Neonatal Adaption and Breathing Flashcards
When is a baby premature?
There are sub-categories of preterm birth, based on gestational age: extremely preterm (less than 28 weeks) very preterm (28 to 32 weeks) moderate to late preterm (32 to 37 weeks)
When does surfactant production start?
24 weeks gestation
What are the different stages of embryonic lung development?
What growth factors are required for lung development?
• Forkhead transcription factors FOXA1/2 (HNF 3β) -proliferation, branching, cell differentiation, regulation SH
• Fibroblast growth factor-10, Sonic Hedgehog, bone
morphogenetic protein 4 – outgrowth of new end buds
• Gli proteins – transcription factors, controlled by SH,
branching
• Vascular endothelial growth factor (VEGF) – angiogenesis
When does alveolar development occur?
24 weeks of gestation
What occurs in alveolar development?
Saccules develop, capillaries develop around each (VEGF)
Most development post term
• Mainly by growth in number
• Adult numbers of alveoli by 4-5 years
Pneumocytes
• Type I and II present at 22 weeks
• From 24 weeks, lamellar bodies present (storage for surfactant)
What are lamellar bodies?
lamellar bodies are secretory organelles found in type II pneumocytes. They are oblong structures and fuse with the cell membrane and release pulmonary surfactant into the extracellular space
What impact does malnutrition (vit A) have on structural pathology of foetal lung?
Malnutrition and Vit A: reduced lung function (PEFR), reduced lung growth
Vit A: reduced septation
What impact does smoking have on foetal lungs?
Smoking – reduces fetal lung volumes. Reduced PEFR Alveoli reduced in number, and increased in size – in animal models due to reduced formation of saccule partitions, hence a reduce surface area for gas exchange.
Extrinsic vs intrinsic restriction
Extrinsic restriction:
- Congenital diaphragmatic hernia (CDH)
- Effusions
- Thoracic or vertebral abnormalities
Intrinsic restriction
-Lung cysts (Cystic adenomatoid malformation)
How is structural pathology affected before and after 16 weeks gestation?
Time of onset
< 16 weeks, branching irreversibly affected, potentially permanent reduction in number of alveoli
> 16 weeks, predominantly alveolar numbers
How does the fluid filing foetal lungs change over time?
Increases closer to term
4-6mls/kg mid-gestation -> 20mls/kg at term
Helps with lung growth
Secondary active transport of chloride from interstitium to lumen (passive absorption of sodium and water into lung fluid)
Liquid production allows for positive pressure of 1cmH20
What is lung fluid required for?
Lung fluid required for lung growth, but NOT branching
How does absorption occur in lung fluid?
- active sodium transport in apical membranes
- labour & delivery: adrenaline release -> reduced secretion and resorption begins.
- thyroid hormone and cortisol required for maturation of the fetal lung response to adrenaline
- exposure to postnatal oxygen increases sodium transport across the pulmonary epithelium
What lung liquid pathologies could occur in foetus?
- OLIGOJUDRAMNIOS- too little amniotic fluid, usually due to membrane rupture or kidney abnormalities
- FOETAL BREATHING ABNORMALITIES- due to neuromuscular disorders, CDH (congenital diaphragmatic hernia)
Why are foetal breathing abnormalities bad for lung fluid?
Normally foetal breathing SLOWS liquid loss and maintains expansion, without this more lung liquid would be lost and foetus wouldn’t be able to maintain expansion.
What can result in TTN (transient tachypnoea newborn)?
Delivery without labour- elective caesarean section
What produces surfactant, where is it stored and how does it work?
Produced by type II pneumocytes
• Surfactant phosphatidylcholine (PC) produced in
endoplasmic reticulum
• Stored in lamellar bodies
Degraded in alveoli
• Absorbed and recycled by alveolar cells
• > 90% PC is reprocessed
• Turnover time 10 hours
Negative feedback system to regulate release
• Also stretch receptors
• ß-adrenergic receptors on type 2 cells – increases with
gestation
What does surfactant prevent? How does it do this?
Prevents atelectasis – reduces work to breathe
Achieved by reduced surface tension
• Solid at body temperature – becomes a solid monolayer,
stabilises alveoli
• Laplace equation
• Internal pressure =
2 x Surface tension / radius
What happens to surface tension with an increased radius?
Surface tension reduced
Surfactant cycle
The surfactant cycle involves surfactant being produced by type II pneumocytes and stored in lamellar bodies.
Surfactant is then released into the aqueous hypophase from where it is converted into tubular myelin (intermediate form of surfactant). From this surfactant multilayers and monolayers are formed. Finally an active layer is formed at the air–liquid interface. Once the surfactant has been used a proportion is reabsorbed as liquid vesicles by type II pneumocytes, the rest is taken up by alveolar macrophages and other processes. This pathway is underdeveloped within premature infants
Respiratory distress and surfactant- how are they related?
