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Pediatrics 2019

Syllabus for Pediatrics

Syllabus for Pediatrics 1
General Pediatrics 3
Child organism in the different age periods. Development of the child 3
Rational nutrition of the child. Conditions of malnutrition 7
Primary and secondary prophylactic. Screening-diagnostics. Immunizations and
immunization schedule 9
Characteristics of the water-salt metabolism. Acid-base balance 10
Differential diagnosis of Coma 13
Principles of therapy in childhood 15
Neonatology 15
Pulmonary pathology in the neonatal period. Hyaline membrane disease, aspiration
syndrome, bronchopulmonary dysplasia 15
Infection pathology in the neonatal period. Sepsis neonatorum, necrotising
enterocolitis, pneumonias, osteoarthritis 17
Neurological diseases in the neonatal period. Neonatal seizures, hypoxemia,
ischemic encephalopathy, periventricular leukomalacia, intracranial hemorrhages 21
Pediatric Pulmonology 24
Acute infections of the upper respiratory passages. Foreign body aspiration 24
Acute pneumonia. Bronchiolitis 27
Bronchial asthma 30
Cystic Fibrosis. Bronchiectasis 32
Respiratory insufficiency in childhood 33
Congenital malformations of respiratory system 35
Tuberculosis 36
Pediatric Gastroenterology 37
Jaundices in the period of the neonate and the breast-fed infant 37
Ulcer diseases, chronic gastritis 39
Enteritis and enterocolitis 40
Malabsorption and maldigestion syndrome. Celiac disease. Mucoviscidosis 43
Chronic hepatitis. Cirrhosis 45
Pediatric Nephrology 47
Congenital malformations of the excretory system. Pyelonephritis 47
Acute and chronic glomerulonephritis 50
Nephrotic syndrome 50
Acute renal insufficiency and chronic renal failure 51
Pediatric Cardiology 52
Congenital heart disease 52
Inflammatory cardiac diseases: Myocarditis, pericarditis, endocarditis 56
Arterial hypertension - essential and symptomatic 57
Cardiac failure 59
Pediatric Autoimmune disease 60

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 Reactive arthritis related to infections, septic arthritis 60
Juvenile idiopathic arthritis (chronic) 61
Systemic lupus erythematosus 62
Vasculitis syndromes - classification, henoch-schonlein purpura, kawasaki disease 63
Physiology and Pathology of calcium-phosphorus metabolism. Rickets 65
Pediatric Endocrinology 66
Differential diagnosis of growth disturbances, diseases of the pituitary gland 66
Disease of thyroid gland 68
Diseases of the adrenal glands, congenital adrenal hyperplasia 71
Physiology and pathology of puberty 72
Diabetes mellitus 74
Obesitas and metabolic syndrome 76
Genetic Abnormalities and Pediatric Neurology 76
Chromosomal disorders 77
Inborn errors of Metabolism - Intoxication type 79
Inborn errors of metabolism - disorders involving energy metabolism and complex
molecules 81
Cerebral palsy in children 82
Neuromuscular diseases 83
Epilepsy - Idiopathic epilepsy and epileptic syndrome. 86
Epilepsy - epileptic encephalopathies 86
Pediatric Hemoncology 88
Anemias due to ineffective hematopoiesis & 49. Hemolytic anemias in childhood 89
Hemorrhagic diseases 91
Leukemia in childhood and adolescent 94
Pediatric lymphomas 97
Solid tumors in children: Nephroblastomas, neuroblastomas, rhabdomyosarcomas 98

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General Pediatrics

1. Child organism in the different age periods. Development of the

child

We can separate the development of the child into five major areas:
- Gross motor
- Fine motor
- Speech and Language
- Cognitive
- Social/Emotional

The table below distinguishes the stages that a child should develop throughout the first five
years of their life.

Lets review this table below:

- Newborn
- Gross motor: primitive reflexes such as step, babinski and flexor posture
- Fine motor: grasp reflex
- Speech and language: suck reflex and startles to loud noises
- Cognitive: fix and follow horizontal arc, prefers high pitched noises

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 - Emotional: Self-regulation/soothing
- 2 months
- Gross motor: Head steady when held at 45 degrees
- Fine motor: bats at object
- Speech and language: turns to voice, cooing
- Cognitive: prefers usual caregiver and attends to moderate novelty
- Emotional: Attachment with parent and social smile
- 4 months
- Gross motor: sits with support, head up at 90 degrees, rolls front to back
- Fine motor: palmar grasp, reaches for objects
- Speech and language: laugh, razz, ‘ga’, squeal
- Cognitive: anticipates routines, sensory exploration of objects
- Emotional: turn-taking conversations, explores parents face
- 6 months
- Gross motor: postural reflex, rolls both ways, sits with tripod
- Fine motor: raking grasp, transfers hand to hand
- Speech and language: babble
- Cognitive: stranger anxiety, looks for dropped or hidden objects
- Emotional: expresses emotions (happy, sad, mad) with 24hr memory
- 12 months
- Gross motor: Walks a few steps, wide-based gait
- Fine motor: Fine pincer with fingers, voluntary release, throws, self feeds
- Speech and language: 1 word with meaning (not mama, dada), understands
name and no
- Cognitive: cause and effect, trial and error understood. Uses objects
functionally
- Emotional: explores and points at wanted items, narrative memory begins
- 18 months
- Gross motor: Stoops and recovers, runs
- Fine motor: carries toys while walking, removes clothing, scribbles
- Speech and language: points to objects and body parts. 10-15 words.
- Cognitive: problem solving, searches for hidden objects
- Emotional: shared attention, points at interesting items to show parents
- 2 years
- Gross motor: jumps on two feet, up and down stairs
- Fine motor: handedness established, uses fork, tower of 6 blocks
- Speech and language: follows 2 step commands, 50+ words, 2 word phrases
- Cognitive: new problem solving strategies, searching for hidden objects
- Emotional: starts testing limits, tantrums and negativists
- 3 years
- Gross motor: pedals tricycle, up stairs with alternating feet
- Fine motor: undresses and toilet trained. Draws a circle and cross, can turn
pages in book
- Speech and language: 3-step commands, 200+ words, 3-4 word phrases, W
questions
- Cognitive: simple time concepts, identifies shapes, compares items
- Emotional: separates easily, sharing, empathetic, cooperative play, role play
- 4 years

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 - Gross motor: hops on one foot
- Fine motor: draws shapes, can cut shapes with scissors
- Speech and language: full sentences, all words intelligible, tells a story
- Cognitive: counts to 4, understands opposites and colours
- Emotional: has preferred friend with elaborate fantasy play

Newborn Check in Hospital

- Head to toe - look for syndromes
- Listen to heart and lungs and pulse
- Look for femoral pulse
- Hip abduction (dislocatable hip??)
- Skin crease in buttocks, sacral dimple (spina bifida)
- Head circumference and length
- Eyes - look for red reflex (absent is congenital cataracts)

Six week check

- As above

The primitive brain structures of the hindbrain and midbrain mature within the first three
years of life, by the age of 2 the brain is 80% the size of an adult brain, however the frontal
lobe doesn’t fully begin to function until between 5-7.

The main stages of neurodevelopment were summed up by Piaget in

three stages:
- Schemas of the world (basic building blocks such as cognitive
models that allow for mental representation of the world)
- Assimilation and Accommodation (using an existing schema
to deal with a new object or information and the adaptation of a
schema to accommodate new knowledge that doesn’t fit an
existing schema)
- Cognitive development, of which four stages where identified
- Sensorimotor stage (0-2) ith development of object
permanence
- Preoperational stage (2-7) brining the ability to think
conceptually
- Concrete operational stage (7-11) gives the child the
ability to think logical or operational thought
- Formal operational stage (11+) the child is able to think
about abstract concepts, and logically test hypotheses

The life of a ‘child’ can be broken up as follows:

- Neonatal period (from 0-28 days)
- Infancy period (from 28 days to 1 year/ 18 months)
- Childhood (from 1 year to puberty)
- Puberty/Adolescence (from the point of puberty begins, 7-12 in women, 9-14 in
males)

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Growth
- Fetal growth is the fastest period of growth, accounting for 30% of eventual height
- Size at birth is determined by the size of the mother, nutrient supply and
insulin like growth factor 1 and 2 (IGF 1 and 2) - this is largely independent from
fathers size and GH
- The infantile phase accounts for 15% of adult height and is a continuation of the
fetal growth, all be it at a slower rate, with nutrition, thyroid hormone and
psychosocial health being the key growth factors
- Childhood accounts for 40% of adult height, all of the elements of the infantile
phase that controlled growth also apply here, however growth hormone now plays
an important role as well
- The final phase of growth is the pubertal part, which accounts for 15% of adult size,
testosterone and oestrogen and growth hormone are the most important
mediators here.

Measurement
- Growth is measured with weight and length (height)
- Children aged 2 years and below should be measured in a supine position
- We can also measure head circumference, BMI and body area (often used for certain
drugs)
- Significant abnormalities of height are:
- Below 0.4th or above 99.6th percentile or outside the midparental height
range - any discrepancies in weight should also be evaluated

Puberty

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 - The first sign in women is breast development followed by pubic hair growth and raid
height growth
- In males testicular enlargement to over 4ml volume (measured with orchidometer) is
the first clinical sign of puberty. Pubic hair growth and rapid height growth then occur
- In both sexes there will be development of acne, axillary hair, body odor and mood
changes
- X-rays can also be used to determine skeletal maturation and detect if growth has
finished by observing the growth plates

Short stature
- Defined as height below the second centile
- Causes include
- Familial
- Constitutional delay in growth and puberty
- Small for gestational age and extreme prematurity
- Chromosomal disorders
- Nutritional/long-term illness
- Psychosocial deprivation
- Endocrine (hypothyroidism, growth hormone deficiency, corticosteroid
excess/cushings)

Assessment of child with short stature

- Examination of the growth chart
- History (birth measurements, pregnancy history, feeding history, FH, medications)
- Examination (dysmorphic features e.g. Turner, chronic illness, skeletal dysplasia)

For physical developmental milestones of the child, see question 1.

Developmental Milestones simplified

2 months Head steady and preferes caregiver

4 months Sits with support

6 months Rolls and sits, can babble

12 months Walks, 1 word

18 months Runs, 10-20 words

2 years Jumps, follows commands (2 steps)

3 years Tricycle, phrases

4 years Hops, full sentences

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Normal Body weight at birth is 2.5-4kg. There is an 8% reduction in the first week after
birth, we then expect body weight to multiply by 3 by the end of the first year of life.

2. Rational nutrition of the child. Conditions of malnutrition

Infants and children are more likely to have issues of malnutrition than adults, this is down to
low nutritional stores and a high nutritional demand for growth, especially brain growth. Good
nutrition is key for growth, and good nutrition leads to increased growth of the child.
Additionally, it has been established that there is an optimal birth weight to avoid coronary
heart disease, around 4kg, with significant increases in lower weights.

Infant feeding
Breastfeeding is universally advocated for the first six months of baby development, it
leeds to improved GI and respiratory tract health with fewer infections. Additionally
breastfeeding is associated with reduced obesity, diabetes mellitus and hypertension
later in life.

The colostrum produced in the first few days after birth has an amount of protein and
immunoglobulins that are highly beneficial for the baby.

Infants should not be given cow's milk before the age of 1 year, and some say not
before 18 months as it can lead to low levels of iron.

Solid foods should be introduced gradually, not before 17 weeks, but not after 26
weeks. Foods should be low in salt and sugar.

The amount of milk that should be consumed by the infant is as follows:

- 1st month - 100ml 7-8x daily
- 2nd month - 120 ml 5-6x daily
- 3rd month - 130 ml 4x daily

Weight faltering is the term used to describe weight loss in infants. It is defined as a
sustained drop down two centile spaces. After the first 4 months only 0.5% of children
in the uk will do this. In order to identify this, all babies should be weighed during 1st,
8th, 12th, 16th and 52nd weeks. Any child whose weight crosses two centile lines or is
below the 0.4th centile, or a BMI less than the second centile should be evaluated.

Causes of weight faltering can be:

- Inadequate intake
- Inadequate retention
- Malabsorption
- Failure to utilize nutrients
- Increased requirements due to pathology

Investigations in weight faltering

- Full blood count

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 - Serum creatinine, urea, electrolytes, acid-base
- LFTs
- Thyroid function
- CRP
- Immunoglobulins
- Ferritin

Malnutrition
Assessment of malnutrition can be via anthropometry (weight, height, skinfold thickness),
laboratory tests (albumin, specific mineral and vitamin levels), dietary intake and
immunological assessment.

Malnutrition is a multisystem disorder that causes impairment of immunity, reduced

wound healing, delays diseases recovery and more. Enteral nutrition should be given
while the digestive tract is functioning, while parenteral nutrition is given where enteral
nutrition is inappropriate.

Symptoms of severe malnutrition include flaky skin, distended abdomen and enlarged
liver, angular stomatitis, sparse hair, diarrhea and hypotension.

Severe malnutrition should be treated with ready-to-use therapeutic food, a mix based on
peanut butter and dried skimmed milk and vitamins and minerals. Acute treatment includes:
- Treat hypoglycemia
- Treat hypothermia
- Treat dehydration (avoid fluid overload)
- Correct electrolytes
- Treat infection
- Correct micronutrient deficiency
- Initiate feeding

Common micronutrient deficiencies:

- A - found in children with fat malabsorption, increased susceptibility to infection and
impaired adaptation to dark, dry eyes and excessive blinking
- D - found in children with darker skin who live further away from the equator, causes
rickets, a disease of the bones
- E - found in children with fat malabsorption, causes haemolytic anemia, retinopathy
and progressive neuropathy
- K - found in newborn infants, causes clotting abnormalities that lead to bruising from
vitamin k deficiency bleeding (haemorrhagic disease of the newborn)
- B1 - children from SE Asia with a polished rice diet - can cause cardiomyopathy,
aphonia, encephalopathy and others
- B2 - due to malnutrition, causes angular stomatitis
- C - rare, but can occur in children with neurodisabilities. Causes petechiae, poor
growth, and painful joints
- Folic acid - causes macrocytic anemia

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 3. Primary and secondary prophylactic. Screening-diagnostics.
Immunizations and immunization schedule

Primary prevention is the promotion of a healthy lifestyle including eating well with exercise
and not playing on rubbish dumps.

Secondary prevention is the management of latent diseases and the attempts to prevent
asymptomatic diseases from becoming symptomatic.

4. Characteristics of the water-salt metabolism. Acid-base balance

Water control
Water (and electrolyte) homeostasis is controlled by three hormones:

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 - Aldosterone (ADH) - released from the adrenals, responds to increased osmolarity
- Vasopressin - released from the posterior pituitary, responds to decreased blood
volume
- Atrial natriuretic peptide- released from atria in response to increased blood volume

The table below summs of the action of all the hormones shown in the image above

Hormone Action

Vasopressin Released in response to increased plasma osmolarity and decreased blood

volume. Causes increase in aquaporins with increase in H2O
reabsorption. Net effect ↑H2O

Aldosterone Released in response to decreased blood volume and high K+

concentrations. Causes reabsorption of Na+ and water, with increased
secretion of K+ and H+. Net effect: ↑H2O ↑Na+, ↓K+ and ↓H+

Atrial natriuretic Released in response to decreased blood volume. Causes afferent arterial
peptide vasoconstriction, leading to increased GFR and increased Na+ excretion,
with no compensatory increase in reabsorption. Net effect ↓H2O ↓Na+

Angiotensin II Released in response to decreased BP. Causes efferent arteriole

constriction leading to increased GFR filtration and increased Na+

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 excretion, WITH a compensatory increase of Na+ reabsorption.
Net effect preserved GFR in low volume states

PTH Released in response to low calcium, high phosphorous. Causes increased

Ca2+ reabsorption and increased PO4- excretion. Net effect ↓PO4- ↑Ca+.

Characteristics of the water-salt metabolism

Water is approximately 70% of the human lead body mass in adults, and even more in
newborns. Water is found in the ICF and ECF, with the ECF further divided into interstitial
fluid, plasma and transcellular fluid. Two forces govern the movement of water, osmosis
and hydrostatic pressure.

Water balance is governed by balancing the gains and losses of the system. Water required
is approximately 2.6L/day, with 1.6L coming from drinking, and another 1 L from food
and metabolic processes. Water losses also total 2.6L, with 1.5L of that coming from urine,
another 1 L from skin and lungs, and 100ml from faeces. The value there that is capable of
significant change is the urine. This is controlled by the Antidiuretic hormone (ADH aka
Vasopressin) which is released from the hypothalamus. Where plasma osmolality is
low, little ADH is produced and copious dilute urine is produced thanks to the action
of ADH on collecting tubules and the outer and inner medullary collecting duct. Where
plasma osmolality is high, ADH secretion is increased and the volume of urine decreases.

Note - Low Vasopressin = increased, more dilute, urine secretion. High vasopressin =
more fluid reabsorbed, less, more concentrated urine.

The collecting ducts are central to understanding the water-salt relationship. Water follows
salt, so in order to create the required concentration gradient where water wants to be
reabsorbed, we need to actively transport sodium out of the lumen of the tubules and into
the interstitium. Sodium is actively transported (with potassium going the other way) in
the distal tubule and collecting ducts back into the interstitial fluid of the body. This
creates an osmolality of up to 1200mOsmol kg-1.

As water follows sodium everywhere, the balance of sodium is very important, Na+ should
be at 135-145 mmol-1, this is controlled by glomerular filtration, aldosterone and other
factors such as angiotensin 2 and dopamine. Hypernatremia (aka hyperosmolality)
occurs when there is too much salt for the amount of fluid, this can be hypervolaemic
hypernatraemia (when one has consumed too much salt) or hypovoleaemic
hypernatraemia (when one has consumed too little water). The opposite condition,
hyponatremia may be due to lack of salt intake or due to the intake of too much water.
Severe hyponatremia is a serious but rare condition.

Volume depletion in Children/Hypernatraemia

- Mild volume depletion, use oral rehydration solutions (ORS)
- Use hypotonic ORS with 75 mEq/L sodium + 75 mmol/L glucose with total
of 245 mOsm/L

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 - Severe volume depletion use isotonic saline (crystalloids or colloids IV) or
intraosseous (start 20 mL/kg over 5 mins, repeated 3 times in rapid succession)

Hyponatraemia
- Acute onset: Hypertonic 3% saline infusion 2-4ml/kg in 100ml increments over 10
minutes (usually bolus)

Acid-Base balance
PH is important. Normal pH is between 7.35 and 7.45, even small deviation from this range
can cause developmental delay in chronic cases, and can be life threatening in severe
cases. The two organs responsible for the acid-base balance are the kidneys and the
lungs.

The lungs remove the acidic CO2, while the kidneys do two things, they excrete the
acidic hydrogen ions and reabsorb filtered bicarbonate. Let's take a look at what the
kidneys do in a bit more detail as it's a bit complicated.

Within the kidneys two areas are involved in the acid base balance: the proximal tubular
mechanism and distal tubular mechanism. The proximal tubules reabsorb bicarbonate
(base) which is filtered at the glomerulus and excretes H+ (acid) while simultaneously
excreting ammonia (base). The distal tubular mechanism sees additional excretion of
ammonium and H+, with reabsorption of the remaining bicarbonate.

Acidemia is a pH below 7.35, with alkalemia a pH above 7.45. Acid-Base imbalances can be
simple or complex. A simple imbalance is one with a single underlying metabolic cause, a
complex one has multiple causes. We can also define acid-base balances as metabolic or
respiratory, and describe them as compensated or not compensated.

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The pH and PCO2 are the most important labs to consider. Remember range for PCO2 is
35-45mmHg, if the PCO2 and the pH go the same direction, it is metabolic
acidosis/alkalosis, if they go in the opposite direction it is respiratory. We should suspect a
mixed acid-base disorder if either the pCO2 or HCO3- is abnormal but pH normal, or if there
is a greater than expected compensation response.

Now lets say something about compensation. This is fairly self evidence in the sense that
the body will try and ensure the pH stays neutral by removing/adding more acid/base
depending on the problem. So where we have respiratory acidosis (high pCO2) the body
will try to retain more HCO3- to compensate. If we have high pCO2 and high HCO3- but
normal pH we can describe this as compensated. Metabolic disorders can be
compensated for by the lungs very rapidly, however the kidneys can only compensate for the
lungs in a matter of days.

The anion gap is the difference between the concentration of unmeasured anions and
the concentration of unmeasured cations. The calculation is: Na+ - CL- - HCO3-. A
normal anion gap is 3-11. The anion gap is useful for evaluating patients with metabolic
acidosis, as it divides such patients into two, those with normal and those with an abnormal
anion gap, each of which have their own causes. A normal anion gap metabolic acidosis
(aka hyperchloremic acidosis) means that we have a loss of HCO3- compensated with
an increase in Cl- meaning the anion gap is the same. A high anion gap means that there
has been no compensatory increase of Cl-.
- Causes of high anion gap are MUDPILES
- Methanol
- Uremia
- Diabetic ketoacidosis
- Paraldehyde
- Isoniazid or ion overdose
- Lactic acidosis
- Ethylene glycol intoxica
- Salicylate intoxication
- Causes of normal anion gap are FUSEDCARS
- Fistula (pancreatic, biliary)
- Uretero Gastric conduit
- Saline administration
- Endocrine (addisons)
- Diarrhea
- Carbonic anhydrase inhibitor
- Ammonium chloride
- Renal tubular acidosis
- Spironolactone

Treatment
- Respiratory acidosis - treat underlying respiratory cause (COPD, opioid intoxication
etc)
- Respiratory alkalosis - treat hyperventilation symptoms, breath into a bag
- Metabolic acidosis - acute + severe (pH < 7.1) give sodium bicarbonate IV, chronic,
give oral sodium bicarbonate

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 - Metabolic alkalosis - if volume depletion give isotonic saline, if bicarbonate excess
give acetazolamide

Disease Change in CO2, H2CO3- Cause

Respiratory Acidosis Increase CO2 CO2 retention e.g. COPD,

Increase H2CO3- (compensation) pneumonia, asthma, CNS
depression

Respiratory Alkalosis Decrease CO2 Hyperventilation, CO2 washout

Decrease H2CO3- (compensation)

Metabolic Acidosis Decrease CO2 (compensation) Increased H+ production or loss

Decrease H2CO3- of H2CO3 e.g. in Diabetic
ketoacidosis or Renal diseases

Metabolic Alkalosis Increase CO2 (compensation) Due to loss of H+ or increased

Increase H2CO3- H2CO3 retention e.g. in
Vomiting or diuretic use

5. Differential diagnosis of Coma

OK, going to broaden this question out to include all altered mental states.

Consciousness is one's awareness of self and environment while arousal represents

the system that initiates and maintains consciousness. Consciousness is the product
of the cerebral cortex, while arousal is the product of the reticular activating system
(RAS) of the brain stem. Patients can be described as having a reduced level of
consciousness, the most extreme end of this being that of a Coma, where the patient is
totally unresponsive in their unconscious state - this is the result of bilateral cerebral
hemisphere and/or brainstem dysfunction.

Altered mental states can be due to Infection, Trauma, Toxins, hypoxia-ischemia,

epilepsy, stroke, increased intracranial pressure, migraine, systemic disorders or
metabolic derangements. When a patient presents with altered mental state there are
basic diagnostic procedures one should perform, these are:
- Routine labs (glucose, electrolytes, AST, ALT, blood gases, ammonia, blood and
urine tox screen)
- CSF analysis (where ICP is normal)
- Neuroimaging (CT, MRI)
- Electrodiagnostic studies
- Secondary lab testing if still unsure
The most common cause of long-term morbidity in a patient with depressed consciousness
is hypoxia as a result in all cases the airway should be secured, with vital signs assessed.
Also pay close attention to the physical examination, symptoms such as Cheyne-Stokes
respiration may be present, suggesting loss of cerebral, thalamic or hypothalamic

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modulation of respiration. This pattern can also be seen in patients with metabolic
disorders, heart failure or primary respiratory disease.

The glasgow coma scale should be used to assess unresponsive patients, scoring between
0-15, with a detailed neurological examination of the comatose patient (including pupillary
responses) to assess brain stem function.

When considering altered mental state, consider that not all changes will be acue,
diseases such as viral meningoencephalitis (particularly herpes simplex virus) can present
subacutely, with the presence of fever, petechiae, chills and sweats suggesting infection.

Certain clinical manifestations can help us assess the precise cause(s) of the altered
consciousness, concomitant symptoms of infection suggest meningitis/encephalitis,
while papilledema* or paralysis of CN II or VI strongly suggest elevated ICP.

Treatment is dependent on the underlying cause, but in call cases ABCDE should be
observed. Prognosis is poorer in cases of hypoxia, and generally children have better
outcomes than adults.

