Paediatric updates

Pediatrics Important one-liners & latest points from Nelson 20th ed for quick revision.

- Absence seizures to be treated with ethosuximide, as effective and less toxic than Valproate. Ethosuximide is more effective than lamotrigine. Lamotrigine & Valproate are more effective in atypical absence seizures/absence seizures associated with GTCS.
- In a preterm neonate at risk for RDS, CPAP started at birth is as effective as surfactant therapy & is the approach of choice for initial management in delivery room. In other words, first step in management of suspected RDS is CPAP. (No difference for mild, moderate or severe HMD).
- Indications to start mechanical ventilation in neonates & infants:
1. Arterial blood pH <7.20
2. Arterial blood pCO2 of 60 mm Hg or higher
3. Oxygen saturation (SpO2) <90% even at inhaled oxygen concentration of 40-70% & CPAP of 5-10 cm H2O.
4. Persistent apnea
Points 1, 2 and 3 are measures of respiratory failure in infants and children.
- A major breakthrough in Cystic Fibrosis therapy is IVACAFTOR, a small molecule potentiator of the CFTR mutation, G551D. Available as oral therapy in CF patients with G551D mutation (seen in 5 % patients). Improves FEV1 by 10%, decreases pulmonary exacerbations by 55% and also decreases sweat chloride levels. Given only at or above 6 yrs of age.
- Most common complication of pancreatic enzyme replacement therapy is colonic strictures.
- Hypoglycemia in neonates: Random whole blood glucose less than 45 mg/dl. (AIIMS-WHO definition). Any value below 55 should be viewed with suspicion. Hypoglycemia in infants and children is random whole blood glucose below 55 mg/dl. (Nelson 20th ed )
- MC symptom of hypoglycaemia in neonates is jitteriness & tremors.
- MC form of childhood hypoglycaemia is Ketotic hypoglycaemia, seen due to inadequate feeding. More common in malnourished with intercurrent illness.
- A new potential treatment, but still under investigation in Duchenne’s muscular dystrophy is use of antisense oligonucleotide drugs. Two drugs effective: Drisapersen & Eteplirsen. Both are exon-51 skipping antisense oligonucleotides, that can produce a shorter but potentially functional dystrophin protein.
- Microorganisms causing Infective endocarditis in children: Viridans streptococci, followed by Staph aureus are most common. Staph more common in no underlying heart disease, whereas viridans more common in children with underlying heart disease who undergo invasive dental procedures. Pseudomonas and Serratia more common with IV drug abuse & Coagulase negative Staph more common in those with indwelling central venous catheter. Fungal IE seen after open heart surgeries.
- Children with RHD: Mitral insufficiency is more common than Mitral stenosis (rarely seen before adolescence).
- Corrective surgery in TOF is done as soon as possible in TOF presenting early or having frequent cyanotic spells. For well tolerated TOF, age of corrective surgery is between 4 to 6 months of age. Palliative surgeries less common now.
- Right sided aortic arch seen MC in TOF, followed by Truncus arteriosus.
- MC cause of sudden cardiac death in children is valvular AS
- MC cause of sudden cardiac death in adolescents is HOCM
- Duration of antibiotic therapy in post neonatal & childhood meningitis has been decreased to 10-14 days maximum. For meningococcal meningitis its as short as 5-7 days and for H. influenzae its 7-10 days. 
- Streptococcus milleri is now MC organism causing brain abscess in children (more than Staph aureus). 
- HSP is MC vasculitis in childhood (Yes! Nelson finally says it clearly!)
- MCC of hematuria/gross hematuria in children is UTI (Overall)
- MC glomerular cause of hematuria in children is Post streptococcal GN
- Microscopic hematuria is rare in UTI. Recurrent hematuria raises suspicion of IgA nephropathy.
- The primary immunodeficiency disease with excellent prognosis even without specific therapy is Myeloperoxidase (MPO) deficienc

Blood Transfusion

THE RIGHT WAY OF ADMINISTERING BLOOD PRODUCTS

[ from "THE CLINICAL USE OF BLOOD: HAND BOOK , World Health Organization & Blood Transfusion Safety , GENEVA ]

✔️Prefer a larger cannula: A doubling of the diameter of the cannula increases the flow rate of most fluids by a factor of 16.

✔️In case of Whole blood, red cells, plasma and cryoprecipitate
>Use a new, sterile blood administration set containing an integral 170–200 micron filter

>Change the set at least 12-hourly during blood component infusion
>In a very warm climate, change the set more frequently and usually after every four units of blood, if given within a 12-hour period

✔In case of Platelet concentrates

>Use a fresh blood administration set or platelet transfusion set, primed with saline.

