*** 2013 Remembered ***
weight loss in CF despite improving FEV, no stool symptoms
child with longstanding history of respiratory disease
- ph 7.35
- pCO2 63
- HCO3 33
Type of acidosis/compensation
Respiratory acidosis with metabolic compensation
hypoglycaema without ketosis, low insulin levels
- GH def
- cortisol deficiency
***2013 Remembered Qs***
??diagnosis - fever, sore throat, rash with amoxycillin, LN, splenomegaly.
EBV or scarlett fever
HPV vaccine covers all of these except –
- respiratoy papillomatosis
- penile cancer
- anal warts
plantar warts (Molluscum contagiosum)
***2013 Remembered Q***
Child with gastro illness and brief GTC seizure ?cause
- ranging from asymptomatic to severe dehydration, seizure and death
- immunization reduce the incidence of seizure.
How does Fragile X premutation manifest in males?
- Mental Retardation
- Premutation have 50-200 CGG repeats
- mental retardation gene remains transcriptionally active
- FXTAS (FX associated tremor ataxia syndrome) in the later age
- Classical FXS does not occur
- Premature ovarian insufficiency
*** 2013 Remembered ***
deafness most likely cause
- connexin 26
Mutations in the GJB2 gene that encodes the protein connexin 26 (CX26) on chromosome 13 cause approximately half of all bilateral moderate-to-profound congenital hearing loss in nonsyndromic children
mother father unaffected - three sons affected one daughter not which inheritance pattern – options including two possibilities each
- XL recessive/AD,
- XL recessive/AR
- mitochondrial/XL dominant)
Complete Androgen Insensitivity Syndrome in a boy, who is most likely to be affected
- maternal aunt
- paternal aunt
X linked recessive pattern, brother is 50% chance of disease, aunty is 50% carrier
genogram with affected males and females, non-affected female passes to children both male and female, male passes to female child
- AD with variable penetrance
AD with variable penetrance
heteroplasmy due to
- number of mitochondria in cell
- wild mitochondria DNA
Mixture of mitochondria containing mutant DNA and normal DNA
Dysphagia, raynauds, calcinosis and telagiectasia and....?
- systemic sclerosis
- idiopathic Raynauds
Calcinosis, Raynauds, Eosophageal dysmotility, Scleroderma, Talengiactasia
Pauciarticular JIA, partial response to ibuprofen
- intra-articular steroids
Intra-articular steroids (because pauciarticular, if polyarticular next line would be infliximab because too many joints to inject)
Which drug increases half life of lamotrigine?
- sodium valproate
Side effect of tacrolimus
Complication of diazoxide
- fluid overload and CCF,
fluid overload and CCF, mechanism unknown
***2013 Remembered Qs***
Non-diarrhoeal HUS caused by defect in??
Complement dysregulaton accounts for most of the non-Shiga toxin producing E Coli cases of HUS.
Complement gene mutation or antibody to complement factor B
Family history present
Infections: Shiga Toxin E Coli, Strep Pneumoniae, HIV
Child with day time sleepiness, sometimes snores, asleep in class, difficult to rouse in morning, collapses when laughing
- seizure disorder
Collapsing when laughing (or with extreme emotion) called cataplexy - specific to narcolepsy.
absorption not affected by pancreatic insufficiency
- vitamin a
**Remembered Q 2013**
In DKA, what is the source of increased anions on a blood gas?
Normal anion gap is 8-16
15 mo elevated TSH, elevated T4, developmental delay
- pituitary tumour
- ectopic thyroid
Resistance to TH:
High serum T3, free T3, T4 and free T4 within normal range or increase TSH.