RDS is the direct consequence of surfactant deficiency. Surfactant has three predominant roles; to increase pulmonary compliance to prevent atelectasis at the end of expiration and to facilitate recruitment of collapsed airways. In addition surfactant has a role in protecting the lungs from injury and infection caused by foreign bodies and pathogens. Surfactant is synthesized and stored in type II pneumocytes from about 22 weeks gestation. Surfactant is present within an intra-alveolar and intracellular pool. Maintaining adequate surfactant pools within the air spaces is crucial for lung function and dependant on the surfactant metabolism cycle. The surfactant pool is less than 10 mg/kg in preterm infants with RDS compared with term infants who have on average 100 mg/kg.
Tubular myelin
As phospholipid bilayer is compressed:
less water exposed, reducing surface tension
prevents further collapse
at 37C surfactant forms tubular myelin
TM is: Highly organized structure
When compressed transforms from gel to liquid crystal phase
–> Surface tension approaches zero
Surfactant composition
Mix of phospholipids, neutral lipids and protein
Lipids most important: phosphatidylcholine 80%
phosphatidylglycerol 10%
Neutral lipids: cholesterol, alter fluidity of membranes
Proteins: 4 types of SP- A, B, C, D
(5-10% of surfactant)
Why are glucocorticoid steroids given to premature babies?
• Increased production at end of gestation
• Increases dipalmitophophatidylcholine
• Dexamethasone enhances β2-adrenoreceptor gene
expression – leads to increased surfactant secretion
Promotes lung development
What two steroids are typically given to preterm babies?
Betamethasone
Dexamethasone
Why are thyroid hormones important for premature baby lung development?
T4 increases surfactant production
T3 crosses placenta
TRH increases phospholipid independent of T3,4
Why are thyroid hormones important for premature baby lung development?
T4 increases surfactant production
T3 crosses placenta
TRH increases phospholipid independent of T3,4
Why does gestational diabetes mean a baby would have delayed lung growth?
Increased sugar levels delay lung maturation
insulin delays maturation of type 2 cells, decreases % saturated PC and delayed PG
Surfactant composition in prematurity
• PC relatively unsaturated – unstable monolayer
which buckles on expiration
• Phosphatidylglycerol replaces Phosphatidylinositol
with increased gestation
• Leaky capillary membranes – fibrin deposition –
inhibits reduction of surface tension – hyaline
membranes
What is the key factor in the development of RDS?
Surfactant deficiency is the key factor in the development of RDS. Surfactant deficiency results in a ventilation–perfusion mismatch.
The combination of deficient synthesis or release of surfactant within small respiratory units and a compliant chest wall results in the alveoli being perfused but not ventilated which results in hypoxia and atelectasis. The decreased lung compliance, small tidal volumes, increased physiologic dead space, increased work of breathing and poorly ventilated alveoli leads to hypercapnia. The end result is hypoxia, hypercapnia and acidosis.
This state results in right to left intrapulmonary shunting of blood through collapsed lung and extrapulmonary shunting across the patent ductus arteriosus and the foramen ovale
What deficiencies occur in surfactant proteins?
SP – B: Absence leads to markedly reduced PG
No secretion of normal surfactant
Lethal.
SP – C: Interstitial lung disease
What happens to lung liquid at birth?
Lung liquid production ceases during labour
Fetal breathing ceases
Cooling stimulates breath along with other senses
Central chemoreceptor detection of hypoxia
First breath median time 10 sec
High inspiratory pressure
Active expiration with high pressure
How long does it take for air to replace fluid in lungs at birth and where does the fluid go?
Air replaces fluid within minutes
Some squeezed out
Most absorbed into lymphatics (1 hour) and capillaries (6-24 hours)
Rapid fall in airway resistance, increase FRC
Slower increase in compliance over 24 hours
What is a normal rhythm of breathing?
Inspiration – inspiratory muscle contraction
Passive expiration
Active expiration
Where is breathing generated?
Generated in respiratory centre -> Ventrolateral brainstem
How is breathing control in prematurity?
Respiratory centre less well developed
Very immature neonate responds like a fetus – Apnoea
Cold babies don’t have initial hyperventilation
Sometimes, preterm babies just stop breathing
How are neonatal brains built to withstand labour?
Newborn brains utilise non-oxidative (anaerobic) glycolysis
Utilise ketone bodies as energy source
? Fewer synapses and reduced oxygen requirement
Hypoxia leads to redirection of blood flow in the fetus
What is the purpose of the placenta?
Foetus totally dependant on it for nutrients, vitamins, water and oxygen.
The uterine arteries deliver oxygen and nutrients to the placenta and the veins remove the waste products (CO2 and urea). There is a large surface area between the maternal and foetal circulation.
How is oxygen carried in placenta?
Oxygen carried in two forms
2% Dissolved in Plasma and RBC water
98% Haemoglobin
What prenatal globin chains are similar to alpha and beta?
Zeta -> alpha
Epsilon -> beta
Foetal Hb affinity for oxygen
HbF binds Oxygen with greater affinity than HbA
Allows Oxygen to be transferred from mother to baby across placenta
At a lower level of oxygen the HbF is better saturated than adult Hb.
What does 2,3 bisphosphoglycerate do?