Episodic alterations of consciousness occur one should consider seizures, migraine,

syncome or metabolic abnormalities such as hypoglycemia. Syncope is probably the most
common cause of abrupt, episodic loss of consciousness, this can be neurogenic or
cardiogenic and both should be considered in the work up.

*Observe through Fundoscopy with disc selling (usually bilateral)

Potential causes of Coma

TITIMO
- T - Trauma
- I - Infection
- T - Tumour

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 - I - Infarction
- M - Metabolic
- O - Oxygen

6. Principles of therapy in childhood

………….

Neonatology

7. Pulmonary pathology in the neonatal period. Hyaline membrane

disease, aspiration syndrome, bronchopulmonary dysplasia

Firstly, let’s address what is neonatal?

- Early neonatal period - birth to 7 days
- Late neonatal period - 7 days to 28 days
- Post neonatal period - 28 days to 1 year
- Perinatal = 28 week - 7 days
So, neonatal is birth to 28 days.

Newborn infants have the following symptoms of respiratory distress:

- Tachypnoe (>60 breaths/min)
- Laboured breathing, with chest wall recession and nasal flaring
- Expiratory grunting
- Cyanosis

Let’s review some of the key causes of respiratory distress.

Transient tachypnoea of the newborn

- The most common cause of respiratory distress, especially after C section
- Chest x-ray shows fluid in the horizontal fissure
- Usually resolves spontaneously within 1st day of life

Hyaline membrane disease

- This is a disease of the premature infant, it is now commonly known as Respiratory
Distress Syndrome (RDS) and is the result of insufficient surfactant which is
responsible for keeping the alveoli open
- The condition affects about 50% of babies born at 26-28 weeks, and about 25% at
30-31 weeks
- The disease is a type of hypoplasia, with type II pneumocytes failing to fully develop
- Diagnosis is via clinical picture (tachypnea, tachycardia, cyanosis) and X-ray which
shows decreased lung volumes and a ground glass infiltrates, uniform throughout the
lungs

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 - Oxygen should be given with a small amount of CPAP, with IV fluids and exogenous
surfactant which should be given through the breathing tube into the lungs

Meconium aspiration (aspiration syndrome)

- Meconium is a sticky dark green substance that contains GI secretions amniotic fluid,
bile acids, blood, mucus, cholesterol and pancreatic secretions.
- Meconium accumulates in the foetal GI tract through the third trimester of pregnancy
and is usually released in the first 48 hours after birth - however, in cases of foetal
distress such as hypoxia, or in post term babies, the fetus can pass the meconium
into the amniotic fluid
- Stress may cause the fetus to gasp reflexively, thus inhaling amniotic fluid containing
meconium into their lungs
- Meconium aspiration predisposes the infant to infection and causes irritation, known
as lung pneumonitis. Lungs are often overinflated, accompanied by patches of
collapse and consolidation with a high risk of pneumothorax complication
- Treatment is mechanical ventilation, infants may develop persistent pulmonary
hypertension of newborn making adequate ventilation difficult

Pneumonia
- Prolonged rupture of the membranes, chorioamnionitis (infection of the amniotic fluid)
and low birthweight all predispose an infant to pneumonia
- Broad-spectrum ABs are started early until the results of the infection screen are
available

Pneumothorax
- Can occur spontaneously in 2% of cases, it is generally asymptomatic but may cause
symptoms of respiratory distress

Persistent pulmonary hypertension of the newborn

- Life threatening and associated with birth asphyxia, meconium aspiration,
septicaemia or respiratory distress syndrome (aka hyaline membrane disease)
- The result of high pulmonary vascular pressure causing right to left shunting
within the lungs and atria.
- Cyanosis occurs occurs soon after birth, echocardiogram is often the only method of
diagnosis
- Most infants require mechanical ventilation and circulatory support, with nitric oxide
being beneficial

Bronchopulmonary dysplasia
- Infants who have an oxygen requirement at a postmenstrual age of 36 weeks are
described as having bronchopulmonary dysplasia (aka chronic lung disease).
Often a complication of Respiratory Distress Syndrome
- The lung damage is due to delay in lung maturation, and possibly from pressure
and volume trauma from artificial ventilation
- Chest x-ray shows widespread areas of opacification, with some cystic changes
- Infants should be weaned onto CPAP followed by additional ambient oxygen over
several months. Corticosteroid therapy may also be required.

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 8. Infection pathology in the neonatal period. Sepsis neonatorum,
necrotising enterocolitis, pneumonias, osteoarthritis

Preterm infants are at an increased risk of infection as IgG is mostly transferred across
the placenta in the last trimester and therefore, where born early, they do not get their full
complement of antibodies. Additionally, infection around the cervix is often a cause of
preterm labor and this may cause the postpartum infection. Such infections are known
as congenital infections. Common causes include toxoplasmosis, rubella,
cytomegalovirus, herpes simplex, varicella zoster, syphilis and others. Where the
infection is intrauterine we can see growth restriction and infant deformities.

In early onset infection (<24hrs), bacteria have ascended from the birth canal and invaded
the amniotic fluid. The fetus is secondarily infected as the fetal lungs are in direct contact
with infected amniotic fluid. These infants have pneumonia and secondary
bacteraemia/septicemia aka sepsis neonatorum.

The most common infectious agents in neonates post birth are group b
streptococcus, e. Coli and enterococcus. With the recommended first line treatment
being Benzylpenicillin + Gentamicin. When treating neonates with ABs, always also
give fluconazole as a prophylactic antifungal medications, candida can commonly affect
newborns on ABs and can be a severe complication of treatment.

The below are the ABs that should be considered for all neonatal infections

Intrapartum antibiotics
- Offer intrapartum AB prophylaxis with IV benzylpenicillin to prevent early onset
neonatal infection in any women who had group B strep colonisation, bacteriuria or
infection in current or past pregnancy

Dosage Benzylpenicillin
- 25mg/kg every 12 hours (shortened to 8 if infant very ill)

Dosage Gentamicin
- 5mg/kg every 12 hours

Monitor CRP 18-24 hours after presentation and continue to monitor, consider halting ABs
after 36 hours if signs of infection have abated.

Dosage of Amoxicillin (for meningitis)

- <7 days old - 50mg/kg/dose every 12 hours
- >7 days old - 50mg/kg/dose every 8 hours
Double dose if Meningitis. IV infused over 30 minutes, may be given oral

Start with Amoxicillin + gentamicin if unknown cause of meningitis, if it is proved to be

group B strep, change ABs to benzylpenicillin (50mg/kg)

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Early symptoms of infection include respiratory distress with transient apnea, changes
in muscle tone, an increase in liver and spleen size, often with abdominal
enlargement, with a petechial rash sometimes present. Laboratory analysis should be
performed, the WBC can be raised or decreased, with a count <5000 being a very poor
prognostic indicator. A decreased platelet count can also indicate an infection, as can a
change in the ratio between immature and total neutrophils. Finally, consider CRP and
procalcitonin levels, an increase in either can indicate a pathology. Note, IgM antibodies do
not cross the placental barrier, as such any increase can tell us for sure that the neonate has
an infection, and not the mother.

Sepsis neonatorum
The infections described above can very quickly become systemic in neonates given their
small size and decreased immunity, this risk is even more acute where the child is preterm
(due to an even more suppressed immune system).

Sepsis neonatorum is therefore a common complication in preterm children, most commonly

caused by group B strep, E.coli and L. monocytogenes, while Klebsiella is more common in
less developed countries.

Sepsis prevents in three periods:

- Early onset sepsis - begins in utero and is usually the result of infection caused by
the bacteria in the mothers genitourinary tract (group B strep, e.coli, klebsiella)
- Most infected infants are prem and show cardiorespiratory signs such as
grunting, tachypnea and cyanosis
- Onset birth -7 days - an overwhelming multiorgan system disease which manifests
with respiratory failure, meningitis, DIC, acute tubular necrosis and symmetrical
peripheral gangrene.
- Clinical manifestations at the early stages may be non-specific and care
should be taken to evaluate CSF, CBC, chest radiograph to evaluate for
pneumonia as well as ABG.
- Ampicillin + Gentamicin 10-14 days is recommended treatment
- Late onset (8-24 days)
- May present as lethargy, poor feeding, hypotonia, apathy, seizures, bulging
fontanelle, fever and hyperbilirubinemia
- Similar evaluation to early onset

Lab analysis for Sepsis

- CBC
- Differential smear
- Blood culture
- Urine culture
- Lumbar puncture
- Chest x-ray (if respiratory symptoms)
Diagnosis is given based on isolation of the pathogen in culture.

Treatment
Use IV benzylpenicillin with gentamicin as first choice AB.#

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 - Benzylpenicillin dose 25mg/kg every 12 hours
- Gentamicin 5mg/kg, single dose, only give second after 36 hours

In the community, if you suspect meningitis give IM Benzylpenicillin

Necrotising enterocolitis
This is a syndrome of intestinal injury and is the most common intestinal emergency
occurring in preterm infants, with an incidence of 3/1000. Prematurity is a constant
contributor to the disease, and is infrequent in term infants. The cause is thought to be a
combination of suppressed intestinal host defense, decreased intestinal motility and
lack of blood flow autoregulation.

Clinical signs include abdominal distention, feeding intolerance, emesis, rectal bleeding
and occasional diarrhea. WBC is often depressed, but can be elevated. Patients may also
present with electrolyte imbalance, hypo/hyperglycemia and metabolic acidosis.

Radiographic imaging is the gold standard diagnosis, the differential includes sepsis with
intestinal ileus or volvulus. Management is discontinuation of enteral feeding, GI
decompression with nasogastric suction, fluid and electrolyte replacement with
systemic broad-spectrum ABs. 50% of infants with NEC require surgical intervention,
this decision is based on presence of pneumoperitoneum. Can be complicated by infection
from C. Perfuringis.

Antibiotics should be:

- Ampicillin/Gentamicin/Cefotaxime
- + Metronidazole or Clindamycin

Pneumonias
Onset may be within hours of birth as part of a generalised sepsis syndrome or after 7 days
and confined to the lungs, defined as early onset or late onset.

Most common organisms are gram positive group A and B streptococci, MRSA, E. coli and
Klebsiella. Early onset pneumonia may present with generalised poor condition, often
presenting along with neonatal sepsis. Late onset hospital acquired pneumonia manifests
with worsening of respiratory status, with grunting, tachypnea, etc. Lab results will show
temperature with neutropenia.

Diagnosis is via chest x-ray with gram staining and culture of tracheal aspirate. Infiltrate
should be present on x-ray (although diagnosis may be complicated by severe
bronchopulmonary dysplasia). In all cases a full evaluation for sepsis (including CSF
analysis) should be done due to the tendency for the spread of infection across the body.

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Treat with vancomycin and broad-spectrum beta-lactam drug (e.g. ampicillin or cefepime -
see above for antibiotics in the neonate).

Osteoarthritis
Also known as pediatric septic arthritis, this is a disease due to microbial
agents in a joint space, with osteoarthritis of the hip being a true orthopedic
emergency that can result in the loss of the leg if not detected. The signs of
the disease are subtle, with any non traumatic joint pain with evidence of
swelling, warmth or redness requiring emergency medical attention. The joint
may also present pseudoparalysis, with no motion permitted due to the pain.
Fever is very common, and any patient presenting with any kind of joint
limitations + fever should be considered for osteoarthritis.

The most common etiology is hematogenous spread of bacteria into the

synovium. Often osteoarthritis exists with osteomyelitis. The most common
infectious agent in neonates is staphylococcus aureus, followed by E.coli and
group B strep as two other common causative agents. In older children (2 months - 5 years)
H. influenzae is the most common cause prior to vaccines, now S. aureus is the main culprit.

Lab analysis should include full CBC, glucose, gram stain and culture, a radiograph and/or
ultrasound should then be performed, with eventually analysis of the synovial fluid. Shows
on X-ray with Sunbeam presentation.

Treatment should be 2-3 days of immobilization with antibiotic therapy.

9. Neurological diseases in the neonatal period. Neonatal seizures,

hypoxemia, ischemic encephalopathy, periventricular
leukomalacia, intracranial hemorrhages

Neonatal seizures
Clinical types of neonatal seizures
- Focal clonic - repetitive rhythmic contractions of muscle groups of the limbs, face or
trunk. May be unilateral or multifocal and cannot be suppressed
- Focal tonic - sustained posturing of single limbs, sustained asymmetric posturing of
the trunk with sustained eye deviation.
- Myoclonic - arrhythmic contractions of muscle groups of limbs, face, or trunk.
Typical not repetitive and may be provoked by stimulation
- Generalised tonic - sustained symmetric posturing of limbs, trunk and neck.
- Ocular signs - random and roving eye movements of nystagmus
- Orobuccolingual movements - sucking, chewing or tongue protrusions
- Progression movements - rowing/swimming of arms, pedaling of legs, may be
suppressed unlike tonic and clonic movements

Seizures in the neonatal period are due to a range of causes, we have listed the most
common causes, and the symptoms to look for, below:

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 - most commonly due to hypoxic-ischemic encephalopathy (post asphyxial
seizures) within the first 24 hours of birth
- intraventricular hemorrhages, between days 1-3 of life, look for bulging fontanelle,
hemorrhagic spinal fluid, anemia, lethargy and coma
- metabolic seizures, due to hypoglycemia, hypocalcemia and hypomagnesemia
- Seizures after the first five days of life may be due to infection or drug withdrawal
- seizures that occur with acidosis and lethargy may be due to inborn errors of
metabolism
- An infant with a FH of seizures may be suffering from benign familial seizures
- Where there is a very sudden onset on day 1-3 with short seizures, one must
consider a subarachnoid hemorrhage.

Seizures can be differentiated with the help of EEGs and MRIs. Subtle seizures are a
common manifestation in newborns and will include apnea, eye deviation, tongue
thrusting, eye blinking and staring. In all infants with seizures full blood analysis should
be done, reviewing sodium, calcium, glucose and bilirubin, and an LP done if there are no
signs of increased intracranial pressure.

Treatment of neonatal seizures may be specific if the cause is metabolic (e.g. collection of
hypoglycemia, hypocalcemia, hypomagnesemia, hyponatremia etc), treatment of the
underlying cause (e.g. treatment of meningitis) or general anticonvulsant therapy if the
underlying cause cannot be identified. Anticonvulsants that can be used in infancy
include phenobarbital (20-40mg/kg), phenytoin (10-20mg/kg) or diazepam (0.1-03
mg/kg).

Causes of Seizures - VITAMINS

- V = Vascular
- I = Infections
- T = Toxins and Trauma
- A = Autoimmune (e.g. SLE)
- M = Metabolic
- I = Idiopathic (epilepsy)
- N = Neoplasm
- S = Syncope

Febrile seizures occur ages 6mths - 6 years. They can be simple or complex:
- Simple seizure - no investigation required, all of the following criteria
required:
- General Tonic-Clonic
- <15 mins
- Once in 24 hours
- No focal defect
- Complex seizure - investigation required (is it Meningitis??)
- Focal
- >15 mins
- More than once in 24 hours
- With deficit

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Ischemic encephalopathy
Known as Hypoxic-Ischemic encephalopathy, this is the result of reduced uteroplacental
blood flow or reduced spontaneous respiration, characterised by evidence of brain injury
due to asphyxia. Both of these lead to perinatal hypoxia, followed by lactic acidosis, and if
severe enough to reduce cardiac output or cause cardiac arrest, ischemia.

Reduced availability of oxygen for the brain due to hypoxia, in combination with reduced
blood flow (ischemia) leads to reduced glucose metabolism and an increase in lactate that
produces tissue acidosis. After reperfusion, hypoxic-ischemic injury is complicated by
cell necrosis and vascular endothelial edema which reduces blood flow to the
affected area.

The classic clinical picture is that of cerebral edema, cortical necrosis and involvement
of the basal ganglia. The specific symptoms will depend on the ‘stage’ of the injury, with
details listed in the table below. Generally symptoms include reduced consciousness,
seizures, respiratory difficulty and depression of muscle tone. Infants often present with
low apgar scores, and are often diagnosed with cerebral palsy.

Neonatal encephalopathy can be treated with hypothermia therapy which reduces brain
damage and future disability.

Periventricular leukomalacia
PVL is a type of white matter hypoxic brain injury, histologically characterised by white
matter necrosis near the lateral ventricles. It is significantly more common amongst
premature infants, and can lead to neonatal encephalopathy. This of this as one of the
causes of neonatal encephalopathy and cerebral palsy.

PVL undergoes three pathogenic stages, necrosis, resorption and formation of gliosis
scars or cysts. PVL is incredibly hard to distinguish clinically in a newborn, symptoms
include hypotonia, respiratory distress, vision defects, apnea, seizures and
bradycardia. Later motor development is invariably affected and it is often later in childhood
as patients miss developmental milestones that they are diagnosed.

There are no clear treatment methods for PVL, management is largely supportive.

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Intracranial hemorrhages
There are three categories of neonatal intracranial hemorrhage; subdural, subarachnoid
and periventricular. Let's discuss these below.

First, subdural hemorrhages. These are seen in trauma, generally in the case we’re
talking here, birth trauma. Often due to cephalopelvic disproportion, forceps delivery,
large gestational injury of infant, skull fractures and postnatal head traumas.
Subdurals do not always present immediately, and may be asymptomatic, however after a
number of weeks the child may present with anemia, vomiting, seizures and macrocephaly.
Child abuse should also always be considered.

Subarachnoid hemorrhages are rare in neonates, they may be spontaneous and

associated with hypoxia or caused by bleeding from a cerebral arteriovenous malformation.
Seizures are the most common presenting factor.

Periventricular hemorrhage and Intraventricular hemorrhages are common in very low

birth weight infants, with the risk decreasing with increasing gestational age, as many as
50% of infants weighing less than 1.5kg have evidence of intracranial bleeding. The
exact pathogenesis is not known, but the vessels rupture and hemorrhage due to passive
change in cerebral blood flow occurring with the variation of blood pressure that sick
premature infants often exhibit due to a failure of autoregulation. Most of these kinds of
hemorrhage occur in the first 3 days of life, with clinical manifestations including
bradycardia, lethargy, coma, hypotension, metabolic acidosis, anemia, bulging
fontanelle and cutaneous mottling. Periventricular/intraventricular hemorrhages are
graded 1 - 4, with 4 the most severe. Upon resolution, cysts/gliosis may occur, causing
periventricular leukomalacia, a precursor to cerebral palsy.

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Pediatric Pulmonology

10. Acute infections of the upper respiratory passages. Foreign

body aspiration

PO2 <85mmHg and PCO2 >45mmHg are abnormal.

Children have an average of 5 upper respiratory tract infections (URTIs) per year in the first
few years of life, 80% of which involve the nose, throat, ears or sinuses. Common conditions
are:
- Common cold
- Sore throat (pharyngitis, including tonsillitis)
- Acute otitis media
- Sinusitis

Generally speaking children have a combination of these diseases.

Common causes of URTI - RIAERC

- Rhinovirus
- Influenza (parainfluenza)
- Adenovirus
- Enterovirus
- RSV
- Coronavirus

The common cold

- This is a viral infection of the upper respiratory tract that affects the nose, throat and
sinuses.
- The classic feature is that of clear or mucopurulent (indicating possible bacterial
secondary infection) nasal discharge
- The most common pathogen is rhinoviruses, coronaviruses and respiratory syncytial
virus
- Pain is best treated with paracetamol, cough may persist for weeks after

Pharyngitis and tonsillitis

- The pharynx and soft palate are inflamed and local lymph nodes enlarged and tender
- Mostly due to adenovirus, enterovirus and rhinovirus
- In the older child group A beta-haemolytic strep is a common bacterial
pathogen, although uncommon under the age of 3
- Tonsillitis is a form of pharyngitis where there is inflammation of the tonsils, this is
only possible in children older than 6mths as before this children have a tiny tonsils
that do not become inflamed.
- It is not really possible to distinguish between bacterial and viral inflammation
of the tonsils, headache, apathy, abdominal pain and white tonsillar exudate

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 are all more common in the bacterial form, however a lack of these features
does not exclude a bacterial infection
- Penicillin V or erythromycin should be given if bacterial infection is suspected.
Amoxicillin is best avoided as it may cause widespread maculopapular rash if
the tonsilitis is due to infectious mononucleosis
- Scarlet fever is occasionally a secondary consequence of group A streptococcal
infections, most common in ages 5-12. A fever appears along with a sandpaper like
maculopapular rash with flushed cheeks and a white swollen tounge. Group A strep
can also cause IgA glomerulonephritis and endocarditis and as such should be
treated.

Remember, viruses are the most common cause, ABs not required.

Treatment should be delayed until culture confirms diagnosis (even when fever,
swollen lymph nodes and tonsillar exudate there is only a 66% chance of bacterial
infection).

If confirmed dosage is:

- Penicillin VK 40mg/kg/day PO for twice daily 10 days
Or second line
- Clindamycin 20mg/kg/day PO three times daily for 10 days
- Or Erythromycin 40mg/kg/day PO three times daily for 10 days

Acute otitis media

- most common ages 6-12 months, up to 20% will have three or more episodes
- Pain in ear and fever are the most common features, every child with fever should
have tympanic membrane examined
- Most common pathogens include RSV and rhinovirus, and bacteria such as
pneumococcus
- Serious complications include mastoiditis and meningitis
- Treat with paracetamol or ibuprofen, ABs do not reduce risk of hearing loss -
consider delayed prescription amoxicillin
- Recurrent infections can lead to otitis media with effusion (glue ear), children may
have decreased hearing in some cases - gromets can be inserted in recurrent cases

Antibiotics are rarely indicated for acute otitis media, only consider if under 2 years and
bilateral or otorrhea AND has lasted more than 3 days. In which case, can give:
- Amoxicillin
- 1-11 months 125mg 3x daily for 5-7 days
- 2-4 years 250 mg 3x daily for 5-7 days
- 5-17 years 500 mg 3x daily for 5-7 days
- Second line Clarithromycin

Sinusitis

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 - Generally rare, swelling and tenderness over the sinus is common, note frontal
sinuses do not develop until late in childhood
- Treat with Clindamycin

Stridor
Stridor is not an infection per se, rather it is a symptom precipitated by a number of
infectious processes. It is a harsh musical sound due to partial obstruction of the lower
portion of the upper airway (trachea and larynx). The most common cause is laryngeal and
tracheal infection, where swelling can rapidly occlude the airway. Severe obstruction causes
cyanosis, tachypnoe, tachycardia and agitation with central cyanosis suggesting severe
hypoxia.

The most common cause is viral laryngotracheobronchitis (aka Croup), rarer causes include
epiglottitis, bacterial tracheitis, foreign bodies, allergic laryngeal angioedema and a small
host of other causes.

There are four grades of stridor:

- I - on inspiration only
- II - inspiration and on passive expiration
- III - inspiration and on active expiration
- IV - as III and recessions, cyanosis and tiredness

Treatment of stridor is with full monitoring of oxygen levels, dexamethasone, 0.6mg/kg

single dose, and in severe cases with race epinephrine in severe cases, 0.25-0.5ml in
2.5ml saline with a nebulizer.

As the oxford handbook says “Never blame yourself for forgetting anything, except
your humanity (and the dose of adrenaline!)

- Aged up to 6 years 0.15mL (150mcl) 1:1000 Adrenaline

- Aged 6-12 years 0.3mL (300mcl) 1:1000 Adrenaline
- Aged 12+ 0.5mL (500mcl) 1:1000 Adrenaline

Right, so laryngotracheobronchitis (croup) is the most common cause of stridor. It is

commonly caused by parainfluenza, rhinovirus and influenza virus. Typical features
include hoarseness, a barking cough (like a cute sea lion), harsh stridor and all of the above
symptoms of stridor. The child can usually be managed at home, although those under 1
year should be readily admitted. Inhalation of warm moist air is common but not shown to
be beneficial. Oral dexamethasone, prednisolone or budesonide as a nebulizer are first
line therapy.

Symptoms are worse at night due to decreased cortisol levels.

Acute epiglottitis
Acute epiglottitis is a medical emergency with intense swelling of the epiglottis and
surrounding tissues. It is caused by H influenzae type b (Hib), there is universal
immunization in infancy that has led to more than 99% reduction in incidence. Onset is very
acute, with high fever in very ill looking child, intensely painful throat that prevents

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speech or swallowing of saliva while cough is minimal or absent. Child should have
airway secured by senior ENT surgeon, paediatrician and anaesthetist.

NOTE - IF THEY HAVE ACUTE EPIGLOTTIS DO NOT LOOK IN THROAT, INCREASES

RISKS OF SPASM AND AIRWAY COLLAPSE - As a result, you should also not look in
throat for STRIDOR

Children may present with ‘Tripod’ sign, where they hyperextend their neck and put their arm
down to support themselves.

Foreign body aspiration

This is when an object is inhaled and becomes lodged in a child’s airway or lungs. Diagnosis
can be through the observation of child swallowing food or object closely followed by
respiratory distress, alternatively Chest X-ray, Inspiratory and expiratory phase x-ray and
bronchoscopy can all help with diagnosis. FB aspiration is most common aged 1-3 as this
is the ‘mobile and stupid’ age!