✔️WARMING BLOOD:

>There is no evidence that warming blood is beneficial to the patient when infusion is slow.

>At infusion rates greater than 100 ml/minute, cold blood may be a contributing factor in cardiac arrest. However, keeping the patient warm is probably more important than warming the infused blood.

>Warmed blood is most commonly required in: [1]Large volume rapid transfusions:
    -Adults: greater than 50 ml/kg/hour      -Children: greater than 15 ml/kg/hour
[2]Exchange transfusion in infants  [3]Patients with clinically significant cold agglutinins.

>Blood SHOULD ONLY BE WARMED in a blood warmer. Blood warmers should have a visible thermometer and an audible warning alarm and should be properly maintained.

>Blood should never be warmed in a bowl of hot water as this could lead to haemolysis of the red cells which could be life-threatening.

✔️Severe reactions most commonly present during the first 15 minutes of a transfusion. All patients and, in particular, unconscious patients should be monitored during this period and for the first 15 minutes of each subsequent unit.

✔️The transfusion of each unit of the blood or blood component should be completed within four hours of the pack being punctured. If a unit is not completed within four hours, discontinue its use and dispose of the remainder through the clinical waste system.

Odours from Metabolic diseases

Odor originating from Metabolic Disorder

a. Trimethylaminuria

Trimethylaminuria also called fish odor syndrome or TMAU is a genetic disease. It is due to abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. The odor produced is similar to decaying fish. The smell consists of sulfur compounds, plus nitrogen compounds (amines). The trimethylamine is made by bowel bacteria that break down certain amino acids, carnitine and choline that are in high concentrations in marine fish, egg yolks, certain beans and liver.

b. Maple Syrup Urine Disease

Maple syrup urine disease or MSUD refers to a rare inherited metabolic condition. The first form results from a deficient enzyme (branched-chain alpha-keto acid dehydrogenase, BCKD) necessary for the breakdown of the amino acids leucine, isoleucine, and valine. Without this enzyme, these amino acids build up to toxic levels in the body. If left untreated, this leads to brain damage and progressive nervous system degeneration in infants. Babies that suffer from the mild form have a sugary smell. Adults may have a burned sugar smell to urine. There second form responds well to the vitamin thiamine. It is reported that the patients smell like caramel, maple syrup or have a malty odor.

c. Phenylketunuria

Phenylketunuria or PKU is another inherited metabolic disorder. In this case the body cannot completely break down the protein phenylalanine because it lacks the enzyme phenylalanine hydroxylase. Because of this, phenylalanine builds up in the body’s cells and causes nervous system and brain damage. High levels of phenylalanine leads to increased levels of phenylketones in the blood which are excreted in the urine. The person may present a musty, mousy, wolflike, barny, horsey or stale smell.

d. Multiple Acyl-CoA Dehydrogenase Deficiency

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited fatty acid oxidation disorder (FOD). A person with MADD cannot efficiently breakdown fats and protein into energy. Once the body uses up its first source of energy, blood sugar (glucose), the body becomes weaker because it cannot then make energy from fats. Therefore, people with this disorder must eat on a very regular basis and should not go long without food. The person presents variable body odor of sweaty feet.

e. Isovaleric Acidaemia

Isovaleric acidaemia is a rare genetic condition in which the body is unable to process certain proteins properly. People with this disorder have abnormal levels of an enzyme that helps break down the amino acid leucine, a building block of proteins. It is related to the genetic metabolic disorder Maple syrup syndrome. A symptom of isovaleric acidemia is a odor of cheesy, acrid,sweaty feet. This odor is result of the buildup of isovaleric acid compound.

f. Tyrosinaemia

Tyrosinaemia is an error of metabolism, inherited, in which the body can not effectively break down the amino acid tyrosine, found in most animal and plant proteins. It is an autosomal recessive, that means two copies of an abnormal gene must be present in order for this to develop. There are three types of tyrosinemia, each with distinctive symptoms and caused by the deficiency of a different enzyme. One of the symptoms of Tyrodinaemia type 1 is a odor like cabbage or rancid butter.

g. Diabetes Mellitus

Diabetes Mellitus. Almost all of the food we eat is broken down into glucose (sugar in the blood). Glucose is the main source of fuel for the body and is used by cells for growth and energy. Glucose needs insulin to get into cells. Insulin is a hormone made by the pancreas. In individuals with diabetes, the pancreas may create little or no insulin, or the cells do not react appropriately to the insulin that is produced. Glucose builds up in the blood, and is excreted in the urine. So the body loses its primary source of fuel. Fruity breath is present in people with diabetes.