8yo not obese, no acanthosis with high HbA1c
Uncle/aunt have similar not obese
Three Main Features of MODY are:
- Diabetes often develops before the age of 25
- Diabetes runs in families from one generation to the next
- Diabetes may be treated by diet or tablets and does not always need insulin treatment
Autosomal Dominant inheritance
Genes involved in 87% of MODY include:
HNF1A (70% of cases-lowers amount of insulin secreted by pancreas, worsens with age)
Glucokinase (glucose sensor for pancreas to secrete insulin in response to high glucose. Changes in this gene lead to a fasting glucose of 5.5-8mmol/L. Normal is around 5.5)
HNF1B (including Renal Cysts and Diabetes (RCAD))
HNF4A (switch to turn genes on and off. Acts by decreasing amount of insulin secreted by pancreas. Decreased insulin with increasing age)
Teenager with heavy backpack - intact sensation but winging of the scapula.
Which nerve affected?
Long thoracic nerve affecting the latsimus dossi
Genogram with affected males and females, non-affected female passes to children both male and female, male passes to female child
A. AD with variable penetrance
A. AD with variable penetrance
Heteroplasmy due to
?number of mitochondria in cell
?wild mitochondria DNA
mixture of mitochondria containing mutant DNA and normal DNA
The occurrence in a single cell of more than one different population of mitochondrial DNA sequence.
Langerhans Cell Histiocytosis- which hormone is deficient?
ADH is low.
Diabetes insipidus is most frequent endocrine abnormality in LCH.
Multisystem disease is usually in younger children (<3yrs) and single organ disease in older children. Single organ in 55%.
5/52 with worsening positing and FTT, loose stools from birth - hypochloraemic hypokalaemic metabolic alkalosis - most likely cause?
- pyloric stenosis
- congenital chloride losing diarrhea
congenital chloride losing diarrhea
prominent forehead, jaundice (conjugated) systolic murmur ?cause
- peripheral PS
- supravalvular AS
peripheral PS (85%-90%)
Alagille syndrome — Alagille syndrome is characterized by the paucity of interlobular bile ducts and the following associated features:
●Chronic cholestasis (approximately 90 percent)
●Cardiac anomalies, most commonly peripheral pulmonic stenosis (85 to 91 percent)
●Butterfly vertebrae (39 to 87 percent)
●Posterior embryotoxon (prominent Schwalbe line) of the eye (61 to 88 percent)
●Dysmorphic facies, consisting of broad nasal bridge, triangular facies, and deep set eyes (77 to 95 percent)
Up to Date
Neonatal cooling for HIE...what temperature?
Cause of bradycardia in HIE ??
Normal GGT with elevated conjugated bilirubin and cholestasis
- a1 antitrypsin
- choledochal cyst
- biliary atresia
- neonatal hepatitis
- progressive familial intrahepatic cholestasis
alpha 1 antitrypsin
Progressive familial intrahepatic cholestasis
- biliary atresia, a1 antitrypsin, neonatal hepatitis, choledochal cyst: elevated GGT
- PFIC types 1 and 2 normal or decreased GGT, type 3 increased GGT
CGH is limited in diagnosing turners in which situation?
- Mosaic turners
- Ring chromosome
- Short arm deletion
- Xp duplicate chromosome
Ans: mosaic turners
Array CGH cannot detect “balanced” chromosome rearrangements such as reciprocal translocations and inversions and polyploidy. However, ~40% of patients with apparently balanced de novo rearrangements and abnormal clinical phenotypes will have imbalances detected by arrays. Array CGH will also detect imbalances which are the unbalanced products of balanced parental rearrangements. The follow up studies are designed to confirm these. aCGH will not detect either mixtures of normal and abnormal cells (mosaicism) where the proportion of abnormal cells is < 30%, or triploidy, but both of these are extremely rare conditions and, if suspected, can be tested with other methods.
Metabolic alkalosis and HTN with high renin and normal electrolytes
- 11 beta hydroxylase def
- renal artery stenosis
Ans: Renal Artery Stenosis
Liddle syndrome is a genetic disorder with increased function of collecting tubule sodium channel. Present young with triad of hypertension, hypokalemia and metabolic alkalosis. Low renin, low serum and urinary aldosterone.