Suspicion of FB aspiration is raised with sudden paroxysms of coughing when not directly
supervised or after eating. FBs generally fall directly down into the right bronchus
(anatomically straighter), of greater risk is if the FB is too large and blocks the trachea,
causing total respiratory failure.

Management of the obstruction depends on the location. Laryngeal and subglottic FBs need
urgent intervention in the form of tracheostomy or urgent bronchoscopy, while FB in the
broncohus causes less of a problem. Rigid bronchoscopy offers good visualization and
is the preferred method for FB removal in neonates and children.

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 11. Acute pneumonia. Bronchiolitis

Acute Pneumonia
Pneumonia is the leading infectious killer of children under the age of 5.

The most common etiologies in children vary based on age, lets take a look:
- Newborns - organisms from mothers genital tract, particularly group B strep, but
also gram -ve enterococci and bacilli
- Infants and young children - respiratory viruses, such as RSV are most common, but
other causes include streptococcus pneumoniae or Haemophilus influenzae.
Bordetella pertussis and chlamydia trachomatis are also possible
- Children > 5 one should suspect Mycoplasma pneumoniae, streptococcus
pneumoniae and chlamydia pneumoniae.

Pneumonia is lung inflammation due to infection with alveolar consolidation in the presence
of fever and/or acute respiratory systems with evidence of parenchymal infiltrates on chest
radiograph.

Clinical features are as expected, fever, cough, tachypnoe, accessory muscles in breathing.
A chest x-ray is the first line method for confirming the diagnosis, although this cannot
reliably tell the difference between bacterial and viral. Additional tests include
nasopharyngeal aspirate, blood tests, full blood count and acute-phase reactants can all be
performed.

Full work up:

- CBC
- CRP
- Sputum culture (note that mycoplasma pneumonia cannot be detected on sputum as
it is intracellular, do PCR/serum culture)
- Blood cultures
- Rapid antigen detection test

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Classifications of pneumonia include:
- Morphological
- Bronchopneumonia
- Lobular pneumonia
- Diffuse pneumonia
- Etiology (bacterial/viral)
- Depending on onset (acute/chronic)
- Depending on site of infection (hospital/community)

Management for many children can be at home, however if oxygen saturation drops below
92%, grunting and/or recurrent apnoea occurs, children should be admitted. Supportive
care should be oxygen for hypoxia and analgesia if there is pain. IV fluids should also
be given to maintain hydration.

In terms of medication, broad spectrum antibiotics can be given in infants, while most older
infants can be managed with oral amoxicillin, the broader more potent co-amoxiclav can
then be kept for unresponsive pneumonia. Over the age of 5, amoxicillin or oral macrolides
such as erythromycin is the choice of treatment. IV or oral are both effective.

Same ABs as for acute otitis media.

- Amoxicillin
- 1-11 months 125mg 3x daily for 5-7 days
- 2-4 years 250 mg 3x daily for 5-7 days
- 5-17 years 500 mg 3x daily for 5-7 days
- Second line Clarithromycin
- 1 month to 11 years:
- Under 8 kg, 7.5 mg/kg twice a day for 5 days
- 8 to 11 kg, 62.5 mg twice a day for 5 days
- 12 to 19 kg, 125 mg twice a day for 5 days
- 20 to 29 kg, 187.5 mg twice a day for 5 days
- 30 to 40 kg, 250 mg twice a day for 5 days
- 12 to 17 years: 250 mg to 500 mg twice a day for 5 days

Common causes of Pneumonia by age

0 - 1 month 1 month - 3 months 4 months - 4 years 5 years - 15 years

Gram -ve bacteria RSV RSV M.Pneumonia

Listeria Parainfluenza S.pneumonia S.pneumonia

Grp B Strep S.pneumonia m.pneumonia C.pneumonia

Is the Pneumonia Viral or Bacterial

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 Viral Low grade fever, appears more generalised on Chest X-ray, usually with
hyperinflation. WBC<20k, usually increased lymphocytes

Bacterial High grade fever with hacking cough and rigors. Usually consolidates to
one lobe. WBC>20k, usually increased granulocytes

Bronchiolitis

Bronchiolitis is the most common serious respiratory infection of infancy, with 3% of all
infants admitted to hospital with the disease. Respiratory syncytial virus is the main
causative agent in 80% of cases, other causes include parainfluenza, rhinovirus, adenovirus
and influenza virus. Not all cases require hospitalization, only around 1-2%.

Simply put, if you have a baby (under 2) coming in wheezing, they almost certainly
have bronchiolitis, over the age of 2, it is generally bronchitis.

Bronchiolitis is the inflammation, edema and necrosis of smaller airway epithelial cells,
with increased mucus production and bronchospasm. The clinical manifestations
include cough, wheeze, and laboured breathing along with the general features of
respiratory difficulty in more severe cases (cyanosis, accessory muscles for breathing,
nasal flaring, grunting, cyanosis and poor feeding).

Risk factors include being below 12 weeks of age, passive smoking, crowding at home,
attendance of daycare, prematurity, concomitant underlying cardiopulmonary disease,
immunodeficiency and severe neuromuscular diseases. These risk factors should be
searched for in examination, along with the key clinical features by way of diagnosis. Note,
fever is generally <40 degrees C.

First line investigation is pulse oximetry to ensure the child is maintaining good oxygen
saturation. Additional investigations such as CBC, CXR and Viral panels are not actually
indicated. CBC does not help distinguish between viral and bacterial infections, CXR has a
very high false positive for pneumonia, meaning that ABs are given unnecessarily, and it
does not matter which virus is causing the disease, the management is the same.

Treatment where the patient has no history of wheeze:

- Supportive care
- Superficial suctioning with saline drops
- Adjunctive: supplemental oxygen and ribavirin (inhalater)

Treatment with history of wheeze

- Supportive care
- Superficial suctioning with saline drops
- Adjunctive: oral corticosteroid, supplemental oxygen and ribavirin (inhalation)

Prophylaxis prevention to the RSV can be achieved through the Palivizumab IM injection
during high risk months (15mg/kg November - March). Although, worth saying, this is not at

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all cost effective, and does not reduce mortality. Breastfeeding is also thought to reduce
incidence.

Bronchial asthma (below) and bronchiolitis have a great deal of similarities in the clinical
picture and it can be hard to distinguish. Take a look below to consider some of the
differences:

12. Bronchial asthma

Asthma is the reversible constriction and obstruction of the bronchial walls caused by an
inflammatory process as an allergic response to house dust mites. The key diagnostic
factors are:
- Presence of risk factors (FH, smoking in household etc)
- Wheezing episodes
- Wheezing is typically exhalational, while croup is typically inhalatory
- Increased work of breathing
- Features of atopic disease
- History of response to treatment
Additional indicative features include a dry night-time cough, expiratory wheezing and
dyspnoea.

Your physical examination should look for the following:

- Overall appearance and respiratory distress
- Respiratory rate and lung exam
- Heart rate and cardiac exam
- Exam of liver (patients are hyperinflated and as such we expect to palpate the liver
border)
- Allergic stigmata (e.g. eczema)

Where bronchial asthma is suspected, firstlly perform spirometry followed by a dose of

bronchodilator and then a repeat of the spirometry. If there is a positive response we can
diagnose asthma. Additional tests include peak flow meter, CXR, FBC, sweat test, sputum
culture and ABG if the patient is presenting with signs and symptoms of hypoxia.

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 Taking a ‘suspected asthma’ history
- When did wheezing begin (age)
- Episodic or persistent
- Sudden onset (FB) or gradual
- Associated triggers
- Has it responded to albuterol
- Was this child premature (much higher risk)
Signs and symptoms
- Events per week?
- Nighttime awakenings
- Interference with normal activity
- Systemic steroids in the last year?
- Previous hospitalization?

Treatment
- Age 0-4
- Step 1 - short acting beta-2 agonist when required
- Step 2 - low dose inhaled corticosteroid + short acting beta-2 agonist when
required
- Step 3 - medium dose-inhaled corticosteroid + short acting beta-2 agonist
when required
- Step 4 high dose corticosteroid + montelukast
- Age 4-11
- Step 1 - short acting beta-2 agonist when required
- Step 2 - leukotriene receptor antagonist + short acting beta-2 agonist when
required
- Step 3 - Medium dose inhaled corticosteroid + short acting beta-2 agonist
when required
- Step 4 - corticosteroid + leukotriene receptor antagonist or short acting beta-
2 agonist when required

Short acting beta 2 agonist =

Salbutamol 100 micrograms - 200 micrograms (1-2 puffs) 5 mins before exercise or
when required

Corticosteroid =
Budesonide 0.25-1 mg/day inhaled/nebulised or beclometasone inhaler 90-200
micrograms/dose up to 400 micrograms/day (if severe, add prednisolone 0.25-
2mg/kg orally and salmeterol 50 micrograms/dose twice daily)

Long acting beta 2 agonist =

Salmeterol 0.05mg twice daily
- NOTE - NEVER USE LABA WITHOUT A STEROID

Leukotriene receptor antagonist =

Montelukast 5mg orally once daily

Use step up policy, start with SAB2A, add Corticosteroid, then LAB2A and then

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 Leukotrienes as it gets more severe.

Chronic management of asthma means we need to categorise patients into one of four
categories:
- Intermittent
- Mild persistent
- Moderate persistent
- Severe persistent
This category is based on whether the patient wakes up at night, the frequency of their
salbutamol use, if their asma interferes with normal activity, and what use of systemic
steroids are being applied.

Acute management is visualised below:

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 Differential diagnosis of wheezing

0-1 year 1-4 years >5 years

- Bronchiolitis - Viral induced - Asthma

- Bronchopulmonary wheeze (bronchiolitis - Vocal cord
dysplasia or pneumonia) dysfunction
- FB - Early asthma - Hypersensitivity
- Aspiration - FB pneumonitis
- Anatomic - Cystic fibrosis - Allergic

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 abnormality bronchopulmonary
aspergillosis

13. Cystic Fibrosis. Bronchiectasis

Mucoviscidosis = Cystic fibrosis. For an illustration of just how out of date this term is, its
first hit on google is an article in French form 1988…

Cystic fibrosis is an AR disorder more common in the whte population. The error occurs on
the long arm of the 7th chromosome, affecting CF transmembrane regulator (CFTR). This
gene is responsible for chloride ion conductance in the epithelial cells. It is this defect
that gives rise to its clinical manifestations.

CF is a chronic progressive disease, many infants are diagnosed on initial screening using
the sweat chloride skin test (>60 mEq/L is positive). Older children will present with
poorly controlled asthma and chronic respiratory infections, the respiratory
epithelium will show marked impermeability to chloride and excessive reabsorption of
sodium causing dehydration of the airway secretions and in return impairment of
mucociliary transport. It is this impairment that leads to recurrent infections and wheezing
that we see in CF patients. Digital clubbing is common as is chronic sinusitis and nasal
polyposis.

The pathogenesis of the disease should be clear, impairment of chloride ion transport means
that sodium is retained in the epithelial cells, where sodium goes water follows, as such the
epithelial cells are unable to properly secrete, causing highly viscous mucous (hence its old
term, mucoviscidosis).

90% of patients also present with exocrine pancreatic insufficiency as a result of the
dehydration of the pancreatic ducts. This leads to malabsorption of proteins, sugars and fat,
manifesting as steatorrhea, vitamin deficiencies and FTT. Can present in neonatal period
with meconium ileus.

Diagnosis is via the skin sweat chloride test previously mentioned, along with DNA analysis
or demonstration of the failed ion transport across the nasal epithelium.

Treatment is multifactorial but primarily geared towards GI and pulmonary complications of

the disease. Airway treatment includes airway secretion clearance techniques (chest physio)
and antibiotic therapy, while GI treatment is that of enteric coated pancreatic enzyme
capsules, including lipase and proteases along with diet change (avoidance of fat).

Bronchiectasis
Bronchiectasis is irreversible dilation of the bronchial tree, it may be generalized or
restricted to a single lobe. The generalised form can be a result of cystic fibrosis,
primary ciliary dyskinesia, immunodeficiency or chronic aspiration, while the focal form can
be the result of severe pneumonia, congenital lung abnormalities or due to
obstruction by a foreign body.

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A plain CRX may show gross bronchiectasis however it is often difficult to fully assess by x-
ray and CT is preferred, if the cause is unknown in focal cases a bronchoscopy may be
required for diagnosis.

Bronchiectasis can present with infectious flair ups, in such cases sputum cultures should be
taken to guide treatment, but first choice is generally Amoxicillin (see above doses)

14. Respiratory insufficiency in childhood

Respiratory insufficiency is the failure of the lungs to maintain adequate gas

exchange. This may be due to alveolar hypoventilation, diffusion impairment,
intrapulmonary shunting or ventilation-perfusion mismatch.

Respiratory failure causes hypoxaemia (PO2 <85mmHg) and/or hypercapnia (PCO2

>45mmHg), the former causing tissue hypoxia and the later leading to carbon dioxide
narcosis. Respiratory failure with hypercapnia has a worse prognosis than hypoxaemia
alone.

Early signs of respiratory distress are:

- Accessory muscle use
- Flaring of nose
- Intercostal recessions
- Compelled position
This can progress to respiratory failure which is the failure of compensatory mechanism. The
key sign is change in mental status.

Symptoms of respiratory distress in infancy include:

- Tachycardia
- Respiratory rate >50bpm
- Nasal flaring
- Use of accessory muscles
- Intercostal recession
- Head retraction
- Unable to feed
- Cyanosis
- Reduced conscious level
- Low O2 saturation
- High CO2 saturation

In acute cases, patients should be placed on oxygen (via face mask, to non-invasive
ventilation and finally endotracheal intubation of PCO2 >50mmHg) and reversible causes
identified and treated where possible.

Where respiratory failure is suspected the following bloods should be performed:

- ABGs
- CBC

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 - Electrolytes
- X-ray

For extrathoracic airway obstruction (e.g. croup):

- Inspired humidity to liquefy secretions
- Heliox (helium + oxygen)
- Racemic epinephrine 2.25%
- Dexamethasone
- Nebulized hypertonic saline (3%)

As lung and respiratory pump support:

- Oxygen therapy
- Humidified high flow nasal cannula therapy, CPAP and NPPV

Adjunctive therapies for severe hypoxemia

- Prone position
- Inhaled NO
- Exogenous surfactant

Note, patients in a chronic hypercapnic state should not be put on oxygen unless their
PO2 is very low. The high CO2 levels keep the bran centre stimulated, removing this
stimulus will result in the patient decreasing their breathing effort.

15. Congenital malformations of respiratory system

Congenital malformations of the respiratory system are rare, we can divide them based on
the structures that are affected:
- Malformation of the thorax (specifically the diaphragm)
- The lung (lung sequestration, cystic adenomatoid malformation, bronchogenic cyst,
foregut cyst)
- Blood supply (aberrant vasculation, double arch of the aorta)
- Airways (tracheal rings, tracheomalacia, tracheal atresia)
- Larynx and oral cavity

Below we highlight some of the main types and give an overview of the disease.

Congenital diaphragmatic hernia

The most common malformation of the respiratory system, with multiple subtypes including
the Bochdalek hernia, Morgagni hernia, diaphragm eventration and central tendon
type. The malformation allows abdominal organs to push into the chest cavity limiting lung
formation. Pulmonary distress will occur within the first 24 hours and can lead to
pulmonary hypoplasia and pulmonary hypertension, both of which can lead to death if
not properly treated. Treatment is with an orogastric tube and intubation, with
extracorporeal membrane oxygenation in some cases. Following securing of the
airways, thoracoscopic surgery can be performed.

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Tracheoesophageal fistula
This is an abnormal congenital connection between the trachea and the esophagus. It
will present in newborns with copious salivation along with choking, coughing, vomiting
and cyanosis. It is the product of the failed fusion of the tracheoesophageal ridges at
the fourth week of embryological development.

TEF should be suspected once the baby fails to swallow after his first feed, a diagnosis
can be made by a Ryle nasogastric tube, where the tube fails to pass into the stomach then
this can indicate loss of communication between the stomach and the esophagus. We
classify TEF as type A, B, C (most common), D or H depending on the precise location of
the connection. Treatment is surgical resection

Choanal atresia
This is the blockage of the nasal passage to the
nasopharynx. This blockage can be due to soft tissue or
bone and can be unilateral or bilateral (in unilateral
cases it is often not picked up until quite late). Bilateral
cases are very serious as babies are obligate nasal
breathers following birth, as such babies will present as
cyanotic, and may require incubation early in life.
Presentation often occurs with Coloboma, heart defects,
intellectual disability and FTT.

Congenital lobar emphysema

Also known as congenital lobar overinflation is a
disease where air enters the lungs and cannot escape. The lobe (or more) becomes
distended and may or may not have an overabundance of alveoli. There are many
mechanisms for this, including obstruction, cartilage deficiency, dysplasia and immaturity.

The clinical presentation is that of respiratory distress within the first six months of life, with
diagnosis through radiography.

Pulmonary atresia
This is actually a cardiovascular congenital disorder, but it affects the lungs and as such is
included in here. The pulmonary valve does not form properly, and blood from the right side
of the heart cannot go into the lungs. This most commonly occurs with Tetralogy of Fallot.

Congenital cystic adenomatoid malformation (congenital pulmonary airway

malformation)
This is a congenital disorder where an entire lobe of lung is replaced by a non functioning
cstic piece of abnormal tissue. Three quarters of patients are asymptomatic, while 25%
develop cyanosis, pneumothorax and tachypnoea, whether the patient is symptomatic or not
depends on the size of the congenital cyst. Treatment is surgical removal of the cyst.

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 16. Tuberculosis

Tuberculosis is a bacterial infection caused by the bacterium mycobacterium tuberculosis.

Since the development of the BCG vaccine, the incidence of TB has been on the decrease,
however, this trend may be reversing as we see the emergence of multidrug-resistant
mycobacterium TB (MDR-TB).

Diagnosis in infants and children can be tricky. 90% of children and 50% of infants are
asymptomatic following infection, and the disease will remain latent in their body, with
the potential to develop disseminated miliary TB (where the disease can affect a
multitude of organs, not just the lungs) at a later date.

The symptomatic form of TB occurs when the host fails to contain the bacteria,
allowing spread via the lymphatic system. Lung lesion plus the lymph node constitutes
the ‘Ghon complex’. Typical symptoms include fever, anorexia and weight loss, cough
and chest x-ray changes. The primary complex often calcifies, and the lesion may cause
bronchial obstruction and/or pleural effusion.

Both the symptomatic and asymptomatic forms of the disease can become dormant, and
eventually reactivate as secondary TB (Miliary TB).

Diagnosis of TB in children and infants is a little tricky. Our options are:

- Sputum samples (generally unobtainable from under 8s, specific techniques would
need to be used)
- Gastric washings on three consecutive mornings
- Tuberculin skin test (Mantoux test) however this may be +ve due to vaccine
- Interferon-gamma release assays (IGRAs) are especially useful for dormant TB
- Coinfection with HIV makes it even more of a challenge as X-ray changes may be
due to lymphoid interstitial pneumonitis which looks very similar and affects 20% of
HIV children.

Treatment is triple or quadruple therapy = rifampicin, isoniazid, pyrazinamide,

ethambutol. If MDR-TB is suspected, just use rifampicin and isoniazid until antibiotic
sensitivities are known. Treatment is for 6 months in ordinary pulmonary TB.

Differences to adult TB:

1. Harder to diagnose (more often asymptomatic)
2. Increase in percentage of disseminated extrapulmonary TB
3. All latent TB in children should be treated
4. Very young children are not contagious

Pediatric Gastroenterology

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 17. Jaundices in the period of the neonate and the breast-fed
infant

Jaundice in the period of the neonate

Jaundice is caused by an excess of bilirubin, this can be conjugated or unconjugated.
Over 50% of all newborn infants will become visible jaundiced, it is most common due to:
- Physiological release of haemoglobin from the breakdown of red blood cells
due to the high hemoglobin concentration at birth
- The short lifespan of red blood cells
- The reduced function of hepatic function in the first few days of life

However, neonatal jaundice can also be a sign of a more sinister disease. Take a look at the
list below which shows the differential diagnosis of jaundice.

If unconjugated hyperbilirubinemia
- Hemolysis and reticulocytosis
- +ve Coombs test (tests for autoimmune hemolysis)
- ABO and Rh incompatibility/ lupus/drug induced hemolytic anemia
- -ve Coombs test
- RBC enzyme defect/hemoglobinopathy/RBC membrane
defect/Wilsons
- No hemolysis
- Gilbert syndrome/physiologic jaundice of newborn/breast milk jaundice/pyloric
stenosis/hypothyroidism

If conjugated hyperbilirubinemia
- Obstructive
- Biliary atresia/Choledochtal cyst/cholelithiasis/bile duct stenosis
- Infectious
- Hepatitis (A-G), any other viral infection that bothers the liver
- Metabolic
- Wilsons/galactosemia/Niemann-Pick
- Toxic
- Total parenteral nutrition/ethanol/salicylates/iron/valproic acid
- Idiopathic
- Idiopathic neonatal hepatitis/familial benign recurrent cholestasis/shock
- Autoimmune
- AI chronic hepatitis/sclerosing cholangitis/graft vs host

We already know a great deal about jaundice, there is a yellowish discoloration of the whites
of the eyes and skin. Complications can include seizures, cerebral palsy or kernicterus
(bilirubin-induced brain dysfunction due to bilirubin deposition in the basal ganglia).
A bilirubin level greater than 34 μmol/l (2 mg/dL) may be visible as jaundice, a level of 80
μmol/l is described as being ‘clinically jaundice’ while severe brain damage will occur at
levels greater than 308 μmol/L (18 mg/dL).

We can get a better idea about the cause of jaundice based on the age of onset:

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 - <24 hours
- Most commonly due to haemolysis e.g. rhesus haemolytic disease, ABO
incompatibility, spherocytosis
- Can also be due to a congenital infection
- 2 days - 2 weeks
- Physiological jaundice
- Breast milk jaundice (below)
- Dehydration
- Infection
- >2 weeks
- May be caused by biliary atresia which must be treated promptly
- May also be due to breast milk jaundice
- Infection
- Congenital hypothyroidism

Jaundice tends to start in ones head and face before spreading down through the body.
Management of jaundice should be ensuring proper hydration of the infant, and
management of any underlying causes (e.g. infection, autoimmune diseases).
Phototherapy can be used to convert unconjugated bilirubin into a harmless water
soluble pigment, while exchange transfusion is required if the bilirubin rises to
dangerous levels. Use NICE Threshold table to determine if therapy is needed in the early
hours of life.

Breastfeeding jaundice
Breastfed infants are more susceptible to elevated concentrations of bilirubin. Infants who do
not intake enough milk and have poor weight gain will also have decreased stools. This
means less bilirubin will be excreted from the body, leading to higher serum levels. Breast
milk jaundice commonly occurs after the first few days of life and does not persist beyond 1-
2 weeks after onset. Vitamin D supplementation is recommended in such infants.

18. Ulcer diseases, chronic gastritis

Chronic gastritis and ‘Ulcer diseases’ are the product of an imbalance between the
corrosive effects of gastric acids and the protective effects of the gastrointestinal
mucosa. The esophagus, stomach and duodenum are all at risk for inflammation and
ulceration.

Chronic gastritis can be seen as an early part of ulcer disease, left untreated it will progress
to a peptic ulcer. The disease is often asymptomatic, although can present with pain,
abdominal bloating, nausea and vomiting. Causes include NSAIDs, Zollinger-Ellison
syndrome, Crohn's, Autoimmune gastritis and H.pylori infection. In children, chronic
gastritis most commonly affects the duodenum.

Peptic ulcers present with ‘Alarm’ symptoms, that is to say, they are suspicious of many
forms of malignancy. They include weight loss, hematemesis, melena, chronic
vomiting, microcytic anemia, nocturnal pain and other general abdominal symptoms.

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An endoscopy is the primary and most effective method of diagnosis and all patients should
be afforded the study to rule out malignancy. H.pylori fecal analysis or breath tests should
also be performed. H. pylori is responsible for more than half of ulcers in adults, and while it
is still important in children, it is not as important.

Once confirmed, H.pylori related ulcers and gastritis should be treated with
omeprazole-azithromycin-metronidazole combinations. In the absence of h.pylori,
simple omeprazole will be sufficient.

Reflux in Infants
Reflux is very common affecting nearly half of babies, usually no treatment is needed, and
tends to start before 8 weeks old, resolving by 1 year. It can occur multiple times daily (up to
6) although this reduces as the infant gets older. One should be concerned if the
regurgitation becomes more forceful, if there is bile in the reflux, or there are additional
general symptoms.

