GEP (Life support) Week 5

Question 1

What is the placenta and what are its roles and function

Answer 1

-Facilitates bidirectional exchange of nutrients & waste products, without mixing maternal & foetal blood
-Mum to foetus:
Nutrients, oxygen, antibodies (IgG), vitamins, water
-Foetus to mum:
Carbon dioxide, urea, hormones
-Achieved via 3 mechanisms:
Concentration/pressure gradients
Differences between adult & foetal Hb
Bohr effect

Question 2

How does the exchange at the placenta occur between mother and baby

Answer 2

• Relative concentration/pressure gradient:
  Maternal blood = ↑O2, ↓ CO2
  Foetal blood = ↑CO2, ↓ O2
  Pressure gradient established –> nutrient delivery & waste removal
• Differences between adult & foetal Hb:
  Foetal Hb (HbF = 2ɑ2𝛄) –> no binding site for 2,3-DPG –> increased affinity for O2
  Adult Hb (HbA = 2ɑ2β, HbA2 = 2ɑ2δ) –> reduced affinity for O2
• The Bohr Effect:
  Foetus gives CO2 to mum –> ↑CO2 in maternal blood
  Right shift (maternal blood) –> HbA has decreased affinity for O2
  Increased off-loading of O2 at placenta to foetus

Question 3

What is foetal haemoglobin

Answer 3

HbA - Adult: 2 alpha chains, 2 beta chains
HbF - Foetal: 2 alpha chains, 2 gamma chains

HbF binds oxygen with greater affinity than HbA
Allows oxygen to be transferred from mother to baby across the placenta

Question 4

Why does HbF have higher affinity

Answer 4

2,3-DPG binds to deoxygenated Hb with greater affinity than oxygenate Hb, promoting the release of oxygen
2,3-DPG does not bind to HbF as effectively as it binds to HbA
Oxygen binds to HbF with greater affinity than HbA

Question 5

When does the haemoglobin transition occur

Answer 5

No sickle cell until beta chain level increases and abnormalities can be seen (6 months onwards)

Question 6

What are the key anatomy of foetal circulation

Answer 6

• Umbilicus: 2 arteries (deoxygenated), 1 vein (oxygenated)
• IVC: oxygenated from umbilicus (note: partial bypass of RV into LA due to foramen ovale)
• SVC: deoxygenated from the brain
• Ductus Arteriosus: muscular wall, kept open by low oxygen tension (connects pulmonary artery to aorta)
• Ductus Venosus: bypass hepatic circulation into the IVC
• Descending Aorta: low saturation as gut not functioning, preferential supply to thorax and brain
• Low Oxygen Requirement: no respiratory effort, no digestion, little movement, little heat generation

Question 7

Summarise foetal circulation and the pathways

Answer 7

Question 8

What is ductus arteriosus and the changes you see after birth and issues that can happen with it

Answer 8

Ductus Arteriosus
Function: shunt blood from pulmonary artery to aorta
Closure: pressure in aorta > pulmonary artery
Becomes: ligamentum arteriosum
Pathology: patent ductus arteriosus
Symptoms: poor weight gain, poor feeding, tachypnoeic, tachycardia, cyanosis, pan-systolic machinery murmur
Risk Factors: trisomy 21, asphyxia, rubella
Treatment: NSAIDs

-At Risk: prematurity, down syndrome (Trisomy 21), rubella, congenital heart disease
-Issue: pulmonary over circulation = blood flows back into pulmonary artery from aorta and can lead to heart failure
(heart failure see description)
-Presentation: asymptomatic other than continuous machinery murmur
-Treatment: indomethacin, ibuprofen, paracetamol (see description), surgery

-NSAIDs: the DA is kept open by the presence of prostaglandins, NSAIDs is believed to inhibit the cox pathway reducing PGs
-Paracetamol Mechanism to Close Ductus Arteriosus: the DA is kept open by the presence of prostaglandins (E2), paracetamol is believed to inhibit the cox-1 pathway reducing PGE2

Question 9

What is ductus venosus and the changes you see after birth and issues that can happen with it

Answer 9

Ductus Venosus
-Function: carry oxygenated blood from umbilical vein to IVC
-Closure: BP decreases so reduced flow
-Becomes: ligamentum venosum
-Pathology: patent ductus venosus (intrahepatic shunt)
-Symptoms: hypoxemia, hepatic dysfunction, hyperammonaemia, hyperbilirubinemia
-Risk Factors: premature, rubella, born at altitude
-Treatment: surgical clip

Question 10

What is foreman ovale and the changes you see after birth and issues that can happen with it

Answer 10

Foramen Ovale

-Function: shunt blood from RA to LA
-Closure: pressure on L > R
-Becomes: fossa ovalis
-Pathology: patent foramen ovale (atrial-septal defect)
-Symptoms: poor weight gain, poor feeding, recurrent chest infection, split S2 heart sound, systolic ejection murmur (left sternal border)
-Risk Factors: congenital heart disease
-Treatment: surgical repair

