DEVELOP - SYSTEMS Flashcards
What are the 5 stages in respiratory development? 3-8wks 5-16wks 16-26wks 24wks-term 36wks to 5yrs
Embryonic Pseudoglandular Canalicular Saccular Alveolar
In which stages of respiratory development does the blood-gas barrier thin and the surfactant system maturation begin?
Canalicular and saccular stages
At birth 1/2 the number of alveoli are present, when do we have them all
by 5yrs
Branching of bronchi forms bronchioles and terminal bronchioles. Each bronchiole divides to form 2+……which divide into 3-6…….which delvelop…..
Bronchiole –> form 2+.. RESPIRATORY BRONCHIOLES which divide into 3-6 ALVEOLAR DUCTS which delvelop TERMINAL SACS
Forkhead TFs (FOXA1/2) factors is involved in proliferation, branching and differentiation of the developing airway. Name 2 other growth factors required:
- Fibroblast GF-10, Sonic Hedgehog, bone morphic protein 4
- GH
- VEGF (vascular endo. GF) for angiogensis round alveoli
Saccules develop with capillaries around them at 24wks under which GF?
When do shallow indentations appear in the alveoli?
VEGF
32wks
Type I and Type II pneumocytes are present from 22wks. From 24wks what arise? What do they do?
Lamellar bodies in Type II pneumocytes
Fuse with cell membrane and release surfactant into extracellular space
Suggest 3 abnormalities that may affect resp development via extrinsic restriction of the lungs:
- CDH so thoracic contents pushed up
- effusions around lung
- thoracic/vertebral abnormalityies
Suggest 2 abnormalities that may affect resp development intrinsically:
- lung cysts (cystic adenomatoid malformation)
- malnutrition e.g. vit A deficient reduces septation
- smoking reduces foetal lung volumes
At mid-gestation foetal lungs make 5ml/kg fluid..at term 20ml/kg. How do the fluid composition of Cl and HCO3- compare to that of plasma?
-higher Cl-, lower HCO3-, lower protein
Lung fluid is produced by actively pumping which ion form the interstitium to the lung lumen? Result?
Cl-
Na+ moves passively into lumen, H20 follows by osmosis
Results in a positive pressure in the lung (1cm H20) and this distention keeps the lungs open
To adapt to survive extra-uterine life, the lung fluid must be absorped before birth. How is this done? Via active pumping of …..into the cell from the lumen..
Na+ into cell then secreted into interstitium by Na/K ATPase. Cl- and H20 flow passively to interstitium.
What stimulates the absorption of lung fluid in labour? Before the 02 exposure exaggerates reabsorption…(Name 3 hormones)
In labour, adrenaline stimulates the Na+ transporters.
THs and cortisol are needed for maturation of the foetal lung response to adrenaline.
What effect can oligohydramnios have on the lung development?
- fluid is pushed out the lungs, they are hypoplastic/underdeveloped
- vasculature develops abnormally
What is TTN when does it occur (resp)?
Transient Tachyponea of the Newborn
-in C-section, baby doesnt get signal to absorb lung fluid (steroids/adren.) so pumps not activated
What is the main component of surfactant made in the endoplasmic reticulum?
PC-Phosphatidycholine
Surfactant is made in what cell? Stored where? Released then degraded where? Absorbed and how much is recycled? Turnover time is 10hrs
Made in Type II pneumocytes
Stored in Lamellar bodies
Degraded in alveoli
90% recycled
What type of receptors regulate release via negative feedback?
Stretch receptors, B adrenergic
What is the function of surfactant? 3 things
Decrease surface tension so alveoli dont collapse Prevents atelectasis (incomplete inflation) Reduces work of breath
At 37degrees what organised structure does surfactant form compared to when complressed into a gel and a certain phase with a surface tension of O?
37: forms organized tubular myelin
Compressed: from gel to a liquid crystal phase
Surfactant is a mix of phospholipids, neutral lipids and protein. 80% is phosphatidylcholine of which 60% is in what form? What does this do?