We can reduce reflux by giving the infant smaller more frequent feedings and burping the
baby in the middle of feeding. Holding the baby upright for 20 minutes after feeding can also
help.

19. Enteritis and enterocolitis

Enteritis is an inflammation of the small intestine, enterocolitis is an inflammation of the large

and small intestines.

It is useful at this juncture to remind ourselves of some termanology:

- Gastritis = inflammation of the stomach
- Gastroenteritis = inflammation of the stomach and small intestines
- Colitis = inflammation of the large intestine
- Enterocolitis = inflammation of the large and small intestine
- Enteritis = inflammation of the small intestine

Enteritis
There are four main types of enteritis:
- Autoimmune (including Chron’s, Celiac and eosinophilic enteropathy)
- Infectious (the vast majority of cases, caused by four main pathogens, Norovirus,
Rotavirus, Campylobacter and Salmonella)
- Vascular (due to hypoperfusion of the small intestine, can be due to an infarction of
systemic shock)
- Radiation

Enteritis is most commonly acute, and has the universal symptom of diarrhea. Diarrhea is
the leading cause of morbidity worldwide due to the tendency to cause dehydration.
As mentioned above, in children, an infectious etiology is far and away the most common
cause of the disease. As such, we shall consider infectious enteritis and its consequences
predominantly.

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Infectious diarrhea has two main mechanisms, secretory or mucosal invasion. The
secretory form is most common in cholera, toxigenic e.coli, carcinoid, c.diff and others
and results in watery stools with high loss of sodium and potassium. This form persists
during fasting and there is no blood in the stool. Mucosal invasion type diarrhea causes
blood and leukocytosis in stool. Agents include celiac, salmonella, shigellosis and
rotavirus enteritis.

The most important aspect to consider is dehydration, certain patients are at high risk of
dehydration, these are:
- Infants under 6 months
- Those with low birth weight
- Children who have passed 6 or more stools in the past 24 hours
- Children who have vomited 3 or more times in the past 24 hours
- If they have not had additional fluids/have malnutrition

Clinical assessment of dehydration is tricky, but can be done by observation of loss of body
weight, 5%-10% reduction of body weight equates to clinical dehydration, while more than
10% would indicate shock.

Dehydration has different classifications based on the changes to the electrolyte balance.
- Isonatremic and hyponatremic dehydration
- In diarrhea dehydration there is a total body deficit of sodium and water
- Generally the losses are proportional, so the body remains isonatremic.
- Where the patient drinks lots of water, but fails to replace the sodium, the
patient becomes hyponatremic.
- In the most severe cases this can cause seizures
- Hypernatremic dehydration
- Infrequently, water loss exceeds sodium loss
- This leads to a shift of water into the extracellular space, meaning the obvious
signs of dehydration are less obvious (skin turgor remains, as does elasticity)
- This form of dehydration is more deadly doe to the tendency of cells to
dehydrate faster

Apparently there is no place for medications for the vomiting or diarrhea of gastroenteritis,
the answer to the problem is always oral rehydration solution, followed by IV therapy for
rehydration. ABs are not routinely required, and only indicated for cases of protozoal
infections, sepsis or salmonella if under 6 months.

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Enterocolitis
Enterocolitis has three main causes in pediatric medicine
- Due to Hirschsprung disease
- Infectious
- Necrotizing enterocolitis

Lets address each one in turn.

Hirschsprung disease is a motility defect caused by failure of ganglion cell precursors

to migrate to the distal bowel during fetal life. This aganglionic distal segment has a
lack of motility and is functionally obstructed. This generally affects the sigmoid colon,
although can in rare cases affect the descending colon. 95% of infants pass stool
spontaneously by 24 hours, while 95% of those with Hirschsprung do not. If a

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diagnosis is not made quickly, enterocolitis can result. Enterocolitis is the greatest cause
of morbidity in children with Hirschsprung disease.

Necrotizing enterocolitis is the most common intestinal emergency occurring in preterm

infants. Most cases of NEC occur in prem infants born before 34 weeks, who have been
fed enterally. This prematurity of the gut, and lack of use of the gastrointestinal system
leaves the GI tract with decreased integrity, depressed mucosal enzymes, suppressed GI
hormones and differences in blood flow autoregulation. Clinical signs include abdominal
distention, feeding intolerance, emesis, rectal bleeding and occasional diarrhea. WBC
can be elevated or depressed, thrombocytopenia is common. The underlying
pathophysiology is thought to be due to decreased blood circulation leading to ischemic
injury of the intestine. Management is with discontinuation of enteral feedings, GI
decompression with nasogastric suction, fluid and electrolyte replacement, total parenteral
nutrition, and systemic broad-spectrum ABs.

Infectious enterocolitis is very similar to enteritis, common bacteria include salmonella,

shigella, e.coli, viruses include enterovirus, rotaviruses and norwalk virus while fungi
and parasites can also be problematic.

Causes of lower GI bleed:

- Common
- Infectious colitis (Shigella, Salmonella, Yersina, Campylobacter, E.coli, C.
diff)
- Meckel’s diverticulum
- Intussusception (look for red currant/jelly stool
- Rare
- Peptic ulcer (H.pylori)
- Juvenile polyposis (AD disease)
- Arteriovenous malformations

Occult bleeding -common causes

- Meckel's Diverticulum
- Peptic ulcer disease
- Juvenile polyposis
- IBD

Ulcerative Colitis Crohn's

Affects Colon + retum (mostly distal colon) Iliac + Cecal area mostly, but can affect all
of GI

Continuous (distal to proximal) Skip lesions

Superficial lesions Transmural lesions

Develops pseudopolyps Presents with more severe complications

(perforations, colon cancer)

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 20. Malabsorption and maldigestion syndrome. Celiac disease.
Mucoviscidosis

Malabsorption is the term we give when nutrients are not being properly absorbed
through the intestinal tract. Malabsorption disorders manifest as abnormal stools, poor
weight gain or faltering growth, or specific nutrient deficiencies.

The precise clinical features depend on the exact thing that is being malabsorbed (more on
this later) however in general symptoms include abdominal distention, muscle wasting,
loss of subcutaneous fat with loose skin folds as well as the above mentioned.

Specific findings on clinical examination of the malabsorption patient will suggest different
causes of malabsorption. For instance edema is associated with protein-losing
enteropathy, clubbing with cystic fibrosis and celiac, perianal excoriation (scraped off
skin around anus) with gaseous bloating suggests carbohydrate malabsorption, etc.

Diarrhea is the main clinical expression of malabsorption, early onset in infancy

suggests a congenital defect. Different forms of diarrhea can indicate different types of
malabsorption, explosive diarrhea suggests carbohydrate malabsorption, loose bulky
stools are associated with celiac, yellowish smelly stools suggest exocrine pancreatic
insufficiency.

The initial workup in the malabsorbing child includes stool analysis, full bloods and a
peripheral smear to check for anemias and oncological causes. To better understand
what is being poorly absorbed we have different tests to evaluate the patient:
- Test for carbohydrate malabsorption using breath hydrogen test or small bowel
mucosal biopsies
- Test for fat malabsorption by evaluating fat content in stool. Fat malabsorption
usually indicates exocrine pancreatic insufficiency and is associated with deficiencies
of the fat-soluble vitamins (DEAK). The most common cause of exocrine pancreatic
insufficiency in children is cystic fibrosis
- Test for protein-losing enteropathy is the evaluation of blood albumin,
hypoalbuminemia with diarrhea suggests loss of protein in the feces.
- Test for intestinal mucosal disorder is through histological biopsy via endoscope

It is useful to consider the symptoms of various specific vitamin deficiencies, these are listed
below.

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Some diseases are more common in causing malabsorption, we shall consider two here,
Celiac and ‘Mucoviscidosis’ (aka Cystic fibrosis).

Celiac
Coeliac disease is gluten intolerance, specifically, intolerance of the gliadin fraction of
gluten. Gluten is found in wheat, barley and rye (but not rice). Coeliac has an incidence of
about 1/100, in its classical form, children present between 8-24 months with severe
symptoms (see below) after eating wheat containing meals. What happens in practice is that
the wheat causes an inflammatory response in the proximal small intestinal mucosa.
This in turn damages the enterocytes, specifically the villi, of the small intestine. If left
untreated, and if patients continue to consume gluten, then they can irreparably damage
the mucosa of the small intestine and can cause various forms of malnutrition.

Many forms of coeliac diagnosed today however are not the classical form, instead there are
less severe forms that may not be picked up until later in childhood or adolescence.

Symptoms include diarrhea, abdominal pain and abdominal distention. Any child with
prolonged abdominal symptoms should be considered for coeliac. Diagnosis is through

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serological markers, positive IgA antiendomysial antibody and IgA tissue
transglutaminase antibody results can give us a 95% specificity for coeliac, while
certain diagnosis can be achieved by small bowel biopsy via an endoscope.

Treatment is total exclusion of gluten from the diet, with oversight from a dietitian.

Mucoviscidosis
For full details see question 15. Here we will only discuss the GI manifestations of the
disease.

90% of all patients with CF are born with exocrine pancreatic insufficiency. This is due to
the poor quality of the mucous which causes the exocrine pancreatic ducts to block.
This causes malabsorption of proteins and sugars, but most notably, fats (due to the
lack of pancreatic lipase being excreted). This manifests as steatorrhea along with
deficiencies of fat-soluble vitamins (DEAK). Protein malabsorption will present what
hypoproteinemia and peripheral edema.

Note as well that 10% of CF patients will have some form of intestinal obstruction
caused by inspissated meconium (meconium ileus), and as the child gets older, they are
at higher risk for distal intestinal obstruction syndrome.

21. Chronic hepatitis. Cirrhosis

Chronic hepatitis
Hepatitis has a range of causes, from viruses A-G, Autoimmune hepatitis, steatohepatitis
and others. The most common causes of chronic hepatitis in pediatrics are:
- Hepatitis B virus
- Hepatitis C virus
- Metabolic disorders (e.g. Glycogen storage disease, Wilson disease
- Biliary atresia

Chronic hepatitis is commonly asymptomatic, however when symptoms do present it is often

in periods of metabolic stress, and will present with tiredness, low energy, jaundice, weight
loss, ease of bruising and hypotonia.

Lets consider each one below.

Hepatitis B is a DNA virus (the only DNA virus) that can cause acute and chronic liver
disease, with high prevalence in sub-saharan africa and the far east. Transmission is
perinatal, inoculation with infected blood or sexual. Infants who contract HBV
perinatally are asymptomatic but most will become chronic carriers. Older children
who contract HBV through blood may have classical features of acute hepatitis, most
of these cases will spontaneously resolve, however 10% will become chronic carriers.
Diagnosis is through observation of HBV antigens and antibodies.

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30-50% of asymptomatic chronic HBV carriers will develop HBV liver diseases, of which
10% will become cirrhotic. Such cases have a higher risk of HCC. Treatment is currently
fairly ineffective however there are good prevention mechanisms with HBV vaccine
available.

Hepatitis C is an RNA virus with a high prevalence amongst IV drug users. Vertical
transmission is the most common cause of HCV transmission in children. HCV very
rarely causes acute infection, however the majority become chronic carriers with a 20-
25% risk of developing cirrhosis or hepatocellular carcinoma. HCV however does have
successful treatment regimes. Drugs such as sofosbuvir are 100% curative. Treatment
should not be taken under the age of 3 as HCV may resolve spontaneously before this.

Metabolic disorders
The two most common causes of metabolic liver inflammation are glycogen storage
disease and wilson's disease. Here we review briefly both conditions.

Glycogen storage diseases are a group of diseases that cause hypoglycemia and
hepatomegaly. In all diseases there is an affected enzyme which prevents the proper
formation of glycogen in the liver. GSDs present can present with any combination of
hypoglycemia, hepatomegaly, hyperlipidemia and muscle symptoms. Diagnosis is
histological.

Wilson's disease is an error of copper metabolism. It is a genetic disease where the

enzyme responsible for copper metabolism is defective, leading to a build up of copper in the
liver, eye (Kayser-Fleischer ring) and the brain. Symptoms include vomiting, weakness,
ascites, jaundice, and pruritus

Biliary Atresia is a congenitally narrow, blocked or absent bile duct. Such an anomaly
will lead to obstructive jaundice, with eventual cirrhosis and portal hypertension. The
jaundice that the newborn presents with is indistinguishable from benign neonatal jaundice.
Surgery is required to restore bile flow and reduce the jaundice, this also saves the liver.

Cirrhosis
Liver cirrhosis is a histological definition, it is defined as extensive fibrosis with
regenerative nodules in the liver and it is the end result of many hepatic diseases. The
main pathophysiological effects are diminished hepatic function and portal hypertension
with splenomegaly, varices, plantar and palmar erythema, telangiectasia, spider naevi and
ascites. Liver cirrhosis is also a significant risk factor for hepatocellular carcinoma.

There are some important differences from adult cirrhosis in children. Children are better
able to compensate cirrhosis, and may be asymptomatic if liver function is adequate.

Upon suspicion of cirrhosis screening of known causes of chronic liver diseases should be
done, with upper GI done to detect varices and a liver biopsy to indicate the extent of
fibrosis.

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Pediatric Nephrology

22. Congenital malformations of the excretory system.

Pyelonephritis

The kidneys in a full-term newborn are approximately 6cm and 24g, compared to 12cm
and 150g in an adult. As an anatomical reminder, each kidney is supplied by a renal artery
and renal vein, with a cortex and medulla (outer and inner), the nephron is the functional unit
of the kidney, with its glomerulus and associated tubules. Nephron development is
complete at 36-40 weeks gestation, and new nephrons cannot be formed after birth.

Newborns have decreased kidney function compared to adults. GFR doesn't achieve the
adult rates of 80-120ml/min until the age of 1-2 years of age. Premature babies have this
problem even worse, with children aged 28 weeks only having 10% of the GFR of a full term
baby.

Lets now discuss a bit about the embryonic development and congenital malformations of
the kidney and associated bits!

Kidney development beings in the 5th week of gestation, with the ureteral bud arising
from the mesonephric (wolfan) duct and then developing into the collecting system.
The cells of the wolffian duct induce mesenchymal cells to condense, proliferate and develop
into the nephron. By the 20th week approximately 30% of the nephrons are developed.
Defects in any of the signaling activities can cause renal agenesis or dysgenesis
(dysgenesis includes aplasia, dysplasia, hypoplasia and renal cystic diseases).

Renal agenesis
- Absent kidney development secondary to defect of the wolffian duct, ureteric bud,
or metanephric blastema
- Unilateral incidence is 1 in 1000, bilateral agenesis is incompatible with extrauterine
life and produces potter syndrome, where death occurs after birth from pulmonary
hypoplasia
- In Potter syndrome the eyes are widely separated with epicanthic folds, the
ears are low set and the nose is broad and compressed with a receding chin
and limb abnormalities
- Diagnosis is usually by ultrasound

Renal dysgenesis: Dysplasia, Hypoplasia and cystic anomalies

- Renal dysgenesis is the maldevelopment of the kidney, of which there are three
types, dysplasia, hypoplasia and cystic anomalies
- Multicystic dysplasia
- Results from the failure of union of the ureteric bud with nephrogenic
mesenchyme creating a non-functioning structure with large fluid filled
cysts and no renal tissue and no bladder connection - potter syndrome
will occur if bilateral as patient becomes oliguric
- Autosomal recessive polycystic kidney disease
- Diffuse bilateral enlargement of both kidneys

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 - Autosomal dominant polycystic kidney disease
- Individual large cysts between normal parenchyma
- Horseshoe kidney
- Failure of the kidneys to properly separate
- Duplex kidney
- Two ureters from a single kidney
- Unilateral hydronephrosis
- Can be due to pelviureteric junction obstruction or vesicoureteric junction
obstruction
- Bilateral hydronephrosis
- Can be due to bladder neck obstruction or posterior urethral valves

GFR @ Birth = 25ml/min/1.75m2. This should tripple after three months to

75ml/min/1.75m2 before increasing through childhood to adult levels.

Pyelonephritis
First, lets talk about UTIs as they’re not covered in this syllabus.

3-7% of girls and 1-2% of boys have at least one symptomatic UTI before the age of 6, and
up to 30% will recur. Where fever and systemic involvement are present, pyelonephritis
may be indicated. At least half of those with UTIs in childhood will have structural
abnormalities, while pyelonephritis can cause permanent scarring.

UTIs in infants present with fever, vomiting, lethargy, poor feeding, jaundice and febrile
seizures while children will present with more traditional symptoms of dysuria, abdominal
pain, fever with or without rigors, lethargy, haematuria, cloudy urine and vomiting.

Proper diagnosis of UTIs first requires a proper collection of sample, the sample should be a
‘clean-catch’, and in larger children it should be a midstream urine collection. The nitrite
dipstick test is the most common method of testing, a positive result will indicate a true
UTI, but a negative result cannot categorically rule out a UTI. We can do more detailed
investigations, looking at nitrite and leukocyte esterase, their presence indicates UTIs.

UTIs are most commonly due to E. coli, Klebsiella, Proteus, Pseudomonas and
Streptococcus faecalis.

Atypical UTIs should be investigated with Ultrasound to look for a possible structural
abnormalities of the urinary system.

OK, so now we progress to pyelonephritis. It is thought that most infants and young
children who have febrile UTIs have acute cases of pediatric pyelonephritis. The signs
and symptoms are as we described for a UTI above, neonates, especially males, may
develop hyponatremia and hyperkalemia as a result of pseudohypoaldosteronism.
Infants and young children will have very non specific symptoms and as such urine samples
should be taken as part of a general workup where the child is unwell. Antibiotic treatment

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should be swift and should include cephalosporin, amoxicillin-clavulanic acid,
trimethoprim-sulfamethoxazole or aminoglycosides.

It is worth noting that a high proportion of those with pyelonephritis will have vesicoureteral
reflux, a developmental anomaly of the vesicoureteric junctions.

Children have a high risk of sepsis from pyelonephritis. Safety net with the following:
- CRP
- Procalcitonin

UTI care
- If risk of serious illness/younger than three months, admit
- Otherwise:
- Trimethoprim if low risk of resistance
- 3-5 months 4mg/kg (max 200 mg/dose) or 25mg 2x daily for 3 days
- ½ - 5 years 4mg/kg (max 200 mg/dose) or 50mg 2x daily for 3 days
- 6-11 years 4mg/kg (max 200 mg/dose) or 100mg 2x daily for 3 days
- 12-15 years 200mg twice daily for 3 days
- Nitrofurantoin if risk of resistance and eGFR >45 ml/min
- 3 months -11 years 750 micrograms/kg 4xdaily for 3 days
- 12-15 years 50 mg 4x daily for 3 days
Note, Trimethoprim is much cheaper, but generally not used as E.coli is now generally
resistant)

Pyelonephritis care
- Again, if under 3 months or systemically unwell, admit
- Otherwise
- Cefalexin
- 3-11 months, 12.5mg/kg or 125mg 2xdaily for 7-10 days
- 1-4 years, 12.5mg/kg or 125mg 3xdaily for 7-10 days
- 5-11 years, 12.5mg/kg or 250mg 3xdaily for 7-10 days
- 12-15 years, 500mg twice or three times daily for 7-10 days
- Co-amoxiclav (only if culture results indicate susceptibility)
- 3 mths - 5 yrs, 0.25 ml/kg or 125/31 suspension 3x a day for 7-10 days
- 6-11 years, 0.15 ml/kg or 250/62 suspension 3x daily for 7-10 days
- 12-15 years, 250/125 mg or 500/125 mg 3x a day for 7-10 days

UTI give nitrofurantoin/Trimethoprim

Pyelonephritis give cephalexin

23. Acute and chronic glomerulonephritis

Acute glomerulonephritis
There are different types of acute nephritis, they all possess the same basic symptoms:
decreased urine output and volume overload, hypertension, oedema, haematuria and

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proteinuria. All forms of glomerulonephritis damage the glomerular, they can be
nephritic or nephrotic. We will only cover nephritic below as nephrotic is covered in the
question below.

The different types of acute nephritis are:

- Post-streptococcal and post-infectious nephritis
- Following a streptococcal sore throat or skin infection and is diagnosed by
evidence of recent infection, low C3 levels and nephritic symptoms.
- ABs (Amoxicillin) to destroy any remaining infection, then supportive
- Henoch-Schonlein purpura (aka vasculitis)
- Nephritic syndrome with characteristic skin rash on extensor surfaces,
arthralgia, periarticular oedema and abdominal pain. It is common aged 3-10
in boys, of unknown cause.
- Supportive, although IV methylprednisolone may be given
- IgA nephropathy
- Episodes of macroscopic haematuria, commonly associated with upper
respiratory tract infections
- Familial nephritis
- Most common type is Alport syndrome, an X-linked recessive disorder that
progresses to end-stage chronic kidney disease
- Systemic lupus erythematosus
- A type of autoimmune nephritis

Chronic glomerulonephritis is defined as abnormal urinalysis and/or a decreased GFR for 3

months or more.

24. Nephrotic syndrome

In nephrotic syndrome, there is damage to the podocytes that surround the glomerulus,
leading to proteinuria which causes low plasma albumin and oedema. Classic signs include:
- Periorbital oedema on waking
- Scrotal or vulval, leg and ankle oedema
- Ascites
- Pleural effusion
- Infections

Nephrotic syndrome can be a result of a number of different diseases:

- Primary
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis
- Membranoproliferative glomerulonephritis
- Rapidly progressive glomerulonephritis
- Secondary
- Diabetic nephropathy

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 - SLE
- Sarcoidosis
- Syphilis
- Hepatitis B
- Amyloidosis

In 90% of children with nephrotic syndrome, proteinuria resolves with corticosteroid

therapy (steroid-sensitive nephrotic syndrome). These children do not progress to
chronic kidney disease. The most common dosage is 60mg/m2 of prednisolone for 4
weeks, then reduced to 40 mg/m2 on alternate days for another 4 weeks before being
stopped. If children do not respond then they have what is known as steroid resistant
nephrotic syndrome. These children should be referred to a paediatric nephrologist and
may have Focal segmental glomerulosclerosis, mesangiocapillary glomerulonephritis or
membranous nephropathy.

Children with nephrotic syndrome are susceptible to hypovolemia, thrombosis, infections and
hypercholesterolaemia.

25. Acute renal insufficiency and chronic renal failure

Acute kidney injury (or renal insufficiency) is a reduction in renal function, with oliguria (0.5
ml/kg/hour) usually present. Causes of acute kidney injury are:
- Prerenal
- Hypovolaemia
- Circulatory failure
- Renal
- Vascular (e.g. haemolytic uraemic syndrome, vasculitis, embolus)
- Tubular (e.g. acute tubular necrosis, ischaemic, toxic, obstructive)
- Glomerular (glomerulonephritis)
- Interstitial (interstitial nephritis, pyelonephritis)
- Post renal
- Obstruction (congenital or acquired)

Children with acute renal failure should have their circulation and fluid balance meticulously
monitored with investigation by ultrasound of the kidneys and ureters to try and detect the
cause.

Chronic kidney disease is progressive loss of renal function due to numerous conditions and
has five stages, these are:
- Stage 1 - GFR >90 ml/min per 1.73 m2 (hyperfiltration stage)
- Stage 2 - GFR 60-89 ml/min per 1.73 m2
- Stage 3 - GFR 30-59 ml/min per 1.73 m2
- Stage 4 - GFR 15-29 ml/min per 1.73 m2
- Stage 5 - GFR <15 ml/min per 1.73 m2

The clinical features of stage 4 and 5 chronic kidney disease are:

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 - Anorexia and lethargy
- Polydipsia and polyuria
- Faltering growth/growth failure
- Bony deformities and renal osteodystrophy
- Hypertension
- Acute-on-chronic renal failure
- Incidental proteinuria
- Unexplained normochromic, normocytic anemia

Management is to prevent the symptoms and metabolic abnormalities of chronic kidney

disease to allow normal growth and development. Key elements that should be managed
include diet, renal osteodystrophy, control of salt and water balance, anaemia and hormonal
abnormalities.

We can define individuals as being at risk of AKI, having AKI or having Acute
Kidney failure. Definitions are:
- Risk - Serum creatinine greater than 1.5-2 x or GFR decrease of 25%
- Injury - Serum creatinine greater than 2-3 x or GFR decrease of 50%
- Failure - Serum creatinine greater than 3 x or GFR decrease of 75%

Indications for dialysis

- Hyperkalemia >7 mmol/l
- Hyponatremia <125 mmol/l
- Fluid overload
- Progressive deterioration

Pediatric Cardiology

26. Congenital heart disease

Congenital heart diseases are divided into two types; acyanotic and cyanotic. Alternatively,
and probably more commonly, these can be divided as Left-to-right, right-to-left and
obstructive (stenotic) lesions. The left-to right and stenotic are acyanotic generally, while
the right to left is cyanotic.

