Sunday, January 11, 2015

Lung Surfactant and Factors affecting its maturation


Origin- Type II alveolar cells and Lamellar bodies

Recycling- 90% is reprocessed, average time for turnover is around 10 hours.
CPAP can prevent excessive loss of surfactant drainage into airways by decreasing depth and length of respiration.

Composition-
Phophatidylcholine ( 70-80%) and phosphatidylglycerol (5-10%)
Phosphatidylinositol, Phosphatidylserine,Phosphatidylethalomine - 10%
Other lipids- 10%, 2% surfactant lipids
Surfactant Proteins- SP-A, SP-B, SP-C, SP-D (5-10%)



Function-
Decreases surface tension of alveoli in Laplace equation ie P= 2 gamma/ r


Factors Affecting Surfactant maturation-

1. Glucocorticoids- Intrinsic cortisol accelerates surfactant maturation. Dexamethasone administered increases expression of beta-adrenergic receptors with resultant increase in surfactant production.

2.Beta- adrenergic Drugs- Terbutalline, Formeterol increase cAMP and increase production and secretion of Surfactant

3. Thyroid Hormones- T4 has enhancing property on lung maturation and surfactant secretion however, it does not cross placenta.

4.Prolactin is under study. However low prolactin has been seen in infants with RDS.

5.Epidermal growth factor- Has shown to increase SP-A and L:S ratio in non-human models.

6. Fibroblast pneumocyte factor- under study

7. Insulin- delays the maturation of alveolar type II cells and decrease production of saturated Phosphatidylcholine. It inhibits the expression of SP-A gene.

8, Testosterone- delays the lung maturation through its action on lung fibroblast.


Errors of Surfactant Metabolism-
Polymorphism of SP-A expression- predisposition to sever RSV infection and increase risk for BPD.
SP-B polymorhism- RDS 
SP-C deficiency- Interstitial Lung disease
SP-D- Alveolar accumulation of lipids and proteins.


Monday, January 5, 2015

The Newborn Book - Janelle Aby : Review


I happened to be one of the lucky people to receive a Complimentary copy of this book " The Newborn Book" by Dr Janelle L. Aby . Well I am forgetting this fact for a while and I am writing a Sincere review of this book.

" The Newborn Book" has focused on 'the Significance of Physical Findings in the Neonate' which by far is the first book of its kind.
We are well known to Books like Avery, Roberton, Also Meherban Singh and Cloherty are equally popular in our institutes. All excellent books that have elaborated on the Disease and Management protocols in newborn.




This book particularly is a Basic for every pediatrician, neonatologist and wanna be people. The book is an Atlas of all physical findings in newborn with collections of best photos of such findings. It has an elaborate column on all sorts of findings we may encounter in our nurseries and Outpatient doors , seen commonly even in well babies. Most often we miss findings in newborn and often we are perplexed by findings we have never seen before in any books. I think this book is an answer to this gap that been seen. It can be even used as reference in such cases.Along with the photos, there are useful description and management plan as well.

The content includes
- Prenatal USG findings- commonly encountered conditions
-General Characteristics
- Findings from Head to Toe- Body part wise including Rare findings ( many of which we may have encounter and ignored)
-Body fluids and substances.

What is Good about the book?
1. Simple and concise topics - 250 neonatal findings
2. Excellent photo galleries of findings ( Kind of like Kanski )- 600+ full color photographs
3. Well referenced writings
4. Reviewed by great people
5. The Quality of the book is top-class including design and paper quality

Most importantly the Author is a well-experienced pediatrician indulged in academics.


I believe that This book is one Every Library in Medical college will eventually have and most Pediatrician and Neonatologist will have in near future, as I see this will be one of the best references in Neonatology. We must be able to know and identify findings before proceeding to management part.

As this is the first edition, there might be still rooms for improvement. More topics can be included and book can be made broader and longer , so as to make it more attractive and atlas like.

You can Visit
http://thenewbornbook.org/ for more details and in case you want to keep a copy of it.

Hope you benefited from my review. I am still going through topics in the book, as I am keen in Neonatology and actually I am already into my interest in my Hospital.
Any Comments are welcomed.

Friday, January 2, 2015

Approach to a Child with Short stature


Short Stature-

Height Below 3rd Centile or more than -2 SD height for Age and Gender for the standard population.
When height is > -3 SD its most likely pathological.




