 ANA neg, SMA neg, LKM pos
 More chronic, more steroid dependent
Type 3:
 Seronegative
 ?Soluble liver antibody

Respiratory stuff

Alveolar gas equation = [FiO2 x [barometric pressure – water vapour pressure] – (pCO2/0.8)
barometric pressure @ sea level = 760mmHg
water vapour pressure = 47mmHg
usual pCO2 = ~40mmHg
A-a gradient Normal = 2.5 + 0.2xage (in years)
Laryngomalacia Variable extrathoracic
Obstructive spirometry
findings
FEV1↓
FEV1:FVC ↓
Scooped out curve (see below – emphysema)
TLC ⓝnless A1AT def
RV ↑↑↑
RV:TLC is > 30%
FRC ↑
DDx: asthma, bronchiectasis, BPD, trachea-bronchomalacia
Restrictive spirometry findings FEV1 & FVC ↓ in proportion
FEV1:FVC ⓝor ↑
TLC < 80%, VC < 80% pred
RV ⓝor ↓
FRC ↓
DDx: poor effort/technique, neuromuscular disease
Chest wall deformity, scoliosis, interstitial disease (e.g. bleomycin, idiopathic
fibrosis)
Neuromuscular disease normal FRC
high RV
low TLC
FEV1 is reduced in proportion to FVC ∴ FEV1/FVC ⓝ
Most sensitive tests of resp muscle strength = max insp and max exp pressure,
measured while pt breathes against closed shutter

>7% ↓ in VC from sitting to supine could suggest that diaphragmatic weakness is
out of proportion to chest wall weakness
Small airway obstruction Scooped out on top
Normal shaped inspiratory loop, small & scooped out expiratory loop
Restrictive disease Very pointy d/t ↑ elastic recoil

Developmental Milestones

Hearing

U shaped audiogram: think SNHL (hereditary)

BELOW: TYMPANOGRAM INTERPRETATION
A = normal
AD = ↑ compliance e.g. loss of ossicular chain continuity
AS = stiff e.g. otosclerosis
B = little mobility e.g. middle ear effusion
C = negative pressure + retracted TM

Psychiatry

NMS vs SS vs MH
Neuroleptic malignant syndrome d/t D2 blockade or dopamine
insufficiency e.g. from
antipsychotics, antiemetics
(maxalone, Phenergan)

FEATURES:
hyperthermia
autonomic stimulation: tachycardia,
diaphoresis
arrythmia
seizures
**Rhabdomyolysis**
↑CK

Mx:
Dopamine agonist eg.
Bromocriptine, levodopa
Serotonin syndrome - less severe hyperthermia + rigidity
- nausea + diarrhoea
- HYPERREFLEXIA
Serontonin antangonists e.g.
Malignant hyperthermia AD ryanodine ® mutation (C ach)
Sustained release of intracellular Ca

Triggers; inhaled anaesthetics,
depolarizing muscle relaxants (e.g.
sux)

Rigidity incl. masseter
Rhabdomyolysis
Tachycardia
Met acidosis
Sux: fasciculation
Mx: dantrolene

Neonatology
Meconium aspiration Hyperinflated Asymmetrical coarse peri-hilar
markings
GBS pneumonia Low volumes Diffuse granular opacities ± pleural
effusion
(looks like RDS + effusion)
Other neonatal pneumonia High lung volumes Patchy asymmetrical perihilar
densities – looks like mec asp!
RDS/HMD Low lung volumes Ground glass opacities
Air bronchograms
TTN Normal volumes Coarse interstitial markings
Pulmonary oedema with promiment
vascular markings