Question 11

Summary of anatomical changes at birth

Answer 11

Patent ductus arteriosus maintained in utero due to prostaglandins released by the placenta

Question 12

What are the respiratory changes at birth and development

Answer 12

**Pulmonary Vascular Resistance **
Falls enabling lung perfusion and expansion -> x8-10 perfusion
Pulmonary stretch receptors stimulated -> increased oxygen tension

Alveolar Development
24 Weeks – Saccules Develop: capillaries develop around each (VEGF)
32 Weeks – shallow indentations
Post Term – mainly grow in number to adult levels by 4-5 years of age
Pneumocytes – Type I and II present at 22 weeks, from 24 weeks lamellar bodies present

Question 13

What are the foetal lung development

Answer 13

Foetal lung fluid:
* Where: produced in epithelial lining of developing lung
* Role: keep lungs in distended state & encourage lung growth
* Production: Cl- pumped into alveoli via chloride channels (active)
Na+ & H2O follows Cl- (passive)
* Quantity: 4-6 ml/kg (mid-gestation), 20 ml/kg (full-term)

Chloride ions enter the lung epithelial cell across the basolateral membrane via a Na/K/2CL cotransporter (the transporter on which furosemide acts)
Foetal lung fluid is NOT the same as amniotic fluid

Question 14

What are the changes seen in foetal lung fluid at birth

Answer 14

• Surge of adrenaline during labour is sensed by beta-adrenoreceptors on Type II pneumocytes
• Leads to reduced secretion & resorption begins
• Increased expressed of epithelial sodium channels (ENaC)
• ENaC passively transports Na+ from alveoli due to gradient created by Na/K ATPase pump
• Water follows salt –> H2O moves out of alveoli & is reabsorbed into circulation & lymphatics
• Postnatal oxygen exposure, thyroid hormone & cortisol –> Na+ absorption**

Question 15

What is surfactant

Answer 15

Surfactant:
* 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 is 10hrs
* Negative Feedback System: regulates release, beta-adrenergic receptors on type II cells – increases with gestation

Produced by type II pneumocytes in the endoplasmic reticulum  stored in lamellar bodies  secreted into alveolar space
Made from 24 weeks gestation  enough to breathe at 34 weeks

Question 16

What is the role of surfactatant

Answer 16

Role of Surfactant:
* Prevent atelectasis
* Reduces work to breathe
* Reduced surface tension (solid at body temperature – monolayer stabilises alveoli)
* Laplace Equation: Internal Pressure = [2 x surface tension] / radius

Reduction of surface tension:
Hydrophilic heads attracted to polar water molecules
This disrupts bonds between water molecules that are necessary for maintaining surface tension
-> reduced surface tension at the air-water interface in alveoli
-> prevents collapse of alveoli  breathing

Question 17

What are the factors that affect surfactant maturation

Answer 17

**Glucocorticoids (Steroids): **
Increased production at end of gestations
Increases dipalmitoyl phosphatidylcholine (surfactant)
Dexamethasone enhances beta-2-adrenoreceptor gene expression (increasing surfactant secretion) – lasts 7 days ideally

Thyroid Hormones:
T4 increases surfactant production
T3 crosses placenta
TRH increases phospholipid independent of T3/T4

Insulin:
Delays maturation of type II cells, decreases % saturated PC
Delayed PG
Increased sugar levels delay lung maturation

Being premature decreases surfactant production

Question 18

What are action of insulin

Answer 18

Actions of Insulin:
Increased glucose uptake in muscle, fat, and liver
Decreased lipolysis
Decreased amino acid release from muscle
Decreased gluconeogenesis in liver
Decreased ketogenesis in liver

Question 19

What are the fuels needed for Infants

Answer 19

~5g glucose/kg/day
Substrates are principally glucose and amino acids
Insulin is the dominant hormone (acts as growth factor increasing adipose stores)

Fats – Formation of Ketone Bodies
Beta-oxidation removes 2-carbon units acetyl-CoA
These are used to make ketone bodies

Fats – Post-Prandial State
Blood glucose rise
Insulin acts to lower blood glucose
Active uptake of glucose by peripheral tissues

Fats – Post-Absorptive State
Blood glucose levels fall
Substrates are mobilised peripherally through action of counter regulatory (catabolic) Hormones (glucagon) to maintain blood glucose
Insulin is opposed

Question 20

What is prolactin and how does it affect lactation

Answer 20

Prolactin (PRL)
PRL Production: produced by lactotroph cells of the anterior pituitary gland

PRL Functions:
Lactogenic – initiate milk production by alveolar cells (breast not lung)
Galactopoietic – maintain milk production
Mammogenic – proliferation of alveolar and duct cells (growth)

Question 21

How is Prolactin regulated

Answer 21

PRL Regulation
PRL Inhibitor – dopamine
PRL Stimulant – suckling + oxytocin + thyrotropin releasing hormone (TRH)