2,3 Bisphosphoglycerate binds to deoxygenated Hb with greater affinity than oxygenated Hb
Promotes release of Oxygen
In adults and older children.
By selectively binding to deoxyhemoglobin, 2,3-BPG stabilizes the T state conformation, making it harder for oxygen to bind hemoglobin and more likely to be released to adjacent tissues. 2,3-BPG is part of afeedback loopthat can help prevent tissuehypoxiain conditions where it is most likely to occur.
What happens to 2,3 bisphosphoglycerate in pregnant women?
In pregnant women, there is a 30% increase in intracellular 2,3-BPG. This lowers the maternal hemoglobin affinity for oxygen, and therefore allows more oxygen to be offloaded to the fetus in the maternal uterine arteries. The foetus has a low sensitivity to 2,3-BPG, so its hemoglobin has a higher affinity for oxygen. Therefore although the pO2 in the uterine arteries is low, the foetal umbilical arteries (which are deoxygenated) can still get oxygenated from them.
Why does oxygen bind to HbF with a greater affinity than HbA?
2,3 BPG does not bind to HbF as effectively as it binds to HbA
So oxygen binds to HbF with greater affinity than to HbA
O2 and 2,3 BPG levels in mother vs foetus
Mother: O2 13kPa -> 7kPa when crosses placenta
Foetus: O2 2kPa -> 4kPa when received from placenta
A baby’s foetal haemoglobin levels will be less than 10% at…
1 year of age
Where does blood travel through before reaching the right side of the heart in foetal circulation?
Oxygenated haemoglobin travels from placenta through umbilical vein- some goes to liver via portal sinus, while 60% bypasses hepatic circulation via ductus venosus to inferior vena cava (IVC)
Saturations of blood from:
Legs
Left atrium
Superior vena cava
in foetal circulation?
Legs- 25-40%
LA- 65%
SVC 25-40%
What is the junction of IVC and right atrium?
Junction of IVC and R Atrium is a tissue flap Eustachian valve
Directs oxygenated blood across dorsal aspect of IVC across Foramen Ovale into LA
Why are left atrium sats 65% in foetal circulation?
Sats in LA 65% so myocardium and brain get blood with higher oxygen
What keeps the ductus arteriosus open?
The “E” series ofprostaglandinsare responsible for maintaining the openness of the ductus arteriosus (by dilation of vascular smooth muscle) throughout the fetal period.Prostaglandin E2 (PGE2), produced by both the placenta and the DA itself, is the most potent of the E prostaglandins, but prostaglandin E1 (PGE1) also has a role in keeping the DA open
What is the journey of blood after it reaches the inferior vena cava in foetal circulation?
Blood enters right atrium passes Eustachian valve which streams blood through foramen ovale between RA and LA. Therefore most oxygenated blood travels to LA then LV and then up to aorta -> carotid arteries and brain, some goes down to abdomen and lower limbs, some goes back to placenta via umbilical arteries
Some blood goes to RV, joined by blood coming back from brain to SVC -> pulmonary artery -> ductus arteriosus which allows blood to go from pulmonary artery to aorta
Why is there very little blood flow to lungs in foetus?
Pulmonary vessels very narrow so vascular resistance very high
Where does blood in pulmonary artery go in foetal circulation?
Through ductus arteriosus to aorta
Umbilical artery course vs umbilical vein course
The umbilical arteries course downward to the internal iliac arteries before entering the aorta. They supply the buttocks and the lower extremities via the latter part of the internal iliac arteries
The umbilical vein courses upward along the falciform ligament to the underside of the liver. Here it divides into two vessels, the portal vein and the ductus venosus. The ductus venosus joins with the inferior vena cava.
Where does gas exchange occur in foetal circulation?
Gas exchange occurs in Placenta
Receives deoxygenated blood
Delivers oxygenated blood
Umbilical Vein (80-90% saturated, 4.7kPa)
Foetal circulation: where is preferential streaming of oxygenated blood?
Myocardium and brain
In the foetus blood flows through the ductus arteriosus between
The pulmonary artery and the aorta
What happens to placental circulation and shunts at birth?
Placental circulation ceases
-Umbilical vessels constrict: stretch and rise in oxygen tension
Shunts close
- Flow through ductus venosus falls
- Fall in venous return through IVC
- Closes over 3 – 10 days
Right ventricular input comes only from the IVC, SVC and coronary sinus – normal child/adult venous return
What happens to the vessels when pulmonary vascular resistance falls?
Lung expansion
Pulmonary stretch receptors
Increased Oxygen tension
8-10x rise in blood flow
How are the foramen ovale and ductus arteriosus closed?
Fall in Pulmonary Vascular Resistance (PVR) leads to massive rise in venous return to left atrium
RA and LA pressures equalise
Flap of foramen ovale pushed against atrial septum
Foramen Ovale closes within minutes to hours of birth
Fall in PVR leads to bidirectional flow in DA
Mechanism of DA closure: Oxygen rise
What closes the ductus arteriosus?