Understanding Cardiac Murmurs

- Most are innocent, it is important to be able to identify what is causing the murmur,
and whether it is benign or pathologic.
- All symptomatic murmurs are pathologic, but not all pathologic murmurs are
symptomatic
- Innocent cardiac murmurs generally soft, short, early systolic murmurs, best heard
at the sternal edge. Generally deeper.

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 - All diastolic murmurs (except venous hum) and pansystolic murmurs are
pathologic. Long, loud, harsh with radiation all also suggest a pathologic murmur.
Where a thrill is palpated, assume the murmur is pathologic.
- S2 should split in inspiration and become single on expiration.
- A widely split fixed S2 can be heart in Atrial-septal defects
- Heart murmurs are ranked 1-6. Grades 1 and 2 are generally innocent, 3 may or
may not be pathological, while 4+ (with thrill) is always pathological.

Acyanotic congenital defects

Ventricular septal defect
This is a hole between the left and right ventricle, through the ventricular septum. As the left
side of the heart is always under greater pressure than the right side, blood is pushed from
the left to the right. Small VSDs can be asymptomatic, but the typical finding is a
pansystolic murmur, heard best at the lower left sternal border, sometimes with a thrill.
There may also be a splitting of S2 depending on the size of the shunt.

⅓ of VSDs will spontaneously close, initial treatment is diuretics with or without digoxin
to reduce heart load. If the infant continues to fail to develop, surgery may be required to
close the VSD.

Atrial septal defect

ASDs represent 10% of all congenital heart defects, the most common being foramen ovale
remaining open. Some flow through the foramen ovale is normal just after birth, however it
should usually close within a week for birth. ASDs are very rarely symptomatic, even in large
shunts. A soft systolic ejection murmur can sometimes be detected, as can a fixed split S2
sound.

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Treatment is rarely needed, if a significant shunt still exists at the age of 3, then treatment
may be indicated through surgery or an ASD closure device.

Patent ductus arteriosus

As with foramen ovale, the ductus arteriosus is part of the fetal vasculation. It connects the
aorta to the pulmonary artery, allowing blood to bypass the non-functioning lungs in-utero.
Failure of the DA to close is known as patent ductus arteriosus, causing a left to right
shunting of blood and increasing pulmonary blood flow. PDAs account for 5-10% of all
congenital heart failures.

Symptoms as always depend on the size of the shunt, however the big risk here is an
increase in pulmonary pressure, possibly leading to pulmonary hypertension and
eventually heart failure.

Physical examination shows a widened pulse pressure, and a continuous machine-like

murmur which can be heard in the left infraclavicular area. Ductus arteriosus should close
within 2 days of birth.

Treatment is with diuretics initially, and then coil embolization or a PDA closure device later
if required. Medication can also be used to induce constriction of a PDA, including
indomethacin, ibuprofen and acetaminophen (paracetamol)

Endocardial cushion defect

Also known as atrioventricular canal defects, this is a complete or partial failure of the
septum to fuse with the endocardial cushion causing abnormal atrioventricular
valves, a ventricular septal defect and an atrial septal defect. In effect, you end up with
almost two chambers instead of the four, connected by a pathological common valve.

This is a very severe congenital malformation, and symptoms of heart failure develop due
to the increased pulmonary vascular resistance within the first two months. Treatment
is diuretics (with or without digoxin) and then surgical repair which is almost always required.
This defect is common in children with Down Syndrome.

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Cyanotic congenital defects
Tetralogy of Fallot
Tetralogy of fallot is the most common cyanotic (right to left) congenital defect. There are
four separate structural defects:
- Ventricular septal defect
- Pulmonary stenosis
- Overriding aorta
- Right ventricular hypertrophy

All four defects occur due to the fact that the

truncus arteriosus has failed to properly
separate into the aorta and pulmonary
artery (gestation weeks 3-4).

Infants may appear cyanotic initially, and

will become hypoxic in spells (tet spells)
which will prolong as time goes by.
Eventually if untreated spells will increase to
the length where there is a decrease in
consciousness, fitting and even death may
occur. Treatment is complete surgical
repair.

How blue a baby is at birth, depends on the extent of stenosis of the pulmonary valve. This
will determine if the infant is a blue tet (more cyanotic, more stenosis), or a pink tet (less
cyanosis, less stenosis).

Transposition of the Great Arteries

Here we see the pulmonary artery coming out of the left ventricle, and the aorta
coming out of the right ventricle! However the veins are still in the same location, so
the inferior and superior vena cava both go into the right side of the heart, and the
pulmonary veins go into the left side. What this means in practice is that oxygenated blood
goes around in its own little circle and deoxygenated blood goes around in its own
little circle. As one can imagine this isn’t great news. Without an additional defect (ASD,
VSD or PDA) death happens pretty quickly.

Cyanosis is always present, heart is hyperdynamic and murmurs will often be present
depending on the additional defects of the heart. Treatment initially is prostaglandin E1
to maintain ductal patency if present. A balloon atrial septostomy improves mixing between
two circulations, and a complete surgical arterial switch can eventually be done.

Tricuspid atresia
This is a disease where the tricuspid valve (that usually sits between the right atrium and
right ventricle) fails to develop, meaning there is no connection between the RA and the
RV. To compensate patent foramen ovale is maintained, so blood comes into the RA and
goes straight into the left atria. From blood moves into the left ventricle, where it crosses a
VSD into the right ventricle as well as going out through the aorta.

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Infants with tricuspid atresia are severely cyanotic, treatment depends on the presence of a
VSD and the amount of antegrade blood flow to the lungs. Prostaglandin E2 can be given
to keep the VSD open, but surgery will eventually be required.

Truncus Arteriosus
A very rare congenital abnormality, results in the failure of separation of
truncus arteriosus into its two normal offspring, the aorta and the
pulmonary artery. This means that there is a mixing of blood through both
the aorta and the pulmonary artery. Treatment is anticoagulation with
surgical repair. The single trunk with a single valve overrides a VSD,
resulting in mixing of blue (cyanotic) and red (oxygenated) blood.

Total anomalous pulmonary venous return

Again, very rare. This is disruption of the normal pulmonary venous
drainage during the third week of gestation that leads to one of four abnormalities. All
of the pulmonary veins fail to connect to the left atrium and return abnormally via the
right side of the heart. They have supracardiac, infracardiac, cardiac, or mixed drainage. In
order for this to be compatible with life, atrial-level communication must exist within the
heart.

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Hypoplastic left heart syndrome
Again…..very rare, however, is the most common cause of death from cardiac defects.
There is a failure of development of the mitral or aortic valve or the aortic arch, leaving
a small left ventricle that is unable to support normal systemic circulation. There is a
right to left shunt at the ductus arteriosus for systemic blood flow, however this is usually not
enough to save the patient.

27. Inflammatory cardiac diseases: Myocarditis, pericarditis,

endocarditis

Myocarditis
Myocarditis is rare in young children, it is generally viral, often caused by influenza virus,
coxsackie virus, parvovirus and adenovirus, although it can also be a complication of
diseases such as lyme disease.

Symptoms include FTT, feeding difficulties, fever, listlessness, low urine output,
decreased circulation, tachycardia, tachypnea and chest pain. Many of these symptoms
are nonspecific and as such the condition can be missed. Physical examination will show
signs of decreased cardiac output, with reduced capillary refill, muffled heart sounds and
sometimes S3 is audible with or without atrioventricular valve regurgitation.

Do CBC, remember acute anemia of any origin may cause heart failure, and chronic anemia
exacerbates heart failure. Do CRP, nasopharyngeal and rectal swabs, Creatinine kinase,
lactate dehydrogenase isoenzyme 1 and Troponin 1. If cardiac damage is suspected
chest x-ray/echo/MRI can be performed.

Management of viral myocarditis is that of minimizing the body’s hemodynamic

demands, use of digoxin, diuretics and afterload reduction can be useful.
Immunosuppression does not seem to improve outcome.

Pericarditis
Pericarditis is inflammation of the parietal and visceral surfaces of the pericardium,
most commonly it is viral, however staphylococcus aureus and streptococcus
pneumonia are the most likely causes in bacterial cases. Bacterial cases are much
more severe than viral cases. Symptoms depend on the amount of pericardial effusion,
they include chest pain, dyspnea, malaise, compelled position, fever, tachycardia,
friction rub, enlarged heart and distant heart sounds.

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Where the effusion is very large there is a risk of cardiac tamponade, a condition where
cardiac output is restricted due to the amount of fluid in the pericardial sac.

Echocardiography is the most specific and useful diagnostic test for pericarditis, while an
ECG may show elevated ST and reduced QRS amplitude. Treatment is
pericardiocentesis if fluid has built up significantly, if bacterial origin is proved then specific
antibiotics can be given, but in the majority of cases which are viral, we just use supportive
anti-inflammatory medications.

Endocarditis
Infective endocarditis is an uncommon life-threatening condition with an incidence of about
0.1/1000 in children. Congenital heart disease is the most common underlying
condition which increases the risks of endocarditis. In most cases, the condition is
secondary to an indwelling central venous catheter near the heart or associated with
immunosuppression.

The most common microorganism is viridans streptococci, with s. Aureus and coagulase
negative staphylococci important causes. The early symptoms are nonspecific, with
fever, malaise, and weight loss. Subtle hemorrhages may also be noted under the
finger nails. Endocarditis is usually subacute and slowly progressive, although can be
acute, secondary to sepsis.

Required labs include CBC, blood cultures, CRP, ESR with echo and ECG. Treatment is first
stabilization and supportive for cardiac failure, pulmonary edema and low cardiac
output, with antibiotics given once blood cultures are obtained. High doses are
required for 4-8 weeks, often penicillin G.

28. Arterial hypertension - essential and symptomatic

In children, hypertension is a blood pressure greater than the 95th percentile for age, gender
and height based on at least three different occasions. A hypertensive emergency is defined
as a severe elevation of BP associated with target organ damage (e.g. encephalopathy,
heart failure).

Causes of arterial hypertension can be primary or secondary.

- Primary
- Essential
- Metabolic
- Renal
- Congenital anomalies (renal dysplasia, obstructive uropathy)
- Structural disorders (Wilms tumor, polycystic kidney disease)
- Glomerulonephritis
- Acquired injury
- Endocrine
- Catecholamine-secreting tumour

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 - Hypercortisolism (cushings)
- Hyperaldosteronism
- Hyperthyroidism
- Neurological
- Increased sympathetic activity
- Dysautonomia
- Increased intracranial pressure
- Vascular causes
- Coarctation of the aorta
- Renal artery embolism
- Renal vein thrombosis
- Renal artery stenosis
- Vasculitis

Comfortably the most common cause of HTN is essential hypertension, with obese
children more likely to be HTN, meanwhile renal disease is the most common cause of
secondary HTN.

Most children are asymptomatic, unless there is a secondary cause which gives symptoms.
In severe cases, encephalopathy, heart failure, stroke and retinopathy may present.
History and family history are important to the case.

Children with HTN should have basic urinalysis, electrolytes, and other lab tests to rule
out renal conditions, with any other secondary causes indicated by the history also
examined. Treatment should be diet and exercise while hypertension is in stage 1 without
organ damage, medication should be started when the patient is in stage 2 HTN. CCBs or
ACE inhibitors are commonly first line in children, angiotensin receptor blockers, beta
blockers or diuretics can also be used.

Untreated HTN can lead to long term consequences for the child, including diseases of the
cardiovascular, CNS and renal systems.

Blood pressure category Blood pressure percentile

Normal <90th

Prehypertension 90th-95th

Stage 1 hypertension 95th-99th +5mmHg

Stage 2 hypertension >99th + 5 mmHg

29. Cardiac failure

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Cardiac muscle contractility depends on the preload, which itself depends on fiber length
and left ventricular filling pressure. Changes to the preload will affect the cardiac output,
leading to cardiac failure, which is properly defined
as the heart being unable to pump blood at a rate
required for metabolic needs. Therefore, we can
say that cardiac failure may be due to changes in
myocardial contractility or abnormal loading
conditions being placed on the myocardium.
Volume overload is the most common cause of
heart failure in children, although the exact cause
will change depending on the age group.

Heart failure can be divided into right sided and left

sided heart failure, each will present with different
symptoms and has separate etiologies. Left sided
heart failure will present with tachypnea,
orthopnea, wheezing, pulmonary edema while
right sided heart failure will present with edema,
distended neck veins and signs of right-sided
heart failure.

Treatment of childhood heart failure can be divided as

follows:
- General care
- Rest (reduced CO)
- Oxygen
- Sodium and fluid restrictions
- Diuretics
- Furosemide
- Combination of distal and loop diuretics
- Inotropic agents
- Digitalis
- Dopamine
- Dobutamine
- Amrione
- Afterload reduction
- Hydralazine (arteriolar vasodilator)
- Nitroprusside (vasodilator)
- Captopril/enalapril (ACEI)
- Other
- Mechanical counterpulsation
- Transplantation
- Extracorporeal membrane oxygenation
- Carvedilol (beta-blocker).

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Pediatric Autoimmune disease

30. Reactive arthritis related to infections, septic arthritis

Reactive arthritis
Reactive arthritis is the most common form of arteritis in childhood, characterised by
transient joint swelling, lasting less than 6 weeks, and most commonly affecting the
ankles or knees. It follows some form of extra articular infection, generally enteric
(Salmonella, Shigella, Campylobacter, Yersinia) in young children, in adolescence,
more commonly it is the result of viral STIs in adolescents.

Reactive arthritis presents with a triad of symptoms, conjunctivitis/uveitis, urethritis

(men)/cervicitis (women) and of course, inflammation of the joint. This combination of
symptoms was known as Reiter's syndrome, but then Reiter committed war crimes in WWII
so now we just call it reactive arteritis….seems safer. Wikipedia gives us a great mnemonic
for this - ‘can’t see, can’t pee, can’t climb a tree’, seems to cover it!

The classical presentation is that of urinary symptoms first (such as dysuria and
frequency) followed by monoarthritis, often of the keen or sacroiliac joint. Later ocular
involvement may develop if there has been no treatment. In some cases, nodules and
mucocutaneous skin lesions can develop.

Reactive arthritis is associated with HLA-B27 gene, upon the triggering of the immune
system, due to an error on the HLA gene, a as of yet not understood autoimmune reciton
occursion, causing attack to the ureters, joints and eyes. The synovial fluid cultures are
negative for any form of bacteria.

Treatment is generally supportive, ABs if there is still an infection present, otherwise

Analgesics, steroids and immunosuppressants may be given. The condition is self
limiting and patients generally make a full recovery, however complications can occur
including heart disease, amyloidosis, ankylosing spondylitis, aortitis and aortic regurgitation.

Septic arthritis
This is a more traditional infection of the joint space, hematogenous spread of bacteria
(often Staphylococcus aureus, and before immunization, H.influenza) into the synovial
fluid of the joint. This will cause a local infection with an erythematous, warm and acutely
tender joint with limited range in movement. The younger the child the more likely this is to
present with generalized illness.

Investigation includes CBC and acute-phase protein investigation, an Ultrasound may

also be useful to assess effusion, while X-rays can be used to exclude trauma if the history
suggests it. Treatment is the washing out of the joint with surgical drainage and a
prolonged course of antibiotics required (possibly IV). Joints such as the hip are more
dangerous and the patient should ensure they they work on their mobilization of the joint
else a long term deformity may occur.

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The diff dx includes lyme disease, osteomyelitis, suppurative bursitis, fasciitis, myositis,
cellulitis and soft tissue abscesses.

Hot Joint policy

- Most UK hospitals have a Hot Joint Policy.
- Generally, joint should be aspirated, and synovial fluid should be investigated to
look for WBC and percentage of polymorphonuclear cells along with gram staiting

31. Juvenile idiopathic arthritis (chronic)

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory joint disease
in children and adolescence. It is defined as persistent joint swelling (lasting longer
than 6 weeks), presenting before the age of 16, without any identifiable cause, it is
clinically and immunol genetically distinct from rheumatoid arthritis in adults.

JIA has seven subtypes, these are listed below:

- Oligoarthritis (49%) - 1-4 joints involved, mostly knee, ankle or wrist, can include
anterior uveitis in 20%
- Oligoarthritis extended (8%) - more than 4 joints, all the above also true
- Polyarthritis RF -ve (16%) - symmetrical large and small joints involved, fingers,
cervical spine and temporomandibular joints commonly affected
- Polyarthritis RF +ve (3%) - as above
- Systemic arteritis (9%) - oligoarthritis or polyarthritis, starts with myalgia and or
arthralgia but no inflammation - presents with acute illness, malaise, fever, rash,
hepatosplenomegaly and others.
- Psoriatic arthritis (7%) - asymmetrical distribution of large and small joints with
psoriasis
- Enthesis related arthritis (7%) - lower limb, large joint arthritis initially, with lumbar
spine involved later, localised inflammation at the insertion of tendons or ligaments
(often achilles) occurs
- Undifferentiated (1%)

Certain clinical characteristics are carried through all forms of the disease, including
stiffness after inaction (car journeys, in the morning). In young infants look for changes in
behaviour that might be explained by pain in a joint that they cannot articulate as
presentation can be indolent and bloods and inflammatory markers may be normal until quite
late. Treat the patient, not the results.

Complications:
- Chronic anterior uveitis
- Flexion contractures of the joints
- Growth failure
- Anemia of chronic disease
- Osteoporosis
- Amyloidosis

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Management is done by a specialist paediatric rheumatology team, using
immunosuppressive treatment such as methotrexate, systemic corticosteroids,
cytokine modulators and biological therapies.

The clinical path progresses through the following:

- Persistent synovitis
- Joint destruction
- Bone, Tendon and Ligament destruction

There are only three which are really common;

- Oligoarticular JIA - 2-3 years, fewer than five joints, non-destructive, not hips,
asymmetric
- Polyarticular JIA - 2-5 years and 10-14 years, destructive, any number of joints, not
hips
- Systemic JIA - over 17 y.p, any number of joints, destructive, increase fever, with
rash and systemic symptoms.

32. Systemic lupus erythematosus

So named as in the 13 century, the characteristic butterfly rash was thought to resemble a
wolf bite (really!!?), lupus is an autoimmune disease where circulating autoantibodies
affect healthy tissue. The origin is thought to be due to loss of T-lymphocyte control of
B-lymphocyte activity, leading to hyperactive B-lymphocytes which leads to non
specific and specific antibody and autoantibody production.

SLE can present abruptly or in an indolent manner. Symptoms are varied and complex,
the initial signs and symptoms can include almost any number of symptoms. Skin diseases
are found in 95% of cases, specifically the raised erythematous rash on the cheeks is
very common, as is photosensitivity. Raynauds is also common as are mouth and
nasal sores. There is activation of the reticuloendothelial system, causing
lymphadenopathy and splenomegaly, and renal involvement is also a very common
feature, with proteinuria or hematuria, progressing to renal failure, a distinct possibility.
Further potential symptoms include hypertension, arthralgias, arteritis, myalgias and even
CNS symptoms such as seizures.

The diagnostic criteria for SLE is a combination of factors, one should look for:
- Physical signs
- Malar butterfly rash
- Discoid skin lesions
- Photosensitivity
- Oral and nasopharyngeal ulcers
- nonerosi ve arthritis
- Pleuritis or pericarditis
- seizures or psychosis
- Laboratory data

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 - Renal diseases
- Proteinuria (>500mg/24hrs)
- Cellular casts (RBC, granular)
- Hematologic
- Hemolytic anemia
- Leukopenia
- Lymphopenia
- Thrombocytopenia
- Serological data
- Positive anti-double strand DNA
- Positive anti-smith
- Evidence of presence of antiphospholipid antibodies (IgG or IgM
anticardiolipin antibodies or lupus anticoagulant)
- Positive ANA

Treatment is corticosteroids. Initial use of pulse methylprednisolone and high dose oral
prednisolone (up to 2 mg/kg) is frequently required, followed by tapering to minimize
recurrence of symptoms. NSAIDs have also been used to some symptoms, while
hydroxychloroquine used topically can help with skin manifestations. The worst cases will
have additional therapy of cyclophosphamide, with especial effect in patients who have CNS
lupus.

Complications of SLE include infections, myocardial infarction, atherosclerosis as well

as the various complications of using long term corticosteroids.

33. Vasculitis syndromes - classification, henoch-schonlein

purpura, kawasaki disease

Vasculitis is a group of disorders where blood vessels are damaged by inflammation,

both arteries and veins can be affected. There are various different ways of classifying
vasculitis. We can classify based on:
- Underlying cause (e.g. syphilitic aortitis)
- Location of the affected vessel
- Type or size of the blood vessel (i.e. arteritis/phlebitis)
- Mechanism (the categories used in the text book)
- Antineutrophil cytoplasmic antibody-associated vasculitis
- Hypersensitivity vasculitis
- CT disease vasculitis
- Giant cell arteritis
- Others

Henoch-Schonlein purpura
A type of vasculitis of unknown etiology characterized by inflammation of small blood
vessels with leukocytic infiltration of tissue, hemorrhage and ischemia. The immune
complexes found in HSP are composed of IgA.

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HSP presents as a rash, arthritis and GI or renal vasculitis (although this is less
common). The palpable purpura of HSP is the hallmark of the disease and one of the
best diagnostic features. The rash can begin with small macules or urticarial lesions,
but rapidly progresses to purpura with areas of ecchymosis, sometimes with edema.
The calves and dorsum of the feet are areas that are most commonly affected. The
arteritis which affects 80% of patients is also most common in the lower extremities,
specifically the ankles and the knees. All of these symptoms are due to IgA deposition.

Lab results show ESR, CRP and WBC elevation, with a normal or high platelet count
(one of the key differentiating factors from other causes of purpura such as AI
thrombocytopenia, SLE or leukemia, in all cases we expect a decrease in platelets).
Urine Analysis helps to confirm if there has been renal vasculitis and testing the stool for
blood may identify evidence of gut ischemia.

Where two of the four following criteria are met, HSP can be diagnosed:
- Palpable purpura
- Bowel angina
- Diagnostic biopsy showing granulocytes in walls with IgA deposits
- Pediatric age group (<20)

Treatment is supportive, NSAIDs can be given for acute arteritis, systemic

corticosteroids are given if there is evidence of GI involvement causing significant
discomfort.

Kawasaki disease
This is a multisystem form of vasculitis with unknown origin which results in the
inflammation of small to medium sized arteries and causes aneurysms to form. It is
the second most common form of vasculitis (HSP the most common) and it is especially
common in Asian communities.

The clinical manifestations are put into three groups:

- Acute
- Lasts 1-2 weeks, starts with sudden onset of high fever (>40) of no obvious
source.
- This is followed by conjunctival erythema, mucosal changes, with dry
cracked lips and strawberry tongue and cervical lymphadenopathy
- Conjunctivitis is bilateral, bulbar and nonsuppurative, a rash of varying
appearance then appears in 80% of children
- Other symptoms such as abdominal pain, hydrops of gallbladder,
cerebrospinal fluid pleocytosis and arthritis may occur
- Subacute phase
- Lasts weeks 2-4 is marked by gradual resolution of fever and other
symptoms
- Desquamation of the skin at the fingers and toes occurs
- Platelet count now increases significantly
- This phase sees the onset of coronary artery aneurysms which increase
mortality
- Convalescent phase

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 - Symptoms begin to disappear until ESR (previously high) returns to normal,
usually about 6-8 weeks from the acute phase.

Remember, CRASH symptoms:

- C - Conjunctivitis
- R - Rash
- A - lymphAdenopathy
- S - Strawbery Tongue
- H - Hand and feet edema

Lab analysis requires blood and urine cultures along with chest x-ray to try and exclude
other sources of fever. Early phases see all inflammatory parameters elevated including
CBC, CRP and ESR. The development of coronary aneurysms can be monitored with 2D
dopler.

Treatment is IV immunoglobulin, although nobody knows why this works which is highly
amusing. Aspirin can also be given at an antiinflammatory dose (80-100 mg/kg/day
divided every 6 hours) and then at an antithrombotic dose later (3-5 mg/kg/day as a single
dose).

34. Physiology and Pathology of calcium-phosphorus

metabolism. Rickets
Calcium metabolism
99% of calcium is in the bone, 0.99% in the extracellular space, and 0.01% in the
intracellular space. Calcium is controlled by Parathyroid hormone. Ca2+ is detected by PTH
cells, causing PTH to be released. The hormone that causes bones to release calcium and
phosphorous, and encourages kidney reabsorption of calcium. PTH also stimulates the
conversion of Calcidiol (the inactive form of vitamin D) to be activated into calcitriol (the
active form) which then encourages GI absorption of Ca2+ in the GI tract.

In Acidosis we see forms of effective hypocalcemia. Ca2+ binds to albumin in the serum, in
acidic states albumin is capable of having increased Ca2+ binding, meaning there is
reduced free Ca2+ available causing functional hypocalcemia. Below we consider some of
the other common causes of hypocalcemia.