Renal artery stenosis: In response to perceived low BP (distal to stenosis) sensed by granular cells of afferent arterioles, renin-angiotensin-aldosterone system activated leading to hypertension. Metabolic alkalosis due to ECF fluid changes (complex mechanims) (look for high renin, hypertension and normal electrolytes with metabolic alkalosis).
11 beta hydroxylase deficiency: 2nd most common cause of congenital adrenal hyperplasia. Decreased cortisol production causing increased ACTH secretion. Subsequent adrenal stimulation leads to excessive production of adrenal androgens. Look for low renin, HTN, hypokalaemia
Cushings syndrome: ACTH-dependent cushing’s syndrome is most common cause of endogenous hypercortisolism. Low renin, low K+, alkalosis
Phaechromocytoma : tumoural hypersecretion of noradrenaline, adrenaline and dopamine. Classic symptom triad is episodic headache, sweating, and tachycardia usually accompanied by hypertension.
Hepatoblastoma associated with??
- FAP association
- li fraumeni
Familial adenomatous polyposis is due to a germ line mutation in APC gene mutation and is associated with hepatoblastoma.
(VZV perianal) dermatome S2 vs S1 vs L1-3 vs L4-5
Ans: S1 , 2, 3, 4, 5 (from outside to inside - anus =S4)
Most common malignant bone tumour in preschool
Preschool bone tumour: Ewing’s
<10yo , Ewing is more common, >10yo , Osteosarcoma is more common
Chloroma : AML deposits muscle/bone
Best BBB penetration
8yo with chronic moist cough, CT chest ?bronchiectasis, OM with grommets x4 and sinus disease
- Primary Ciliary Dyskinesia
- Cystic Fibrosis
- IgA deficiency
- recurrent aspiration
Primary Ciliary Dyskinesia
Autosomal recessive disorder characterized by chronic cough, bronchiectasis, chronic rhinitis, and chronic sinusitis.
Best anti epileptic for sexually active adolescent with complex partial seizures
consider interaction with OCP, teratogens etc
Slight anaemia otherwise normal FBC, APTT and PT with bruising and bleeding boy bleeding frenulum at 15mo ?cause
- FXIII deficiency
- Bernard soulier
- liver disease
Glanzamans: manifests usually with mucocutaneous bleeding with normal platelets but no platelet aggregation on smear (due to absence of fibrinogin receptor which allows platelet bridging)
Bernard-Soulier : low platelet, abnormal function
FXIII: stabilization of clot, umbi adhesion defect, no easy brusing
ECG tall R) wave and upright T in V1
- biventricular hypertrophy
- Criteria for RVH on ECG
- Right axis deviation
- Dominant R wave in V1 (>7mm tall or R/S ratio >1)
- Dominant S wave in V5 (>7mm deep or R/S ration <1)
- QRS duration <120 ms
??child diagnosed with ?CHD asymptomatic parasternal heave, systolic and diastolic murmur LLSE ?RBBB and R) axis on ECG
- tricuspid atresia
Tricuspid atresia: cyanosis at birth, systolic murmur , left or superior axis, tall P in V2
Truncus arteriosus: parasternal heave, ejection systolic murmur, ejection click, diastolic murmur, ECG : Right , left or combined hypertrophy
Ebstein: cyanosis, or asymptomatic, soft systolic murmur/diastolic murmur, RAD, RBBB
AVSD: superior axis
Which is part of revised jones criteria
- erythema marginatum
Migratory arthritis, syndenham chorea, erythema marginatum, carditis, subcut nodules: 5 major symptoms
Fever, raised ESR/CRP, prolong PR, artharalgia : 4 minor symptoms
Dx: 2 major or 1major with 2 minor plus evidence of GAS infection
What is this lesion in a 5 month old with motor delay?