Oxygen increase
Why would the circulation transition after birth not be permanent?
Pulmonary arterioles very reactive and constrict to certain stimuli Hypoxia Hypercarbia Acidosis Cold
Rise in PVR and Right to Left shunting: foetal circulation
Why would the circulation transition after birth not be permanent?
Pulmonary arterioles very reactive and constrict to certain stimuli Hypoxia Hypercarbia Acidosis Cold
Rise in PVR and Right to Left shunting: foetal circulation
Patent ductus arteriosus
Asymptomatic:
Continuous machinery murmur
Heart failure: Fast breathing Increased work of breathing Sweating during feeding Poor feeding Poor growth Rapid pulse Bounding pulse
Treatment:
Indomethacin, Ibuprofen, paracetamol
Surgery
Occurs in: Premature babies Down syndrome Rubella Congenital heart disease
Atrial septal defect
Most common congenital cardiac malformation in adults.
Atrial septal defect causes left to right shunt due to the high compliance of the right atrium and the difference in pressure between the two atria. Secondary to this mechanism, the pressure in the pulmonary circulation is increased.
A person with no other heart defect, or a small defect (less than 5 millimeters) may not have symptoms, or the symptoms may not occur until middle age or later.
Symptoms that do occur may begin at any time after birth through childhood.
They can include:
Difficulty breathing (dyspnea)
Frequent respiratory infections in children
Feeling the heart beat (palpitations) in adults
Shortness of breathwith activity
In infants, small ASDs (less than 5 mm) will often not cause problems, or will close without treatment. Larger ASDs (8 to 10 mm), often do not close and may need a procedure.
Important factors include the size of the defect, the amount of extra blood flowing through the opening, and whether the person has any symptoms.
Some people with ASD may have other congenital heart conditions. These may include a leaky valve or a hole in another area of the heart.
Auscultation- what sounds would you hear in a patient with ASD? Why?
Because the pressure in the left atria initially exceeds that in the right, the blood flows in a left to right shunt. This high volume of blood next passes into the right ventricle, and the ejection of the excess blood through a normal pulmonary valve produces the prominent mid-systolic flow murmur. This murmur is best heard over the “pulmonic area” of the chest, and may radiate into the back as with the murmur of pulmonary stenosis. The most characteristic feature of an atrial septal defect is the fixed split S2. A split S2 is caused physiologically during inspiration because the increase in venous return overloads the right ventricle and delays the closure of the pulmonary valve.
With an atrial septal defect, the right ventricle can be thought of as continuously overloaded because of the left to right shunt, producing a widely split S2. Because the atria are linked via the defect, inspiration produces no net pressure change between them, and has no effect on the splitting of S2.
Thus, S2 is split to the same degree during inspiration as expiration, and is said to be “fixed.”
Why are neonates at an increased risk of heat loss?
Their surface area to volume ratio is much higher- higher relative surface area, the more likely you are to lose heat
Relative percentage of fat increases as you get older, this acts as an insulator but is low in newborns
SO Less insulation as subcutaneous fat less
Thermogenesis: brown fat
Non-shivering thermogenesis
Highly vascular
Sympathetic innervation
High Mitochondrial content
Can double heat production
Brown fat uncouples oxidative phosphorylation so instead of producing ATP it produces heat
Adverse effects of hypothermia
Increases risk of: Respiratory distress Acidosis Hypoglycaemia Hypoxia Hyperbilirubinaemia
What do we do to reduce risk of baby developing hypothermia?
Energy needed to maintain a normal temperature
Environment which minimises energy required to maintain core temperature (36.5-37.5oC)
Thermoneutral zone- minimum energy required to maintain body temp
Heat can be lost in babies through:
Conduction
Convection
Lack of fat
Evaporation
Radiation
What happens to total body water over time?
Decreases with age, while fat increases
Where is the bulk of total body water in foetus vs adult?
Foetus: extracellular
Adult: intracellular
Where is fluid lost?
Resp tract- depends on temp and humidity of inspired gas, resp rate, tidal volume and dead space
Skin
Kidneys
Stool
Why is water lost so easily through preterm neonatal skin?
Adult epidermis much thicker and keratinised, epidermis barely visible in 20 weeker
How to reduce fluid loss in preterm babies?
High humidity, 80%+
Why do preterm babies have diluted urine?
Kidneys not well developed, nephrons only fully complemented at 34 weeks and are already functionally immature at birth
Reduced GFR and limited concentrating ability as a result
What substrates does the foetus use near term?
~5g glucose/kg/day moves across placenta
Glucose and Amino Acids
Dominant hormone in foetus near term? Why?
Insulin
There is increased growth of the beta cells of the pancreas in the third trimester, with concomitant increased production of insulin. Most of the baby’s fat stores are laid down in the third trimester
Actions of insulin in foetus?
In the foetus insulin acts as a growth factor
Increases adipose tissue stores
Generally: Increases glucose uptake in muscle, fat and liver (so blood sugar falls) Decreases lipolysis Decreases amino acid release from muscle Decreases gluconeogenesis in liver Decreases ketogenesis in liver
How does insulin act as a growth hormone in pregnancy?