Hypocalcemia - <8.5mg/dL
- Hypoparathyroidism
- Iatrogenic
- DiGeorge
- Decreased Magnesium
- Kidney failure
- Causes increased Ca2+ excretion
- Tissue injury

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 - Phosphorous is released from cells (it is mostly intracellular) and binds to
Ca2+ causing effective hypocalcemia
- Low vitamin D
- Due to low calcium in diet, malabsorption, cirrhosis, decreased sunlight or
chronic renal failure
Symptoms are unstable, more excitable neurons causing tetani, Chvostek's sign (touching of
the facial nerve just below the zygomatic bone leads to twitch), muscle cramps, seizures,
tingling and possibly prolonged QT.

Hypercalcemia - >10.5 mg/dL

- Osteoclastic bone resorption due to increased PTH (often due to a parathyroid
adenoma)
- Excess vitamin D (due to increase in diet or medication)
Symptoms are as a result of the neurons being less likely to ‘fire’. Decreased reflexes,
increased calcium in kidneys causing dehydration and stones, with confusion and short QT.

Phosphate metabolism
85% of phosphate is in the bone, 1% is extracellular and 14% is intracellular. Phosphate is
the other main component of bone and its metabolism is also controlled by PTH, however, it
differs from calcium in the sense that an increase in PTH causes a decrease in phosphorus
in the blood, the opposite to the way that calcium reacts, as we shall explain below.

When PTH is released, it causes calcium and phosphate to be released from the bone, both
are then filtered by the glomerulus. However, while PTH encourages the reabsorption of
calcium in the tubules, this is not the case for phosphorus, so phosphorus ends up being
excreted in the urine, causing a reduction in serum levels.

Hypophosphatemia <2.5mg/dL
- Primary hyperparathyroidism (increased PTH causes increased loss of PO4-)
- Fanconi syndrome (Proximal convoluted tubule of the kidney loses ability to reabsorb
PO4-)
- Poor GI absorption (poor phosphate absorption in the GI due to alcohol or
medications
- Severe malnutrition followed by feeding - refeeding syndrome
Symptoms are ‘stones, thrones, groanes, bones, psychiatric overtones’.
- Kidney stones, Polyuria, constipation with weakness, bone pain, and depressed
mood

Hyperphosphatemia - >4.5mg/dL
- Acute/Chronic kidney disease (decreased GFR = decreased volume of fluid filtered =
decreased PO4- excretion causing increased serum phosphate)
- Pseudohypoparathyroidism (genetic disease causes PTH receptor defect so no
response to hormone)
- Hypoparathyroidism (DiGeorge syndrome, Iatrogenic)
- Excessive intake
- Release of Phosphate from cells (e.g. crush injury, tumour lysis syndrome
Rhabdomyolysis)
- Respiratory acidosis/diabetic ketoacidosis

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Symptoms come from over excitability of the nerves along with nephrocalcinosis in long term
cases.

Rickets

Vitamin D deficiency presents as Rickets in children and osteomalacia in post

pubertal adolescents. Vitamin D is metabolised in the liver to calcidiol, or 25-
hydroxyvitamin D, this metabolite is then transported by blood proteins to the kidney where
it is converted into the more active calcitriol. Calcitriol decreases the concentration of
messenger RNA for collage in bone and increases the concentration of mRNA for vitamin D-
dependent calcium binding protein in the intestine, allowing for an increase in calcium
absorption in the gut. Additionally vitamin D seems to have a direct anabolic effect on
bone along with direct feedback to the parathyroid gland to inhibit secretion of PTH.

Rickets can occur when there is inadequate direct sun exposure and therefore Vitamin D
intake is deficient, this is known as primary rickets. Other causes of Vitamin D deficiency
include various drugs (phenobarbital, phenytoin) and malabsorption while rickets can also
be caused by various enzyme deficiencies that limit conversion of vitamin D into its
metabolites. Breast fed infants and those with darker skin are at greatest risk.

Rickets sees defective bone growth at the epiphyseal cartilage matrix, which fails to
mineralize. This uncalcified osteoid causes a wide irregular zone of poorly supported
tissue which can in turn cause skeletal deformities. The clinical manifestations are most
common during the first two years of life. Clinical features include Craniotabes (thinning of
the outer skull making it feel like a ping pong ball), enlargement of the costochondral
junction, thickening of wrists and ankles, anterior fontanelle is enlarged and its
closure may be delayed. In more advanced forms we see scoliosis and exaggerated
lordosis with bowlegs in some infants.

Serum phosphorus is usually reduced and serum alkaline phosphatase activity is

elevated. When serum calcium is below 7.5mg/dL tetany can occur.

Diagnosis is based on general clinical picture and radiographic changes to the distal ulna
and radius. Treatment is vitamin D supplementation.

Pediatric Endocrinology
Endocrine disorders can manifest in one of four ways:
- Excess hormone e.g. Cushing
- Deficient hormone
- Abnormal response of end organ to hormone
- Gland enlargement

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 35. Differential diagnosis of growth disturbances, diseases of the
pituitary gland

First we will consider the Hypothalamic-Pituitary axis, and diseases of the pituitary gland,
from here we will then consider the differential diagnosis of growth disturbance as the former
can cause the latter.

Diseases of the pituitary gland

The hypothalamus controls many endocrine systems either directly or via the pituitary gland.

The hypothalamus is a small neuroendocrine organ that sits anterior-inferiorly to the

thalamus and superior to the pituitary. We have listed below what is shown in the above
image, the hormones released by the hypothalamus and the effect they have on the
pituitary.
- Growth Hormone Releasing Hormone - stimulates growth hormone
- Corticotropin Releasing Hormone - stimulates Adrenocorticotropic hormone
- Dopamine - Inhibits Prolactin
- Gonadotropin Releasing Hormone - stimulates Follicle stimulating hormone and
luteinizing hormone
- Thyroid releasing hormone - stimulates of Thyroid stimulating hormone

Meanwhile, the pituitary gland is a pea-sized structure, suspended inferiorly to the

hypothalamus by the infundibulum, seated within the sella turcica. The pituitary gland sits
inferior to the optic chiasm. It has three main parts, the anterior part for hormone secretion,
the intermediate part, and the posterior part (neurohypophysis) which is in essence an
extension of the hypothalamus and secretes ADH and oxytocin.

We broadly classify diseases of the pituitary into hyperpituitarism and hypopituitarism.

Here we consider the clinical manifestations and review the causes of both diseases.

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Hyperpituitarism is commonly due to a pituitary adenoma. Classic symptoms depend on
the specific cells involved in the adenoma, although an overlap is not uncommon:
- Cushing’s syndrome (hypercorticortisolsm) - due to increased ACTH
- Acromegaly (excessive growth hormone)
- Prolactinoma (excessive prolactin) can lead to irregular lactation and decreased sex
drive - Prolactinomas are the most common type of pituitary adenoma
- Hyperthyroidism (increased TSH) leads to nervousness, tachycardia, weight loss,
fatigue and muscle weakness
Labs should be done to measure levels of hormones where imbalance is suspected, MRI
can then be done to confirm the tumor if required. Note however, all causes of
hyperpituitarism are fairly rare in children, to the extent we don’t even have a section on
this in the book.

Hypopituitarism is more common, it is similar here to look at the clinical manifestations

and then consider the possible causes:
- Growth failure/hypothyroidism or both - can be due to GH, TRH/TSH deficiency
- Hypoglycemia - GH deficiency, ACTH insufficiency or both
- Micropenis, pubertal delay or arrest - hypogonadotropic hypogonadism with or
without GH deficiency
- Polyuria/Polydipsia - ADH deficiency (Diabetes insipidus)
The underlying cause of hypopituitarism is most commonly a form of destructive lesion of
the pituitary or hypothalamus. Including craniopharyngioma (a tumor of the Rathke
pouch) that can damage the glands function. Acquired hypopituitarism may result from
pituitary infections or due to iatrogenic causes. Congenital hypopituitarism can be
caused by the absence of hypothalamic releasing factors, this is more common in
premature children with neurological congenital defects.

Where all or most of the hormones are decreased, we call this panhypopituitarism.

Growth disturbance
Growth should be measured for all children and plotted on the appropriate growth charts,
where the child is below the 0.4th or above the 99.6th percentile, alarm bells should ring.
Where a child is below the age of two they should be measured in a supine position, where
older, they should stand straight with their shoes off.

The causes of short stature can be summed up below:

- Natural variation (constitutional or genetic)
- Endocrine (GH, IGF, hypothyroidism or diabetic disturbances)
- Syndromes (e.g. Turner, Noonan, Trisomy 13,18,21, Prader-Willi)
- Chronic diseases (congenital cardiac disorders, pulmonary disorders, GI disorders,
hepatic disorders, hematologic disorders, renal disorders and others)

Growth hormone, Thyroid hormone and Insulin-like growth factor 1 are the most
important hormones in human growth, these should be considered early when a child is
failing to reach their developmental milestones. However it should also be remembered that
nutrition is the most important and most common cause of FTT. The table below
illustrates the full differential diagnosis and therapy of short stature.

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 36. Disease of thyroid gland

Thyrotropin releasing hormone is released from the hypothalamus and binds to the
anterior pituitary, where thyroid stimulating hormone (TSH) is released into the
systemic blood stream. TSH then binds to receptors in the thyroid to stimulate the
secretion of thyroxine (T4) and triiodothyronine (T3). These then act via a negative feed-
back loop on the pituitary to control TSH secretion.

T3 and T4 do not readily cross the placenta, as such concentrations in the neonate
represent the neonates own thyroid hormone production. However, maternal thyroid
antibodies and iodides, as well as treatment for hyperthyroidism, will cross the
placental barrier, and as such may cause congenital hypothyroidism. Serum TSH
increases just after birth but then decreases to lower values, as such it is important to
consider age adjusted values when reviewing neonatal hormone levels.

The majority of circulating thyroid hormone is T3, T4 converted into the more potent T3
in the periphery. Both T3 and T4 exist in the periphery in a bound state, keeping them
inactive, until they are needed, and become unbound. They are bound to the carrier
protein thyroxine-binding globulin, and to a lesser extent, albumin. If we have a

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 deficiency of thyroxine-binding globulin, then we’ll have an increased proportion of
free thyroid hormone which will exert a negative feedback on the pituitary and
therefore decrease the overall levels of thyroid hormone.

It should come from the above therefore be clear that different levels of T3/4, TSH and TBG
can tell us different things about the pediatric patient. The table below provides a guide for
distinguishing different types of anomaly.

Abnormality Total T4 Free T4 Serum TSH Serum TBG

Primary Decreased Decreased Increased Normal

hypothyroidism

Hypothalamic Decreased decreased decreased Normal

tertiary
hypothyroidism

Pituitary Decreased Decreased Decreased Normal

secondary
hypothyroidism

TBG deficiency Decreased Normal Normal Decreased

TBG excess Increased Normal Normal Increased

Let us take a look at some of the thyroid disorders.

Hypothyroidism - Congenital hypothyroidism

Caused by dysgenesis of the thyroid gland (agenesis, aplasia, ectopia) or less commonly
dyshormonogenesis (enzyme defect, with failure to properly produce the hormone). In
cases of dyshormonogenesis, we see goiter, a logical step if we think about it, as we have
low T4, and therefore increased TSH which further stimulates the thyroid gland.

Causes of hypothyroidism in infancy and childhood:

- Newborn - no goiter
- Thyroid gland dysgenesis or ectopic location
- Exposure to iodies
- TSH or TRH deficiency
- Newborn - goiter
- Inborn defect in hormone synthesis
- Severe iodine deficiency
- Child - no goiter
- Thyroid gland dysgenesis, hypothalamic-pituitary insufficiency
- Child - goiter
- Hashimoto thyroiditis, inborn defect in hormone synthesis, iatrogenic

Manifestations are subtle, and neonatal screening is required to make an early diagnosis
and initiate thyroid replacement therapy at less than one month of age to prevent long
term developmental problems. Findings include hypothermia, respiratory distress,

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large fontanels, abdominal distention, lethargy and poor feeding and others.
Treatment is with levothyroxine (10-15 ug/kg for newborn, 3ug/kg in later childhood). If
treatment is delayed there are severe long term consequences.

Acquired hypothyroidism
Acquired hypothyroidism should be suspected in a child who has a decline in growth
velocity, especially if not associated with weight loss. The most common cause is
Hashimotos in the developed world, in the undeveloped world, iodine deficiency is the
etiology of endemic goiter.

Clinical manifestations of hashimotos include firm, nontender, euthyroidism or

hypothyroidic diffuse goiter with a pebble like surface. Onset typically after the age of
6, more common in women. See above for symptoms of hypothyroidism, treatment is again
levothyroxine.

Hyperthyroidism - Graves Disease

Graves is by far the most common cause of hyperthyroidism. The body produces
autoantibodies (thyroid stimulating immunoglobulins) that stimulate the thyroid. In
graves serum T4 and T3 are both raised, with TSH suppressed. Clinical manifestation is
nervousness, tachycardia, hypertension ,tremor, increased sweating, shiny smooth
skin, fatigue, heat intolerance, weight loss, hyperkinesis, goiter and increased bowel
movement. The disease if five times more common in girls than in boys.

Treatment can be pharmacological, radioactive iodine or surgical.

Thyroid storms are a rare medical emergency consisting of tachycardia, disorientation,

elevated BP and hyperthermia. Treatment is symptomatic (cooling, beta blockers etc) and
iodine to block the thyroid hormone release after an antithyroid medication is started.

Hyperthyroidism - Congenital
Occurs due to maternal thyroid-stimulating immunoglobulin passing across the
placental barrier. The condition is often masked in the first few days due to the natural
increase in T4 in neonates, only later are symptoms of irritability, tachycardia, poor
feeding and FTT present. Treatment includes the anti thyroid drug methimazole and beta
blockers to reduce BP

It is noteworthy that about 2% of all children develop

solitary thyroid nodules and remain euthyroidism,
however such patients should still have a full evaluation.
Carcinoma of the thyroid is rare, only 1% of all pediatric
cancers.

37. Diseases of the adrenal glands,

congenital adrenal hyperplasia

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The adrenals have an outer cortex (for synthesis of steroids) and an inner medullary
(which synthesizes catecholamines).

So, let's consider the regulation of each of the different hormones here:
- Renin-angiotensin releases aldosterone from the cortex
- Adrenocorticotropic hormone releases cortisol and dehydroepiandrosterone
sulfate (DHEAS - precursor to testosterone) from the cortex
- Preganglionic sympathetic fibers release epinephrine and norepinephrine from
the medulla

Adrenal insufficiency
The inadequate glucocorticoids and/or mineralocorticoids are generally the first presenting
factors of adrenal insufficiency;
- Cortisol deficiency
- Hypoglycemia, low stress tolerance, vasomotor collapse, hyperpigmentation,
apneic spells, weakness
- Aldosterone deficiency
- Hypotonia, hyperkalemia, urinary sodium wasting, salt carving, acidosis, FTT,
volume depletion, hypotension, diarrhea
- Androgen excess - hirsutism

Adrenal insufficiency can be primary (pertaining to the adrenals themselves), secondary

(due to hypopituitarism) or tertiary (a result of decreased hypothalamic action).

Addison's disease is a rare acquired disorder of childhood associated with the

autoimmune destruction of the adrenal glands. The clinical symptoms are as above for
adrenal insufficiency, and can occur in the context of autoimmune syndromes. Treatment
is replacement of the missing hormones, 10-15mg/m2/24 hours of hydrocortisone with
mineralocorticoid replacement with fludrocortisone, serum sodium and potassium.

Cushing's syndrome is the opposite disease, classic clinical manifestation includes

central or generalised obesity with failure of longitudinal growth, hirsutism, weakness,
nuchal fat pad, acne, striae, hypertension and hyperpigmentation when there is increased
ACTH. The key diagnostic test is urinary cortisol levels. Cushing’s can be primary,
secondary or tertiary, it can also be as a result of corticosteroid drug prescription.
Congenital adrenal hyperplasia
This is an AR disease that causes a primary lack of adrenal steroid synthesis leading to
increased ACTH production from the pituitary gland and therefore adrenal hyperplasia. One
of three enzymes is affected that leads to a reduction in steroid synthesis:
- 21 - hydroxylase - responsible for the synthesis of aldosterone and cortisol
- 11 - hydroxylase - responsible for the synthesis of aldosterone and cortisol
- 17 - hydroxylase - responsible for the synthesis of cortisol and androgens
What is also notable is that whichever of the three enzymes of the adrenal gland that is still
able to be synthesized (androgens in 21 and 11 form and aldosterone in 17 form) is over

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produced, so the clinical picture presents with the symptoms of the decreased enzymes and
increased enzyme.

This means the most common form (21-hydroxylase) typically presents with hyper-
androgenism, along with high diuresis and decreased cortisol levels. Often females present
with androgenised genitalia.

38. Physiology and pathology of puberty

Physiology
Puberty is marked by the first appearance of pubarche (the first appearance of pubic
hair) and gonadarche (earliest gonadal changes). Pubarche is the result of adrenal
maturation, with an increase in androgen secretion. Other simultaneous features include
oiliness of hair and skin, acne, axillary hair and body odor. Gonadarche is due to the
increase in sex steroids generally, which of course differe based on gender
(testosterone from the testes, estradiol and progesterone from the ovaries). The increase of
these features account for the secondary sexucal characteristics we associated with the
different genders.

Hypothalamic gonadotropin-releasing hormone (GnRH) is secreted from the

hypothalamus into the pituitary which then releases LH and FSH. This axis is active in the
newborn but suppressed in childhood until activity increases in puberty. In females FSH
stimulates ovarian production of estrogen and later in puberty the formation of the corpus
callosum. While in males LH stimulates the production of testosterone from the Leydig cells,
and then later the seminiferous tubules. The normal age of puberty onset is 13 years for girls
and 14 for boys.

Delayed puberty
There are a number of different causes of delayed puberty, we have listed these below:
- Constitutional growth delay
- A temporary delay in skeletal growth and thus height and puberty.
- Puberty will naturally occur when bone age reaches about 12
- All other causes of delay must be first ruled out and a FH of constitutional
growth delay should be present for the diagnosis to be reached
- Hypogonadotropic hypogonadism
- Due to hyposecretion of the hypothalamus (GnRH) or pituitary (LH and FSH)
- LH acts on Leydig cells in males and theca cells in females while FSH acts on
sertoli cells in the male and follicular cels in the female. Combined this casues
secretion of gonadal sex steroids and initiation of folliculogenesis and
spermatogenesis
- Can be acquired or congenital
- Isolated Gonadotropin deficiency
- Also known as congenital hypogonadotropic hypogonadism (see above) is a
small subset of HH due to deficiency of GnRH where the function of the

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 anterior pituitary is otherwise normal and the secondary causes of HH are not
present
- Can occur with Kallmann syndrome (50% of cases) where smell is also
affected, or smell can be preserved
- Abnormalities of the CNS
- CNS tumors such as pituitary adenoma, glioma, prolactinoma and others a
cause gonadotropin deficiency
- Craniopharyngiomas have a peak incidence in teenage years and can cause
any type of anterior or posterior pituitary hormone deficiency
- Syndromes of hypogonadotropic hypogonadism
- Anorexia nervosa and hypothyroidism can both cause puberty delays
- Hypergonadotropic hypogonadism
- Increased GnRH but low se steroid levels due to primary gonadal failure
- Almost always diagnosed at the point of failure to enter gonadarche
- Ovarian failure is common in Turners, while testicular failure is common in
Llinefleters

Sexual Precocity (early onset puberty)

Can be diagnosed when secondary sexual development occurs before 9 in boys or 8 in
girls. Let's look at some types
- Central precocious puberty (GnRH-dependent precocious puberty
- All developments are normal, just slightly early
- Commonly idiopathic and harmless, occurs with positive family history
- Can also however be due to conditions that affect the CNS including
hydrocephalus, meningitis, encephalitis, cysts, trauma and epilepsy, so these
must be excluded
- Germinomas, hamartomas and gliomas can all also cause the condition
- GnRH-Independent Precocious puberty
- The most common cause is MCune-Albright syndrome, more frequent in girls
than boys, and occurs with polyostotic fibrous dysplasia, precocious
gonadarche and hyperpigmented cutaneous macules (cafe au lait spots)
- The disorder is due to a mutation in the G protein intracellular signalling
system which causes misregulation and over stimulation of ovary, bone and
skin .
- Hyperthyroidism, hyperadrenalism and acromegaly can all also occur

Development in puberty is measured based on the Tanner Scale which relies on pubic hair
+ testicle size and penile length/breast size to judge how an individual is developing through
puberty. The scale moves from 1 (no start of puberty) to 5, puberty completed.

39. Diabetes mellitus

There are about 30,000 young people under the age of 19 with diabetes in the UK, giving a
prevalence of 2/1000. The condition is more common in Northern countries (Scotland,
Finland etc).

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Let's take a quick look at the classification of diabetes according to aetiology:
- Type 1 (most childhood diabetes)
- Destruction of pancreatic beta-cells by autoimmune process
- Type 2 (insulin resistance followed by beta cell failure)
- Usually older children, obesity related, positive FH and not as prone to ketosis
- Maturity onset diabetes of the young (MODY)
- Various types caused by genetic defects in beta-cell function
- Drug induced diabetes (i.e. corticosteroids)
- Endocrine disorders (e.g. Cushings)
- Genetic/chromosomal syndromes (e.g. Downs and Turner)
- Neonatal diabetes (transient and permanent secondary to defective B cells
- Gestational diabetes

Criteria for diagnosis of diabetes:

- Fasting plasma glucose > 7 mmol/l, or
- Symptoms of hyperglycemia and a casual plasma glucose > 11.1 mmol/l, or
- 2 hour plasma glucose > 11.1 mmol/l
Criteria for diagnosis of impaired glucose tolerance (aka pre-diabeties)
- Fasting plasma glucose 5.6-7 mmol/l
- 2 hour plasma glucose 7.8 - 11.1 mmol/l

Type 1 diabetes

Type 1 diabetes is the result of genetic and environmental causes. Early clinical features
include polydipsia, polyuria, weight loss and acanthosis nigricans, an indicator of
insulin resistance. In more progressive, uncontrolled diabetes, diabetic ketoacidosis can
develop, with acetone on the breath, vomiting, dehydration, abdominal pain, hyperventilation
(kussmaul breathing), hypovolemia, coma and eventual death.

The management of type 1 diabetes is centered around education and insulin injections.
There are five types of insulin preparation:
- Rapid-acting insulin analogues (e.g. Insulin lispro)
- Short acting soluble insulin (e.g. Actrapid)
- Intermediate-acting insulin (e.g. insulatard)
- Long acting insulin (e.g. Glargine)
- Predetermined combinations of the above

Insulin type Trade name Start of action Cleared from system

Rapid Lispro 15 mins 5 hours

Short Actrapid 1 hour 8 hours

Intermediate Insulatard 2 hours 18 hours

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 Long Gargine 2 hours 24 hours
Most common preparation is a mix of short and long acting (e.g. 70/30). Usually begin
therapy with 10u before bed, then check glucose in the morning. Where glucose is high
increase base dose, if low, decrease base dose. From here, if after 3 months HbA1c is high
then add rapid insulin before each main meal.

Most children are started on a continuous subcutaneous insulin pump or multiple daily
injection regimen of long acting insulin in the late evening or morning and fast acting
just prior to meals. Diet is also an important element of diabetes that must be controlled,
simple carbohydrates should be avoided, replaced by complex carbs and fiber, with a
reduction in fats as well.

Diabetes can lead to a number of acute complications, we review the important ones below.
- Hypoglycemia - a blood glucose below 4 mmol/l, presents with a wobbly feeling in
legs, and can present to seizures and coma if untreated. Glucose in an easy to
absorb form should be administered immediately (e.g. glucose tablet or sugary drink)
and children should always have access to such a glucose source
- Diabetic ketoacidosis - blood glucose >11. mmol/l and blood ketones >3 mmol/l. See
the box below for full investigations and treatment

Hypoglycemia
This is defined as a blood glucose less than 2.6mmol/L and is actually quite common in
neonates. Clinical features include sweating, pallor and signs of CNS irritability (including
seizures).

Blood glucose should be checked in any child who becomes septicaemic or is seriously ill,
has prolonged seizures, or develops an altered state of consciousness.

Causes of hypoglycemia include insulin excess (from tumor or drugs), liver diseases,
ketotic hypoglycemia of childhood, or any number of GI disorders that may prevent proper
carbohydrate absorption of glucose.

Treatment is IV bolus of glucose (max 5ml/kg) e.g. dextrose followed by 10% glucose
infusion.