Disinhibition – stimulation of nipple sends signals via afferent pathway -> inhibits dopaminergic neurons, therefore inhibiting an inhibitory neurotransmitter = disinhibition

TRH – TRH stimulates prolactin release. How = oestrogen increase sensitivity of lactotrophs to TRH and decrease sensitivity to dopamine inhibition

TRH = thyrotropin releasing hormone

Question 22

What are the two main forms of breast infections

Answer 22

Mastitis
Infection and inflammation of breast tissue, due to milk stasis and bacterial overgrowth
Symptoms: breast pain, swelling, warmth, redness
Treatment: continue expressing or feeding and antibiotics

Breast Abscess
Pus filled infection (often staph aureus)
Symptoms: breast pain, swelling, warm abscess, fever, tender ipsilateral lymphadenopathy in axilla
Treatment: antibiotics and US guided aspiration

Question 23

Where can fluid loss occur

Answer 23

Fluid Loss
Stool: 5 ml/kg/day
Respiratory Tract: humidity of inspired gas, RR, tidal volume, dead space
Kidneys: reduce reabsorption in premature
Skin: lack of protective layer

Management of Fluid Loss: increased humidity prevents water loss in neonates

Question 24

What are the theromoregulation adaptations of infants

Answer 24

Neonatal Heat Loss
Large surface area to body mass

Thermogenesis
Brown Fat: Non-shivering thermogenesis, high vascular, sympathetic innervation, increased mitochondrial content -> double heat production

Question 25

What are the NICU management of complication of prematurity

NICU = neonatal intensive care unit

Answer 25

• Control Temperature: Resuscitaire
• Control Respiration: ET Tube (30% Oxygen)
• Control Feeding: NG Tube
• Control Light: normal lighting (10-600 lux), procedure (2000 lux), glazed windows, window >2ft from bed
• General Environment: sound should never exceed >75db, at night >50db
• Staffing: 1 nurse for each patient

Question 26

What is the apgar score and assesment

Answer 26

0-3 = critical -> intensive management

4-6 = low -> management needed

7-10 = normal > observation only

Note: APGAR score is taken at 1 and 5 minutes and can be used to predict complications and long term health consequences such as -> autism, adhd, cerebral palsy, learning difficulties, neurological conditions

Question 27

What are the main casues of respiratory distress of newborns

Answer 27

• Sepsis
• Inhalation of harmful substances
• Pneumonia
• Head injury
• Chest injury
• Coronavirus
• Lack of type II pneumocytes

Question 28

What is respiratory distress syndrome

Answer 28

Definition: immature lung development resulting in difficulty breathing and lack of oxygen intake, caused by lack of surfactant productions (begins at 26 weeks)

Risk Factors: Sibling with RDS; Twins or multiple birth; C-Section (lack of adrenaline); Gestational diabetes (insulin dysregulation); Infection; Cold, Stress, Hypothermic baby

DDx: asthma, COPD, congestive heart failure, acute hypoxia, meconium aspiration

Epidemiology: 1.7% of live births; 0.1% of term births (25% of NICU admissions); 99% before 26 weeks; 50% between 28-32 weeks

**Aetiology: **infection, injury, lack of type II pneumocytes

Clinical S&S: Tachypnoea, Hypotension, Expiratory grunt, Cyanosis, Flaring of nostrils, Chest retractions (skin pulls on inspiration)

Question 29

What is the pathophysiology of respiratory distress syndrome

Answer 29

**Pathophysiology: **
Surfactants in alveoli have hydrophobic polar end, sitting on the border of air-liquid interaction preventing water attraction on opposite sides, preventing alveolar collapse
Prior to 26 weeks of gestation, the lungs do not have functioning type II alveolar cells (pneumocytes), and so surfactant is not produced
Without surfactants, alveoli collapse resulting in VQ mismatch and type I respiratory failure

Light lung appereance ( ground glass appereance) in an X-ray indicates ARDS

Question 30

What are the management, prognosis and complication of respiratory distress syndrome

Answer 30

**Management: **
Prophylaxis: 48hr ANC steroids
Oxygen: nasal cannula, CPAP, ventilation (see description)
Surfactant
IV Catheter Treatment (on umbilical cord)
Medications: Antibiotics, corticosteroids, diuretics

Prognosis:
Recovery after several months up to two years
Long-term SOB and fatigue in some

Complications:
Poor vision, hearing, mobility and learning difficulties

Question 31

Overview of what, why, signs and symptoms, and treatment of sepsis

Answer 31

What: Life-threatening organ dysfunction due to dysregulated host response to infection
**Why: **Largely due to systemic bacterial infection
Signs & symptoms:
Vital signs instability
Sleepiness/lethargy/floppiness/irritability
Low/high temperature
Tachycardia/tachypnoea
Treatment:
“3 in, 3 out”