Assessment of Short stature-

1. Accurate height measurement using Stadiometer for <2yrs and on Frankfurt plane for older children.

2.Assess height velocity-  cm/year

3. Mid-parental height-
Estimated Final Height = 
(Ht of father in cm  + height of mother in cm + 13 cm)/2 in Males
(Ht of father in cm  + height of mother in cm - 13 cm)/2 in Females 
 Also see Assessment of height.

4. Assessment of Body Proportion- Upper segment Lower segment ratio- Normal, low or high

5. Sexual Maturity Rating- Normal, Delayed or Advanced


Etiological Assessment and Classification-

Click on the chart to enlarge-



Legend- CDGP: Constitutional delay in Growth and puberty

Can be classified on the basis of Upper:Lower segment ratio, then Physiological and pathological causes.

Keeping in mind the causes, 
history should be sought for-
- history of Low birth weight, IUGR
- family history of short stature ( Achndroplasia, Familial short stature), delayed puberty and menstruation ( CDGP) , bowing legs and skeletal deformities ( Skeletal dysplasias)

Symptoms - systemic
- Renal- polyuria, Hypertension, Pallor, hematuria
-CNS- Cerebral palsy, 
- history of jaundice, white stool, bulky stool
- Recurrent UTI

Neonatal history- hypoglycemia, jaundice, micropenis
Any chronic illness, drug or hormone intake
Social environment


Examination-
Body Proportions, Skeletal ratios- Rhizomelia, phocomelia etc
Skeletal abnormalities
Dysmorphism
Kypho-scoliosis
Pallor, Hypertension, Jaundice, abdominal distension
Frontal bossing, depressed nasal bridge, Webbed neck
Goitre, corase hair, 
Central obesity, striae


Evaluation-

1. Assess Bone Age and tally with Chronological age-

Bone age is asses by- Tanner's and Whitehouse method or Gruelich-Pyle atlas

Delayed Bone age compared to Chronological age-
All organic cases 
Bone age proportionate to height age
  • CDGP
  • Malnutrition and Systemic Illness- 

Bone age is less than height age-

  • Growth Hormone Deficiency
  • Hypothyroidism
  • Delayed Pubertry  

Bone age is Normal for Chronological Age-
Familial Short stature


Advanced Bone Age -
Cushing Syndrome
Precocious Puberty


Investigations-

If Height is  not below 2 SD, no evaluation- weight and watch 3-6 monthly

If Height < -2 SD, look for SD score-
If > 1 SDS- Physiological varaint
If <-1 SDS- look for Facies, proportions- if abnormal - Genetic, skeletal dysplasias

If Normal Proceed with-

Level I-
Complete blood count, ESR
Bone Age
Renal function test ( CKD)
Urine specific gravity, pH ( RTA, CKD)
Stool RME, Culture, occult blood, pH -( GI inflammations, celiac, malabsorptions)
Liver function test ( CLD, Hepatitis, Obstructive jaundice)
ABG- ( RTA, Barter and Gittelman syndrome, CKD, Any metabolic acidosis)
Blood Sugar- (GH deficiency, Diabetes type I, Addisons disease, Metabolic disorders)

Level II-
Thyroid function Tests
Karyotyping

Level III-

Celiac - TTG for > 2yrs child, Antigliadin Ab for < 2yrs
GH stimulation assay
IGF1 and IGF-BP3 assessment
MRI brain


Managment -

For CDGP and Familial- Counselling

GH therapy for GH deficiency, failure to catch-up Low birth weight children, 
GH is currently approved in the United States for treating children with growth failure as a result of Turner syndrome, end-stage renal failure before kidney transplantation, Prader-Willi syndrome, intrauterine growth retardation, and idiopathic short stature

As per pathology for other causes.

References-
Nelson Textbook of Pediatrics
OP Ghai Essentials of Pediatrics
Review articles



Thursday, January 1, 2015

A Case of Child with Mucopolysaccharidosis - Hunter Syndrome


A 6 year old patient was found to have course facial features and short stature. Parents have noticed a developmental stasis since 4-5 years of age. The weight was normal. There was no any chronic illness, any significant birth and postnatal history contributing to the condition. There was no history of short stature or pubertal delay in the family members. Nutritional status was good.