Disaturated at DPPC (dipalmitoyl phosphatidylcholine)
This is what decreases surface tension and promotes the spreading of surfactant through lungs
10% surfactant by mass is made up of proteins Sp-A,, B C & D. Sp-A is a large glycoprotein. On what gene is it expressed? When is production high? What does it do?
- chromosome 10 (only expressed in lung)
- production increases lots after week 28
- determines tubular myelin structure, immunity, spreading of phospholipids..
Sp-B makes up 2% of surfactnat is coded by gene on chromosome 2. What increases its expression and what is it needed for?
Increased by glucocorticoids
Needed for tubular myelin, spreading, increases lung compliance and protects surfactant
What does Sp-C (chrs 8, 35a.acids long) enhance? As well as the spreading of phospholipids.
Absorption of surfactant
Sp-D has no structural function, what does it do?
Immune protection from ext pathogens, expression increases with gestation
What is produced more at the end of gestation and increases the % of DPPC?
Glucocorticoids
TRH increases phospholipid independent of T3/4.
T3 crosses the placenta. What effect does T4 have on surfactant production?
Increases production
What effect does insulin have on the maturation of type II pneumocytes and the amount of DPPC? Hence effect of diabetes to baby’s lungs?
Insulin delays maturation, and decreases amount of DPPC.
So diabetes, hyperinsulinism –> delayed lung maturation
What surfactant pathology may arise with prematurity? PC? capillary membrane?
PC less saturated, unstable, buckles on expiration
Leaky cap. membranes->fibrin deposition->inhibits reduction of s.tension, less gas diffusion
What surfactant pathology may arise with no Sp-B?
Less PG no secretion of normal surfactant. Lethal
Interstitial lung disease may present with a deficiency in which Sp protein?
Sp-C deficiency
In labour liquid production stops, foetal breathing stops. What stimulates breath? What detects hypoxia? Where is the fluid absorbed?
- cooling stimulates breath
- central chemoreceptor detects hypoxia
- some fluid squeezed out, most absorbed into lymphatics and capillaries
What 3 areas in the ventrolateral brainstem regulate breathing?
VRG (ventral resp. group)
DRG
Pneumotaxic areas
Normal breathing rhythm is active inspiration and passive expiration. As adults become hypoxic they breathe harder and faster, what about in utero foetus? Premature?
Opposite, efforts decrease until almost not breathing
Premature baby’s respond like foetus (apnoea)
V. premature baby’s after labour may respond to the hypoxia like a foetus, apnoea. What is given pos-delivery to prevent this?
Caffeine. Improves breathing, decreases hypoxia, avoids apnonea
What do baby’s utlise for energy to the vital organs throughout labour with is to a degree hypoxic?
Anaerobic glycolysis
Ketone bodies
Surfactant forms a tubular myelin network that live the alveolus keeping it open. What cell degrades it and what is re-used?
- Macrophage
- phospholipids reused in type II cell
- some choline fatty acids are lost
Why is the immune response in early life dampened vs. adult?
- immunosuppressive environment of the womb
- regulated immune responses to avoid inflamm. response to benign antigens
Give 3 consequences of the decreased immune response in newborns:
- more susceptible to pathogens e.g. group B strepto.
- reduced vaccine response
- may influence asthma/allergy development
Non-antigen specific immunity you are born with. What is antigen specific immunity?
- responds to specific antigens, potentiates response
- commits to memory for enhanced subsequent response
- B and T lymphocytes
What do infants recognise pathogens by that they have receptors for on leukocytes e.g. TLR?
PAMPs - Pathogen Associated Molecular Patterns (these are highly conseverd and are required for pathogen to function)
Name the 2 primary lymphoid organs:
- Thymus
- Bone Marrow
Suggest 3 secondary lymphoid organs:
- spleen
- lymph nodes
- tonsils, adenoids
- mesenteric meyers patch
The mesoblastic stage of immune development is predominately morphologically recognised what cells in the yolk sac? From 18days gestation, persists for how many weeks?