There is increased growth of the beta cells of the pancreas in the third trimester, with increased production of insulin acting as a growth hormone. Most of the baby’s fat stores are laid down in the third trimester to help periods of fasting
What happens to nutrients at birth?
Abrupt cessation of transplacental flow of nutrients
Huge surge of catecholamines – counter regulatory hormones: cortisol, adrenaline (act to oppose insulin actions - catabolic to insulin’s anabolic)
Switch on catabolic processes of gluconeogenesis and glycogenolysis
How much milk is available when a mother first starts breastfeeding?
Very little milk available at first
Average intake of colostrum 7mls/feed in first 24 hours
How does a newborn make up for the low milk availability when breastfeeding starts?
Meets demands from stores in tissues (energy requirement 4-6g glucose/kg/day)
How do blood glucose concentrations change in newborns?
Declines to less than 2mmol/l in first 6 postnatal hours then starts to rise spontaneously
How do babies protect themselves from hypoglycaemia?
MANAGING DEMAND
- brain accounts for higher proportion of resting energy expenditure than in adults
- but cerebral metabolic rate only 30% of adult values (this increases as you get older when brain does more complex things)
MANAGING SUPPLIES
- astrocyte glycogen stores
- use of alternative cerebral fuels- ketone bodies
- baby by weight is 1% glycogen and 16% fat
How are stores converted to fuels in babies?
PROCESSES: Gluconeogenesis - create new glucose Glycogenolysis - glycogen breakdown to glucose Ketogenesis - forming ketone bodies from Beta oxidation of fatty acids
HORMONAL CONTROL Anabolic actions of insulin opposed by counter-regulatory (catabolic) hormones - Glucagon - Adrenaline - Cortisol - Growth hormone
Glucose is converted into what before becoming pyruvate and acetyl CoA? What are the missing products and processes?
Glucoose-8-phosphate
Fructose 1,6 bisphosphate
What is the function of gluconeogenesis?
The main function of gluconeogenesis is to produce glucose from noncarbohydrate sources such as glucogenic amino acids, glycerol
Provides glucose when dietary intake is insufficient or absent
3 key rate limiting steps of gluconeogenesis?
G-6-phosphatase converts G-6-phosphate into glucose
Fructose- 1,6-bisphosphatase converts F-6-phosphate into F1,6-diphosphate
PEPCK converts axaloacetic acid into phosphoenolpyruvate
What are the 3 important metabolic processes that occur after birth?
Gluconeogenesis - new glucose from non carbohydrate precursors
Lipolysis- breakdown of fat (infant diet = 50% fat)
Fatty acid breakdown (beta oxidation)
What are the 3 important metabolic processes that occur after birth?
Gluconeogenesis - new glucose from non carbohydrate precursors
Lipolysis- breakdown of fat (infant diet = 50% fat)
Fatty acid breakdown (beta oxidation)
How are ketone bodies formed?
Beta oxidation removes 2 carbon units from the end of fatty acid chain in successive steps (acetyl CoA units)
These are used to make ketone bodies
What happens to blood glucose levels in the fed (post-prandial) state?
Blood glucose levels RISE
Insulin acts to lower blood glucose (pack it into peripheral tissues)
Active uptake of glucose by peripheral tissues
What happens to blood glucose levels in fasting (post-absorptive) state?
Blood glucose levels FALL
Substrates are mobilised peripherally via counter-regulatory hormones to maintain blood glucose (amino acids fatty acids and glyocgen released to restore glucose levels)
Insulin is opposed
What problems can babies have with regulating blood glucose?
Demand exceeds supply
Too much insulin (hyperinsulinism)
Deficiency in counter regulatory hormones
Inborn errors of metabolism
Demand exceeds supply in a sick baby
Sepsis
Asphyxia
Cardiopulmonary disease
Need to give IV blood glucose otherwise demand will exceed supply
Demand exceeds supply issues in extremely small preterm baby
High demands and small nutrient stores (missed 3rd trimester so not laid down those fat stores)
Immature intermediary metabolism
Establishment of enteral feeding delayed
Poor fat absorption
Demand exceeds supply in IUGR (in utero growth restriction) baby
Baby mature but too teeny
High demands especially in brain
Low stores (liver, muscle, fat)
Immature gluconeogenic pathways
What leads to fetal and neonatal hyperinsulinism?
High maternal glucose -> high fetal glucose (diabetic mother)
Excessive insulin produced while foetus in utero, expressed as neonatal macrosomia
Insulin acts as growth hormone at 3rd trimester so too much means you grow excessively
Then can’t switch on counter regulatory hormones properly -> neonatal hypoglycaemia
Congenital adrenal hyperplasia
21 hydroxylase deficiency
-> too much testosterone and no cortisol or aldosterone
Can become hypoglycaemic due to lack of cortisol
Can have salt wasting and dehydration due to lack of aldosterone
Glycogen storing disease Type 1
Deficiency of glucose-6-phosphatase (affects rate limiting step in gluconeogenesis so cant convert G6p into glucose)
- > hypoglycaemia and lactic acidosis in newborn
- > hepatomegaly in older infant (due to build up of glycogen that cant be broken down in liver)
MCADD (medium chain acyl-coA dehydrogenase deficiency)
MCADD is a disorder where the body is unable to break down medium chain fatty acids into acetyl- CoA.