Diabetic ketoacidosis
- Do glucose and ketone investigation to assess the extent of ketoacidosis. Add
electrolytes and creatinine to assess for dehydration, blood gas analysis and
cardiac monitor to look for T-wave changes.
- Management
- ABC - if BP <90mmHg give 500mL bolus saline, repeat as needed
- 50u actrapid to 50mL 0.9% saline. Infuse continuously at 0.1u/kg/h - ai for
ketones below 0.5mmol/L/h
- Assess K+ for replacement
- Consider catheter if not passed urine after 2 hour
- Avoid hypoglycemia, give 10% glucose at 125mL/h to run alongside saline
- Fluids - 0.9% saline (10ml/kg) if in shock, then correct gradually. Avoid
- Acidosis - metabolic acidosis will be present, but avoid bicarbonate unless

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 the child is shocked
- Do not stop IV insulin until 1 hour after subcutaneous insulin has been
given
- Identify any potential causative factor for the ketoacidosis (e.g. infection)

Long term complications include micro and macrovascular damage including retinopathy,
nephropathy, neuropathy, hypertension, coronary heart disease and cerebrovascular
disease.

40. Obesitas and metabolic syndrome

In the US, 17% of 2-20 year olds are obese, with more than 30% of the adult population are
obse. Obesity is a definition based on BMI, a calculation of weight in kg/height2 (m). A
BMI between 18 and 25 is normal, 25-29 is overweight, and 30+ is considered obese.

Children born to parents with obesity are 5x more likely to be obese, and women are more
likelly to have an increased BMI post pregnancy. Additionally, some small gestational age
newborns have higher risks for abnormal postnatal weight gain and diabetes.

The risk of obesity is the risk of complications to almost every nervous system, let's take a
look at the main complications:
- Psychosocial
- Growth - increase height, advanced bone age, early menarche
- CNS - pseudotumor cerebri
- Respiratory - obstructive sleep apnea
- Cardiovascular - hypertension, cardiac hypertrophy, arrhythmias, ischemic heart
disease
- Orthopedic - slipped capital femoral epiphysis
- Metabolic - insulin resistance, type 2 diabetes, hypertriglyceridemia,
hypercholesterolemia, gout, hepatic steatosis, PCOS

Certain syndromes and diseases also increase the risk of childhood obesity, these include
Prader-Willi, hypothyroidism, cushings, turner’s and others.

Routeine evalulation of obese patients hould include anthropometric data, dietary and
physical activity, physical examination (BP, adiposity distribution, orthopedic abnoramlities)
and Lab studies. Prevention and treatment is around eating good foods and increasing
exercise.

Metabolic syndrome
Five elements:
- Obesity
- Low HDL
- High TAGs
- High BP
- Insulin resistance

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Genetic Abnormalities and Pediatric Neurology

First, let's consider some general stuff that isn’t really included in these questions. First, a list
of AD diseases:
- Achondroplasia thanatophoric dysplasia crouzon syndrome with acanthosis nigricans
- Nonsyndromic craniosynostosis
- Neurofibromatosis 1
- Neurofibromatosis 2
- Huntington's
- Myotonic dystrophy
- Marfans
- Hereditary angioneurotic edema

Next, consider some important AR diseases

- Adrenal hyperplasia
- Phenylketonuria
- Cystic fibrosis
- Friedreich ataxia
- Gaucher diseases
- Sickle cell anemia

And finally some important X-linked diseases

- Fragile X
- Duchenne MD
- Hemophilia A
- Rett syndrome (subset of autism with loss of regulation for genes, is lethal for males)
- Colour blindness
- Adrenoleukodystrophy
- Glucose 6-phosphate dehydrogenase

41. Chromosomal disorders

These are disorders that are caused by change in the number of chromosomes
(aneuploidy) or changes in chromosomal structure (duplications, deletions or inversions).
The normal karyotype for humans is 46 XX or XY, with 23 pairs include one pair of sex
chromosomes. Here we review some diseases where this is not the case.

Down Syndrome (Trisomy 21)

This is the most common abnormality of chromosome number, with a rate of 1/1000. It
occurs as a result of nondisjunction in maternal meiosis phase I which causes three
copies of chromosome 21 (47, XX +21 for a boy with down’s). In a proportion of those with
DS, mosaicism occurs, this means that there are two populations of cells, one with the
triplicate and one that is normal. These patients will present with a less severe form of the
disease.

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DS infants tend to have a normal birth weight and length but are hypotonic. Facial
features include brachycephaly, flattened occiput, hypoplastic midface, flattened nasal
bridge, upslanting palpebral fissures, epicanthal folds and a large protruding tongue.
Infants also have short broad hands with a transverse palmar crease.

50% of children will have some form of congenital heart disease (e.g. AV canal, VSD or
ASD), with 10% having some form of GI anomaly (most commonly duodenal atresia,
annular pancreas and imperforate anus). 18% have congenital hypothyroidism and many
go on to acquire hypothyroidism. DS children have an increased risk of leukemia and
are more susceptible to infection, are more likely to develop cataracts, and 10% have
atlantoaxial instability increasing the risk of cervical spinal cord damage. Risk of DS
increases significantly with maternal age over 40.

Trisomy 18 (aka Edward’s syndrome)

The seonc most common autosomal trisomy, ore than 95% of cases cause spontaneous
abortion in the first trisomy, only patients with mosaicism will survive. Most infants are
born with low birth weight, features include hypotonia,microcephaly with prominent
occiput, micrognathia, low-set malformed ears, hypoplastic nails, clenching of fists
and rocker-bottom feet. Congenital heart disease is common as is limited hip
abduction and lower limb deformities. Only 5% live more than 1 year.

Trisomy 13 (aka Pataue’s syndrome)

The third most common of the trisomies, is usually fatal in the first year of life with only
8% surviving more than 1 year. Infants are of small birth weight and microcephalic with
midline facial defects such as cyclopedia, cebocephaly, cleft lip and cleft palate all
being common. The forehead is sloping, ears are small and malformed. Limbs show
polydactyly of the hands, with clubfeet or rocker bottom feet as well. Most have some
form of congenital heart disease with many having a punched out scalp lesion over the
occiput called aplasia cutis congenita, one of the key diagnostic features of the
disease.

Klinefelter syndrome
1 in 500 male births is affected, and is the most common cause of genetic
hypogonadism and infertility in men, it is the result of an extra X chromosome (47,XXY).
15% of cases are mosaic. Before puberty boys are indistinguishable from others, diagnosis
is generally made after puberty should have fully developed, as puberty is delayed and
there is decreased pubic and axillary hair along with infantile testis. KS adolescence tend to
be tall with long limbs and develop gynecomastia. Such men have decreased
testosterone and additional supplementation is needed. If no treatment is given not only is
there infertility but osteopenia and osteoporosis will develop.

Turner syndrome (Monosomy X)

This is the only monosomal disorder which is compatible with life, however 99% of those
with 45,X are spontaneously aborted. TS presents in a relatively mild fashion, women
affected tend to have normal intelligence and life expectancy. Females will present with
low-set malformed ears, triangular face, flattened nasal bridge and epicanthal folds.
There is also an interesting webbing of the neck with a shield-like chest and widened
internipple distance.

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Internal error include congenital heart defect, with coarctation of the aorta, the most
common anomaly. Renal anomalies are also common, found in 50% of patients. Women
with TS are short stature and will have streak glands leading to estrogen deficiency
and therefore no secondary sexual characteristics along with amenorrhea. Most women
require estrogen replacement. Only 33% of infants with TS are diagnosed around birth,
another 33% are recognised in childhood during a workup for short stature, while the
remainder are detected when there is no normal onset of puberty.

An additional few words here about structural chromosomal disorders, none of these were
mentioned in the lecture so I just want to touch on them.
- Cri du Chat syndrome
- Deletion of the short arm of chromosome 5 - leads to catlike cry during
infancy due to tracheal hypoplasia. FTT, cleft lip and palate and congenital
heart disease are all possible. The severity of the disease depends on the
size of the deletion
- Williams Syndrome
- Small deletion of 7th chromosome - 80% have congenital heart disease, will
have ‘elfin facies’ with median flare of eyebrows and a slight puffiness of the
face. Will develop intellectual disability, individuals will be loquacious and
gregarious, described as ‘striking personality’
- Prader-Willi Syndrome
- Small deletion on 15th chromosome, in paternal chromosome - present with
hypotonia, FTT, hypogonadotropic hypogonadism and obesity after infancy
- Angelman Syndrome
- Also a deletion on the 15th chromosome, in maternal chromosome -
moderate intellectual disability, absence of speech, ataxia and characteristic
craniofacial appearance along with spontaneous laughter.

42. Inborn errors of Metabolism - Intoxication type

Inherited metabolic diseases (IMDs) are individually rare but collectively significant. More
significant as the symptoms alone are rarely diagnostic, specific tests for metabolites for
defective enzymes will need to be done in order to identify the disorder. IMDs are quite
simple in principle, either an enzyme, organel or specific energy system fails (due to
loss of enzyme or genetic abnormality of the organel) resulting in the production of a
toxic byproduct, or no reaction at all, leading to a buildup of the metabolite to toxic
levels.

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Presentation of inborn errors of metabolism is highly varied, but a physician should consider
such errors when children present with:
- Sudden severe presentation when previously well
- Significant metabolic acidosis
- Unexplained respiratory alkalosis
- Hypoglycaemia
- Cardiac failure/cardiomyopathy
- Hepatomegaly
- Unexpected drowsiness, coma or irritability
- Seizures
- Dysmorphia
- Loss of skills
- Loss of size/weight

There are two main inborn errors that we are asked to consider in this question, PKU and
Galactosemia.

Phenylketonuria
An autosomal recessive disease and the most common inborn error of metabolism.
There are four types of PKU but all three results in decreased metabolism of the amino acid
phenylalanine (usually converted into tyrosine).

The types of PKU are:

- Hyperphenylalaninemia
- Milk PKU
- Moderate/variant PKU
- Classic PKU

Classic PKU is the result of a genetic mutation in the PAH gene which leads to low
levels of phenylalanine hydroxylase in the liver. When phenylalanine cannot be
converted it causes accumulation, which is toxic to the brain, and causes severe
intellectual disability, brain function abnormalities, microcephaly, mood disorders,
poor motor function and other physical symptoms such as a ‘musty’ odor, eczema
and unusually light colouration.

PKU screening is now done in most countries. The simple blood test looks for values of
phenylalanine greater than 360 uM (6mg/dL). Once detected patients must begin a life long
diet of avoiding a low phenylalanine diet. The diet aims to keep plasma phenylalanine
values between 120-360 mM, this diet should be continued until early adolescence. Certain
foods that must be restricted include soy, egg whites, shrimp, chicken, watercress, fish, nuts
and others. As a result of this patients may have to have certain supplements in order to
ensure they achieve the correct balance of micronutrients.

Galactosemia
Galactosemia is an autosomal recessive disease caused by a deficiency of one of three
enzymes, galactose-1-phosphate uridyltransferase, galactokinase or UDP galactose
epimerase (types 1, 2 and 3), making milk intolerable to the infant. Infants who continue to

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consume milk will present with liver failure (hyperbilirubinemia, disorders of coagulation,
hypoglycemia), disordered renal tubular function and cataracts. Neonatal screening
should be done early (first week of life) to detect high levels of plasma glucose and
erythrocyte galactose 1-phosphate, when detected the patient should stop consuming
galactose.

Where galactose is not removed from the diet the infant will develop intellectual
disturbances, ataxia, dysmetria, diminished bone density, haptic failure and eventually die.

Common symptoms include increased intraocular pressure, cataracts, liver cirrhosis, neural
death in CNs and aminoaciduria, jaundice, vomiting, diarrhea, lethargy and FTT are all also
common early symptoms.

Homocystinuria
- An error in the metabolism of methionine
- Methionine is converted to homocysteine which is converted to cystathionine which is
then converted to cysteine. Homocystine to cystathionine is mediated by
Cystathionine Beta-synthase, then enzyme that is defective
- Can be familial or acquired (B6/B12 defect)
- Increased homocysteine levels lead to atherosclerosis, increased clotting, weaker
bones, ectopic lenze and neural degeneration. Can present with marfan habitus,
kyphosis and near sightedness

Maple syrup urine disease

This is a disease where the patient is unable to break down branched amino acids, namely
valine, leucine and isoleucine. It is an AR disease that presents as a classic or intermediate
form. Symptoms appear in the first 48 hours, presenting with lethargy, irritability and poor
feeding. Within the first week, cerebral edema and seizures will present.

43. Inborn errors of metabolism - disorders involving energy

metabolism and complex molecules

Mucopolysaccharidosis (MPS)
This was not mentioned in the lecture, however seems important so lets mention it. This is a
lysosomal storage disorder with a number of subtypes types. All forms of the disease
see the loss of a lysosomal enzyme that is required to break down
glycosaminoglycans. The lack of breakdown means that the GAGs buildup and cause
toxicity.

The main types of MSP are:

- MPS I (Hurler and Hurler-Scheie subtypes)
- MPS II (Hunter)
- MPS III (Sanfilippo A-D)
- MPS IV (Morquio A and B)
- MPS VI (Maroteaux-Lammy)

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 - MPS VII (Sly)
- MS IX (Natowicz)

All forms of the disease are AR except Hunter which is X linked. Exact symptoms
depend on the type, however generally we see contraction of limbs, neurological
damage, cataracts, FTT, behavioural problems, dwarfism, hepatosplenomegaly,
hernias, contraction of the limbs and digits and progressive joint and skeletal
deformities.

The three most common forms of MPS are I, II and III. We touch on the most important
elements of each below:
- MPS I (Hurler)
- AR - Affects alpha-L-Iodorinidase
- Causes accumulation of dermatan sulfate and heparan sulfate which are
produced in the urine
- Presents with short stature, kyphosis, coarse facial features, cardiomyopathy,
neurosensorial hearing loss and developmental delay
- MPS II (Hunter)
- X-linked, effects Iodorinidase sulfate
- Causes accumulation of dermatan sulfate and heparan sulfate
- Presents with enlarged spleen and liver, abdominal hernia, recurrent otis
media, short stature, prominent forehead, thickened umms, heart valve
damage and stiff joints
- MPS III (Sanfillipo)
- AR
- Four subtypes with different enzymes affected, breaks down heparan sulfate
- Presents with facial dysmorphism, ADHD like symptoms, and eventual early
death

44. Cerebral palsy in children

Cerebral palsy is a group of nonprogressive motor impairment syndromes secondary to

anomalies or lesions of the brain arising before or after birth. The prevalence ais
3.6/1000, higher in prematurity and in twins. Cerebral palsy can develop later, with 10% of
cases being due to brain trauma of some sort in early childhood.

80% of cases of CP are due to antenatal cerebrovascular haemorrhage or ischemia,

cortical migration disorders or structural maldevelopment of the brain.

Most forms are diagnosed in the first 18 months, as children fall behind on
developmental milestones and presenting with hyper or hypotonia. Children will also
present with feeding difficulties, asymmetric hand function and abnormal gait. Primitive
reflexes may also persist beyond the normal point of disappearance.

Cerebral palsy can be categorised as follows:

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 - Spastic: bilateral, unilateral or other (90%)
- Dyskinetic (6%)
- Ataxic (4%)
- Other

We also use a classification system known as Gross motor function classification

system to illustrate the level of disability:
- Level 1 - walks without limitation
- Level 2 - walks with limitations
- Level 3 - walks with handheld mobility device
- Level 4 - self-mobility with limitations, may use powered mobility
- Level 5 - transported in manual wheelchair

By far the most common form is the spastic form. Spastic cerebral palsy is damage to the
upper motor neurone (pyromidal or corticospinal tract) pathway. Limb tone is increased
with brisk deep tendon reflexes and extensor plantar responses. There are three main
types of spastic cerebral palsy; unilateral, diplegia (all limbs affected, but legs more than
arms), or quadriplegia (all limbs affected equaly).

The dyskinetic form of CP will present with chorea, athetosis and/or dystonia. Intellect is
commonly unimpaired. In the past, the most common cause was hyperbilirubinemia
(kernicterus) due to rhesus disease of the newborn, however hypoxic-ischaemic
encephalopathy at term is now the most common cause.

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 45. Neuromuscular diseases

Neuromuscular diseases lead to weakness and disabilities associated with that. This can
be due to disorders of the upper motor neurons (neurons from the brain) or lower motor
neurons (anterior horn cells, their motor roots, peripheral motor nerves, neuromuscular
junctions and muscles).

Let us consider the key diseases that cause weakness in infants and children:
- CNS - brain
- Tumor, trauma, infection, ischemia, hemorrhage, metabolic disease, inborn
error of metabolism, latic acidosis, degenerative disease

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 - CNS - spinal cord
- Transverse myelitis, tumor, abscess, trauma, infection
- Anterior horn cell
- Spinal muscular atrophy, poliomyelitis
- Peripheral nerve
- Guillan-Barre’ syndrome, hereditary motor sensory neuropathy (HMSN), tick
paralysis, bell's palsy
- Neuromuscular junction
- Myasthenia gravis, botulism
- Muscle
- Muscular dystrophies (Duchenne, Becker, Limb-girdle), myotonic dystrophies,
congenital myopathies, dermatomyositis, polymyositis

As we already know, upper motor neurons cause increased tone and reflex, with
babinski reflex and fasciculations absent, the opposite is true for lower motor
neurons.

Now let us sit back and consider first how does one tell if a child has some kind of
neuromuscular weakness. We are looking for them to miss key milestones, these include:
- Head control at 2 months
- Ability to grab things with both hands at 4 months
- Can sit and roll over at 7 months
- Should be walking by 12-15 months

Where our patient misses these targets, or fails to meet them appropriately we must start
suspecting some form of neurological/neuromuscular damage.

This question is specifically asking about neuromuscular damage (i.e. lower motor neuron
diseases), so below we consider some of the key diseases.

Spinal muscular atrophy

A progressive degeneration of the anterior horn cells with three forms. SMA 1, the most
severe that generally leads to death in the first two years, SMA 2 where the patient will
struggle to ever walk, and SMA 3 where the patient may struggle to walk up stairs but will
generally live a relatively normal life.

The most important clinical manifestation is that of proximal motor weakness, in type 1,
hypoxia will present early while in type 2 we will see the patient missing developmental
milestones, decreased or absent deep tendon reflexes, and the presence of pathological
reflexes in the child.

Diagnosis is secured with genetic testing, but CK analysis should be done (should be
normal or mildly elevated), while EMG will show fasciculations, fibrillations and other
signs of denervation.

Treatment is genetic treatment which has a good prognosis however is very expensive.

Guillain-Barre’ syndrome

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This is a true peripheral neuropathy, a post infectious demyelinating autoimmune
disease that can occur 10 days after a respiratory or GI infection (commonly
mycoplasma pneumonia or campylobacter jejuni). While it can occur in people of all
ages it is most common in children. Symptoms include areflexia, flaccidity and
symmetrical ascending weakness with progression in hours or weeks. Symptoms
begin with numbness of the hands and feet and eventually ascend through the limbs
into the bulbar muscles which can eventually cause respiratory insufficiency.

The loss of sensation along with weakness is typical of Guillain-Barre and where both
occur, bilaterally, this should be notable in our differential. The CSF may have elevated
protein levels without pleocytosis, MRI and EMG can help with the diagnosis.

Treatment is IV immunoglobulin with plasma exchange and immunosuppressive drugs. The

illness eventually resolves spontaneously, 80% recover within 1 year.

Chronic inflammatory Demyelinating Polyneuropathy

CIDP is an immune mediated peripheral neuropathy that presents with proximal and distal
weakness, with an episodic pattern affecting the extremities. Patients may also note
numbness, tingling or pain. Treatment is glucocorticoids and plasmapheresis.

Hereditary Motor Sensory Neuropathy (aka Charcot-Marie-Tooth CMT)

A large group of disorders with the most severe type being type 1. Peroneal and tibial
nerves are first affected, with symptoms beginning in pre-school. Examination shows
arches of the feet and bilateral weakness of food dorsiflexion. Patient will complain of
paresthesia however sensation is normal. In some patients the condition is very mild, with
only a slight foot deformity, in severe cases, the patient may be confined to a wheelchair or
indeed it may be a fetal diseases. Genetic testing is done to confirm the condition, no
treatment is available although braces can help improve function.

Myasthenia gravis
An AI condition where antibodies block the acetylcholine receptors at the
neuromuscular junction, this means that there are fewer working receptors and the
muscles tire quickly. The key diagnostic feature is increased fatigue of muscles.
Commonly also affects facial muscles so patient may develop ptosis for example throughout
the day

Myasthenia can be juvenile, transient or congenital.

Duchenne Muscular Dystrophy

A group of diseases caused by error of the Duchenne muscular dystrophy gene (X-
linked) which causes progressive myofiber degeneration and replacement of muscle by
fibrotic tissue. It is one of the most common genetic disorders of childhood.

Clinical manifestations are usually present aged 2-3, boys develop an awkward gait and
are unable to run, sometimes with poor head control. Calf hypertrophy and proximal
leg weakness are both common. Gower sign is also observed (using arms to stand, a
sign of proximal muscle weakness).

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CK will be seriously elevated, this plus clinical manifestations is enough to trigger genetic
testing, which can confirm diagnosis. Steroid therapy will help to slow progression of the
disease.

Myotonic dystrophies (DM)

Second most common muscular dystrophy, and most common to present in adulthood. It is
the result of an AD mutation with CTG inserts into the myotonic dystrophy protein
kinase gene. Presentation depends on the number of CTG repeats. Distal weakness is the
most common presentation, with a classic facial appearance of hollowed out muscles
around temples, jaw, neck, ptosis and drooping of the lips. While this commonly only
appears in adults, severe forms will present in the young.

46. Epilepsy - Idiopathic epilepsy and epileptic syndrome.

47. Epilepsy - epileptic encephalopathies

Seizures are a paroxysmal abnormality of motor, sensory, autonomic and/or cognitive

function due to brain dysfunction. Seizures can be epileptic, syncopal (anoxic),
brainstem, emotional or functional in nature. What makes a seizure epiletpic is the
electrical activity of the brain, where we see excessive hypersynchronous electrical
activity in the brain.

Causes of seizures include:

- Epilepsies
- Genetic
- structural/metabolic
- Acute symptomatic seizures
- Stroke, TBI, infarction, hypoglycemia, hypocalcaemia, hypomagnesemia,
hyponatraemia/hypernatraemia
- Febrile seizures
- Non-epileptic seizures
- Convulsive syncope
- Sudden rise in intracranial pressure
- Sleep disorders
- Unexplained

Before we can properly embark on the world of epilepsy, we must talk about seizures in
general. The most common of these seizures in young people is ‘febrile seizures’, an
epileptic seizure accompanied by a fever without an intracranial infection. Children
with a family history of such seizures have a 10% risk in childhood, between the ages of 6
months and 6 years. Such seizures are usually tonic-clonic seizures and recurrence is
common, the risk of developing epilepsy does not significantly increase. Acute
management is in line with the box below for acute seizure management, while rescue
therapy with buccal midazolam can be given if seizures are longer than 5 minutes. Always
confirm that the patient does not have meningitis.

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 First febrile seizure should always be sent into hospital to be reviewed!

Paroxysmal disorders are a broad term for a group of ‘funny turns’ including
- Blue breath holding spells’
- Toddlers when upset hold their breath in expiration and go blue, sometimes
losing consciousness
- Reflex asystolic syncope (aka reflex anoxic seizures)
- Infants and toddlers, in pain or discomfort or cold foods, can have a seizure
possibly inducing a tonic-clonic seizure
- Syncope
- Common in hot and stuffy environments, sometimes has clonic movements
- Migraine
- Benign paroxysmal vertigo

Now let’s talk about the question (finally), Epilepsies of childhood. These are relatively
uncommon, with an incidence of 0.05%. Most epilepsy is idiopathic with complex
inheritance. We classify epilepsies as below:
- Generalized (discharge arises from both hemispheres
- Absence
- Myoclonic (sudden very rapid jerky movements)
- Tonic (increased tone in extensors)
- Clonic (rhythmic twitching of groups of muscles)
- Tonic-clonic
- Atonic (loss of muscular tone)
- Focal (seizures arise from one or part of one hemisphere)
- Frontal
- Temporal
- Occipital
- Parietal
- Can define as complex (loss of consciousness) or simple (maintain
consciousness)

Diagnosis is based on detailed history from eyewitnesses, ECG, EEG and brain imaging
(including MRI and CT). Further metabolic investigations are also indicated, glucose should
be done, along with all electrolytes (calcium, magnesium, sodium, etc). In order to be able to
diagnose epilepsy, we should be able to confirm two separate unprovoked seizures
(unprovoked = not febrile, not due to trauma, not from a hypo or from dehydration etc).

Where the patient has a history of partial seizures, we should do an MRI as it may be a
result of a local issue (e.g. bleed or tumour). In cases where we get refractory status
epilepticus (see below), we should also be doing an MRI.

EEGs will show abnormal synchronisation of brain waves, with spike and slow wave
complexes visible in absence seizures.

Treat all generalised seizures with Sodium valproate (Depakene) parental.