Haematopoetic cells
Persists for 10 weeks
What 3 stages of immune development follow the Mesoblastic stage for site of blood production:
- 6-8th week
- 7-9th week
- 10th-birth
Hepatic
Splenic
Myeloid/Bone Marrow
Infants having more of which inteleukin makes them have heightened stimulation of Treg. cells?
IL-6
T cells migrate from the bone marrow to thymus for gene rearrangements and maturation. Then what happens?
- each has a unique antigen receptor on cell surface
- mature T cells exit, re-circulate 2dry lymphoid organs
Do T cells cross the placenta?
No
From which pharyngeal pouch does the Thymus develop?
3rd
Why is there a trough in IgG levels 3 months after birth?
- newborns are deficient in their own generated IgG
- have transplacental maternal IgG
- maternal IgG half life is 1 month
When are full adult levels of IgG reached?
4-5yrs
Infants have higher plasma neutrophils but are less effective. Give 3 reasons why:
- dont migrate to sites of infection
- poor phagocytosis
- less efficient bacteriocidal activity
- dont adhere well
- express less co-stimulatory molecules (less activation)
Neonates have “developmental immunodeficiency” what does this mean? Why is this the case?
- reduced quality &function of immune response and physiochemical barriers
- to shape dynamically to the demands of early life and adapt appropriately
Neonates have increased susceptibility to infections, suggest 1 common bacterial and 1 common viral infection and why they get it more.
- Group B streptococcus (Ig and complement deficient, less phagocytic cells at infection)
- Herpes Simplex (Ig, cytokine, MO and NK deficiency and less cytotoxicity of T cells)
State 3 components of breast milk and their function.
Complement for opsonisation
Lysozyme attacks bacterial cell wall
Lactoperoxidase is antistreptococcal
Lactoferrin inhibits bacteria growth
Why are IUGR baby’s especially immunocompromised?
Smaller Thymus
Poorer T cell function, less T cells as less proliferation
BCG vaccine is given at birth, from 2months name 3 vaccines given.
- DTaP (diptheria, tetanus, pertussis, haemophilus influenza)
- Type B Polio
- Streptococcus pneumoniae
- Nisseria Meningitis
What effect would maternal vaccination during pregnancy have on immune response? Why?
Better, antibodies increase, cross placenta providing specific protection for first few months of high risk life (before vaccine administered)
Adult Hb has 4pp chains. 2a, 2beta, what about foetal Hb? Where is foetal Hb synthesised before wk 6, after, and before birth?
- 2a, 2γ chains
- yolk sac makes it up to 6wks gestation
- from 6wks liver takes over
- before birth spleen takes over
Foetal Hb is made up of 2a, 2γ chains, how does this change at birth? And what after birth does synthesis?
- at birth beta shoots up and γ plummets
- bone marrow takes over synthesis (2a, 2b)
Which way is O2-dissociation curve shifted in the foetus? Why?
Left
-increased O2 affinity so binds it at lower partial pressures/ is “stickier”
What binds to deoxygenated Hb in adults, that shifts O2-dissociation curve to the right? What happens to this in pregnancy?
2,3 DPG - promotes further O2 release and makes it harder for O2 to bind
-30% increase in 2,3 DPG in pregnancy
The umbilical vein travels towards the liver, ~55% of foetal blood bypasses the hepatic vessels via what vessel? That shunts the blood where? Where does the rest go?
- The ductus venosus shunts this blood to IVC
- Rest will enter the portal vein
The blood in the RA of foetus is mixed as the deoxygenated blood from the legs in the IVC is combined with what?
The oxygenated blood from the umbliical vein
Most foetal blood in the RA is shunted through where?
The foramen ovale into LA
Give 3 reasons blood is unlikely to enter lungs in the foetus.
-lungs are fluid filled
-lung capillaries are v.constricted -> high pressure&resistance
~no blood enters RV (RA–>LA)
-if does, will be shunted via ductus arteriosus -> aorta
The umbilical artery where some blood goes to placenta for CO2/waste removal and oxygenation is a branch of which vessel?