This means that there is a reduced ability to tolerate fasts
Also part of newborn blood spot screening
Disorder of fatty acid oxidation that impairs the body’s ability to break down medium-chain fatty acids into acetyl-CoA
-> Hypoglycemia and sudden death without timely intervention, often brought on by periods of fasting or vomiting.
Hypoglycaemia rapid bc don’t have normal ability to compensate by using fatty acids as an energy source.
Treatment of MCADD is mainly preventative, by avoiding fasting and other situations where the body relies on fatty acid oxidation to supply energy.
Galactosaemia
Caused by absence of key enzymes involved in converting lactose -> galactose -> glucose
Autosomal recessive
Presents with vomiting, lethargy, failure to thrive and jaundice
Typically get cataracts, can be within first week
About 1/3 have life threatening sepsis, often with E Coli
Maple syrup urine disease
Inability to metabolise branched chain amino acids ( Leucine, Isoleucine, Valine)
Build up of these amino acids and their by products
Part of newborn blood spot screening
Presents with hypoglycaemia and acidosis within first few days of life
Presents with vomiting, drowsiness, seizures and a metabolic acidosis, as well as hypoglycaemia
Autosomal recessive
Why do we need to modulate the rate of ventilation?
Ventilation rate constantly adjusted to meet body’s demand for O2 and production of CO2.
(greater breathing rate -> increased ventilation -> increased O2 in alveoli -> less Co2)
Adequate O2 absorption and CO2 expulsion from body achieved via maintaining pressure gradients between alveoli and blood
In what circumstances does O2 demand and/or CO2 production increase?
PHYSICAL ACTIVITY - O2 demand and Co2 production increases (exercise -> increased ATP = increased VO2 aka vol of O2 consumed)
INFECTION, INJURY, METABOLIC DYSFUNCTION (VO2 in healthy subject lessvs < burns subject < burns and infected subject, so poor hurt rats used more vol of O2 )
How does modulated ventilation change breathing?
- INCREASING TIDAL VOLUME
- INCREASING BREATHING FREQUENCY
Increases overall VO2
Increasing overall minute volume
As well as ventilation, what else ensures there is an increase in total O2 transported?
Cardiac output
In healthy, exercising individuals, increased O2 delivery achieved by increasing cardiac output, not PaO2
Hb is 98% saturated at rest, so hyperventilating alone has little effect on O2 delivery therefore increased CO helps w oxygen delivery
What physiological processes initiate breathing?
Respiratory muscles provide the movement required for ventilation.
As resp. muscles consist of skeletal muscle, they require neural inputs/stimulation to contract.
Innervation from motor neurons synapsing from descending spinal tracts provide the contractile signal.
Which muscles are used in:
quiet expiration/inspiration?
forced expiration/inspiration?
QUIET:
Insp: diaphragm
Exp: elastic recoil
FORCED:
Insp: respiratory - external intercostals
accessory - pectorals, sternomastoid, scalene
Exp: respiratory - elastic recoil, internal intercostals
accessory - abdominals
What generates the basic breathing pattern?
Neuronal systems in brain:
Medulla (brainstem) has complex network of neurones (central pattern generator) determines overall rate frequency and depth of breathing
takes inputs from parts of body and decides the breathing rate
sends signals first to inspiratory muscles
then to expiratory muscles
How does central pattern generator determine rate and depth of breathing?
Takes various inputs (physiological readings) from different parts of body eg chemoreceptors responding to levels of oxygen, acidity etc
feeds back to CPG -> triggers increased rate of ventilation etc
receives inputs from higher brain centres
What chemoreceptors are key in responding to changes in arterial PCO2?
CENTRAL CHEMORECEPTORS
Central respiratory chemo-receptors (CRC) present in the medulla indirectly monitor changes in arterial CO2.
Co2 increases -> CO2 levels in blood increase -> increased CO2 diffuses from blood through BBB into cerebrospinal fluid -> indirectly activates CRC via converting into carbonic acid which dissociates into H+ ions
Although CRC respond to changes in [H+] within cerebrospinal fluid, as H+ does not cross the blood brain barrier, CRC do not directly respond to changes in blood pH (except via CO2).
So increased activation of CRCs signals to respiratory control centres to increase ventilation
so negative feedback
What chemoreceptors respond to changes in arterial O2, Co2 and pH?
PERIPHERAL CHEMORECEPTORS
Activated by ↓PaO2, ↑PaCO2 and acidaemia (low O2, high CO2 and low pH)
.
Signal to respiratory centres in medulla (via sensory nerves) to increase ventilation (negative feedback).