Usually congenital, aetiologies include:
- perinatal cerebral ischaemia
- antenatal intraparenchymal haemorrhage
- Well defined
- Often corresponds with vascular territory
- Lined with white matter
- NOT lined with grey matter, unlike in schizencephaly and arachnoid cysts
Progressive ataxia, decreased power, decreased DTR, upgoing plantars
- Friedrich's ataxia
Ans: Frederich's Ataxia
FA : progressive ataxia, decreased power, DTR, upgoing plantars
AT: progressive ataxia, talengiatasia, high alpha feto protein, muscular atrophy
Heriditary motor sensory neuropathy: not ataxic
PFT flattened exp curve normal FVC, decreased IF50
Subglottic has flat inspiratory curve
Hb 85 low MCV and low RDW 9
- Iron Def Anaemia
- lead poisoning
- sideroblastic anaemia
- chronic disease
RDW normal in thalassaemia and high in Iron def anaemia, B12 and folate deficiency, blood loss.
Low MCV typical of iron deficiency.
Only drug with randomized placebo controleed ?blinded evidence in management of behavioural problems in Autism
Staph liver abscess ?immunodeficiency associated
- hyper iGE
- Chronic granulomatous disease
Ans: Chronic granulomatous disease , catalase positive organism Staph abscess, most common in skin, liver, lung, lymph node, fungal infection
Hyper IgE : skin, sinopulmonary Staph infection
CVID: poor immunization response, diarrhoea, FTT
hepatic tumour elevated tumour marker
HVA: catecholamine tumour
Ca 19 Breast
G6PD drug to avoid
Cotrimoxazole causes haemolysis in G6PD.
Hereditary Spherocytosis is a defect in?
calculate NPV of screening test
NPV = # true negatives/true negatives+false negatives
Boy with history of seizures and facial rash
- Tuberous Sclerosis
- Sturge Weber Sydrome
- incontinentia pigmenti
Sturge Weber - facial port wine stain, seizures, mental retardation and ipsilateral leptomeningeal angioma.
What is part of HLH diagnostic criteria?
- elevated triglycerides
HLH manifests with fever, hepatosplenomegally, lymphadenopathy, jaundice and a rash.
HLH Criteria = 5 out of 8 of below
- Cytopenias affecting at least two of three lineages (haem/plt/neut)
- High triglycerides and/or low fibrinogen
- High ferritin
- Low NK cell activity
- High CD25
Bloods will also show markely raised ESR and CRP (but not park of criteria)
Mechanism of action atomoxetine?
Selective NA reuptake inhibitor.
Associated with priapism.
CSF with lymphocytosis, negative microscopy, low glucose, high protein
The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, M. tuberculosis is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding.
6yo with seizures and encephalopathy.
CSF is negative for HSV PCR, negative microscopy.
Aciclovir started for suspected HSV with no improvement in 24 hours. ? management
change to valaciclovir or ganciclovir
continue and repeat LP for PCR
treatment for gram negative coccobacillus on CSF culture
- penicillin and gentamicin
- cefotaxime and gent
- vancomycin and penicillin
- vancomycin and flucloxacillin
cefotaxime and gent
Ampicillin and cefotaxime in neonate - apart from listeria what else does ampicillin cover specifically that cef doesn’t
- e coli
GBS is covered by Ampicillin, penicillin, 1st and 2nd generation cephalosporin.
Cefotaxime is 3rd gen.
characteristic of X-Linked Agammglobulinaemia (Bruton’s)
- absent tonsillar bed tissue
Only charatersitc sign of XLA is absent B cell rich tonsillar bed tissue
What is bioavailability?
Fraction of administered drug that reaches the circulation unchanged. A medication given IV has 100% bioavailability.
Bioavailability is less in PO medications due to incomplete absorption and first pass metabolism.
Loading dose is determined by?