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 - 10 years + 10-15 mg/kg parental or IV, increase by 5-10mg/kg/week if required.
Maximum dose 60mg/kg daily

First line for focal seizures is Carbamazepine (oral suspension).

- Less than 6 years: Initial dose 10-20mg/kg/daily orally in ⅔ divided doses (max dose
35 mg/kg/day
- 6-12 years: 100mg orally four times daily (max 1000mg/day)
- 12+ 100 mg orally four times daily (max 1000mg/day)

Management for status epilepticus

Status epilepticus is divided into four stages, each stage has certain steps that must be performed:
- 1st stage 0-10 mins (early status)
- Secure airway (high flow oxygen)
- Check glucose

- 2nd stage 0-30 mins

- Consider, could it not be epileptic status?
- Vascular access
- Yes - give Lorazepam IV 0.1mg/kg usually 4mg bolus repeated after 10-20 mins
- No - give Midazolam (buccal 10mg) or Diazepam (rectal 10-20mg or 0.5kg/mg)
- Perform emergency investigations (blood gases, renal, LFTs, Ca2+, Mg+, CBC and tox
- Give 50ml of 50% glucose and/or 250mg thiamine if suggestion of impaired nutrition

- 3rd stage 0-60 mins (established status)

- Establish etiology, alert ITU
- Give phenytoin infusion 15-18mg/kg at 50 mg/minute

- 4th stage 30 - 90 mins (refractory period)

- Give general anaesthesia + one of:
- Propofol 1-2mg/kg bolus then 2-10 mg/kg/hour
- Midazolam 0.1-0.2mg/kg bolus then 0.05-0.5mg/kghour
- Thiopentone 3-5mg/kg bolus then 3-5mg/kg/hour

Pediatric Hemoncology

48. Anemias due to ineffective hematopoiesis & 49. Hemolytic

anemias in childhood

Anemia is defined as any hemoglobin or hematocrit value that is 2 standard deviations below
the mean for age and gender (16g/dL Hb 27% Hct for adult males). Anemias are classified
based on the size and hemoglobin content of the cells, they can be described as
Normocytic, macrocytic or microcytic (based on size) and hypochromic or
normochromatic based on the colour (an indicator of hemoglobin content), to evaluate this
a CBC, reticulocyte count and blood smear should be done. Lets review the types of anemia
and the causes:

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 - Hypochromic, microcytic
- Iron deficiency*
- Thalassemia*
- Chronic inflammatory disease
- Copper insufficiency
- Sideroblastic anemia
- Aluminium or lead intoxication
- Normochromic, Normocytic
- Chronic inflammatory disease*
- Recent blood loss*
- Malignancy
- Chronic renal failure*
- Transient erythroblastopenia of childhood
- Marrow aplasia
- HIV infection
- Macrocytic
- Vitamin B12 deficiency*
- Folate deficiency*
- Hypothyroidism*
- Chronic liver disease
- Lesh-Nyhan syndrome
- Down syndrome
- Marrow failure
- Drugs
- Reticulocyte production index >3 = Hemolytic disorders
- Hemoglobinopathy
- Enzymopathy
- Membranopathy
- Extrinsic factors (e.g. Wilson, DIC, Burns)
- Immune hemolytic anemia
*Relatively common in children

The general clinical features of anemia are quite well known, including tachycardia, flow
murmur, poor exercise tolerance, headache, fatigue, poor feeding, syncome and
paleness. However, chronic anemia is quite well tolerated in children due to their
cardiovascular reserve. Anemia at any age requires search for blood loss, the patient must
be asked about melena, any evidence of jaundice, pallor and splenomegaly which may
indicate hemolytic anemia.

Congenital hemolytic disorders often present in the first six months of life and are
closely associated with neonatal jaundice.

Here we consider some of the most common forms of anemia.

Hypochromic, microcytic anemia

- Iron deficiency anemia
- Can occur in infants fed cow's milk when longer than 1 year, and
menstruating teenagers who are not receiving supplemental iron

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 - Also found in cases of chronic blood loss
- Most common form of anemia in the world
- Presents with anemic symptoms plus CNS irritability and apathy
- Treatment is iron, response should be rapid
- Thalassemia minor
- Prevalent in mediterranea, SE Asian and African populations
- Characterised by mild hypochromic, microcytic anemia with low reticulocyte
count
- No treatment for thalassemia minor, only major form requires treatment
- Lead poisoning
- History of living in an older home, may accidentally consume lead dust
- Pica (psychological disorder where px wants to eat non-food things e.g. paint,
sharp objects) and basophilic stippling on blood smear are common

Normocytic anemia
- Common with chronic inflammatory disease
- Hepcidin is a protein made in the liver that is important fr iron homeostasis, in
inflammation production of this is increased thereby disrupting iron release by
macrophages and restricting iron absorption from the intestines
- Anemia of inflammation may be normocytic or less commonly microcytic
- Neoplasm
- Invasion of the bone marrow with malignant cells can also cause
normochromic normocytic anemia

Macrocytic anemia
- See above for the various types of deficiency (B12 and Folate are the most common)
- Marrow failure
- Presents with pancytopenia, this is usually a gradual process causing chronic
anemia
- The most common cause is Aplastic anemia (caused by disappearance of
hematopoietic elements and replaced by fat, may be induced by drugs or
idiopathic). The most common type of aplastic anemia is Fanconi anemia, a
genetic disease that can be treated with marrow replacement.

Hemolytic anemias
- B-Thalassemia Major
- Sickle Cell disease
- Single amino acid substitution meaning that RBCs become sickle shaped
when deoxygenated, before becoming disc shaped when oxygenated.
However, this reversibility does not last and whats known as ‘sickling’ may
occur.
- Clinical manifestations in a child include splenic dysfunction and severe risk
of infections.
- Patients can go into a Sickle crisis, where there is a life-threatening decline of
hemoglobin, either due to failure of the spleen or failure of the bone marrow
- Vaso Occlusive painful events may also occur in any organ of the body,
leading to a pain crisis.
- Treatment is chronic RBC transfusions

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 - Enzymopathies
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most
common. It is X-linked (more common in males).
- Patients most commonly present with acute episodes of hemolysis triggered
by bacterial infections - histologically the cells look as if they’ve had ‘bites’
taken out of them.
- Patients will present with sudden onset jaundice, dark urine, hemoglobinuria
when hemolysis is intravascular and decreased haptoglobin. Lab analysis will
show decreased NADPH formation
- Treatment is supportive, transfusions indicated when there is cardiovascular
compromise
- The other enzymopathy is pyruvate kinase deficiency but it is much less
common
- Membrane disorders
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Isoimmune hemolysis
- Maternal immune system acts against fetal antigens
- Autoimmune hemolytic anemia
- Develops after an acute infection or as part of a wider autoimmune
disease (e.g. SLE)

Aplastic anemia
- Causes pancytopenia
- RBC production is limited in bone marrow so liver can become enlarged as it tries to
compensate (liver has hematopoietic function in first year of life)
- Most common cause is autoimune destruction of haemopoetic stem cells
- This may be idiopathic, post viral or due to environmental changes
- May also be due to medications, radiations or Fanconi syndrome the most
common genetic cause.
- Fanconi presents with short stature, microcephaly, developmental
delay and hypoplastic thumbs

50. Hemorrhagic diseases

Hemostasis (the normal coagulation of blood) is a dynamic process that requires the
interaction of platelets, the vascular wall, and procoagulant and anticoagulant
proteins. An error in any of these factors can result in hemorrhage disorders. First it is
useful to remind ourselves of the normal coagulation process.

Upon an injury to the vascular endothelium, subendothelial collagen induces a

conformational change in von Willebrand factor, with an adhesive protein to which platelets
bind via their glycogen protein Ib receptor. After adhesion, platelets undergo activation and
release intracellular contents, including ADP, which induces aggregation of additional
platelets. Simultaneously, tissue factor, collagen, and other matrix proteins in the tissue
activate the coagulation cascade leading to the formation of thrombin which further

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aggregates platelets via positive feedback activation of factors 5 and 8. With the conversion
of fibrinogen to fibrin, a platelet plug forms and bleeding stops within 7 minutes.

Where a patient is bleeding too readily and failing to clot one should suspect hemorrhagic
diseases. Certain disorders are inherited (Hemophilia, X linked, and Von Willebrand, AD) are
usually both elucidated from a good FH.

The clinical manifestations of patients with hemorrhage diseases are as one would expect,
bleeding does not stop when one would expect it to, the patient will bruise with unnatural
ease, and petechiae may be visible on physical examination.

Patients where a hemorrhagic disease is considered should have extensive labs, including
platelet count, prothrombin time, partial thromboplastin time, fibrinogen and bleeding
time.

There are two general categories of bleeding disorder, these are Thrombocytopenic
disorders (increased bleeding due to lack of thrombocytes) or coagulopathies
(increased bleeding due to an issue somewhere else in the coagulation process).
Additionally, bleeding disorders can be non-hematologic, but instead vascular. These
disorders see an issue in the vessels, e.g. Ehlers-Danlos syndrome, vasculitis etc. The
image below summarises the causes of bleeding.

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Lets now look in some more detail about some of the causes of bleeding disorders.

Differential diagnosis for thrombocytopenia

- Due to decreased production
- Thrombocytopenia with absent radii syndrome
- Amegakaryocytic thrombocytopenia - marrow is devoid of megakaryocytes,
usually progresses to aplasia of all hematopoietic cell lines
- Pancytopenia due to bone marrow failure
- Cyanotic congenital heart disease with polycythemia
- Viral infections and some drugs
- Due to peripheral destruction
- Neonatal alloimmune thrombocytopenic purpura
- Idiopathic thrombocytopenic purpura (usually post viral)
- Autoimmune Thrombocytopenia (most common cause, major Dx with ALL)

Disorders of platelet function

- Bernard-Soulier syndrome
- Glanzmann thrombasthenia

Disorders of clotting factors

- Hemophilia
- A and B types, clinically indistinguishable
- X linked disease
- A affects factor 8, B affects factor 9, patients will bleed spontaneously
- Treatment is replacement of missing factor
- Von Willebrand disease
- AD, loss of von Willebrand factor and factor 8
- Causes mucocutaneous bleeding, epistaxis, gingival bleeding and cutaneous
bruising.
- Treatment is Desmopressin and/or vWF-containing concentrate
- Vitamin K deficiency

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 - Disseminated intravascular coagulation (DIC)
- Has two phases, thrombotic and bleeding phase
- Can be a complication of surgery or obstetrics procedure
- Also a side effect of Cytostatic treatment for ALL

51. Leukemia in childhood and adolescent

Given this is our first foray into childhood cancers, take a look at the graph below which
shows the incidence of cancers in children, and the graph that demonstrates the most
common ages that these occur.

Note how leukemias are the most common type of cancer in childhood, incidence peaking
about 4, while CNS tumors follow a close second, with lymphomas the third most common
type of pediatric cancer.

Most childhood cancers present in the same way, fatigue, anorexia, malaise, possibly pain,
fever, abnormal lump or mass, vomiting, night sweats and other general symptoms of ‘not
feeling well’.

This question asks us to consider leukemias specifically.

Leukemia is a group of cancers, originating in the bone marrow, that cause high numbers
of (immature) white blood cells.

First, we need to remember, what are myeloid and lymphoid cells, and more specifically,
what are myeloblasts and lymphoblasts?

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Right, types of leukemia
- We can divide based on the lineage affected:
- Myeloid
- Lymphoid
- And based on onset
- Chronic
- Acute

First, let’s take an overall look at the four main types of leukemia.

Acute lymphoblastic leukemia - By far the most common in children (80%)

- Overproduction of immature white blood cells (lymphoblasts). This
overproduction occurs in the bone marrow, and sees a reduction in lymphoblast
quality
- Most common occurrence in childhood 2-5 years of age
- Symptoms include increased risk of bacterial infection, dyspnea, chest pain,
tendency to bleeding and general anemic symptoms
- Thought to be a cancerous gene affecting the lymphoblast
- Can be further subcategories based on if it affects T- or B-lymphocytes more
- T-ALL goes on to cause thymic mass (Thymoma), more common in
teenagers
- Most common blood neoplasm in children

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Acute Myeloid leukemia - the second most common cause in children (20%)
- Cancer of myeloid line with rapid growth of cells that build up in bone marrow and
effect other normal cell production
- Rare, treated with bone marrow replacement therapy, more common in older
adults
- One important subtype is acute promyelocytic leukemia (t(15;17)), these increase
risk of DIC
- Can also categorise based on cell, monoblast AML or Megakaryoblast AML
- Symptoms include infections, anemia, and frequent bleeding

Chronic Myeloid leukemia (more common >40)

- Gradual proliferation of myeloid cells in bone marrow
- Linked with genetic abnormality known as the Philadelphia chromosome (t9;22,
BCR-ABL)
- Causes myeloid cells to divide beyond what they should normally, creating many
myeloblasts
- Causes hepato and splenomegaly
- Most common blood neoplasm in adults
- Has a Chronic and Accelerated phase

Chronic lymphoblastic leukemia (only really occurs in elderly)

- Most common type of leukemia affecting adults
- B-cells grow in an uncontrolled manner and accumulate in bone marrow where
they crowd out healthy blood cells
- Results in swollen lymph nodes, spleen and liver, eventually with anemia and
infections. Eventually, these develops into lymphomas (masses in the lymph nodes)

In acute leukemias, peripheral blood smears show a high prevalence of lymphoblast

cells, these are larger than normoblast cells and lower in cytoplasm than their
contemporaries. Myeloblast and Lymphoblast cells look identical under the microscope,
and chemical markers must be used to distinguish between the two.
- Lymphoblasts have TdT+ nuclear staining
- Myeloblasts have myeloperoxidase enzyme (cytoplasmic staining/observation
of auer rod)
In chronic leukemias, the cells are partially matured, more mature than acute form however.
In CML, cells divide too quickly, in CLL cells don’t die as they should.

In both acute and chronic forms we have this ‘crowding out’ of normal cellular development
in the bone marrow. This means reduced RBCs (anemia and fatigue), thrombocytopenia
(increased bleeding) and leukopenia (reduced white blood cells and so more infections).

Given that ALL is by far the most common cause in children, we shall only consider this
regarding treatment. Chemotherapy, platelet transfusion and additional hydration are given
to protect renal function, remission rates are about 95%.

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 52. Pediatric lymphomas

What is a lymphoma? A lymphoma is simply tumour cells in lymph nodes as a localised

mass that can progress into leukemia.

There are two main classes of lymphoma:

- Hodgkin's lymphomas
- Distinctive neoplastic Reed-Sternberg giant cells
- Generally affect axial lymph nodes (cervical, mediastinal, para-aortic)
- Histological types, based on cellular morphology and cell infiltration in lymph
node biopsy:
- Classical
- Nodular sclerosing
- Lacunar cells
- Mixed-cellularity subtype
- Lymphocyte rich
- Lymphocyte depleted
- Nodular lymphocyte-predominant
- Symptoms include swelling of lymph nodes, fatigue, fever, sweats and weight
loss
- Spread in in a stepwise fashion along lymph chains
- Two peaks of incidence, adolescence and >50 y.o.
- Non-Hodgkin's lymphoma - Most common childhood lymphoma
- Can start in almost any part of the body (unlike Hodgkin's which starts in a
single node)
- Many subtypes but generally
- Aggressive
- Indolent (slow development)

Hodgkin Lymphoma Non-Hodgkin Lymphoma

Localised to single group of nodes Frequent involvement of multiple nodes

Orderly stepwise spread Non orderly spread

Mesenteric nodes and Waldeyer's ring Mesenteric nodes and waldeyer's ring
rarely involved commonly involved

Extranodal involvement uncommon Extranodal involvement common

All types of lymphoma have four clinical stages:

- Stage I - involvement of a single lymph node region
- Stage II - involvement of two or more lymph node regions
- Stage III - involvement of lymph node regions on both sides of diaphragm
- Stage IV - disseminated involvement of one or more extralymphatic organs

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Most common clinical presentation of lymphoma is a firm, painless lymphadenopathy, this
plus any three of: cough, fever, night sweats, weight loss, has a high level of prognostic
value.

Treatment for children is a combination of chemotherapy and low-dose, involved-field

radiation therapy.

53. Solid tumors in children: Nephroblastomas, neuroblastomas,

rhabdomyosarcomas

First, I am going to address the chapter on CNS tumours in general (the second most
common type of malignancy in children) before then looking at Nephroblastomas,
neuroblastomas and rhabdomyosarcomas each in turn.

CNS tumors
Most CNS tumors in children and adolescents are primary tumors that originate in the CNS,
including low-grade astrocytoma or embryonic neoplasms (such as medulloblastomas,
ependymomas and germ cell tumors). Incidence of CNS tumors peak at around 10, and
then decrease until age 70.

Clinical manifestations of most CNS tumors are the result of impingement of the growth
on normal tissue (usually cranial nerves) or by an increase in IC pressure (due either to
obstruction of CSF movement or mass effect). Symptoms of increased IC include lethargy,
headaches and vomiting, with additional symptoms include irritability, anorexia, poor school
performance and loss of developmental milestones, and of course, depending on the CN
affected, the specific symptoms will vary (e.g. squint, loss of muscle movement etc).

Neuroblastomas
These are derived from neural crest cells that form the adrenal medulla and sympathetic
nervous system, that is to say, it originates from neuroendocrine tissue. Most cases
occur in young children, with 98% being sporadic (2% hereditary). These are extracranial
solid tumors, the most common malignancy in infancy, with a mean age at diagnosis of
20 months.

Neuroblastomas can occur anywhere in the body anywhere within the sympathoadrenal
(anywhere). Most start in the adrenals (40%), followed by connective/subcutaneous/soft
tissue, then the retroperitoneum and mediastinum.

Initial symptoms include fatigue, loss of appetite, fever, joint pain along with the
formation of a mass. The tumor is highly aggressive and metastasis will occur rapidly if the
disease is not caught.

Diagnosis is generally made through observation on X-ray (the mass commonly calcifies)
or MRI. Important differential diagnosis is against Wilms tumor, which also presents as
an abdominal flank mass.

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Treatment is based on staging. Gross resection is the first line, however if not possible due
to the location of the tumor then high-dose chemotherapy with autologous stem cell
resquire is indicated. Prognosis is generally around 50%.

Nephroblastoma aka Wilms tumor

Nephroblastomas originate from embryonal renal tissue and it is the most common renal
tumor of childhood. 80% of patients present before the age of 5 and it very rare beyond the
age of 10.

Presentation is of a large abdominal mass, often found incidentally, with a pretty well child.
Haematuria may also present, with rarer symptoms including abdominal pain, anorexia,
anaemia and hypertension.

Ultrasound is the key diagnostic test, with CT often done to confirm. Treatment in the UK is
initial chemotherapy followed by a nephrectomy, after which the tumour is staged
histologically and specific treatment can be targeted at the tumour. Prognosis is good, with
80% of patients going into full remission.

Rhabdomyosarcomas
Rhabdomyosarcomas are soft connective tissue diseases. They are derived from
mesenchymal cells committed to skeletal muscle lineage. Less common CT malignancies
including Ewing sarcoma (bone), fibrosarcoma and synovial sarcoma.

Rhabdomyosarcoma peaks at incidence between 2-6 years of age. Clinical presentation

depends on the exact site of origin and the subsequent mass effect and presence of
metastatic disease. Most common site of tumor is head, neck or genitourinary tract in
children, while teenagers generally have paratesticular, trunk or abdominal tumors.

Additional excluded questions

1. Meningitis and Encephalitis in Children
Meningitis
Meningitis is the inflammation of the leptomeninges and is generally the result of bacteria or
viruses. We know a great deal about meningitis already, so here we will focus on the few bits
that we maybe know less well.

The most common pathogen for meningitis changes based on age:

- Neonatal - group B strep, e.coli, klebsiella, enterobacter
- >1 month - streptococcus, pneumoniae, N. meningitidis

CSF analysis is one of the best mechanisms for detecting meningitis, review the table below
to see the key indicators of meningitis. Signs of meningeal irritation will be present, the
infant/child will be irritable, may have problems feeding, and may have a decreased level of
consciousness (see additional question below).

Treatment depends on age:

- Newborn - Cefotaxime or ceftriaxone + ampicillin with or without gentamicin
- Infants up to 4 - ceftriaxone or cefotaxime + vancomycin
- Children 5-13 - ceftriaxone or cefotaxime + vancomycin

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Remember, routine imms are recommended against H.influenzae and S.pneumoniae for all
children beginning at 2 months, while vaccines against N.meningitidis are recommended for
adolescents.

Encephalitis
Encephalitis is an inflammation of the brain parenchyma leading to cerebral dysfunction. It is
usually acute, although chronic processes can occur. Viruses are the pain causes, listed in
order of frequency below:
- Enterovirus and parechovirus
- Herpes simplex viruses 1, 6, 7
- Arthropod-borne viruses (West Nile, St Louis, California etc)
- Epstein-Barr
- Adenovirus

Clinical manifestations are that of a stiff or painful neck, headaches, ataxia, altered mental
status, hearing loss and polyuria with seizures being common. An EEG and CSF analysis
should be performed to try and narrow down the diagnosis.

Treatment options are limited. With the exception of HSV, varicella, cytomegalovirus and
HIV there is no specific therapy and only supportive care and often admission to ITU can be

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done. IV acyclovir (HSV) and ganciclovir (cytomegalovirus) are two common drugs we can
prescribe.

Most patients will spontaneously resolve over several days through to 3 week, although in
severe cases death or substantial neurological disability can go on to occur.

2. Headaches

Headaches are common, and as such worthy of consideration. The first question to ask is
regarding timings, there are four distinct timing patterns for childhood headaches:
- Acute - single episode of sudden pain, commonly due to febrile illness relating to
upper respiratory tract infection
- Acute recurrent - a series of single acute attacks separated by time. Migraines or
tension type headaches usually cause this pattern, occasionally can be due to
epilepsy
- Chronic progressive - the most ommonous type, gradually increasing frequency and
severity. Correlates to increased ICP, can be due to pseudotumor cerebri, tumor,
hydrocephalus, chronic meningitis, brain abscess, and subdural collections
- Chronic nonprogressive or chronic daily - frequent constant headache (>4month
history), with headaches lasting >4 hours

The two most common types of headache are both primary, they are the Tension-type
headache, generally mild and without additional symptoms, and migraine headaches, the
details of which we are well associated with and are the same for children as adults.

Neuroimaging is not usually necessary unless there are variations in the neurological
examination or the child has signs or symptoms of increased ICP. It should be noted
however, when the headache has a sudden, severe onset, a CT should be used to evaluate
for intracranial bleeding.

Treatment of migraines includes analgesics, rest and sleep in a quiet and dark room.
Medication such as hydration and antiemetics can also be given, moving onto the likes of
sumatriptan as second line. Where children suffer more than one disabling headache per
week, we can give tricyclic antidepressants (amitriptyline), anticonvulsants (valproic acid),
antihistamines (cyproheptadine) or beta blockers (propranolol).

3. Altered Mental state

4. Dehydration
Can often be due to gastroenteritis in children. It is important toass the extent of dehydraiton
(mild, moderate or severe). Look at vitals, tachycardic with decreased pulse and BP will
indicate severe dehydration, mucous membranes will dry out and skin turgor will be reduced.
Lab analysis will show increases in BUN and creatinine concentration, along with an
increase in urine specific gravity. Treatment if hypotensive is with normal saline or Ringer’s
lactate, only use blood if there is acute blood loss. Once normotensive, child can now be
given oral fluids

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Appendix 1
Useful drugs and drug doses

Drug Name Dose

Diazepam 0.5mg/kg

Lorazepam 0.1mg/kg

Prednisolone 10-20mg/kg

Adrenaline (1:1000) for anaphylaxis 0.15mL (0-6 years)

0.3mL (6-12 years)
0.5mL (12+)

Amoxicillin 30mg/kg

Nitrofurantoin 750ug

Trimethoprim 4mg/kg

Cephalexin 125mg/kg

Furosemide 1-2mg/kg

Benzylpenicillin 25mg/kg

Gentamicin 5mg/kg

Valproate 10mg/kg

Absolute Contraindications in children

- Tetracyclines
- Fluroquinolones
- Codeine
- Ceftriaxone

Relative Contraindications
- Aminoglycosides (increased nephrotoxicity)
- Aspirin (only give in Kawazaki - can cause Reye syndrome)

Rehydration therapy
48 hour fluid replacement is calculated as follows:
( 48 hour maintenance+ Deficit −Fluids given)/48=volume ∈ml/hour

48 hour maintenance is based on weight, Deficit is based on 3%, 5%, 8% dehydration

approximation x 10 x weight in kg, fluids given is any volume of fluids previously given.

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Appendix 2
Important Vitals and Reference Values

Vital Value

HR 100-160

RR (0-6 months) 30-40

RR (6-12 months) 24-30
RR (1-5 years) 20-30
RR (5 years +) 12-20

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