Present in carotid and aortic bodies
Hypercapnic drive
Ventilation is generally proportional to PaCO2
CO2 primarily determines respiratory rate more than O2
Hypoxic drive
Hypoxaemia (low PaO2) stimulates increased ventilation, only occurs at very low levels of oxygen
Sleep apnoea
Temporary cessation of breathing during sleep
Characterised by >5 episodes per hour lasting >10 seconds.
Durations of apnoeas may be as long as 90 seconds and the frequency of episodes as high as 160 per hour.
Sleep apnoea
Temporary cessation of breathing during sleep
Characterised by >5 episodes per hour lasting >10 seconds.
Durations of apnoeas may be as long as 90 seconds and the frequency of episodes as high as 160 per hour.
Effects of sleep apnoea on health?
Tiredness (poor sleep quality)
Cardiovascular complications (stress + increased sympathetic tone)
Obesity/Diabetes (inflammation + metabolic dysfunction) patient w sleep apnoea more likely to get diabetes
Ventilation in the transition from wakefulness to sleep
↓metabolic rate = ↓respiratory demands
Postural changes alter mechanics of breathing
↓SNS & ↑PNS tone = ↓HR, BP & CO.
↓tidal volume, ↓breathing frequency = ↓minute volume
↓SaO2 (≈96%), ↑PaCO2 (≈7kPa)
↓upper airway calibre (tone of muscle in upper airway)
Polysomnography
Sleep clinic, patient comes in and sleeps while various physiological readings are taken eg airflow through nose and mouth, level of oxygen saturation etc
Obstructive sleep apnoea
Blockade of upper respiratory tract during sleep
- due to decreased tone (relaxation) of pharyngeal dilator muscles
- displacement of genioglossus (/tongue muscle) falls back into throat, adding pressure
- increased pressure on neck due to fat deposition (obesity)
Risk factors for sleep apnoea
Obesity
Alcohol/sedatives
Smokers
Central sleep apnoea
Dysfunction in process that initiates breathing
-airways open, but problem with central pattern generator or brainstem, muscles not receiving signals anymore
Causes:
Stroke – damage to respiratory centres in brain
Drugs (e.g. opioids) – suppression of neuronal activity
Central hypoventilation syndrome – injury/trauma to brainstem, or congenital (‘Ondine’s curse’)
Neonates – continuing development of respiratory centres
Altitude – e.g. Cheyne-Stokes respiration
Central pattern generator in obstructive vs central sleep apnoea?
Obstructive: CPG working, blocked airways
Central: CPG not working, airways open
Which type of sleep apnoea does each patient have?
Patient A: CENTRAL
Patient B: OBSTRUCTIVE
Why?
Airflow stops but airways still open, but CPG not sending signals to diaphragm so diaphragm excursions stopping then starting due to lack of signals
Whereas for patient B, CPG is fine so diaphragm contracting, but due to blocked airway the airflow stops
Cheyne-Stokes respiration
Oscillating apnoea and hyperpnoea
Overcompensation in not enough breathing and then too much ventilation
Goes through period of apnoea due to environmental circumstances, eg lower rate of breathing and peripheral chemoreceptors respond to increase level of breathing because we need oxygen, but it overshoots due to dysfunction in CPG
Central chemoreceptors then sense this overcompensation, pH change due to not enough CO2 now so stops breathing and so overcompensates
What are the causes of Cheyne-Stokes respiration?
Altitude - less #O2 in environment
CR dysfunction
Heart failure
What indicates emergency in a newborn?
Cardiac arrest Shock Respiratory arrest Cyanosis Recession/tachypnoea Specific sign
Emergency management strategy for acutely unwell baby
SUPPORTIVE CARE
IDENTIFICATION OF PROBLEM
TREAT THE TREATABLE
SUPPORTIVE CARE ventilation fluids isotopes nutrition
IDENTIFY PROBLEM
cultures
scans
blood tests
TREAT THE TREATABLE antibiotics surgery steroids immunosuppression
What problems do you look for in an unwell baby?
LIFE SUPPORT:
Cardiovascular- HR (umbilical artery), colour (lips, palms, soles), pulse
Respiratory: apnoea, gasping, recession
ORGAN FUNCTION: Brain: AVPU score Heart: bradycardia, tachycardia (HR below 100 is abnormal) Renal: oliguria Gut: vomiting, NG aspirates
Apgar score
Which bacteria is the top cause of neonatal sepsis?
Group B streptococcus
Causes of neonatal sepsis
- Congenital infection
- present at birth
- infection direct from mother
- TORCH (toxoplasmosis, other, rubella, CMV (cytomegalovirus), HSV (herpes simplex virus) - Late-onset sepsis
- onset beyond 1 week
- maternal or external source of infection - Early-onset sepsis
- onset birth to 1 week
- infection from birth canal
Sepsis bugs and their antibiotics
Group B streptococcus
Listeria
Gram negative organisms like E. coli
From genital tract
ANTIBIOTIC TREATMENT
Penicillin/gentamicin
Cefotaxime/Ampicillin
Sepsis presentation
Specific features: positive cultures, low white cell count, platelets
Non-specific signs: fever, low temp, poor feeding, vomiting, pallor, tachypnoea, sleepiness, irritability
What does this CXR indicate in a neonate?