- volume of distribution
- half life
- first pass
loading dose is determined by Vd
Loading dose = desired concentration x Vd
time to achieve stable trough levels of IVIG with monthly infusion
Stable state concentration is 4-5 t½
4 months because t ½ of IVIG is 4weeks
risk of bee sting anaphylaxis post extended local reaction
General risk 2 %
Localised big reaction and generalised urticarial is <10%
Anaphylaxis reaction, 40% risk
Which clotting factor is low in neonate?
- protein C
Neonate is low in antithrombin, protein C
li fraumeni gene defect
Li Fraumeni is an extremely rare autosomal dominant disorder of p53 predisposing patients to multiple cancers throughout their lifetime starting at a young age.
High occurances of breast cancer, brain tumors, acute leukemia, soft tissue sarcomas, bone sarcomas, and adrenal cortical carcinoma.
Recommended treatment for malaria
- artemesinin combination
Proteinuria, glycosuria, phosphaturia (proximal RTA) cause
Cyclophosphamide : haemorrhagic cystitis
urinalysis showing proximal RTA – fanconis and corneal deposits
Lowe: cataract, fanconi anemia, proximal RTA, phosphaturia (occulo cerebral renal syndrome)
Cystinosis: cysteine deposits, fanconi syndrome, metabolic acidosis
Fanconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed.
- Normal anion gap acidosis
Proximal (Type 2 RTA) - pH<5.3 (Variable - may increase with alkali therapy)
Distal (Type 1 RTA )
- pH >5.5
- Na+ >25 meq/L
- decreased ammonium
Proximal (Type 2) RTA
- Defect in proximal HCO3- resorption.
- Most common causes - ifosfamide, cystinosis. May be assoc with fanconi syndrome (generalised prox tubular dysfunction... ie also losing glucose, phosphate, amino acids etc)
Distal (Type 1) RTA
Impaired H+ secretion in distal nephron
- so urine pH is inappropriately high
- Hereditary distal RTA (most common), ifosfamide
Finding least in keeping with diagnosis of minimal change disease in child with nephrotic syndrome
- low complement
- elevated Cr
MCD + FSGS major causes of nephrotic syndrome in kids
Increased T cell dysfunction causes podocyte effacement.
Histo - normal appearing glomeruli with absence of complement and immunoglobulin deposits
Low complement GN:
- Systemic: SLE, endocarditis, cryoglobulinemia, shunt nephritis
- Isolated renal:post-infectious GN, MPGN
Normal complement GN:
- Systemic: HSP, ANCA-associted (Wegener’s, PAN), Goodpasture’s syndrome, hypersensitivity vasculitis
- Isolated renal: IgA nephropathy, anti-GBM disease, RPGN
embryological origin of glomerulus
- ureteric bud
- wolfian duct
- metanephric blastema
metanephric blastema forms nephrons not including collecting duct
Ach acts on what at NMJ
Ach binds to Ach Receptor present on sarcolemma in NMJ
1st line treatment in depression?
- family therapy
UTI and low sodium (122) high potassium (6.5) vomiting and pseudohypoaldosteronism assoc with UTI ?
Adrenal insufficiency - decreased production of glucocorticoids (cortisol) and sometimes mineralocorticoids (aldosterone).
Look for hyperpigmentation of the skin, particularly areas not exposed to sunlight (due to excess melanocyte-stimulating hormone).
Differentiate primary (adrenal insufficiency) from secondary (ACTH def from anterior pituitary) and tertiary (CRH from hypothalamus).
Primary - Low cortisol, high ACTH
Secondary - Low cortisol response to ACTH test (Chronic lack of ACTH causes impaired sensitivity of adrenal cortex)
Addisonian Crisis is severe adrenal insufficiency. Presents with:
Cortisol stimulates gluconeogenisis....so impaired secretion causes hypoglycemia.
Papilloedema, Normal CT, diploplia on lateral gaze
- Benign Intracranial Hypertension
Benign intracranial hypertension
14yo suprasellar solid/cystic lesion with GH deficiency and delayed puberty
- pilocytic astrocytoma
- optic glioma
- germ cell tumour
Slow growing tumour of Rathkes pouch.