The internal iliac
At birth what causes the umbilical vessels to constrict? As a result what closes after 3-10days?
- cooler temps after cord is clamped
- d.venosus closes as blood no longer flows in umbilical vein
Upon birth and air breathed, fluid is pushed out lungs. What causes the pulmonary arterioles to dilate reducing resistance? What closes in minutes-hrs of birth? How?
- O2 causes the v.dilation
- less pulmonary resistance, RA and RV at lower pressure as more blood returns to LA
- RA/LA pressures equalise
- foramen ovale closes
What 2 things cause the ductus arteriosus to close in 96hrs?
- O2 rise
- prostoglandin decrease as placenta gone
Abnormal circulation or reversion to foetal anatomy can occur. Esp as the pulmonary arteries are v. reactive. Suggest 2 causes of them constricting?
- hypoxia
- hypercarbia
- acidosis
- cold
- -> rise in PVR causing L->R shunting
PDA (patent d. arteriosus) can increase the work of breathing and lead to congestive HF by 1yr. List 3 symptoms:
- fast breathing
- sweating during feeding, poor feeding
- poor growth
- rapid pulse, bounding pulse
PDA (patent d. arteriosus) can increase the work of breathing, how?
- the defect causes increased blood to enter the lungs
- pressure in the lungs is greater
- harder to inflate
Give 3 groups that the defect PDA (patent d. arteriosus) is common in.
- premature
- resp. distress due to hypoxia
- Down’s S.
- Rubella
- Congenital HD
PDA (patent d. arteriosus) is treated by which NSAID? How does this help? (Or surgery to ligate)
-Indomethacin: inhibits prostoglandins so encourages closure
What kind of shunting does an ASD (atrial septal defect) cause?
-acyanotic L–>R due to high compliance of RA and change in pressure across the 2 atria
Give 3 symptoms of an ASD (atrial septal defect).
- dysponea
- frequent resp. infections
- palpitations
- SOB on activity
Give 2 reasons why neonates are at risk of heat loss.
- high SA:body mass
- lower % body fat, less subcut fat
- cannot shiver
How do babies do non-shivering thermogenesis?
-brown fat mitochondria with uncoupled movement of H+ to ATP, instead makes heat via uncoupling protein
Babies brown fat non-shivering thermogenesis is controlled by what innervation?
Sympathetic innervation of brown fat
Highly vascularised to warm blood
Why is it important to dry the baby after birth?
- hypothermia is a major cause of neonatal death
- heat can be lost from wet skin by evaporation
Neonates have a v.high total body water that decreases with age. Before vs after birth where is the water distributed?
- most extracellular before
- near birth this decreases and more into ICFV
- at 6months ICFV>ECFV
Fluid in the neonate is lost from kidneys, stool, the resp tract (humidity and temp. dependent)…where else that particularly impacts premature babies?
-the skin as skin isnt fully developed in preterms
Completion of nephrons occurs at 34wks but they are immature at birth so how is GFR vs adult?
GFR is reduced in neonates
What about the renal tubules concentrating ability of a neonate?
Limited concentrating ability as transporters not at optimum function to transport Na+ and gluc. from tubule to blood to make a conc grad for H20 re-absorption in interstitial space
What is the definition of intelligence?
-persons cognitive ability to learn
Suggest 4 things intelligence is associated with:
- school performance
- IQ, logic
- abstract thought
- emotional knowledge
- memory, planning, creativity
Intelligence has 2 important feautures, what are they?
- capacity to learn from experience
- ability to adapt to environment
Intellegence is seen as a broad, underlying category, “g” then multiple specialist skills e.g. visuospatial..why is intellegence hard to define/test?
-poor learners find test hard, good learners find tests easier and perform better
What does Jean Pinget’s Model of Cognitive development say about how a child functions and develops modes of thought?
- child is like scientist solving problems
- development progresses as child manipulates its environment
- actively works to develop more rational/logical modes of thought
According to Jean Pinget’s Model of Cognitive development, what are “operations”?