h. Diabetic Ketoacidosis

Diabetic ketoacidosis. When the level of the blood sugar gets too high, the body creates "ketones" as a by-product of fat digestion. These ketones create blood acidity which causes "acidosis" of the blood. At the same time, the kidneys excrete large amounts of glucose-rich urine, causing dehydration. The patient may have a fruity breath, a sweet taste on the skin, or emanate a distinctive, chemical smell.

i. 3-Methylcrotonylglycinuria

3-Methylcrotonylglycinuria, multiple carboxylase deficiency or 3MCC is another autosomal recessive genetic trait means that this faulty gene usually appears when two carriers have children together and pass it to their offspring. In this case the body is unable to process certain proteins properly. Patients have abnormal levels of an enzyme that helps break down proteins containing the building block (amino acid) called leucine. As a carboxylase enzyme, 3-MCC requires biotin for activity. There are four carboxylases in humans that use biotin and each can be deficient singly or together. If biotin metabolism is defective, functions of all four carboxylases will be low, resulting in Multiple Carboxylase Deficiency. MCC is predominantly located in the inner membrane of the mitochondria. The patient presents an odor like male cat urine.

j. Cystinuria

Cystinuria is an inherited, metabolic disorder. It is characterized by the accumulation of cystine crystals (uroliths, caculi or stones) in the kidneys, ureter and bladder. People with cystinuria cannot properly reabsorb cystine into their bloodstream during the filtering process in the kidneys. Cystine is a amino acid, a building block of proteins. Most of the time, this excess cystine is simply excreted in the urine. But in some cases the cystine cannot stay dissolved and forms crystals. Because cystine is one of the sulfur-containing amino acids, the urine may have a characteristic "rotten egg" odor.

k. Hypermethioninemia

Hypermethioninemia this condition can happen when methionine (amino acid) is not metabolized correctly in the body. Individuals with this condition may experience a fishy, sweety and fruity, rancid butter or boiled cabbage odor. It has been said that tyrosinosis-tyrosinemia is the same as hypermethioninemia.

l. Oast-House Syndrome

Oast-house syndrome also called Smith-Strang diesease is an inherited disease (autosomal recessive) due to malabsorption of methionine and secondary malabsorption of other amino acids. Part of the unabsorbed methionine is converted by colonic bacteria to a-hydroxybutyric acid. The urine has an odor similar to that of dried celery, yeast or malt, or an oasthouse (a building for drying hops). The patients have white hair, mental retardation among other symptoms.

m. Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia – CAH is a group of inherited disorders which causes an enzyme deficiency (most commonly 21-hydroxylase) resulting in the inability of the adrenal glands to make hormones: cortisol and/or aldosterone. Since the body can't make enough cortisol (and in some cases aldosterone), it stimulates the production of other adrenal hormones that are called androgens. Three main forms of Congenital Adrenal Hyperplasia (CAH) exist: the severe salt-wasting, non-salt wasting forms, and a milder form. The non classical or milder form of CAH can produce body odor during childhood because of the premature puberty.

Opthalmology - Diabetes

OPHTHALMOLOGY
Diabetes mellitus
Ocular involvement in diabetes is very common. Structure-wise ocular lesions are as follows:
1. Lids. Xanthelasma and recurrent stye or internal
hordeolum
2. Conjunctiva.Telangiectasia,sludgingoftheblood
in conjunctival vessels and subconjunctival
haemorrhage
3. Cornea. Pigment dispersal at back of cornea,
decreased corneal sensations (due to trigeminal neuropathy), punctate kerotapathy, Descemet’s folds, higher incidence of infective corneal ulcers and delayed epithelial healing due to abnormality in epithelial basement membrane
4. Iris. Rubeosis iridis (neovascularization)
5. Lens. Snow-flake cataract in patients with IDDM, posterior subcapsular cataract, early onset and
early maturation of senile cataract
6. Vitreous.Vitreoushaemorrhageandfibre-vascular
proliferation secondary to diabetic retinopathy 7. Retina. Diabetic retinopathy and lipaemia retinalis
8. Intraocular pressure. Increased incidence of
POAG, neovascular glaucoma and hypotony in diabetic ketoacidosis (due to increased plasma bicarbonate levels)
9. Optic nerve. Optic neuritis
10. Extraocular muscles. Ophthalmoplegia due to
diabetic neuropathy
11. Changes in refraction. Hypermetropic shift in
hypoglycemia, myopic shift in hyperglycemia and decreased accommodation