Sepsis
Management of sepsis in a neonate
INVESTIGATIONS
FBC (white cell, platelet)
Clotting, urine, blood, CSF
RESUSCITATE
ANTIBIOTICS
PREPARE FOR CONSEQUENCE
Ventilation, fluid resuscitation, coagulopathy, inotropes
What signs would predict birth asphyxia?
IUGR (intrauterine growth restriction) Prematurity Abnormal CTG Abnormal foetal blood gas 'difficult' delivery
Is cerebral palsy due to birth asphyxia?
Not really, majority of reasons why cerebral palsy develops due to problems before birth and labour (genetic, pregnancy related, even postnatal like meningitis). Only 10-12% of cerebral palsy cases are related to ‘asphyxia’
At what point would you discontinue treatment where a baby is not responding to resuscitation?
Prolonged resuscitation over 20 minutes, half die in immediate period after and other half severely neurologically impaired
Features of birth asphyxia at early and late stages
EARLY: acute bradycardia/asystole at delivery
LATE: hypoxic ischemic encephalopathy
Late birth asphyxia features grades
Grade 1 - irritability, poor feeding
Grade 2 - fits, bad feeding, hypertonia
Grade 3 - floppy, intractable seizures, apnoea
Sagittal USS in asphyxia- what are the two features being pointed out?
Periventricular flare - oedema in this watershed area
Cystic leukomalacia - loss of some brain area
What does cooling the baby down do?
Prevents apoptosis after asphyxia event, routine management for babies with asphyxia
Differential diagnosis for respiratory distress
Pneumothorax Sepsis Abdominal emergency Cardiac malformation Pneumonia
Risk factors for respiratory distress syndrome
prematurity asphyxia cold stress diabetic mum multiple births LSCS
Main cause of respiratory distress
Lung immaturity and lack of surfactant production
Type 2 pneumocytes hasn’t started producing it yet
Functional residual capacity (FRC) normal vs respiratory distress syndrome
FRC established by surfactant
Prevents alveolar collapse, after first breath (breath in very hard, then surfactant keeps it open)
But if not enough surfactant then breathing in very hard but when breathing out goes back to initial state because no scaffold to hold it open and no establishment of FRC
What problems occur if FRC is not established?
No oxygen transfer in expiratory phase because no air left in lung
More work to keep opening up lungs, effort of opening will cause baby to tire and damage lungs by sheer stress
Features of respiratory distress syndrome (RDS)
Non-specific features:
low temp, fever, poor feeding, vomiting, pallor, tachypnoea, sleepiness, irritability
apnoea, CXR
Specific features: recession ++
4 components of RDS
- weak chest wall
- excess lung liquid
- no blood-air approximation (blood vessls not close to alveoli)
- surfactant deficiency
What do you expect to see in CXR of baby with RDS?
Later complications of RDS
Pulmonary interstitial emphysema
Chronic lung disease of prematurity
Treatment of RDS
SUPPORTIVE Oxygen Expanding strategies - CPAP - Ventilation – PEEP & PIP Fluids / feeds Inotropes Sedation ?NO ECMO
OF CAUSE
Surfactant via ETT
Meconium aspiration syndrome
Baby asphyxiated in utero and bowels open, gasp and meconium fills amniotic fluid and into lungs
Prediction
- Post term
- Asphyxia
Treatment for meconium aspiration syndrome
SUPPORTIVE Oxygen CPAP Ventilation Inotropes Fluids ? Antibiotics ECMO
SPECIFIC
surfactant?
Abdominal emergencies
PREDICTING
polyhydramnios
other congenital malformations
SPECIFIC FEATURES
abdominal distension. Bilious vomiting, obvious loops
NON SPECIFIC SIGNS
poor feeding, vomiting, pallor, tachypnoea, sleepiness, irritability
EXAMPLES Necrotizing enterocolitis Malrotation Volvulus Gastroschisis (Exomphalos) Meconium Ileus Hirshprung’s disease
Malrotation
Early in pregnancy, the bowel is a long straight tube leading from the stomach to the rectum. The bowel then moves into the umbilical cord temporarily while it develops into the large and small bowel. Around the tenth week of pregnancy, the bowel moves back into the abdomen and coils up to fit into the limited space there. If the bowel does not coil up in the correct position, this is called malrotation.
Volvulus
Malrotation is an abnormality of the bowel, which happens while the baby is developing in the womb. Volvulus is a complication of malrotation and occurs when the bowel twists so the blood supply to that part of the bowel is cut off. This can be a life threatening problem.
Duct dependant heart defects
Pulmonary atresia Critical pulmonary stenosis Critical coarctation Transposition of the great arteries Hypoplastic left ventricle
Features of duct dependance
Specific features:
minimal recession for cyanosis
absent femoral pulses
echocardiogram, CXR
Non-specific signs:
poor feeding, vomiting, pallor, cyanosis, tachypnoea, sleepiness, irritability