- via environment interaction, child forms a set of internal cognitive rules that allow child to make sense of the world.
- these are operations
According to Jean Pinget’s Model of Cognitive development, “operations”, what happens if the event is in disequilibrium with thought? 2 processes
- Assimilation: modifies percieved environment to fit existing knowledge structure
- Accomodation: modifies knowledge to fit new environmental challenge
Give an example of assimilation and accomodation to disequelibrium when a child knows “4legs+tail=dog”…
Assimilation - 4 legs+tail+bark = dog
Accomodation - 4 legs+tail + meow = cat
What are schemas?
-internalised representations of generalised classes of actions/situations
Jean Pinget's Model of Cognitive development has 4 stages, what are they? Birth-2yrs 2-7 7-12 12+
Birth-2yrs: SENSORIMOTOR
2-7: PREOPERATIONAL
7-12: CONCRETE OPERATIONAL
12+: FORMAL OPERATIONAL
What does the Sensorimotor stage of Jean Pinget’s Model of Cognitive development say about how you act and develop?
- realise your separate from objects and are an agent of action so begin to act intentionally
- develop “object permanence” (Aware object still exists if hidden)
What does the Preoperational stage of Jean Pinget’s Model of Cognitive development say about how you learn, think and develop?
- learn to use language
- egocentric and animistic thinking
- conservation of numbers
What does the Concrete Operational stage of Jean Pinget’s Model of Cognitive development say about how you develop?
- think logically about objects/events
- conservation of mass and weight
- can order objects in series/categories
What does the Formal operational stage of Jean Pinget’s Model of Cognitive development say about how you think/develop?
- think logically about abstract prepositions and test hypothesises systematically
- can consider the hypothetical, future and ideology
Separation anxiety begins at 9months to 3yrs, when does it peak?
18months
What does “The Bolby Theory of Attachment” say about attachment an social releasers driving care?
- children are pre-programmed to form attachments to survive
- social releasers e.g. cry/smile are innate behaviours to keep care giver close. These are instinctive
What did Rutter have to say about the effect of loss/disruption of care on children?
e.g. maternal deprivation due to cancer…vs arguements…child more likely -> crime
- its the quality of the relationship lost
- its the conflict/stress before the separation that causes antisocial behaviour
“The Bolby Theory of Attachment” says Attachments can be secure or insecure. And forms a template for our future relationships. Name the 4 characteristics of attachment:
- Safe Haven
- Secure Base
- Proximity Maintenance
- Separation Distress
Only long alleles on the 5-HTTLPR gene is v likely to lead to secure attachments in development. What about 2 short alleles on this gene?
- only secure if care is sensitively responsive
- otherwise insecure attachments will form
What is meant by a child’s “temperment”?
- style of behaviour/”how” of behaviour
- biological, born with
What are the 3 aspects of temperment?
- emotionality
- activity
- sociability
Kohlberg argued we develop from
-a selfish desire to avoid punishment…..
-to concern for group functioning…
-to concern for consistent application of universal ethical principles.
What do each of these represent?
Personal
Societal
Morality
Erikson’s theory of development aka Crisis resolution is based on what?
- stages in early life
- each stage has own dilemmas, you remain in the stage until you adapt to that
Morality development begins with pre-conventional morality in primary school to conventional morality is society, what do these represent? NB: post-conventional morality is an ideal
- pre-conventional: punishment and obedience, reward, what is fair
- conventional: be good for approval, uphold laws and societal rules
Family life cycle says we pass through distinct stages from crib-coffin and must master the skills of each stage to move on, give an adv of smooth transitions and a disadv of not mastering skills?
- adv: less disease, and emotional/stress-related disorder
- disadv: more likely to have difficulty with relationships and future transitions
What are the 5 stages in the Family Life Cycle model
- idependence
- coupling
- parenting children
- empty nest
- senior
Parenting can be authoritative, authoritarian or permissive, what makes up the best parenting?
- authoritative (firm boundaries but nuturing)
- flexible boundaries that fit childs emotional needs
- attachment with child will form the template for their future relationships