- Visual abnormalities due to direct pressure on optic chiasm
Endocrine abnormalities due to pressure or damage to normal structures
- Deficiency of GH, TSH, ACTH, gonadotropin.
- DI frequent when Pituitary stalk is involved.
- Headache in 50%
Neonatal hearing screening is most likely to miss..?
- ruptured TM
- stapes disease
- obstructed external canal
otoacoustic emission 1st performed test in neonates, if fail, proceed with ABR (auditory brainstem response)
Babies with a risk factor who pass the neonatal screening test should have at least one diagnostic audiology assessment by 12 months of age. More frequent assessment may be indicated for children with a family history of hearing loss, cytomegalovirus (CMV) infection, syndromes associated with progressive hearing loss, craniofacial abnormalities, neurodegenerative disorders, birth trauma or culture-positive postnatal infections associated with sensorineural hearing loss.
B symptoms include...?
- 5% weight loss
- drenching night sweats
- bone pain
Ans: night sweats
Fever, night sweats, wt loss >10%
Suicide risk in adolescent male
- depressed mood
- ideation with no plan
- FHx suicide
Ans: FHx suicide
- Psychiatric disorders
- Previous suicide attempt
- Family history of mood disorder and/or suicidal behavior
- History of physical or sexual abuse
- Exposure to violence
- Biologic factors
What do the diamond, squares and lines mean on a Forest Plot?
Diamond - measure of effect of all studies, with lateral tips the confidence intervals.
Square - Odds ratio for each study, with lines that indicated the confidence intervals.
Vertical line - line of no effect. If the confidence intervals cross the line, the study cannot be said to differ from "no effect"
How many puffs in a salbutamol MDI
100 mcg per dose and 200 doses per MDI
How many mmol of normal saline in 1L of 1/2 normal saline?
One litre of 0.9% Saline contains:
- 154 mEq of sodium ion = 154 mmol/L
- 154 mEq of chloride ion = 154 mmol/L
So half normal saline contains 77 mmols sodium ion
***2013 Remembered Q***
What differentiates Leukocyte Adehsion Deficiency from other neutrophil disorders?
- periodic fever
- delayed umbi detachment
Delayed Umbilicus detachment.
In patients with a Leukocyte Adhesion Deficiency (LAD) syndrome, leukocytes (particularly neutrophils) cannot leave the vasculature to migrate normally into tissues under conditions of inflammation or infection.
Leukocyte adhesion deficiency I — LAD I is characterized clinically by recurrent bacterial infections, a persistent neutrophilia that increases markedly during infection, absent pus formation (a hallmark finding), and impaired wound healing. A classic presenting infection is omphalitis, with delayed separation of the umbilical cord.
***2013 Remembered Q***
What is the reason for irradiating blood products?
Used to prevent trasfusion associated GVHD. (TA-GVHD)
Transfusion-associated graft-versus-host disease (TA-GVHD) is caused by viable donor lymphocytes that are transfused into a patient who either does not recognize these cells as foreign or does not have the capacity to destroy them. TA-GVHD usually begins 8 to 10 days following transfusion and is almost inevitably fatal.
GVHD does not occur after most transfusions because the donor lymphocytes are destroyed by the recipient's immune system. However, this protective response does not occur in two settings, thus necessitating the use of irradiated red cells:
- “Directed donor” blood products – The first occurs in immunocompetent individuals. TA-GVHD may develop in a partial HLA match when the recipient is heterozygous at an HLA allele for which the donor is homozygous. In these instances, donor WBCs will not be recognized as foreign by the host, but the donor cells may recognize host cells as foreign and mount a TA-GVHD reaction. There is an increased likelihood of this occurring in blood relatives. As a result, blood products donated by family members should be irradiated before transfusing into a blood relative.
- Immunodeficient recipients – The second setting is in the recipient with decreased cellular immunity who is unable to mount a response against donor lymphocytes.