On examination- The child had coarse facial features, with low anterior hair line and prominent angles of face. Looked stunted and no skin changes,no thyroid enlargement. Abdominal examination revealed Hepatosplenomegaly. Cornea was clear but sclera looked muddy.
There were no major limb deformity or bending. No pallor.

Anthropometric measurements-
Ht- less than 3 rd centile
Wt/Ht- Normal
Upper segment: Lower segment ration was - 1:1 at 6 years
Arm span was normal.

We suspected Mucopolysaccharidosis. 
Differentials were- Hypothyroidism, Mucolipidosis, or other Metabolic storage disorders. As TSH, T4 were normal hypothyroidism was ruled out. Other conditions were less likely from clinical information and findings.

We sent Xray of Hand and Spine-

Xray showed- Increased trabeculation with Bullet shaped phalanges. Bone trabeculation is coarse and the cortices are thin.
Spine - mild changes with Beaking of vertebrae.





Review : Mucopolysaccharidosis-

Mucopolysaccharidoses are hereditary, progressive diseases caused by mutations of genes coding for lysosomal enzymes needed to degrade glycosaminoglycans. Products of GAG, Keratan sulphate, Dermatan Sulphate , chondroitin sulphate  accumulates in body and cause various manifestations.

As a general rule, the impaired degradation of heparan sulfate is more closely associated with mental deficiency and the impaired degradation of dermatan sulfate, chondroitin sulfates, and keratan sulfate with mesenchymal abnormalities

There are 7 variants. Recognition of type depends on clinical manifestations, severity and corneal involvement.

I- Hurler Syndrome
II- Hunter Syndrome
III- San Filippo
IV- Morquio
VI-Maroteaux-Lamy
VII- Sly
IX- Hyaluronidase deficiency

Among these all are inherited via Autosomal recessive inheritance except Hunter Syndrome which is an X-linked disorder.


Here is a summary of involvement of organs in different MPS variants-
Hepatosplenomegaly, Coarse facial features, Short stature- disproportionate with Bony changes and Mental deficiency are main features. Corneal clouding in seen in most variants as disease progresses except in Hunter and San filippo syndromes.

In this Child:
We found Short stature, coarse facial features, Dysostosis multiplex, Clear Cornea and visceromeglay with minimal mental deficiency. Likely to be Hunter Syndrome.

This is how a patient with Hunter Syndrome looks like-



Investigations-
Routine CBC, LFT, RFT and urine were normal in the child. On evaluation eye was normal, no cherry red spot on retina.

Urinary GAG quantification was too expensive and could not be done in this patient, likewise Genetic analysis and carrier mapping was not feasible.

Treatment Options-
Available options today are-

1. Hematopoetic Stem cell transplant 
which can be curative. If done before 2 yrs can prevent progression of mental deficiency but this modality does not treat bone and eye problems.
 Transplantation prevents neurocognitive degeneration but does not correct existent cerebral damage. Hence, the main target group are young children with severe MPS I, anticipated neurodegeneration, who undergo transplantation before 24 mo of age and have a baseline mental development index >70.- Nelson textbook of Pediatrics 19th Edition.

2.Replaement Therapy- recombinant enzymes is approved for patients with MPS I, MPS II, and MPS VI.

3.Management of Complications like Hydrocephalus, Orthopedic and vision issues etc.


As we could not objectively prove our Diagnosis, if you have a different diagnosi or opinion for this case, you are free to comment. 

Monday, December 1, 2014

RDS or Hyaline membrane Disease - Classic X ray

A Preterm 33+ weeks male with Perinatal asphyxia presented with Rerpiratory distress at 16 Hour of life. The baby was in respiratory failure so was Intubated immediately and put under mechanical ventilation. The baby required high PIP as lungs were stiff.

Xray was ordered with showed-


Bilateral White out lung field with Air Brochogram.


In Such cases of RDS of Prematurity, best management would have been-
1, Dexamethasone or Betamethasone therapy intrauterine atleast 24 hrs before delivery to provide maturation of lungs.
2. Early CPAP to prevent collapsing of alveoli after delivery if any signs of Distress
3. If feasible , Surfactant therapy within 6 hours with FiO2 requirement increases.