GEP (Life support) Week 5 Flashcards
What is the placenta and what are its roles and function
-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
How does the exchange at the placenta occur between mother and baby
- 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
What is foetal haemoglobin
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
Why does HbF have higher affinity
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
When does the haemoglobin transition occur
No sickle cell until beta chain level increases and abnormalities can be seen (6 months onwards)
What are the key anatomy of foetal circulation
- 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
Summarise foetal circulation and the pathways
What is ductus arteriosus and the changes you see after birth and issues that can happen with it
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
What is ductus venosus and the changes you see after birth and issues that can happen with it
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
What is foreman ovale and the changes you see after birth and issues that can happen with it
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
Summary of anatomical changes at birth
Patent ductus arteriosus maintained in utero due to prostaglandins released by the placenta
What are the respiratory changes at birth and development
**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
How does the foetal lung fluid develop
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
What are the changes seen in foetal lung fluid at birth
- 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**
What is surfactant
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
What is the role of surfactatant
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
What are the factors that affect surfactant maturation
**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
What are action of insulin
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
What are the fuels needed for Infants
~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
What is prolactin and how does it affect lactation
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)
How is Prolactin regulated
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
What are the two main forms of breast infections
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
Where can fluid loss occur in infants
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
What are the theromoregulation adaptations of infants
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
What are the NICU management of complication of prematurity
NICU = neonatal intensive care unit
- 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
What is the apgar score and assesment
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
What are the main casues of respiratory distress of newborns
- Sepsis
- Inhalation of harmful substances
- Pneumonia
- Head injury
- Chest injury
- Coronavirus
- Lack of type II pneumocytes
What is respiratory distress syndrome
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)
What is the pathophysiology of respiratory distress syndrome
**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
What are the management, prognosis and complication of respiratory distress syndrome
**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
Overview of what, why, signs and symptoms, and treatment of sepsis
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”
